Peptic ulcer disease endoscopy

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2017 ACG Guidelines for Peptic Ulcer Disease

Guidelines for the Indications to Test for, and to Treat, H. pylori Infection

Guidelines for First line Treatment Strategies of Peptic Ulcer Disease for Providers in North America

Guidlines for factors that predict the successful eradication when treating H. pylori infection

Guidelines to document H. pylori antimicrobial resistance in the North America

Guidelines for evaluation and testing of H. pylori antibiotic resistance

Guidelines for when to test for treatment success after H. pylori eradication therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Fahad Hasan, M.D.[2] Manpreet Kaur, MD [3]

Overview

Peptic ulcer disease (PUD) is one of the most common causes of upper gastrointestinal bleeding (UGIB), accounting for approximately 35–50% of all acute UGIB cases.[1] Esophagogastroduodenoscopy (EGD), also called upper endoscopy, is the primary diagnostic and therapeutic modality for peptic ulcer disease and its complications. EGD allows direct visualization of gastric and duodenal ulcers, permits biopsy for detection of Helicobacter pylori infection and exclusion of malignancy, and enables endoscopic hemostasis in patients with active bleeding or high-risk stigmata of recent hemorrhage.[2]

Peptic ulcers are most commonly caused by infection with Helicobacter pylori or the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs). Other recognized etiologies include Zollinger-Ellison syndrome, Crohn's disease, stress-related mucosal disease in critically ill patients, and idiopathic causes. The endoscopic appearance and the presence or absence of active bleeding at the time of endoscopy guide both prognosis and management decisions.

The cornerstone of endoscopic risk stratification in peptic ulcer bleeding is the Forrest classification, first described in 1974, which categorizes ulcer stigmata and guides decisions regarding the need for endoscopic hemostasis. Pre-endoscopic risk stratification using validated scoring systems — most importantly the Glasgow-Blatchford Score (GBS) — allows identification of very-low-risk patients who may be safely managed as outpatients, as well as high-risk patients who require urgent inpatient endoscopy and intervention.[1][2]

The most recent governing guidelines are the ACG Clinical Guideline: Upper Gastrointestinal and Ulcer Bleeding (2021),[1] the ACG Clinical Guideline: Treatment of Helicobacter pylori Infection (2024),[3] and the ESGE Guideline – Update 2026 on Endoscopic Diagnosis and Management of Peptic Ulcer Bleeding.[4]

Differential Diagnosis of Upper Gastrointestinal Bleeding

Diagnosis Key Distinguishing Features
Peptic ulcer disease Most common cause of UGIB (35–50%); H. pylori or NSAID-related; found in stomach or duodenum
Erosive gastritis / erosive esophagitis Mucosal erosions (not frank ulcers); NSAID, alcohol, or acid reflux-associated
Esophageal varices History of liver disease or portal hypertension; stigmata of cirrhosis; variceal bleed is less common but higher mortality
Mallory-Weiss tear History of forceful retching or vomiting; linear mucosal tear at gastroesophageal junction
Dieulafoy lesion Large submucosal artery without ulceration; difficult to identify endoscopically; recurrent profuse bleeding
Gastric antral vascular ectasia (GAVE) "Watermelon stomach"; chronic occult blood loss; associated with cirrhosis and systemic sclerosis
Gastric cancer Irregular, heaped ulcer margins; associated mass; requires multiple biopsies
Aortoenteric fistula Prior aortic aneurysm repair; herald bleed may precede massive hemorrhage; CT angiography
Hemobilia Bleeding from biliary tract; Quincke's triad: right upper quadrant pain, jaundice, and GI bleeding
Stress ulcer (stress-related mucosal disease) ICU patients; mechanical ventilation ≥48 h or coagulopathy; prophylaxis with PPI or H2RA

Endoscopic Therapy

Pre-endoscopic Risk Stratification

The Glasgow-Blatchford Score (GBS) is the preferred pre-endoscopic risk stratification tool for patients presenting with suspected UGIB. The GBS incorporates blood urea nitrogen, hemoglobin, systolic blood pressure, pulse rate, presence of melena or syncope, and history of liver disease or heart failure, and ranges from 0 to 23. Patients with a GBS of 0–1 have a risk of requiring hospital-based intervention or death of ≤1% and may be safely discharged with outpatient follow-up rather than admitted to hospital.[1][4] A GBS ≥6 identifies patients with a greater than 50% likelihood of requiring clinical intervention.

