Endoscopy essentials
Gastrointestinal bleeding
Authors
Angeline O. S. Lo1, 2, James Y. W. Lau1, 3
Institutions
1
Institute of Digestive Disease, The Chinese University of Hong Kong Department of Medicine and Therapeutics, The Chinese University of Hong Kong 3 Department of Surgery, The Chinese University of Hong Kong 2
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1365294 Published online: 3.3.2014 Endoscopy 2014; 46: 310–313 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X Corresponding author James Y. W. Lau, MD Department of Surgery Prince of Wales Hospital 30–32 Ngan Shing Street Shatin, Hong Kong Fax: +852-26377974
[email protected] Endoscopy Essentials Reviews in the Endoscopy essentials series cite publications from the past year which, in the authors’ opinion, reflect the state-ofthe-art in endoscopy. Alongside a short summary of each paper, authors explain why they consider their selected articles to be of importance.
Risk stratification of upper GI bleeding with an esophageal capsule (Chandran et al., Gastrointest Endosc 2013 [1]) !
Current guidelines recommend early endoscopy within 24 hours of admission for patients presenting with acute upper gastrointestinal bleeding (UGIB). In selected high risk patients, urgent and often out-of-hours endoscopy is indicated [2]. Risk stratification scores for acute UGIB include the Rockall score [3] and the Glasgow – Blatchford score (GBS) [4]. The Rockall score combines clinical variables before endoscopy with endoscopic findings, in order to predict mortality. The GBS uses solely pre-endoscopic clinical parameters to predict the need for intervention. It can accurately identify the low risk patients (those with GBS of 0) who do not need admission. In a UK multicenter, comparative study, GBS was shown to be superior to the Rockall score in predicting the need for either endoscopic or surgical intervention (area under the receiver operating characteristic curve 0.85 vs. 0.71; P < 0.001) [5]. These scores require validation in individual centers. We prospectively validated the use of both scores in a large cohort of patients with acute UGIB for the prediction of those who required endoscopic intervention [6]. A threshold GBS of 1 or above was used to designate a “high risk” group. The specificity was only 6.3 % and the positive predictive value was 28.6 %. Only 4.6 % of the entire cohort had a score of 0. These scores, while useful in identifying low risk patients for early discharge, do not define a cutoff score above which urgent endoscopy becomes mandatory; they also lack specificity in predicting endoscopic intervention. Video capsule endoscopy (VCE) allows real-time diagnosis of luminal blood and mucosal lesions. Endoscopic appearances of stigmata of bleeding in mucosal lesions are prognostic. It would not
Lo Angeline O S et al. Gastrointestinal bleeding … Endoscopy 2014; 46: 310–313
be difficult to understand why VCE is superior to risk scores in guiding clinicians in patient triaging. In a single-blind, multicenter study of 83 adult patients, Chandran et al. assessed the efficacy of esophageal VCE in identifying low risk patients with acute UGIB who could safely wait for elective esophagogastroduodenoscopy (EGD) [1]. The first-generation PillCam ESO capsule (Given Imaging, Yoqneam, Israel) was used, and metoclopramide was given intravenously before capsule ingestion. Overall, 62 of 83 patients (75 %) had the cause of bleeding identified on either VCE or EGD. VCE identified a bleeding site in 41 patients (66 %) and EGD in 55 (89 %). Findings were concordant across both modalities in 34 patients (55 %). In those who underwent VCE, visualization to the second part of the duodenum was possible in 44 patients (53 %). VCE missed 21 of the 55 bleeding sites (38 %) identified by EGD. Seven of these identification failures were due to the lack of duodenal visualization. The authors attributed the failure to the short battery life of the first-generation esophageal capsule (1223 seconds). In 28 patients with normal EGD results, VCE identified 7 significant pathologies (Mallory – Weiss tear, gastric erosion, duodenal angioectasia, erosions, and an ulcerated jejunal polyp). Four of them re-bled and required repeat inpatient endoscopic treatments. In 44 patients with adequate visualization of the duodenum on VCE, the examination correctly identified 23 low risk lesions (Forrest III lesions) among 25 identified on EGD. Only four of them were considered suitable for outpatient EGD based on their GBS. The authors suggested that VCE saves healthcare costs by identifying more low risk patients for outpatient EGD. This study confirms the potential advantages of utilizing esophageal VCE over scoring systems for the triage of low risk patients for outpatient endoscopy. To further justify the cost of an additional VCE examination, the sensitivity of VCE in
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diagnosing low risk lesions should be sufficiently high. The esophageal capsule is not ideal for the purpose. The capsule should traverse the pylorus more readily, allowing for adequate duodenal visualization. The availability of expertise to interpret VCE images in emergency rooms also needs to be addressed.
