Major Stigmata Research Articles

Ideal strategy for nonvariceal upper gastrointestinal bleeding.

Over 300 000 hospital admissions in the United States each year are due to patients with upper gastrointestinal (GI) bleeding (UGIB). Common etiologies of nonvariceal UGIB include peptic ulcers, mucosal erosions of the esophagus, stomach or duodenum, Mallory-Weiss tears, Dieulafoy lesions, upper GI tract malignancy, or other etiology. Peptic ulcers classified as Forrest Ia, Ib, or IIa require endoscopic hemostasis, while IIb ulcers may be considered for endoscopic clot removal with endoscopic treatment of any underlying major stigmata. Endoscopic hemostasis for ulcers classified as Forrest IIc or III is not advised due to the low risk of recurrent bleeding. Endoscopic hemostasis in ulcer bleeding can be achieved using injection, thermal, and/or mechanical modalities. This review focuses on the currently recommended endoscopic therapies of patients presenting with acute nonvariceal upper gastrointestinal hemorrhage.

A216 MODERATE TO SEVERE ACUTE UPPER GASTROINTESTINAL BLEEDING IN RURAL NORTHERN ONTARIO: AN EPIDEMIOLOGICAL ANALYSIS OF AETIOLOGIES, GEOGRAPHIC LIMITATIONS, AND OUTCOMES

Abstract Background Hospitalizations for upper gastrointestinal bleeds (UGIBs) are resource-demanding as they often require blood transfusion, endoscopy, and intensive care unit admission. Referral centers that provide higher levels of care to remote regions treat illnesses, including UGIB, in much later stages of disease and of higher severity. The Thunder Bay Regional Health Sciences Center (TBRHSC) is a referral center servicing over 250,000 people over a geographically expansive region of Northern Ontario. Despite known barriers to accessing care, little data is currently available to guide our understanding of UGIB aetiologies, severity, and outcomes among patients living remotely in Canada. Aims This retrospective study aimed to evaluate epidemiological data among patients with UGIB at TBRHSC. Methods Of 441 patients with a discharge diagnosis of gastrointestinal hemorrhage from 2016–2022, inclusion criteria were met for 333. Patients under 18 y or with lower GIB were excluded. Patients were classified as regional if their primary address was outside the District of Thunder Bay. Results Patients were highly comorbid (median CCI = 5) and presented with a median (IQR) GBS of 9 (6) and Clinical Rockall Score of 3 (1). Of those who received inpatient endoscopy (n=248), findings included erosive gastritis (21%), gastric ulcer (14%), esophagitis (12%), duodenal ulcer (8%), AVM (7%), and variceal (6%). No definite lesion was observed in 62 patients (22%). The median (IQR) Complete Rockall Score was 4 (2) with major stigmata of recent hemorrhage found in 20%. There was a high prevalence (19%) of cirrhosis, of which 83% had a history of liver decompensation. In 49% of cirrhotic patients, culprit lesions did not include portal hypertensive gastropathy or variceal bleeding. Regional patients accounted for 14% of the population and travelled an average of 424 km to seek care at TBRHSC. Regional patients were younger and required more ICU admissions (p=0.01). ICU admission primarily due to UGIB was 5.4% and all-cause thirty-day mortality was 3.3%. Oral anti-coagulation use prevalence was 43.2% and was associated with a longer length of stay (pampersand:003C0.0001), higher proportion of all-cause 30-day mortality (pampersand:003C0.005). Forty-eight patients did not receive endoscopy due to bleeding stability, palliation, and preference. Conclusions Patients with UGIB at TBRHSC are a highly multimorbid population with a significantly burden of anticoagulant use, cirrhosis, and variceal bleeding. Comparative analysis with metropolitan centers will expand our understanding for providing UGIB care in Northern Ontario. Funding Agencies NOAMA

