Open research questions in Gastrointestinal Bleeding Diagnosis and Treatment

What the literature leaves open

• Accepted Manuscript diagnostic yield and feasibility of such systems in patients with HHT have not been systematically evaluated. Telangiectatic lesions have been reported throughout the gastrointestinal tract; however, their distribution and characterisation remains incompletely characterised. Consequently, the true pan-enteric distribution and burden of telangiectatic lesions in HHT remain uncertain.

  Pan-enteric video capsule endoscopy in hereditary haemorrhagic telangiectasia: gastrointestinal manifestations and feasibility · 2026 · DOI

• Second, four previous meta-analyses were limited to the comparison between APC and formalin or BEC [88, 90, 91], and focused on RFA alone [89], but ours included nearly all types of endoscopic treatment.

  Efficacy and Safety of Endoscopic Treatment for Chronic Hemorrhagic Radiation Enteropathy: A Systematic Review and Meta-analysis · 2026 · DOI

• Abstract Background The optimal timing of endoscopy for acute variceal bleeding (AVB) remains uncertain in real-world clinical practice.

  Timing of endoscopy and short-term outcomes in cirrhotic patients with acute variceal bleeding: a single-center retrospective study · 2026 · DOI

• Compared to other endoscopic hemostatic methods; such as epinephrine injection, hemoclips, thermal devices, or topical agents like Hemospray - ABS has a multifactorial mechanism involving erythrocyte and fibrinogen gamma aggregation, though head-to-head comparative data remain limited. Additionally, pharmacokinetic studies and long-term outcome data are warranted to address remaining questions regarding systemic effects and recurrence risk.

  Ankaferd blood stopper application in gastrointestinal bleeding: An updated narrative review · 2026 · DOI

• restricted test was the analytic This study has several limitations. For this cohort to histopathologically confirmed GI GVHD episodes; the study cannot estimate the diagnostic accuracy of CEUS for distinguishing GVHD from infectious, drug-related, vascular, or other post-transplant gastrointestinal complications. No prespecified sample size calculation was performed. The post- hoc precision around the primary Spearman correlation (95% CI width 0.304 for rho = 0.684) is consistent with adequate characterisation of moderate-to-strong associations but the precision for smaller effect sizes, including stratified subgroups. The data are clustered at the patient level (10 of 41 patients contributed two episodes each). The four-level ordinal scale for the contrast wash-out parameter (~30 s; ~1 min; ~2 min; >2 min) was established empirically by the imaging team. Individual parameter scores were recorded in real time by a single ultrasonographer blinded to histopathology, but cine-loops were available only for a subset of examinations, precluding formal blinded re-scoring and intra- observer reproducibility analysis. Histopathological evaluation was performed by a single pathologist per specimen from the institutional team, without limits formal adjudication or inter-observer agreement analysis. Future studies with central blinded re- reading by multiple pathologists would strengthen reproducibility.

  Contrast-enhanced Ultrasound and the Lerner Histopathological Grade in Gastrointestinal Graft-versus-host Disease: A Prospective Single-centre Study · 2026 · DOI

• However, whether GIB is associated with a higher incidence of in-hospital ACI in gastroenterology inpatients remains insufficiently studied, and clinically practical risk stratification tools are lacking.

  Predictive model for in-hospital acute cerebral infarction in patients with acute gastrointestinal bleeding: a retrospective cohort study · 2026 · DOI

• Level of evidence ACCF/ACG/AHA 2008 expert consensus document on reducing the GI risk of antiplatelet therapy and NSAID use40 The combination of ASA and anticoagulant therapy (including unfractionated heparin…

  Management of Peptic Ulcer Disease in Patients Taking Antithrombotic Agents · 2026 · DOI

• The present system shows notable improvements but it also presents some operational limitations. The custom instruction set provides functionality for specific image-processing tasks through its extended ISA. The current system needs additional hardware components to achieve advanced kernel processing capabilities. The histogram Equalization technique needs a LookUp Table (LUT) to be stored because this Pre-fetching method avoids delays due to external memory access. The static power consumption of the Artix-7 platform establishes the primary power consumption pattern, making it difficult to determine the dynamic power efficiency advantages from custom instruction operations. The future research will focus on expanding the instruction set architecture through additional image-processing instructions including convolution, Gaussian filtering, and edge-preserving filters. System performance will reach higher efficiency levels through DSP block implementations that can handle multiply and accumulate operations. The transition to an ASIC design process will provide better assessment of power consumption and space efficiency by removing FPGA static power consumption. The combination of on-chip memory buffers will enable better scalability for real-time high-resolution image processing.

