Recurrent Duodenal Ulcer After Gastroduodenal Artery Embolization Due to Coil Migration Successfully Removed Endoscopically Resulting in Ulcer Healing.

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.

A Retrospective Analysis of Porcine Circovirus Type 3 in Samples Collected from 2008 to 2021 in Mexico.

Porcine circovirus type 3 (PCV3) is a nonenveloped virus of the Circoviridae family. This virus has been identified in pigs of different ages and pigs with several clinical manifestations of the disease or even in apparently healthy pigs. While PCV3 was first reported in 2015, several retrospective studies have reported the virus before that year. The earliest report indicates that PCV3 has been circulated in swine farms since 1996. In this study, we evaluated the presence of PCV3 in samples collected in Mexico in 2008, 2015, 2020, and 2021. This study assessed PCV3 DNA by qPCR and antibodies against CAP protein by indirect ELISA. The results showed that PCV3 (DNA and anti-CAP antibodies) was detected in the samples collected from 2008 to 2021. The highest prevalence was in 2008 (100%), and the lowest was in 2015 (negative). Genetic analysis of ORF2 showed that the virus identified belonged to genotype a, as most of the viruses identified thus far. PCV3 was detected in samples from piglets with respiratory signs and growth retardation, sows with reproductive failure, or asymptomatic piglets and sows. Pigs with respiratory signs, growth retardation, or reproductive failure had a higher prevalence of antibodies and qPCR-positive samples. In conclusion, this study showed that PCV3 has been circulating in Mexico since 2008 and that PCV3 DNA and antibodies were more prevalent in samples from pigs with clinical manifestations of diseases.

Acute Pancreatitis in a Patient Taking Semaglutide.

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.

Disparities in esophageal cancer incidence and esophageal adenocarcinoma mortality in the United States over the last 25-40 years.

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.

Expanding beyond endoscopy: A review of non-invasive modalities in Barrett's esophagus screening and surveillance.

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.

Tokyo Guidelines (TG18) for Acute Cholangitis Provide Improved Specificity and Accuracy Compared to Fellow Assessment.

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.

Consensus Molecular Subtypes Efficiently Classify Gastric Adenocarcinomas and Predict the Response to Anti-PD-1 Immunotherapy.

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.

An Unusual Long-Term Complication of Bariatric Surgery.

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.

Inhibition of Colon Cancer Cell Growth by Phosphodiesterase Inhibitors Is Independent of cGMP Signaling.

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.

Type-2 cGMP-dependent protein kinase suppresses proliferation and carcinogenesis in the colon epithelium.

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.

Barrett's Esophagus: Diagnosis, Management, and Key Updates.

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.

Characteristics of Serrated Adenomas in Non-Hispanic Whites and African Americans Undergoing Screening Colonoscopy.

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.

It's the Bloody Gallbladder! Spontaneous Gallbladder Hemorrhage Following Factor Xa Inhibition.

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.

Association of Eosinophilic Esophagitis and Human Immunodeficiency Virus.

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.

Effect of a physician led education invention on colon cancer screening at underserved clinics in Georgia.

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.

The Epidemiology of Pancreatic Cancer and the Association With Acetylsalicylic Acid in the United States: A Population-Based Study.

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.

Potential proton pump inhibitor-related adverse effects.

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.

How to approach esophagogastric junction outflow obstruction?

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.

Reverse engineering a predictive signature characterized by proliferation, DNA damage, and immune escape from stage I lung adenocarcinoma recurrence.

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.