High-throughput digital quantification of Alzheimer disease pathology and associated infrastructure in large autopsy studies.

High-throughput digital pathology offers considerable advantages over traditional semiquantitative and manual methods of counting pathology. We used brain tissue from 5 clinical-pathologic cohort studies of aging; the Religious Orders Study, the Rush Memory and Aging Project, the Minority Aging Research Study, the African American Clinical Core, and the Latino Core to (1) develop a workflow management system for digital pathology processes, (2) optimize digital algorithms to quantify Alzheimer disease (AD) pathology, and (3) harmonize data statistically. Data from digital algorithms for the quantification of ß-amyloid (Aß, n = 413) whole slide images and tau-tangles (n = 639) were highly correlated with manual pathology data (r = 0.83 to 0.94). Measures were robust and reproducible across different magnifications and repeated scans. Digital measures for Aß and tau-tangles across multiple brain regions reproduced established patterns of correlations, even when samples were stratified by clinical diagnosis. Finally, we harmonized newly generated digital measures with historical measures across multiple large autopsy-based studies. We describe a multidisciplinary approach to develop a digital pathology pipeline that reproducibly identifies AD neuropathologies, Aß load, and tau-tangles. Digital pathology is a powerful tool that can overcome critical challenges associated with traditional microscopy methods.

Diversity-oriented synthesis encoded by deoxyoligonucleotides.

Diversity-oriented synthesis (DOS) is a powerful strategy to prepare molecules with underrepresented features in commercial screening collections, resulting in the elucidation of novel biological mechanisms. In parallel to the development of DOS, DNA-encoded libraries (DELs) have emerged as an effective, efficient screening strategy to identify protein binders. Despite recent advancements in this field, most DEL syntheses are limited by the presence of sensitive DNA-based constructs. Here, we describe the design, synthesis, and validation experiments performed for a 3.7 million-member DEL, generated using diverse skeleton architectures with varying exit vectors and derived from DOS, to achieve structural diversity beyond what is possible by varying appendages alone. We also show screening results for three diverse protein targets. We will make this DEL available to the academic scientific community to increase access to novel structural features and accelerate early-phase drug discovery.

Integrated and automated high-throughput purification of libraries on microscale.

We herein report the development of an automation platform for rapid purification and quantification of chemical libraries including reformatting of chemical matter to 10 mM DMSO stock solutions. This fully integrated workflow features tailored conditions for preparative reversed-phase (RP) HPLC-MS on microscale based on analytical data, online fraction QC and CAD-based quantification as well as automated reformatting to enable rapid purification of chemical libraries. This automated workflow is entirely solution-based, eliminating the need to weigh or handle solids. This increases process efficiency and creates a link between high-throughput synthesis and profiling of novel chemical matter with respect to biological and physicochemical properties in relevant assays.

Identification of a PCSK9-LDLR disruptor peptide with in vivo function.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-density lipoprotein cholesterol (LDL-C) levels by promoting hepatic LDL receptor (LDLR) degradation. Therapeutic antibodies that disrupt PCSK9-LDLR binding reduce LDL-C concentrations and cardiovascular disease risk. The epidermal growth factor precursor homology domain A (EGF-A) of the LDLR serves as a primary contact with PCSK9 via a flat interface, presenting a challenge for identifying small molecule PCSK9-LDLR disruptors. We employ an affinity-based screen of 1013in vitro-translated macrocyclic peptides to identify high-affinity PCSK9 ligands that utilize a unique, induced-fit pocket and partially disrupt the PCSK9-LDLR interaction. Structure-based design led to molecules with enhanced function and pharmacokinetic properties (e.g., 13PCSK9i). In mice, 13PCSK9i reduces plasma cholesterol levels and increases hepatic LDLR density in a dose-dependent manner. 13PCSK9i functions by a unique, allosteric mechanism and is the smallest molecule identified to date with in vivo PCSK9-LDLR disruptor function.

Treating Positive Axillary Disease in Elderly Breast Cancer Patients: The Impact of Age on Radiation Therapy.