A142 PROGNOSTICATING FACTORS AND OUTCOMES OF EARLY ENDOSCOPIC EVALUATION IN ACUTE UPPER GASTROINTESTINAL BLEEDING

Abstract Background Current guidelines recommend esophagogastroduodenal endoscopy (EGD) early (ampersand:003C24 hours after presentation) for all suspected acute upper gastrointestinal bleeds (AUGIB). Among referral centers providing advanced tiers of care to large regions, treatment is often delayed secondary to geographic constraints. Metropolitan centers meet early EGD recommendations in up to 87.5% of patients. Some centers limit endoscopy to the ICU setting outside of normal hospital operational times. There is currently no data assessing Canadian referral center endoscopic timing, including factors delaying AUGIB endoscopy and outcomes. Aims The aim of this study was to report the prevalence of early EGD in AUGIB at a Northern Ontario referral center. Factors associated with delayed EGD and poor outcomes associated with AUGIB were also evaluated. Methods Of 441 patients retrospectively identified with an ICD-10 discharge diagnosis of gastrointestinal hemorrhage from 2016–22, 327 patients met inclusion criteria. Patients were excluded if they were below the age of 18 years at the time of presentation, had chronic UGIB, or lower gastrointestinal hemorrhage. Results Pre-endoscopic risk stratification via GBS and clinical Rockall score was high at 10 and 3, respectively. There were 279 patients who received early EGD for AUGIB, of which 56% were male. The median (IQR) time to endoscopy was 27.4 (29.3) hours with early EGD achieved in 46% of presentations. A significantly greater proportion of patients presenting to hospital on the weekend (n=105) had delayed EGD (pampersand:003C0.0001; Phi effect size 0.45). Patients presenting at times when EGD was unavailable (n=157) also experienced delayed EGD (pampersand:003C0.05). regional patients did not experience a greater proportion of delayed EGD. In multivariate analysis, presentation on the weekend, higher CCI, absence of pre-existing evidence of liver cirrhosis, and absence of major stigmata of recent hemorrhage on EGD were independent predictors of delayed EGD (Nagelkerke R2 = 0.379, pampersand:003C0.0001). The odds ratio for receiving late EGD was 8.9 times greater (95% CI 3.7–21.3) for patients presenting on the weekend (pampersand:003C0.0001). Longer endoscopy wait time was significant correlated with higher pre-EGD blood transfusions and longer length of stay (pampersand:003C0.001). Delayed EGD did not increase all-cause 30-day mortality. Conclusions Prevalence of delayed EGD in AUGIB was markedly elevated and associated with hospital presentation during times of limited endoscopic capabilities. Outcomes of delayed GED included increased length of stay and higher blood transfusion rates. Funding Agencies NOAMA

Precise application of topical tranexamic acid to enhance endoscopic hemostasis for peptic ulcer bleeding: a randomized controlled study (with video)

Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis. This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy. Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P= .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P= .023). No adverse events from TXA were recorded. The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.).

Craniofacial Malformations as Fundamental Diagnostic Tools in Syndromic Entities.

Background: A long list of syndromic entities can be diagnosed immediately through scrutinizing the clinical phenotype of the craniofacial features. The latter should be assisted via proper radiological interpretations. Patients and Methods: Different children aged from 1 month to 12 years were referred to our departments seeking orthopedic advice. Primarily, all received variable false diagnoses in other institutes. Two unrelated boys of one month and 12 months were falsely diagnosed as having positional plagiocephaly associated with contractures of idiopathic origin. Two unrelated boys of 14 months and 2 years were diagnosed with pseudo-hydrocephalus and non-specific syndrome, and were referred to explore their skeletal development. Two unrelated girls of 4 years old and 12 years old presented with multiple contractures were referred because of progressive scoliosis. A 4-year-old girl was referred with a false provisional diagnosis of facial diplegia. All children underwent detailed clinical, radiological and tomographic phenotypic characterizations and genetic testing, respectively. Results: Idaho syndrome (craniosynostosis associated with multiple dislocations) was the final diagnosis in the two unrelated boys with plagiocephaly and multiple contractures. Two children falsely diagnosed with pseudo-hydrocephalus and non-specific syndrome, were diagnosed with Silver–Russell syndrome (RSS). Contractural arachnodactyly Beals (CAB) was confirmed as the definitive diagnosis in the two unrelated girls with progressive scoliosis and multiple contractures. Parry–Romberg syndrome (PRS) associated with congenital lumbar kyphosis was the final diagnosis of the girl with the diagnosis of facial diplegia. Hypomethylation of ICR1 was confirmed in the RSS patients. Whole exome sequencing (WES) revealed a heterozygous mutation in the PRS patients. WES and array-CGH showed that no relevant variants or copy number variations (CNV) were identified in the CAB patients. Conclusions: On the one hand, newborn children can manifest diverse forms of abnormal craniofacial features, which are usually associated with either major or minor dysmorphic stigmata. A cleft lip/ palate is a major craniofacial malformation, and frontal bossing or a disproportionate craniofacial contour can be falsely considered as a transient plagiocephaly, which is spontaneously resolved by time. On the other hand, many physicians fall into the problem of deeming a countless number of diseases, such as contractures, as an idiopathic or non-specific syndrome. The latter stems from limited clinical experience. Therefore, failing to establish between the onset of the deformity and other inexplicit abnormal features that the patient or their immediate families or relatives carry is the final outcome. In this study, we used, for the first time, a reconstruction CT scan to further delineate the congenital disruption of the craniofacial anatomy and the other skeletal malformation complex.