  Design of a low-power RISC-V based intelligent endoscopy detection processor: EndoRISC-V · 2026 · DOI

• This case has several strengths, including detailed chronological documentation of multimodal diagnostics, the use of dynamic computed tomography angiography to precisely localize the source of cecal bleeding, and the integration of endoscopic, interventional, and surgical perspectives within a single clinical pathway. At the same time, it also highlights important limitations. First, the initial technical success of selective transcatheter arterial embolization may have created a false sense of security, potentially delaying consideration of definitive right hemicolectomy despite persistent transfusion‑dependent bleeding. Second, from an interventional standpoint, embolization of cecal angiodysplasia is intrinsically challenging because of the rich collateral network of the ileocolic and right colic branches and the small caliber of the vasa recta, which increase the risk of incomplete penetration of embolic material and early rebleeding. In our case, distal embolization with microparticles achieved angiographic stasis but may have favored suspected early recanalization of the treated branches; more durable liquid embolic agents (such as cyanoacrylate glues or Onyx™ (Medtronic, Minneapolis, USA)) can provide deeper and more permanent occlusion but carry a higher risk of non‑target embolization and bowel ischemia in this vascular territory. Finally, this report is limited by its single‑patient design and the absence of angiographic images suitable for publication, as well as the lack of a standardized algorithm to define the optimal threshold for transitioning from repeat endovascular therapy to surgery, underscoring the need for individualized multidisciplinary decision‑making in similar cases.

  Right Hemicolectomy for Refractory Hematochezia in Cecal Angiodysplasia After Failed Embolization: A Case Report · 2026 · DOI