INTRODUCTION: Breast cancer is the second most common cause of cancer death in females, and 30% of these patients are over the age of 70 years. Studies have shown deviation from the standard treatment paradigms in the elderly, especially in regard to radiation treatment. METHODS: We performed a retrospective chart review on 118 patients over the age of 70 years diagnosed with breast cancer and pathologically proven axillary disease over an 8-year period at an urban academic hospital to examine which patient factors influenced radiotherapy. RESULTS: Increasing patient age was associated with a decrease in the probability of receiving radiotherapy, while HER2-negative patients were more likely to receive radiation. Neither race, number of coexisting medical conditions, or insurance status showed any influence on radiation treatment. CONCLUSION: Patient age has a significant influence if elderly patients with axillary disease receive radiotherapy. Further investigation and validation are needed to understand why chronological age rather than biological age influences treatment modalities.

Roux-en-Y gastric bypass decreases serum inflammatory markers and cardiovascular risk factors in obese diabetics.

BACKGROUND: Obesity and type 2 diabetes mellitus are associated with elevated levels of inflammatory markers. This chronic inflammation is known to contribute to increased risk of cardiovascular disease in these populations. Laparoscopic Roux-en-Y gastric bypass is associated with a high rate of diabetes remission. We hypothesize that laparoscopic Roux-en-Y gastric bypass decreases systemic inflammatory markers and cardiovascular disease risk factors in obese diabetics. METHODS: This was a single-institution prospective cohort study of 61 obese patients with type 2 diabetes mellitus. A total of 30 patients underwent laparoscopic Roux-en-Y gastric bypass surgery, and 31 patients underwent standard medical therapy with diabetes support and education. Collected data included preoperative and postoperative inflammatory biomarkers and clinical parameters. RESULTS: Twelve months after undergoing laparoscopic Roux-en-Y gastric bypass, controlling for sex and age, there was a significant correlation between a change in interleukin-6 and a change in systolic blood pressure (Spearman r = 0.41, P = .03). Similarly, when sex and age were controlled for in the laparoscopic Roux-en-Y gastric bypass group, a statistically significant relationship remained between percent excess weight loss and change in interleukin-6 (P = .001). CONCLUSION: A significant relationship exists between decreased systemic interleukin-6 levels and both excess weight loss and lowered systolic blood pressure after laparoscopic Roux-en-Y gastric bypass in obese patients with diabetes mellitus. These correlations may explain the decreased risk of cardiovascular disease after surgical weight reduction in this patient population.

Should Pre-Transplant Hemoglobin A1c Be Used to Predict Post-Transplant Compliance in End-Stage Renal Disease Patients Undergoing Kidney Transplantation?

BACKGROUND Patient compliance with immunosuppressive therapy after transplant has impacts on both graft and patient outcomes. For diabetic end-stage renal disease (ESRD) patients who are undergoing evaluation for kidney transplantation in our program, hemoglobin A1c (HbA1c) level of >10% is used as a flag that the patient may be at risk for noncompliance and that more comprehensive psychosocial screening is needed prior to transplant. We evaluated the association between pre-transplant HbA1c level and post-transplant compliance, as no study to date has looked at this in the transplant population. MATERIAL AND METHODS The charts of 392 patients who received a kidney transplant at a single institution between July 2008 and June 2012 were retrospectively reviewed. One hundred and sixty-five diabetic patients who received a kidney transplant alone were included in the final analysis. Our predictive variable was HbA1c level greater than 7.7% based on previous reports in the diabetic population. Outcome measures were graft survival, rejection episodes, unexplained low immunosuppressant levels, and documented noncompliance. RESULTS There were no statistically significant differences between the HbA1c groups of ≤7.7% and >7.7% in outcomes of failed grafts (22.0% and 17.8%, p=0.2), rejection episodes (15.0% and 6.7%, p=0.3), unexplained low immunosuppressant level (46.6% and 37.9%, p=0.3), and documented noncompliance (25.0% and 16.7%, p=0.4). CONCLUSIONS In diabetic ESRD patients selected for renal transplantation, elevated pre-transplant HbA1c levels, defined as HbA1c >7.7%, are not predictive of post-transplant medication compliance. We advocate that this group of patients should not be denied transplant solely on their elevated pre-transplant HbA1c.

Value of an interactive phone application in an established enhanced recovery program.

