Marc Bardou

International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding

DESCRIPTION A multidisciplinary group of 34 experts from 15 countries developed this update and expansion of the recommendations on the management of acute nonvariceal upper gastrointestinal bleeding (UGIB) from 2003. METHODS The Appraisal of Guidelines for Research and Evaluation (AGREE) process and independent ethics protocols were used. Sources of data included original and published systematic reviews; randomized, controlled trials; and abstracts up to October 2008. Quality of evidence and strength of recommendations have been rated by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RECOMMENDATIONS Recommendations emphasize early risk stratification, by using validated prognostic scales, and early endoscopy (within 24 hours). Endoscopic hemostasis remains indicated for high-risk lesions, whereas data support attempts to dislodge clots with hemostatic, pharmacologic, or combination treatment of the underlying stigmata. Clips or thermocoagulation, alone or with epinephrine injection, are effective methods; epinephrine injection alone is not recommended. Second-look endoscopy may be useful in selected high-risk patients but is not routinely recommended. Preendoscopy proton-pump inhibitor (PPI) therapy may downstage the lesion; intravenous high-dose PPI therapy after successful endoscopic hemostasis decreases both rebleeding and mortality in patients with high-risk stigmata. Although selected patients can be discharged promptly after endoscopy, high-risk patients should be hospitalized for at least 72 hours after endoscopic hemostasis. For patients with UGIB who require a nonsteroidal anti-inflammatory drug, a PPI with a cyclooxygenase-2 inhibitor is preferred to reduce rebleeding. Patients with UGIB who require secondary cardiovascular prophylaxis should start receiving acetylsalicylic acid (ASA) again as soon as cardiovascular risks outweigh gastrointestinal risks (usually within 7 days); ASA plus PPI therapy is preferred over clopidogrel alone to reduce rebleeding.

Consensus Recommendations for Managing Patients with Nonvariceal Upper Gastrointestinal Bleeding

Upper gastrointestinal (GI) bleeding represents a substantial clinical and economic burden. It has a prevalence of approximately 170 cases per 100 000 adults per year (1), at an estimated total cost of

Magnetic Resonance Cholangiopancreatography: A Meta-Analysis of Test Performance in Suspected Biliary Disease

