Antiplatelet Monotherapy Is Associated with an Increased Risk of Bleeding After Endoscopic Sphincterotomy.

BACKGROUND: Clinical guidelines recommend continuing antiplatelet monotherapy with aspirin and, in certain situations, other antiplatelet agents in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy. AIMS: Given the scant evidence supporting this recommendation, our primary objective was to determine if the risk of post-sphincterotomy bleeding was increased in patients on antiplatelet monotherapy. METHODS: We performed a systematic search of Cochrane Library, Ovid Embase, Ovid Medline, Pubmed, Scopus, and Web of Science Core Collection databases. Inclusion criteria were adult patients undergoing ERCP and sphincterotomy on antiplatelet monotherapy with the comparator of no antithrombotic therapy. Our primary outcome was post-sphincterotomy bleeding. Methodological quality was assessed with the ROBINS-I tool and the Newcastle-Ottawa Scale. Meta-analysis with random-effects model was performed. RESULTS: The search identified 4676 unique citations, with six cohort studies meeting our inclusion criteria. Post-sphincterotomy bleeding was increased in patients on antiplatelet monotherapy: OR = 1.53 (95% CI 1.03-2.28) without substantial heterogeneity (I2 = 0%). The number needed to harm (the number of patients who would have to receive antiplatelet monotherapy for one additional patient to have a post-sphincterotomy bleeding episode) was 185(95% CI 80-2272). All included studies had methodological shortcomings. CONCLUSION: Antiplatelet monotherapy was associated with a modestly increased risk of post-sphincterotomy bleeding in our systematic review and meta-analysis. More high-quality studies are needed to improve certainty regarding the estimated effect size. REGISTRATION: PROSPERO CRD42020153019.

Spray cryotherapy versus continued radiofrequency ablation in persistent Barrett's esophagus.

Radiofrequency ablation (RFA) is the first-line treatment for flat Barrett's esophagus (BE) with dysplasia, however its role for persistent Barrett's esophagus (PBE) is unclear. PBE requires additional RFA sessions or application of cryotherapy to improve therapeutic response. We performed a retrospective cohort study evaluating cases of PBE treated by endoscopic eradication programs, with and without spray cryotherapy, and evaluated their safety and efficacy. We retrospectively identified patients with PBE, defined as ≤50% BE reduction or unchanged dysplasia after at least two RFA sessions. PBE was treated either by continued RFA (RFA Group) or converting to spray cryotherapy (CRYO Group), both followed by surveillance period. The rate of adverse events (AE), complete response of intestinal metaplasia (CRIM) and complete response of dysplasia (CRD) were recorded. A total of 46 patients, 23 per group, underwent 622 endoscopic therapies. Circumferential BE length was longer in the CRYO Group, but other baseline characteristics were similar, including maximal BE length. Esophageal strictures accounted for 14/16 total AE, 71% of which were RFA related, compared with 14% related to spray cryotherapy (P = 0.02). Overall CRIM/CRD rates in CRYO (83%) and RFA (96%) groups were not statistically different (P = 0.16), however cases in the CRYO Group required more treatment encounters (Median 19 vs. 12, P ≤ 0.01). Multimodal endotherapy is effective for eradicating PBE. Treatment programs incorporating spray cryotherapy are associated with less esophageal strictures but may require more treatment sessions to achieve eradication.

Safety and histologic outcomes of endoscopic submucosal dissection with a novel articulating knife for esophageal neoplasia.

