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Many patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for appendiceal adenocarcinoma peritoneal metastases (APM) undergo preoperative systemic chemotherapy. The primary aim of this study is to evaluate differences in oncologic outcomes among two popular chemotherapy approaches in patients with APM undergoing CRS-HIPEC.We performed a multicenter retrospective review of patients who underwent CRS-HIPEC for APM due to high or intermediate grade disease between 2013 and 2019. Patients in the total neoadjuvant therapy group (TNT) received 12 cycles of preoperative chemotherapy. Patients in the "sandwich" chemotherapy group (SAND) received six cycles of preoperative chemotherapy with a maximum of six cycles of postoperative chemotherapy. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS) defined as months from date of first treatment or surgery, respectively.A total of 39 patients were included in this analysis, with 25 (64%) patients in the TNT group and 14 (36%) patients in the SAND group. Patients in the TNT group had a median OS of 62 mo, while median OS in the SAND group was 45 mo (P = 0.01). In addition, patients in the TNT group had significantly longer RFS compared to the SAND group (35 versus 12 mo, P = 0.03). In a multivariable analysis, TNT approach was independently associated with improved OS and RFS.In this multicenter retrospective analysis, a TNT approach was associated with improved overall and recurrence-free survival compared to a sandwiched chemotherapy approach in patients undergoing CRS-HIPEC for high or intermediate grade APM.

As surgical training shifts toward a competency-based paradigm, deliberate practice for procedures must be a point of focus. The purpose of this study was to assess the impact of an educational time-out intervention on educational experience and operative performance in endocrine surgery.For 12 months, third-year general surgery residents used the educational time-out to establish an operative step of focus for thyroidectomy and parathyroidectomy procedures. Data were collected using the System for Improving and Measuring Procedural Learning application and post-rotation surveys. The Zwisch scale was used to classify supervision, with meaningful autonomy defined as passive help or supervision only.Eight residents and 3 attending surgeons performed the educational time-out for a total of 211 operations (93% completion rate). At the end of each rotation, there was improvement in the frequency of goal setting. There was strong agreement (90%) that the intervention strengthened the educational experience. For most cases (52%), the residents were rated at active help. Residents performed a median of 3/6 thyroidectomy steps at meaningful autonomy and a median of 2/5 parathyroidectomy steps at meaningful autonomy. Review of the qualitative data revealed that optimal feedback was provided in 46% of cases.The educational time-out strengthened educational experiences. Stepwise procedural data revealed the varying levels of supervision that exist within an operation. Broader implementation of this intervention could facilitate competency-based procedural education.

Our institution has recently experienced an increase in sledding-related injuries, particularly when towed behind motorized vehicles. The purpose of this study was to characterize injury severity and clinical outcomes between pediatric patients who sustain injuries owing to motorized sledding accidents to aid in injury prevention messaging.This retrospective study queried all patients who presented with a sledding-related injury to a single ACS-verified Level 1 Pediatric Trauma Center located in the Southeastern United States between 01/2015 and 01/2022. Demographics, injury details, and clinical outcomes were compared between two groups: patients towed behind a motorized vehicle (MOTOR) and those who were not (GRAVITY).Of the 67 patients included in our analysis, 15 (22%) were in the MOTOR group. Patients in the MOTOR group presented with significantly higher injury severity (ISS) and lower Glasgow coma scale (GCS) scores. Additionally, patients in this MOTOR group more often received a blood transfusion and intubation, had longer intensive care and overall hospital lengths of stay, and incurred higher hospital costs. In a multivariate analysis, the use of a motorized vehicle to sled was independently associated with increased ISS (OR: 9.7, 95% CI 1.9-17.5; p = 0.02). Two deaths occurred after sledding while being towed behind a motorized vehicle.Children experiencing sledding accidents while being towed by motorized vehicles sustain significantly more severe injuries and require more intensive treatments that together lead to increased hospital costs. These findings provide the framework for community educational initiatives and injury prevention measures to mitigate risk among children engaged in sledding.IV retrospective cohort study.

IMPORTANCE: The clinical significance of gangrenous, suppurative, or exudative (GSE) findings is poorly characterized in children with nonperforated appendicitis. OBJECTIVE: To evaluate whether GSE findings in children with nonperforated appendicitis are associated with increased risk of surgical site infections and resource utilization. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study used data from the Appendectomy Targeted Database of the American College of Surgeons Pediatric National Surgical Quality Improvement Program, which were augmented with operative report data obtained by supplemental medical record review. Data were obtained from 15 hospitals participating in the Eastern Pediatric Surgery Network (EPSN) research consortium. The study cohort comprised children (aged ≤18 years) with nonperforated appendicitis who underwent appendectomy from July 1, 2015, to June 30, 2020. EXPOSURES: The presence of GSE findings was established through standardized, keyword-based audits of operative reports by EPSN surgeons. Interrater agreement for the presence or absence of GSE findings was evaluated in a random sample of 900 operative reports. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day postoperative surgical site infections (incisional and organ space infections). Secondary outcomes included rates of hospital revisits, postoperative abdominal imaging, and postoperative length of stay. Multivariable mixed-effects regression was used to adjust measures of association for patient characteristics and clustering within hospitals. RESULTS: Among 6133 children with nonperforated appendicitis, 867 (14.1%) had GSE findings identified from operative report review (hospital range, 4.2%-30.2%; P

Adrenocortical carcinoma (ACC) is a rare but highly aggressive malignancy. Nearly half of ACC tumours overproduce and secrete adrenal steroids. Excess cortisol secretion, in particular, has been associated with poor prognosis among ACC patients. Furthermore, recent immunotherapy clinical trials have demonstrated significant immunoresistance among cortisol‐secreting ACC (CS‐ACC) patients when compared to their non‐cortisol‐secreting (nonCS‐ACC) counterparts. The immunosuppressive role of excess glucocorticoid therapies and hypersecretion is known; however, the impact of the cortisol hypersecretion on ACC tumour microenvironment (TME), immune expression profiles and immune cell responses remain largely undefined. In this study, we characterized the TME of ACC patients and compared the immunogenomic profiles of nonCS‐ACC and CS‐ACC tumours to assess the impact of differentially expressed genes (DEGs) by utilizing The Cancer Genome Atlas (TCGA) database. Immunogenomic comparison (CS‐ vs. nonCS‐ACC tumour TMEs) demonstrated an immunosuppressive expression profile with a direct impact on patient survival. We identified several primary prognostic indicators and potential targets within ACC tumour immune landscape. Differentially expressed immune genes with prognostic significance provide additional insight into the understanding of potential contributory mechanisms underlying failure of initial immunotherapeutic trials and poor prognosis of patients with CS‐ACC.

The complications encountered in colorectal surgery can be categorized into early and late. The most consequential early complication is anastomotic leak, which can be managed with percutaneous drainage or reoperation, depending on the patient's clinical status. Other early complications include anastomotic bleeding, surgical site infection, ileus, postoperative urinary retention, and stoma-related complications. Most stoma-related complications can be managed without reoperation. Late complications, such as bowel dysfunction, sexual dysfunction, and anastomotic stricture, are usually managed expectantly and should be discussed in the preoperative setting. There is growing interest in prevention of postoperative outcomes with preoperative nutritional supplementation and prehabilitation.

The Necrotizing Enterocolitis Surgery Trial (NEST) highlights the importance of distinguishing necrotizing enterocolitis (NEC) from spontaneous intestinal perforation (SIP) when developing surgical treatment plans. Further research is needed to increase the accuracy of this distinction, but even with our current abilities to do this initial laparotomy appears to be optimal for infants with presumed NEC. The preferred initial operation for those with SIP is more equivocal. Rates of NEC are likely decreasing slowly, whereas those with SIP are not. New imaging modalities, especially ultrasound, are becoming more useful but require more detailed investigation. Understanding the mechanisms causing these two conditions remains of paramount importance.

