Endoscopic Treatment of Upper Gastrointestinal Bleeding
Article information
Abstract
Upper gastrointestinal bleeding remains an important gastrointestinal condition despite a decline in its incidence, the introduction of acid-suppressive therapy, and advances in endoscopic techniques. Based on etiology, it is classified as variceal or nonvariceal bleeding, with peptic ulcers constituting the majority of nonvariceal bleeding. Before endoscopy, it is essential to stabilize the patient by administering appropriate fluids, blood transfusions, proton pump inhibitors, vasoconstrictors, and antibiotics, followed by an early endoscopic examination and treatment whenever possible. Endoscopic management can be facilitated by accessories such as transparent caps, water-jet pumps, overtubes, and multi-bending endoscopes. Studies have reported emerging tools, including machine learning models for risk prediction, swallowable bleeding sensors, and hemostasis guided by endoscopic ultrasound or Doppler. Endoscopic hemostasis includes injections, mechanical therapy, electrocautery, and topical therapies. Once the bleeding source is identified, an appropriate endoscopic modality can be selected according to the lesion. For nonvariceal bleeding, injections, coagulation, and mechanical methods are used when endoscopic hemostasis is indicated. Band ligation is commonly used to treat esophageal variceal bleeding, whereas gastric variceal bleeding is typically treated with cyanoacrylate injections. If endoscopic therapy fails or rebleeding occurs, angiography with embolization or surgery may be required, and in acute variceal bleeding, a transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration can be considered. Second-look endoscopy may be performed selectively in patients at high risk of rebleeding or when repeat evaluation is needed. In peptic ulcer disease, early biopsy should be performed when malignancy is suspected, and Helicobacter pylori testing and eradication should be ensured.
INTRODUCTION
Upper gastrointestinal bleeding (UGIB) refers to bleeding from the esophagus, stomach, or duodenum [1], and is anatomically defined as bleeding proximal to the ligament of Treitz [2]. It may present with hematemesis and melena, whereas massive bleeding can present with hematochezia [1,2].
The incidence and mortality of UGIB have decreased with the introduction of acid-suppressive drugs such as proton pump inhibitors (PPIs) and potassium-competitive acid blockers, Helicobacter pylori eradication, improved access to endoscopy, and advances in endoscopic hemostasis techniques [3-5]. In a Spanish study, the incidence decreased from 87 per 100000 to 47 per 100000 between 1996 and 2005 [4], and a large US study reported a similar trend [5]. Despite this decline, UGIB remains a major cause of emergency department visits and hospitalization, and mortality remains at approximately 2%–10% [2].
UGIB is commonly classified as variceal or nonvariceal bleeding [2]. The leading cause of nonvariceal UGIB is peptic ulcer disease. In a large Korean study, peptic ulcers accounted for approximately 96% of nonvariceal UGIB [6]. Other important causes include esophagitis, angiodysplasia, Mallory–Weiss tears, Dieulafoy lesions, and malignancies.
This review aims to summarize the latest research findings on the epidemiology, etiology, risk stratification, endoscopic diagnosis, and hemostasis of UGIB and assist endoscopists in clinical practice. Relevant literature published within the last 30 years was identified through a narrative search of PubMed.
PRE-ENDOSCOPY PREPARATION
Patients presenting with UGIB often have hypovolemic shock and are at high risk of respiratory compromise. It is advisable to assess the patient’s condition and implement appropriate stabilization before endoscopy.
Risk stratification
Several risk stratification tools (Table 1) have been developed to help clinicians rapidly assess patient history and current status, estimate the risk of rebleeding or death, and guide objective treatment decisions. These tools typically incorporate comorbidities, vital signs, and overall clinical status at presentation, as well as endoscopic stigmata of bleeding. Common tools include the Glasgow-Blatchford score (GBS), Rockall score, AIMS65, and ABC score [6,7]. In variceal bleeding, the Child–Pugh classification and MELD score are frequently used to reflect liver function [8].
Risk stratification scores
Timing of endoscopy
The optimal endoscopy timing for UGIB has been debated for several decades. Large meta-analyses showed that endoscopic therapy was associated with an approximately 30% reduction in mortality [9,10], and it also reduced rebleeding and the need for surgery [10]. Interest then shifted to whether faster endoscopy improves clinical outcomes and costs. Early endoscopy appears intuitively beneficial, but a large study of 30-day mortality after peptic ulcer bleeding reported that the major causes of death were not bleeding itself but multi-organ failure (23.9%) and pulmonary disease (23.5%) [11]. This emphasized the importance of stabilizing comorbid conditions. In a Danish cohort study (12601 patients with peptic ulcer bleeding), among patients with at least one severe comorbidity and hemodynamic instability, those who underwent endoscopy 6–24 hours after admission had lower mortality than those who underwent endoscopy within 6 hours or after 24 hours [12]. This can be interpreted as supporting initial resuscitation, correction of coagulopathies, and stabilization of comorbidities for at least several hours, followed by endoscopy within 24 hours when feasible. In a randomized controlled trial by Lau et al. [13], 516 patients with UGIB and GBSs of ≥12 were assigned to urgent endoscopy within 6 hours versus early endoscopy at 6–24 hours. Urgent endoscopy did not reduce rebleeding or 30-day mortality rates. A large retrospective study of 6474 patients with UGIB also found that endoscopy within 6–24 hours was associated with the lowest mortality compared with endoscopy within 6 hours or after 24 hours [14].