750 million in U.S. dollars (2). Peptic ulcer disease accounts for 50% to 70% of cases of acute nonvariceal upper GI bleeding (3, 4). Despite recent advances in therapy, mortality rates have remained essentially unchanged at 6% to 8% (1, 2, 5). This could be explained by the fact that patients are older and have more concurrent illnesses; it may also be due to underuse of endoscopic hemostatic techniques. The Canadian Registry in Upper Gastrointestinal Bleeding and Endoscopy (RUGBE) initiative and international data have demonstrated wide variations in the utilization and timing of different diagnostic and therapeutic technologies, as well as disparate management approaches (4-10). In this context, it is surprising that, except for the recent British Society of Gastroenterology guidelines (9), the last widely disseminated consensus conference and publication of practice guidelines occurred more than 10 years ago (11, 12). Since publication of the British Society of Gastroenterology guidelines, new data have become available and are strengthened by a series of evidence-based systematic reviews and meta-analyses performed for this consensus (13, 14). The current guidelines are a consensus paper with multisociety representation. Methods The recommendation statements were developed according to generally accepted standards (15, 16). A 7-step approach addressing most of 37 pertinent criteria of validity was followed (16-20). The process of guideline development is described in the Figure. Figure. The adopted process of guideline development . Determination of Need for Guidelines The need for clinical practice guidelines on the management of patients with nonvariceal upper GI bleeding was identified by an initial review of the existing literature, current recommendations, and the timing of previously published guidelines. Recommendations are directed primarily to the management of nonvariceal bleeding largely due to peptic ulcers. Membership of the Consensus Group An organizing committee selected a multidisciplinary group of 25 voting participants for their expertise in the management of patients with acute nonvariceal upper GI bleeding, evidence-based medicine, and continuing medical education. The group included Canadian and international gastroenterologists, endoscopists, surgeons, family physicians, emergency medicine physicians, pharmacologists, epidemiologists (with methodologic and health economic expertise), and a hospital pharmacist. The attendees represented 11 national societies (Appendix). A representative from the Canadian Association of General Surgeons reviewed the consensus guidelines a posteriori. Nonvoting observers included representatives from government (Health Canada), the pharmaceutical industry, and distributors and manufacturers of endoscopic equipment (Appendix). Determination of Clinically Relevant Issues The issues were determined according to perceived clinical importance, likelihood of being resolved with the existing knowledge base, applicability to current practice, and perceived need for change (16). The RUGBE data were critical to this process (4). The conference organizer and a small working group generated a list of topics and circulated it electronically in advance (21, 22). For each topic, a statement was proposed to the consensus conference participants for discussion, revision, and voting. Nature and Extent of Background Preparation Literature review methods for relevant articles included MEDLINE searches and manual searches of bibliographies of key articles published in English between 1966 and June 2002. Search terms included upper GI bleeding, non-variceal, guidelines, meta-analysis, naso-gastric tube, risk stratification, re-bleeding, mortality, surgery, endoscopy, second-look, clot, stigmata, injection, thermal coaptive, laser, hemostatic clips, proton pump inhibitor, histamine-receptor antagonist, somatostatin, and octreotide. We referred to past reviews, meta-analyses, and published consensus conferences to summarize data up to 1992. New systematic reviews were conducted on data from the past 10 years on the prevalence and natural history of nonvariceal GI bleeding, risk stratification, and various management strategies. Economic considerations were recognized, but the country-specific nature of most cost data limited the review. Data were formally reviewed, including previous consensus opinions (for recommendations 1, 2, 3, and 18), narrative reviews (for recommendations 4, 11, 12, 13, 14, and 19), systematic reviews (for recommendations 5.1, 5.2, 6, and 20), and meta-analyses (for recommendations 7, 8, 9, 10, 15, 16, and 17). Data available only in abstract form were not considered, with the exception of results from 2 meta-analyses by Bardou and colleagues from McGill University (13, 14) and the RUGBE initiative (4), which had been submitted for publication at the time of writing of this manuscript. In addition, for recommendations 7 and 10, data from pivotal abstracts were discussed in detail and were published within 3 months following the conference (23, 24). Consequently, a postconference Delphi process was carried out and results from this final vote were included. More than 875 articles were initially reviewed, and the Delphi process identified 20 issues for discussion. A series of original meta-analyses, including 71 articles and nearly 9000 patients, were performed (13, 14). The key results of specific meta-analyses follow individual statements when appropriate, and full methods and results are available in separate publications (13, 14). Delphi Consensus Process Each statement was graded to indicate the level of evidence available and the strength of the recommendation by using the classification system of the Canadian Task Force on the Periodic Health Examination (Table 1) (25). This scheme was developed to assess therapeutic literature, not literature addressing prognosis (25). Table 1. Categorization of Evidence, Classification of Recommendations, and Voting Schema General Organization A 2-day consensus conference was held in June 2002 under the auspices of the Canadian Association of Gastroenterology. The conference was conducted according to generally accepted standards for the development of clinical practice guidelines (15, 16). At the consensus conference, data were presented and the statements and the grades attributed to evidence were discussed, modified if necessary, and voted on by each participant according to the recognized criteria shown in Table 1 (26). The Canadian Association of Gastroenterology, which administered all aspects of the meeting, secured multipartner funding from industry sponsors. Additional funds were obtained through a peer-review grant received by the Canadian Institutes of Health Research and an internal award from the Research Institute of the McGill University Health Centre. Statements of conflicts of interest were obtained from all voting participants, and additional ethical information was collected (27). Preparation Process and Format of the Report A working group drafted the manuscript, which was then reviewed by all voting conference participants and the nonvoting chair, who approved the final draft. A brief narrative summary regarding the pediatric patient was prepared and can be accessed at www.cag-acg.org/cag_at_glance/positions.htm. An algorithm specifically designed for use in Canada is also under development. Role of the Funding Sources The funding sources had no role in the design, conduct, and reporting of the study or in the decision to submit the results for publication. Recommendation Statements A summary of all of the recommendations is provided in Table 2. Table 2. Summary of Consensus Recommendations for the Management of Patients with Nonvariceal Upper Gastrointestinal Bleeding Initial Management Recommendation 1: Hospitals should develop institution-specific protocols for multidisciplinary management, which should include access to an endoscopist with training in endoscopic hemostasis. Recommendation: C (vote: a, 100%); Evidence: III Previous consensus groups have recommended a multidisciplinary approach with early involvement of a gastroenterologist and surgeon (9, 11, 12, 28). Hospitals with endoscopy services should have a multidisciplinary team in place with a prespecified chain of notification. Not all institutions have immediate access to these specialists, and not all patients require urgent endoscopy; thus, institution-specific protocols should be developed and updated. Endoscopy privileges should be reserved for practitioners who are properly trained according to established credentialing recommendations (29, 30). Recommendation 2: Support staff trained to assist in endoscopy should be available for urgent endoscopy. Recommendation: C (vote: a, 92%; b, 8%); Evidence: III Support staff, including appropriately trained endoscopy assistants, should be available to assist with urgent endoscopies. Any patient identified as high risk for rebleeding ideally should be admitted to a monitored setting for at least the first 24 hours (9). If intensive care beds are unavailable, wards with more intensive monitoring than standard units can be considered. Recommendation 3: Immediate evaluation and appropriate resuscitation are critical to proper management. Recommendation: C (vote: a, 96%; b, 4%); Evidence: III Patients with acute bleeding should be evaluated immediately on presentation. Resuscitation, including stabilization of blood pressure and restoration of intravascular volume (9, 11, 12, 28), should precede further diagnostic and therapeutic measures. Recommendation 4: In selected patients, the placement of a nasogastric tube can be considered because the findings may have prognostic value. Recomme

