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Endoscopic cryotherapy is a technique utilized for the ablation of target tissue within the gastrointestinal tract. A cryotherapy system utilizes the endoscopic application of cryogen such as liquid nitrogen, carbon dioxide or liquid nitrous oxide. This leads to disruption of cell membranes, apoptosis, and thrombosis of local blood vessels within the target tissue. Several trials utilizing cryotherapy for Barrett's esophagus (BE) with variable dysplasia, gastric antral vascular ectasia (GAVE), esophageal carcinoma, radiation proctitis, and metastatic esophageal carcinomas have shown safety and efficacy. More recently, liquid nitrogen cryotherapy (cryodilation) was shown to be safe and effective for the treatment of a benign esophageal stricture which was refractory to dilations, steroid injections, and stenting. Moreover, liquid nitrogen cryotherapy is associated with less post procedure pain as compared to radiofrequency ablation in BE with comparable ablation rates. In patients with GAVE, cryotherapy was found to be less tedious as compared to argon plasma coagulation. Adverse events from cryotherapy most commonly include chest pain, esophageal strictures, and bleeding. Gastric perforations did occur as well, but less often. In summary, endoscopic cryotherapy is a promising and growing field, which was first demonstrated in BE, but the use now spans for several other disease processes. Larger randomized controlled trials are needed before its role can be established for these different diseases.

A 73-year-old woman with a history of right hemicolectomy for advanced ascending colon cancer 14 years earlier was referred to our facility for a 2-month history of solid food dysphagia. An esophagogastroduodenoscopy revealed a 7-cm fungating and ulcerated mass in the middle to lower esophagus. The biopsy from the esophageal mass showed a moderately to poorly differentiated squamous cell carcinoma. A colonoscopy showed an end-to-end ileocolonic anastomosis with a 7-mm ulceration in the transverse colon. The biopsy of the ulceration at the anastomotic site showed a moderately to poorly differentiated squamous cell carcinoma with a morphology similar to that of the esophageal mass, rendering the diagnosis of metastatic esophageal squamous cell carcinoma. Colonic metastasis from esophageal squamous cell carcinoma, especially at the anastomotic site, is extremely rare. Although surgical trauma may not have contributed to the anastomotic site metastasis, given the distant timeline, its role in the pathogenesis of metastasis cannot be completely ruled out.

The risk of lymph node metastasis (LNM) of malignant colon polyps (MCPs) is partly estimated by histologic features of the sampled polyp. However, the routinely available histologic data is limited to tumor grade and status of lymphovascular invasion (LVI).The NCDB for colon cancer 2004-2018 was utilized. Patients with pT1Nx adenocarcinoma arising in a polyp and undergoing partial colectomy with ≥ 12 retrieved nodes were selected. NCDB 2004-2017 was used as a training cohort to develop two scoring systems based on a multivariable regression for predictors of LNM including clinical characteristics, grade, and LVI: a nomogram scoring system (NSS) and a simplified scoring system (SSS). These models were internally validated using NCDB 2018 to calculate precision metrics for each model.Six thousand sixty-nine patients were selected in the training cohort. 64.5% of MCPs were in the sigmoid, and LNM rate was 11.2%. Multivariable regression identified younger age, females, hindgut location, higher grade, and LVI as significant predictors of LNM. LNM risk was 1.2% when all unfavorable predictors were absent and exceeded 10% when NSS 70 or SSS ≥ 3. In the 2018 validation cohort, 723 patients were scored per NSS and SSS, and the negative predictive value for both was 96%.Estimating LNM risk in MCPs by applying clinical characteristics along with limited histologic data can help inform decision-making when considering formal oncologic resection. The NSS and SSS demonstrated comparable predictability of LNM among pT1Nx MCPs. The models require external validation and may be strengthened by incorporating additional endoscopic and pathologic characteristics.

We hypothesized that first-generation cephalosporins (G1CEP) provide adequate antimicrobial coverage for pancreaticoduodenectomy (PD) when no biliary stent is present but might be inferior to second-generation cephalosporins or broad-spectrum antibiotics (G2CEP/BS) in decreasing surgical-site infection (SSI) rates when a biliary stent is present.The National Surgical Quality Improvement Program 2014-2019 was used to select patients who underwent elective open PD. We divided the population into no-stent versus stent groups based on the status of biliary drainage and then divided each group into G1CEP versus G2CEP/BS subgroups based on the choice of perioperative antibiotics. We matched the subgroups per a propensity score match and analyzed postoperative outcomes.Six thousand two hundred forty five cases of 39,779 were selected; 2821 in the no-stent (45.2%) versus 3424 (54.8%) in the stent group. G1CEP were the antibiotics of choice in 2653 (42.5%) versus G2CEP/BS in 3592 (57.5%) cases. In the no-stent group, we matched 1129 patients between G1CEP and G2CEP/BS. There was no difference in SSI-specific complications (20.3% versus 21.0%; P = 0.677), general infectious complications (25.7% versus 26.9%; P = 0.503), PD-specific complications, overall morbidity, length of stay, or mortality. In the stent group, we matched 1244 pairs. G2CEP/BS had fewer SSI-specific complications (19.9% versus 26.6%; P 0.001), collections requiring drainage (9.6% versus 12.9%; P = 0.011), and general infectious complications (28.5% versus 34.1%; P = 0.002) but no difference in overall morbidity, mortality, length of stay, and readmission rates.G2CEP/BS are associated with reduced rates of SSI-specific and infectious complications in stented patients undergoing open elective PD. In patients without prior biliary drainage, G1CEP seems to provide adequate antimicrobial coverage.

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.

Background Monitored anesthesia care (MAC) and general anesthesia (GA) are the 2 most common methods of sedation used for endoscopic retrograde cholangiopancreatography (ERCP). We performed a systematic review and meta-analysis to compare the overall safety between MAC vs. GA in ERCP. Methods We conducted a comprehensive search of electronic databases to identify studies reporting the use of MAC or GA as a choice of sedation for ERCP. The primary outcome was to compare the overall rate of sedation-related adverse events in MAC vs. GA groups. The secondary endpoint was to investigate the total duration of the procedure, recovery time, ERCP cannulation rates, and conversion rate of MAC to GA. The meta-analysis was performed using a Der Simonian and Laird random-effects model. Results A total of 21 studies reporting on 11,592 patients were included. The overall sedation-related side-effects were similar in the GA (12.76%, 95% confidence interval [CI] 5.80-21.73; I2=95%) and MAC (12.08%, 95%CI 5.38-20.89; I2=99%) groups (P=0.956). Hypoxia, arrhythmias, hypotension, aspiration and other sedation-related side-effects were similar between the 2 groups. The mean duration of the procedure was longer in the MAC group, but the mean recovery time was shorter. Significant heterogeneity was noted in our meta-analysis. Conclusions In our meta-analysis, the overall sedation-related side-effects were similar between the MAC and GA groups. MAC could be used as a safer alternative to GA when performing ERCP. However, large multicenter randomized control trials are needed to further validate our findings.

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.

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.

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.

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