To evaluate whether redosing antibiotics within an hour of incision is associated with a reduction in incisional surgical site infection (iSSI) in children with appendicitis.Existing data remain conflicting as to whether children with appendicitis receiving antibiotics at diagnosis benefit from antibiotic redosing prior to incision.This was a multicenter retrospective cohort study using data from the Pediatric National Surgical Quality Improvement Program augmented with antibiotic utilization and operative report data obtained though supplemental chart review. Children undergoing appendectomy at 14 hospitals participating in the Eastern Pediatric Surgery Network from 7/2016-6/2020 who received antibiotics upon diagnosis of appendicitis between 1-6 hours prior to incision were included. Multivariable logistic regression was used to compare odds of iSSI in those who were and were not redosed with antibiotics within one hour of incision, adjusting for patient demographics, disease severity, antibiotic agents, and hospital-level clustering of events.3,533 children from 14 hospitals were included. Overall, 46.5% were redosed (hospital range: 1.8%-94.4%, P0.001) and iSSI rates were similar between groups (redosed: 1.2% vs. non-redosed: 1.3%; OR 0.84, [95%CI 0.39-1.83]). In subgroup analyses, redosing was associated with lower iSSI rates when cefoxitin was used as the initial antibiotic (redosed: 1.0% vs. non-redosed: 2.5%; OR 0.38, [95%CI 0.17-0.84]), but no benefit was found with other antibiotic regimens, longer periods between initial antibiotic administration and incision, or with increased disease severity.Redosing of antibiotics within one hour of incision in children who received their initial dose within 6 hours of incision was not associated with reduction in risk of incisional site infection unless cefoxitin was used as the initial antibiotic.

The primary aim of this study is to evaluate the oncologic outcomes of two popular systemic chemotherapy approaches in patients with colorectal peritoneal metastases (CPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).We performed a dual-center retrospective review of consecutive patients who underwent CRS-HIPEC for CPM due to high or intermediate-grade colorectal cancer. Patients in the total neoadjuvant therapy (TNT) group received 6 months of preoperative chemotherapy. Patients in the "sandwich" (SAND) chemotherapy group received 3 months of preoperative chemotherapy with a maximum of 3 months of postoperative chemotherapy.A total of 34 (43%) patients were included in the TNT group and 45 (57%) patients in the SAND group. The median overall survival (OS) in the TNT and SAND groups were 77 and 61 months, respectively (p = 0.8). Patients in the TNT group had significantly longer recurrence-free survival (RFS) than the SAND group (29 vs. 12 months, p = 0.02). In a multivariable analysis, the TNT approach was independently associated with improved RFS.In this retrospective study, a TNT approach was associated with improved RFS, but not OS when compared with a SAND approach. Further prospective studies are needed to examine these systemic chemotherapeutic approaches in patients with CPM undergoing CRS-HIPEC.

This case details the presentation and surgical management of a 15-year-old male patient with multiple endocrine neoplasia syndrome type 1 (MEN1) who required distal pancreatectomy for multiple nonfunctional pancreatic tumors. An intraoperative ultrasound was utilized to allow for proper location of the distal pancreatectomy, as well as visualization of the splenic vessel relationships and to ensure all lesions were contained within the specimen. Pathology demonstrated 5 well-differentiated neuroendocrine tumors with no evidence of malignancy. This case utilized innovative technology and a multidisciplinary approach in a challenging case to achieve a safe minimally invasive resection. The use of ultrasound intraoperatively provided confidence that all lesions had been identified, as well as demonstration of safe planes separate from the nearby vasculature.

Supplemental Table 1. Five mice lacking intestinal SMAD4 expression ("KO") and five littermate control mice ("WT") had their colon microbiome composition compared. 16S targeted sequencing was performed on mouse stool pellets ("Pellet") and colon mucosal scrapings ("Scraping") and compared at the phylum, class, order, family, genus, and species levels. Values represent proportion of organisms detected per sample. Genotypes were split evenly between sexes. The five female mice were co-housed and the five male mice were co-housed, with bedding mixed between cages weekly., This research was funded in part by National Cancer Institute grants (F32 CA236309; T32 CA106183; R01 CA235016), the Burroughs Wellcome Fund Physician-Scientist Institutional Award #1018894/Vanderbilt Supporting Careers in Research for Interventional Physicians and Surgeons (SCRIPS), the Vanderbilt Ingram Cancer Center (VICC) grant (P30 CA068485), the Vanderbilt Digestive Diseases Research Center Grant (P30 DK058404), and the Department of Veterans Affairs Career Development Award (IK2BX004648).