However, conflicting results have previously been reported. In a retrospective study of 961 patients with nonvariceal UGIB and GBSs of ≥7, endoscopy within 6 hours was associated with lower 28-day mortality rates than endoscopy performed between 6 and 48 hours [15]. A recent meta-analysis of nonvariceal UGIB reported the highest mortality in the group with endoscopy within 12 hours, and showed no mortality benefit of endoscopy within 24 hours [16].
However, these recommendations differ in cases of suspected variceal bleeding. A large meta-analysis in variceal bleeding reported that early endoscopy significantly reduced mortality [17], although the definition of “early” varied across studies. The current US and European guidelines commonly use 12 hours as the target.
These heterogeneous findings likely reflect that UGIB has diverse etiologies, heterogeneous patient risk profiles even within the same etiology, and differences in healthcare systems and resources.
We can summarize that it is essential to perform endoscopy within 24 hours after hemodynamic resuscitation and stabilization in patients suspected to have nonvariceal UGIB [18-20], and within 12 hours in variceal bleeding [21-23].
Although the recommended windows may not be optimal for every patient, a cautious approach that prioritizes stabilization, acid suppression (to stabilize clots and promote ulcer healing), optimal use of antibiotics and vasoactive agents for variceal bleeding, and management of comorbidities is likely to be more important than pursuing the fastest possible endoscopy. However, urgent endoscopy may be necessary in patients who remain hemodynamically unstable despite resuscitation or have ongoing bleeding symptoms [24].
Pre-endoscopy patient preparation
Because patients with UGIB are at risk of hypovolemic shock and respiratory failure, airway protection should be considered, and large-bore intravenous access should be secured. Hemodynamic stabilization should be achieved with intravenous fluids and blood transfusions, when indicated. Patients should be monitored using pulse oximetry, electrocardiography, and automated blood pressure measurement [25].
A focused history and review of medical records should confirm comorbidities and the use of antiplatelet agents, anticoagulants, and nonsteroidal anti-inflammatory drugs [26]. The possibility of variceal bleeding should be assessed by a history of liver disease and signs such as jaundice, spider angiomas, or palmar erythema. Some patients may refuse the transfusion for religious reasons [27], which should be identified in advance.
Prophylactic antibiotics should be administered before endoscopy in patients at high risk of bacteremia and related complications, including those with cirrhosis, a history of infective endocarditis, or prior prosthetic heart valve replacement [28]. In patients with implanted electronic cardiac devices such as pacemakers or implantable cardioverter-defibrillators, cardiology consultation is recommended before the procedure, with device mode adjustment if electrosurgical unit use is anticipated [29].
Fasting for at least 8 hours is not an absolute prerequisite for emergency endoscopy. However, documenting the fasting interval remains useful when planning the timing of endoscopy and estimating aspiration risk.
Endoscopy and accessories
Cap (transparent hood)
Attaching a transparent cap to the endoscope tip can improve visualization by focusing the endoscopic field and reducing blind spots [30]. It can also facilitate clip deployment in anatomically challenging locations [31]. When the lesion moves with respiration, stabilizing the cap against the gastric wall may help maintain a steady position [25]. These advantages are particularly helpful in the duodenum, where luminal angulation and prominent folds can make identification of the bleeding source and precise hemostasis difficult.
Water-jet pump
A water-jet system can rapidly irrigate the blood, improve identification of the bleeding source, and help dislodge adherent clots using water pressure [25]. It can shorten the procedure time and confirm whether the bleeding vessel is adequately compressed when using hemostatic forceps.
Overtube
An overtube is useful when repeated insertion of the endoscope is anticipated, such as in multiple-band ligation, when clots need to be removed, or when the lens requires cleaning. This may reduce the risk of aspiration. However, overtube placement can cause complications, including laryngopharyngeal or esophageal mucosal injury, perforation, vocal cord paralysis, and pneumomediastinum [32]. The endoscope should first be inserted, and the overtube should then be advanced over the endoscope. Adequate lubrication of the overtube tip is necessary, and the overtube should be gently inserted without resistance.
Carbon dioxide insufflation
Carbon dioxide is rapidly absorbed into the bloodstream after intraluminal insufflation and can reduce post-procedural abdominal pain and distension. When used during hemostasis, it may reduce patient discomfort and belching [33]. It may also be advantageous if perforation occurs, which is a potential complication of electrocautery. However, room air is preferred for patients with chronic respiratory diseases, obstructive sleep apnea, moderate-to-severe obesity, or known carbon dioxide retention [25].
Multi-bending (two-channel) endoscopy
Certain gastric locations, including the lesser curvature or posterior wall of the body, the cardia, and the lesser curvature of the antrum, are technically demanding for endoscopic hemostasis because of limited access. A multibending endoscope has two bending sections at the distal end, which can facilitate a closer approach to difficult sites [25,34]. The two channels of this endoscope also provide practical advantages. One can be used to suction fluid or clots, while the other is used for the insertion of endoscopic devices [25].