Score Risk Category Clinical Action
GBS 0–1 Very low risk (≤1% false-negative rate for intervention or death) Consider outpatient management and discharge with early follow-up
GBS 2–5 Low-to-moderate risk Hospital admission; early endoscopy within 24 hours
GBS ≥6 High risk (>50% likelihood of requiring intervention) Urgent inpatient endoscopy; consider ICU-level monitoring

Pre-endoscopic Medical Preparation

Appropriate pre-endoscopic preparation improves the safety, yield, and effectiveness of emergency upper endoscopy:

  • Hemodynamic resuscitation: Patients with hemodynamic instability should receive immediate intravascular volume replacement with crystalloid fluids.[2][4]
  • Red blood cell transfusion: A restrictive transfusion policy with a threshold of hemoglobin 7 g/dL is recommended for most patients with UGIB. A threshold of 8 g/dL may be appropriate in patients with significant comorbid cardiovascular disease or hemodynamic instability.[1][2]
  • Proton pump inhibitor (PPI) therapy: Pre-endoscopic high-dose intravenous PPI therapy should be considered in patients presenting with acute UGIH, as it may downstage endoscopic stigmata and reduce the need for endoscopic therapy; however, it must not delay early endoscopy and has not been shown to reduce mortality or rebleeding rates.[2][4]
  • Prokinetic agents: Intravenous erythromycin 250 mg administered over 20–30 minutes, given 20–90 minutes before endoscopy, is recommended in patients with suspected active bleeding or large amounts of blood in the stomach. Erythromycin acts as a motilin receptor agonist, accelerates gastric emptying, improves endoscopic visualization, and reduces the need for repeat endoscopy.[2] The ESGE 2026 update additionally suggests that if intravenous erythromycin is unavailable, pre-endoscopy intravenous metoclopramide may be used in selected patients with clinically severe or ongoing active UGIH.[4]
  • Tranexamic acid: Routine use of tranexamic acid is not recommended for patients with acute UGIB. The HALT-IT randomized trial (n = 12,009) demonstrated that tranexamic acid did not reduce death from GI bleeding (3.7% vs 3.8%; RR 0.99) but was associated with an increased risk of venous thromboembolic events compared with placebo.[5]
  • Video capsule endoscopy / telemetric blood-sensing capsules: Routine use of these modalities in the management of suspected upper GI hemorrhage is not recommended.[4]

Timing of Endoscopy

Following hemodynamic resuscitation, early upper GI endoscopy within 24 hours of patient presentation is recommended.[2][4]

The ESGE 2026 guideline further specifies that emergent (≤6 hours) or urgent (≤12 hours) upper GI endoscopy is not recommended unless the patient remains hemodynamically unstable despite adequate resuscitation.[4] This represents a strengthening of the 2021 position, which had previously allowed very early endoscopy as an option in selected high-risk patients with hemodynamic instability, in-hospital bloody hematemesis or bloody nasogastric aspirate, or contraindication to interruption of anticoagulation.