Full-thickness diaphragm resection (FT-DR) during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is sometimes required to achieve a complete cytoreduction. It is conventionally performed with electrocautery with primary repair or mesh repair. FT-DR using a linear cutting stapler is a novel technique that avoids entry to the chest cavity and minimizes the use of electrocautery on the diaphragm. We performed an institutional retrospective review of a prospectively maintained database of 145 patients who underwent CRS-HIPEC between 2013 and 2019. Patients were divided into the Conventional or Stapled group based on the FT-DR approach indicated in the operative report. Of the 145 patients who underwent CRS-HIPEC, 27 underwent FT-DR, with 63% (n = 17) in the Stapled group. There were no significant demographic or oncologic differences between the 2 groups. Patients in the Stapled group underwent tube thoracostomy (13.3% vs 60%; p = 0.008), were diagnosed with pneumonia (12% vs 50%; p = 0.04), required reintubation (6% vs 40%; p = 0.03), and required mechanical ventilation more than 48 hours (6% vs 50%; p = 0.02) less frequently than the Conventional group. There was no difference in pleural recurrence between the 2 groups (Conventional 20% vs Stapled 12%, p = 0.56). Stapled full-thickness diaphragm resection is a novel approach to achieving a complete cytoreduction that excludes the pleural cavity, minimizes diaphragm manipulation, and is associated with improved postoperative pulmonary outcomes in patients undergoing CRS-HIPEC.

Background & AimsChronic inflammation in the colon is a predisposing factor for colon cancer. We previously reported that colon epithelial cell silencing of Smad4, the central downstream mediator of TGFβ family signaling, increased epithelial expression of inflammatory genes, including the chemokine CCL20, and increased susceptibility to colitis-associated cancer. Here, we examine the role of the chemokine/receptor pair CCL20/CCR6 in mediating colitis-associated colon carcinogenesis induced by SMAD4 loss.MethodsMice with conditional, epithelial-specific Smad4 loss with and without germline deletion of the Ccr6 gene were subjected to three rounds of dextran sodium sulfate and followed for up to 3 months. Tumors were quantified histologically, and immune cell populations were analyzed by flow cytometry and immunostaining.ResultsIn humans, SMAD4 expression inversely correlated with CCL20 expression. Smad4 loss in mouse colon epithelium led to enlarged gut-associated lymphoid tissues and recruitment of specific immune cell subsets to the mouse colon epithelium and underlying stroma, particularly Treg, Th17, and dendritic cells. Loss of CCR6 abrogated these immune responses and significantly reduced the incidence of colitis-associated tumors observed with loss of SMAD4 alone.ConclusionsRegulation of mucosal inflammation is a critical role of SMAD4 signaling within the colon epithelium and central to its tumor suppressor function in the colon. A key downstream node in this regulation is suppression of CCL20 signaling by the epithelium to CCR6 in immune cells. Loss of SMAD4 in the colon epithelium increases CCL20 expression and chemoattraction of CCR6+ immune cells, contributing to greater susceptibility to colon cancer.