Hemospray in the treatment of upper gastrointestinal hemorrhage in patients on antithrombotic therapy (Holster et al., Endoscopy 2013 [7]) !
Hemospray (Cook Medical, Winston-Salem, North Carolina, USA) is a hemostatic powder made from a proprietary granular mineral that is inorganic and therefore not absorbed by the gastrointestinal tract. In contact with moisture, the powder clumps together, forming a mechanical barrier that adheres to the bleeding site " Video 1). The mechanical barrier may also concentrate plate(● lets and clotting factors and shorten the clotting time. We reported the first gastrointestinal use of Hemospray in 20 patients with actively bleeding gastroduodenal ulcers [8]. Hemostasis was successfully achieved in 19 of them. The only treatment failure was in a patient with a bleeding angular notch ulcer that eroded into the left gastric artery and resulted in a pseudo-aneurysm. Chen et al. reported its use in five patients with bleeding malignant gastric ulcers [9]. More recently, there have been anecdotal reports of its use in gastric variceal bleeding. Holster et al. reported a case series involving 16 patients who presented with acute UGIB (8 were on antithrombotic therapy [ATT] and 8 were not) [7]. Hemospray (maximum 20 g) was applied to the active bleeding site through a 10-Fr catheter (Cook Medical) in short bursts, propelled by pressurized CO2 contained in a canister. Successful initial hemostasis was defined when Hemospray application led to hemostasis after 5 minutes of visual inspection. Hemostasis was achieved in 5/8 patients on ATT and in the entire non-ATT group. In these successful cases, Hemospray was used as monotherapy in three ATT patients (38 %) and five non-ATT patients (63 %). Among the three ATT patients in whom Hemospray failed to achieve hemostasis, two had a spurting arterial bleed, which could be controlled by additional clipping. Angiography with coiling of the bleeding vessel was necessary to achieve hemostasis in the third patient. Rebleeding within 7 days occurred in five patients (three in the ATT group and two in non-ATT group; P = 1.0). The rebleeding cases in the non-ATT group involved peptic ulcer-related arterial bleeds. There was no mortality at Day 30 in either group. The authors concluded that endoscopic hemostasis by Hemospray is not hampered by the effects of systemic ATT. Patients on warfarin or new oral anticoagulation drugs represent special challenges. In a recent UK national audit study, coagulopathy was present in 16.4 % of patients with acute UGIB, with a fivefold increase in adjusted mortality [10]. Newer oral anticoagulants are increasingly being prescribed. In a meta-analysis of randomized controlled trials that compared the use
Video 1 A case of successful hemostasis by Hemospray application at a large bleeding angular ulcer. online content including video sequences viewable at: www.thieme-connect.de
of new oral anticoagulant (n = 42 411) with warfarin (n = 29 272) in patients with chronic atrial fibrillation, new oral anticoagulants, such as direct thrombin or factor Xa inhibitors, were associated with an increased risk of gastrointestinal bleeding (relative risk 1.25, 95 % confidence interval, 1.01 – 1.55; P = 0.04) [11]. There is no antidote to these new oral anticoagulants. The small series by Holster et al. does not allow us to be conclusive about the efficacy of Hemospray in patients with bleeding who are taking ATT. The study tells us that in a small cohort of patients with active UGIB treated by Hemospray, there were more episodes of rebleeding in anticoagulated patients. In a proper design to elucidate the true merit of Hemospray in anticoagulated patients, the comparator should be anticoagulated patients treated by existing endoscopic methods. Several roles of Hemospray have been proposed. It can be used as a stop-agent in massive bleeding before definitive treatment, as a rescue therapy when others fail, or as monotherapy in less-severe bleeding. Although initial results with the use of Hemospray appear promising even in severe bleeders, its exact role needs to be further defined in comparative studies with sufficient numbers of patients.