• ESGE suggests that early oral nutrition, within 24 hours following endoscopic hemostasis, be initiated in patients with peptic ulcer bleeding in whom durable hemostasis has been achieved. Conditional recommendation, low quality evidence. A recent meta-analysis of 10 RCTs, including 1051 patients with UGIH, compared the outcomes of early versus delayed oral nutrition following endoscopic hemostasis. The definitions for early and delayed nutrition were accepted as specified by the included studies. In the subgroup of peptic ulcer bleeding patients (n = 560) who received either early or delayed oral nutrition, there was no significant difference in early rebleeding (within 7 days; RR 0.95, 95%CI 0.54 to 1.68) or late rebleeding (within 30 days; RR 1.14, 95%CI 0.16 to 7.98). Moreover, there was no statistically significant difference in early (RR 0.98, 95%CI 0.85 to 1.14) or late mortality (RR 0.51, 95%CI 0.03 to Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved.. d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE recommends that, in patients with peptic ulcer hemorrhage who require ongoing anticoagulation therapy, anticoagulation should be resumed as soon as clinically indicated based on thromboembolic risk. Strong recommendation, low quality evidence. A recent UK audit of 5141 patients with acute UGIH found that 30.6% were receiving an anticoagulant (direct oral anticoa- gulant [DOAC], vitamin K antagonist [VKA]) at the time of their bleeding episode [94], this being an increase from the 13% level of reported anticoagulant use in a similar UK audit in 2007 [95]. However, the evidence to guide the resumption of anticoagula- tion therapy (e. g. VKA, DOAC) following a peptic ulcer bleed remains limited. The decision to restart anticoagulation thera- py must balance the risk of recurrent bleeding with the risk of thromboembolic events and/or the sequelae of these events, including death. As compared with patients with peptic ulcer bleeding who were not restarted on anticoagulation, patients who were restarted on anticoagulation after their peptic ulcer bleed (57% restarted; median 15 days) had a lower risk of . d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l . y n o e s u l a n o s r e p r o f d e d a o n w o d l s a w t n e m u c o d i s h T Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved. thrombosis and death at 1 year (hazard ratio [HR] 0.14 [95%CI 0.05 to 0.43]), with no significantly increased risk of recurrent bleeding (HR 1.42 [95%CI 0.10 to 19.8]) [96]. However, the precise timing for restarting anticoagulation in patients with peptic ulcer hemorrhage remains undefined. Those patients at the highest thrombotic risk should restart anticoagulant therapy as soon as possible and the use of subcu- taneous low molecular weight heparin as a bridge to oral anti- coagulation may be a good option. Early consultation with a cardiologist and/or hematologist is desirable.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE recommends that recurrent bleeding be defined as bleeding following initial successful endoscopic hemo- stasis. Strong recommendation, high quality evidence. RECOMMENDATION ESGE recommends, for patients with clinical evidence of recurrent bleeding, repeat upper GI endoscopy with hemostasis if indicated. Strong recommendation, high quality evidence. RECOMMENDATION ESGE recommends that, for patients with clinical evi- dence of recurrent peptic ulcer bleeding, use of an OTS clip should be considered. Should this second attempt at endoscopic hemostasis also be unsuccessful, TAE should be considered. Surgery is indicated when TAE is either locally unavailable or after unsuccessful TAE. Strong recommendation, moderate quality evidence. Recurrent bleeding is defined as bleeding following initial successful endoscopic hemostasis [93]. Clinical evidence of re- current bleeding is defined as recurrent hematemesis or bloody nasogastric aspirate after the first endoscopy, recurrent tachy- cardia or hypotension after achieving hemodynamic stability, melena and/or hematochezia following normalization of stool color, or a reduction in Hb ≥2 g/dL after a stable Hb value has been attained [1]. We were unable to identify any recent stud- ies that directly addressed the PICO question regarding the role of repeat endoscopy for recurrent bleeding after endoscopic therapy for peptic ulcers with high risk endoscopic stigmata. 3.4 Restarting anticoagulation RECOMMENDATION ESGE recommends that, in patients with peptic ulcer hemorrhage who require ongoing anticoagulation therapy, anticoagulation should be resumed as soon as clinically indicated based on thromboembolic risk. Strong recommendation, low quality evidence. A recent UK audit of 5141 patients with acute UGIH found that 30.6% were receiving an anticoagulant (direct oral anticoa- gulant [DOAC], vitamin K antagonist [VKA]) at the time of their bleeding episode [94], this being an increase from the 13% level of reported anticoagulant use in a similar UK audit in 2007 [95]. However, the evidence to guide the resumption of anticoagula- tion therapy (e. g. VKA, DOAC) following a peptic ulcer bleed remains limited. The decision to restart anticoagulation thera- py must balance the risk of recurrent bleeding with the risk of thromboembolic events and/or the sequelae of these events, including death. As compared with patients with peptic ulcer bleeding who were not restarted on anticoagulation, patients who were restarted on anticoagulation after their peptic ulcer bleed (57% restarted; median 15 days) had a lower risk of . d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l . y n o e s u l a n o s r e p r o f d e d a o n w o d l s a w t n e m u c o d i s h T Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved. thrombosis and death at 1 year (hazard ratio [HR] 0.14 [95%CI 0.05 to 0.43]), with no significantly increased risk of recurrent bleeding (HR 1.42 [95%CI 0.10 to 19.8]) [96]. However, the precise timing for restarting anticoagulation in patients with peptic ulcer hemorrhage remains undefined. Those patients at the highest thrombotic risk should restart anticoagulant therapy as soon as possible and the use of subcu- taneous low molecular weight heparin as a bridge to oral anti- coagulation may be a good option. Early consultation with a cardiologist and/or hematologist is desirable.