PURPOSE: An interactive mobile phone application was added to an established Enhanced Recovery After Surgery (ERAS) program to determine the impact on ERAS compliance as well as clinical outcomes. METHODS: We identified patients undergoing elective colorectal surgery enrolled in our ERAS program from February 2017 to July 2018. Patients enrolled in a phone application were compared with those not enrolled in terms of age, sex, diagnosis, operative approach, bowel preparation, oral intake and solid food intake, ERAS pathway adherence, and clinical outcomes. RESULTS: A total of 289 patients were included: 147 enrolled and 142 not enrolled in the phone application. The mean age of enrollees was 53.0 years, compared with 58.3 years for the non-enrollees (p = 0.003). The mean ERAS pathway medication adherence for enrollees was 82.1% versus 76.8% for those not enrolled (p = 0.005). The mean LOS and SSI rates for those enrolled versus not enrolled in the phone application was 4.4 days versus 6.4 days (p = 0.006) and 3.4% versus 11.3% (p = 0.019), respectively. There was no significant difference in readmission rates between enrollees and non-enrollees (15% versus 10.6%, p = 0.345). The mean total cost of patients enrolled was $11,560; total cost of those not enrolled was $13,946 (p = 0.024). CONCLUSIONS: Use of an interactive phone application is associated with improved medication ERAS adherence along with significant reduction in length of stay and SSI rates without increasing total cost.

Risk factors associated with positive resection margins in patients with adrenocortical carcinoma.

BACKGROUND: Positive resection margins are associated with worse survival after surgery for adrenocortical carcinoma (ACC). We aimed to identify risk factors for positive margins post-resection. METHODS: The NCDB was queried for ACC patients from 2006 to 2015. Patients with positive versus negative resection margins post-surgery were compared using Chi-square tests. Survival based on adjuvant treatment was assessed using Kaplan-Meier curves. RESULTS: 1,973 patients with ACC were identified, 217 (11.0%) with positive margins. Multivariable analysis identified extra-adrenal extension (HR 4.92, p < 0.001), lymph node metastases (HR 2.64, p = 0.001), and distant metastases (HR 1.53, p = 0.03) as risk factors for positive margins. No significant difference in margin status existed between patients who had an open versus minimally invasive procedure (p = 0.6). Positive margin patients receiving adjuvant radiation (p = 0.007) or combined chemo-radiation (p = 0.001) had the longest survival. CONCLUSION: No modifiable risk factors were identified, but patients with positive margins receiving adjuvant radiation or chemo-radiation had the longest survival.

Operative resection in early stage pancreatic neuroendocrine tumors in the United States: Are we over- or undertreating patients?

BACKGROUND: Many current guidelines recommend nonoperative management for pancreatic neuroendocrine tumors <2 cm. The objective of this study was to evaluate the utilization and outcomes of resection for these pancreatic neuroendocrine tumors in the United States. METHODS: Using the National Cancer Database (2004-2014), 3,243 cases of T1 (≤2.0 cm) pancreatic neuroendocrine tumors were identified. Additional patient and tumor characteristics were examined. Multivariate models were used to identify factors that predicted resection and to assess patient survival after resection. RESULTS: 75% of pancreatic neuroendocrine tumors measuring 0 to 1.0 cm and 80% of pancreatic neuroendocrine tumors measuring >1.0 and ≤2.0 cm were resected. Eighty-four pancreatic neuroendocrine tumors were functional, of which 82% were resected. Variables influencing resection included positive lymph nodes, tumor in body or tail of pancreas, well or moderately differentiated tumors, and resection at academic medical centers (odds ratio 1.5-4.9). When controlling for other variables, patients with pancreatic neuroendocrine tumors 1 to 2 cm who underwent resection had a prolonged 5-year survival rate (hazard ratio 0.51, confidence interval 0.34-0.75) when compared with those who did not undergo resection. This survival benefit of resection was not found for pancreatic neuroendocrine tumors 0 to 1 cm (hazard ratio = 0.63, confidence interval 0.36-1.11). CONCLUSIONS: Contrary to many current recommendations, most patients with pancreatic neuroendocrine tumors ≤2.0 cm undergo surgical resection in the United States. A survival benefit was found for resection of pancreatic neuroendocrine tumors 1 to 2 cm, suggesting that current recommendations should perhaps be revised.

National Treatment Practice for Adrenocortical Carcinoma: Have They Changed and Have We Made Any Progress?

