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Background/objectives: The Oakland score was developed to predict safe discharge in patients who present to the emergency department with lower gastrointestinal bleeding (LGIB). In this study, we retrospectively evaluated if this score can be implemented to assess safe discharge (score ≤ 10) at WellStar Atlanta Medical Center (WAMC)., Methods: A retrospective cohort study of 108 patients admitted at WAMC from January 1, 2020 to December 30, 2021 was performed. Patients with LGIB based on the ICD-10 codes were included. Oakland score was calculated using 7 variables (age, sex, previous LGIB, digital rectal exam, pulse, systolic blood pressure (SBP) and hemoglobin (Hgb)) for all patients at admission and discharge from the hospital. The total score ranges from 0 to 35 and a score of ≤ 10 is a cut-off that has been shown to predict safe discharge. Hgb and SBP are the main contributors to the score, where lower values correspond to a higher Oakland score. Descriptive and multivariate analysis was performed using SPSS 23 software., Results: A total of 108 patients met the inclusion criteria, 53 (49.1%) were female with racial distribution was as follows: 89 (82.4%) African Americans, 17 (15.7%) Caucasian, and 2 (1.9%) others. Colonoscopy was performed in 69.4% patients; and 61.1% patients required blood transfusion during hospitalization. Mean SBP records at admission and discharge were 129.0 (95% CI, 124.0-134.1) and 130.7 (95% CI,125.7-135.8), respectively. The majority (59.2%) of patients had baseline anemia and the mean Hgb values were 11.0 (95% CI, 10.5-11.5) g/dL at baseline prior to hospitalization, 8.8 (95% CI, 8.2-9.5) g/dL on arrival and 9.4 (95% CI, 9.0-9.7) g/dL at discharge from hospital. On admission, 100/108 (92.6%) of patients had an Oakland score of > 10 of which almost all patients (104/108 (96.2%)) continued to have persistent elevation of Oakland Score greater than 10 at discharge. Even though, the mean Oakland score improved from 21.7 (95% CI, 20.4-23.1) of the day of arrival to 20.3 (95% CI, 19.4-21.2) at discharge, only 4/108 (3.7%) of patients had an Oakland score of ≤ 10 at discharge. Despite this, only 9/108 (8.33%) required readmission for LGIB during a 1-year follow-up. We found that history of admission for previous LGIB was associated with readmission with adjusted odds ratio 4.42 (95% CI, 1.010-19.348, p = 0.048)., Conclusions: In this study, nearly all patients who had Oakland score of > 10 at admission continued to have a score above 10 at discharge. If the Oakland Score was used as the sole criteria for discharge most patients would not have met discharge criteria. Interestingly, most of these patients did not require readmission despite an elevated Oakland score at time of discharge, indicating the Oakland score did not really predict safe discharge. A potential confounder was the Oakland score did not consider baseline anemia during calculation. A prospective study to evaluate a modified Oakland score that considers baseline anemia could add value in this patient population., (© 2024. The Author(s).)

Transarterial angiographic embolization using coils is an effective, common, and safe treatment for non-variceal upper gastrointestinal bleeding (UGIB) refractory to endoscopic therapy/management. Coil migration is a complication that can lead to rebleeding. Our patient experienced UGIB due to a recurring duodenal ulcer with coil protrusion following previous embolization for a bleeding duodenal ulcer that was not responsive to endoscopic therapy. The ulceration was successfully managed with endoscopic partial coil removal and medical therapy to achieve hemostasis and ulcer healing. Endoscopists should be aware of coil embolization complications and consider endoscopic removal in the appropriate clinical setting., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Perry et al.)

Background: Esophageal carcinoma presents as 2 types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) with the frequency of both changing in the United States (US)., Aim: To investigate EAC/ESCC incidence time trends among the 3 main US racial groups and investigate trends in US EAC survival by ethnicity., Methods: Twenty-five years (1992-2016) of data from SEER 13 program was analyzed to compare incidence trends in EAC and ESCC between non-Hispanic whites (nHW), non-Hispanic Blacks (nHB) and Hispanics (Hisp) using SEERStat ® . In addition, SEER 18 data, from 1975-2015, on EAC in the US was analyzed to evaluate racial disparities in incidence and survival using SEERStat ® and Ederer II method., Results: In the 3 major US ethnic groups, age-adjusted incidence of ESCC has declined while EAC has continued to rise from 1992-2016. Of note, in Hisp, the EAC incidence rate increased while ESCC decreased from 1992 to 2016, resulting in EAC as the predominant esophageal cancer subtype in this group since 2011, joining nHW. Furthermore, although ESCC remains the predominant tumor in nHB, the difference between ESCC and EAC has narrowed dramatically over 25 years. EAC survival probabilities were worse in all minority groups compared to nHw., Conclusion: Hisp have joined nHW as US ethnic groups more likely to have EAC than ESCC. Of note, EAC incidence in nHB is increasing at the highest rate nationally. Despite lower EAC incidence in all minority groups compared to nHW, these populations have decreased survival compared to nHW., Competing Interests: Conflict-of-interest statement: All the authors have no relevant financial or non-financial interests to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6) trial showed that semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is effective in managing type 2 diabetes by stimulating insulin secretion and promoting weight loss. Though recent evidence suggests no increased risk of acute pancreatitis (AP) with subcutaneous semaglutide use, some studies report an increase in pancreatic inflammation with GLP-1 RAs. We present a case of AP in a patient recently started on subcutaneous semaglutide for type 2 diabetes. As GLP-1 RA use increases, clinicians should be aware of their potential to cause acute pancreatitis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Patel et al.)

Barrett's esophagus (BE) is a condition that results from replacement of the damaged normal squamous esophageal mucosa to intestinal columnar mucosa and is the most significant predisposing factor for development of esophageal adenocarcinoma. Current guidelines recommend endoscopic evaluation for screening and surveillance based on various risk factors which has limitations such as invasiveness, availability of a trained specialist, patient logistics and cost. Trans-nasal endoscopy is a less invasive modality but still has similar limitations such as limited availability of trained specialist and costs. Non-endoscopic modalities, in comparison, require minimal intervention, can be done in an office visit and has the potential to be a more ideal choice for mass public screening and surveillance, particularly in patents at low risk for BE. These include newer generations of esophageal capsule endoscopy which provides direct visualization of BE, and tethered capsule endomicroscopy which can obtain high-resolution images of the esophagus. Various cell collection devices coupled with biomarkers have been used for BE screening. Cytosponge, in combination with TFF3, as well as EsophaCap and EsoCheck have shown promising results in various studies when used with various biomarkers. Other modalities including circulatory microRNAs and volatile organic compounds that have demonstrated favorable outcomes. Use of these cell collection methods for BE surveillance is a potential area of future research., Competing Interests: Conflict-of-interest statement: No conflict of interest exists for any author of this manuscript., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background Acute cholangitis results in significant mortality unless treated promptly. The diagnostic grading criteria of the 2018 Tokyo Guidelines (TG18) are used worldwide as the standard for acute cholangitis (AC) management but validation in clinical practice is required. Aim Use of the Tokyo 2018 (TG18) guidelines in improving the diagnostic accuracy and early detection of AC compared to fellow clinical assessment. Methods A retrospective review of patient records from 1/2010-9/2019 seen at Augusta University - Medical College of Georgia with the International Classification of Diseases, Ninth Revision (ICD-9) code "cholangitis" and/or ICD-10 codes "acute cholangitis, other cholangitis, and calculus of bile duct with cholangitis" was performed. Inclusion criteria were gastroenterology inpatient consult fellow evaluation and clinical diagnosis of AC. A definitive diagnosis of AC was determined following endoscopic retrograde cholangiopancreatography (ERCP). TG18 scoring for AC was then performed, categorized as either diagnostic/non-diagnostic, and compared to fellow clinical assessments following definitive diagnosis post-ERCP. Data were analyzed with chi-square testing. Results Two hundred six patients were identified using ICD codes. Ninety-one met inclusion criteria and were analyzed. The mean patient age of the overall group was 67 years old (standard deviation of 13.3 years) with males comprising 69% and non-Hispanic white 56% of the study group. TG18 criteria assessment had a sensitivity of 86% and specificity of 63% for patients with AC post ERCP (p <0.05). TG18 accuracy was 81%. In comparison, fellow clinical suspicion had a sensitivity of 90.3% and specificity of 0% (NS). Fellow accuracy was 71%. No difference in fellows' diagnosis of suspected AC was noted based on the training year. Conclusion Application of the TG18 criteria for AC reduces the false positive rate and improves diagnostic accuracy, thus decreasing costs along with avoiding unnecessary ERCPs with associated complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hudgi et al.)