Ischemic colitis as a cause of severe hematochezia: A mini review.

Ischemic colitis (IC) is a common cause of severe lower gastrointestinal bleeding (LGIB) in the elderly. There are very few studies of patients with IC as a cause of severe LGIB in the literature. This article aims to review diagnosis, colonoscopic findings, medical treatment, and outcomes of patients with IC as a cause of severe hematochezia. The majority of IC patients with severe hematochezia can be successfully managed with medical treatment. Colonoscopic hemostasis with hemoclips is safe and feasible in treating major stigmata of recent hemorrhage in focal ischemic ulcers. Colon surgery is indicated in patients who fail medical treatment and/or have severe ongoing bleeding, clinical deterioration, or peritoneal signs. Overall, the morbidity rates in patients with IC range from 10% to 79%. Clinical outcomes in patients who need colon surgery for IC are worse than those treated with medical management. Patients who develop hematochezia from IC during hospitalization for other medical conditions have worse clinical outcomes than those with an outpatient start of bleeding. Further research is warranted for the prevention, early diagnosis, and treatment of patients with severe hematochezia from IC.

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

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. 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. 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. 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).

497 WHAT TREATMENT TO USE FOR SEVERE NON-VARICEAL UGI HEMORRHAGE: STANDARD ENDOSCOPIC HEMOSTASIS, DOPPLER GUIDED HEMOSTASIS, OR OVER-THE-SCOPE-CLIP (OTSC)?

Non-variceal UGI hemorrhage (NVUGIH) is common but 26-28% of high risk patients with bleeding peptic ulcers (PUB’s) or Dieulafoy’s lesions (DL) rebled after standard, visually guided endoscopic hemostasis in 2 recently reported randomized controlled trials (RCT’s). See references in Table. These were separate comparisons of Doppler probe assisted hemostasis (DEP) or OTSC with STANDARD endoscopic hemostasis, but the 3 have never been compared in a head-to-head study before. Our purposes were to compare rates of recurrent bleeding and other 30 day clinical outcomes after endoscopic treatment with DEP, OTSC or STANDARD hemostasis of patients with severe NVUGIH. Individual patient data from 2 successive RCT’s were analyzed. Only patients with PUB’s & DL’s were included in 3 treatment groups: 69 DEP, 24 OTSC, & 101 STANDARD patients. We utilized SAS for data management & a biostatistician for the statistical analyses (JG). Patients were randomized if they had either major stigmata of hemorrhage – SRH (spurting arterial bleeding, non-bleeding visible vessel, or adherent clot) or lesser SRH (oozing bleeding or flat spot). In all treatments of spurting arterial bleeding or adherent clots, epinephrine injection was used prior to hemostasis with hemoclips (HC) &/or multipolar electrocoagulation (MPEC), or OTSC. DEP patients had visually guided hemostasis & if still positive for residual blood flow, more MPEC or HC’s was applied to obliterate underlying arterial blood flow, if feasible & safe. All patients received high dose proton pump infusions – PPI’s - X 72 hours & then BID PPI’s. Patients & their healthcare teams were blinded to endoscopic treatments & made all decisions after randomization about transfusions, further intervention for rebleeding, & level of care. Patients in the 3 treatment groups had similar baseline risk factors. However, there were significantly higher rates of 30 day rebleeding for STANDARD vs. DEP or OTSC (25.7% vs. 10.1% vs. 4.2%). The numbers needed to treat (NNT) for OTSC vs. STANDARD are 4.6 & for DEP vs. STANDARD are 6.4. Severe complications, number of RBC’s after randomization & number of bleeding episodes were also significantly higher in the STANDARD group – See Table & Kaplan-Meier Curves (p = 0.0141 for overall difference). For patients with severe UGIH from PUB’s or Dieulafoy’s lesions treated by the same investigators in 2 consecutive RCT’s: 1. STANDARD hemostasis resulted in significantly higher rates of further bleeding than DEP assisted hemostasis or OTSC. 2. Post-randomization rates of severe complications, units of RBC transfused, & number of bleeds were also significantly higher in the STANDARD treatment group. Either DEP assisted or OTSC are recommended as the new initial treatments of choice for severe NVUGIH from PUB’s or DL’s.Legend: Kaplan-Meier curves of time to first rebleed. Overall p = 0.0141 by log rank test.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Topical haemostatic powder as a novel endoscopic therapy for severe colonic diverticular bleeding.

