The Impact of Difficult Biliary Cannulation on Post-ERCP Pancreatitis: A Secondary Analysis of the Stent versus Indomethacin Trial Dataset.

BACKGROUND AND AIMS: Difficult biliary cannulation (DBC) is a known risk factor for developing post-ERCP pancreatitis (PEP). To better understand how DBC increases PEP risk, we examined the interplay between technical aspects of DBC and known PEP risk factors. METHODS: This was a secondary analysis of a multicenter, randomized controlled trial comparing rectal indomethacin alone with the combination of rectal indomethacin and prophylactic pancreatic duct (PD) stent placement for PEP prophylaxis in high-risk patients. Participants were categorized into 3 groups: 1) DBC with high pre-procedure risk for PEP, 2) DBC without high pre-procedure risk, and 3) non-DBC at high pre-procedure risk. RESULTS: In all, 1601 (84.1%) participants experienced DBC, which required a mean of 12 (SD 10) cannulation attempts and mean duration of 14.7 minutes (SD 14.9). PEP rate was highest (20.7%) in DBC with high pre-procedure risk, followed by non-DBC with high pre-procedure risk (13.5%) and then DBC without high pre-procedure risk (8.8%). Increasing number of PD-wire passages (aOR:1.97, 95% CI:1.25-3.1) was associated with PEP in DBC, but PD injection, pancreatic sphincterotomy and number of cannulation attempts were not associated with PEP. Combining indomethacin with PD stenting lowered PEP risk (aOR:0.61, 95% CI:0.44-0.84) in DBCs. This protective effect was evident in up to at least 4 PD wire passages. CONCLUSIONS: DBC confers higher PEP risk in additive fashion to pre-procedural risk factors. PD wire passages appear to add the greatest PEP risk in DBCs, but combining indomethacin with PD stenting reduces this risk, even with increasing PD wire passages.

Development and Usability of an Endoscopist Report Card Assessing ERCP Quality.

BACKGROUND AND AIMS: Audit and feedback (A&F) for endoscopic retrograde cholangiopancreatography (ERCP) is relatively understudied despite the demonstrated effectiveness of A&F for endoscopic procedures such as colonoscopy. Endoscopist 'report cards' are one A&F tool. We aimed to develop an ERCP report card and assess its appropriateness, acceptability and feasibility through usability testing. METHODS: A prototype report card was designed using a combination of published quality indicators and established predictors of adverse events (AE). Exploratory analyses from a prospective multi-center registry were performed to further identify novel and/or understudied parameters for possible inclusion. Semi-structured interviews with ERCP endoscopists were conducted and framework analysis performed. Validated post-interview usability instruments were administered. Feedback was incorporated to create a final report card. RESULTS: The report card included domains of technical parameters, AE rates/prevention, and patient-reported experience measures (PREMs). Qualitative feedback was positive, with respondents agreeing with inclusion of relevant content in most domains. Post-interview instruments revealed adequate appropriateness and acceptability. PREMs were felt by respondents to be poorly actionable and were replaced with appropriateness of indication and fluoroscopy usage parameters in the final report card. Concerns were raised regarding the feasibility of implementation due to reliance on difficult-to-obtain granular intraprocedural data. CONCLUSIONS: We designed and tested an ERCP report card that has potential to be an effective A&F intervention for endoscopists in clinical practice. Though feasibility of data capture and implementation are currently limitations, advances in video recording and artificial intelligence technologies could accelerate widespread adoption of such a tool.

Technical Factors Associated With the Benefit of Prophylactic Pancreatic Stent Placement During High-Risk Endoscopic Retrograde Cholangiopancreatography: A Secondary Analysis of the SVI Trial Data Set.

INTRODUCTION: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain. METHODS: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP). RESULTS: Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37-1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73-3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63-1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65-1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49-1.41). DISCUSSION: The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach.

Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial.

BACKGROUND: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. METHODS: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. FINDINGS: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. INTERPRETATION: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. FUNDING: US National Institutes of Health.

Development of an automated ERCP Quality Report Card using structured data fields.