Obesity and colorectal cancer

Context Noninvasive imaging of the biliary tree with magnetic resonance cholangiopancreatography (MRCP) may detect certain abnormalities better than others. Contribution This meta-analysis summarized 67 studies that compared MRCP with other gold standard tests for diagnosing biliary obstruction (for example, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, and intraoperative or intravenous cholangiography). Magnetic resonance cholangiopancreatography compared well with most other tests, but it seemed slightly less sensitive for diagnosing stones (92%) and for differentiating benign from malignant obstruction (85%) than it was for identifying the presence (99%) and level (96%) of biliary obstruction. Cautions Study quality varied, and some sensitivity estimates had wide confidence intervals. The Editors Biliary diseases and conditions associated with biliary obstruction are a major cause of morbidity and mortality in North America. The accurate diagnosis of the presence and cause of biliary obstruction is key to the cost-effective work-up of patients with suspected biliary disease. Since its introduction in 1968, endoscopic retrograde cholangiopancreatography (ERCP) has become the gold standard in this setting. However, 1.3% to 9% of patients undergoing ERCP will have clinically significant pancreatitis, and 0.2% to 0.5% of patients will die of procedural complications (1-5). In a larger series, diagnostic ERCP was associated with a mortality rate of 0.2% and a moderate to severe pancreatitis rate of 0.7% (1). In 1992, the development of magnetic resonance cholangiopancreatography (MRCP), which used heavy T2-weighting and rapid image acquisition (thus avoiding breathing artifact), allowed the accurate noninvasive imaging of the biliary and pancreatic trees. The weighting involved in selected MRCP sequences is unique because it allows relatively stagnant fluids, such as bile and pancreatic juice, to have a high-signal intensity. Without use of a contrast agent, these fluids appear bright compared with the dark, low-signal intensity of adjacent solid hepatic and pancreatic tissue and fast-flowing fluids (such as circulating blood). Concurrently performed enhanced T1-weighted magnetic resonance imaging (MRI) of the liver and pancreatic parenchyma can complement MRCP by adding important staging information when a malignant disorder is suspected. Although MRCP offered the potential of avoiding ERCP and its attendant risks, evidence for this is lacking because some patients undergoing MRCP will also require ERCP for invasive diagnostic tests (for example, bile sampling or cytologic testing) or for therapy (sphincterotomy, stone removal, or stenting) (6). The possible morbid implication of false-positive and false-negative results also needs to be considered. The identification of clinical scenarios for which MRCP may have limitations is therefore important for the development of adapted clinical guidelines and work-up algorithms in this area. Over the past decade, a plethora of reports have dealt with the accuracy of MRCP in biliary imaging. Most have shown excellent performance in comparison to ERCP or composite gold standards that have included computed tomography (CT), percutaneous transhepatic cholangiography, intraoperative cholangiography, intravenous cholangiography, endoscopic ultrasonography, and surgery, with or without subsequent clinical follow-up (772). However, individually, the studies are too small to allow precise comment on the performance of MRCP in selected diagnostic subgroups, such as patients with suspected stone disease or biliary cancer. In addition, because of variation in study quality, patient samples, MRI technology, and gold standards used, simple pooling of performance characteristics would be inappropriate and potentially misleading. Therefore, we undertook a meta-analysis to better characterize MRCP performance, stratified by clinically important diagnostic scenarios. Methods Search Strategy We searched MEDLINE (from January 1987 to March 2003) and bibliographies using magnetic resonance imaging and biliary tract diseases as Medical Subject Headings terms. The search was a priori restricted to English- and French-language articles. Because of the nature of the articles and subject matter of interest, we believed that MEDLINE would contain all relevant articles and that the use of other databases would be unlikely to reveal additional published studies. We manually screened and assessed abstracts to identify comparative studies with a single or composite gold standard. Most abstracts described articles that were reviews, comparisons of MRI techniques, or case series without comparison with any gold standard (Figure 1). Figure 1. Flowchart of study and abstract exclusions. Inclusion Criteria We included the following types of articles: 1) comparative studies with a defined single or composite gold standard and 2) articles that contained sufficient detail