Background Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) among patients with peritoneal carcinomatosis (PC) depend largely on the extent of peritoneal disease. Since PC is not reliably evaluated with cross-sectional imaging, tumor burden is often evaluated with diagnostic laparoscopy (DLS). The aims of this study are to evaluate the safety of DLS in patients with peritoneal disease and determine if DLS delays time to CRS-HIPEC. Methods We performed an institutional retrospective review of 145 patients who underwent CRS-HIPEC between 2013 and 2020. Patients were divided into 2 groups: those who underwent an electively scheduled DLS prior to CRS-HIPEC and those who did not. Intraoperative and postoperative complications associated with DLS were determined from the surgeon’s operative report. Time from diagnosis of PC to CRS-HIPEC was compared between the 2 groups. Results Of the 145 patients available for analysis, 47% (68) underwent DLS and 44% (64) did not. Of all the diagnostic laparoscopies performed, there was 1 (1.5%) intraoperative complication. The duration between diagnosis of peritoneal carcinomatosis and surgery was 4.9 months among patients who underwent DLS prior to CRS-HIPEC and 4.3 months among patients who did not ( P = .79). Conclusion In this retrospective analysis, diagnostic laparoscopy prior to CRS-HIPEC demonstrated a comparable rate of DLS-associated complications compared to other gastrointestinal malignancies and does not prolong time from diagnosis to CRS-HIPEC. Thus, in patients undergoing evaluation for CRS-HIPEC, diagnostic laparoscopy provides significant value in patient selection without incurring perioperative risk or delay in CRS-HIPEC.

The complications encountered in colorectal surgery can be categorized into early and late. The most consequential early complication is anastomotic leak, which can be managed with percutaneous drainage or reoperation, depending on the patient's clinical status. Other early complications include anastomotic bleeding, surgical site infection, ileus, postoperative urinary retention, and stoma-related complications. Most stoma-related complications can be managed without reoperation. Late complications, such as bowel dysfunction, sexual dysfunction, and anastomotic stricture, are usually managed expectantly and should be discussed in the preoperative setting. There is growing interest in prevention of postoperative outcomes with preoperative nutritional supplementation and prehabilitation.

BACKGROUND The effects of blood transfusions on oncologic outcomes after surgery remain inconclusive. Thus, we examined the association between receiving a perioperative blood transfusion and oncologic outcomes in patients undergoing curative rectal cancer resection. OBJECTIVE The purpose of this study was to assess the association between receiving a perioperative blood transfusion with disease-free and overall survival in patients undergoing curative resection of clinical stage I to III rectal cancer. We hypothesized that blood transfusion is associated with worse disease-free and overall survival in this patient cohort. DESIGN This was a retrospective cohort study using a propensity score-matched analysis. SETTINGS The study involved 6 tertiary academic medical centers in the United States contributing to the United States Rectal Cancer Consortium. PATIENTS Patients who underwent curative resection for rectal cancer from 2010 to 2018 were included. MAIN OUTCOME MEASURES The primary outcome was disease-free survival. The secondary outcomes were overall survival, intensive care unit length of stay, hospital length of stay, surgical site infection, and readmission. RESULTS Of the 924 patients eligible for matching, 312 patients were matched, including 100 patients who received a transfusion and 212 who did not. In a propensity score-matched analysis, receiving a perioperative blood transfusion was not associated with worse 5-year disease-free survival (transfused, 78%; not transfused, 83%; p = 0.32) but was associated with worse 5-year overall survival (transfused 65% vs not transfused 86%; p < 0.001) and increased hospital length of stay (transfused, 9.9 d; not transfused, 7.6 d; p = 0.001). LIMITATIONS Despite propensity matching, confounding may remain. Propensity matching may limit the power to detect a difference in disease-free survival. CONCLUSIONS Receiving a perioperative blood transfusion is not associated with worse disease-free survival but is associated with worse overall survival. Such findings are important for clinicians and patients to understand when considering perioperative blood transfusions. See Video Abstract at http://links.lww.com/DCR/B531. LAS TRANSFUSIONES DE SANGRE PERIOPERATORIAS SE ASOCIAN CON UNA PEOR SOBREVIDA GLOBAL, PERO NO CON LA SOBREVIDA LIBRE DE ENFERMEDAD POSTERIOR A LA RESECCIN CURATIVA DEL CNCER DE RECTO UN PUNTAJE DE PROPENSIN POR ANLISIS DE CONCORDANCIA ANTECEDENTES:El impacto de las transfusiones de sangre en los resultados oncologicos posteriores a la cirugia no son concluyentes. Por lo anterior, estudiamos la asociacion entre recibir una transfusion de sangre perioperatoria y los resultados oncologicos en pacientes llevados a reseccion curativa de cancer de recto.OBJETIVO:El proposito de este estudio fue evaluar la asociacion entre recibir una transfusion de sangre perioperatoria con la sobrevida libre de enfermedad y la sobrevida general en pacientes llevados a reseccion curativa de cancer de recto en estadio clinico I-III. Nuestra hipotesis es que la transfusion de sangre se asocia con una peor sobrevida global y libre de enfermedad en esta cohorte de pacientes.DISENO:Es un estudio de cohorte retrospectivo que utilizo un puntaje de propension por analisis de concordancia.AMBITO:El estudio se realizo en seis centros medicos academicos de tercer nivel en los Estados Unidos que contribuian al Consorcio de Cancer de Recto de los Estados Unidos.PACIENTES:Se incluyeron pacientes que fueron llevados a reseccion curativa por cancer de recto entre 2010 y 2018.PRINCIPALES VARIABLES EVALUADAS:El objeitvo principal fue la sobrevida libre de enfermedad. Los objetivos secundarios fueron la sobrevida global, el tiempo de estancia en la unidad de cuidados intensivos, el tiempo de la estancia hospitalaria, la infeccion del sitio quirurgico y el reingreso.RESULTADOS:De los 924 pacientes elegibles para el emparejamiento, se emparejaron 312 pacientes, incluidos 100 pacientes que recibieron una transfusion y 212 que no. En el puntaje de propension por analisis de concordancia, recibir una transfusion de sangre perioperatoria no se asocio con una peor sobrevida libre de enfermedad a 5 anos (TRANSFUSION 78%; NO TRANSFUSION 83%; p = 0,32), pero se asocio con una peor sobrevida global a 5 anos (TRANSFUSION 65% vs NO TRANSFUSION 86%; p