Preparation to optimize endoscopic visualization
In patients with UGIB, pooled blood clots in the stomach not only prolong procedure times but can also impede adequate examination and endoscopic therapy [35-37]. The reported frequency of inadequate endoscopic evaluation due to clots in the gastric fundus ranges from 5.6% to 13% [37]. It has been associated with significantly higher rates of rebleeding, longer hospital stays, greater transfusion requirements, emergency surgery, and higher bleeding-related mortality rates [37]. Approaches to improve visualization include endoscopic suction, administration of prokinetics, nasogastric lavage, patient repositioning, and using endoscopic accessories [35].
Prokinetics
Erythromycin is an antibiotic with a prokinetic effect that acts as an agonist of motilin receptors in the gastroduodenal smooth muscle. It has been used in UGIB before endoscopy to promote gastric emptying [38]. In a meta-analysis including eight studies, pre-endoscopic erythromycin improved visualization of the gastric mucosa and reduced the need for repeat endoscopy and the length of hospital stay [39]. US guidelines recommend its use to promote gastric emptying before endoscopy in UGIB [19], and European guidelines recommend selective use in patients with massive active bleeding [20]. However, injectable erythromycin is not available in Korea. The evidence for intravenous metoclopramide is inconsistent, and a meta-analysis found no significant effect on adequate mucosal visualization, transfusion requirements, length of stay, or the need for repeat endoscopy [40].
Nasogastric lavage
Nasogastric tube insertion and lavage have long been used in patients with suspected or confirmed UGIB, although evidence of its clinical benefits is limited. The rationale is to confirm the presence of UGIB, remove blood and clots, reduce aspiration risk during endoscopy, and improve the endoscopic field [41,42]. In a randomized controlled trial of 39 patients with UGIB, nasogastric lavage of up to a maximum of 15 L until the effluent became clear improved visualization compared with controls. However, it did not improve the identification of the bleeding source, hemostasis success, rebleeding, the need for repeat endoscopy, length of stay, or mortality [43]. A subsequent large retrospective study also found that nasogastric lavage did not improve mortality, length of stay, surgery rates, or transfusion requirements [41]. Although nasogastric lavage is commonly performed in emergency settings, it can cause substantial discomfort and carries risks of complications without clear clinical benefit. Therefore, routine nasogastric lavage is not recommended in patients with UGIB [44]. However, the diagnostic and decompressive effects of nasogastric tube placement may still be clinically relevant in selected situations.
Patient repositioning
When visualization is limited by clots in the gastric fundus, changing the patient’s position may allow clots to move inferiorly, improving the endoscopic field [35]. In practice, repositioning to a supine or right lateral decubitus position may be difficult, and aspiration risk may increase. In a report of patients in whom fundus inspection was difficult, elevating the upper body while maintaining a left lateral position allowed the clot to shift toward the gastric body under gravity in all 44 patients, thereby permitting fundus visualization and enabling detection of additional bleeding lesions [36]. Mori et al. [45] reported a case in which a newly developed U-shaped overtube was used to facilitate safe and effective repositioning to a right lateral decubitus position, allowing successful endoscopic hemostasis.
Sedative endoscopy
Endoscopic hemostasis often requires a long time, which can increase patient discomfort. Sedation can improve patient tolerance. However, concerns include hypotension, hypoxemia, paradoxical drug reactions, and unexpected adverse events during emergency procedures [46].
Available studies suggest that sedation during endoscopic hemostasis in UGIB may increase transient hypotension or hypoxemia, but most events respond to supportive measures [46,47], and some studies report shorter procedure times without excess complications [48,49]. These findings should be interpreted with caution because most studies excluded patients who remained hemodynamically unstable and typically included only those who were alert with stable vital signs and respiratory statuses.
Sedative endoscopy for patients with UGIB should be reserved for appropriately selected patients and performed with oxygen supplementation, close monitoring (blood pressure, electrocardiography, and oxygen saturation), and experienced personnel and resources able to manage complications [46,47].
Emerging diagnostic and therapeutic approaches
Image-enhanced endoscopy
The Olympus EVIS X1 system includes a red dichromatic imaging (RDI) function and an image-enhanced endoscopy modality (Fig. 1). RDI can facilitate the identification of bleeding points and prominent submucosal vessels [50]. RDI may be considered when available.
RDI of bleeding vessel. A: White light endoscopic reveals a peptic ulcer with active bleeding. B: RDI function allows for clear observation of bleeding vessels. RDI, red dichromatic imaging.
Machine learning models
Machine learning models developed for risk prediction in UGIB integrate a broad range of clinical variables, including demographics, vital signs, comorbidities, medication use, and laboratory results [51]. Representative methods include Random Survival Forests, Regularized Cox regression, XGBoost, and long short-term memory models [52]. These models have been reported to outperform conventional risk scores, including identifying patients at low risk, predicting mortality, assessing bleeding risk, and estimating transfusion requirements [51]. Wider clinical adoption will likely require further validation and cost-effectiveness evaluation.
