Randomized Controlled Trial of Over-the-Scope Clip as Initial Treatment of Severe Nonvariceal Upper Gastrointestinal Bleeding.

BACKGROUND AND AIMS: No prior randomized controlled trial (RCT) has reported patient outcomes of large over-the-scope clip (OTSC) compared to standard hemostasis as initial endoscopic treatment of severe NVUGIB. This was our study aim. METHODS: Patients with bleeding ulcers or Dieulafoy's lesions and major stigmata of hemorrhage - SRH (active spurting bleeding, visible vessel, or clot) - or lesser SRH (oozing bleeding or flat spots - with arterial blood flow by Doppler probe) were randomized to OTSC or standard endoscopic hemostasis (with hemoclips or multipolar electrocoagulation - MPEC). Patients and their healthcare providers were blinded to treatments and made all post-randomization management decisions. Ulcer patients received high dose intravenous infusions of proton pump inhibitors (PPI) for 3 days, then 27 days of oral PPI. 30 day outcomes were prospectively recorded; data management was with SAS; and data analysis was by a statistician. RESULTS: 53 patients (25 OTSC, 28 Standard) were randomized, with similar baseline risk factors. However, there were significant differences in OTSC vs. Standard groups in rates of rebleeding (4% vs. 28.6%; p = .017; relative risk 0.10, 95% confidence intervals 0.01, 0.91; number needed to treat 4); severe complications (0 % vs. 14.3%); and post-randomization units of red cell transfusions (0.04 vs. 0.68). All rebleeds occurred in patients with major SRH and none with lesser SRH. CONCLUSION: 1. OTSC significantly reduced rates of rebleeding, severe complications, and post-randomization red cell transfusions. 2. Patients with major stigmata benefited significantly from hemostasis with OTSC, but those with lesser stigmata did not. (ClinicalTrials.gov, Number: NCT03065465).

Trends in Esophageal Cancer Mortality and Stage at Diagnosis by Race and Ethnicity in the United States.

INTRODUCTION: Esophageal cancer (EC) is an aggressive malignancy with poor prognosis. Mortality and disease stage at diagnosis are important indicators of improvements in cancer prevention and control. We examined United States trends in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) mortality and stage at diagnosis by race and ethnicity. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) data to identify individuals with histologically confirmed EAC and ESCC between 1 January 1992 and 31 December 2016. For both EAC and ESCC, we calculated age-adjusted mortality and the proportion presenting at each stage by race/ethnicity, sex, and year. We then calculated the annual percent change (APC) in each indicator by race/ethnicity and examined changes over time. RESULTS: The study included 19,257 EAC cases and 15,162 ESCC cases. EAC mortality increased significantly overall and in non-Hispanic Whites from 1993 to 2012 and from 1993 to 2010, respectively. EAC mortality continued to rise among non-Hispanic Blacks (NHB) (APC = 1.60, p = 0.01). NHB experienced the fastest decline in ESCC mortality (APC = - 4.53, p < 0.001) yet maintained the highest mortality at the end of the study period. Proportions of late stage disease increased overall by 18.5 and 24.5 percentage points for EAC and ESCC respectively; trends varied by race/ethnicity. CONCLUSION: We found notable differences in trends in EAC and ESCC mortality and stage at diagnosis by race/ethnicity. Stage migration resulting from improvements in diagnosis and treatment may partially explain recent trends in disease stage at diagnosis. Future efforts should identify factors driving current esophageal cancer disparities.

Esophageal IgG4: Clinical, Endoscopic, and Histologic Correlations in Eosinophilic Esophagitis.

OBJECTIVE: Recent studies show increased serum and esophageal IgG4 in patients with eosinophilic esophagitis (EoE), suggesting a possible IgG4-involved process. The role of IgG4 in pediatric EoE has not been extensively investigated. Our aim was to analyze IgG4 in esophageal tissue in children in parallel to that in adults with EoE. METHODS: In a retrospective institutional review board-approved study, we performed immunohistochemical staining of IgG4 in esophageal biopsy specimens from 39 subjects: children with EoE (n = 16), adults with EoE (n = 15), children with reflux esophagitis (n = 4), and pediatric controls (n = 4). We assessed the relationships between IgG4 staining and clinical, endoscopic, and histopathologic characteristics. RESULTS: Patients with EoE were significantly more likely to stain positively for IgG4 than children with reflux esophagitis or controls (P = 0.015). Fifteen of 31 (48%) EoE cases stained positively for IgG4. None of the reflux esophagitis or control cases stained positively. IgG4 staining had 48% sensitivity and 100% specificity for EoE. There was a trend toward IgG4 staining being associated with foreign body/food impaction (P = 0.153). There was a strong association between distal IgG4 staining and basal zone hyperplasia (P = 0.003). CONCLUSIONS: Our study suggests IgG4 is not a consistent finding of EoE at disease diagnosis. Although IgG4 staining was specific for EoE, it had a poor sensitivity with positive staining in only 48% of EoE patients. Further studies are warranted to fully elucidate the role of IgG4 in EoE.