Background: Gastric adenocarcinoma (GAC) is highly heterogeneous and closely related to colorectal cancer (CRC) both molecularly and functionally. GAC is currently subtyped using a system developed by TCGA. However, with the emergence of immunotherapies, this system has failed to identify suitable treatment candidates. Methods: Consensus molecular subtypes (CMSs) developed for CRC were used for molecular subtyping in GAC based on public expression cohorts, including TCGA, ACRG, and a cohort of GAC patients treated with the programmed cell death 1 (PD-1) inhibitor pembrolizumab. All aspects of each subtype, including clinical outcome, molecular characteristics, oncogenic pathway activity, and the response to immunotherapy, were fully explored. Results: CMS classification was efficiently applied to GAC. CMS4, characterized by EMT activation, stromal invasion, angiogenesis, and the worst clinical outcomes (median OS 24.2 months), was the predominant subtype (38.8%~44.3%) and an independent prognostic indicator that outperformed classical TCGA subtyping. CMS1 (20.9%~21.5%) displayed hypermutation, low SCNV, immune activation, and best clinical outcomes (median OS > 120 months). CMS3 (17.95%~25.7%) was characterized by overactive metabolism, KRAS mutation, and intermediate outcomes (median OS 85.6 months). CMS2 (14.6%~16.3%) was enriched for WNT and MYC activation, differentiated epithelial characteristics, APC mutation, lack of ARID1A, and intermediate outcomes (median OS 48.7 months). Notably, CMS1 was strongly correlated with immunotherapy biomarkers and favorable for the anti-PD-1 drug pembrolizumab, whereas CMS4 was poorly responsive but became more sensitive after EMT-based stratification. Conclusions: Our study reveals the practical utility of CMS classification for GAC to improve clinical outcomes and identify candidates who will respond to immunotherapy.

A large body of evidence has demonstrated that cyclic-guanosine monophosphate (cGMP), signaling has anti-tumor effects that might be used for colon cancer prevention. The tumor-suppressive mechanism and the signaling components downstream of cGMP remain largely unknown. The present study has characterized the expression of cGMP-dependent protein kinases (PKG1, PKG2) in normal and cancerous tissue from human colon. PKG1 was detected in both normal and tumor tissue, where it localized exclusively to the lamina propria and stroma (respectively). In contrast, PKG2 localized specifically to the epithelium where its expression decreased markedly in tumors compared to matched normal tissue. Neither PKG isoform was detected at the RNA or protein level in established colon cancer cell lines. To test for a potential tumor-suppressor role of PKG2 in the colon epithelium, Prkg2 knockout (KO) mice were subjected to azoxymethane/dextran sulfate-sodium (AOM/DSS) treatment. PKG2 deficiency was associated with crypt hyperplasia (Ki67) and almost twice the number of polyps per mouse as wild-type (WT) siblings. In vitro culture of mouse colon epithelium as organoids confirmed that PKG2 was the only isoform expressed, and it was detected in both proliferating and differentiating epithelial compartments. Colon organoids derived from Prkg2 KO mice proliferated more rapidly and exhibited a reduced ability to differentiate compared to WT controls. Taken together our results highlight PKG2 as the central target of cGMP in the colon, where it suppresses carcinogenesis by controlling proliferation in an epithelial-cell intrinsic manner., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Roux-en-Y gastric bypass (RNYGB) has become the standard of care in treating obesity, a global health concern with associated comorbidities contributing to rising health care costs [1]. The positive outcomes of RNYGB have been well documented along with adverse effects such as nutrient deficiencies, hernia, postprandial dumping syndrome, chronic kidney disease and hypoglycemia. A lesser-known long term complication of RNYGB is liver failure. Here, we present a case where RNYGB performed 10 years prior contributed to acute liver failure., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Voong et al.)

There is growing interest in the potential use of phosphodiesterase (PDE) inhibitors for colorectal cancer (CRC) prevention and treatment. The present study has tested the idea that PDE inhibitors inhibit growth and viability of CRC cell lines by increasing cyclic guanosine monophosphate (cGMP) and activating cGMP-dependent protein kinase (PKG). Colon cancer cell lines and those with ectopic PKG2 expression were treated with membrane-permeable 8Br-cGMP or inhibitors of PDE5, PDE9, and PDE10a. Levels of cGMP capable of activating PKG were measured by immunoblotting for phosphorylation of vasodilator-stimulated phosphoprotein (VASP). The effects of treatment on CRC cell proliferation and death were measured using hemocytometry with trypan blue. Treatment with 8Br-cGMP had no effect on CRC cell proliferation or death. Endogenous PKG activity was undetectable in any of the CRC cells, but expression of ectopic PKG2 conferred modest inhibition of proliferation but did not affect cell death. Extremely high concentrations of all the PDE inhibitors reduced proliferation in CRC cell lines, but none of them increased cGMP levels, and the effect was independent of PKG expression. The inability of the PDE inhibitors to increase cGMP was due to the lack of endogenous cGMP generating machinery. In conclusion, PDE inhibitors that target cGMP only reduce CRC growth at clinically unachievable concentrations, and do so independent of cGMP signaling through PKG. SIGNIFICANCE STATEMENT: A large number of in vitro studies have reported that PDE inhibitors block growth of colon cancer cells by activating cGMP signaling, and that these drugs might be useful for cancer treatment. Our results show that these drugs do not activate cGMP signaling in colon cancer cells due to a lack of endogenous guanylyl cyclase activity, and that growth inhibition is due to toxic effects of clinically unobtainable drug concentrations., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)

Competing Interests: Competing interests: None declared.