Forrest Classification

The Forrest classification is recommended in all patients with peptic ulcer hemorrhage to differentiate low-risk from high-risk stigmata and guide endoscopic treatment decisions.[2][4]

Forrest Class Endoscopic Appearance Approximate Rebleeding Risk (Untreated) Endoscopic Therapy
Ia Spurting (arterial) hemorrhage 55–90% Required — combination therapy (see below)
Ib Oozing hemorrhage 10–55% Required — combination therapy (see below)
IIa Nonbleeding visible vessel 43–55% Required — monotherapy or combination therapy
IIb Adherent clot 22–33% Recommended — clot removal + treat underlying stigma if high-risk
IIc Flat pigmented spot (hematin) 7–10% Not required — oral PPI; consider early discharge
III Clean-base ulcer 3–5% Not required — oral PPI; consider early discharge

Indications for Endoscopic Therapy

  • Patients with active spurting or oozing bleeding (Forrest Ia, Ib) or a non-bleeding visible vessel (Forrest IIa)[6]
  • Patients with an adherent clot (Forrest IIb) resistant to vigorous irrigation — recommended provided the endoscopist has the technical competence to safely remove the clot and manage potential conversion to a higher-risk bleeding lesion.[4]

Endoscopic Hemostasis Techniques

Injection Therapy

  • Injection of diluted epinephrine (1:10,000 dilution) achieves tamponade through a volume and vasoconstriction effect and is commonly used as part of combination therapy[7][8]
  • Epinephrine injection alone must NOT be used as monotherapy.[2][1][4] It should always be combined with a second hemostatic modality (contact thermal, mechanical, or sclerosant injection)
  • Injection of sclerosants (e.g., polidocanol, ethanolamine, absolute ethanol), fibrin sealant, and n-butyl cyanoacrylate represent additional injectable agents used in combination or as monotherapy[9][10]
  • The ESGE 2026 guideline notes that for Forrest IIa (nonbleeding visible vessel) ulcers, injection of a sclerosing agent — as monotherapy or in combination with epinephrine — is a recommended endoscopic treatment option[4]

Thermal Coagulation

  • Contact thermal methods: heater probe thermocoagulation, bipolar (BICAP) electrocoagulation, soft monopolar electrocoagulation, and hemostatic forceps with soft coagulation
    • Hemostatic forceps with soft coagulation may be used as monotherapy in the treatment of peptic ulcer bleeding with high-risk stigmata (Forrest Ia, Ib, IIa).[4]
  • Noncontact thermal methods: laser treatment, argon plasma coagulation (APC)[11]
  • Bipolar electrocoagulation and heater probe monotherapy are recommended therapies; argon plasma coagulation and soft monopolar electrocoagulation are supported by low- to very-low-quality evidence[1]

Mechanical Devices

  • Through-the-scope (TTS) clips apply mechanical compression to bleeding vessels; effective and widely used.[12][13]
  • Over-the-scope (OTS) clips provide a larger area of tissue capture using a nitinol clip mounted on a cap affixed to the endoscope tip. The ESGE 2026 guideline suggests OTS clips may be used as monotherapy as an alternative to combination therapy as first-line treatment for peptic ulcer bleeding with high-risk stigmata (Forrest Ia, Ib), owing to a lower risk of further bleeding compared with standard endoscopic hemostatic therapy.[4] OTS clips are also recommended for recurrent peptic ulcer bleeding (see below).[14]
  • Band ligation is an additional mechanical device occasionally used for specific bleeding lesions.

Combined Therapy

Combination therapy — dilute epinephrine injection followed by contact thermal coagulation or mechanical clip placement — is the standard first-line approach for Forrest Ia and Ib active bleeding ulcers.[11][2][4] Combining epinephrine with a second modality significantly reduces further bleeding (RR 0.34; 95% CI 0.23–0.50; NNT 5) compared with epinephrine alone.[6]

Hemostatic Powder (TC-325 / Hemospray)

TC-325 (Hemospray, Cook Medical) is a nanopowder with adsorptive and procoagulant properties that is sprayed directly onto the bleeding site via a catheter through the endoscope working channel. It achieves rapid hemostasis by mechanically concentrating clotting factors at the bleeding lesion.[15] The ACG conditionally recommends TC-325 for patients with actively bleeding ulcers (Forrest Ia, Ib).[1] Per ESGE 2026, hemostatic agents (including TC-325) should not be used as monotherapy for first-line treatment of high-risk peptic ulcer bleeding stigmata; however, TC-325 and other topical hemostatic agents should be considered as rescue therapy in patients with persistent bleeding refractory to standard hemostatic modalities.[4]

