A narrative review of sociodemographic risk and disparities in screening, diagnosis, treatment, and outcomes of the most common extrathoracic malignancies in the United States.

There is a well-established association between multiple sociodemographic risk factors and disparities in cancer care. These risk factors include minority race and ethnicity, low socioeconomic status (SES) including low income and education level, non-English primary language, immigrant status, and residential segregation, and distance to facilities that deliver cancer care. As cancer care advances, existing disparities in screening, treatment, and outcomes have become more evident. Lung cancer remains the most common and fatal malignancy in the United States, with breast, colorectal, and prostate cancer being the three most common and deadly extrathoracic malignancies. Achieving the best outcomes for patients with these malignancies relies on strong physician-patient relationships leading to robust screening, early diagnosis, and early referral to facilities that can deliver multidisciplinary care and multimodal therapy. It is likely that challenges experienced in developing patient trust and understanding, providing access to screening, and building referral pipelines for definitive therapy in lung cancer care to vulnerable populations are paralleled by those in extrathoracic malignancies. Likewise, progress made in delivering optimal care to all patients across sociodemographic and geographic barriers can serve as a roadmap. Therefore, we provide a narrative review of current disparities in screening, treatment, and outcomes for patients with breast, prostate, and colorectal malignancies.

Prevention of Postoperative Prolonged Air Leak After Pulmonary Resection.

Postoperative prolonged air leaks (PALs) occur after thoracic surgery in which lung parenchyma is resected, divided, or manipulated. These air leaks can place patients at risk for intensive care unit readmissions, longer hospital length of stay, and infectious complications. Studies have been conducted to identify patients who are at risk for air leak and several methods have been examined for the prevention and treatment of PALs. A standard method of air leak prevention or treatment has not been established. This article discusses the prophylactic measures that have been studied for the prevention of PALs following lung surgery.

Presentation, Treatment, and Outcomes of Vulnerable Populations With Esophageal Cancer Treated at a Safety-Net Hospital.

Social determinants of health have been associated with poor outcomes in esophageal cancer. Primary language and immigration status have not been examined in relation to esophageal cancer outcomes. This study aims to investigate the impact of these variables on stage of presentation, treatment, and outcomes of esophageal cancer patients at an urban safety-net hospital. Clinical data of patients with esophageal cancer at our institution between 2003 and 2018 were reviewed. Demographic, tumor, and treatment characteristics were obtained. Outcomes included median overall survival, stage-specific survival, and utilization of surgical and perioperative therapy. Statistical analysis was conducted using Chi-square test, Fisher's exact tests, Kaplan-Meier method, and logistic regression. There were 266 patients; 77% were male. Mean age was 63.9 years, 23.7% were immigrants, 33.5% were uninsured/Medicaid, and 16.2% were non-English speaking. Adenocarcinoma was diagnosed in 55.3% and squamous cell in 41.0%. More patients of non-Hispanic received esophagectomies when compared to those of Hispanic origin (64% vs 25%, P = 0.012). Immigrants were less likely to undergo esophagectomy compared to US-born patients (42% vs 76%, P = 0.001). Patients with adenocarcinoma were more likely than squamous cell carcinoma patients to undergo esophagectomy (odds ratio = 4.40, 95% confidence interval 1.61-12.01, P = 0.004). More commercially/privately insured patients (75%) received perioperative therapy compared to Medicaid/uninsured (54%) and Medicare (49%) patients (P = 0.030). There was no association between demographic factors and the utilization of perioperative chemoradiation for patients with operable disease. Approximately 23% of patients with operable disease were too frail or declined to undergo surgical intervention. In this small single-center study, race and primary language were not associated with median survival for patients treated for esophageal cancer. US-born patients experienced higher surgical utilization and privately insured patients were more likely to receive perioperative therapy. Many patients with operable cancer were too frail to undergo a curative surgery. Studies should expand on the relationships between social determinants of health and nonclinical services on delivery of care and survival of vulnerable populations with esophageal cancer.

Evaluation of incidental adrenal masses at a tertiary referral and trauma center.