What Does Lesion Blood Flow Tell Us About Risk Stratification and Successful Management of Non-variceal UGI Bleeding?

PURPOSE OF REVIEW: There has been a decline in mortality associated with upper gastrointestinal (UGI) hemorrhage as the use of urgent endoscopy has increased. This review will examine endoscopic risk stratification of non-variceal UGI bleeding (e.g., ulcers, Dieulafoy lesions, and Mallory-Weiss tears), including the use of the Doppler endoscopic probe (DEP). RECENT FINDINGS: Prospective studies evaluating the use of DEP in non-variceal UGI hemorrhage showed that lesions with high-risk stigmata of recent hemorrhage (SRH) have a higher rate of a positive DEP signal compared to those with intermediate-risk SRH. Additionally, lesions with a persistently positive DEP signal after endoscopic hemostasis were seen with high-risk SRH and had a higher 30-day rebleeding rate. Residual arterial blood flow underneath ulcers is a significant risk factor for rebleeding. However, if more endoscopic treatment is applied, clinical outcomes for patients with severe non-variceal UGI hemorrhage are improved, as documented by a recent CURE Hemostasis randomized controlled trial (RCT).

Doppler endoscopic probe as a guide to risk stratification and definitive hemostasis of peptic ulcer bleeding.

BACKGROUND AND AIMS: For more than 4 decades endoscopists have relied on ulcer stigmata for risk stratification and as a guide to hemostasis. None used arterial blood flow underneath stigmata to predict outcomes. For patients with severe peptic ulcer bleeding (PUB), we used a Doppler endoscopic probe (DEP) for (1) detection of blood flow underlying stigmata of recent hemorrhage (SRH), (2) quantitating rates of residual arterial blood flow under SRH after visually directed standard endoscopic treatment, and (3) comparing risks of rebleeding and actual 30-day rebleed rates for spurting arterial bleeding (Forrest [F] IA) and oozing bleeding (F IB). METHODS: Prospective cohort study of 163 consecutive patients with severe PUB and different SRH. RESULTS: All blood flow detected by the DEP was arterial. Detection rates were 87.4% in major SRH-spurting arterial bleeding (F IA), non-bleeding visible vessel (F IIA), clot (F IIB)-and were significantly lower at 42.3% (P < .0001) for an intermediate group of oozing bleeding (F IB) or flat spot (F IIC). For spurting bleeding (F IA) versus oozing (F IB), baseline DEP arterial flow was 100% versus 46.7%, residual blood flow detected after endoscopic hemostasis was 35.7% versus 0%, and 30-day rebleed rates were 28.6% versus 0% (all P < .05). CONCLUSIONS: (1) For major SRH versus oozing or spot, the arterial blood flow detection rate by the DEP was significantly higher, indicating a higher rebleed risk. (2) Before and after endoscopic treatment, spurting (F IA) PUB had significantly higher rates of blood flow detection than oozing (F IB) PUB and a significantly higher 30-day rebleed rate. (3) The DEP is recommended as a new endoscopic guide with SRH to improve risk stratification and potentially definitive hemostasis for PUB.

Comparison of Three Risk Scores to Predict Outcomes of Severe Lower Gastrointestinal Bleeding.

BACKGROUND AND AIMS: Improved medical decisions by using a score at the initial patient triage level may lead to improvements in patient management, outcomes, and resource utilization. There is no validated score for management of lower gastrointestinal bleeding (LGIB) unlike for upper gastrointestinal bleeding. The aim of our study was to compare the accuracies of 3 different prognostic scores [Center for Ulcer Research and Education Hemostasis prognosis score, Charlson index, and American Society of Anesthesiologists (ASA) score] for the prediction of 30-day rebleeding, surgery, and death in severe LGIB. METHODS: Data on consecutive patients hospitalized with severe gastrointestinal bleeding from January 2006 to October 2011 in our 2 tertiary academic referral centers were prospectively collected. Sensitivities, specificities, accuracies, and area under the receiver operator characteristic curve were computed for 3 scores for predictions of rebleeding, surgery, and mortality at 30 days. RESULTS: Two hundred thirty-five consecutive patients with LGIB were included between 2006 and 2011. Twenty-three percent of patients rebled, 6% had surgery, and 7.7% of patients died. The accuracies of each score never reached 70% for predicting rebleeding or surgery in either. The ASA score had a highest accuracy for predicting mortality within 30 days (83.5%), whereas the Center for Ulcer Research and Education Hemostasis prognosis score and the Charlson index both had accuracies <75% for the prediction of death within 30 days. CONCLUSIONS: ASA score could be useful to predict death within 30 days. However, a new score is still warranted to predict all 30 days outcomes (rebleeding, surgery, and death) in LGIB.