BACKGROUND AND AIMS: Treatment of large esophageal neoplasia is gradually evolving from piecemeal to en bloc resections. Endoscopic submucosal dissection (ESD) is known to achieve more complete resections than piecemeal EMR for large lesions, yet it remains underused in the West because of technical and safety concerns with traditional electrosurgical knives. We aimed to evaluate a novel endoscopic articulating knife used with ESD (ESD-AR) to determine its safety and efficacy for large esophageal neoplasms in comparison with EMR. METHODS: We retrospectively studied clinically indicated cases of ESD-AR and EMR for esophageal lesions that were 15 mm or greater. All EMR cases had at least 3 simultaneous EMRs to adequately compare resection area. Rates of perforation, GI bleeding, technical performance, and pre- and postendoscopic resection diagnoses were evaluated. RESULTS: Seventy-two ESD-AR and 72 widespread EMR cases were evaluated for Barrett's esophagus (56%), adenocarcinoma (36%), squamous nodularity (2%), and squamous cell carcinoma (6%). There were no statistical differences in age, sex, Barrett's esophagus length, and lesion or resection size between the 2 groups. No perforations occurred. Two adverse events were recorded with ESD-AR and none with EMR (3% vs 0%, P = .50); these were associated with anticoagulation use (P = .04) and greater resection area (P = .02). There were more upgraded diagnoses post-ESD versus EMR (27% vs 12%, P = .05). CONCLUSIONS: ESD-AR by an experienced endoscopist has a comparable safety profile with widespread EMR for large esophageal neoplasia and may have advantages for diagnostic staging.

Severity and Outcomes of Upper Gastrointestinal Bleeding With Bloody Vs. Coffee-Grounds Hematemesis.

OBJECTIVES: Numerous reviews indicate bloody hematemesis signifies more severe bleeding than coffee-grounds hematemesis. We assessed severity and outcomes related to bleeding symptoms in a prospective study. METHODS: Consecutive patients presenting with hematemesis or melena were categorized as bloody emesis (N=1209), coffee-grounds emesis without bloody emesis (N=701), or melena without hematemesis (N=1069). We assessed bleeding severity (pulse, blood pressure) and predictors of outcome (hemoglobin, risk stratification scores) at presentation, and outcomes of bleeding episodes. The primary outcome was a composite of transfusion, intervention, or mortality. RESULTS: Bloody and coffee-grounds emesis were similar in pulse ≥100 beats/min (35 vs. 37%), systolic blood pressure ≤100 mm Hg (12 vs. 12%), and hemoglobin ≤100 g/l (25 vs. 27%). Risk stratification scores were lower with bloody emesis. The composite end point was 34.7 vs. 38.2% for bloody vs. coffee-grounds emesis; mortality was 6.6 vs. 9.3%. Hemostatic intervention was more common (19.4 vs. 14.4%) with bloody emesis (due to a higher frequency of varices necessitating endoscopic therapy), as was rebleeding (7.8 vs. 4.5%). Outcomes were worse with hematemesis plus melena vs. isolated hematemesis for bloody (composite: 62.4 vs. 25.6%; hemostatic intervention: 36.5 vs. 13.8%) and coffee-grounds emesis (composite: 59.1 vs. 27.1%; hemostatic intervention: 26.4 vs. 8.1%). CONCLUSIONS: Bloody emesis is not associated with more severe bleeding episodes at presentation or higher mortality than coffee-grounds emesis, but is associated with modestly higher rates of hemostatic intervention and rebleeding. Outcomes with hematemesis are worsened with concurrent melena. The presence of bloody emesis plus melena potentially could be considered in decisions regarding timing of endoscopy.

Cryotherapy for persistent Barrett's esophagus after radiofrequency ablation: a systematic review and meta-analysis.