to reconstruct 2 2 tables expressing MRCP results by disease status. Acceptable gold standards included ERCP, intraoperative cholangiography, percutaneous transhepatic cholangiography, intravenous cholangiography, endoscopic ultrasonography, and surgical exploration. We also allowed composite gold standards, including CT and clinical follow-up until clinical and biological abnormalities had resolved or until a diagnosis had been made. If the study type was unclear from the abstract or if no abstract was available but the title suggested a comparative study, the full manuscript was manually reviewed. For bibliographic screening, we also examined relevant reviews. Two international experts were also contacted in an attempt to identify any additional relevant unpublished reports; however, no such reports were found. Exclusion Criteria We excluded case series of patients with a particular diagnosis who were undergoing MRCP and studies in which only patients with positive results on MRCP had other imaging techniques or ERCP to confirm the diagnosis. If a comparative study preselected only patients with a positive test result by using a gold standard to see how MRCP could visualize the abnormalities, we judged the study to be inadequate (even if a group of healthy control persons had been added for comparison). In addition to an artificially set prevalence of disease in such studies and somewhat artificial corresponding predictive values, hand selection of clearly positive and clearly healthy cases may lead to bias. This spectrum bias can occur when a diagnostic test seems to have better performance because more easily diagnosed extremes have been chosen (73, 74). If more than 1 study was included from the same author, we carefully assessed the absence of overlap by using the recruitment periods noted in the manuscript or by contacting the author if the report did not provide these data. Quality Assessment Two authors independently assessed the quality of acceptable manuscripts, and a third author independently settled discrepancies. Studies were graded by using 4 criteria for quality, defined a priori, as described by Irwig and colleagues [75, 76]: 1) blinding, 2) consecutive recruitment of patients, 3) single [versus composite] gold standards, and 4) the nonselective use of the gold standard (that is, the gold standard was performed in all patients). The latter criterion was used to avoid verification bias, which occurs when only abnormal results on the index test lead to the performance of the gold standard to verify the diagnosis (77, 78). To compare the result of MRCP versus that of the gold standard, we then reconstructed 2 2 tables from each study to determine the presence, level, and cause of biliary obstruction, as well as to distinguish benign from malignant obstruction and to detect common bile duct stones. In a particular study, if 22 tables could be reconstructed for more than 1 radiologist, we used the overall results reported in this study, as determined by consensus or a third-party arbitrator, depending on the protocol of the study. Data Stratification and Definition of Imaging End Points We extracted data from the studies and categorized the imaging end points into 4 groupings to diagnose 1) the presence of obstruction; 2) the level of obstruction (here, a diseased patient in terms of the 2 2 table was considered to have hilar or intrahepatic disease, except for the study by Zidi and colleagues [35], which exclusively studied hilar tumors and considered intrahepatic extension to be diseased]; and the presence of either 3) biliary lithiasis or 4) malignancy. Only studies that had more than 5 patients with common bile duct stones were considered in the stone detection subcategory. Potential Confounders We considered 4 other variables, apart from study quality, to be of potential importance for explaining heterogeneity and interstudy variability: 1) imaging end point of the study [presence of obstruction, level of obstruction, presence of common bile duct stones, or presence of malignancy]; 2) clinical context [suspicion of stone, suspicion of malignancy, suspicion of either stone or malignancy, or suspicion of a wide variety of pancreaticobiliary diseases]; 3) MRCP technology era [dichotomized at December 1996, 5 years after its introduction in 1991]; 4) frequency of direct visualization (79-81) of the common bile duct by a conventional gold standard [dichotomized at greater or less than 90% of patients having had ERCP, intraoperative cholangiography, or percutaneous transhepatic cholangiography]; and 4) prevalence of disease. For the MRCP technology era variable, we divided patients into the post-1996 category if most patients seemed to have been recruited after 1 January 1997. Meta-Analytic Statistical Methods and Modeling We assessed the sensitivity and specificity of MRCP by noting the number of true-positive, false-positive, true-negative, and false-negative results. The overall observed sensit