Origin, Clinical Characteristics and 30-Day Outcomes of Severe Hematochezia in Cirrhotics and Non-cirrhotics.

BACKGROUND: The sites of origin, causes and outcomes of severe hematochezia have not been compared between cirrhotics and non-cirrhotics. In cirrhotics versus non-cirrhotics presenting with severe hematochezia, we aimed at (1) identifying the site and etiology of gastro-intestinal bleeding and independent predictors of bleeding from the upper gastrointestinal tract versus small bowel or the colon, (2) comparing 30-day clinical outcomes, and (3) proposing an algorithm for management of severe hematochezia. METHODS: In this cohort study from two university-based medical centers, 860 consecutive patients with severe hematochezia admitted from 1995 to 2011 were prospectively enrolled with 160 (18.6 %) cirrhotics. We studied (a) general clinical and laboratory characteristics of cirrhotics versus non-cirrhotics, (b) predictors of bleeding sites in each patient group by multiple variable regression analysis, and compared (c) 30-day outcomes, including rebleeding, surgery and deaths. RESULTS: Cirrhosis independently predicted an upper gastrointestinal source of bleeding (OR 3.47; 95 % CI 2.01-5.96) as well as history of hematemesis, melena in the past 30 days, positive nasogastric aspirate, prior upper gastrointestinal bleeding or use of aspirin or non-steroidal anti-inflammatory. The most prevalent diagnoses were esophageal varices (20 %) in cirrhotics and colon diverticular bleeding (27.1 %) in non-cirrhotics. Thirty-day rates of rebleeding, surgical interventions and deaths were 23.1 versus 15 % (P = 0.01), 14.4 versus 6.4 % (P < 0.001), and 17.5 versus 4.1 % (P < 0.001), in cirrhotics versus non-cirrhotics, respectively. CONCLUSIONS: Cirrhosis predicted an upper gastrointestinal site of bleeding in patients presenting with severe hematochezia. The 30-day rates of rebleeding, surgery, and death were significantly higher in cirrhotics than in non-cirrhotics.

Lower GI bleeding: epidemiology and management.

Gastrointestinal (GI) bleeding from the colon is a common reason for hospitalization and is becoming more common in the elderly. While most cases will cease spontaneously, patients with ongoing bleeding or major stigmata of hemorrhage require urgent diagnosis and intervention to achieve definitive hemostasis. Colonoscopy is the primary modality for establishing a diagnosis, risk stratification, and treating some of the most common causes of colonic bleeding, including diverticular hemorrhage which is the etiology in 30% of cases. Other interventions, including angiography and surgery, are usually reserved for instances of bleeding that cannot be stabilized or allow for adequate bowel preparation for colonoscopy. We discuss the colonoscopic diagnosis, risk stratification, and definitive treatment of colonic hemorrhage in patients presenting with severe hematochezia.

A Prospective Multicenter Study Evaluating Endoscopy Competence Among Gastroenterology Trainees in the Era of the Next Accreditation System.

PURPOSE: The Next Accreditation System requires training programs to demonstrate competence among trainees. Within gastroenterology (GI), there are limited data describing learning curves and structured assessment of competence in esophagogastroduodenoscopy (EGD) and colonoscopy. In this study, the authors aimed to demonstrate the feasibility of a centralized feedback system to assess endoscopy learning curves among GI trainees in EGD and colonoscopy. METHOD: During academic year 2016-2017, the authors performed a prospective multicenter cohort study, inviting participants from multiple GI training programs. Trainee technical and cognitive skills were assessed using a validated competence assessment tool. An integrated, comprehensive data collection and reporting system was created to apply cumulative sum analysis to generate learning curves that were shared with program directors and trainees on a quarterly basis. RESULTS: Out of 183 fellowships invited, 129 trainees from 12 GI fellowships participated, with an overall trainee participation rate of 72.1% (93/129); the highest participation level was among first-year trainees (90.9%; 80/88), and the lowest was among third-year trainees (51.2%; 27/53). In all, 1,385 EGDs and 1,293 colonoscopies were assessed. On aggregate learning curve analysis, third-year trainees achieved competence in overall technical and cognitive skills, while first- and second-year trainees demonstrated the need for ongoing supervision and training in the majority of technical and cognitive skills. CONCLUSIONS: This study demonstrated the feasibility of using a centralized feedback system for the evaluation and documentation of trainee performance in EGD and colonoscopy. Furthermore, third-year trainees achieved competence in both endoscopic procedures, validating the effectiveness of current training programs.