Barrett's esophagus (BE) is the precursor lesion for esophageal adenocarcinoma (EAC) development. Unfortunately, BE screening/surveillance has not provided the anticipated EAC reduction benefit. Noninvasive techniques are increasingly available or undergoing testing to screen for BE among those with/without known risk factors, and the use of artificial intelligence platforms to aid endoscopic screening and surveillance will likely become routine, minimizing missed cases or lesions. Management of high-grade dysplasia and intramucosal EAC is clear with endoscopic eradication therapy preferred to surgery. BE with low-grade dysplasia can be managed with removal of visible lesions combined with endoscopic eradication therapy or endoscopic surveillance at present., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Eosinophilic esophagitis (EoE) is thought to be an atopic disorder causing dysphagia. HIV patients have dysphagia from both common (reflux esophagitis) and uncommon causes (idiopathic esophageal ulceration). Only a single case report about the occurrence of EoE in an HIV patient exists in literature., Aim: The aim of this study was to determine if HIV and EoE occur concurrently using a large inpatient database., Methods: Data on hospital admissions of all HIV adult patients were extracted from the 2002-2014 National Inpatient Sample. Comorbidities and outcomes of interest were defined by querying all diagnostic and procedural fields for the corresponding ICD-9 codes. Univariable and multivariable logistic regression analysis was performed to assess the association between HIV and EoE. Similarly, we assessed the relation between HIV and eosinophilic gastroenteritis (EGE)., Results: The total population comprised of 101,137,145 patients, of which 231,691 (0.229%) have HIV and 5038 (0.004%) have EoE. HIV patients were younger (45.2 vs 48 years old and more likely to be male (62.2% vs 41.5%) and African American (53.9% vs 14.2%) compared to non-HIV patients (P < 0.001 for all). After adjusting for potential cofounding factors, HIV patients had a statistically significant higher rate of EoE (Odds Ratio 2.108, with 95% confidence interval 1.268-3.506, P = 0.004) compared to the non-HIV group. On the other hand, HIV was not associated with increased risk of EGE (Odds Ratio 0.78, 95% confidence interval 0.109-5.557, P = 0.804)., Conclusion: Patients with HIV are twice as likely to have EoE compared to those without HIV. Evaluation of dysphagia in HIV patients should include assessment for EoE, especially when empiric antifungal therapy for candida esophagitis does not improve clinical symptoms., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background and aim Adenomatous polyps are precursor lesions for colorectal cancer (CRC). Serrated adenomas/polyps are considered a risk factor for the development of proximal and interval CRC. African-Americans are at higher risk for right-sided CRC. Minimal data evaluating serrated adenoma characteristics by race/ethnicity on initial screening colonoscopy (SC) exist. The aim of this investigation was to compare the characteristics of serrated adenomas found in non-Hispanic whites (nHw) and African-Americans (AA) undergoing initial SC. Methods The University of Florida-Jacksonville endoscopy database was searched for all SC performed between January 2000 and December 2014. Inclusion criteria were nHw or AA race/ethnicity and histologically proven serrated adenoma found at SC. Data were collected for all included age at SC, sex, number, location, and size of serrated adenomas found. Results A total of 8693 individuals (nHw - 4199 and AA - 4494) underwent SC between January 2000 and December 2014. Serrated adenomas were found in 479 individuals (nHw, n=294; AA, n=185), and AA were significantly less likely than nHw to have serrated adenomas on SC (AA 4.1% vs nHw 7%; p< 0.0001). No difference was observed in mean age, location, or size between nHw and AA with serrated adenomas. Conclusions Serrated adenomas are more frequent in nHw compared to AA at initial SC. No difference was seen in size or location of serrated adenomas, as well as patient age, between AA and nHw. A study of genetic factors predisposing to serrated adenoma formation and the impact of socioeconomic disparities should be performed across ethnic groups to understand this difference., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Stemboroski et al.)

Spontaneous gallbladder hemorrhage (SGBH) is a rare diagnosis related to trauma, malignancy or vascular abnormalities, associated with significant morbidity and mortality. We present a case of SGBH in a 55-year-old patient with right upper quadrant (RUQ) pain following initiation of apixaban for deep vein thrombosis post recent kidney transplant. Multiple imaging studies revealed a distended gallbladder with heterogeneous hyperdense material in the lumen and cystic duct obstruction. Surgery revealed a gallbladder with chronic cholecystitis, hemorrhage and hematoma. This case highlights a rare adverse event of anticoagulation, and SGBH should be considered when acute RUQ pain occurs in this setting., (Copyright © 2020 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Objective: Colorectal cancer (CRC) screening rates are much lower at federally qualified health centers (FQHC) than the rest of the nation. The study aim was to determine if a physician led, low cost intervention, can improve CRC screening rates at FQHCs for underserved patients., Methods: A CRC quality improvement outreach program was conducted at 4 FQHCs. The program included direct provider education sessions, systems process improvements, patient education resources and low cost testing. We analyzed pre and post intervention screening rates for all eligible patients, defined as age 50-74 at average CRC risk., Results: CRC screening rates significantly increased at all sites 3 months following intervention: Site 1: 41%-48.3%, p < .0001; site 2: 31.6%-37.8%, p < .0001; site 3: 30.5%-38.2%, p < .0001 and site 4: 43.9%-46.8%, p = .012., Conclusion: The education program successfully increased CRC screening rates in the underserved by 2.9%-7.7% 3 months post-intervention., Practice Implications: This approach of direct provider education sessions, systems process improvements, patient education resources and low cost testing improved underserved CRC screening. Implementation across Georgia would be expected to improve CRC related mortality and morbidity for the state's underserved., Competing Interests: Declaration of Competing Interest The authors report no declarations of any competing interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Esophageal cancer (EC) is a significant cause of cancer death with 5-year survival of 10%-15% and males more frequently affected. Genetic evaluation for loci highlighting risk has been performed, but survival data are limited. The Cancer Genome Atlas (TCGA) data sets allow for potential prognostic marker assessment in large patient cohorts. The study aimed to use the TCGA EC data set to assess whether survival varies by sex and explore genetic alterations that may explain variation observed., Methods: TCGA clinical/RNA-seq data sets (n = 185, 158 males/27 females) were downloaded from the cancer genome browser. Data analysis/figure preparation was performed in R and GraphPad Prism 7. Survival analysis was performed using the survival package. Text mining of PubMed was performed using the tm, RISmed, and wordcloud packages. Pathway analysis was performed using the Reactome database., Results: In EC, male sex/high tumor grade reduced overall survival (hazard ratio = 2.27 [0.99-5.24] for M vs F and 2.49 [0.89-6.92] for low vs high grade, respectively) and recurrence-free survival (hazard ratio = 4.09 [0.98-17.03] for M vs F and 3.36 [0.81-14.01] for low vs high grade, respectively). To investigate the genetic basis for sex-based survival differences in EC, corresponding gene expression data were analyzed. Sixty-nine genes were dysregulated at the P < 0.01 level by the Wilcox test, 33% were X-chromosome genes, and 7% were Y-chromosome genes., Discussion: Female sex potentially confers an EC survival advantage. Importantly, we demonstrate a genetic/epigenetic basis for these survival differences that are independent of lifestyle-associated risk factors overrepresented in males. Further research may lead to novel concepts in treating/measuring EC aggressiveness by sex., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Proton pump inhibitors (PPIs) are one of the most common medications taken by patients worldwide. PPIs are used to treat acid-related disorders, including gastroesophageal reflux disease, peptic ulcer disease, Helicobacter pylori infection, and nonsteroidal anti-inflammatory drug/stress ulceration. For some of these diseases, long-term treatment is necessary. With such prolonged use, concern and investigation into potential adverse effects has increased. In addition, data are available regarding potential anticancer effects of PPIs, especially regarding solid tumors. The aim of this review is to assess the literature on PPIs with regard to common concerns, such as drug-drug interactions, the intestinal microbiome, dementia and central nervous system disease, and osteoporosis, as well as to highlight potential negative and positive impacts of the drug in cancer., (© 2020 New York Academy of Sciences.)

The diagnosis of esophagogastric junction outflow obstruction (EGJOO) is currently based on high-resolution esophageal manometry and is characterized by impaired EGJ relaxation with preserved esophageal peristalsis. This condition has been defined by the Chicago Classification as a major esophageal motility disorder, although its clinical significance is controversial since heterogeneous and irrelevant presentations have been reported. EGJOO commonly has a benign clinical course, with spontaneous resolution, but it can also be associated with opioid usage, early achalasia, and mechanical obstruction. A careful medical, surgical, and medication history coupled with a careful manometry interpretation focused on the factors that might affect the integrated relaxation pressure are the keys for an accurate diagnosis. The advance of esophageal physiological tests can evaluate the clearance of the esophageal contents across the EGJ. The manometry technique, including testing in an upright position and provocative tests, can also complement those tests and demonstrate the evidence of EGJ obstruction. After making a diagnosis, endoscopy should be an initial step to exclude anatomical causes if it has not yet been done. Imaging studies can identify infiltrative lesions, but the reported diagnostic yield is relatively low. Management of EGJOO depends on the underlying etiology. Functional EGJOO patients with persistent dysphagia associated with the presence of outflow obstruction may require EGJ disruption therapy., (© 2020 New York Academy of Sciences.)