Swallowed bleeding sensor
A swallowed bleeding sensor is a device designed for the rapid and accurate detection of UGIB. It consists of an optical sensor capsule that the patient swallows and an external receiver that displays data in real time [51]. In a prospective study by Akiki et al. [53] involving 126 patients, the presence of blood was detected within 10 minutes with a sensitivity of 92.9% and specificity of 90.6%, without notable adverse events. The device may be useful when rapid triage of suspected UGIB is needed; however, it does not provide information on the bleeding location or volume, and additional cost-effectiveness studies are required [51].
Endoscopic ultrasound and Doppler
Endoscopic ultrasound (EUS) and Doppler imaging for endoscopic hemostasis are advantageous for vascular assessment. They have been reported to improve success rates and cost-effectiveness in peptic ulcers or Dieulafoy lesions [54], and have high success rates in gastric varices [55]. However, in emergency endoscopy settings, these techniques may be difficult to perform. They also have limitations, including false-positive findings and difficulty in assessing blood flow in vessels deeper than 4 mm. They require operators with EUS expertise, and whether the published cost-effectiveness findings translate into Korean healthcare settings remains uncertain.
ENDOSCOPIC HEMOSTATIC MODALITIES
Injection therapy
Injection therapy involves the delivery of an agent into or around the target lesion using an injection catheter with a 19- to 25-gauge needle, typically 3–5 mm in length [20,25,56]. Epinephrine or saline provides a tamponade effect. Sclerosants or tissue adhesives, including ethanol, ethanolamine, polidocanol, thrombin, fibrin, and cyanoacrylate, can also be used [57].
Diluted epinephrine
Diluted epinephrine can achieve rapid initial hemostasis and improve the visualization of active bleeding by tamponade from the injected volume, vasoconstriction, and subsequent thrombus formation [57,58]. Compared to pharmacotherapy alone, epinephrine injection provides benefits; however, its effect is often transient and is associated with higher rebleeding rates when used alone. Therefore, it is generally combined with other hemostatic modalities, such as mechanical therapy or thermal coagulation [58,59].
The injection catheter is introduced through the working channel and connected to a syringe. Diluted epinephrine, most commonly at a concentration of 1:10000 or 1:20000 in normal saline, is injected into four quadrants around the bleeding site, typically 0.5 to 2 mL per injection [20]. When the injection is effective, bleeding decreases or stops, and a vessel or any adherent clot may become more clearly visible, and the surrounding mucosa may appear blanched. Inadvertent intra-arterial epinephrine injections can cause marked hypertension [60].
Cyanoacrylate
Cyanoacrylate, a tissue adhesive widely known as histoacryl, is most commonly injected into bleeding gastric varices. In a meta-analysis comparing cyanoacrylate injection with band ligation for gastric variceal bleeding, initial hemostasis rates were similar, but rebleeding rates were lower (relative risk [RR] 0.6) [61]. Two randomized studies also reported better treatment outcomes with cyanoacrylate injections than with band ligation, without a difference in complication rates [62,63].
During the procedure, cyanoacrylate is often mixed in a 1:1 ratio with lipiodol to delay polymerization, and the injection volume is selected according to the varix size. To reduce the risk of damage to the endoscopic channel, a neutral oil, commonly olive oil, can be instilled in advance (approximately 5 mL), and relatively large-bore (21- to 22-gauge) and longer (5 mm) injection needles are used. After flushing the catheter with 1–2 mL of distilled water, the varix is punctured while maintaining an endoscope-to-varix distance of approximately 3–5 cm. Cyanoacrylate is injected over 4–5 seconds, followed by a distilled water flush to deliver any material remaining in the catheter, and the needle is then promptly withdrawn. Suction should be avoided because the polymerized cyanoacrylate can cause channel obstruction. A post-procedure radiograph can confirm the appropriate distribution of the injected material and assess complications, such as pulmonary or splenic embolic events [58].
Mechanical therapy
Through-the-scope clips
Hemostasis with clips is achieved by firmly grasping the target vessel and surrounding tissue to provide mechanical compression [64]. Through-the-scope (TTS) clips are delivered through the working channel of the endoscope either as a preloaded device or by mounting the clip immediately before use. A wide range of clip designs is available, differing in metal composition, jaw length, angulation, rotatability, and ability to reopen and close the clips. For hemostasis, a relatively short clip with jaws angled at 135° may be advantageous, particularly in firm or fibrotic lesions where secure anchoring is needed. The characteristics of commonly used TTS clips in Korea are summarized in Table 2.
Through-the-scope mechanical clips used for endoscopic hemostasis
In a meta-analysis by Sung et al. [65], TTS clipping, alone or in combination, achieved superior hemostasis compared with epinephrine injection alone. A major advantage of TTS clipping is less tissue injury. The limitations include the need for a skilled assistant and suboptimal first placement that can worsen bleeding and complicate subsequent therapy [64]. Technical difficulty can also be encountered in areas such as the gastric fundus, lesser curvature of the gastric body, posterior wall of the duodenal bulb, lesions with marked fibrosis, or large-caliber exposed vessels [66,67].
Accurate clip placement generally benefits from maintaining a perpendicular orientation towards the wall of the target site. Gentle suction during deployment can bring the target closer to the endoscope tip and may be helpful. When retroflexion is required, introducing a clip device into the channel before retroflexion may be helpful. Moving the endoscope while the clip is open may cause mucosal injury or clip deformation; therefore, caution is warranted [64].