BACKGROUND AND AIMS: Measuring adherence to ERCP quality indicators (QIs) is confounded by variability in indications, maneuvers, and documentation styles. We hypothesized that incorporation of mandatory, structured data fields within reporting software would permit accurate measurement of QI adherence rates and facilitate generation of a provider ERCP report card. METHODS: At two referral centers, endoscopy documentation software was modified to generate provider alerts prior to finalizing the note. The alerts reminded the provider to document the following components in a standardized manner: indication, altered anatomy, prior interventions, and QIs deemed high priority by society consensus, study authors, or both. Adherence rates for each QI were calculated in aggregate and by provider via data extraction directly from the procedure documentation software. Medical records were reviewed manually to measure the accuracy of automated data extraction. Accuracy of automated measurement for each QI was calculated against results derived by manual review. RESULTS: During the 9-month study period, 1,376 ERCP procedures were completed by 8 providers. Manual medical record review confirmed high (98-100%) accuracy of automatic extraction of ERCP QIs from the endoscopy report, including cannulation rate of the native papilla and complete extraction of common bile duct stones. An ERCP report card was generated, allowing for individual comparison of adherence to ERCP QIs with colleagues at their institution and others. CONCLUSION: In this pilot study, use of mandatory, structured data fields within clinical ERCP reports permit the accurate measurement of high priority ERCP QIs and the subsequent generation of interval report cards.

Survival analysis among unresectable pancreatic adenocarcinoma patients undergoing endoscopic or percutaneous interventions.

BACKGROUND AND AIMS: Most patients with pancreatic cancer are diagnosed at a late stage and are not candidates for surgical resection. Many have jaundice requiring biliary drainage, which can be accomplished using ERCP or percutaneous transhepatic biliary drainage (PTBD). To date, no studies have evaluated the impact of ERCP or PTBD on survival among patients with unresectable pancreatic cancer. The aims of our study were to compare overall survival between patients with unresectable pancreatic cancer receiving ERCP with those receiving PTBD, to compare overall survival between patients who received a biliary intervention (ERCP or PTBD) versus those who received no biliary intervention, and to compare secondary outcomes, such as length of hospital stay and costs, between ERCP and PTBD. METHODS: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare database. Patients with known pancreatic cancer were included if they had a pancreatic head mass and/or evidence of biliary obstruction. We used a time-varying Cox proportional hazards model to estimate overall survival of patients receiving ERCP versus PTBD and overall survival among patients who received a biliary intervention versus no biliary drainage. Secondary outcomes included length of hospital stay, costs, and admissions within 30 days. RESULTS: Of 14,808 patients with unresectable pancreatic cancer, 8898 patients (60.0%) underwent biliary drainage and 5910 patients (39.9%) received no biliary intervention. ERCP accounted for most biliary interventions (8271, 93.0%), whereas 623 patients (7.0%) underwent PTBD. In multivariable analysis, ERCP was associated with reduced mortality compared with PTBD (adjusted hazard ratio [aHR], .67; 95% confidence interval [CI], .60-.75). When ERCP or PTBD was compared with no biliary intervention, both procedures were associated with a survival benefit (aHR, .51 [95% CI, .49-.54] and .53 [95% CI, .48-.59], respectively). Compared with patients receiving PTBD, those who underwent ERCP had shorter mean length of hospital stay (7.0 ± 5.7 days vs 9.6 ± 6.6 days, respectively; P < .001) and lower hospital charges ($54,899.25 vs $75,246.00, P < .001) but no significant difference in hospitalization or 30-day readmissions. CONCLUSIONS: ERCP is associated with reduced mortality compared with PTBD in pancreatic cancer patients, highlighting the critical role of ERCP in the management of biliary obstruction from pancreatic cancer.

Needle-compatible miniaturized optoelectronic sensor for pancreatic cancer detection.

Pancreatic cancer is one of the deadliest cancers, with a 5-year survival rate of <10%. The current approach to confirming a tissue diagnosis, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), requires a time-consuming, qualitative cytology analysis and may be limited because of sampling error. We designed and engineered a miniaturized optoelectronic sensor to assist in situ, real-time, and objective evaluation of human pancreatic tissues during EUS-FNA. A proof-of-concept prototype sensor, compatible with a 19-gauge hollow-needle commercially available for EUS-FNA, was constructed using microsized optoelectronic chips and microfabrication techniques to perform multisite tissue optical sensing. In our bench-top verification and pilot validation during surgery on freshly excised human pancreatic tissues (four patients), the fabricated sensors showed a comparable performance to our previous fiber-based system. The flexibility in source-detector configuration using microsized chips potentially allows for various light-based sensing techniques inside a confined channel such as a hollow needle or endoscopy.

