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.

Does the Use of Probe-based Near-infrared Autofluorescence Parathyroid Detection Benefit Parathyroidectomy?: A Randomized Single-center Clinical Trial.

OBJECTIVE: To evaluate the benefits of probe-based near-infrared autofluorescence (NIRAF) parathyroid identification during parathyroidectomy. BACKGROUND: Intraoperative parathyroid gland identification during parathyroidectomy can be challenging, while additionally requiring costly frozen sections. Earlier studies have established NIRAF detection as a reliable intraoperative adjunct for parathyroid identification. METHODS: Patients undergoing parathyroidectomy for primary hyperparathyroidism were prospectively enrolled by a senior surgeon (>20 years experience) and a junior surgeon (<5 years experience), while being randomly allocated to the probe-based NIRAF or control group. Data collected included procedure type, number of parathyroids identified with high confidence by the surgeon and the resident, number of frozen sections performed, parathyroidectomy duration, and number of patients with persistent disease at the first postoperative visit. RESULTS: One hundred sixty patients were randomly enrolled under both surgeons to the probe group (n=80) versus control (n=80). In the probe group, parathyroid identification rate of the senior surgeon improved significantly from 3.2 to 3.6 parathyroids per patient ( P <0.001), while that of the junior surgeon also rose significantly from 2.2 to 2.5 parathyroids per patient ( P =0.001). Parathyroid identification was even more prominent for residents increasing significantly from 0.9 to 2.9 parathyroids per patient ( P <0.001). Furthermore, there was a significant reduction in frozen sections utilized in the probe group versus control (17 vs 47, P =0.005). CONCLUSION: Probe-based NIRAF detection can be a valuable intraoperative adjunct and educational tool for improving confidence in parathyroid gland identification, while potentially reducing the number of frozen sections required.

Adrenal Metastasectomy in the Era of Immuno- and Targeted Therapy.

Adrenal metastasectomy has an increasing role in multimodality oncologic care for diverse primary cancer types. In this review, we discuss the epidemiology, evaluation, and contemporary best practices in the management of adrenal metastases from various primaries. Initial evaluation of suspected adrenal metastases should include diagnostic imaging to assess the extent of tumor involvement and determine surgical resectability, as well as biochemical evaluation for hormone secretion. Biopsy has a minimal role and should only be performed in tumors that are established to be non-hormone secreting and when the biopsy results would change clinical management. Adrenal metastasectomy is associated with survival benefit in selected patients. We suggest that adrenal metastasectomy has the greatest benefit in four clinical scenarios: (1) disease limited to the adrenal gland in which adrenalectomy renders the patient disease-free; (2) isolated progression in the adrenal gland in the setting of otherwise controlled metastatic extra-adrenal disease; (3) need for palliation of symptoms related to adrenal metastases; or (4) in the context of tissue-based clinical trials. Both minimally invasive and open adrenalectomy techniques are safe and appear to have equivalent oncologic outcomes. Minimally invasive approaches are favored when technically feasible while maintaining oncologic principles. A multidisciplinary evaluation including clinicians with expertise in the primary cancer type is essential to the successful management of adrenal metastases.

Adoption of Robotic Adrenalectomy: A Two-Institution Study of Surgeon Learning Curve.