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy with a dismal prognosis. Two landmark trials published in 2007 and 2012 showed efficacy for adjuvant mitotane in resectable ACC and etoposide/doxorubicin/cisplatin plus mitotane for unresectable ACC, respectively. In this study, we used the National Cancer Database to examine whether treatment patterns and outcomes changed after these trials. METHODS: The National Cancer Database was used to examine treatment patterns and survival in patients diagnosed with ACC from 2006 to 2015. Treatment modalities were compared within that group and with a historical cohort (1985 to 2005). χ2 tests were performed, and Cox proportional hazards models were created. RESULTS: From 2006 to 2015, 2752 patients were included; 38% of patients (1042) underwent surgery alone, and 31% (859) underwent surgery with adjuvant therapy. Overall 5-year survival rates for all stages after resection were 43% (median, 41 months) in the contemporary cohort and 39% (median, 32 months) in the historical cohort. After 2007, patients who underwent surgery were more likely to receive adjuvant chemotherapy (P = 0.005), and 5-year survival with adjuvant chemotherapy improved (41% vs 25%; P = 0.02). However, survival did not improve in patients with unresectable tumors after 2011 compared with 2006 to 2011 (P = 0.79). Older age, tumor size ≥10 cm, distant metastases, and positive margins were associated with lower survival after resection (hazard ratio range: 1.39 to 3.09; P < 0.03). CONCLUSIONS: Since 2007, adjuvant therapy has been used more frequently in patients with resected ACC, and survival for these patients has improved but remains low. More effective systemic therapies for patients with ACC, especially those in advanced stages, are desperately needed.

Enabling chiral separations in discovery chemistry with open-access chiral supercritical fluid chromatography.

Work from this paper details a novel walk-up open-access (OA) approach to enable chiral analytical method development and preparative separation of enantiomers in early discovery chemistry using supercritical fluid chromatography (SFC). We have demonstrated the success of this OA approach using immobilized chiral stationary phases (CSPs). After screening a diverse set of racemic drug candidates, we have concluded that a simplified OA chiral SFC platform can successfully purify approximately 60% of the analysed racemates. This streamlined OA workflow enables medicinal chemists with limited expertise in chiral method development to successfully and rapidly purify enantiomers for their projects using Waters UPC2 and Prep100-SFC instrumentation.

Evolution of the Surgical Technique for "Breast in a Day" Direct-to-Implant Breast Reconstruction: Transitioning from Dual-Plane to Prepectoral Implant Placement.

BACKGROUND: Direct-to-implant breast reconstruction offers the intuitive advantages of shortening the reconstructive process and reducing costs. In the authors' practice, direct-to-implant breast reconstruction has evolved from dual-plane to prepectoral implant placement. The authors sought to understand postoperative complications and aesthetic outcomes and identify differences in the dual-plane and prepectoral direct-to-implant subcohorts. METHODS: A retrospective review of a prospectively maintained database was conducted from November of 2014 to March of 2018. Postoperative complication data, reoperation, and aesthetic outcomes were reviewed. Aesthetic outcomes were evaluated by a blinded panel of practitioners using standardized photographs. RESULTS: One hundred thirty-four direct-to-implant reconstructions were performed in 81 women: 42.5 percent were dual-plane (n = 57) and 57.5 percent were prepectoral (n = 77). Statistical analysis was limited to patients with at least 1 year of follow-up. Total complications were low overall (8 percent), although the incidence of prepectoral complications [n = 1 (2 percent)] was lower than the incidence of dual-plane complications [n = 7 (12 percent)], with the difference approaching statistical significance (p = 0.07). Panel evaluation for aesthetic outcomes favored prepectoral reconstruction. Pectoralis animation deformity was completely eliminated in the prepectoral cohort. CONCLUSIONS: The authors present the largest comparative direct-to-implant series using acellular dermal matrix to date. Transition to prepectoral direct-to-implant reconstruction has not resulted in increased complications, degradation of aesthetic results, or an increase in revision procedures. Prepectoral reconstruction is a viable reconstructive option with elimination of animation deformity and potential for enhanced aesthetic results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Primary Tumor Site Affects Survival in Patients with Gastroenteropancreatic and Neuroendocrine Liver Metastases.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are commonly present with metastatic disease, and the liver is the most frequent metastatic site. Herein, we studied whether primary tumor site affects survival in patients with GEP-NETs and liver metastases (NELM). As a secondary endpoint, we studied whether extrahepatic disease and surgical resection impact survival in this patient population. METHODS: Patients with NELM diagnosed from 2006 to 2014 were identified from the National Cancer Database. Kaplan-Meier curves and nested Cox proportional hazards were used to assess variables associated with survival. RESULTS: 2947 patients with well- or moderately differentiated GEP-NETs and NELM met the inclusion criteria for this study. Patients with small bowel NETs survived the longest of all GEP-NETs with NELM (median not reached). Rectal and gastric NETs with NELM had the shortest survival (median 31 months). Patients with extrahepatic metastases who underwent any operation survived longer than those managed nonoperatively (median survival 38.7 months vs. 18.6 months, p = 0.01). On multivariable analysis, operations on the primary tumor and distant metastatic site (HR 0.23-0.43 vs. no surgery), treatment at an academic/research hospital, Charlson comorbidity index of 0, no extrahepatic metastases, and younger age were associated with prolonged survival (p < 0.01). CONCLUSIONS: Primary tumor site affects survival in patients with GEP-NETs and NELM. Surgical resection seems beneficial for all GEP-NETs with NELM, even in the presence of extrahepatic metastases.