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE could not reach a consensus for or against the routine use of potassium-competitive acid blockers for patients who have undergone endoscopic hemostasis. No recommendation, very low quality evidence. . d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l . y n o e s u l a n o s r e p r o f d e d a o n w o d l s a w t n e m u c o d i s h T Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE recommends high dose PPI therapy for patients who have undergone endoscopic hemostasis and for patients with FIIb ulcer stigmata (adherent clot) not treated endo- scopically. PPI therapy should be administered as an intravenous bolus followed by continuous infusion (e. g. 80 mg then 8 mg/hour) for 72 hours postendoscopy or high dose PPI therapy given as intravenous bolus dosing (twice daily) or in oral formulation (twice daily) can be considered as alternative regimens. Strong recommendation, high quality evidence. RECOMMENDATION ESGE could not reach a consensus for or against the routine use of potassium-competitive acid blockers for patients who have undergone endoscopic hemostasis. No recommendation, very low quality evidence. . d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l . y n o e s u l a n o s r e p r o f d e d a o n w o d l s a w t n e m u c o d i s h T Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE suggests that prophylactic TAE be considered in selected high risk cases of peptic ulcer bleeding (e. g. patients with hemodynamic instability at presentation, posterior duodenal wall ulcer location, large ulcer size [>2 cm], or when durable endoscopic hemostasis is con- sidered uncertain). Conditional recommendation, very low quality evidence. In patients with bleeding from an FI–FIIb ulcer where initial endoscopic hemostasis has been achieved, but who are consid- ered at high risk for recurrent bleeding (e. g. hemodynamic instability at presentation, large ulcer size, large size visible ves- sel, difficult anatomic location of ulcer [36, 73, 74]), prophylac- tic TAE may be considered. We identified four meta-analyses and three retrospective cohort studies published from 2020 to 2025 evaluating the usefulness of prophylactic TAE [75, 76, 77, 78, 79, 80, 81]. We also included two previously published RCTs in our calculations [82, 83]. The available evidence on prophy- lactic TAE following endoscopic hemostasis for high risk peptic ulcers suggests a reduction in rebleeding rates compared with lower conservative management. The two RCTs rebleeding rates with prophylactic TAE – although not always statistically significant – but no clear difference in mortality. In a post-hoc analysis, prophylactic TAE significantly reduced recurrent bleeding only in patients with ulcers ≥15 mm in size (2 [4.5%] vs. 12 [23.1%]; P = 0.03) [82]. suggest Observational data [77] and meta-analyses [78, 79, 80] re- inforce this trend, reporting significant reductions in rebleed- ing and, in some cases, the need for surgery or reintervention. to differ consistently Overall, mortality does not appear between groups and hospital length of stay varies only mini- mally. Studies exclusively evaluating patients treated with pro- phylactic TAE [75, 76] report rebleeding rates ranging from 12% to 25% and mortality of 15% to 20%, likely reflecting very high risk populations. Taken together, the evidence suggests a potential benefit of prophylactic TAE, primarily in preventing rebleeding, while its impact on mortality and other secondary outcomes remains uncertain. 3.2 Antisecretory therapy RECOMMENDATION ESGE recommends high dose PPI therapy for patients who have undergone endoscopic hemostasis and for patients with FIIb ulcer stigmata (adherent clot) not treated endo- scopically. PPI therapy should be administered as an intravenous bolus followed by continuous infusion (e. g. 80 mg then 8 mg/hour) for 72 hours postendoscopy or high dose PPI therapy given as intravenous bolus dosing (twice daily) or in oral formulation (twice daily) can be considered as alternative regimens. Strong recommendation, high quality evidence. RECOMMENDATION ESGE could not reach a consensus for or against the routine use of potassium-competitive acid blockers for patients who have undergone endoscopic hemostasis. No recommendation, very low quality evidence. . d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l . y n o e s u l a n o s r e p r o f d e d a o n w o d l s a w t n e m u c o d i s h T Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE does not recommend that epinephrine injection be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modal- ity. Strong recommendation, high quality evidence. RECOMMENDATION ESGE suggests that topical hemostatic agents should not be used as monotherapy in the first-line treatment of patients with high risk endoscopic stigmata of peptic ulcer bleeding. Conditional recommendation, very low quality evidence. RECOMMENDATION ESGE recommends that persistent bleeding be defined as ongoing active bleeding refractory to standard hemo- stasis modalities. Strong recommendation, high quality evidence. RECOMMENDATION ESGE suggests that, in patients with persistent bleeding refractory to standard hemostasis modalities, the use of a topical hemostatic agent or OTS clips should be consid- ered. Conditional recommendation, very low quality evidence. RECOMMENDATION ESGE recommends that, in patients with persistent bleed- ing refractory to all modalities of endoscopic hemostasis, including topical hemostatic agents and OTS clips, trans- catheter angiographic embolization (TAE) should be considered. Surgery is indicated when TAE is not locally available or after unsuccessful TAE. Strong recommendation, moderate quality evidence. In patients with peptic ulcer bleeding and high risk endo- scopic stigmata (FIa, FIb, or FIIa), high quality evidence consis- tently supports combination endoscopic therapy over injection monotherapy, with epinephrine plus a second hemostasis mod- ality (mechanical or thermal) achieving superior durable hemo- stasis and reduced rebleeding [1]. Epinephrine injection alone is inferior and should not be used as definitive therapy [1]. Multiple recent RCTs and meta-analyses of these studies evalu- ating cap-mounted OTS clips as first-line monotherapy in high risk nonvariceal UGIH demonstrate a significant reduction in the composite outcome of further bleeding at 30 days, driven primarily by lower rates of recurrent bleeding, compared with standard endoscopic therapy (through-the-scope [TTS] clips and/or thermal therapy ± injection) [48, 49, 50, 51, 52, 53, 54]. A benefit in 30-day rebleeding has been shown, while no clear advantage has been demonstrated for immediate hemostasis, mortality, or need for surgery. However, despite being derived from RCTs, the overall cer- tainty of evidence ranges from very low to low, owing to impor- tant methodological limitations. These include lack of blinding, heterogeneity in patient selection, ulcer characteristics, com- parator therapies, variable use of epinephrine injection, and differences in operator expertise and technical success. Impre- cision for key outcomes, such as mortality, surgery, and persist- ent bleeding, further limits the certainty of evidence, and ex- ternal validity remains a concern as these RCTs were conducted in expert centers. Despite these methodological limitations in the available evidence, thereby leading to downgrading to a conditional recommendation, there was strong support from the guideline group for OTS clips to be considered as an alterna- tive first-line therapy to treat FIa, FIb, and FIIa ulcer bleeding, assuming the endoscopist is competent in OTS clip application. The available randomized evidence exclusively evaluates the OTS clip system made by Ovesco Endoscopy (Tübingen, Germa- ny), and data on other cap-mounted devices are limited to case reports and small case series [55, 56]. Although OTS clip devices are associated with higher upfront costs, recent cost-effectiveness analyses indicate that reduc- tions in rebleeding, fewer repeat endoscopies, and decreased need for rescue therapies render OTS clips a cost-effective strategy in high risk peptic ulcer bleeding, particularly when used upfront, rather than as rescue therapy [57, 58].