Although most diverticular bleeding resolve spontaneously, up to 30% can bleed torrentially, necessitating angioembolization, endoscopic or surgical intervention. Non-contact endoscopic therapies, such as topical haemostatic powders, do not require precise targeting and are attractive because identification of specific culprit diverticulum is difficult. While their use in non-variceal upper gastrointestinal bleeding is well established, its role in lower gastrointestinal bleeding remains unclear. We used topical Hemospray in a novel setting of severe diverticular bleeding, evaluating its efficacy in achieving haemostasis, reducing re-bleeding and the need for re-intervention. Consecutive patients from a tertiary colorectal unit who underwent colonoscopy and Hemospray for severe diverticular bleeding from November 2016 to October 2017 were included. Hemospray was endoscopically applied to colonic segments with major stigmata of recent haemorrhage. Ten patients had a median time to colonoscopy of 22 h (range: 8-54) from admission. Median of 3.5 units (range: 0-10) of packed cells were transfused pre-endoscopy. All achieved immediate haemostasis without further haemodynamic instability or re-bleeding. No endoscopic, radiological or surgical re-intervention was required. Patients were fit for discharge within a median of 3 days (range: 2-7) following Hemospray. There were no morbidities, mortalities or readmissions for diverticular bleeding after a median follow-up of 9.5 months (range: 3-16). This feasibility study shows that topical haemostatic powders can offer a safe and effective therapeutic endoscopic option in severe diverticular bleeding with high haemostatic rate. Prospective controlled trials are required to establish its efficacy compared to conventional therapy.

Outcomes of patients hospitalized with peptic ulcer disease diagnosed in acute upper endoscopy.

The incidence and complications of peptic ulcer disease (PUD) have declined, but mortality from bleeding ulcers has remained unchanged. The aims of the current study were to evaluate the significance of PUD among patients admitted for acute upper endoscopy and to evaluate the survival of PUD patients. In this prospective, observational cohort study, data on 1580 acute upper endoscopy cases during 2012-2014 were collected. A total of 649 patients were included with written informed consent. Data on patients' characteristics, living habits, comorbidities, drug use, endoscopy and short-term and long-term survival were collected. Of all patients admitted for endoscopy, 147/649 (23%) had PUD with the main symptom of melena. Of these PUD patients, 35% had major stigmata of bleeding (Forrest Ia-IIb) in endoscopy. Patients with major stigmata had significantly more often renal insufficiency, lower level of blood pressure with tachycardia and lower level of haemoglobin, platelets and ratio of thromboplastin time. No differences in drug use, Charlson comorbidity class, BMI, smoking or alcohol use were found. Of the PUD patients, 31% were Helicobacter pylori positive. The 30-day mortality was 0.7% (95% confidence interval: 0.01-4.7), 1-year mortality was 12.9% (8.4-19.5) and the 2-year mortality was 19.4% (13.8-26.8), with no difference according to major or minor stigmata of bleeding. Comorbidity (Charlson>1) was associated with decreased survival (P=0.029) and obesity (BMI≥30) was associated with better survival (P=0.023). PUD is still the most common cause for acute upper endoscopy with very low short-term mortality. Comorbidity, but not the stigmata of bleeding, was associated with decreased long-term survival.