Clinical and Economic Outcomes of Patients Undergoing Guideline-Directed Management of Pancreatic Cysts.

INTRODUCTION: Numerous guidelines exist for the management of pancreatic cysts. We sought to compare the guideline-directed management strategies for pancreatic cysts by comparing 2 approaches (2017 International Consensus Guidelines and 2015 American Gastroenterological Association Guidelines) that differ significantly in their thresholds for imaging, surveillance, and surgery. METHODS: We developed a Monte Carlo model to evaluate the outcomes for a cohort of 10,000 patients managed per each guideline. The primary outcome was mortality related to pancreatic cyst management. Secondary outcomes included all-cause mortality, missed cancers, number of surgeries, number of imaging studies, cumulative cost, and quality-adjusted life years. RESULTS: Deaths because of pancreatic cyst management and quality-adjusted life years were similar in both guidelines at a significantly higher cost of $3.6 million per additional cancer detected in the Consensus Guidelines. Deaths from "unrelated" causes (1,422) vastly outnumbered deaths related to pancreatic cysts (125). Secondary outcomes included more missed cancers in the American Gastroenterological Association guideline (71 vs 49), more surgeries and imaging studies in the Consensus guideline (711 vs 163; 116,997 vs 68,912), and higher cost in the Consensus guideline ($168.3 million vs $89.4 million). As the rate of malignant transformation increases, a more-intensive guideline resulted in fewer deaths related to pancreatic cyst management. DISCUSSION: Our study demonstrates trade-offs between more- and less-intensive management strategies for pancreatic cysts. Although deaths related to pancreatic cyst management were similar in each strategy, fewer missed cancers in the more-intensive surveillance strategy is offset by a greater number of surgical deaths and higher cost. In conclusion, our study identifies that if the rate malignant transformation of pancreatic cysts is low (0.12% annually), a less-intensive guideline will result in similar deaths to a more-intensive guideline at a much lower cost.

Correction to: Rectal indomethacin alone versus indomethacin and prophylactic pancreatic stent placement for preventing pancreatitis after ERCP: study protocol for a randomized controlled trial.

An amendment to this paper has been published and can be accessed via the original article.

ACR Appropriateness Criteria® Pancreatic Cyst.

Incidental pancreatic cysts are increasingly detected on imaging studies performed for unrelated indications and may be incompletely characterized on these studies. Adequate morphological characterization is critical due to the small risk of malignant degeneration associated with neoplastic pancreatic cysts, as well as the risk of associated pancreatic adenocarcinoma. For all pancreatic cysts, both size and morphology determine management. Specifically, imaging detection of features, such as pancreatic ductal communication and presence or absence of worrisome features or high-risk stigmata, have important management implications. The recommendations in this publication determine the appropriate initial imaging study to further evaluate a pancreatic cyst that was incidentally detected on a nondedicated imaging study. The recommendations are designed to maximize the yield of diagnostic information in order to better risk-stratify pancreatic cysts and assist in guiding future management. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Family History of Colorectal or Esophageal Cancer in Barrett's Esophagus and Potentially Explanatory Genetic Variants.

INTRODUCTION: We aimed to estimate the effects of a family history of colorectal cancer (CRC) or esophageal cancer on the risk of Barrett's esophagus (BE) and identify variants in cancer genes that may explain the association. METHODS: Men scheduled for screening colonoscopy were recruited to undergo upper endoscopy. Cases and noncases were screenees with and without BE, respectively. The effects of family histories on BE were estimated with logistic regression, adjusting for the potential confounders. We additionally recruited men recently diagnosed with BE by clinically indicated endoscopies. Banked germline DNA from cases of BE with ≥2 first-degree relatives (FDRs) with CRC and/or an FDR with esophageal cancer underwent next-generation sequencing using a panel of 275 cancer genes. RESULTS: Of the 822 men screened for CRC who underwent upper endoscopy, 70 were newly diagnosed with BE (8.5%). BE was associated with family histories of esophageal cancer (odds ratio = 2.63; 95% confidence interval = 1.07-6.47) and CRC in ≥2 vs 0 FDRs (odds ratio = 3.73; 95% confidence interval = 0.898-15.4). DNA analysis of subjects with both BE and a family history of cancer identified one or more germline variants of interest in genes associated with cancer predisposition in 10 of 14 subjects, including the same novel variant in EPHA5 in 2 unrelated individuals. DISCUSSION: We found an increased risk for BE associated with a family history of esophageal cancer or CRC. Although analysis of germline DNA yielded no clinically actionable findings, discovery of the same EPHA5 variant of uncertain significance in 2 of 14 cases merits additional investigation.