BACKGROUND: Incidental adrenal masses are those that are found on imaging performed for any nonadrenal evaluation. Published guidelines define accepted follow-up criteria for incidental adrenal masses; however, adherence to these guidelines and barriers to appropriate follow-up are not well understood. We aimed to describe practice patterns for the discovery, evaluation, and follow-up of incidental adrenal masses. METHODS: Medical records of patients with an incidental adrenal mass underwent retrospective review at a tertiary referral and level-1 trauma center, as well as regional ambulatory care locations. Individuals ≥18 years of age with an incidental adrenal mass identified during 2016 were included. Patterns of evaluation, follow-up, and associated adrenal diagnoses were determined. RESULTS: From a total of 19,171 cross-sectional imaging procedures (computed tomography and magnetic resonance imaging), 244 patients with new incidental adrenal masses were identified. A majority (52%) were discovered as part of an evaluation in the emergency department. Of 153 patients with an identifiable primary care provider, approximately 75% had an in-network primary care provider, and 12 (7.8%) had both follow-up imaging and biochemical evaluation. Twenty-three percent of patients with an in-network primary care provider underwent an appropriate cross-sectional imaging procedure in follow-up compared to 29% for a non-network primary care provider (P = .54). Patients with a mass described with benign terminology were less likely to undergo follow-up imaging compared to those with indeterminate terminology (5% vs 37%, P < .001). Patients with imaging ordered as an outpatient were more likely to receive follow-up with imaging (22.8% outpatient vs 11.5% inpatient, P = .042). There was no difference between any groups regarding biochemical evaluation, which inappropriately was performed in only 15% of patients with an incidental adrenal mass. CONCLUSION: To optimize follow-up of incidental adrenal masses, efforts should be made to assure and prioritize inpatient/emergency department incidental findings and to communicate to the appropriate primary care provider the necessary next steps for evaluation. Further, efforts to increase biochemical testing should be pursued.

Impact of Race, Insurance Status, and Primary Language on Presentation, Treatment, and Outcomes of Patients with Pancreatic Adenocarcinoma at a Safety-Net Hospital.

BACKGROUND: Social determinants of health impact the delivery of care and outcomes in patients with pancreatic cancer. We explored the relationship between social determinants of health and presentation, treatment, and outcomes of patients with pancreatic adenocarcinoma at an urban safety-net medical center. DESIGN: A single-institution retrospective chart review of patients with pancreatic adenocarcinoma was conducted. Demographic, tumor, and treatment characteristics were obtained. Median overall survival, stage-specific survival, receipt of curative operation, and receipt of perioperative therapy were analyzed. Chi-square tests were used for categorical variables. Survival was determined by the Kaplan-Meier method. RESULTS: We identified 240 patients with pancreatic adenocarcinoma treated between January 2006 and December 2017. Median age was 66 years, 51% were female, 48% were non-white, 22% were non-English-speaking, 16% were Hispanic, and 40% were Medicaid/uninsured. There were 74 (31%) patients with early-stage (I/II) disease. There were no statistically significant differences between race, primary language, or ethnicity and receipt of surgical therapy or receipt of perioperative therapy. Relatively more patients with private insurance (100%) received perioperative therapy compared with Medicaid/uninsured (64%) and Medicare-insured (50%) patients (p = 0.018). Nearly 30% of patients with operable disease either declined having an intervention or were found to be too frail to undergo surgical intervention. CONCLUSIONS: There were no statistically significant relationships between examined social determinants of health and use of operation or perioperative therapy. Patients treated at an urban safety-net hospital with a focus on vulnerable patient populations are able to provide outcomes similar to national averages. Additional exploration of factors affecting outcomes for pancreatic cancer in these patients will be important, as many centers absorb higher immigrant and indigent populations.

Detection of Circulating Tumor DNA in Plasma: A Potential Biomarker for Esophageal Adenocarcinoma.