Risk factors determining the need for second-look endoscopy for peptic ulcer bleeding after endoscopic hemostasis and proton pump inhibitor infusion.

Background and study aims: The need for routine second-look endoscopy in cases of peptic ulcer bleeding remains uncertain. We investigated risk factors related to the need for second-look endoscopy after endoscopic hemostasis and proton pump inhibitor (PPI) infusion. Patients and methods: We prospectively enrolled 316 patients with peptic ulcer bleeding after endoscopic hemostasis. Second-look endoscopy was scheduled after 72-hour PPI infusion (Day-3 subgroup) or one day early (Day-2 subgroup). If early rebleeding developed within 3 days, emergent second-look endoscopy was conducted. Risk factors for early rebleeding (use of E2nd score to predict the need for early second-look endoscopy) and persistent major stigmata in the Day-3 subgroup (use of R2nd score to predict the need for routine second-look endoscopy) were analyzed using univariable and multivariable regression. Results: Excluding 10 of 316 patients with early rebleeding, the rate of persistent major stigmata was lower in the Day-3 subgroup than in the Day-2 subgroup (4.8 % vs. 15.4 %, P = 0.002). Endoscopic epinephrine-injection monotherapy and hypoalbuminemia < 3.0 g/dL were two independent risk factors for early rebleeding (P ≤ 0.05). The Forrest Ia-Ib type and hypoalbuminemia < 3.5 g/dL were two independent risk factors for persistent major stigmata on the day-3 second-look endoscopy (P < 0.05). The E2nd score was highly accurate for prediction of early rebleeding (AUROC 0.86; 95 % CI, 0.73~0.99), and the R2nd score could predict persistent major stigmata at second-look endoscopy (AUROC 0.84; 95 % CI, 0.69~0.99). Conclusions: For patients with peptic ulcer bleeding, E2nd and R2nd scores can indicate the need for early and routine second-look endoscopy, respectively(Trial registration identifier: NCT02197039).

Natural history of definitive diverticular hemorrhage based on stigmata of recent hemorrhage and colonoscopic Doppler blood flow monitoring for risk stratification and definitive hemostasis

Few prospective reports describe the short-term natural history of colon diverticular hemorrhage based on stigmata of recent hemorrhage, and none include blood flow detection for risk stratification or as a guide to definitive hemostasis. Our purposes were to report the 30-day natural history of definitive diverticular hemorrhage based on stigmata and to describe Doppler probe blood flow detection as a guide to definitive hemostasis. Different cohorts of patients with severe diverticular bleeding and stigmata on urgent colonoscopy are reported. For 30-day natural history, patients were treated medically. If severe rebleeding occurred, they had surgical or angiographic treatment. We report natural history with major stigmata (active bleeding, visible vessel, or adherent clot) and no stigmata or flat spots after clots were washed away. We also report Doppler probe detection of arterial blood flow underneath stigmata before and after hemostasis in a recent cohort. For natural history, patients with major stigmata treated medically had 65.8% (25/38) rebleeding rates, and 44.7% (17/38) had intervention for hemostasis. Patients with spots or clean bases had no rebleeding. A Doppler probe detected arterial blood flow in 92% of major stigmata--none after hemostasis--and there was no rebleeding. (1) Patients with major stigmata treated medically had high rates of rebleeding and intervention for hemostasis. (2) Patients with clean diverticula or only flat spots had no rebleeding. (3) High rates of arterial blood flow were detected under major stigmata with a Doppler probe, but with obliteration by hemostasis no rebleeding occurred.