Objectives: Pancreatic cancer (PaC) is the third leading cause of cancer-related death in the United States. Multiple studies have investigated the epidemiology and the association between PaC and acetylsalicylic acid (ASA) use, revealing mixed results. Using a large database, we sought to investigate the epidemiology of PaC., Methods: Using a commercial database (Explorys Inc, Cleveland, Ohio), which includes electronic health record data from 26 major integrated US health care systems, all patients 18 years and older diagnosed with PaC for 5 years were identified based on Systematized Nomenclature Of Medicine-Clinical Terms. We determined the prevalence of PaC and the potential associated factors using univariable and multivariable analysis., Results: Of the 32,970,850 individuals, we identified 30,250 individuals with PaC with an overall prevalence of 0.08%. Individuals with PaC were more likely to be males, seniors (age, >65 years), and White, compared with patients without PaC. In subgroup analysis of chronic pancreatitis, individuals on ASA, individuals >65 years, White, and White males were less likely to have PaC, and non-White females were more likely to have PaC., Conclusions: This is the largest population-based study evaluating the epidemiology of PaC. We observed a protective association of ASA on a subgroup of patients with PaC and chronic pancreatitis.

Identifying early-stage cancer patients at risk for progression is a major goal of biomarker research. This report describes a novel 19-gene signature (19-GCS) that predicts stage I lung adenocarcinoma (LAC) recurrence and response to therapy and performs comparably in pancreatic adenocarcinoma (PAC), which shares LAC molecular traits. Kaplan-Meier, Cox regression, and cross-validation analyses were used to build the signature from training, test, and validation sets comprising 831 stage I LAC transcriptomes from multiple independent data sets. A statistical analysis was performed using the R language. Pathway and gene set enrichment were used to identify underlying mechanisms. 19-GCS strongly predicts overall survival and recurrence-free survival in stage I LAC (P=0.002 and P<0.001, respectively) and in stage I-II PAC (P<0.0001 and P<0.0005, respectively). A multivariate cox regression analysis demonstrated the independence of 19-GCS from significant clinical factors. Pathway analyses revealed that 19-GCS high-risk LAC and PAC tumors are characterized by increased proliferation, enhanced stemness, DNA repair deficiency, and compromised MHC class I and II antigen presentation along with decreased immune infiltration. Importantly, high-risk LAC patients do not appear to benefit from adjuvant cisplatin while PAC patients derive additional benefit from FOLFIRINOX compared with gemcitabine-based regimens. When validated prospectively, this proof-of-concept biomarker may contribute to tailoring treatment, recurrence reduction, and survival improvements in early-stage lung and pancreatic cancers., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rapid advances in technology are revealing previously unknown organization, cooperation, and limitations within the population of nontumor cells surrounding the tumor epithelium known as the tumor microenvironment (TME). Nowhere are these findings more pertinent than in the gastrointestinal (GI) tract where exquisite cell specialization supports a complex microenvironmental niche characterized by rapid stemness-associated cell turnover, pathogen sensing, epithelial orchestration of immune signaling, and other facets that maintain the complex balance between homeostasis, inflammation, and disease. Here, we summarize and discuss select emerging concepts in the precancerous microenvironment, TME, and tumor epithelial-TME crosstalk as well as their implications for the management of GI cancers., Competing Interests: The authors declare no conflicts of interest relevant to the contents of this review., (Copyright © 2019 Yang Ge et al.)

Background and Study Aims: Barrett's Esophagus (BE) is a well-recognized pre-malignant condition. Previous data indicate histologically confirmed BE frequency varies by ethnicity in the United States. However, clinical factor assessment to explain this has only occurred in a veteran population to date. The study aim was to determine which clinical factors may be associated with the ethnic variation seen in histologically confirmed BE among a general population., Patients and Methods: The University of Florida-Jacksonville endoscopy database was searched for all cases of endoscopic BE from September 2002 to October 2012. Histologic BE was diagnosed only if salmon colored, columnar-appearing esophageal mucosa was seen at endoscopy and biopsy revealed intestinal metaplasia with Alcian blue-stained goblet cells. Data collected included: age/BMI at diagnosis, ethnicity, sex, GERD history, atypical manifestations, endoscopic BE length, presence of esophageal stricture/ulcer/hiatal hernia, presence/absence of dysplasia and medication use (aspirin/NSAIDs/statin/PPI)., Results: Salmon colored esophageal mucosa was observed in 1105 of 15,564 patients (7.1%) with BE histologically confirmed in 249 of 1105 patients (23%). Ethnic distribution of histologic BE patients: 83% non-Hispanic white (nHw), 13% African American (AA) and 4% other. No difference was seen between groups with regard to BMI, GERD symptom/complications, BE length, and cigarette, alcohol or medication use., Conclusion: BE occurs primarily in nHw in north Florida. This occurs despite similarities in GERD history, cigarette/alcohol use, medications prescribed and BMI. Molecular level investigation is necessary to explain this observed disparity between nHw and AA., (Copyright © 2018 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) incidence has been increasing in the United States for greater than 30 years. For the majority of EAC patients, treatment is limited and prognosis poor. Doublecortin like kinase-1 (DCLK1) is a cancer stem cell marker with elevated expression in BE patients with high grade dysplasia and/or EAC. This prospective cohort study was designed to compare serum DCLK1 levels before and after EAC treatment with endoscopic mucosal resection (EMR) and/or radio-frequency ablation (RFA)., Methods: Barrett's esophagus patients with low or high-grade dysplasia ( n  = 9) and EAC patients (Stage I/II) eligible for treatment were enrolled ( n  = 14). Serum was obtained at enrollment and at end of treatment (EoT) where possible ( n  = 6). Normal control samples ( n  = 5) were obtained from patients with normal upper endoscopies. Serum was analyzed for DCLK1 protein content by ELISA. Kruskal-Wallis, Mann Whitney U, Pearson correlation, and Receiver Operating Characteristic tests were used to analyze the data., Results: Serum DCLK1 levels were increased by > 50% in Barrett's Esophagus ( n  = 9) and EAC patients ( n  = 14) vs controls (n = 5, p  = 0.0007). These levels were reduced > 50% at EoT compared to EAC ( p  = 0.033). Although age was significantly lower in controls, this factor was not statistically related to DCLK1 serum levels ( p  = 0.66)., Conclusions: EAC treatment results in significantly decreased serum DCLK1 levels, suggesting that DCLK1 may be useful as a non-invasive disease regression biomarker following treatment., Impact: Biomarkers for EAC therapeutic response have been poorly studied and no reliable marker has been discovered thus far. These results demonstrate that DCLK1 may have potential as a circulating biomarker of the response to therapy in EAC, which could be used to improve patient outcomes., Competing Interests: All patients provided informed consent and samples were deidentified. The University of Oklahoma Health Sciences Center Institutional Review Board approved the study.Not applicable.NW and CWH have ownership interests in COARE Holdings Inc.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Renal cell carcinoma (RCC) is a common and devastating disease characterized by a hypoxic microenvironment, epithelial-mesenchymal transition and potent resistance to therapy evidencing the presence of cancer stem cells (CSCs). Various CSC markers have been studied in RCC, but overall there is limited data on their role and most markers studied have been relatively nonspecific. Doublecortin-like kinase 1 (DCLK1) is a validated CSC marker in the gastrointestinal tract and evidence for an equivalent role in other cancers is accumulating. We used bioinformatics, immunohistochemistry, flow cytometry, spheroid self-renewal and chemoresistance assays in combination with overexpression and siRNA-knockdown to study the stem cell-supportive role of DCLK1 alternative splice variants (DCLK1 ASVs) in RCC. To target tumor cells expressing DCLK1 ASVs directly, we developed a novel monoclonal antibody (CBT-15) and delivered it systemically to RCC tumor xenografts. DCLK1 ASVs were overexpressed, enriched together with CSC markers and predictive of overall and recurrence-free survival in RCC patients. In vitro, DCLK1 ASVs were able to directly stimulate essential molecular and functional characteristics of renal CSCs including expression of aldehyde dehydrogenase, self-renewal and resistance to FDA-approved receptor tyrosine kinase and mTOR inhibitors, while targeted downregulation of DCLK1 reversed these characteristics. Finally, targeting DCLK1 ASV-positive cells with the novel CBT-15 monoclonal antibody blocked RCC tumorigenesis in vivo. These findings establish DCLK1 as a CSC marker with implications for therapy, disease progression and survival in RCC and demonstrate the therapeutic value of DCLK1-targeted monoclonal antibodies against renal CSCs., (© 2018 UICC.)