BACKGROUND: Recent literature has demonstrated the potential of "liquid biopsy" and detection of circulating tumor (ct)DNA as a cancer biomarker. However, to date there is a lack of data specific to esophageal adenocarcinoma (EAC). This study was conducted to determine how detection and quantification of ctDNA changes with disease burden in patients with EAC and evaluate its potential as a biomarker in this population. METHODS: Blood samples were obtained from patients with stage I to IV EAC. Longitudinal blood samples were collected from a subset of patients. Imaging studies and pathology reports were reviewed to determine disease course. Tumor samples were sequenced to identify mutations. Mutations in plasma DNA were detected using custom, barcoded, patient-specific sequencing libraries. Mutations in plasma were quantified, and associations with disease stage and response to therapy were explored. RESULTS: Plasma samples from a final cohort of 38 patients were evaluated. Baseline plasma samples were ctDNA positive for 18 patients (47%) overall, with tumor allele frequencies ranging from 0.05% to 5.30%. Detection frequency of ctDNA and quantity of ctDNA increased with stage. Data from longitudinal samples indicate that ctDNA levels correlate with and precede evidence of response to therapy or recurrence. CONCLUSIONS: ctDNA can be detected in plasma of EAC patients and correlates with disease burden. Detection of ctDNA in early-stage EAC is challenging and may limit diagnostic applications. However, our data demonstrate the potential of ctDNA as a dynamic biomarker to monitor treatment response and disease recurrence in patients with EAC.

Esophageal Cancer Presentation, Treatment, and Outcomes Vary With Hospital Safety-Net Burden.

BACKGROUND: Social determinants of health affect diagnosis and delivery of care to patients with esophageal cancer. This study hypothesized that hospital safety-net burden affects presentation, treatment, and outcomes in patients with esophageal cancer. METHODS: The National Cancer Database was queried for patients with esophageal cancer (2004 to 2013). Treating facilities were categorized according to their relative burden of uninsured or Medicaid-insured patients. Hospitals with low (LBH), medium (MBH), and high (HBH) safety-net burden were compared with respect to patient demographics, disease and treatment characteristics, and survival using χ2 analysis, Kaplan-Meier survival analysis, and multivariable modeling. RESULTS: There were 56,115 patients from 1,215 facilities. HBH treated a greater proportion of racial and ethnic minorities and patients with lower socioeconomic status. Patients at HBH presented at later stages and received primary surgical therapy less often than at MBH and LBH. Survival for patients with esophageal adenocarcinoma did not differ significantly between HBH and LBH after adjusting for age, sex, race, ethnicity, income, comorbidity, stage, histologic type, tumor location, facility type, insurance status, and treatment modality (hazard ratio, 1.06; 95% confidence interval, 0.99 to 1.14; p = 0.093). HBH were associated with a higher mortality risk than LBH for patients with squamous cell carcinoma (hazard ratio, 1.11; 95% confidence interval, 1.02 to 1.20; p = 0.014). CONCLUSIONS: There is a mortality risk for patients with squamous cell carcinoma, but not for adenocarcinoma at HBH compared with LBH. Further analysis of unadjusted variables such as performance status, completion of therapy, and continuity of care, and others should be undertaken among safety-net hospitals with the goal of creating appropriate clinical pathways for care of esophageal cancer in vulnerable populations.

Plasma circulating tumor DNA as a potential tool for disease monitoring in head and neck cancer.

BACKGROUND: Recommendations for perioperative therapy in head and neck cancer are not explicit and recurrence occurs frequently. Circulating tumor DNA is an emerging cancer biomarker, but has not been extensively explored for detection of recurrence in head and neck cancer. METHODS: Patients diagnosed with head and neck squamous cell carcinoma were recruited into the study protocol. Tumors were sequenced to identify patient-specific mutations. Mutations were then identified in plasma circulating tumor DNA from pre-treatment blood samples and longitudinally during standard follow-up. Circulating tumor DNA status during follow-up was correlated to disease recurrence. RESULTS: Samples were taken from eight patients. Tumor mutations were verified in seven patients. Baseline circulating tumor DNA was positive in six patients. Recurrence occurred in four patients, two of whom had detectable circulating tumor DNA prior to recurrence. CONCLUSION: Circulating tumor DNA is a potential tool for disease and recurrence monitoring following curative therapy in head and neck cancer, allowing for better prognostication, and/or modification of treatment strategies.