Epinephrine injection versus epinephrine injection and a second endoscopic method in high-risk bleeding ulcers

Endoscopic therapy reduces the rebleeding rate and the need for surgery in patients with bleeding peptic ulcers. To determine whether a second procedure improves haemostatic efficacy or patient outcomes or both after epinephrine injection in adults with high-risk bleeding ulcers. For our update in 2014, we searched the following versions of these databases, limited from June 2009 to May 2014: Ovid MEDLINE(R) 1946 to May Week 2 2014; Ovid MEDLINE(R) Daily Update May 22, 2014; Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations May 22, 2014 (Appendix 1); Evidence-Based Medicine (EBM) Reviews-the Cochrane Central Register of Controlled Trials (CENTRAL) April 2014 (Appendix 2); and EMBASE 1980 to Week 20 2014 (Appendix 3). We included randomised controlled trials (RCTs) comparing epinephrine alone versus epinephrine plus a second method. Populations consisted of patients with high-risk bleeding peptic ulcers, that is, patients with haemorrhage from peptic ulcer disease (gastric or duodenal) with major stigmata of bleeding as defined by Forrest classification Ia (spurting haemorrhage), Ib (oozing haemorrhage), IIa (non-bleeding visible vessel) and IIb (adherent clot) (Forrest Ia-Ib-IIa-IIb). We used standard methodological procedures as expected by The Cochrane Collaboration. Meta-analysis was undertaken using a random-effects model; risk ratios (RRs) with 95% confidence intervals (CIs) are presented for dichotomous data. Nineteen studies of 2033 initially randomly assigned participants were included, of which 11 used a second injected agent, five used a mechanical method (haemoclips) and three employed thermal methods.The risk of further bleeding after initial haemostasis was lower in the combination therapy groups than in the epinephrine alone group, regardless of which second procedure was applied (RR 0.53, 95% CI 0.35 to 0.81). Adding any second procedure significantly reduced the overall bleeding rate (persistent and recurrent bleeding) (RR 0.57, 95% CI 0.43 to 0.76) and the need for emergency surgery (RR 0.68, 95% CI 0.50 to 0.93). Mortality rates were not significantly different when either method was applied.Rebleeding in the 10 studies that scheduled a reendoscopy showed no difference between epinephrine and combined therapy; without second-look endoscopy, a statistically significant difference was observed between epinephrine and epinephrine and any second endoscopic method, with fewer participants rebleeding in the combined therapy group (nine studies) (RR 0.32, 95% CI 0.21 to 0.48).For ulcers of the Forrest Ia or Ib type (oozing or spurting), the addition of a second therapy significantly reduced the rebleeding rate (RR 0.66, 95% CI 0.49 to 0.88); this difference was not seen for type IIa (visible vessel) or type IIb (adherent clot) ulcers. Few procedure-related adverse effects were reported, and this finding was not statistically significantly different between groups. Few adverse events occurred, and no statistically significant difference was noted between groups.The addition of a second injected method reduced recurrent and persistent rebleeding rates and surgery rates in the combination therapy group, but these findings were not statistically significantly different. Significantly fewer participants died in the combined therapy group (RR 0.50, 95% CI 0.25 to 1.00).Epinephrine and a second mechanical method decreased recurrent and persistent bleeding (RR 0.31, 95% CI 0.18 to 0.54) and the need for emergency surgery (RR 0.20, 95% CI 0.06 to 0.62) but did not affect mortality rates.Epinephrine plus thermal methods decreased the rebleeding rate (RR 0.49, 95% CI 0.30 to 0.78) and the surgery rate (RR 0.20, 95% CI 0.06 to 0.62) but did not affect the mortality rate.Our risk of bias estimates show that risk of bias was low, as, although the type of study did not allow a double-blind trial, rebleeding, surgery and mortality were not dependent on subjective observation. Although some studies had limitations in their design or implementation, most were clear about important quality criteria, including randomisation and allocation concealment, sequence generation and blinding. Additional endoscopic treatment after epinephrine injection reduces further bleeding and the need for surgery in patients with high-risk bleeding peptic ulcer. The main adverse events include risk of perforation and gastric wall necrosis, the rates of which were low in our included studies and favoured neither epinephrine therapy nor combination therapy. The main conclusion is that combined therapy seems to work better than epinephrine alone. However, we cannot conclude that a particular form of treatment is equal or superior to another.