Endoscopic and Medical Therapy for Bleeding Ulcer

Approach to endoscopic and medical management of peptic ulcer bleeding: Adapted from ESGE Guideline Update 2026 and ACG Clinical Guideline 2021.[4][1]

 
 
 
 
 
 
 
 
Acute upper gastrointestinal bleeding
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hemodynamic resuscitation
(IV crystalloids; restrictive RBC
transfusion at Hb ≤7 g/dL)
Pre-endoscopy: IV PPI,
IV erythromycin 250 mg,
Glasgow-Blatchford Score
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GBS 0–1:
Consider outpatient
management
 
 
 
 
 
 
 
 
 
GBS ≥2:
Hospital admission;
Early EGD within 24 h
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Esophagogastroduodenoscopy
Stratify by Forrest classification
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Forrest Ia/Ib
Active bleeding
 
 
 
 
Forrest IIa/IIb
Visible vessel /
Adherent clot
 
 
 
 
Forrest IIc/III
Flat spot /
Clean base
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Combination therapy:
Epinephrine injection +
contact thermal or TTS/OTS clip
OR: OTS clip monotherapy
OR: Hemostatic forceps
 
 
 
 
Monotherapy ± epinephrine:
Contact/noncontact thermal,
TTS/OTS clip, sclerosant
IIb: Clot removal + treat
underlying stigmata
 
 
 
 
No endoscopic therapy;
Oral PPI once daily;
Consider early discharge
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Post-endoscopic management:
High-dose IV PPI (80 mg bolus + 8 mg/h × 72 h)
then oral PPI; H. pylori testing and eradication;
Iron therapy if deficient; early oral nutrition
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hemostasis achieved:
Manage antithrombotics;
Resume anticoagulation
when clinically indicated
 
 
 
 
 
 
 
 
 
 
 
 
Persistent/recurrent bleeding:
Repeat EGD (OTS clip preferred);
if failed → TAE;
if TAE unavailable/failed → Surgery

Second-Look Endoscopy

Routine second-look endoscopy is not recommended as part of the standard management of peptic ulcer bleeding following initial successful hemostasis.[2][4] A meta-analysis of 9 randomized controlled trials comprising 1,452 patients found no significant difference in recurrent bleeding (RR 0.79; 95% CI 0.51–1.23), need for surgery (RR 0.58; 95% CI 0.29–1.15), or mortality (RR 0.69; 95% CI 0.33–1.45) between routine second-look endoscopy and single-endoscopy management.[16]

However, in patients with clinical evidence of rebleeding (hematemesis, melena, hemodynamic instability, or significant drop in hemoglobin) following initially successful endoscopic hemostasis, repeat upper endoscopy with hemostasis is recommended. For recurrent bleeding, the ESGE 2026 guideline recommends that OTS clip use should be considered at repeat endoscopy. If this second attempt at endoscopic hemostasis is also unsuccessful, transcatheter angiographic embolization (TAE) should be considered. Surgery is indicated when TAE is locally unavailable or after unsuccessful TAE.[4]

Post-endoscopic Medical Therapy

Proton Pump Inhibitor Therapy

Following successful endoscopic hemostasis of high-risk ulcer stigmata (Forrest Ia, Ib, IIa, IIb), high-dose intravenous PPI therapy is recommended. The standard regimen is an 80 mg IV bolus followed by a continuous infusion of 8 mg/hour for 72 hours.[2][1] The ESGE 2026 update specifies that the post-endoscopic PPI regimen may also be delivered as a minimum twice-daily IV bolus for 72 hours, or as high-dose oral PPI, in addition to the standard continuous infusion regimen.[4] This sustained acid suppression promotes clot stability by maintaining intragastric pH above 6.

After the 72-hour post-endoscopic infusion phase, the ACG recommends high-dose oral PPI (≥80 mg daily) administered continuously or intermittently for at least 3 additional days, followed by standard twice-daily oral PPI therapy.[1] Patients should subsequently be maintained on once-daily oral PPI for ongoing acid suppression and ulcer healing.