Longer Operative Time and Intraoperative Blood Transfusion Are Associated with Postoperative Anastomotic Leak after Lower Gastrointestinal Surgery.

Anastomotic leak after lower gastrointestinal surgery is a complication with potential for high morbidity, mortality, and increased costs. A single-institution retrospective chart review was performed on all patients who underwent lower gastrointestinal surgery between June 2009 and June 2013. Fifty-seven variables were included in our analysis and their association with postoperative anastomotic leak was examined. Nine hundred fifty-two patients underwent 983 lower gastrointestinal anastomoses with an overall leak rate in this series of 6 per cent. Type of intestinal anastomosis created (P < 0.00005), operative indication (P < 0.015), operation performed (P < 0.014), intraoperative blood transfusion (P < 0.017), and intraoperative surgical drain placement (P < 0.022) were all predictive of anastomotic leak. Anastomotic leak rate increased by 1.3 times for every additional hour in the operating room after three hours. Both increasing operation time and intraoperative blood transfusions were associated with an increased rate of anastomotic leak. When operative time extends beyond three hours or in those cases were blood transfusions are given, surgeons should consider taking steps to minimize the risks of a potential anastomotic leak.

Obesity Does Not Influence Management of Advanced Breast Cancer in the Elderly.

BACKGROUND: Obesity is becoming increasingly common in the elderly population, and it adds to the complexity of treatment decisions in this population. We aimed to investigate whether body mass index (BMI) affects care in this subset of patients. PATIENTS AND METHODS: We performed a retrospective chart review on 118 patients over the age of 70 years diagnosed with breast cancer and pathologically proven axillary disease over an 8-year period at an urban academic hospital and compared BMI to treatment received, clinical stage, and hormone receptor status. RESULTS: Performance of radiation therapy, axillary surgery, and chemotherapy was compared in the elderly population over lower and higher BMI, and no significant difference was detected. Although there was a trend for increasing clinical stage to be associated with a lower BMI, this was not statistically significant (P = .06). CONCLUSION: Obesity does not appear to influence treatment decisions in patients over the age of 70 years. Breast cancer providers should turn to other patient and clinical factors when deciding treatment plans in this patient population. Further investigation is needed to examine how obesity influences tumor biology, diagnosis, and treatment decisions.

Laparoscopic Parenchymal-Sparing Hepatectomy: the New Maximally Minimal Invasive Surgery of the Liver-a Systematic Review and Meta-Analysis.