Dieulafoyʼs Lesion as a Cause of Severe UGI Hemorrhage: What Is New and How Do We Treat in the Current Era?: Presidential Poster

Purpose: Dieulafoy first described a lesion (DL) more than 130 years ago as a large focal artery without ulceration of the stomach causing massive fatal UGI hemorrhage (UGIH). Endoscopically, DL is reported in patients with severe UGIH when major stigmata of recent hemorrhage (SRH) without ulceration are seen. For endoscopically diagnosed and treated UGI DLs, our purposes were: 1) to report prevalences of SRH, 2) to compare 30-day outcomes after thermal coagulation vs. hemoclipping (HC), and 3) to describe recent changes in hemostasis of DL with Doppler probe ultrasound (DUP) monitoring. Methods: 56 patients with severe UGIH were enrolled in prospective CURE hemostasis studies. Techniques evolved from monotherapy, to combination hemostasis, to use of DUP to complete treatments. Thirty two patients before 6/2006 were treated with thermal coagulation. Twenty four other patients after 8/2006 had hemostasis with hemoclipping. Endoscopic treatments usually included epinephrine pre-injection and tattooing after hemostasis. When it became available, DUP was used for arterial blood flow detection underneath SRH in nine patients, to map the arteries, and to check for blood flow ablation to complete hemostasis. All patients were followed up to 60 days. Data were prospectively collected, entered onto computer databases, and managed with SAS. Results: For all 56 patients, prevalences of SRH were 60.7% active bleeding, 17.9% adherent clot, 2.5% non-bleeding visible vessel (NBVV), and 8.9% spot. For thermal vs. HC treated patients, there were no significant differences in 30 day outcomes: re-bleeding 25% vs. 29%; surgery 16% vs. 17%; or death 6% vs. 0%. However, the non-DUP assisted DL hemostasis group had a significantly higher 30 day re-bleed rate than the DUP assisted patients: 33% (15/45) vs. 0% (0/9). Conclusion: For 56 patients with severe UGIH from Dieulafoy's lesions: 1) SRH were active bleeding 60.7%, clot 17.9%, NBVV 12.5%, and other SRH 8.9%. 2) 30-day outcomes of re-bleeding, surgery, death were similar for thermal & hemoclip treated patients. 3) However, the 30-day re-bleeding rate of DUP assisted hemostasis patients was significantly lower than those without DUP monitoring. Acknowledgements: Partially supported by a Clinical VA Merit Review grant and NIH CURE DDRC CURE grant-Human Studies Core (AM41301).

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.

Endoscopic Treatment of Upper Gastrointestinal Ulcer Bleeding

Peptic ulcer disease is the most common cause of upper gastrointestinal (GI) bleeding. In most of the cases, bleeding from a peptic ulcer stops spontaneously. Arterial diameters in bleeding ulcers can measure up to 3.45 mm, but in most cases the diameter of the bleeding artery is small (< 2 mm). High-dose intravenous proton pump inhibitors after endoscopic therapy for a bleeding ulcer reduce recurrent bleeding risk and surgery. The endoscopic appearance of an ulcer provides important prognostic information. Clean based ulcers and ulcers with a flat pigmented spot have low rebleeding risks. Major stigmata of hemorrhage (an adherent clot, a visible vessel, or active bleeding) are associated with high rebleeding risks. Endoscopic treatment in patients with high-risk stigmata results in improved outcomes. Common endoscopic techniques and the devices used to treat upper GI ulcer bleeding, including injection therapy, thermal coagulation, endoclip application, and hemostatic powder spray are described in the given video. Different clinical scenarios are presented. This article is part of an expert video encyclopedia.

Mallory–Weiss Syndrome: Where to Look, How to Detect

Mallory–Weiss syndrome is a common cause of upper nonvariceal gastrointestinal bleeding. Although considered minor, it can occasionally cause severe bleeding and have fatal outcome in high-risk patients. Careful inspection is needed to assess the depth of the tear and the presence of major stigmata of hemorrhage. Endoscopic therapy is rarely required. Mechanical hemostasis by means of clip application or band ligation is considered the option of choice in these patients. This article is part of an expert video encyclopedia.