Over-the-scope clip
An over-the-scope (OTS) clip is a large-diameter clip (8.5–14 mm) mounted on a cap at the endoscope tip. It has a clawlike configuration and is deployed in a manner similar to band ligation. Tissue is suctioned into the cap, and the clip is released by rotating an external hand wheel connected to the device [67]. After deployment, the final diameter is 14.6–21 mm [59]. OTS clips are typically made of nitinol, a shape-memory alloy composed of nickel and titanium, which provides strong elastic recoil and enables thick tissue capture over a broad area [58]. They may be useful for large ulcers (>2 cm), large vessels, and chronic ulcers [67].
In a prospective randomized study of rebleeding after initial endoscopic hemostasis, OTS clips reduced further bleeding compared with standard therapy (15.2% vs. 57.6%) [68]. In a meta-analysis evaluating OTS clips as first-line therapy for nonvariceal UGIB, they reduced bleeding (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.17 to 0.59), but no difference was observed in 30-day mortality (OR 0.60, 95% CI 0.23 to 1.56) [1]. US guidelines recommend OTS clips for rebleeding [19], and European guidelines recommend it as primary therapy in ulcers larger than 2 cm or with severe fibrosis [20].
The limitations of OTS clips include the need to withdraw the endoscope to mount the device, increased endoscope tip diameter, difficulty with subsequent therapy if misdeployment occurs, and higher costs [64,67]. For effective deployment, close apposition between the cap and lesion is required. Grasping devices may be used to capture tissue into the cap before suction [64]. Long-term data are needed to clarify the durability and potential adverse effects. Under the current Korean National Health Insurance system, OTS clips are only reimbursed for the closure of gastrointestinal perforations.
Band ligation
Band ligation is primarily used for esophageal varices; however, it has also been applied to vascular ectasia, Dieulafoy lesions, Mallory–Weiss tears, and ulcer bleeding with limited fibrosis. A hood containing a rubber band is mounted on the endoscope tip. After approaching, the target is suctioned into the cap, an assistant insufflates air through a tube connected to the device using a syringe, and the band is released. It provides mechanical compression and a tamponade effect [20,25]. Effective therapy depends on adequate suction and perpendicular positioning of the cap to the lesion [25], and suction is maintained gently until the endoscopic view becomes fully occupied by mucosa (the “red-out” sign). Earlier devices required single-band loading; however, multiband ligation systems are now available, allowing repeated ligation without removing the endoscope.
Stents
Covered self-expandable metallic stents (SEMS) have been studied for the treatment of refractory esophageal variceal bleeding. In a multicenter randomized controlled trial involving 28 patients with refractory variceal bleeding, SEMS demonstrated better outcomes than balloon tamponade using a Sengstaken–Blakemore tube in terms of mortality, bleeding control, serious procedure-related complications, and transfusion requirements [69]. Stents can also be maintained for longer periods and cause less patient discomfort. However, under the current Korean National Health Insurance System, SEMS use for esophageal variceal bleeding is not reimbursed.
Endoscopic purse-string suture
Endoscopic purse-string sutures using clips and a detachable snare have been reported as a rescue therapy for nonvariceal UGIB refractory to conventional methods, with promising success rates in small studies [70,71]. This technique uses TTS clips and a detachable snare without requiring specialized equipment. It can be applied to large ulcers and is relatively cost-effective. The limitations include a longer procedure time when multiple clips are required, the need for an experienced endoscopist, and difficulty in anatomically challenging locations.
Electrocautery-based therapy
Argon plasma coagulation
Argon plasma coagulation (APC) is a representative noncontact modality. The ionized argon gas generated at the probe tip delivers a high-energy monopolar current to the tissue, resulting in dehydration and coagulation [56]. As tissue dehydrates, electrical conductivity decreases. For this reason, APC has a limited effect on large vessels or deeper tissue and is mainly used for superficial vessels [25,56,59]. In a meta-analysis that included two randomized controlled trials, APC monotherapy for peptic ulcer bleeding showed comparable efficacy to other endoscopic modalities such as heater probe, hemostatic forceps, and clipping (97% vs. 95%) [72]. In addition, combination therapy using epinephrine injection followed by APC did not differ in initial hemostasis or rebleeding compared with other combination approaches [73-75].
For the procedure, an APC catheter is introduced through the endoscope channel and positioned perpendicular to the target area, followed by activation using the foot pedal [25]. The optimal probe-to-tissue distance is reported to be 2–8 mm, and coagulation becomes ineffective if the probe is too far. The coagulation effect can be adjusted through settings such as power (W), argon gas flow rate (L/min), distance to the tissue, and application time [20,56]. As argon gas can cause luminal distension and may obscure the field, intermittent suction is often required. Caution is required in the duodenum because of the risk of gas-related distension and perforation. The risk of perforation is influenced by power settings, application time, and probe-to-tissue distance.