BACKGROUND: A growing body of research has shown that underinsured patients are at increased risk of worse health outcomes compared to insured patients. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is performed largely at highly specialized cancer centers and may pose challenges for the underinsured. This study investigates surgical outcomes following CRS-HIPEC for insured and underinsured patients with peritoneal carcinomatosis. METHODS: We performed a retrospective cohort study of 125 patients undergoing CRS-HIPEC between 2013–2019. Patients were categorized into two groups. The insured group was comprised of patients with private insurance at the time of CRS-HIPEC or who obtained it during the follow-up period, while the underinsured group consisted of patients with Medicare, Medicaid, or self-pay. Perioperative and oncologic outcomes were compared between the two groups. RESULTS: A total of 102 (82.3%) patients were insured and 22 (17.7%) patients were underinsured. There were no significant differences in age, medical morbidities, primary tumor characteristics, peritoneal carcinomatosis index, or completion of cytoreduction score between the two groups. The median overall survival (OS) for insured patients was 64.8 months and was 52.9 months for underinsured patients (p=0.01). Additionally, insured patients had a significantly longer follow-up time. Underinsurance status was also associated with increased hospital and intensive care unit length of stay, and higher rate of Clavien-Dindo classification III-IV complications. CONCLUSION: In this retrospective study conducted at a large urban specialized cancer center, private insurance status was associated with increased overall survival and longer follow-up period. Furthermore, underinsurance status was associated with increased perioperative morbidity.

IntroductionImmunotherapeutic response failure of adrenocortical carcinomas (ACC) highlights a need for novel strategies targeting immune cell populations in the tumor microenvironment (TME) to overcome tumor resistance and enhance therapeutic response. A recent study explored a new link between tumor mast cell (MC) infiltration and improved outcomes in patients with ACC. We further dissect the role of MC in TME of ACC by examining the tumor MC expression signatures and MC activity within TME to provide additional insight into potential novel immunotherapeutic targets.MethodsUsing CIBERSORTx computational immunogenomic deconvolution algorithm to analyze ACC tumor gene mRNA expression data (TCGA, N=79), we estimated the abundance of tumor immune infiltrating MC, and assessed prognostic potential of MC signaling genes as pro- or anti- tumor signatures, as well as the impact on overall (OS) and disease-free (DFS) survival.ResultsWe stratified MC signaling genes with survival prognostic values (OS, DFS, pConclusionThe deconvolution analysis of TCGA data identified MC infiltration in ACC microenvironment as predominantly associated with anti-tumor activity. Future studies stemming from our findings may help define the role of MC in TME and the impact on patient survival in patients with ACC. Modulation of tumor MC infiltration may serve as a potential target for novel synergistic immunotherapies for the treatment and improved survival of patients with ACC.