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE suggests, for patients with an ulcer with a non- bleeding visible vessel (FIIa), OTS clips may be used as alternative monotherapy. Conditional recommendation, very low quality evidence. RECOMMENDATION ESGE suggests hemostatic forceps with soft coagulation may be used as monotherapy in the treatment of peptic ulcer bleeding with high risk stigmata (FIa, FIb, and FIIa). Conditional recommendation, very low quality evidence. . d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l . y n o e s u l a n o s r e p r o f d e d a o n w o d l s a w t n e m u c o d i s h T Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE recommends, for patients with an ulcer with a non- bleeding visible vessel (FIIa), contact or noncontact thermal therapy, mechanical therapy (e. g. through-the- scope [TTS] or OTS clips), or injection of a sclerosing agent, each as monotherapy or in combination with epinephrine injection. Strong recommendation, moderate quality evidence. RECOMMENDATION ESGE suggests, for patients with an ulcer with a non- bleeding visible vessel (FIIa), OTS clips may be used as alternative monotherapy. Conditional recommendation, very low quality evidence. RECOMMENDATION ESGE suggests hemostatic forceps with soft coagulation may be used as monotherapy in the treatment of peptic ulcer bleeding with high risk stigmata (FIa, FIb, and FIIa). Conditional recommendation, very low quality evidence. . d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l . y n o e s u l a n o s r e p r o f d e d a o n w o d l s a w t n e m u c o d i s h T Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE recommends, for patients with actively bleeding ulcers (FIa, FIb), combination therapy using epinephrine injection plus a second hemostasis modality (contact thermal or mechanical therapy). Strong recommendation, high quality evidence. RECOMMENDATION ESGE suggests the use of over-the-scope (OTS) clips as monotherapy as an alternative to combination therapy as first-line therapy for peptic ulcer bleeding with high risk stigmata (FIa, FIb) owing to a lower risk of further bleeding compared with standard endoscopic hemo- static therapy. Conditional recommendation, very low quality evidence. RECOMMENDATION ESGE recommends, for patients with an ulcer with a non- bleeding visible vessel (FIIa), contact or noncontact thermal therapy, mechanical therapy (e. g. through-the- scope [TTS] or OTS clips), or injection of a sclerosing agent, each as monotherapy or in combination with epinephrine injection. Strong recommendation, moderate quality evidence. RECOMMENDATION ESGE suggests, for patients with an ulcer with a non- bleeding visible vessel (FIIa), OTS clips may be used as alternative monotherapy. Conditional recommendation, very low quality evidence. RECOMMENDATION ESGE suggests hemostatic forceps with soft coagulation may be used as monotherapy in the treatment of peptic ulcer bleeding with high risk stigmata (FIa, FIb, and FIIa). Conditional recommendation, very low quality evidence. . d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l . y n o e s u l a n o s r e p r o f d e d a o n w o d l s a w t n e m u c o d i s h T Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE recommends the Forrest (F) classification be used in all patients with peptic ulcer hemorrhage to differentiate low and high risk endoscopic stigmata. Strong recommendation, high quality evidence. RECOMMENDATION ESGE recommends that peptic ulcers with spurting or oozing bleeding (FIa and FIb respectively) or with a nonbleeding visible vessel (FIIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or recurrent bleeding. Strong recommendation, high quality evidence. RECOMMENDATION ESGE suggests that patients with peptic ulcers presenting with an adherent clot (FIIb) should undergo endoscopic therapy, with clot removal and subsequent endoscopic hemostasis if indicated, provided that the endoscopist has the technical competence to safely remove the clot and manage potential conversion to a higher risk bleeding lesion. Conditional recommendation, very low quality evidence. RECOMMENDATION ESGE does not recommend endoscopic hemostasis in patients with peptic ulcers that have a flat pigmented spot (FIIc) or clean base (FIII), as these stigmata have a low risk of adverse outcomes. In selected clinical settings, these patients may have an expedited hospital discharge. Strong recommendation, moderate quality evidence. RECOMMENDATION ESGE could not reach a consensus for or against the routine use of a Doppler endoscopic probe in treatment decisions of high risk endoscopic stigmata of peptic ulcer bleeding. No recommendation, very low quality evidence. The Forrest (F) classification was developed more than 50 years ago to standardize the endoscopic characterization of peptic ulcers. It is defined as follows: FIa, spurting hemorrhage; FIb, oozing hemorrhage; FIIa, nonbleeding visible vessel; FIIb, adherent clot; FIIc, flat pigmented spot; and FIII, clean base ulcer. This classification has been used in numerous studies to identify patients at risk of persistent ulcer bleeding, recurrent ulcer bleeding, and mortality (▶ Fig. 3). Most of these studies have shown that the presence of an ulcer endoscopically classified as FIa or FIb is an independent risk factor for persistent bleeding or recurrent bleeding. A potential limitation of the Forrest classification is that endoscopic stigmata recognition and identification, as well as interobserver agreement, may be less than optimal. Artificial intelligence is being evaluated for improving endoscopic recognition of stigmata of recent hemorrhage in peptic ulcer bleeding, but as yet data remain limited. Two contemporary systematic reviews and meta-analyses demonstrate that, in patients with peptic ulcers presenting with an adherent clot (FIIb), endoscopic therapy in addition to medical therapy significantly reduces rebleeding compared with medical therapy alone [39, 40]. In the larger meta-analysis by Beran et al., which included 11 studies (9 RCTs) comprising 833 patients (431 endoscopic vs. 402 conservative therapy), endoscopic therapy was associated with significantly lower odds of overall rebleeding (OR 0.41, 95%CI 0.22 to 0.79; P = 0.007) and 30-day rebleeding (OR 0.43, 95%CI 0.21 to 0.89; P = 0.002) compared with conservative treatment. Endoscopic management was also associated with significantly lower odds of overall mortality (OR 0.47, 95%CI 0.23 to 0.95; P = 0.04), as well as a reduced need for surgery (OR 0.44, 95%CI 0.21 to 0.95; P = 0.04) and a mean shortening of hospital stay by 3.17 days (mean difference −3.17, 95%CI −4.14 to −2.19; P<0.001). However, in a subgroup analysis restricted to the nine RCTs, the mortality difference was not significant (OR 0.78, 95%CI 0.24 to 2.52; P = 0.68), but endoscopic therapy was associated with a trend toward a reduced overall rebleeding rate (7.2% vs. 18.5%; OR 0.42, 95%CI 0.17 to 1.05; P = 0.06) and a statistically significant reduction in the need for surgery (OR 0.28, 95%CI 0.08 to 0.96; P = 0.04). A second meta-analysis by Tassone et al., restricted to seven RCTs with 268 patients, confirmed a significant reduction in recurrent bleeding with endoscopic hemostatic treatment (risk ratio [RR] 0.40, 95%CI 0.16 to 0.95) compared with medical therapy alone. In this pooled cohort, there were no statistically significant differences in mortality (RR 0.90, 95%CI 0.23 to 3.59) or need for surgery (RR 0.48, 95%CI 0.10 to 2.28) Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved.. d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE recommends adopting the following definitions regarding the timing of upper GI endoscopy in acute UGIH relative to