Background: Barrett's esophagus (BE) is rare in African Americans (AA). However, the risk difference magnitude in histologic BE prevalence between AA and non-Hispanic whites (nHw) has not been quantified to date., Objective: The objective of this article is to determine the degree of histologic BE risk difference between AA and nHw., Methods: PubMed, Web of Science and EMBASE were searched for studies reporting histologic BE in AA/nHw for inclusion. Pooled odds ratios (ORs) with risk estimates of histologic BE occurrence between AA/nHw were calculated along with 95% confidence intervals (CIs). Forest plots were used to quantify heterogeneity. Funnel plots and the Cochrane Collaboration Risk of Bias tool were used to assess bias risk., Results: Eight studies reported BE histologic confirmation in AA/nHw. Analysis demonstrated a nearly 400% increased histologic BE risk in nHw patients compared to AA (OR 3.949, 95% CI 3.069-5.082). In the model without the case-control study, histologic BE risk remained elevated at approximately 360% in nHw compared to AA (OR 3.618, 95% CI 2.769-4.726). Heterogeneity was not present in either model. Risk of bias was significant., Conclusions: Histologic BE risk is elevated in nHw by 3.6-4 times compared to AA. Investigation into understanding any clinical, molecular or genetic mechanisms underlying this risk disparity is warranted.

Background: Barrett's esophagus (BE) is the primary risk factor for esophageal adenocarcinoma (EAC). Limited data exists regarding the frequency of histologically confirmed BE by both gender and ethnicity in the United States. The study aim was to determine whether the frequency of histologically confirmed BE varies by ethnicity and gender., Methods: The University of Florida-Jacksonville endoscopy database was reviewed for all cases of salmon colored esophageal mucosa from September 2002 to August 2007. Histologic BE was diagnosed only if salmon colored esophageal mucosa was seen endoscopically and biopsy confirmed intestinal metaplasia with goblet cells. Data collected included: age at diagnosis, self-reported ethnicity [non-Hispanic white (nHw) or African American (AA)], gender, procedure indication, gastroesophageal reflux disease (GERD) history, atypical manifestations, cigarette smoking, alcohol use, proton pump inhibitor (PPI) use, BE endoscopic length, absence/presence of hiatal hernia, stricture or ulcer, and absence/presence/grade of dysplasia., Results: Salmon colored esophageal mucosa was identified in 391/7,308 patients, distributed ethnically as 306 nHw and 85 AA. Histologic BE was confirmed in 111/391 patients with ethnic distribution of: 95 nHw and 16 AA. Histologically confirmed BE frequency varied both by gender and ethnicity with nHw males having the highest (42.3%) and AA females the lowest (12.3%). Histologically confirmed BE frequency differed significantly between nHw males and nHw/AA females only (P<0.005)., Conclusions: Histologically confirmed BE frequency varies by ethnicity and gender with nHw males having the highest frequency/risk and AA females the lowest. Investigation to improve understanding of the impact of race and gender in BE formation should be performed., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Doublecortin-like kinase 1 (DCLK1) is a gastrointestinal (GI) tuft cell kinase that has been investigated as a biomarker of cancer stem-like cells in colon and pancreatic cancers. However, its utility as a biomarker may be limited in principle by signal instability and dilution in heterogeneous tumors, where the proliferation of diverse tumor cell lineages obscures the direct measurement of DCLK1 activity. To address this issue, we explored the definition of a miRNA signature as a surrogate biomarker for DCLK1 in cancer stem-like cells. Utilizing RNA/miRNA-sequencing datasets from the Cancer Genome Atlas, we identified a surrogate 15-miRNA expression signature for DCLK1 activity across several GI cancers, including colon, pancreatic, and stomach cancers. Notably, Cox regression and Kaplan-Meier analysis demonstrated that this signature could predict the survival of patients with these cancers. Moreover, we identified patient subgroups that predicted the clinical utility of this DCLK1 surrogate biomarker. Our findings greatly strengthen the clinical significance for DCLK1 expression across GI cancers. Further, they provide an initial guidepost toward the development of improved prognostic biomarkers or companion biomarkers for DCLK1-targeted therapies to eradicate cancer stem-like cells in these malignancies. Cancer Res; 76(14); 4090-9. ©2016 AACR., Competing Interests: Courtney Houchen and Edwin Bannerman-Menson are co-founders of COARE Biotechnology Inc., (©2016 American Association for Cancer Research.)

Aim: To evaluate if differences exist between self-expanding esophageal metal stents (SEMS) and self-expanding esophageal plastic stents (SEPS) when used for benign or malignant esophageal disorders with regard to safety, efficacy, clinical outcomes, placement ease and cost., Methods: A retrospective analysis was performed to evaluate outcome in patients having SEPS/SEMS placed for malignant or benign esophageal conditions from January 2005 to April 2012. Inclusion criteria was completed SEMS/SEPS placement. Outcomes assessed included technical success of and time required for stent placement, procedure-related complications, need for repeat intervention, hospital stay, mortality and costs., Results: Forty-three patients underwent stent placement for either benign/malignant esophageal disease during the study period. Thirty patients had SEMS (25 male, mean age 59.6 years old) and 13 patients had SEPS (10 male, mean age 61.7 years old). Placement outcome as well as complication rate (SEPS 23.1%, SEMS 25.2%) and in-hospital mortality (SEPS 7.7%, SEMS 6.7%) after placement did not differ between stent types. Migration was the most frequent complication reported occurring equally between types (SEPS 66.7%, SEMS 57.1%). SEPS was less costly than SEMS, decreasing institutional cost by $255/stent., Conclusion: SEPS and SEMS have similar outcomes when used for benign or malignant esophageal conditions. However, SEPS use results in decreased costs without impacting care.