Educator and Trainee Perspectives on the Need for a "Real World" Curriculum in General Surgery.

BACKGROUND: The necessity of a nonclinical education for surgery residents is a topic of exploration. We examine chief resident (CR) and program director (PD) perspectives on the need for a standardized nonclinical curriculum. METHODS: PDs and CRs from accredited general surgery programs were solicited to partake in an anonymous survey. Data were analyzed using descriptive statistics. RESULTS: There were 42 PD and 68 CR responses. Half or more CRs lack confidence to independently determine their own worth, find a job, negotiate a contract, select disability insurance, and formulate retirement plans. PDs recognize that education in several nonclinical topics is essential for surgical residents. CRs and PDs agree on the necessity for formal education on all topics except "Burnout" (P < 0.0001). CONCLUSIONS: CRs lack the confidence to navigate several nonclinical topics. PDs recognize that education in these topics is necessary. PDs and CRs agree on the need for a nonclinical education except for "Burnout", indicating a positive change in education over time, as most CRs feel they are educated adequately on this topic. Validation of a uniform curriculum is needed.

Percutaneous thermal ablation for stage IA non-small cell lung cancer: long-term follow-up.

BACKGROUND: Surgical resection is the most effective curative therapy for non-small cell lung cancer (NSCLC). However, many patients are unable to tolerate resection secondary to poor reserve or comorbid disease. Radiofrequency ablation (RFA) and microwave ablation (MWA) are methods of percutaneous thermal ablation that can be used to treat medically inoperable patients with NSCLC. We present long-term outcomes following thermal ablation of stage IA NSCLC from a single center. METHODS: Patients with stage IA NSCLC and factors precluding resection who underwent RFA or MWA from July 2005 to September 2009 were studied. CT and PET-CT scans were performed at 3 and 6 month intervals, respectively, for first 24 months of follow-up. Factors associated with local progression (LP) and overall survival (OS) were analyzed. RESULTS: Twenty-one patients underwent 21 RFA and 4 MWA for a total of 25 ablations. Fifteen patients had T1a and six patients had T1b tumors. Mean follow-up was 42 months, median survival was 39 months, and OS at three years was 52%. There was no significant difference in median survival between T1a nodules and T1b nodules (36 vs. 39 months, P=0.29) or for RFA and MWA (36 vs. 50 months, P=0.80). Ten patients had LP (47.6%), at a median time of 35 months. There was no significant difference in LP between T1a and T1b tumors (22 vs. 35 months, P=0.94) or RFA and MWA (35 vs. 17 months, P=0.18). Median OS with LP was 32 months compared to 39 months without LP (P=0.68). Three patients underwent repeat ablations. Mean time to LP following repeat ablation was 14.75 months. One patient had two repeat ablations and was disease free at 40-month follow-up. CONCLUSIONS: Thermal ablation effectively treated or controlled stage IA NSCLC in medically inoperable patients. Three-year OS exceeded 50%, and LP did not affect OS. Therefore, thermal ablation is a viable option for medically inoperable patients with early stage NSCLC.

Basal-A Triple-Negative Breast Cancer Cells Selectively Rely on RNA Splicing for Survival.

Prognosis of triple-negative breast cancer (TNBC) remains poor. To identify shared and selective vulnerabilities of basal-like TNBC, the most common TNBC subtype, a directed siRNA lethality screen was performed in 7 human breast cancer cell lines, focusing on 154 previously identified dependency genes of 1 TNBC line. Thirty common dependency genes were identified, including multiple proteasome and RNA splicing genes, especially those associated with the U4/U6.U5 tri-snRNP complex (e.g., PRPF8, PRPF38A). PRPF8 or PRPF38A knockdown or the splicing modulator E7107 led to widespread intronic retention and altered splicing of transcripts involved in multiple basal-like TNBC dependencies, including protein homeostasis, mitosis, and apoptosis. E7107 treatment suppressed the growth of basal-A TNBC cell line and patient-derived basal-like TNBC xenografts at a well-tolerated dose. The antitumor response was enhanced by adding the proteasome inhibitor bortezomib. Thus, inhibiting both splicing and the proteasome might be an effective approach for treating basal-like TNBC. Mol Cancer Ther; 16(12); 2849-61. ©2017 AACR.