BACKGROUND AND AIMS: A small but significant proportion of patients with Barrett's esophagus (BE) have persistent dysplasia or intestinal metaplasia (IM) after treatment with radiofrequency ablation (RFA). Cryotherapy is a cold-based ablative modality that is increasingly being used in this setting. We aimed to better understand the efficacy of second-line cryotherapy in patients with BE who have persistent dysplasia or IM after RFA by conducting a systematic review and meta-analysis. METHODS: We performed a systematic literature search of Pubmed, EMBASE, and Web of Science through September 1, 2017. Articles were included for meta-analysis based on the following inclusion criteria: ≥5 patients with BE treated with RFA had persistent dysplasia or IM; they subsequently underwent ≥1 session of cryotherapy with follow-up endoscopy; the proportions of patients achieving complete eradication of dysplasia (CE-D) and/or IM (CE-IM) were reported. The main outcomes were pooled proportions of CE-D and CE-IM by using a random effects model. RESULTS: Eleven studies making up 148 patients with BE treated with cryotherapy for persistent dysplasia or IM after RFA were included. The pooled proportion of CE-D was 76.0% (95% confidence interval [CI] 57.7-88.0), with substantial heterogeneity (I2 = 62%). The pooled proportion of CE-IM was 45.9% (95% CI, 32.0-60.5) with moderate heterogeneity (I2 = 57%). Multiple preplanned subgroup analyses did not sufficiently explain the heterogeneity. Adverse effects were reported in 6.7% of patients. CONCLUSION: Cryotherapy successfully achieved CE-D in three fourths and CE-IM in half of patients with BE who did not respond to initial RFA. Considering its favorable safety profile, cryotherapy may be a viable second-line option for this therapeutically challenging cohort of patients with BE, but higher-quality studies validating this remain warranted.

Volumetric laser endomicroscopy interpretation and feature analysis in dysplastic Barrett's esophagus.

BACKGROUND AND AIM: Volumetric laser endomicroscopy (VLE) is used to identify Barrett's esophagus (BE) dysplasia. Selection of a dysplastic region of interest (ROI) can be challenging due to feature variability across a large amount of data. The degree of agreement among VLE users in selecting a ROI has not been studied. METHODS: High-definition videos that divided a VLE scan from 18 patients with biopsy-proven BE dysplasia into 1-cm segments were reviewed using a four-quadrant grid superimposed for systematic interpretation. VLE scans were selected based on image quality and appropriate visualization of BE epithelium. Four experienced VLE users rated each quadrant as dysplastic or non-dysplastic. For quadrants rated as dysplastic, reviewers selected a single timeframe with representative features. A high-degree of agreement among reviewers was defined as ≥75% agreement on the quadrant diagnosis and ≥50% agreement on selected timeframe (±2 s). RESULTS: Thirty-one videos, each 32 s in length, comprising 124 quadrants were reviewed. There was high-agreement among reviewers in 99 (80%) quadrants, of which 68 (69%) were rated as dysplastic. Compared with quadrants rated as non-dysplastic, ROIs of quadrants rated as dysplastic contained a higher number of epithelial glands (12.7 vs 1.2, P < 0.001) with atypical architecture (54 vs 1, P < 0.001). A statistically significant difference was observed between the signal intensity profiles of quadrants rated as dysplastic and quadrants rated as non-dysplastic (P = 0.004). CONCLUSION: This study highlights that experienced VLE users can identify ROIs with high-degree of agreement. Selected ROIs contained VLE features associated with BE dysplasia.

Mucosal Ablation in Patients with Barrett's Esophagus: Fry or Freeze?

The management of Barrett's esophagus and early esophageal adenocarcinoma has shifted away from esophagectomy and toward endoscopic techniques, including endoscopic resection and ablative therapies. The most commonly used ablative therapies are radiofrequency ablation and cryotherapy. Radiofrequency ablation has risen to the top of the management algorithm due to its favorable safety profile and established track record of efficacy in patients with dysplastic Barrett's. Cryotherapy offers early promise as an alternatively safe and effective ablative modality. We review radiofrequency ablation and cryotherapy techniques, and updated data regarding their efficacy and safety as well as their roles in the management of Barrett's esophagus.

No Benefit From Platelet Transfusion for Gastrointestinal Bleeding in Patients Taking Antiplatelet Agents.