the time of patient presentation: urgent ≤12 hours, early ≤24 hours, and delayed >24 hours. Strong recommendation, moderate quality evidence. RECOMMENDATION ESGE recommends that, following hemodynamic resuscitation, early (≤24 hours) upper GI endoscopy be performed. Strong recommendation, low quality evidence. RECOMMENDATION ESGE does not recommend emergent (≤6 hours) or (≤12 hours) upper GI endoscopy unless the urgent patient remains hemodynamically unstable despite adequate resuscitation. Strong recommendation, moderate quality evidence. Evidence on the timing of upper GI endoscopy in acute UGIH is derived from four contemporary systematic reviews and meta-analyses [30, 31, 32, 33], incorporating randomized and observational studies, and one recent RCT. Importantly, the available evidence is based mainly on nonrandomized observational studies with high inconsistency due to high heterogeneity. In addition, owing to high variability of the definitions of “high risk” bleeding, timing of upper GI endoscopy, the endoscopic modalities applied, and the mix of older and contemporary endoscopic practices, the guideline group has downgraded the quality of the evidence. However, across this body of evidence, early endoscopy, performed within 24 hours of hospital presentation following adequate hemodynamic resuscitation, is associated with a higher likelihood of the use of endoscopic hemostasis therapy and a modest reduction in hospital length of stay. There is however no observed reduction in mortality or rebleeding compared with delayed endoscopy, with reported mortality (3%–6%) and rebleeding rates (7%– 11%) remaining similar between the groups [30, 31, 32, 33]. In contrast, very early or urgent endoscopy (≤12 hours), and in particular emergent endoscopy (≤6 hours), has not shown clinical benefit over early endoscopy in randomized trials or in observational studies, and is frequently associated with higher rates of rebleeding and, in some cohorts, increased rates Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved.. d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l. y n o e s u l a n o s r e p r o f d e d a o n w o d l s a w t n e m u c o d i s h T of mortality, surgery, or repeat endoscopy, findings likely influenced by confounding by indication and incomplete hemodynamic resuscitation. A pivotal RCT by Lau et al. similarly demonstrated no improvement in 30-day mortality, rebleeding, transfusion requirements, or length of hospital stay with endoscopy performed within 6 hours of GI consultation, compared with that performed at 6–24 hours, despite the greater use of endoscopic hemostasis.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE does not recommend routine prophylactic endo- tracheal intubation for airway protection prior to upper GI endoscopy in patients with acute UGIH. Strong recommendation, high quality evidence. RECOMMENDATION ESGE recommends prophylactic endotracheal intubation for airway protection prior to upper GI endoscopy only in selected patients with acute UGIH (i. e. those with ongo- ing active hematemesis, agitation, or encephalopathy with inability to adequately control the airway). Strong recommendation, low quality evidence. Since publication of the 2021 ESGE guideline on nonvariceal UGIH, only additional observational retrospective data on pro- phylactic endotracheal intubation have emerged. These data confirm earlier concerns regarding increased pulmonary ad- verse events (e. g. aspiration, pneumonia) and longer hospital stays without a consistent mortality benefit. These new studies remain at high risk of confounding and fail to resolve key uncer- tainties regarding clear indications, patient selection, or cost- effectiveness [29]. Consequently, the 2021 recommendations against routine prophylactic intubation and for selective use only in high risk patients remain unchanged.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE suggests that pre-endoscopy high dose intravenous proton pump inhibitor (PPI) therapy be considered in this patients presenting with acute UGIH; however, should not delay early endoscopy. Conditional recommendation, low quality evidence. In 2019, the International Consensus Group on nonvariceal UGIH recommended that “pre-endoscopic PPI therapy may be considered to downstage the endoscopic lesion and decrease the need for endoscopic intervention but should not delay endoscopy”. In 2021, The American College of Gastroenterology could not reach a recommendation for or against preendoscopic PPI therapy in patients presenting with acute UGIH. In our 2021 guideline, we have previously suggested that “pre-endoscopy high dose intravenous PPI be considered in patients presenting with acute UGIH to downstage endoscopic Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved.. d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE recommends pre-endoscopy administration of intravenous erythromycin in selected patients with clinically severe and/or ongoing active UGIH. Strong recommendation, high quality evidence. RECOMMENDATION ESGE suggests, if intravenous erythromycin is unavailable, pre-endoscopy administration of intravenous metoclopramide in selected patients with clinically severe or ongoing active UGIH. Conditional recommendation, low quality evidence. Since the publication of ESGE’s guideline on peptic ulcer bleeding in 2021, there have been several published studies, including six RCTs, examining the efficacy of prokinetics (erythromycin, metoclopramide, azithromycin) for improving endoscopic visualization of the upper GI tract in patients with acute UGIH [17, 18, 19, 20, 21, 22]. We performed a meta-analysis using data from the four RCTs (two fully published original articles and two published conference abstracts) that evaluated intravenous metoclopramide versus placebo in patients presenting with UGIH, both nonvariceal and variceal in etiology. We found that, compared with placebo, intravenous metoclopramide administered prior to upper GI endoscopy significantly improved mucosal exposure and endoscopic visualization (▶ Fig. 1). There were however no significant differences in units of blood transfused or hospital length of stay, although there was a possible trend toward a reduced need for second-look endoscopy (▶ Fig. 2). Our risk of bias assessment found the quality of the included studies to be of moderate quality. The lack of imprecision, indirectness, and inconsistency led to uprating the level of evidence and strength of recommendation according to GRADE. A meta-analysis by Waseem et al., published after our initial search strategy was performed, reported similar results. The widespread availability, feasibility, and low costs associated with metoclopramide are factors that support its use; however, the potential for serious adverse events with its use, including anaphylaxis, serotonin syndrome, extrapyramidal reaction, and cardiac arrhythmia must be acknowledged. Only a single RCT among those included in our meta-analysis provided insights regarding adverse events following metoclopramide use, with the investigators reporting no adverse events. Intravenous metoclopramide could be considered for use as part of the pre-endoscopy management of patients presenting with acute UGIH but, given the potential for adverse events, caution should be exercised. Therefore, the use of intravenous erythromycin is preferred as per ESGE’s prior strong recommendation, but the use of intravenous metoclopramide is a Gralnek Ian M et al. Endoscopic diagnosis and … Endoscopy | © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved.. d e t i b h o r p i y l t c i r t s s i n o i t u b i r t s d i d e z i r o h t u a n U l.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