Management of Acute Bleeding from a Peptic Ulcer

Excess body weight, as defined by the body mass index (BMI), has been associated with several diseases and includes subjects who are overweight (BMI≥25–29.9 kg/m2) or obese (BMI≥30 kg/m2). Overweight and obesity constitute the fifth leading risk for overall mortality, accounting for at least 2.8 million adult deaths each year. In addition around 11% of colorectal cancer (CRC) cases have been attributed to overweight and obesity in Europe. Epidemiological data suggest that obesity is associated with a 30–70% increased risk of colon cancer in men, whereas the association is less consistent in women. Similar trends exist for colorectal adenoma, although the risk appears lower. Visceral fat, or abdominal obesity, seems to be of greater concern than subcutaneous fat obesity, and any 1 kg/m2 increase in BMI confers additional risk (HR 1.03). Obesity might be associated with worse cancer outcomes, such as recurrence of the primary cancer or mortality. Several factors, including reduced sensitivity to antiangiogenic-therapeutic regimens, might explain these differences. Except for wound infection, obesity has no significant impact on surgical procedures. The underlying mechanisms linking obesity to CRC are still a matter of debate, but metabolic syndrome, insulin resistance and modifications in levels of adipocytokines seem to be of great importance. Other biological factors such as the gut microbita or bile acids are emerging. Many questions still remain unanswered: should preventive strategies specifically target obese patients? Is the risk of cancer great enough to propose prophylactic bariatric surgery in certain patients with obesity?

Effect of statin therapy on colorectal cancer

The mortality associated with acute bleeding from a peptic ulcer remains high (5 to 10%), and the condition accounts for more than 400,000 hospital admissions per year in the United States. This review summarizes the approach to patient triage and risk stratification, the goals of early endoscopy, the options for medical therapy, and the role of surgery and interventional radiology.

Proton Pump Inhibitors vs. Histamine 2 Receptor Antagonists for Stress-Related Mucosal Bleeding Prophylaxis in Critically Ill Patients: A Meta-Analysis

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also called statins, are commonly prescribed medications that lower serum cholesterol and decrease cardiac morbidity and mortality. They also possess beneficial effects beyond their cholesterol-lowering properties. Preclinical data suggest statins exhibit pleiotropic antineoplastic effects in a variety of tumours, but clinical studies have provided conflicting data as to whether statins influence the risk of cancer. The biological underpinning of potential effects of statins in colorectal cancer and their role in its prevention or as adjuvant therapy are reviewed. Following a meta-analysis of both randomised clinical trials and epidemiological studies, it is concluded that available clinical data only support a modest, although statistically significant, protective effect of statins in colorectal cancer. Statins may impact on outcomes by decreasing the invasiveness or metastatic properties of colorectal cancer. The data supporting these hypotheses, however, are few and further studies are required to better assess these hypotheses. Statins may also exert a beneficial effect on colorectal cancer by sensitising the tumour to chemotherapeutic agents. Further research is needed to better define the role of statins in overcoming chemoresistance. The combination of statins with other drugs, such as low-dose aspirin or safer non-steroidal anti-inflammatory medications, may be useful in both the prevention and treatment of colorectal cancer.