EUS-guided coil versus cyanoacrylate therapy for the treatment of gastric varices: a multicenter study (Romero-Castro et al., Gastrointest Endosc 2013 [12]) !
In the treatment of gastric varices, injection with cyanoacrylate glue (CYA) is the current endoscopic treatment of choice [13]. However, the technique is known to be associated with serious adverse events, including embolism and hemorrhage from postinjection ulcers. The glue can cause blockage to the channel of the endoscope. Endoscopic ultrasound (EUS) guidance may assist in the above situation. Previous reports on EUS-guided injection of CYA and EUS-guided coil application (ECA) have been described by the same group of investigators [14, 15]. In a more recent cohort of 30 patients with gastric varices, Romero-Castro et al. compared the efficacy of EUS-guided CYA injections (n = 19) with ECA (n = 11) [12]. During EUS, the veins feeding into the varices were identified in all patients. Access was possible in 29 of them. Contrast was injected following puncture of these veins in order to ensure the veins were not efferent, because of concern about embolization. Overall, obliteration of gastric varices was achieved in 29 of the 30 patients – 19 of 19 with CYA, and 10 of 11 with coils. Complete obliteration within a single session was possible in 10 of 19 patients (52.6 %) who received CYA and in 9 of 11 patients who received fibered coils (81.8 %). The treatment was repeated if there was remaining flow in the perforating or feeding vein under EUS. In 2 of 11 patients who underwent coiling, additional CYA injection was required. Adverse events occurred in 57.9 % (11/19) patients in the CYA group compared with 9.1 % (1/11) in the ECA group (P < 0.01). All patients in the CYA group underwent computed tomography scan after injection. Asymptomatic pulmonary embolism was evident in nine patients after CYA injection. No recurrent gastric varices were observed in either group over a mean follow-up of 17.2 ± 1.8 months (range 6 – 41 months). There was a significant difference in the duration of hospital stay between the CYA group (17.3 ± 2.7 days) and the coil group (6.0 ± 2.4 days; P = 0.007). Treatment with coils is significantly more expensive than glue injection, although the additional costs for the prolonged hospital stay in the CYA group were not calculated.
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Endoscopy essentials
Endoscopy essentials
The authors concluded that ECA is safe and feasible in the management of bleeding gastric varices. The feeding veins can be identified by EUS and obliterated effectively with either CYA or coils. Although endoscopic insertion of fibered coils is technically more demanding, the adverse event of glue embolization can be avoided. The study was not a randomized one; the authors stated that coil embolization would be preferred to glue injection. In this cohort of patients, it is not clear how each technique was chosen. The best option is probably the combined use of fiber coils followed by small-volume injection of CYA [16]. Blind injection of CYA into fast-flowing varices is associated with the risk of embolization. The main bulk of gastric varices should initially be filled with fibered coils. The feeding vein is then injected with CYA in small volumes. Fibered coils form a scaffold within the varix for the subsequently injected glue. The study represents a novel approach, combining radiologic and endoscopic techniques. With improved accessories, an endovascular approach from within gastrointestinal lumens will become possible.
Rescue endoscopic bleeding control for nonvariceal upper gastrointestinal hemorrhage using clipping and detachable snaring (Lee et al., Endoscopy 2013 [17]) !
Application of hemoclips or thermocoagulation are the current standards in the endoscopic treatment of nonvariceal causes of UGIB. Pre-injection with diluted epinephrine can often stop or slow down bleeding, allowing a clear view of the bleeding vessel. Cushions of fluid injected in the submucosa lead to a tamponade effect. A second modality targeting the vessel should be added, as combination therapy substantially reduces the rate of rebleeding, surgery, and mortality [18]. Despite effective endoscopic treatment, recurrent bleeding occurs in 8 % – 10 % of cases. Mortality in these patients is high. These difficult-to-treat lesions are usually larger chronic ulcers located in the lesser curvature of the stomach or the posterior bulbar duodenum, which can erode into the gastroduodenal or the left gastric artery complexes, respectively. Combined clipping and detachable snaring (CDS) has previously been reported for the successful management of colonic perforation and post-polypectomy bleeding [19, 20]. CDS appears to work by tissue compression on the bleeding artery. Hemoclips are applied around the bleeding lesion. An endoloop is then tightened around the bundle of clips as a purse string and draws the tissue together. Curcio et al. reported a case in which this technique was successfully applied in treating a high risk gastric ulcer in a pregnant woman on extracorporeal membrane oxygenation because of acute respiratory distress syndrome [21]. Lee et al. retrospectively reviewed the use of CDS as a rescue method for controlling refractory bleeding from nonvariceal causes of UGIB [17]. Of 100 patients with Forrest class Ia, Ib, or IIa lesions over a 17-month period at a tertiary center in Korea, there were nine initial endoscopic failures in hemostasis and seven cases of recurrent bleeding after hemostasis. The technique was applied in three patients after initial failure and four patients who had re-bled. The series included a mixed array of lesions (peptic ulcers, Dieulafoy’s lesion, arteriovenous malformation, postbiopsy bleeding, and postsurgical lesions). Hemostasis was achieved in six of the seven patients. The remaining patient had a chronic gastric ulcer, which was successfully treated by thermocoagulation. The authors suggested that CDS might be an ef-
Lo Angeline O S et al. Gastrointestinal bleeding … Endoscopy 2014; 46: 310–313
fective rescue therapy for UGIB, especially in cases of rebleeding after multiple clipping, which leaves little room for further endoscopic re-treatment. CDS can be added to the other modalities available for the endoscopic treatment of rebleeding patients. The described series is small and heterogeneous. It is not entirely clear why CDS was chosen over other existing and emerging methods. Perseverance with the same method can often work. CDS is more likely to work in lesions with soft pliable edges (e. g. Dieulafoy’s lesion). CDS may not work in chronic ulcers with a fibrotic base, as illustrated by the single failure in the series. How best to manage patients with recurrent bleeding after initial endoscopic control has not been well studied. In a randomized, controlled trial, we compared surgery with further endoscopic treatment in patients with significant rebleeding after epinephrine injection and heat probe treatment [22]. We found that in the majority of patients, further endoscopic treatment would again secure hemostasis and avoid surgery. Perforation occurred in two of 44 patients treated by further thermocoagulation. The more important question is how to identify those patients who are unlikely to respond to further endoscopic treatment. In a subgroup analysis, larger chronic ulcers (> 2 cm) and exigent bleeding in patients with hypotension were independent factors predicting failure of further endoscopic treatment. There can be many reasons why bleeding recurs. Patient factors include uncorrected coagulopathy and platelet dysfunction. Certain lesions are more difficult to access, making endoscopic treatment suboptimal. These areas include the posterior bulbar duodenum and the proximal lesser curvature of the stomach. In some cases, we use a duodenoscope for better access. The design of the current commercially available clips is clearly not ideal. The clip retention rate remains low. As clips are dislodged, bleeding ensues. An adequate amount of tissue needs to be captured underneath the “sentinel clot” of the vessel in order to achieve hemostasis. There remains a subgroup of patients with eroded arteries too large to be controlled by endoscopic means. Early angiographic embolization may be the solution in these patients. In the management of patients with refractory bleeding, one should consider all of the above and tailor individual treatment. The choice of endoscopic treatment will therefore depend, to a large extent, on the local characteristics of the lesion.
Multipurpose use of the ‘bear claw’ (over-the-scopeclip system) to treat endoluminal gastrointestinal disorders (Mönkemüller et al., Dig Endosc 2013 [23]) !
Gastrointestinal bleeding lesions with visible vessels of large diameter or located in peculiar positions may not be amenable to treatment with standard endoscopic devices, such as clips and loops. Similarly, defects from perforations, fistulas, and leaks with fibrotic borders make clip application very difficult. The over-the-scope-clip (OTSC, also called “bear claw”) system (Ovesco Endoscopy, Tübingen, Germany), is a novel endoscopic device made of nitinol, which allows entrapment and closure of mucosal " Video 2). The use of the defects of up to ~20 mm in size [24] (● OTSC has been reported in a number of animal studies and case reports to be useful in treating bleeding lesions and in closure of fistulas and leaks. Mönkemüller et al. reported a retrospective series of 20 clip applications in 16 patients with fistulas, perforations, bleeding that were not treatable with other endoscopic means, and after resection of small submucosal tumors [23]. In
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the series, there were five refractory bleeding peptic ulcers located at the classical high risk positions (four posterior bulbar and one lesser curvature of the stomach), and one duodenal Dieulafoy’s lesion, all of which were successfully treated. The OTSC device has the advantage of being able to capture a larger amount of tissue with considerable closure force. It is particularly useful in inflamed or fibrotic tissue; the sharp-toothed device can readily penetrate deeply into fibrotic tissue. The nitinol cage is housed over a transparent hood. The bleeding lesion is aspirated into the hood, and the OTSC is deployed by the turn of a cogwheel. In fibrotic ulcers, the base is first punctured with an anchor device. The hood is then gently pushed onto the base before the OTSC is released. The design represents an advance over existing clips for hemostasis. Tissue compression is a critical element for hemostasis. The device captures tissue of up to 20 mm in diameter. After deployment, these clips are retained almost indefinitely. The gaps between these teeth allow for vascular inflow and avoid tissue strangulation and perforation. OTSC are therefore ideal for large ulcers predicted to fail conventional endoscopic methods, and for Dieulafoy’s lesions with large tortuous arteries that can traverse a wide area in the submucosa. The use of the OTSC should be considered before angiography or surgery in patients with refractory bleeding. Competing interests: None
References 1 Chandran S, Testro A, Urquhart P et al. Risk stratification of upper GI bleeding with an esophageal capsule. Gastrointest Endosc 2013; 77: 891 – 898 2 Barkun AN, Bardou M, Kuipers EJ et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2010; 152: 101 – 113 3 Rockall TA, Logan RF, Devlin HB et al. Risk assessment after acute upper gastrointestinal hemorrhage. Gut 1996; 38: 316 – 321 4 Blatchford O, Murray WR, Blatchford M. A risk score to predict need for treatment for upper gastrointestinal hemorrhage. Lancet 2000; 356: 1318 – 1321 5 Stanley AJ, Dalton HR, Blatchford O et al. Multicenter comparison of the Glasgow Blatchford and Rockall Scores in the prediction of clinical endpoints after upper gastrointestinal hemorrhage. Aliment Pharmacol Ther 2011; 34: 470 – 475 6 Pang SH, Ching JY, Lau JY et al. Comparing the Blatchford and pre-endoscopic Rockall score in predicting the need for endoscopic therapy in patients with upper GI hemorrhage. Gastrointest Endosc 2010; 71: 1134 – 1140 7 Holster IL, Kuipers EJ, Tjwa ET. Hemospray in the treatment of upper gastrointestinal hemorrhage in patients on antithrombotic therapy. Endoscopy 2013; 45: 63 – 66
8 Sung JJ, Luo D, Wu JC et al. Early clinical experience of the safety and effectiveness of Hemospray in achieving hemostasis in patients with acute peptic ulcer bleeding. Endoscopy 2011; 43: 291 – 295 9 Chen YI, Barkun AN, Soulellis C et al. Use of the endoscopically applied hemostatic powder TC-325 in cancer-related upper GI hemorrhage: preliminary experience. Gastrointest Endosc 2012; 75: 1278 – 1281 10 Jairath V, Kahan BC, Stanworth SJ et al. Prevalence, management, and outcomes of patients with coagulopathy after acute nonvariceal upper gastrointestinal bleeding in the United Kingdom. Transfusion 2013; 53: 1069 – 1076 11 Ruff CT, Giugliano RP, Braunwald E et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomized trials. Lancet 2013: [Epub ahead of print] DOI 10.1016/S0140-6736(13)62343-0 12 Romero-Castro R, Ellrichmann M, Ortiz-Moyano C et al. EUS-guided coil versus cyanoacrylate therapy for the treatment of gastric varices: a multicenter study. Gastrointest Endosc 2013; 78: 711 – 721 13 Irani S, Kowdley K, Kozarek R. Gastric varices. An updated review of management. . J Clin Gastroenterol 2011; 45: 133 – 148 14 Romero-Castro R, Pellicer-Bautista FJ, Jimenez-Saenz M et al. EUS-guided injection of cyanoacrylate in perforating feeding veins in gastric varices: results in 5 cases. Gastrointest Endosc 2007; 66: 402 – 407 15 Romero-Castro R, Pellicer-Bautista F, Giovannini M et al. Endoscopic ultrasound (EUS)-guided coil embolization therapy in gastric varices. Endoscopy 2010; 42: E35 – 36 16 Binmoeller KF, Weilert F, Shah JN et al. EUS-guided transesophageal treatment of gastric fundal varices with combined coiling and cyanoacrylate glue injection (with videos). Gastrointest Endosc 2011; 74: 1019 – 1025 17 Lee JH, Kim BK, Seol DC et al. Rescue endoscopic bleeding control for nonvariceal upper gastrointestinal hemorrhage using clipping and detachable snaring. Endoscopy 2013; 45: 489 – 492 18 Calvet X, Vergara M, Brullet E et al. Addition of a second endoscopic treatment following epinephrine injection improves outcome in high risk bleeding ulcers. Gastoenterology 2004; 126: 441 – 450 19 Katsinelos P, Chatzimavroudis G, Zavos C et al. Closure of an iatrogenic rectal perforation by using the endoloop/clips technique. Gastrointest Endosc 2009; 70: 405 – 406 20 Chou KC, Yen HH. Combined endoclip and endoloop treatment for delayed postpolypectomy hemorrhage. Gastrointest Endosc 2010; 72: 218 – 219 21 Curcio G, Traina M, Panarello G et al. Refractory gastric ulcer bleeding treated with new endoloop/clips technique. Dig Endosc 2011; 23: 203 – 204 22 Lau JY, Sung JJ, Lam YH et al. Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers. N Engl J Med 1999; 340: 751 – 756 23 Mönkemüller K, Peter S, Toshniwal J et al. Multipurpose use of the ‘bear claw’ (over-the-scope-clip system) to treat endoluminal gastrointestinal disorders. Dig Endosc 2013: [Epub ahead of print] DOI 10.1111/ den.12145 24 Kirschniak A, Kratt T, Stüker Königsrainer A et al. A new endoscopic over-the-scope clip system for treatment of lesions and bleeding in the GI tract: first clinical experiences. Gastrointest Endosc 2007; 66: 162 – 167
Video 2 Application of the over-the-scope-clip system as a rescue therapy in a bleeding duodenal ulcer not amenable to conventional endoscopic treatment. online content including video sequences viewable at: www.thieme-connect.de
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Endoscopy essentials
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