Regional Delivery of Chimeric Antigen Receptor (CAR) T-Cells for Cancer Therapy.

Chimeric Antigen Receptor (CAR) T-cells are T-cells with recombinant receptors targeted to tumor antigens. CAR-T cell therapy has emerged as a mode of immunotherapy and is now being extensively explored in hematologic cancer. In contrast, CAR-T cell use in solid tumors has been hampered by multiple obstacles. Several approaches have been taken to circumvent these obstacles, including the regional delivery of CAR-T cells. Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery. We reviewed completed clinical trials for the treatment of glioblastoma and metastatic colorectal cancer and examined the data in these studies for safety, efficacy, and potential advantages that regional delivery may confer over systemic delivery. Our appraisal of the available literature revealed that regional delivery of CAR-T cells in both glioblastoma and hepatic colorectal metastases was generally well tolerated and efficacious in select instances. We propose that the regional delivery of CAR-T cells is an area of potential growth in the solid tumor immunotherapy, and look towards future clinical trials in head and neck cancer, mesothelioma, and peritoneal carcinomatosis as the use of this technique expands.

miRNA profiling of primary lung and head and neck squamous cell carcinomas: Addressing a diagnostic dilemma.

OBJECTIVE: To determine whether microRNA (miRNA) profiling of primary lung and head and neck squamous cell carcinomas could be useful to identify a specific miRNA signature that can be used to further discriminate between primary lung squamous carcinomas and metastatic lesions in patients with a history of head and neck squamous cell cancer. METHODS: Specimens of resected primary head and neck and lung squamous cell carcinomas were obtained from formalin-fixed, paraffin-embedded blocks. Paraffin blocks were sectioned and deparaffinized, and total RNA was isolated and profiled. Quantitative polymerase chain reaction was performed to verify array results. RESULTS: Twelve head and neck and 16 lung squamous cell carcinoma samples met quality control metrics and were included for analysis. Forty-eight miRNAs were differentially expressed (P < .05) between the 2 groups. Of these, 30 were also significantly associated (q < .25) with tumor type in 2 independent sets of primary head and neck and lung squamous carcinomas profiled by The Cancer Genome Atlas consortium, including miR-34a and miR-10a. The ratio of miR-10a and miR-10b was especially predictive of primary cancer site in all 3 data sets, with area under the (receiver operating characteristics) curve values ranging from 0.922 to 0.982. Quantitative polymerase chain reaction confirmed the association of miR-34a expression and the miR-10:miR-10b ratio with tumor type. CONCLUSIONS: MicroRNA expression may be useful for discriminating between head and neck and lung squamous cell carcinomas, including miR-34a and the miR-10a:miR-10b ratio. This differentiation has clinical importance because it could help determine the appropriate therapeutic approach.

Endoscopic Fundoplication: Effectiveness for Controlling Symptoms of Gastroesophageal Reflux Disease.