BACKGROUND: Parenchymal-sparing hepatectomies (PSH) are liver resections with preservation of as much liver parenchyma as possible. PSH can be performed laparoscopically (LPSH), but access to the posterosuperior segments is difficult and they are challenging when there are multiple bilobar lesions; the procedure may require repositioning and may be long and cumbersome. The objective of this systematic review is to analyze the feasibility and limitations of laparoscopic PSH in the literature. METHODS: A systematic review of the literature was performed by searching Medline/PubMed, Scopus, and Cochrane databases. Resections were categorized by segment(s), and data regarding operative time, blood loss, length of hospital stay, complications, and R0 resection were analyzed. RESULTS: Of 351 studies screened for relevance, 48 studies were reviewed. Ten publications fulfilled inclusion criteria, reporting data from 579 patients undergoing LPSH. The most common indication was CRLM (58%) followed by hepatocellular carcinoma (16%). Only 92 patients were reported to have resections of more than one tumor; the maximum number of lesions resected was seven. Of resected lesions, 21.5% were located in the cranial segments. Mean operating time was 335.2 min, estimated blood loss was 462 cc, and hospital stay was 7.6 days. Conversion rate was 9.7%, and complications occurred in 19.4% of cases. No perioperative mortality was reported. R0 resections were achieved in 87.7% of cases. CONCLUSION: Laparoscopic PSH is performed and reported, but the data quality is low so far. The main limitation of LPSH is the low number of lesions resected, especially for bilobar, metastatic disease. Prospective reports with tumor-specific oncological data are desirable.

Do All Abdominal Neuroendocrine Tumors Require Extended Postoperative VTE Prophylaxis? A NSQIP Analysis.

BACKGROUND: Venous thromboembolism (VTE) occurs at high incidence in abdominal cancer surgery; therefore, a 4-week postoperative VTE prophylaxis is advocated. However, most patients with neuroendocrine tumors (NETs) have more favorable prognoses. This study aimed to determine the incidence of VTE in patients with abdominal NETs, compare these rates to other abdominal malignancies, and identify VTE risk factors. METHODS: The ACS-NSQIP database was queried to identify patients with abdominal NETs and other abdominal malignancies who underwent surgery from 2008 to 2015. A 30-day postoperative VTE incidence for each group was compared. Univariable and multivariable analyses were used to identify VTE risk factors. RESULTS: Of the 7226 operations for patients with benign (2154) and malignant (5072) abdominal NETs, 144 patients experienced a VTE without significant differences between groups. Subgroup analysis revealed a spectrum of VTE rates. Compared to VTE rates of other abdominal malignancies, patients with benign (1.1% vs. 2.4%, p < 0.001) or malignant (1.7% vs. 2.4%, p < 0.001) non-pancreatic abdominal NETs had significantly lower rates, malignant pancreatic NETs (PNETs) (3.4% vs. 2.4%, p = 0.03) had significantly higher rates, and benign PNETs (3.2% vs. 2.4%, p = 0.21) had comparable rates. Multivariable analysis identified pre-operative albumin (p < 0.001), bleeding disorders (p < 0.001), operative time (p < 0.001), and having a PNET (p = 0.04) as risk factors for VTE in abdominal NET patients. CONCLUSION: Routine extended VTE prophylaxis after surgery may be necessary in PNETs, but probably unnecessary in other abdominal NETs. However, clinicians should use risk factors identified in this study when considering to forego extended VTE prophylaxis in NET patients.

Expression of programmed death ligand 1 and 2 in adrenocortical cancer tissues: An exploratory study.

BACKGROUND: Inhibition of the interaction of programmed death 1 with programmed death ligand 1 and 2 has been used successfully for treatment of multiple advanced cancers, but expression has not been studied in adrenocortical carcinoma. In this study, we investigated programmed death ligand 1 and 2 expression in adrenocortical carcinoma to determine the potential usefulness of checkpoint inhibitors in these malignant neoplasms. METHODS: A total of 56 tissue samples from patients with adrenocortical carcinoma (34) and benign adrenal tissues (22) were identified. Immunohistochemistry was performed for programmed death ligand 1, programmed death ligand 2, and CD8 and scored for membranous staining on adrenal and stromal tissue according to the immunoreactive score and absolute percentage, respectively. Descriptive statistics, a Mann-Whitney U test, and Fisher exact tests were calculated. RESULTS: In total, 15 adrenocortical carcinoma (44%) stained positive for programmed death ligand 2 and 1 adrenocortical carcinoma for programmed death ligand 1 (P = .03). Adrenocortical carcinoma samples were more likely to express programmed death ligand 2 on tumor cells or in stromal tissues than benign samples (OR = 2.3, P = .03). There was no relationship between programmed death ligand 2 and CD8 expression (P = .08). There were also no relationships between programmed death ligand 2 or CD8 expression and tumor characteristics. CONCLUSION: Programmed death ligand 2, but not programmed death ligand 1, is expressed commonly in adrenocortical carcinoma samples. The utility of certain checkpoint inhibitors should, therefore, be evaluated in further studies.