BACKGROUND: Immunotherapeutic response failure of adrenocortical carcinomas highlights a need for novel strategies targeting immune cell populations in the tumor microenvironment to overcome tumor resistance and enhance therapeutic response. A recent study explored a new link between tumor mast cell infiltration and improved outcomes in patients with adrenocortical carcinomas. We further dissect the role of mast cells in the tumor microenvironment of adrenocortical carcinomas by examining the tumor mast cell expression signatures and mast cell activity within the tumor microenvironment to provide additional insight into potential novel immunotherapeutic targets. METHODS: Using the CIBERSORTx computational immunogenomic deconvolution algorithm to analyze adrenocortical carcinoma tumor gene messenger RNA expression data (The Cancer Genome Atlas, N = 79), we estimated the abundance of tumor immune infiltrating mast cells and assessed prognostic potential of mast cell signaling genes as pro or antitumor signatures, as well as examined the impact on overall and disease-free survival. RESULTS: We stratified mast cell signaling genes with survival prognostic values (overall survival, disease-free survival, P < .05) into antitumor (ALOX5, CCL2, CCL5, CXCL10, HDC, IL16, TNF, TPSAB1, VEGFD) and protumor (CXCL1, CXCL3, CXCL8, IL4, IL13, PTGS3, TNSF4, VEGFD) groups. Antitumor mast cell signature, as the predominant phenotype, was associated with improved overall and disease-free survival. CONCLUSION: The deconvolution analysis of The Cancer Genome Atlas data identified mast cell infiltration in the adrenocortical carcinoma microenvironment as predominantly associated with antitumor activity. Future studies stemming from our findings may help define the role of mast cells in the tumor microenvironment and the impact on patient survival in patients with adrenocortical carcinomas. Modulation of tumor mast cell infiltration may serve as a potential target for novel synergistic immunotherapies for the treatment and improved survival of patients with adrenocortical carcinomas.

Adrenocortical carcinoma (ACC) is a rare but highly aggressive malignancy and nearly half of ACC tumors have been shown to overproduce and secrete adrenal steroids. Excess cortisol secretion, in particular, has been associated with poor prognosis among ACC patients. Furthermore, recent immunotherapy clinical trials demonstrated significant immunoresistance among cortisol-secreting ACC (CS-ACC) patients when compared to their non-Cortisol-secreting (nonCS-ACC) counterparts. The immunosuppressive role of excess glucocorticoid therapies and secretion is well established, however, the impact of the cortisol hypersecretion on ACC tumor microenvironment (TME), immune expression profiles, and immune cell responses remain largely undefined. In this study, we characterized the TME of ACC patients and compared the immunogenomic profiles of nonCS-ACC and CS-ACC tumors to assess the impact of differentially expressed genes (DEGs) related to immune processes on patient prognosis. Comprehensive multiplatform immunogenomic computational analyses of ACC tumors deciphered an immunosuppressive expression profile with a direct impact on patient survival. We identified several primary immunogenomic prognostic indicators and potential targets within the tumor immune landscape of CS-ACC that define a distinct TME and provide additional insight into the understanding of potential contributory mechanisms underlying failure of initial immunotherapeutic trials and poor prognosis of patients with CS-ACC.

A tracheal bronchus is a rare anatomic variant characterized by a bronchus originating from the trachea rather than the carina. These are most commonly asymptomatic and found incidentally but can cause recurrent pneumonias in children. Here, we present a case of a thoracoscopic resection of an azygous lobe with a tracheal bronchus in a 9-year-old female.