In the 2010 Census, just over one-third of the United States (US) population identified themselves as being something other than being non-Hispanic white alone. This group has increased in size from 86.9 million in 2000 to 111.9 million in 2010, representing an increase of 29 percent over the ten year period. Per the American Cancer Society, racial and ethnic minorities are more likely to develop cancer and die from it when compared to the general population of the United States. This is particularly true for colorectal cancer (CRC). The primary aim of this review is to highlight the disparities in CRC among racial and ethnic minorities in the United States. Despite overall rates of CRC decreasing nationally and within certain racial and ethnic minorities in the US, there continue to be disparities in incidence and mortality when compared to non-Hispanic whites. The disparities in CRC incidence and mortality are related to certain areas of deficiency such as knowledge of family history, access to care obstacles, impact of migration on CRC and paucity of clinical data. These areas of deficiency limit understanding of CRC's impact in these groups and when developing interventions to close the disparity gap. Even with the implementation of the Patient Protection and Affordable Healthcare Act, disparities in CRC screening will continue to exist until specific interventions are implemented in the context of each of racial and ethnic group. Racial and ethnic minorities cannot be viewed as one monolithic group, rather as different segments since there are variations in incidence and mortality based on natural history of CRC development impacted by gender, ethnicity group, nationality, access, as well as migration and socioeconomic status. Progress has been made overall, but there is much work to be done.

Background: In the United States, African Americans (AA) have the highest incidence and mortality from colorectal cancer (CRC) of any racial group. Few studies have evaluated if AA who undergo colonoscopy are more likely to have aggressive neoplasia (polyp) tumor biology compared to Caucasians (C). The primary aim of the study was to compare polyp characteristics between AA and C undergoing outpatient colonoscopy., Methods: A single center retrospective cohort study was performed at a single Veteran Administration (VA) health care system. The charts of 4,038 veterans undergoing colonoscopy from 2005 to 2008 were reviewed. After applying exclusion criteria, data was analyzed for 1,388 persons. Categorical variables were compared using the chi-square test and data were expressed as percentages. Continuous variables were compared using student's t-test and the data were expressed as mean with standard deviation., Results: A total of 37% of AA had proximal polyps compared to 21% of C (P<0.0001). Twenty-four percent of AA had polyps with villous histology compared to 16% of C (P=0.01). Twelve percent of AA had hyperplastic polyps compared to 20% of C (P=0.02). There was no difference in the overall prevalence of tubular adenomas, adenomatous polyps with high-grade dysplasia, number, size or polyp morphology between groups., Conclusions: In an equal access healthcare system and under varying indications, AA have more proximal polyps and polyps with more aggressive histology compared to C. This could partially explain the higher incidence of CRC in AA, and the increased likelihood for AA to develop advanced proximal neoplasia.

Background: Barrett's oesophagus is the primary risk factor for oesophageal adenocarcinoma; erosive oesophagitis is considered an intermediate step with Barrett's oesophagus development potential upon healing. Barrett's oesophagus occurs in 9-19% following erosive oesophagitis but minimal data exists in African Americans. The study aim was to determine if ethnicity is associated with Barrett's oesophagus formation following erosive oesophagitis., Methods: Retrospective review of endoscopies from September 2007 to December 2012 was performed. Inclusion criteria were erosive oesophagitis on index endoscopy, repeat endoscopy ≥6 weeks later and non-Hispanic white or African American ethnicity. Barrett's oesophagus frequency following erosive oesophagitis by ethnicity was compared., Results: A total of 14,303 patients underwent endoscopy during the study period; 1636 had erosive oesophagitis. Repeat endoscopy was performed on 125 non-Hispanic white or African American patients ≥6 weeks from the index procedure. Barrett's oesophagus occurred in 8% of non-Hispanic whites while no African American developed it on repeat endoscopy following erosive oesophagitis (p=0.029). No significant difference was seen between ethnic groups in any clinical parameter assessed., Conclusions: African American ethnicity appears to result in decreased Barrett's oesophagus formation following erosive oesophagitis. Further investigation to demonstrate factors resulting in decreased Barrett's oesophagus formation among African Americans should be performed., (Copyright © 2015. Published by Elsevier Ltd.)

Kaposi's sarcoma (KS) of the gastrointestinal tract is not an uncommon disease among individuals with acquired immunodeficiency syndrome (AIDS). The majority is asymptomatic, and for this reason, gastrointestinal KS (GI-KS) remains undiagnosed. With continued tumor growth, considerable variation in clinical presentation occurs including abdominal pain, nausea, vomiting, iron deficiency anemia (either chronic or frank gastrointestinal bleeding), and rarely mechanical obstruction alone or combined with bowel perforation. Endoscopy with biopsy allows for histological and immunohistochemical testing to confirm the diagnosis of GI-KS among those with clinical symptoms. In previous studies, dual treatment with highly active antiretroviral therapy and systemic chemotherapy have been associated with improved morbidity and mortality in individuals with visceral KS. Therefore, investigators have suggested performing screening endoscopies in select patients for early detection and treatment to improve outcome. In this review, we describe a 44 years old man with AIDS and cutaneous KS who presented for evaluation of postprandial abdominal pain, vomiting, and weight loss. On upper endoscopy, an extensive, infiltrative, circumferential, reddish mass involving the entire body and antrum of the stomach was seen. Histologic examination later revealed spindle cell proliferation, and confirmatory immunohistochemical testing revealed human herpes virus 8 latent nuclear antigen expression consistent with a diagnosis of gastric KS. Following this, we present a comprehensive review of literature on KS with emphasis on gastrointestinal tract involvement and management.

Background: Doublecortin-like kinase 1 (DCLK1), a putative tumor stem cell marker has been shown to be highly expressed in the stromal and epithelial compartments in colon and pancreatic cancer as well as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC)., Aim: To prospectively investigate whether the immunohistochemical expression of DCLK1 was associated with detectable DCLK1 plasma expression in patients with existing BE and EAC., Methods: Immunohistochemistry was performed on paraffin-embedded sections using DCLK1 antibody and scored based on staining intensity and tissue involvement. Purified human plasma samples were subjected to Western blot and ELISA analysis., Results: Forty (40) patients were enrolled: 10 controls (normal endoscopy) and 30 with BE/EAC (13 nondysplastic BE [NDBE], 9 dysplastic BE [DBE] and 8 EAC). Mean epithelial DCLK1 staining was as follows: controls = 0.11, NDBE = 3.83, DBE = 6.0, EAC = 7.17. Mean stromal DCLK1 staining was as follows: NDBE = 5.83, DBE = 5.375, EAC = 10.83. DCLK1 was detected by plasma Western blot in 1 control and in all patients with BE/EAC p < 0.0005. Plasma DCLK1 was elevated by ELISA in EAC compared to other groups, p < 0.05., Conclusions: Increased expression of DCLK1 was observed in the epithelium, stroma and plasma of patients with BE/EAC. Furthermore, the presence of detectable DCLK1 in plasma of BE/EAC patients may provide a less invasive, detection tool in those patients as well as represent a novel molecular marker distinguishing between normal esophageal mucosa and BE or EAC.

Neuroendocrine tumors (NET) previously called carcinoid tumors are neoplasms of enterochromaffin/neuroendocrine cell origin which display neurosecretory capacity that may result in the carcinoid syndrome. The annual incidence of patients with NET is 8.4 per 100000; yet many NET remain asymptomatic and clinically undetected. A majority of NET follows a benign course; however, some will display malignant characteristics. NET most commonly occur in the gastrointestinal tract (67%) and bronchopulmonary system (25%). Gastrointestinal NET occur within the stomach, small intestine, liver, and rectum. We report a retrospective study of 11 subjects: Eight with benign carcinoid tumors: duodenal bulb (n = 2), terminal ileum (n = 1), sigmoid colon (n = 2), and rectum (n = 3); three with malignant carcinoid: liver (n = 1) and intra-abdominal site (n = 2). The diagnosis, endoscopic images, outcome, treatment and review of the literature are presented.