OBJECTIVE: Transoral incisionless fundoplication (TIF) is a completely endoscopic approach to treat gastroesophageal reflux disease (GERD). We previously reported our initial results demonstrating safety and early effectiveness. We now present an updated experience describing outcomes with longer follow-up. METHODS: For a three-year period, TIF procedures were performed on 80 patients. Preoperative workup routinely consisted of contrast esophagram and manometry. PH testing was reserved for patients with either atypical symptoms or typical symptoms unresponsive to proton-pump inhibitors (PPIs). Heartburn severity was longitudinally assessed using the GERD health-related quality of life index. Safety analysis was performed on all 80 patients, and an effectiveness analysis was performed on patients with at least 6-month follow-up. RESULTS: Mean procedure time was 75 minutes. There were seven (8.75%) grade 2 complications and one (1.25%) grade 3 complication (aspiration pneumonia). The median length of stay was 1 day (mean, 1.4). Forty-one patients had a minimum of 6-month of follow-up (mean, 24 months; range, 6-68 months). The mean satisfaction scores at follow-up improved significantly from baseline (P < 0.001). Sixty-three percent of patients had completely stopped or reduced their PPI dose. Results were not impacted by impaired motility; however, the presence of a small hiatal hernia or a Hill grade 2/4 valve was associated with reduced GERD health-related quality of life scores postoperatively. CONCLUSIONS: At a mean follow-up of 24 months, TIF is effective. Although symptoms and satisfaction improved significantly, many patients continued to take PPIs. Future studies should focus on longer-term durability and comparisons with laparoscopic techniques.

Bowel Ischemia and Portal Venous Gas: What to Do?

The etiology of pneumatosis and portal venous gas in ischemic colitis is debated, but one theorized cause is transmural ischemia and subsequent bacterial translocation. Traditionally though as a surgical emergency, today not all patients with pneumatosis and portal venous gas need an operation. We have reviewed recent published algorithms and applied them to our practice.

Mediastinal parathyroid adenoma with osteitis fibrosis cystica: robot-assisted thoracic surgical resection.

Mediastinal parathyroid adenomas can be resected by sternotomy or video-assisted thoracoscopic surgery. Robot-assisted thoracic surgical approaches have recently been described. We report robot-assisted thoracic surgical resection of a mediastinal parathyroid in a morbidly obese patient. Additional comorbidities included multiple pathological fractures related to hypercalcemia. Intraoperative parathyroid hormone levels confirmed successful removal of the adenoma. Hungry bone syndrome developed after surgery but eventually resolved. Robot-assisted thoracic surgery avoided the need for sternotomy and associated concerns related to poor bone healing. Robot-assisted thoracic surgery has potential advantages over video-assisted thoracoscopic surgery in patients with obesity because of easier instrument articulation within the thoracic cavity rather than at the chest wall.

FDG PET metabolic tumor volume segmentation and pathologic volume of primary human solid tumors.

OBJECTIVE: The purpose of this study was to establish the correlation and reliability among the pathologic tumor volume and gradient and fixed threshold segmentations of (18)F-FDG PET metabolic tumor volume of human solid tumors. MATERIALS AND METHODS: There were 52 patients included in the study who had undergone baseline PET/CT with subsequent resection of head and neck, lung, and colorectal tumors. The pathologic volume was calculated from three dimensions of the gross tumor specimen as a reference standard. The primary tumor metabolic tumor volume was segmented using gradient and 30%, 40%, and 50% maximum standardized uptake value (SUVmax) threshold methods. Pearson correlation coefficient, intraclass correlation coefficient, and Bland-Altman analyses were performed to establish the correlation and reliability among the pathologic volume and segmented metabolic tumor volume. RESULTS: The mean pathologic volume; gradient-based metabolic tumor volume; and 30%, 40%, and 50% SUVmax threshold metabolic tumor volumes were 13.46, 13.75, 15.47, 10.63, and 7.57 mL, respectively. The intraclass correlation coefficients among the pathologic volume and the gradient-based and 30%, 40%, and 50% SUVmax threshold metabolic tumor volumes were 0.95, 0.85, 0.80, and 0.76, respectively. The Bland-Altman biases were -0.3, -2.0, 2.82, and 5.9 mL, respectively. Of the small tumors (< 10 mL), 23 of the 35 patients had PET segmented volume outside 50% of the pathologic volume, and among the large tumors (≥ 10 mL) three of the 17 patients had PET segmented volumes that were outside 50% of pathologic volume. CONCLUSION: FDG PET metabolic tumor volume estimated using gradient segmentation had superior correlation and reliability with the estimated ellipsoid pathologic volume of the tumors compared with threshold method segmentation.