Racial Disparities and Trends in Pancreatic Cancer Incidence and Mortality in the United States.

BACKGROUND & AIMS: Pancreatic cancer is one of the few cancers in the United States that is increasing in incidence. Little is known about racial disparities in incidence and mortality. We characterized racial disparities in pancreatic cancer incidence and mortality in different locations, time periods, age groups, and disease stages. METHODS: We obtained data on the incidence of pancreatic cancer from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results program of cancer registries from 2001 through 2015 on incidence, demographics, tumor characteristics, and population estimates for all 50 states and the District of Columbia. We obtained data on mortality from pancreatic cancer from the National Center for Health Statistics during the same time period. We plotted incidence rates by 10-year age group (30-39 years through 70-79 years and 80 years or older) separately for white and black patients. We calculated incidence and mortality rate ratios with 95% CIs for categories of age and race. To determine racial disparities, we calculated incidence rate ratios (IRR) for black vs white patients and mortality rate ratios by state. RESULTS: Disparities in pancreatic cancer incidence and mortality in black vs white patients decreased over 5-year time periods from 2001 through 2015. However, among all age groups, from 2001 through 2015, pancreatic cancer incidence and mortality were higher among blacks than whites (incidence, 24.7 vs 19.4 per 100,000; IRR, 1.28; 95% CI, 1.26-1.29; mortality, 23.3 vs 18.4 per 100,000; IRR, 1.27; 95% CI, 1.26-1.28). Black patients had a higher incidence of distant pancreatic cancer (IRR, 1.32; 95% CI, 1.31-1.34) and a lower incidence of local cancer. Incidence increased in whites and blacks of younger age groups and was most prominent among persons 30-39 years old. Incidence increased by 57% among younger whites (IRR, 1.70; 95% CI, 1.43-2.02) and by 44% among blacks (IRR, 1.47; 95% CI, 1.01-2.15) from 2001 through 2015. Mortality remained stable among blacks and slightly increased among whites during this time period. CONCLUSIONS: In the United States, there are racial disparities in pancreatic incidence and mortality that vary with location, patient age, and cancer stage. Further research is needed to identify factors associated with increasing incidence and persistence of racial disparities in pancreatic cancer.

Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial.

BACKGROUND: Although rectal indometacin 100 mg is effective in reducing the frequency and severity of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients, the optimal dose is unknown, and pancreatitis incidence remains high. The aim of this study was to compare the efficacy of two dose regimens of rectal indometacin on the frequency and severity of pancreatitis after ERCP in high-risk patients. METHODS: In this randomised, double-blind, comparative effectiveness trial, we enrolled patients from six tertiary medical centres in the USA. Eligible patients were those at high risk for the development of pancreatitis after ERCP. We randomly assigned eligible patients (1:1) immediately after ERCP to receive either two 50 mg indometacin suppositories and a placebo suppository (standard-dose group) or three 50 mg indometacin suppositories (high-dose group). 4 h after the procedure, patients assigned to the high-dose group received an additional 50 mg indometacin suppository, whereas patients in the standard-dose group received an additional placebo suppository. The randomisation schedule, stratified according to study centre and with no other restrictions, was computer generated by an investigator who was uninvolved in the clinical care of any participants, distributed to the sites, and kept by personnel not directly involved with the study. These same personnel were responsible for packaging the drug and placebo in opaque envelopes. Patients, study personnel, and treating physicians were masked to study group assignment. The primary outcome of the study was the development of pancreatitis after ERCP. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01912716, and enrolment is complete. FINDINGS: Between July 9, 2013, and March 22, 2018, 1037 eligible patients were enrolled and randomly assigned to receive either standard-dose (n=515) or high-dose indometacin (n=522). Pancreatitis after ERCP occurred in 141 (14%) of 1037 patients-76 (15%) of 515 patients in the standard-dose indometacin group and 65 (12%) of 522 patients in the high-dose indometacin group (risk ratio [RR] 1·19, 95% CI 0·87-1·61; p=0·32). We observed 19 adverse events that were potentially attributable to study drug. Clinically significant bleeding occurred in 14 (1%) of 1037 patients-six (1%) of 515 patients in the standard-dose indometacin group and eight (2%) of 522 patients in the high-dose indometacin group (p=0·79). Three (1%) of 522 patients in the high-dose indometacin group developed acute kidney injury versus none in the standard-dose group (p=0·25). A non-ST elevation myocardial infarction occurred in the standard-dose indometacin group 2 days after ERCP. A transient ischaemic attack occurred in the high-dose indometacin group 5 days after ERCP. All 19 adverse events, in addition to the 141 patients who developed pancreatitis after ERCP, were considered serious as all required admission to hospital. We observed no allergic reactions or deaths at 30 day follow-up. INTERPRETATION: Dose escalation to rectal indometacin 200 mg did not confer any advantage compared with the standard 100 mg regimen, with pancreatitis incidence remaining high in high-risk patients. Current practice should continue unchanged. Further research should consider the pharmacokinetics of non-steroidal anti-inflammatory drugs to determine the optimal timing of their administration to prevent pancreatitis after ERCP. FUNDING: American College of Gastroenterology.