• ESGE does not recommend the routine use of video capsule endoscopy or telemetric blood-sensing capsules in the management of patients with suspected UGIH. Strong recommendation, very low quality evidence. Given the lack of new evidence directly comparing outcomes between patients admitted to hospital and those discharged from the emergency department based on pre-endoscopic risk stratification scores, we did not change the recommendation from the previous guideline. To ensure safe and feasible outpatient management, the patient must receive prompt outpatient GI/endoscopy follow-up, have the ability to return to the emergency department if needed, be instructed to be aware of any recurrent signs/symptoms of bleeding, and have an understanding of the follow-up clinical plan. The guideline group also wished to reiterate that no risk stratification tool should replace clinicians’ judgement. Across recently published studies, capsule-based strategies for acute UGIH have shown signals of benefit, although these have been primarily in patient triage, rather than in hard outcomes. Randomized and cohort data suggest that video capsule endoscopy performed in the emergency department safely increases same-day discharge and reduces the need for urgent inpatient upper GI endoscopy in hemodynamically stable patients, without evidence of rebleeding or mortality at 7–30 days. Telemetric blood-sensing capsules may aid in patient triage and guide clinical decision-making for individuals presenting with suspected UGIH [12, 13]. These blood-sensing capsules demonstrate high technical success and diagnostic accuracy for detecting blood in the upper GI tract. Negative tests are associated with the absence of rebleeding and may allow for downgrading of the need for urgent upper GI endoscopy or the avoidance of endoscopy altogether [12, 13]. Systematic reviews/meta-analyses also appear to support these findings: as compared with standard risk stratification scores alone, capsule-based triage pathways reduce hospital admissions and the need for early upper GI endoscopy in suspected UGIH [14, 15]. A meta-analysis of artificial intelligenceassisted wireless capsule endoscopy further suggests that automated analyses could enhance the speed and consistency of capsule interpretation, although this did not translate into patient-level outcome data. Most datasets are however small, often observational, heterogeneous in inclusion criteria and end points, and are powered for process outcomes (need for hospital admission and/or upper GI endoscopy) rather than mortality, which results in overall low certainty and restriction recommendations to selected, hemodynamically stable of patients in experienced centers. Moreover, cost-effectiveness, availability, and training have been incompletely addressed.

  Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · 2026 · DOI

Most-cited papers in Gastrointestinal Bleeding Diagnosis and Treatment

• Robotic wireless capsule endoscopy: recent advances and upcoming technologies · Nature Communications · 2024 · 135 citations
• Detection of various gastrointestinal tract diseases through a deep learning method with ensemble ELM and explainable AI · Expert Systems with Applications · 2024 · 87 citations
• A Review on Treatment of Perforated Peptic Ulcer by Minimally Invasive Techniques · MAEDICA – a Journal of Clinical Medicine · 2022 · 9 citations
• Gastrointestinal Bleeding on Oral Anticoagulation: What is Currently Known · Drug Safety · 2022 · 8 citations
• Assessment of Prognostic Scores for Emergency Department Patients With Upper Gastrointestinal Bleeding · Annals of Emergency Medicine · 2024 · 6 citations
• Decompensated portal hypertension complicated by bleeding · EMERGENCY MEDICINE · 2024 · 6 citations
• Treatment of portal hypertension complicated by variceal bleeding · EMERGENCY MEDICINE · 2024 · 5 citations
• EVALUATION OF CLINICAL FEATURES AND RISK FACTORS AFFECTING BLEEDING IN PATIENTS WITH GASTROINTESTINAL ANGIODYSPLASIA · Ankara Eğitim ve Araştırma Hastanesi Tıp Dergisi · 2022 · 4 citations
• The role of BUN/creatinine ratio in determining the severity of gastrointestinal bleeding and bleeding localization · Northern Clinics of Istanbul · 2025 · 4 citations
• Understanding acute upper gastrointestinal bleeding in adults · Nursing · 2020 · 3 citations

Most recent work

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• Endoscopic diagnosis and management of peptic ulcer bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2026 · Endoscopy · 2026
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