Monopolar and bipolar electrocautery
In monopolar electrocautery, the active electrode makes contact with the target lesion, and a grounding pad attached to the patient serves as the return electrode. A grounding pad is not used for the bipolar electrocautery. These contact methods achieve hemostasis by generating heat or delivering currents, leading to tissue edema and activation of the coagulation cascade [56].
Hemostatic forceps
Hemostatic forceps resemble biopsy forceps and achieve hemostasis through direct contact with the tissue. Soft coagulation uses a lower voltage, which may reduce the risk of perforation. In a study of 50 patients with nonvariceal UGIB, bipolar hemostatic forceps showed better hemostatic outcomes than clips (100% vs. 78%) [76]. In high-risk peptic ulcers (Forrest Ia, Ib, and IIa), monopolar hemostatic forceps were associated with higher hemostasis success, shorter procedure times, and lower rebleeding rates compared with TTS clips [77]. A recent meta-analysis also reported that monopolar hemostatic forceps provided higher hemostasis success and lower rebleeding rates than TTS clips, APC, or heater probes [78].
The device is rotatable and is useful for treating spurting bleeding or exposed vessels. Hemostasis can be achieved either by opening the forceps to grasp a vessel or by keeping it closed and in contact with it. Gentle traction on the grasped tissue may reduce deep-tissue injury. The coagulation efficacy may decrease if blood, clots, or water remain.
Topical hemostatic agents
Topical hemostatic agents include powders and gels. They are technically simple, cover broad areas, and are non-contact modalities that do not cause secondary tissue injury. They are useful in several situations, including bleeding that persists despite conventional methods (“can’t stop”), lesions in anatomically difficult locations (“can’t reach”), areas where contact therapy carries a higher risk of perforation or pancreatitis such as diverticula, the papilla, or a resection surface (“can’t touch”), diffuse oozing bleeding difficult to control (“can’t finish”), and tumor bleeding refractory to standard therapy (“can’tcer”) [79]. The primary mechanism involves the formation of a physical barrier that promotes hemostasis. Serious complications have not been reported, but visualization can be limited, and powder can obstruct the endoscope channel [79].
Globally, five types of hemostatic powder and one type of gel are used (Table 3) [79,80]. In Korea, three products are currently available: EndoClot, Nexpowder, and CGGel [81]. The general approach involves introducing a catheter through the endoscope channel and applying the powder or gel onto the target lesion. Hemosprays were the earliest commercially available products. Prior studies in nonvariceal UGIB reported initial hemostasis rates ranging from 73% to 100% and definitive hemostasis rates ranging from 39% to 100% [80]. The wide variation likely reflects differences in study size, case mix, and outcome definitions. In a recent multicenter randomized trial by Lau et al. [82], 224 patients with nonvariceal UGIB were randomized to receive hemospray (n=111) or conventional therapy (n=113). The 30-day hemostasis success rates were 90.1% and 81.4% in the hemospray and conventional therapy groups, respectively. In a prospective multicenter study, Sung et al. [83] evaluated hemospray monotherapy in 67 patients with peptic ulcer bleeding classified as Forrest Ia or Ib and reported an initial hemostasis rate of 90.9%, with a rebleeding rate of 13.3%. They concluded that high initial hemostasis could be achieved, but the potential for rebleeding should be considered.
Hemostatic powders and gels available in the market
In Korea, a multicenter randomized controlled trial involving 216 patients with peptic ulcer bleeding compared Endo- Clot with conventional therapy and reported a hemostasis rate of 87.6% and a 30-day rebleeding rate of 7.8%. These outcomes were comparable to the conventional therapy group (86.5% and 9.3%, respectively) [84]. The same investigators conducted a prospective multicenter study evaluating CGGel as first-line therapy for nonvariceal UGIB and reported an initial hemostasis rate of 96.3%, which was comparable to 91.8% in the control group [85].
Currently, major guidelines generally position topical hemostatic agents as a rescue therapy after the failure of conventional endoscopic methods [19,20]. Whether they can be routinely used as primary therapy or as an adjunct in UGIB requires further study. Under the current Korean National Health Insurance system, reimbursement is available for rebleeding cases, whereas primary hemostasis is fully out-of-pocket.
HEMOSTATIC STRATEGY BY LESION
Nonvariceal bleeding
Peptic ulcer bleeding
Endoscopic findings in bleeding peptic ulcers are commonly classified using the Forrest classification (Table 4 and Fig. 2), which is associated with rebleeding risk and prognosis, and guides endoscopic therapy. Endoscopic treatment is recommended for spurting (Forrest Ia), oozing (Forrest Ib), and a non-bleeding visible vessel (Forrest IIa) [18-20]. In a meta-analysis including [19] randomized controlled trials, Laine and McQuaid [86] reported that endoscopic therapy was associated with a lower risk of rebleeding in Forrest I lesions (RR 0.29) and Forrest IIa lesions (RR 0.49). Forrest IIb lesions remain debated. In a meta-analysis by Laine and McQuaid [86], endoscopic treatment did not reduce the risk of persistent bleeding or rebleeding in Forrest IIb lesions. A recent meta-analysis performed by Beran et al. [87] concluded that endoscopic therapy for Forrest IIb lesions was associated with lower rates of rebleeding, mortality, and surgery than conservative therapy alone. However, another meta-analysis conducted by Tassone et al. [88] described that endoscopic hemostasis reduced recurrent bleeding from peptic ulcers with adherent clots compared with medical management alone, but there was no difference in the rates of mortality or need for surgery. Further large-scale randomized controlled trials are required to validate these findings. The current American and European guidelines neither recommend nor oppose endoscopic therapy for Forrest IIb lesions. They recommended vigorous irrigation to remove the adherent clot [19-20]. Immediate endoscopic hemostasis should be performed if a high-risk stigma is identified. Removal of an adherent clot can clearly identify the characteristics of the bleeding lesion but can also convert the lesion into spurting or oozing bleeding, which may complicate subsequent hemostasis. The decision for endoscopic therapy in Forrest IIb lesions should consider multiple factors, including the endoscopist’s judgment and the availability of surgical or interventional radiology backup [18-20]. High-dose PPI therapy with follow-up endoscopy can be considered, or if endoscopic therapy is pursued, diluted epinephrine can be injected around the lesion, followed by cautious attempts at clot removal. Forrest IIc and III lesions have a low risk of rebleeding and generally do not require endoscopic treatment.