Regional and racial variations in the utilization of endoscopic retrograde cholangiopancreatography among pancreatic cancer patients in the United States.

BACKGROUND: Pancreatic cancer is projected to become the second leading cause of cancer-related deaths by 2030. Endoscopic retrograde cholangiopancreatography (ERCP) is recommended as first-line therapy for biliary decompression in pancreatic cancer. The aim of our study was to characterize geographic and racial/ethnic disparities in ERCP utilization among patients with pancreatic cancer. METHODS: Retrospective cohort study using the US Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify patients diagnosed with pancreatic cancer from 2003-2013. The primary outcome was receipt of ERCP, with or without stent placement, vs any non-ERCP biliary intervention. RESULTS: Of the 36 619 patients with pancreatic cancer, 37.5% (n = 13 719) underwent an ERCP, percutaneous drainage, or surgical biliary bypass. The most common biliary intervention (82.6%) was ERCP. After adjusting for tumor location and stage, Blacks were significantly less likely to receive ERCP than Whites (aOR 0.84, 95% CI 0.72, 0.97) and more likely to receive percutaneous transhepatic biliary drainage (PTBD) (aOR 1.38, 95% CI 1.14, 1.66). Patients in the Southeast and the West were more likely to receive ERCP than those in the Northeast (Southeast aOR 1.21, 95% CI 1.04, 1.40; West aOR 1.16, 95% CI 1.01, 1.32). CONCLUSION: Racial/ethnic and geographic disparities in access to biliary interventions including ERCP exist for patients with pancreatic cancer in the United States. Our results highlight the need for further research and policies to improve access to appropriate biliary intervention for all patients.

Non-variceal upper gastrointestinal bleeding.

Non-variceal upper gastrointestinal bleeding (NVUGIB) is bleeding that develops in the oesophagus, stomach or proximal duodenum. Peptic ulcers, caused by Helicobacter pylori infection or use of NSAIDs and low-dose aspirin (LDA), are the most common cause. Although the incidence and mortality associated with NVUGIB have been decreasing owing to considerable advances in the prevention and management of NVUGIB over the past 20 years, it remains a common clinical problem with an annual incidence of ∼67 per 100,000 individuals in the United States in 2012. NVUGIB is a medical emergency, and mortality is in the range ∼1-5%. After resuscitation and initial assessment, early (within 24 hours) diagnostic and therapeutic endoscopy together with intragastric pH control with proton pump inhibitors (PPIs) form the basis of treatment. With a growing ageing population treated with antiplatelet and/or anticoagulant medications, the clinical management of NVUGIB is complex as the risk between gastrointestinal bleeding events and adverse cardiovascular events needs to be balanced. The best clinical approach includes identification of risk factors and prevention of bleeding; available strategies include continuous treatment with PPIs or H. pylori eradication in those at increased risk of developing NVUGIB. Treatment with PPIs and/or use of cyclooxygenase-2-selective NSAIDs should be implemented in those patients at risk of NVUGIB who need NSAIDs and/or LDA.