High-dose intravenous proton pump inhibition following endoscopic therapy in the acute management of patients with bleeding peptic ulcers in the USA and Canada: a cost-effectiveness analysis

OBJECTIVES:H2-receptor antagonists (H2RA) have been shown to reduce stress-related mucosal bleeding (SRMB), yet randomized controlled trials assessing proton pump inhibitors (PPIs) have yielded conflicting results. The objective of this study was to evaluate the efficacy of PPIs vs. H2RAs in the prophylaxis of SRMB in critically ill adults with risk factors for bleeding.METHODS:Tailored literature searches of the past four decades were conducted. Outcomes measured were the decreases in rates of clinically significant bleeding (B, primary outcome of the meta-analysis), nosocomial pneumonia (P), and mortality (M) (secondary outcomes). Study heterogeneity was sought and quantified. Results are reported as odd ratios (ORs) with 95% confidence intervals (CIs).RESULTS:Eight fully published randomized controlled trials and five abstracts met the inclusion criteria. Prophylactic PPI administration significantly decreased the incidence of bleeding (N=1,587 patients, OR=0.30; 95% CI: 0.17–0.54), number needed to treat=39; 95% CI: 21–303 with no observed statistical heterogeneity among the relevant comparisons (P=0.93, I2=0.0%). No statistical differences were noted for the development of nosocomial pneumonia (n=7, N=1,017 patients, OR=1.05; 95% CI: 0.69–1.62) or mortality (n=8, N=1,260 patients, OR=1.19; 95% CI: 0.84–1.68) or (and no heterogeneity was found for either: P=0.85, I2=0.0%, and P=0.96, I2=0%, respectively).CONCLUSIONS:In critically ill patients at risk for the development of SRMB, PPI prophylaxis significantly decreased rates of clinically significant bleeding compared with H2RA, without affecting the development of nosocomial pneumonia or mortality rates. The magnitude of the beneficial effect, and its clinical relevance, now requires further characterization using cost-effectiveness analysis considering the incidence of stress-related mucosal disease-related bleeding.

Is routine second-look endoscopy effective after endoscopic hemostasis in acute peptic ulcer bleeding? A meta-analysis

Background : The efficacy of high‐dose intravenous proton pump inhibition has recently been shown, yet its cost‐effectiveness remains poorly studied.

Cost-Effectiveness of Proton-Pump Inhibition Before Endoscopy in Upper Gastrointestinal Bleeding

BACKGROUND Routine second-look endoscopy in modern-era peptic ulcer bleeding (PUB) remains controversial. OBJECTIVE To assess the effectiveness of routine second-look endoscopy in patients with PUB exhibiting high-risk stigmata after standard medical care and endoscopic therapy. DESIGN Comprehensive literature searches (1990-2011) were performed, seeking randomized trials comparing a routine with an as-needed second endoscopy. MAIN OUTCOME MEASUREMENTS The main outcome was rebleeding. Secondary outcomes were surgery and mortality. Subanalyses assessed the influence of study quality, rebleeding definitions, endoscopic hemostasis modality, and proton pump inhibitor (PPI) therapies. Analyses were performed with Revman 5.1. Results are shown as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Only 4 published articles completely reporting studies and 4 abstracts (of 577 citations) were included (938 patients). Rebleeding was significantly decreased by a routine second-look endoscopy (OR 0.55; 95% CI, 0.37-0.81), as was surgery (OR 0.43; 95% CI, 0.19-0.96), but not mortality (OR 0.65; 95% CI, 0.26-1.62). Results remained robust with varying definitions of rebleeding, but not with varying endoscopic hemostasis modalities and PPI therapies; the only trial in which high-dose PPI was used did not show a benefit of a second-look endoscopy. When removing the 2 trials that included patients at highest risk of rebleeding, no significant benefit attributable to a second-look endoscopy was noted (OR 0.65; 95% CI, 0.42-1.00). LIMITATIONS The small number of trials and patients in each of these studies. CONCLUSIONS In the absence of high-dose PPI, especially in patients at very high risk (eg, active bleeding), routine second-look endoscopy appears effective in these selected patients with PUB. However, the generalizability of these results to the era of high-dose PPI and otherwise unselected patients with high-risk stigmata is unclear.