Gastric acid inhibition in the treatment of peptic ulcer hemorrhage.

Upper gastrointestinal bleeding from peptic ulcer disease is a common clinical event, resulting in considerable patient morbidity and significant health care costs. Inhibiting gastric acid secretion is a key component in improving clinical outcomes, including reducing rebleeding, transfusion requirements, and surgery. Raising intragastric pH promotes clot stability and reduces the influences of gastric acid and pepsin. Patients with high-risk stigmata for ulcer bleeding (arterial bleeding, nonbleeding visible vessels, and adherent clots) benefit significantly from and should receive high-dose intravenous proton pump inhibitors (PPIs) after successful endoscopic hemostasis. For patients with low-risk stigmata (flat spots or clean ulcer base), oral PPI therapy alone is sufficient. For oozing bleeding (an intermediate risk finding), successful endoscopic hemostasis and oral PPI are recommended. Using intravenous PPIs before endoscopy appears to reduce the frequency of finding high-risk stigmata on later endoscopy, but has not been shown to improve clinical outcomes. High-dose oral PPIs may be as effective as intravenous infusion in achieving positive clinical outcomes, but this has not been documented by randomized studies and its cost-effectiveness is unclear.

The Cutting Edge: Doppler Probe in Guiding Endoscopic Hemostasis.

This article examines use of the Doppler endoscopic probe (DEP) for risk stratification and as a guide to definitive hemostasis of nonvariceal upper gastrointestinal (NVUGI) bleeding and colonic diverticular hemorrhage. Studies report that lesions with high-risk stigmata of recent hemorrhage (SRH) have a higher rate of a positive DEP signal compared with those without such SRH. Lesions with a persistently positive DEP signal after endoscopic hemostasis have a higher 30-day rebleeding rate. Studies document arterial blood flow underneath stigmata of recent hemorrhage as a risk factor for rebleeding of focal nonvariceal gastrointestinal lesions. With DEP probe as a guide, rates of definitive endoscopic hemostasis and clinical outcomes are improved compared with standard visually guided treatment.

Evolving techniques for gastrointestinal endoscopic hemostasis treatment.

With mortality due to gastrointestinal (GI) bleeding remaining stable, the focus on endoscopic hemostasis has been on improving other outcomes such as rebleeding rate, need for transfusions, and need for angiographic embolization or surgery. Over the past few years, a number of devices have emerged to help endoscopically assess and treat bleeding GI lesions. These include the Doppler endoscopic probe, hemostatic powder, and over-the-scope clip. Also, new applications have been described for radiofrequency ablation. In this article, we will discuss these evolving tools and techniques that have been developed, including an analysis of their efficacy and limitations.

Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage.

AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). METHODS: This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. RESULTS: A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. CONCLUSION: Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT.

Uses of probe-based confocal laser endomicroscopy: responses to a question to practitioners.

Confocal laser endomicroscopy is a novel imaging technology, which allows real-time visualization and interpretation of microscopic details in live tissues. Although several potential uses have been identified for this technology, no data are available regarding its real-world uses. We report the results of an email-based survey of experts in North America regarding their use of the technology.

Complete Resection of Ampullary Paragangliomas Confined to the Submucosa on Endoscopic Ultrasound May Be Best Achieved by Radical Surgical Resection.

Paragangliomas of the gastrointestinal tract generally are benign tumors usually found in the second portion of the duodenum. We present a case of paraganglioma of the ampulla of Vater confined to the submucosa on endoscopic ultrasound examination. This was initially treated by endoscopic resection, followed by pancreaticoduodenectomy after local resection margins were positive. Histopathology showed a well-differentiated ampullary paraganglioma confined to the submucosa, but with involvement of one regional lymph node. Only 25 prior cases of paraganglioma at the ampulla of Vater have been reported, and nine of these have demonstrated local or distant metastases. Because of their malignant potential, ampullary paragangliomas should be treated with radical resection if the goal is to achieve complete resection, even if preoperative imaging shows local confinement.