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Objective: Gastrostomy tubes (g-tubes) have been used with caution prior to esophageal resection due to the risks of inoculation metastasis and of injury to the gastric conduit used for reconstruct...

Background: Well-annotated, high-quality biorepositories provide a valuable platform to support translational research. However, most biorepositories have poor representation of minority groups, limiting the ability to address health disparities. Methods: We describe the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective cohort study and biorepository designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). We provide an overview of stakeholders, study eligibility and design, recruitment strategies, standard operating procedures to collect, process, store, and transfer biospecimens, medical images, and data, our cloud-based data management platform, and progress regarding recruitment and biobanking. Results: The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and questionnaires (62%). Conclusions: This biorepository addresses a critical gap in PaCa research and has potential to advance translational studies intended to minimize disparities and reduce PaCa-related morbidity and mortality.

BackgroundWell-annotated, high-quality biorepositories provide a valuable platform to support translational research and discovery. However, most biorepositories have poor representation of minority groups, limiting the ability to address cancer health disparities and improve disease outcomes. This report describes the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective longitudinal cohort study and biorepository specifically designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L).MethodsWe describe rationale for establishing the FPC and provide an overview of key stakeholders; study eligibility and design; ascertainment and recruitment strategies; and standard operating procedures (SOPs) developed to collect, process, store, and transfer biospecimens, medical images, and data. We also describe the customized cloud-based, secure data management platform built to facilitate recruitment, track study-related workflow, house data, and perform queries. We also present progress to date regarding recruitment and biobanking.ResultsThe FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for study eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and baseline questionnaire data (62%).ConclusionsThis biorepository addresses a critical gap in PaCa research with the potential to advance basic, clinical, population-based, and translational studies intended to minimize disparities, increase quality of life, and reduce PaCa-related morbidity and mortality.ImpactThis multi-institutional infrastructure can serve as a prototype for development of similar resources across the country and disease sites.

Barrett's esophagus (BE) is a condition resulting from an acquired metaplastic epithelial change in the esophagus in response to gastroesophageal reflux. BE is the only known precursor lesion to esophageal adenocarcinoma, and can progress from non-dysplastic BE (NDBE) to low grade dysplasia (LGD) and high grade dysplasia (HGD), and ultimately invasive carcinoma. Although the risk of developing esophageal adenocarcinoma (EAC) in NBDE is less than 0.5% per year, there has been a rising incidence of EAC in Western countries, which continue to drive efforts to optimize screening and surveillance methods. The current gold standard for diagnosis is esophagogastroduodenoscopy (EGD), and there has been significant interest in alternative, minimally invasive methods for screening which would be more readily accessible in the primary care setting. Surveillance endoscopy in 3-5 years is recommended for NDBE given the low progression to EAC. The mainstay of treatment for LGD and HGD is endoscopic eradication therapy (EET). Visible lesions are treated with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Radiofrequency ablation (RFA) is considered first line therapy for flat dysplastic BE and cryotherapy has shown promising results as an alternate form of treatment for of dysplasia. The molecular progression of BE to EAC is a complex process involving multiple pathways involving genetic and epigenetic modifications. Genomic studies have further led to the understanding of the complex molecular landscape that occurs early and late in the disease process. Promising biomarker panels have been investigated to help with the diagnosis of BE as well as aid in the risk stratification of BE during surveillance. In addition, clinical prediction models have been developed to categorize BE patients in low, intermediate, and high risk for progression to HGD and EAC. Further clinical and translational research is needed to help refine markers and techniques in diagnosis, screening, and surveillance.

Fiducial markers are radiopaque markers implanted inside or adjacent to a tumor to aid in image-guided radiation therapy. Image-guided radiation therapy (IGRT) enables precise targeting of the lesion, minimizes toxicity to adjacent normal structures, and takes into account motion of the tumor during respiration. Traditionally, fiducial markers were placed percutaneously or surgically. More recently, endoscopic ultrasound (EUS)-guided fiducial placement has been reported. Both retrospective and prospective studies have demonstrated that EUS-guided fiducial placement is safe and feasible in various malignancies with low complication rates. There are several fiducial deployment techniques and different commercially available fiducial types that have been described in the literature. Technical success rates have ranged between 85 and 100%, with higher success rates in more recent studies even without the use of fluoroscopy. Data on long-term durability of fiducials during radiation therapy are favorable, although studies evaluating survival benefit are lacking. This chapter will summarize the role of EUS in the placement of fiducial markers to aid IGRT to treat various gastrointestinal and nongastrointestinal malignancies.

The careful review of drug-drug interactions is vital to the safe prescribing of medications for chronic medical conditions. The elderly population suffers from multiple medical problems, and polypharmacy leads to further morbidity in this vulnerable group of patients. We discuss gastrointestinal conditions such as GERD, peptic ulcer disease, gastroparesis, diarrhea, constipation, irritable bowel syndrome, inflammatory bowel disease, chronic liver disease and the commonly used medications in these conditions. Treatment options must be individualized and tailored to accommodate the underlying pharmacokinetics and known drug-drug interactions. The indication for the use of a therapeutic agent in the elderly and the duration of use must be frequently readdressed to help prevent polypharmacy and adverse drug reactions. Medications should be started at a low dose with careful titration to achieve a clinical response to prevent toxicity. The aim of this article is to increase awareness of important drug-drug interactions of commonly prescribed gastrointestinal medications in the elderly.

Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanisms by which aldosterone promotes endothelial dysfunction remain unknown. Glucose-6-phosphate dehydrogenase (G6PD) modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO(*)). Here we show that aldosterone (10(-9)-;10(-7) mol/l) decreased endothelial G6PD expression and activity in vitro, resulting in increased oxidant stress and decreased NO(*) levels-similar to what is observed in G6PD-deficient endothelial cells. Aldosterone decreased G6PD expression by increasing expression of the cyclic AMP-response element modulator (CREM) to inhibit cyclic AMP-response element binding protein (CREB)-mediated G6PD transcription. In vivo, infusion of aldosterone decreased vascular G6PD expression and impaired vascular reactivity. These effects were abrogated by spironolactone or vascular gene transfer of G6pd. These findings demonstrate that aldosterone induces a G6PD-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6PD activity.

Corrigendum: Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity