Potential role of new technological innovations in nonvariceal hemorrhage

The present armamentarium of endoscopic hemostatic therapy for non-variceal upper gastrointestinal hemorrhage includes injection, electrocautery and clips.There are newer endoscopic options such as hemostatic sprays, endoscopic suturing and modifications of current options including coagulation forceps and over-the-scope clips. Peptic hemorrhage is the most prevalent type of nonvariceal upper gastrointestinal hemorrhage and traditional endoscopic interventions have demonstrated significant hemostasis success. However, the hemostatic success rate is less for other entities such as Dieulafoy's lesions and bleeding from malignant lesions. Novel innovations such as endoscopic submucosal dissection and peroral endoscopic myotomy has spawned a need for dependable hemostasis. Gastric antral vascular ectasias are associated with chronic gastrointestinal bleeding and usually treated by standard argon plasma coagulation(APC), but newer modalities such as radiofrequency ablation,banding, cryotherapy and hybrid APC have been utilized as well. We will opine on whether the newer hemostatic modalities have generated success when traditional modalities fail and should any of these modalities be routinely available in the endoscopic toolbox.     

Endoscopic advances in the management of non-variceal upper gastrointestinal bleeding:A review

Upper gastrointestinal bleeding is defined as the bleeding originating from the esophagus to the ligament of Treitz and further classified into variceal and nonvariceal gastrointestinal bleeding.Non-variceal upper gastrointestinal bleeding remains a common clinical problem globally.It is associated with high mortality,morbidity,and cost of the health care system.Despite the continuous improvement of therapeutic endoscopy,the 30-d readmission rate secondary to rebleeding and associated mortality is an ongoing issue.Available Food and Drug Administration approved traditional or conventional therapeutic endoscopic modalities includes epinephrine injection,argon plasma coagulation,heater probe,and placement of through the scope clip,which can be used alone or in combination to decrease the risk of rebleeding.Recently,more attention has been paid to the novel advanced endoscopic devices for primary treatment of the bleeding lesion and as a secondary measure when conventional therapies fail to achieve hemostasis.This review highlights emerging endoscopic modalities used in the management of non-variceal upper gastrointestinal related bleeding such as over-the-scope clip,Coagrasper,hemostatic sprays,radiofrequency ablation,cryotherapy,endoscopic suturing devices,and endoscopic ultrasound-guided angiotherapy.In this review article,we will also discuss the technical aspects of the common procedures,outcomes in terms of safety and efficacy,and their advantages and limitations in the setting of non-variceal upper gastrointestinal bleeding.     

New and emerging technologies to endoscopically manage nonvariceal upper gastrointestinal bleeding

A subset of patients with nonvariceal upper gastrointestinal bleeding either fails or is deemed unsuitable for standard endoscopic hemostatic therapy. Newer endoscopic and endosonographic techniques have been developed to offer an alternative treatment and potentially improve patient outcome for the difficult-to-treat lesions. These alternative therapies include over-the-scope clip devices, radiofrequency ablation, cryotherapy, hemostatic sprays, endoscopic suturing, and endoscopic ultrasound-guided angiotherapy. This article serves to review these novel techniques that can be incorporated in the armamentarium to treat nonvariceal upper gastrointestinal bleeding.     

急性非静脉曲张性上消化道出血临床分析

目的分析非静脉曲张性上消化道出血的临床特征。方法回顾分析我院消化内科2009年1月-2011年12月期间收治的经胃镜证实的301例非静脉曲张性上消化道出血病例,分析总结非静脉曲张性上消化道出血的常见病因及临床诊治情况。结果非静脉曲张性上消化道出血的常见病因依次为消化性溃疡、消化道肿瘤、急性胃黏膜病变,内科保守治疗的有效率为96.35%(290/301),内镜下止血成功率93.55%(58/62)。结论消化性溃疡是非静脉曲张性上消化道出血最常见的病因。在消化道出血的救治中,急诊内镜、选择性血管造影以及内外科的紧密配合与协作发挥着重要作用。     

Application of endoscopic hemoclips for nonvariceal bleeding in the upper gastrointestinal tract

AIM： To investigate acute nonvariceal bleeding in the upper gastrointestinal （GI） tract and evaluate the effects of endoscopic hemoclipping. METHODS： Sixty-eight cases of acute nonvariceal bleeding in the upper GI tract were given endoscopic treatment with hemoclip application. Clinical data, endoscopic findings, and the effects of the therapy were evaluated. RESULTS： The 68 cases （male：female = 42：26, age from 9 to 70 years, average 54.4） presented with hernatemesis in 26 cases （38.2%）, melena in nine cases （13.3%）, and both in 33 cases （48.5%）. The causes of the bleeding included gastric ulcer （29 cases）, duodenal ulcer （11 cases）, Dieulafoy＇s lesion （11 cases）, Mallory-Weiss syndrome （six cases）, post-operative （three cases）, post-polypectomy bleeding （five cases）, and post-sphincterotomy bleeding （three cases）; 42 cases had active bleeding. The mean number of hemoclips applied was four. Permanent hemostasis was obtained by hemoclip application in 59 cases; 6 cases required emergent surgery （three cases had peptic ulcers, one had Dieulafoy＇s lesion, and two were caused by sphincterotomy）; three patients died （two had Dieulafoy＇s lesion and one was caused by sphincterotomy）; and one had recurrent bleeding with Dieulafoy＇s lesion 10 mo later, but in a different location. CONCLUSION： Endoscopic hemoclip application was an effective and safe method for acute nonvariceal bleeding in the upper GI tract with satisfactory outcomes.     

Endoscopic clipping for the management of gastrointestinal bleeding

Endoscopic clipping is a safe and effective technique for the treatment of various bleeding gastrointestinal lesions. Randomized controlled trials and a meta-analysis have shown comparable efficacy between clipping and conventional contact thermal therapy for definitive hemostasis of nonvariceal upper gastrointestinal hemorrhage. Clipping also seems to be efficacious for selected lower gastrointestinal bleeding lesions, such as diverticular bleeding and postpolypectomy bleeding. Proficiency in clip application and endoscopic identification of lesions that are amenable to clipping are key determinants of a successful outcome.     

Endoscopic hemostasis state of the art-Nonvariceal bleeding

New endoscopic techniques for hemostasis in nonvariceal bleeding were introduced and known methods further improved. Hemospray and Endoclot are two new compounds for topical treatment of bleeding. Initial studies in this area have shown a good hemostatic effect, especially in active large scale oozing bleeding, e.g., tumor bleedings. For further evaluation larger prospective studies comparing the substanced with other methods of endoscopic hemostasis are needed. For localized active arterial bleeding primary injection therapy in the area of bleeding as well as in the four adjacent quadrants offers a good method to reduce bleeding activity. The injection is technically easy to learn and practicable. After bleeding activity is reduced the bleeding source can be localized more clearly for clip application. Today many different through-thescope(TTS) clips are available. The ability to close and reopen a clip can aid towards good positioning at the bleeding site. Even more important is the rotatability of a clip before application. Often multiple TTS clips are required for secure closure of a bleeding vessel. One model has the ability to use three clips in series without changing the applicator. Severe arterial bleeding from vessels larger than 2 mm is often unmanageable with these conventional methods. Here is the over-the-scopeclip system another newly available method. It is similar to the ligation of esophageal varices and involves aspiration of tissue into a transparent cap before closure of the clip. Thus a greater vascular occlusion pressure can be achieved and larger vessels can be treated endoscopically. Patients with severe arterial bleeding from the upper gastrointestinal tract have a very high rate of recurrence after initial endoscopic treatment. These patients should always be managed in an interdisciplinary team of interventional radiologist and surgeons.     

Endoscopic treatment of upper GI hemorrhage with a novel irrigating hood attached to the endoscope

BACKGROUND: Despite advances in endoscopic treatment methods for upper GI hemorrhage, hemostasis is often difficult to achieve, particularly when the endoscopic view at the site of hemorrhage is poor because of the presence of mucus and blood. The investigators developed an end hood that facilitates endoscopic hemostatic procedures while simultaneously allowing irrigation of the bleeding site. The usefulness of this end hood for treatment of upper GI hemorrhage, excluding hemorrhage from varices, was evaluated. METHODS: The end-hood piece was fabricated by drilling a side hole in the cap portion of a conventional transparent hood. An irrigation tube then was glued to the exterior surface of the hole. The fabricated transparent hood was placed on the tip of an endoscope. With the hood piece in place, hemoclip placement and other endoscopic hemostatic procedures were performed in 15 patients with nonvariceal upper GI hemorrhage. RESULTS: Hemostasis was successfully achieved in all cases. In all cases of active hemorrhage, hemostatic treatment was enhanced by simultaneous irrigation beneath the hood. The median time required for the hemostatic procedure with the attached hood was 4.8 minutes. CONCLUSION: The end-hood irrigation device and technique facilitate endoscopic hemostatic treatment of nonvariceal upper GI hemorrhage.     

Risk stratification and definitive hemostasis of nonvariceal upper gastrointestinal bleeding with blood flow detection and combination techniques

Nonvariceal upper gastrointestinal (UGI) hemorrhage remains a significant health and economic burden. As the use of urgent endoscopy for UGI hemorrhage has increased, there has been a decline in associated mortality. Endoscopic hemostasis is based on risk stratification of stigmata of recent hemorrhage. A Doppler endoscopic probe can provide further risk stratification by detecting arterial blood flow under the lesion and as a guide to successful endoscopic treatment. Standard treatment options for endoscopic hemostasis include submucosal injection therapy usually in combination with either thermal coagulation or through-the-scope clips. A large over-the-scope clip, which has been used to close fistulas and perforations, has been shown to be effective in cases of refractory nonvariceal UGI hemorrhage, and might also be useful in other types of gastrointestinal bleeding.     

Endoscopic band ligation: Beyond prevention and management of gastroesophageal varices

Endoscopic band ligation (EBL) is the preferred endoscopic technique for the endoscopic treatment of acute esophageal variceal bleeding. EBL has also been used to treat nonvariceal bleeding. Recently, Han et al demonstrated that EBL can be a feasible and safe alternate technique for the management of iatrogenic gastric perforation especially in cases in which closure with endoclips is difficult. EBL is technically simpler to perform than other methods and provides a good view of the lesions under direct pressure and suction from the transparent ligation cap. EBL can be used even if the diameter of the perforation is greater than 10 mm or if there is a severe tangential angle. In this commentary, we discuss the efficacy and safety of EBL for the closure of iatrogenic gastrointestinal perforation. We also discuss the advantages and disadvantages of EBL for the treatment of nonvariceal bleeding.     

CLINICAL EVALUATION OF EMERGENCY ENDOSCOPIC HEMOSTASIS WITH BIPOLAR FORCEPS IN NON‐VARICEAL UPPER GASTROINTESTINAL BLEEDING

The present study was designed to evaluate the usefulness and safety of bipolar hemostatic forceps, known as a less invasive and highly safe means of thermal coagulation used for hemostasis in cases of non‐variceal upper gastrointestinal bleeding. This technique of bipolar forceps is simple, safe and unlikely to induce complications, and is therefore promising as a new technique of endoscopic hemostasis. The study involved 39 cases where hemostasis was attempted with bipolar forceps to deal with non‐variceal upper gastrointestinal bleeding, including 28 cases of gastric ulcer, six cases of duodenal ulcer, three cases of bleeding after endoscopic submucosal dissection (ESD), one case of Mallory‐Weiss syndrome and one case of postoperative bleeding from the anastomosed area. There were 34 males and five females, with a mean age of 63.6 years. Bipolar forceps were the first‐line means of hemostasis in cases of oozing bleeding (venous bleeding), pulsatile or spurting bleeding (arterial bleeding) and exposed vessels without active bleeding. The primary hemostasis success rate was 92.3%, and the re‐bleeding rate was 0%. In cases where the bleeding site was located along the tangential line or in cases where large respiration‐caused motions hampered identification of the bleeding site, hemostasis by means of coagulation was easily effected by application of electricity while the forceps were kept open and compressed the bleeding area. In addition, there were no complications. This technique of bipolar forceps is simple, safe and unlikely to induce complications, and is therefore promising as a new technique of endoscopic hemostasis.     

Endoscopic therapy for acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis.

Endoscopic hemostatic therapy for upper gastrointestinal bleeding is gaining widespread acceptance despite often conflicting results of randomized controlled trials. To examine the effect of endoscopic therapy in acute nonvariceal upper gastrointestinal hemorrhage, a meta-analysis was performed using a computerized search of the English-language literature and a bibliographic review. The methodology, population, intervention, and outcomes of each relevant trial were evaluated by duplicate independent review. Thirty randomized controlled trials evaluating hemostatic endoscopic treatment were identified. Endoscopic therapy significantly reduced rates of further bleeding (odds ratio, 0.38; 95% confidence interval, 0.32-0.45), surgery (odds ratio, 0.36; 95% confidence interval, 0.28-0.45), and mortality (odds ratio, 0.55; 95% confidence interval, 0.40-0.76). When analyzed separately, thermal-contact devices (monopolar and bipolar electrocoagulation and heater probe), laser treatment, and injection therapy all significantly decreased further bleeding and surgery rates. The reductions in mortality were comparable for all three forms of therapy, but the decrease reached statistical significance only for laser therapy. Further examination of subgroups indicated that endoscopic treatment decreased rates of further bleeding, surgery, and mortality in patients with high-risk endoscopic features of active bleeding or nonbleeding visible vessels. Rebleeding was not reduced by endoscopic therapy in patients with ulcers containing flat pigmented spots or adherent clots. Endoscopic hemostatic therapy provides a clinically important reduction in morbidity and mortality in patients with acute nonvariceal upper gastrointestinal hemorrhage.     

急性非静脉曲张性上消化道出血常规内镜下止血后再出血的血管栓塞术治疗价值

2017年4月—2020年6月,因急性非静脉曲张性上消化道出血（acute non?variceal upper gastrointestinal bleeding,ANVUGIB）行内镜下止血治疗（包括局部注射药物、电凝、止血夹和套扎等）后再出血,于中国科学技术大学附属第一医院消化内科接受内镜下血管栓塞术（endoscopic vascular embolization,EVE）治疗的病例共46例。46例经EVE治疗后均即刻止血,即刻止血有效率为100.0%。术后出现腹痛13例（28.3%）,腹胀3例（6.5%）,发热2例（4.3%）。术后3、12个月复查胃镜,黏膜逐渐愈合。随访至2021年6月,无一例消化道再出血发生。由此可见,EVE对于初次内镜止血失败的ANVUGIB患者是一种安全、高效的方法,值得临床进一步研究和推广应用。     

Risks versus benefits of gastrointestinal endoscopy during pregnancy

Although gastrointestinal endoscopy is generally safe, its safety must be separately analyzed during pregnancy with regard to fetal safety. Fetal risks from endoscopic medications are minimized by avoiding FDA category D drugs, minimizing endoscopic medications, and anesthesiologist attendance at endoscopy. Esophagogastroduodenoscopy seems to be relatively safe for the fetus and may be performed when strongly indicated during pregnancy. Despite limited clinical data, endoscopic banding of esophageal varices and endoscopic hemostasis of nonvariceal upper gastrointestinal bleeding seems justifiable during pregnancy. Flexible sigmoidoscopy during pregnancy also appears to be relatively safe for the fetus and may be performed when strongly indicated. Colonoscopy may be considered in pregnant patients during the second trimester if there is a strong indication. Data on colonoscopy during the other trimesters are limited. Therapeutic endoscopic retrograde cholangiopancreatography seems to be relatively safe during pregnancy and should be performed for strong indications (for example, complicated choledocholithiasis). Endoscopic safety precautions during pregnancy include the performance of endoscopy in hospital by an expert endoscopist and only when strongly indicated, deferral of endoscopy to the second trimester whenever possible, and obstetric consultation.     

Therapeutic endoscopy for nonvariceal gastrointestinal bleeding

This article reviews the role of therapeutic endoscopy in the diagnosis and treatment of nonvariceal upper and lower gastrointestinal (GI) hemorrhage. The initial approach to patients with GI bleeding is reviewed. Endoscopic treatment of various stigmata of recent peptic ulcer hemorrhage is discussed in detail. Management of less common causes of nonvariceal bleeding, such as Dieulafoy's lesions, Mallory-Weiss tears, angiomas, and bleeding colonic diverticula is described. Recommendations for endoscopic techniques are based on the results of UCLA-CURE hemostasis studies.     

Prospective trial of endoscopic clips versus combination therapy in upper GI bleeding (PROTECCT--UGI bleeding)

BACKGROUND: It is not known if combination therapy of epinephrine injection and multipolar electrocoagulation or hemoclips are a more efficient or effective treatment for patients with acute nonvariceal upper gastrointestinal (GI) bleeding. METHODS: Adult patients with active nonvariceal upper GI bleeding, a nonbleeding visible vessel, or after removal of an adherent clot findings of active bleeding or a visible vessel were studied. Patients were randomized to either therapy and the outcomes were assessed at 30 days. RESULTS: Forty-seven patients were studied: 26 patients randomized to hemoclips and 21 to combination therapy. There were 22 patients with active bleeding, 13 with a nonbleeding visible vessel, and 12 with an adherent clot. The median duration of endoscopic therapy was 17 min in the hemoclip group versus 20 min for the combination therapy, p= 0.29. Primary hemostasis with successful initial control of bleeding occurred in 26 (100%) of 26 hemoclip patients and 20 (95.2%) of 21 combination therapy patients, p= 0.45. The rebleeding rates were: 4 (15.4%) of 26 hemoclip patients versus 5 (23.8%) of 21 combination therapy patients, p= 0.49. Overall, the length of hospital stay, units of blood transfused, surgery rates, and mortality were not different. CONCLUSIONS: In this prospective, randomized controlled trial of endoscopic hemoclips versus combination therapy in the nonvariceal upper GI bleeding, the efficiency, efficacy, and complications of the two treatment modalities were not significantly different.     

New and old methods for endoscopic control of nonvariceal upper gastrointestinal bleeding

Candidates for endoscopic therapy of nonvariceal upper gastrointestinal bleeding include patients with bleeding ulcers, Mallory-Weiss tears, angiodysplasia, and Dieulafoy or other lesions with active bleeding, non-bleeding visible vessel, or adherent clot. Continuous infusion of intravenous proton pump inhibitors lowers rebleeding risk after endoscopic therapy. Of standard methods, a combination of epinephrine injection with thermal coagulation (bipolar or heater probe) has been shown to be optimal, with lower rebleeding rates (5-10%) than for either method alone. Endoscopic clipping is an appealing technique, but comparative data with other methods are limited and conflicting. Band ligation is also suitable for many non-ulcer lesions without a firm base. Argon plasma coagulation is most useful for lesions with a large surface area such as watermelon stomach, but of uncertain advantage for other nonvariceal bleeding lesions. Regardless of method used, technical expertise plays a role in the outcomes of therapy. Of future interest are techniques to image beneath the surface and predict rebleeding risk, and improved methods of mechanical hemostasis.     

Impact of anticoagulation on rebleeding following endoscopic therapy for nonvariceal upper gastrointestinal hemorrhage

OBJECTIVE: Endoscopic therapy for nonvariceal upper gastrointestinal hemorrhage achieves hemostasis in greater than 90% of patients, but up to 20% rebleed. The aim of this study was to determine the impact of anticoagulation on rebleeding in patients undergoing endoscopic therapy for nonvariceal upper gastrointestinal hemorrhage. METHODS: Patients who underwent successful endoscopic therapy for nonvariceal upper gastrointestinal hemorrhage between July 1, 1999, and June 30, 2004, at a large, tertiary care teaching hospital were identified. The primary outcome was rebleeding within 30 days. Secondary outcomes were transfusion requirement, length of stay, surgery, and mortality. Baseline data were analyzed using t-tests and chi(2) tests. Multivariable logistic and linear regression analyses were carried out to calculate the adjusted odds ratios for the international normalized ratio (INR) predicting the primary and secondary outcomes. The multivariable analyses controlled for: age, Charlson comorbidity index, antiplatelet agent use, postprocedure heparin use, postprocedure proton pump inhibitor use, hypotension, ulcer as the bleeding source, and active bleeding at endoscopy. RESULTS: The study included 233 patients. Forty-four percent of the patients had an INR >or=1.3. Ninety-five percent of the anticoagulated patients had an INR between 1.3 and 2.7. The rebleeding rate was 23% in the anticoagulated patients and 21% in the patients with INRs <1.3. On multivariable analyses, INR was not a predictor of rebleeding, transfusion requirement, surgery, length of stay, or mortality. CONCLUSIONS: Mild to moderate anticoagulation does not increase the risk of rebleeding following endoscopic therapy for nonvariceal upper gastrointestinal hemorrhage, suggesting that endoscopic therapy is appropriate in these patients.     

Endoscopic Management of Dieulafoy Lesions in Acute Nonvariceal Upper Gastrointestinal Bleeding

Dieulafoy lesion is an unusual but important cause of upper gastrointestinal bleeding. The study retrospectively reviewed 29 patients (2.1%) with Dieulafoy lesions of 1393 acute nonvariceal upper gastrointestinal bleeding episodes from October 1999 to May 2001. Nineteen patients (66%) were male and the median age was 62 years (range, 19 to 86 years). Two patients underwent emergent surgery after endoscopic diagnosis. The other patients were allocated to four therapeutic endoscopic groups: group I, epinephrine injection (11 patients); group II, epinephrine injection plus heater probe coagulation (10 patients); group III, histoacryl injection (4 patients); and group IV, hemoclipping (2 patients). Initial treatment failure ocurred in three patients (all in group I) and they received surgery, hemoclipping, or band ligation as salvage therapy, respectively. Among those who achieved initial hemostasis, recurrent bleeding developed in two patients (all in group I) and was successfully controlled by endoscopic injection plus thermal therapy. No complication was noted after endoscopic treatment. Group II had a significantly higher successful hemostasis rate than group I (100 vs 54%; P = 0.02). One patient in the therapeutic endoscopy groups died during admission, for a mortality rate of 3.7%. Patients were followed up from 6 to 36 months and no further bleeding was noted. The results suggest that epinephrine injection plus heater probe coagulation was significantly superior to epinephrine injection alone in achieving hemostasis. Histoacryl injection, hemoclipping, and endoscopic band ligation were safe and effective alternate therapies.     

Treatment of upper gastrointestinal bleeding in 2020: New techniques and outcomes

The clinical outcome of upper gastrointestinal bleeding has improved due to advances in endoscopic therapy and standardized peri‐endoscopy care. Apart from validating clinical scores, artificial intelligence‐assisted machine learning models may play an important role in risk stratification. While standard endoscopic treatments remain irreplaceable, novel endoscopic modalities have changed the landscape of management. Over‐the‐scope clips have high success rates as rescue or even first‐line treatments in difficult‐to‐treat cases. Hemostatic powder is safe and easy to use, which can be useful as temporary control with its high immediate hemostatic ability. After endoscopic hemostasis, Doppler endoscopic probe can offer an objective measure to guide the treatment endpoint. In refractory bleeding, angiographic embolization should be considered before salvage surgery. In variceal hemorrhage, banding ligation and glue injection are first‐line treatment options. Endoscopic ultrasound‐guided therapy is gaining popularity due to its capability of precise localization for treatment targets. A self‐expandable metal stent may be considered as an alternative option to balloon tamponade in refractory bleeding. Transjugular intrahepatic portosystemic shunting should be reserved as salvage therapy. In this article, we aim to provide an evidence‐based comprehensive review of the major advancements in endoscopic hemostatic techniques and clinical outcomes.