Exploring Demographic Differences and Outcomes in Early-Onset Colorectal Cancer.

PURPOSE: Early-onset colorectal cancer (EOCRC), defined as CRC diagnosed before age 50 years, has increased significantly worldwide. The majority of EOCRCs do not appear to be driven by genetic factors and may be influenced by environmental factors. We hypothesized that sociodemographic disparities exist in EOCRC. The purpose was of the study was to examine the geographic disparities in patients with EOCRC. METHODS: We retrospectively examined the SEER database from 1976 to 2016 to examine the geographic disparities in EOCRC. A total of 73,378 patients with EOCRC were included in the analysis. We performed univariate and multivariable analyses to evaluate overall survival (OS) and disease-specific survival (DSS). Sociodemographic factors, including the location of residence (metropolitan areas [MA] or rural areas [RA]), sex, race, insurance status, and marital status, were included in the statistical analysis. RESULTS: The incidence and mortality rates were consistently higher in RA versus MA during the study period. Multivariable analysis showed that patients living in RA had worse OS (hazard ratio [HR], 1.14; P < .01) and DSS (HR, 1.15; P < .001) compared with those living in MA. Similarly, non-Hispanic Black ethnicity and uninsured patients had significantly worse survival when compared with non-Hispanic White and insured patients, respectively. Married status showed better survival outcomes. CONCLUSION: Patients with EOCRC living in RA have worse outcomes. Understanding the mechanisms behind such socioeconomic disparities is important so that future studies can reduce these disparities.

Metabolic Dysregulation Explains the Diverse Impacts of Obesity in Males and Females with Gastrointestinal Cancers.

The prevalence of obesity, defined as the body mass index (BMI) ≥ 30 kg/m2, has reached epidemic levels. Obesity is associated with an increased risk of various cancers, including gastrointestinal ones. Recent evidence has suggested that obesity disproportionately impacts males and females with cancer, resulting in varied transcriptional and metabolic dysregulation. This study aimed to elucidate the differences in the metabolic milieu of adenocarcinomas of the gastrointestinal (GI) tract both related and unrelated to sex in obesity. To demonstrate these obesity and sex-related effects, we utilized three primary data sources: serum metabolomics from obese and non-obese patients assessed via the Biocrates MxP Quant 500 mass spectrometry-based kit, the ORIEN tumor RNA-sequencing data for all adenocarcinoma cases to assess the impacts of obesity, and publicly available TCGA transcriptional analysis to assess GI cancers and sex-related differences in GI cancers specifically. We applied and integrated our unique transcriptional metabolic pipeline in combination with our metabolomics data to reveal how obesity and sex can dictate differential metabolism in patients. Differentially expressed genes (DEG) analysis of ORIEN obese adenocarcinoma as compared to normal-weight adenocarcinoma patients resulted in large-scale transcriptional reprogramming (4029 DEGs, adj. p < 0.05 and |logFC| > 0.58). Gene Set Enrichment and metabolic pipeline analysis showed genes enriched for pathways relating to immunity (inflammation, and CD40 signaling, among others) and metabolism. Specifically, we found alterations to steroid metabolism and tryptophan/kynurenine metabolism in obese patients, both of which are highly associated with disease severity and immune cell dysfunction. These findings were further confirmed using the TCGA colorectal adenocarcinoma (CRC) and esophageal adenocarcinoma (ESCA) data, which showed similar patterns of increased tryptophan catabolism for kynurenine production in obese patients. These patients further showed disparate alterations between males and females when comparing obese to non-obese patient populations. Alterations to immune and metabolic pathways were validated in six patients (two obese and four normal weight) via CD8+/CD4+ peripheral blood mononuclear cell RNA-sequencing and paired serum metabolomics, which showed differential kynurenine and lipid metabolism, which corresponded with altered T-cell transcriptome in obese populations. Overall, obesity is associated with differential transcriptional and metabolic programs in various disease sites. Further, these alterations, such as kynurenine and tryptophan metabolism, which impact both metabolism and immune phenotype, vary with sex and obesity together. This study warrants further in-depth investigation into obesity and sex-related alterations in cancers that may better define biomarkers of response to immunotherapy.

Advances in borderline resectable pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is one of the most lethal cancers in oncology. Pancreatic cancer is the third most common cause of cancer-related mortality in the United States. As the years have progressed, the importance of a multidisciplinary and multimodal approach to pancreatic cancer care has been recognized and is now recommended in all major society guidelines. A subset of pancreatic cancer, borderline resectable pancreatic cancer (BRPC), has emerged as a distinct clinical entity for which specialized treatment plans are now being developed. The medical oncologist, surgical oncologist, and radiation oncologist must work jointly to help deliver the best clinical outcome for the patient with pancreatic cancer. In this discussion, we describe the current state of surgical, locoregional therapies and systemic therapy in BRPC.

Treating a Patient with Your Hands Tied: Acute Chest Syndrome in a Jehovah's Witness.

Acute chest syndrome (ACS), a vaso-occlusive crisis in patients with sickle cell anemia, is a life-threatening condition and a leading cause of death in these patients. It is treated with analgesics, antibiotics, intravenous fluid, supplemental oxygen (or ventilatory support in severe cases) with simple or exchange transfusion, being the mainstay of therapy. We report a young Jehovah's Witness (JW) patient with sickle cell anemia who presented with ACS. Her religious beliefs precluded the use of blood products. Despite concomitant hemolytic and aplastic crisis and a hemoglobin nadir of 3.1 g/dL, the patient was treated successfully with supportive care - including mechanical ventilation, sedation, paralysis, and erythropoiesis stimulation - and survived. A maximal supportive strategy consisting of ventilatory support with a high fraction of inspired oxygen, sedation, paralysis, erythropoiesis stimulation, and limitation of blood draws can result in the successful treatment of JW patients who refuse blood products.