Aim: To determine whether a communication instrument provided to patients prior to their primary care physician (PCP) visit initiates a conversation with their PCP about colorectal cancer screening (CRC-S), impacting screening referral rates in fully insured and underinsured patients., Methods: A prospective randomized control study was performed at a single academic center outpatient internal medicine (IRMC, underinsured) and family medicine (FMRC, insured) resident clinics prior to scheduled visits. In the intervention group, a pamphlet about the benefit of CRC-S and a reminder card were given to patients before the scheduled visit for prompting of CRC-S referral by their PCP. The main outcome measured was frequency of CRC-S referral in each clinic after intervention., Results: In the IRMC, 148 patients participated, a control group of 72 patients (40F and 32M) and 76 patients (48F and 28M) in the intervention group. Referrals for CRC-S occurred in 45/72 (63%) of control vs 70/76 (92%) in the intervention group (P ≤ 0.001). In the FMRC, 126 patients participated, 66 (39F:27M) control and 60 (33F:27M) in the intervention group. CRC-S referrals occurred in 47/66 (71%) of controls vs 56/60 (98%) in the intervention group (P ≤ 0.001)., Conclusion: Patient initiated physician prompting produced a significant referral increase for CRC-S in underinsured and insured patient populations. Additional investigation aimed at increasing CRC-S acceptance is warranted.

Colorectal cancer (CRC) remains a highly fatal condition in part due to its resilience to treatment and its propensity to spread beyond the site of primary occurrence. One possible avenue for cancer to escape eradication is via stem-like cancer cells that, through phenotypic heterogeneity, are more resilient than other tumor constituents and are key contributors to cancer growth and metastasis. These proliferative tumor cells are theorized to possess many properties akin to normal intestinal stem cells. Not only do these CRC "stem" cells demonstrate similar restorative ability, they also share many cell pathways and surface markers in common, as well as respond to the same key niche stimuli. With the improvement of techniques for epithelial stem cell identification, our understanding of CRC behavior is also evolving. Emerging evidence about cellular plasticity and epithelial mesenchymal transition are shedding light onto metastatic CRC processes and are also challenging fundamental concepts about unidirectional epithelial proliferation. This review aims to reappraise evidence supporting the existence and behavior of CRC stem cells, their relationship to normal stem cells, and their possible dependence on the stem cell niche.

49-year-old white female with remote h/o sarcoidosis was referred to GI when her liver was noted to be nodular. Physical examination revealed normal vital signs and no icterus, spider nevi, clubbing, ascites, hepatosplenomegaly, or ankle edema. LFTs, hepatitis serologies, ANA, AMA, ASMA, Ferritin, Ceruloplasmin, and α 1-AT, level were unremarkable. Liver biopsy showed cirrhosis. She developed worsening of baseline SOB and was hospitalized. She was eventually diagnosed with constrictive pericarditis. A diagnosis of cardiac cirrhosis was made.

Background: Ambulatory esophageal pH monitoring is, currently, the recommended diagnostic exam for gastroesophageal reflux disease. Data are currently available for African-American (AA) and non-Hispanic white (nHw) volunteers among United States ethnic groups. The purpose of this study was to obtain normal values of 24-h esophageal pH by monitoring healthy adult Hispanic American (HA) volunteers and to compare these with values obtained from healthy AA and nHw volunteers to determine if ethnic variation exists in 24-h esophageal pH., Methods: 24-h Dual esophageal pH monitoring was performed for healthy AA, HA, and nHw. Values for total number of reflux episodes, episodes longer than 5 min, total reflux time, and longest reflux episode in the proximal and/or distal esophagus were obtained for all groups. Differences between groups were considered significant if p<0.05., Results: One-hundred and thirty-six subjects volunteered and completed 24-h pH testing. Fifty-three were AA, 25 HA, and 58 nHw, with males accounting for 52, 47, and 47%, respectively, of each group. AA were older than nHw only and nHw had a lower body mass index than both AA and HA. Shorter study duration was observed for HA than for AA and nHw. No difference was observed between ethnic groups for any measured pH data in the proximal or distal esophagus., Conclusions: No difference exists in values obtained during esophageal pH monitoring among healthy AA, HA, and nHw. This indicates that currently accepted normal values of ambulatory esophageal pH monitoring can be used for all major United States ethnic groups without compromising diagnostic accuracy.

This paper presents commentaries on whether Starling's law applies to the esophagus; whether erythromycin affects esophageal motility; the relationship between hypertensive lower esophageal sphincter and vigorous achalasia; whether ethnic- and gender-based norms affect diagnosis and treatment of esophageal motor disorders; health care and epidemiology of chest pain; whether normal pH excludes esophageal pain; the role of high-resolution manometry in noncardiac chest pain; whether pH-impedance should be included in the evaluation of noncardiac chest pain; whether there are there alternative therapeutic options to PPI for treating noncardiac chest pain; and the usefulness of psychological treatment and alternative medicine in noncardiac chest pain., (© 2013 New York Academy of Sciences.)

Background/aim: Ultrasound marking by radiologists prior to percutaneous liver biopsy (PLB) results in biopsy site adjustment, decreased pain related complications and improved tissue yield. Minimal data exists on the impact of ultrasound marking by gastroenterologists on these parameters. The study aim was to evaluate whether ultrasound marking by gastroenterologists results in improved PLB tissue yield, fewer needle passes and decreased biopsy failure rates compared to blind biopsy, eliminating the need for a separate radiological evaluation., Methodology: All PLB performed by gastroenterologists from June 1999 to February 2003 at the University of Florida College of Medicine, Jacksonville, were reviewed retrospectively. Data collected included ultrasound marked or blind PLB, demographics, indication, number of passes performed, and specimen length, if obtained., Results: Four hundred and eighty PLB were included: 328 performed with ultrasound marking and 152 blind. Ultrasound marking by gastroenterologists prior to PLB resulted in fewer passes and longer specimens as well as a decreased failure rate in ultrasound marked compared to blind PLB., Conclusions: Ultrasound marking by gastroenterologists prior to PLB provided significantly larger tissue samples, fewer needle passes and a decreased biopsy failure rate compared to blind PLB. This removes the need for a separate radiological evaluation on the procedure day.

Ambulatory 24-hour esophageal pH monitoring is the gold standard examination to assess esophageal acid exposure. Gender-related variation is a well-recognized physiologic phenomenon in health and disease. To date, limited gender-specific 24-hour esophageal pH monitoring data are available. The aim of this study was to obtain values of esophageal pH monitoring in males and females without reflux symptoms or gastroesophageal reflux disease (GERD) to determine if gender variation exists in esophageal acid exposure among individuals without these factors. Twenty-four-hour dual esophageal pH monitoring was performed in male and female volunteers without reflux symptoms or GERD. Values for total number of reflux episodes, episodes longer than 5 minutes, total reflux time in minutes, % time with pH below 4, and longest reflux episode in the proximal/distal esophagus were obtained and recorded for both groups. The distal channel was placed 5 cm and proximal channel 15 cm above the manometrically determined lower esophageal sphincter. Means were compared using an independent sample t-test. Sixty-seven males and 69 females were enrolled. All subjects completed esophageal 24-hour pH monitoring without difficulty. There was no age or body mass difference between groups. Females had significantly fewer reflux episodes at both esophageal measuring sites and, significantly less total reflux time and % time with pH below 4 in the distal esophagus than males. All other parameters were similar. Significant gender-related differences exist in esophageal acid exposure, especially in the distal esophagus in individuals without reflux symptoms or GERD. These differences underscore the need for gender-specific reference values for 24-hour pH monitoring, allowing for an accurate evaluation of esophageal acid exposure in symptomatic patients., (© 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Background: Acid suppression therapy (AST) is commonly overprescribed in hospitalised patients. This indiscriminate use increases cost and drug-related side effects. Minimal data is available on interventions aimed at reducing the burden of overprescription. The aim of our study was to evaluate the impact of education and medication reconciliation forms use on admission as well as discharge, on AST overuse in hospitalised patients., Methods: A retrospective chart review of randomly selected patients admitted to the general medicine service at University of Florida Health Science Center/Jacksonville was performed prior to and after the introduction of interventions (education/medication reconciliation) aimed at reducing AST overuse. The percentage of patients started on inappropriate AST, the admitting diagnosis, indications for starting AST and discharge on these medications was compared in the pre and postintervention groups., Results: Acid suppression therapy use declined from 70% (279/400) in the preintervention period to 37% (100/270) postintervention (p < 0.001). There was a reduction in inappropriate prescriptions from 51% (204/400) pre to 22% (60/270) postintervention (p < 0.02). Stress ulcer prophylaxis in low-risk patients or the concomitant use of ulcerogenic drugs continued to motivate inappropriate AST therapy in most patients. Postintervention, only 20% (12/60) of patients were discharged on unneeded AST compared with 69% (140/204) in the preintervention group (p < 0.001)., Conclusion: Interventions consisting of education and use of medication reconciliation forms decreased inappropriate prescription of AST on admission and discharge. This can significantly decrease cost to the healthcare system and the risk of drug interactions., (© 2012 Blackwell Publishing Ltd.)