Forrest classification of bleeding peptic ulcers
Forrest classification of bleeding peptic ulcers. A: Forrest type Ia lesion with active arterial spurting. B: Forrest Ib lesion with oozing blood. C: Forrest IIa lesion without bleeding but with exposed blood vessels. D: Forrest IIb lesion with adherent clots. E: Forrest IIc lesion with black pigmentation on the ulcer base. F: Forrest III lesion with clean base.
Depending on the lesion characteristics, clip monotherapy, electrocautery-based therapy alone, or combination therapy with epinephrine injections may be used. Epinephrine injection alone is not recommended because of high rebleeding rates [19]. When combined with clips or electrocautery-based methods, rebleeding can be reduced [86].
Mallory–Weiss tear
Bleeding from Mallory–Weiss tears usually stops spontaneously, and massive bleeding is uncommon. However, patients receiving antiplatelet agents or anticoagulants, or those with bleeding diathesis, may develop persistent and substantial bleeding. If ongoing bleeding is present, the therapeutic options include clipping, band ligation, epinephrine injection, and APC [1].
Dieulafoy lesion
A Dieulafoy lesion refers to an abnormally large submucosal artery (approximately 1–5 mm) that fails to taper and becomes exposed [89]. Ulceration is typically limited to the vessel apex, resulting in a small mucosal defect with a disproportionately large exposed vessel. Endoscopic findings include spurting arterial bleeding, a pulsatile exposed vessel, or an adherent clot at a small mucosal defect (often 3 mm or less), with otherwise normal surrounding mucosa. Endoscopic therapy generally follows principles similar to those for peptic ulcer bleeding, and clipping or band ligation can be effective [90].
Malignancy
In malignant tumor bleeding, endoscopic therapy is often a bridge to definitive treatment or palliative hemostasis. Tumor bleeding is characterized by a high rebleeding rate, limited durability of the hemostatic effect, frequent coagulopathy, and a friable tumor surface with diffuse oozing [1,81,91]. When ulcerative lesions are present, the principles used for peptic ulcer bleeding can be applied [91]. APC is frequently used, but rebleeding is common [92,93]. Topical hemostatic powders have attracted attention because they can be applied without direct contact and cover a broad surface area. Karna et al. [94] performed a meta-analysis of topical powder therapy for malignant tumor bleeding, including 16 studies and 530 patients. The initial hemostasis rate was 94.1%, and late rebleeding occurred in 11.4% of patients, which was lower than previously reported rates (28.3% to 80%). Hemostatic powder may be more effective than conventional endoscopic methods for malignant tumor bleeding; however, further research is needed to determine whether it can replace existing treatments.
Variceal bleeding
Esophageal varices
Endoscopy may reveal active variceal bleeding, either spurting or oozing, or the bleeding may have stopped with the stigmata of a recent hemorrhage (Fig. 3). The Korean Association for the Study of the Liver, as well as American Association for the Study of Liver Disease and European Baveno VII consensus recommend endoscopic band ligation as the treatment of choice for esophageal variceal bleeding [21-23].
Endoscopic images of esophageal varices with stigmata of recent hemorrhage. A: A fresh white fibrin clot known as a “white nipple sign” on esophageal varix means recent bleeding. B: A blood clot on a varix also means recent bleeding.
Gastric varices
The Sarin classification is commonly used for gastric varices [55]. Gastroesophageal varices type 1 (GOV1) refers to esophageal varices that extend along the lesser curvature at the cardia, whereas GOV2 refers to extension along the greater curvature at the cardia. Isolated gastric varices type 1 (IGV1) are confined to the fundus, whereas IGV2 refers to the varices located in the distal stomach. For gastric variceal bleeding, cyanoacrylate injection is most commonly used [95]. There are reports of favorable outcomes with EUS-guided cyanoacrylate injection or coil embolization [96,97]. However, evidence remains limited, and these approaches require EUS expertise, which may restrict widespread adoption in routine clinical practice.