For Forrest IIc and III ulcers (low-risk stigmata not requiring endoscopic hemostasis), once-daily oral PPI therapy is sufficient.[2]

The ESGE 2026 guideline could not reach consensus for or against the routine use of potassium-competitive acid blockers (P-CABs, e.g., vonoprazan) in place of PPI for patients who have undergone endoscopic hemostasis.[4]

Helicobacter pylori Testing and Eradication

All patients with peptic ulcer bleeding should be tested for Helicobacter pylori at index endoscopy.[2][4] When H. pylori is detected, antibiotic eradication therapy should be initiated promptly. Patients who test negative in the acute setting should be retested within 4 weeks, as false-negative results are common during acute hemorrhage (due to the suppressive effect of blood on bacterial density and concomitant PPI use). Documentation of successful H. pylori eradication is required.[2]

The 2024 ACG Clinical Guideline recommends the following for treatment-naive patients with H. pylori infection:[3]

  • Optimized bismuth quadruple therapy (BQT) for 14 days (preferred when susceptibility is unknown): PPI + bismuth + nitroimidazole + tetracycline. BQT for 14 days achieves eradication in approximately 87% of treatment-naive patients; shortening to 10 days reduces effectiveness to approximately 77%
  • Vonoprazan-based dual or triple therapy (vonoprazan + amoxicillin, or vonoprazan + amoxicillin + clarithromycin): an increasingly supported option particularly where clarithromycin susceptibility is confirmed
  • Clarithromycin-containing triple and sequential regimens should be avoided in the absence of demonstrated macrolide susceptibility, given increasing antibiotic resistance rates

Test-of-cure using a fecal antigen test or urea breath test must be performed at ≥4 weeks after completing eradication therapy in all patients.[3]

Antiplatelet and Anticoagulant Management

In patients receiving low-dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding:

  • Aspirin should be resumed immediately following index endoscopy if the ulcer has low-risk stigmata (Forrest IIc or III)
  • For high-risk stigmata (Forrest Ia, Ib, IIa, IIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended once adequate hemostasis has been established [2]

For patients requiring ongoing anticoagulation therapy following acute peptic ulcer hemorrhage, anticoagulation should be resumed as soon as clinically indicated based on individual thromboembolic risk, preferably within 7 days of the bleeding event.[2][4] The rapid onset of action of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) must be considered when planning resumption.

Iron Therapy and Nutrition

The ESGE 2026 guideline introduces two new post-endoscopic recommendations:[4]

  • Iron therapy should be initiated prior to hospital discharge in patients with peptic ulcer bleeding and iron deficiency and/or anemia.
  • Early oral nutrition within 24 hours following endoscopic hemostasis should be initiated in patients in whom durable hemostasis has been achieved.

Surgical and Radiological Salvage Therapy

Transcatheter Angiographic Embolization (TAE)

Interventional radiology–guided transcatheter arterial embolization (TAE) is indicated for patients with peptic ulcer bleeding refractory to endoscopic hemostasis, or for recurrent bleeding following initial successful endoscopic therapy. [2][4] TAE is generally preferred over surgery as the first salvage strategy given its lower procedural morbidity in high-risk patients.

The ESGE 2026 guideline introduces a new recommendation that prophylactic TAE be considered in selected high-risk cases of peptic ulcer bleeding, specifically in patients with hemodynamic instability at presentation, posterior duodenal wall ulcer location, large ulcer size (>2 cm), or when durable endoscopic hemostasis is considered uncertain. [4]

Surgery

Surgical intervention (ulcer oversewing, vagotomy with pyloroplasty, or partial gastrectomy) is reserved for patients in whom both endoscopic and angiographic approaches have failed or are not feasible, and for cases of free gastric or duodenal perforation. Surgery is indicated when TAE is not locally available or after unsuccessful TAE.[4]

References

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