BACKGROUND & AIMS: Antiplatelet agents decrease cardiovascular events but increase gastrointestinal bleeding (GIB). Guidelines propose platelet transfusion for patients who take antiplatelet agents and have serious GIB. We investigated whether such patients are at decreased risk for rebleeding or increased risk for cardiovascular events after platelet transfusion. METHODS: We performed a retrospective cohort study of patients with GIB admitted to Yale-New Haven Hospital from 2008 to 2013 who were taking antiplatelet agents and had platelet counts higher than 100 × 109/L. Cases (patients who received platelet transfusion, n = 204) were matched with controls (no platelet transfusions, n = 204) for sex, age, and GIB location. The primary outcome was recurrent GIB. Multivariable regression analyses were performed to adjust for differences in baseline characteristics. RESULTS: Cases and controls had similar proportions of GIB due to non-variceal upper GIB (117 of 204, 57% vs 115 of 204, 56%) and colonic GIB (80 of 204, 39% vs 81 of 204, 40%). Cases had more severe GIB than controls, which was based on lower blood pressure and hemoglobin levels and higher heart rates and the proportion admitted to intensive care. Univariate analyses showed that higher proportions of cases had major cardiovascular events (23% vs 13% for controls), died (7% vs 1% for controls), or had hospital stay longer than 4 days (47% vs 33% for controls). However, multivariable analyses showed a significant difference between cases and controls in only risk of death (odds ratio, 5.57; 95% confidence interval, 1.52-27.1). The adjusted odds ratio for recurrent bleeding was 1.47 (95% confidence interval, 0.73-3.05) for cases vs controls. CONCLUSIONS: The use of platelet transfusions in patients with GIB who are taking antiplatelet agents without thrombocytopenia did not reduce rebleeding but was associated with higher mortality. At least some of the increase in mortality could be due to the residual bias of an observational study, but because of the lack of benefit, we do not support the use of platelet transfusions in patients with GIB who are taking antiplatelet agents.

Editorial: The Effect of Bias on Estimation of Improved Survival After Diagnosis of Barrett's Esophagus.

Adjustments for lead and length time bias has been used when examining apparent survival advantages from screening procedures. However, these estimates depend on several assumptions and are modeled from malignancies that are fairly common and large cohorts are available. In smaller retrospective cohorts, adjustments themselves may be based on estimates that may not be biological nor statistically accurate, which can lead to divergent results as has been found in several recent studies of screening in Barrett's esophagus. Only a prospective randomized controlled trial can really determine the benefit though this may not feasible.

A Novel Home for Hemangiomas: Sclerosing Hemangioma in the Pancreas.

Pancreatic hemangiomas, predominantly in female patients, are rare benign vascular tumors. We report a unique case of an incidentally discovered pancreatic sclerosing hemangioma. The patient's clinical presentation and imaging were concerning for an abdominal mass. Endoscopic ultrasound and histopathology confirmed the pancreatic sclerosing hemangioma. Because there were no complications, surgery was not performed, and the patient was monitored. Biopsy confirmation is crucial to rule out malignancy and avoid unnecessary surgical resection.

B-cell count and survival: differentiating chronic lymphocytic leukemia from monoclonal B-cell lymphocytosis based on clinical outcome.

The diagnosis of chronic lymphocytic leukemia (CLL) in asymptomatic patients has historically been based on documenting a characteristic lymphocyte clone and the presence of lymphocytosis. There are minimal data regarding which lymphocyte parameter (absolute lymphocyte count [ALC] or B-cell count) and what threshold should be used for diagnosis. We analyzed the relationship of ALC and B-cell count with clinical outcome in 459 patients with a clonal population of CLL phenotype to determine (1) whether the CLL diagnosis should be based on ALC or B-cell count, (2) what lymphocyte threshold should be used for diagnosis, and (3) whether any lymphocyte count has independent prognostic value after accounting for biologic/molecular prognostic markers. B-cell count and ALC had similar value for predicting treatment-free survival (TFS) and overall survival as continuous variables, but as binary factors, a B-cell threshold of 11 x 10(9)/L best predicted survival. B-cell count remained an independent predictor of TFS after controlling for ZAP-70, IGHV, CD38, or fluorescence in situ hybridization (FISH) results (all P < .001). These analyses support basing the diagnosis of CLL on B-cell count and retaining the size of the B-cell count in the diagnostic criteria. Using clinically relevant criteria to distinguish between monoclonal B-cell lymphocytosis (MBL) and CLL could minimize patient distress caused by labeling asymptomatic people at low risk for adverse clinical consequences as having CLL.