BACKGROUND: Robotic adrenalectomy is feasible and safe, yet concerns over increased operative times and the learning curve (LC) for proficiency have limited its adoption. This study aimed to assess the LC for robotic adrenalectomy. METHODS: This is a two-institution retrospective review of consecutive unilateral minimally invasive adrenalectomies performed by four high-volume adrenal surgeons between 2007 and 2022. Two surgeons transitioned from laparoscopic to robotic adrenalectomy, and two surgeons adopted the approach, with proctoring, after completion of fellowship training without robotic experience. Operative time and complications were analyzed. Multivariable regression was used to identify factors associated with operative time. The number of cases required to overcome the LC was determined using the LC-cumulative-sum (LC-CUSUM) analysis. RESULTS: Of 457 adrenalectomies, 182 (40%) were laparoscopic and 275 (60%) robotic. The robotic approach was associated with shorter median operative time (106 vs 119 min; p = 0.002), fewer complications (6% vs 13%; p = 0.018), and fewer conversions to open adrenalectomy (1% vs 4%; p = 0.030), with no difference between the senior and junior surgeons. On adjusted analysis, factors associated with increased operative time were male sex (p < 0.001), BMI > 30 kg/m2 (p < 0.001), and higher gland weight (p < 0.001). The LC-CUSUM analysis showed proficiency after 8-29 procedures. Compared with the first 10 cases, there was a mean reduction in operative time of 14 min after 10-20 cases, 28 min after 20-30 cases, and 29 min after > 30 cases, regardless of surgeon experience. DISCUSSION: With dedicated teams and proctoring, robotic adrenalectomy can be safely adopted at high-volume centers with a minimal LC.

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.

Adrenalectomy for Secondary Malignancy: Patients, Outcomes, and Indications.

OBJECTIVE: The goal of this study was to examine a multi-institutional experience with adrenal metastases to describe survival outcomes and identify subpopulations who benefit from adrenal metastasectomy. BACKGROUND: Adrenalectomy for metastatic disease is well-described, although indications and outcomes are incompletely defined. METHODS: A retrospective cohort study was performed of patients undergoing adrenalectomy for secondary malignancy (2002-2015) at 6 institutions. The primary outcomes were disease free survival (DFS) and overall survival (OS). Analysis methods included Kaplan-Meier and Cox proportional hazards. RESULTS: Of 269 patients, mean age was 60.1 years; 50% were male. The most common primary malignancies were lung (n = 125, 47%), renal cell (n = 38, 14%), melanoma (n = 33, 12%), sarcoma (n = 18, 7%), and colorectal (n = 12, 5%). The median time to detection of adrenal metastasis after initial diagnosis of the primary tumor was 17 months (interquartile range: 6-41). Post-adrenalectomy, the median DFS was 18 months (1-year DFS: 54%, 5-year DFS: 31%). On multivariable analysis, lung primary was associated with longer DFS [hazard ratio (HR): 0.49, P = 0.008). Extra-adrenal oligometastatic disease at initial presentation (HR: 1.84, P = 0.016), larger tumor size (HR: 1.07, P = 0.013), chemotherapy as treatment of the primary tumor (HR: 2.07 P = 0.027) and adjuvant chemotherapy (HR: 1.95, P = 0.009) were associated with shorter DFS. Median OS was 53 months (1-year OS: 83%, 5-year OS: 43%). On multivariable analysis, extra-adrenal oligometastatic disease at adrenalectomy (HR: 1.74, P = 0.031), and incomplete resection of adrenal metastasis (R1 margins; HR: 1.62, P = 0.034; R2 margins; HR: 5.45, P = 0.002) were associated with shorter OS. CONCLUSIONS: Durable survival is observed in patients undergoing adrenal metastasectomy and should be considered for subjects with isolated adrenal metastases.

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.

Detecting the Near Infrared Autofluorescence of the Human Parathyroid: Hype or Opportunity?

OBJECTIVE: With the recent approval of 2 NIRAF-based devices for label-free identification of PG by the Food and Drug Administration, it becomes crucial to educate the surgical community on the realistic scope of this emerging technology. Here, we have compiled a review of studies that utilize NIRAF and present a critical appraisal of this technique for intraoperative PG detection. BACKGROUND: Failure to visualize PGs could lead to accidental damage/excision of healthy PGs or inability to localize diseased PGs, resulting in postsurgical complications. The discovery that PGs have NIRAF led to new avenues for intraoperatively identifying PGs with high accuracy in real-time. METHODS: Using the following key terms: "parathyroid, near infrared, autofluorescence" in various search engines such as PubMed and Google Scholar, we identified various publications relevant to this review of NIRAF as a technique for PG identification. Articles were excluded if they focused solely on contrast agents, served as commentaries/overviews on NIRAF or were not written in English. RESULTS: To date, studies have investigated the potential of NIRAF detection for (i) identifying PG tissues intraoperatively, (ii) locating PGs before or after dissection, (iii) distinguishing healthy from diseased PGs, and (iv) minimizing postoperative hypocalcemia after total thyroidectomy. CONCLUSIONS: Because NIRAF-based identification of PG is noninvasive and label-free, the popularity of this approach has considerably surged. As the present limitations of various technologies capable of NIRAF detection are identified, we anticipate that newer device iterations will continue to be developed enhancing the current merits of these modalities to aid surgeons in identifying and preserving PGs. However, more concrete and long-term outcome studies with these modalities are essential to determine the impact of this technique on patient outcome and actual cost-benefits.