Endoclipsvslarge or small-volume epinephrine in peptic ulcer recurrent bleeding

To compare the recurrent bleeding after endoscopic injection of different epinephrine volumes with hemoclips in patients with bleeding peptic ulcer. Between January 2005 and December 2009, 150 patients with gastric or duodenal bleeding ulcer with major stigmata of hemorrhage and nonbleeding visible vessel in an ulcer bed (Forrest IIa) were included in the study. Patients were randomized to receive a small-volume epinephrine group (15 to 25 mL injection group; Group 1, n = 50), a large-volume epinephrine group (30 to 40 mL injection group; Group 2, n = 50) and a hemoclip group (Group 3, n = 50). The rate of recurrent bleeding, as the primary outcome, was compared between the groups of patients included in the study. Secondary outcomes compared between the groups were primary hemostasis rate, permanent hemostasis, need for emergency surgery, 30 d mortality, bleeding-related deaths, length of hospital stay and transfusion requirements. Initial hemostasis was obtained in all patients. The rate of early recurrent bleeding was 30% (15/50) in the small-volume epinephrine group (Group 1) and 16% (8/50) in the large-volume epinephrine group (Group 2) (P = 0.09). The rate of recurrent bleeding was 4% (2/50) in the hemoclip group (Group 3); the difference was statistically significant with regard to patients treated with either small-volume or large-volume epinephrine solution (P = 0.0005 and P = 0.045, respectively). Duration of hospital stay was significantly shorter among patients treated with hemoclips than among patients treated with epinephrine whereas there were no differences in transfusion requirement or even 30 d mortality between the groups. Endoclip is superior to both small and large volume injection of epinephrine in the prevention of recurrent bleeding in patients with peptic ulcer.

How evidence-based are current guidelines for managing patients with peptic ulcer bleeding?

Current guidelines for managing ulcer bleeding state that patients with major stigmata should be managed by dual endoscopic therapy (injection with epinephrine plus a thermal or mechanical modality) followed by a high dose intravenous infusion of proton pump inhibitors (PPIs). This paper aims to review and critically evaluate evidence supporting the purported superiority of a continuous infusion over less intensive regimens of PPIs administration and the need for adding a second hemostatic endoscopic procedure to epinephrine injection. Systematic searches of PubMed, EMBASE and the Cochrane library were performed. There is strong evidence for an incremental benefit of PPIs over H2-receptor antagonists or placebo for the outcome of patients with peptic ulcer bleeding following endoscopic hemostasis. However, the benefit of PPIs is unrelated to either the dosage (intensive vs standard regimen) or the route of administration (intravenous vs oral). There is significant heterogeneity among the 15 studies that compared epinephrine with epinephrine plus a second modality, which might preclude the validity of reported summary estimates. Studies without second look endoscopy plus re-treatment of re-bleeding lesions showed a significant benefit of adding a second endoscopic modality for hemostasis, while studies with second-look and re-treatment showed equal efficacy between endoscopic mono and dual therapy. Inconclusive experimental evidence supports the current recommendation of the use of dual endoscopic hemostatic means and infusion of high-dose PPIs as standard therapy for patients with bleeding peptic ulcers. Presently, the combination of epinephrine monotherapy with standard doses of PPIs constitutes an appropriate treatment for the majority of patients.

Role of proton pump inhibitors in the management of peptic ulcer bleeding

Peptic ulcer bleeding is a serious medical problem with significant morbidity and mortality. Endoscopic therapy significantly reduces further bleeding, surgery and mortality in patients with bleeding peptic ulcers and is now recommended as the first hemostatic modality for these patients. The efficacy of large-dose proton pump inhibitor (PPI) therapy in reducing re-bleeding after endoscopic therapy has been supported by evidence derived from randomized controlled trials. It may be premature to recommend small-dose intravenous injection PPI after endoscopic hemostasis in patients with bleeding ulcers. An updated systematic review shows that PPI therapy before endoscopy significantly reduces the proportion with major stigmata and requirement for endoscopic therapy at index endoscopy. Some studies show that there is no significant difference between oral and intravenous PPIs in raising intragastric pH. However, clinical data is lacking in patients with peptic ulcer bleeding to date.