Background and Aim: In Barrett's esophagus (BE), the normal esophageal squamous epithelium is replaced with a specialized metaplastic columnar epithelium. BE is a premalignant lesion that can progress to esophageal adenocarcinoma (EAC). Currently, there are no early molecular indicators that would predict progression from BE to EAC. As the only permanent residents of the epithelium, stem cells have been implicated in this metaplastic progression. The aim of the present study was to determine the expression of doublecortin and CaM kinase-like-1 (DCAMKL-1) and other putative gastrointestinal stem cell markers in normal esophageal mucosa (NEM), BE, and EAC., Methods: Human NEM, BE, EAC, and multitissue microarrays were analyzed for DCAMKL-1, and immunohistochemically scored based on staining intensity and tissue involvement, with epithelia and stroma scored separately. Total RNA isolated from BE and paired NEM was subjected to real-time reverse-transcription-polymerase chain reaction analysis for DCAMKL-1, leucine-rich repeat-containing G-protein-coupled receptor (LGR5), and Musashi-1 (Msi-1) mRNA expression., Results: DCAMKL-1 was minimally expressed in squamous NEM, but increased in BE (with and without dysplasia) and EAC tissues. In EAC, we found increased stromal DCAMKL-1 staining compared to adjacent epithelia. Within the submucosa of dysplastic BE tissues, an increase in the endothelial cell expression of DCAMKL-1 was observed. Finally, an upregulation of DCAMKL-1, LGR5, and Msi-1 mRNA was seen in BE compared to squamous NEM., Conclusions: In the present study, we report the progressive increase of DCAMKL-1 expression in BE from dysplasia to EAC. Furthermore, there was an increase in putative stem cell markers DCAMKL-1, LGR5, and Msi-1 mRNA. Taken together, these data suggest that the regulation of resident stem cells might play an important role in the progression of BE to EAC., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background: Barrett's Esophagus (BE) is a pre-malignant condition. Limited data on BE dysplasia prevalence exists among United States ethnic groups., Aim: The purpose of this study was to determine if the frequency of BE with dysplasia varies among the major ethnic groups presenting to our institution., Methods: The University of Florida-Jacksonville endoscopy database was searched for all cases of endoscopic BE from September 2002 to August 2007. Histologic BE was diagnosed if salmon colored esophageal mucosa was endoscopically seen at least 1 cm above the top of the gastric folds and biopsy revealed intestinal metaplasia with Alcian blue-containing goblet cells. Demographic data collected for all included: age at diagnosis, ethnicity, sex, previous history of esophageal reflux, atypical manifestations (chronic cough, aspiration), endoscopic length of BE, presence or absence of hiatal hernia, esophageal stricture or ulcer, and presence or absence of dysplasia., Results: Salmon colored esophageal mucosa was observed in 405 of 7,308 patients (5.5%) and histologically confirmed in 115 of 405 patients (28%) reflecting an overall prevalence of BE of 115/7308 (1.6%) in this cohort. Ethnic distribution of histologic BE patients was as follows: 95 (83%) non-Hispanic white (nHw), 16 (14%) African American (AA) and 4 (3%) other. Long segment BE (LSBE) and any form of dysplasia was observed less frequently in AA than nHw (LSBE: 12% vs. 26% and dysplasia: 0% vs. 7%)., Conclusions: LSBE and dysplasia are less frequent in AA than nHw. Studies in AA with BE may illustrate factors limiting dysplasia and LSBE risk.

Objectives: The aim of this study was to determine trends in hospitalization rates and in-hospital mortality of cholangitis and also determine predictive factors of in-hospital mortality., Methods: The Nationwide Inpatient Sample database was utilized for inpatient data analysis from 1988 to 2006. Patients with primary cholangitis International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM) discharge diagnosis were included. Age-adjusted procedure rates for endoscopic retrograde cholangiopancreatography (ERCP) with biliary stent placement and sphincterotomy were also analyzed. Analysis of variance was used to evaluate trends, and linear Poisson multivariate regression model was used to control for variations in age, sex, time of diagnosis, and ethnicity. Logistic regression analysis was performed to determine predictive factors of in-hospital mortality., Results: The age-adjusted hospitalization rate of cholangitis decreased 24.8% from 2.34 per 100,000 in 1988 to 1.76 per 100,000 in 2006 (P < 0.01). The age-adjusted in-hospital mortality of cholangitis increased 9.2% from 165.0 to 181.6 per 100,000 from 1988 to 1998 (P < 0.01), and then declined 73% to 48.9 per 100,000 in 2006 (P < 0.01). The age-adjusted procedure rates for ERCP with biliary stenting increased from 0.55 to 15.23 per 100,000 from 1988 to 2006 (P < 0.01), as did the age-adjusted rates for ERCP with sphincterotomy from 1.06 to 35.64 per 100,000 (P < 0.01)., Conclusions: The hospitalization rate of cholangitis has been declining over the past 2 decades. The overall trend in mortality peaked in 1998 and has shown a subsequent decline that may in part be related to increased utilization of endoscopic biliary decompression.

Background: Literature suggests early post-percutaneous endoscopic gastrostomy (PEG) feeding is as safe as delayed feeding. No consensus exists regarding feeding initiation after PEG placement. We performed a national survey to assess current practice regarding feeding initiation after PEG placement as well as clinical and practitioner based factors associated with early or delayed feeding., Methods: A survey assessing feeding initiation in general ward and intensive care unit patients, current literature knowledge, motility agent use, number of PEG placed per year, along with physician demographics was emailed to 5256 gastroenterologists. Statistical analysis was done using SAS software (V.9)., Results: 28% of gastroenterologists responded. Amongst respondents, 59% were private consultants, 25% academic physicians and 16% trainees. Private gastroenterologists initiated feeding earlier (≤12 h) compared to academic gastroenterologists in general ward and intensive care unit patients (p<0.0001). Amongst respondents, 41% of physicians were aware of current literature on post-PEG feeding times. Physicians aware of current literature started feeding earlier (<12h) compared to those not aware in general ward and intensive care unit patients (p=0.0002). Male physicians instituted feeding earlier than females (p<0.0001)., Conclusions: Feeding initiation after PEG placement varies amongst gastroenterologists. Further studies are required to explore obstacles in standardizing post-PEG feeding practices., (Published by Elsevier Ltd.)