Primary Tumor Resection Offers Survival Benefit in Patients with Metastatic Midgut Neuroendocrine Tumors.

BACKGROUND: Approximately 35% of patients with midgut neuroendocrine tumors (MNET) present with distant metastases. Although successful resection of these metastatic foci improves overall survival (OS), the role of primary tumor resection (PTR) in patients with unresectable metastatic disease is unclear. The aim of this study is to evaluate prevalence and survival impact of PTR in patients with unresectable metastatic MNET. PATIENTS AND METHODS: A retrospective cohort study of patients with metastatic MNET was performed using the National Cancer Database (2004-2014). Demographic and clinicopathologic variables were compared between patients who did and did not undergo PTR. Survival analysis was performed using Kaplan-Meier and log-rank tests. Multivariable regression analysis was used to assess factors associated with PTR and all-cause mortality. RESULTS: The cohort included 4076 patients; 2520 (61.8%) underwent PTR. Patients more likely to undergo PTR were younger and diagnosed earlier, underwent treatment at a nonacademic facility, lived on the West Coast or in the Central USA, and presented with smaller lower-grade small bowel primary tumors. Median OS was improved for patients who underwent PTR compared with those who did not (71 vs. 29 months, p < 0.001). On multivariable analysis, younger age, Black race, higher income, later year of diagnosis, treatment at an academic facility, private insurance, fewer comorbidities, small bowel primary, lower grade, and PTR (hazard ratio 0.63, 95% confidence interval 0.51-0.78, p < 0.001) were associated with lower mortality. CONCLUSIONS: PTR was associated with improved OS. Further study is needed to understand how clinicians select patients for PTR.

Update on Pheochromocytoma and Paraganglioma from the SSO Endocrine/Head and Neck Disease-Site Work Group. Part 1 of 2: Advances in Pathogenesis and Diagnosis of Pheochromocytoma and Paraganglioma.

This first part of a two-part review of pheochromocytoma and paragangliomas (PPGLs) addresses clinical presentation, diagnosis, management, treatment, and outcomes. In this first part, the epidemiology, prevalence, genetic etiology, clinical presentation, and biochemical and radiologic workup are discussed. In particular, recent advances in the genetics underlying PPGLs and the recommendation for genetic testing of all patients with PPGL are emphasized. Finally, the newer imaging methods for evaluating of PPGLs are discussed and highlighted.

Update on Pheochromocytoma and Paraganglioma from the SSO Endocrine and Head and Neck Disease Site Working Group, Part 2 of 2: Perioperative Management and Outcomes of Pheochromocytoma and Paraganglioma.

This is the second part of a two-part review on pheochromocytoma and paragangliomas (PPGLs). In this part, perioperative management, including preoperative preparation, intraoperative, and postoperative interventions are reviewed. Current data on outcomes following resection are presented, including outcomes after cortical-sparing adrenalectomy for bilateral adrenal disease. In addition, pathological features of malignancy, surveillance considerations, and the management of advanced disease are also discussed.

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.

Prophylactic Central Compartment Neck Dissection in Papillary Thyroid Cancer and Effect on Locoregional Recurrence.