Duodenal varices
Duodenal variceal bleeding (Fig. 4) should be considered and carefully evaluated in patients with cirrhosis presenting with melena or hematochezia but without esophageal or gastric variceal bleeding. The endoscopic treatment included cyanoacrylate injection, band ligation, and clipping [98,99].
A duodenal varix with an ulceration on its surface highly presents a recent hemorrhage.
Refractory bleeding
In patients in whom active bleeding is anticipated, the bleeding focus may not be visualized during endoscopy because of the presence of blood or other materials. In other situations, massive ongoing bleeding in a narrow lumen, such as the duodenum, can render visualization and therapeutic interventions impractical. Effective treatment can also be limited when endoscopic devices cannot be adequately applied to the target lesions. Some patients may develop a marked deterioration in vital signs or arterial oxygen saturation.
In these situations, continuing endoscopy despite poor visualization or worsening physiology can increase blood loss and worsen the clinical outcomes. Therefore, withdrawing the endoscope and promptly transitioning to an alternative management strategy may be appropriate. Rescue options should be selected according to the underlying lesion and bleeding mechanism. For nonvariceal UGIB, major guidelines recommend angiography with transcatheter arterial embolization (TAE) as the preferred next step, with surgical management considered if embolization fails [18-20]. For refractory variceal bleeding, bridge therapy using balloon tamponade or a SEMS can be considered, followed by definitive interventions such as transjugular intrahepatic portosystemic shunt (TIPS) or balloon-occluded retrograde transvenous obliteration (BRTO) [21-23]. The choice of rescue strategy should reflect patient characteristics and local institutional resources.
POST ENDOSCOPY MANAGEMENT
Second-look endoscopy
Second-look endoscopy is a scheduled repeat endoscopic examination performed within 24 hours after the index endoscopy for a previously identified bleeding lesion. Routine second-look endoscopy is not recommended, but can be performed selectively in patients at high risk of rebleeding or when the success of initial hemostasis is uncertain [18,20]. Because approximately 4% to 6% of peptic ulcers are malignant, second-look endoscopy should be considered in patients in whom malignancy is suspected, if a biopsy was not performed during the initial exam [18].
H. pylori test
European guidelines recommend that an H. pylori test be performed as early as possible during the initial endoscopy in patients with bleeding peptic ulcers, with prompt eradication therapy when the test result is positive. If the initial test is negative, repeat testing is recommended during follow-up [20]. Because intragastric blood and medications, including PPIs or antibiotics, can increase false-negative rates for rapid urease and urea breath tests [100], and an appropriate testing strategy should be selected. The options include histology-based, serological, and stool antigen tests.
Rebleeding
Rebleeding is defined as the recurrence of bleeding symptoms or signs after a successful endoscopic hemostasis. These include hematemesis, bloody aspiration via a nasogastric tube, newly developed tachycardia or hypotension, a change from normal stool to melena or hematochezia, or a decrease in the hemoglobin level of at least 2 g/dL after prior stabilization [20].
For nonvariceal UGIB, repeat endoscopic therapy is the first option. In addition to conventional techniques, OTS clips or topical hemostatic powder may also be considered [19,20]. If the bleeding persists, angiography with TAE should be performed. When embolization fails to achieve hemostasis, surgical management is required [18-20].
In variceal bleeding, rebleeding after successful band ligation or sclerotherapy, despite the use of vasoactive agents, is managed with TIPS or BRTO [21-23].
CONCLUSION
Although UGIB incidence has decreased, it continues to account for a substantial proportion of emergency department visits and inpatient cases. The initial management should prioritize hemodynamic stabilization with intravenous fluid resuscitation and appropriate transfusion. Pharmacological therapies, including PPIs, vasoactive agents, and antibiotics, should be considered based on the suspected etiology and clinical context. Endoscopy should be performed promptly, ideally within 24 hours, and within 12 hours when variceal bleeding is suspected.
For patients who require endoscopic hemostasis, an appropriate endoscopic modality can be selected based on the lesion characteristics. If endoscopic hemostasis fails or rebleeding occurs after initial successful hemostasis, angiography with TAE or surgical management may be required. Definitive interventions, such as TIPS or BRTO, can be considered for refractory or recurrent variceal bleeding. Second-look endoscopy can be performed selectively in patients at high risk of rebleeding or when repeat evaluation is indicated. In peptic ulcer bleeding, early H. pylori testing should be pursued when feasible, with eradication therapy initiated in patients with confirmed infection.
Notes
Authors’ Contribution
Conceptualization: Heung Up Kim. Data curation: Yu Jin Kim. Funding acquisition: Heung Up Kim. Investigation: Yu Jin Kim. Supervision: Heung Up Kim. Writing—original draft: Yu Jin Kim. Writing—review & editing: Heung Up Kim. Approval of final manuscript: Yu Jin Kim, Heung Up Kim.
Availability of Data and Material
Data sharing not applicable to this article as no datasets were generated or analyzed during the study.
Conflicts of Interest
Heung Up Kim, an associated editor of the Korean Journal of Helicobacter and Upper Gastrointestinal Research, was not involved in the editorial evaluation or decision to publish this article. The other author has declared no conflicts of interest.
Funding Statement
This work was supported by the 2026 education, research and student guidance grant funded by Jeju National University.
Acknowledgements
None