Scissor-type knife improves the safety of endoscopic submucosal dissection (ESD) among endoscopists without experience in ESD: a randomized ex vivo study.

Background and study aims Endoscopic submucosal dissection (ESD) is technically challenging, difficult to learn, and carries a substantial risk of perforation, all of which remain significant barriers to its adoptability. We aimed to determine whether use of a novel scissor-type knife improved efficacy and safety among novice performers of ESD. Materials and methods Following a brief didactic session on ESD, participants performed ESD of two lesions (2 cm diameter) in an ex vivo porcine gastric model. One resection was performed with a conventional knife and the other with the scissor knife (order of knife randomized). We recorded procedure time, successful en bloc resection, and adverse events (including full-thickness perforation and muscle injury) for each dissection. Participants completed a post-study survey. Results 10 endoscopists (8 trainees, 2 staff) considered novices in ESD participated. Compared with the conventional knife, use of the scissor knife was associated with a significantly shorter time to completion of submucosal dissection (mean 6.2 [SD 5.6] vs. 15.6 [SD 15.6] minutes; P  = 0.04) and total procedure time was not significantly different (22.1 [SD 13.3] vs. 24.9 [SD 26.5] minutes; P  = 0.65). Scissor knife use was also associated with a significantly lower proportion of perforation and/or muscle injury (10.0 % vs. 70.0 %; P  < 0.01) and proportion of muscle injury alone (10.0 % vs. 60.0 %; P  = 0.02). Conclusions Among novices performing ESD on an ex vivo animal model, use of a scissor knife was associated with a significantly lower proportion of adverse events without prolonging procedure time. Scissor-type knives may improve ESD safety, at least among novices.

Screening and Preventive Strategies in Esophagogastric Cancer.

Gastric adenocarcinoma, esophageal adenocarcinoma, and esophageal squamous cell carcinoma are among the most prevalent and deadly of malignancies worldwide. Screening and prevention programs will be critical to finally improving outcomes in these diseases. For gastric adenocarcinoma, screening in high-risk populations has significantly reduced mortality. More research is needed on screening high-risk individuals in low-risk populations. For esophageal adenocarcinoma, work is needed to develop efficient and effective techniques in mass screening programs. For most Western populations, current screening is not cost effective. Avoiding environmental risk factors is critical to reducing the incidence of this deadly illness.

Screening for Barrett's esophagus.

Barrett's esophagus is the only known esophageal precursor for the development of esophageal adenocarcinoma. However, screening for Barrett's esophagus remains controversial. Although screening is advocated in selected populations, it is unclear how it should be implemented. In this review, the current definition of Barrett's esophagus will be discussed. There will be a review of the emerging evidence supporting the cost-effectiveness of screening and surveillance for Barrett's esophagus in preventing esophageal adenocarcinoma. The known risk factors for Barrett's esophagus and the development of esophageal adenocarcinoma, currently utilized to determine the appropriate populations to screen, will be reviewed. Finally we will review the standard techniques utilized to screen for Barrett's esophagus and examine new technologies that might improve the efficacy and availability of Barrett's esophagus screening.

Radiofrequency Ablation of Barrett's Esophagus: Efficacy, Complications, and Durability.

In the last decade, radiofrequency ablation in combination with endoscopic mucosal resection has simplified and improved the treatment of Barrett's esophagus. These treatments not only reduced the progression of dysplastic Barrett's esophagus to esophageal adenocarcinoma but also decreased treatment-related complications. More recent data from larger series with extended follow-up periods are emerging to refine expectations in patients treated with radiofrequency ablation. Although most patients achieve eradication of neoplasia and intestinal metaplasia, in the long-term a substantial portion of patients develop recurrent disease. This article provides an updated review of radiofrequency ablation efficacy, complications, and durability.