BACKGROUND: Prophylactic central compartment neck dissection (pCCND) in addition to total thyroidectomy (TT) includes removal of central compartment lymph nodes in the absence of clinical involvement on preoperative and intraoperative evaluation. The data regarding the influence of pCCND on oncologic outcomes and surgical complication rates is mixed and, therefore, is the focus of this analysis. METHODS: A systematic review of the literature on total thyroidectomy with prophylactic central compartment neck dissection (TT + pCCND) from January 1990 to October 2017 identified 221 abstracts of which 17 met inclusion criteria and were reviewed (1 randomized-control trial, 13 retrospective cohort studies, and 3 meta-analyses). RESULTS: TT + pCCND was found to detect occult lymph node metastasis in approximately 50% of patients who had no clinical evidence of lymph node metastasis on preoperative imaging. Permanent hypoparathyroidism occurs more frequently following TT + pCCND (TT = 1.55% vs. TT + pCCND = 3.45%), but the rates of permanent recurrent laryngeal nerve dysfunction are similar (TT = 0.89% vs. TT + pCCND = 0.96%). The locoregional recurrence rates across all 14 studies included in this analysis was 6.75% for TT alone and 4.55% for TT + pCCND. The rate of locoregional recurrence was significantly lower in patients who underwent pCCND in a few studies and one meta-analysis, but were not significantly different in the majority of studies. CONCLUSIONS: TT + pCCND in clinically node-negative papillary thyroid cancer will detect occult lymph node metastasis in approximately half of patients. This may change their postoperative management with regard to adjuvant radioiodine therapy. There is a higher risk of hypoparathyroidism with pCCND, and the effect on rates of locoregional recurrence remains uncertain.

Adjuvant and Neoadjuvant Therapy, Treatment for Advanced Disease, and Genetic Considerations for Adrenocortical Carcinoma: An Update from the SSO Endocrine and Head and Neck Disease Site Working Group.

This is the second of a two-part review on adrenocortical carcinoma (ACC) management. While margin-negative resection provides the only potential cure for ACC, recurrence rates remain high. Furthermore, many patients present with locally advanced, unresectable tumors and/or diffuse metastases. As a result, selecting patients for adjuvant therapy and understanding systemic therapy options for advanced ACC is important. Herein, we detail the current literature supporting the use of adjuvant mitotane therapy, consideration of adjuvant radiation therapy, and utility of cytotoxic chemotherapy in patients with advanced disease. Ongoing investigation into molecular targeted agents, immunotherapy, and inhibitors of steroidogenesis for the treatment of ACC are also highlighted. Lastly, the importance of genetic counseling in patients with ACC is addressed as up to 10% of patients will have an identifiable hereditary syndrome.

Evaluation, Staging, and Surgical Management for Adrenocortical Carcinoma: An Update from the SSO Endocrine and Head and Neck Disease Site Working Group.

This is the first of a two-part review on adrenocortical carcinoma (ACC), a rare and aggressive malignancy that often presents at an advanced stage. Most patients present with symptoms related to cortisol and/or androgen excess. Appropriate biochemical evaluation and imaging is important in assessing the extent of disease, operative planning, and oncologic surveillance for patients with ACC. For patients with locoregional disease, potential cure requires margin-negative resection, and accumulating evidence suggests that regional lymphadenectomy should be performed. Although laparoscopic adrenalectomy is reported by some to be adequate for localized ACC, open resection in the hands of an experienced adrenal surgeon is the gold standard for operative management of this disease. Cure is rare following disease relapse, however select patients with severe symptoms related to hormone excess or pain may benefit from resection of local or distant recurrence. For best oncologic outcomes, it is recommended that all patients with ACC be treated at centers with multidisciplinary expertise in management of this rare and aggressive malignancy.

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.

A Novel T-Stage Classification System for Adrenocortical Carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group.

BACKGROUND: The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC. METHOD: Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS). RESULTS: Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p < 0.001). CONCLUSIONS: Compared with the current T-stage system, the proposed T-stage system, which incorporates LVI, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this T-stage classification should be considered for future AJCC staging systems.