Obscure gastrointestinal bleeding: diagnostic and therapeutic approach

Obscure gastrointestinal bleeding (OGIB) is defined as an intermittent or continuous loss of blood in which the source has not been identified after upper endoscopy and colonoscopy. It constitutes a diagnostic and therapeutic challenge for the general internist and the gastroenterologist. This article provides an overview of the etiology, clinical presentation, and diagnostic modalities of OGIB including push enteroscopy, double balloon enteroscopy, wireless capsule endoscopy, enteroclysis, angiography, bleeding scanning with labeled red blood cells, and surgery with intraoperative enteroscopy. Therapeutic modalities including iron replacement, combined hormones, octreotide acetate, therapeutic endoscopy, and surgery are also discussed. In addition, a rational approach to patients with OGIB according to the clinical presentation is presented herein.     

不明原因消化道出血的诊断和处理

不明原因消化道出血(OGIB)的诊断和处理曾是内科医师和消化科医师面临的挑战。胶囊内镜和双气囊小肠镜检查的发展使OGIB的处理发生了根本的变革。本文讨论OGIB的病因、诊断检查手段和诊断处理流程。此外,对OGIB最常见的病因—血管发育不良采用联合激素、奥曲肽或沙利度胺等药物治疗也一并予以讨论。     

Double Balloon Enteroscopy Detects Small Bowel Mass Lesions Missed by Capsule Endoscopy

BACKGROUND: Small bowel mass lesions (SBML) are a relatively common cause of obscure gastrointestinal bleeding (OGIB). Their detection has been limited by the inability to endoscopically examine the entire small intestine. This has changed with the introduction of capsule endoscopy (CE) and double balloon enteroscopy (DBE) into clinical practice. STUDY AIM: To evaluate the detection of SBML by DBE and CE in patients with OGIB who were found to have SBML by DBE and underwent both procedures. METHODS: A retrospective review of a prospectively collected database of all patients undergoing DBE for OGIB at seven North American tertiary centers was performed. Those patients who were found to have SBML as a cause of their OGIB were further analyzed. RESULTS: During an 18 month period, 183 patients underwent DBE for OGIB. A small bowel mass lesion was identified in 18 patients. Of these, 15 patients had prior CE. Capsule endoscopy identified the mass lesion in five patients; fresh luminal blood with no underlying lesion in seven patients, and non-specific erythema in three patients. Capsule endoscopy failed to identify all four cases of primary small bowel adenocarcinoma. CONCLUSIONS: Double balloon enteroscopy detects small bowel mass lesions responsible for OGIB that are missed by CE. Additional endoscopic evaluation of the small bowel by DBE or intraoperative enteroscopy should be performed in patients with ongoing OGIB and negative or non-specific findings on CE.     

Patient burden and patient preference: Comparing magnetic resonance enteroclysis,capsule endoscopy and balloon‐assisted enteroscopy

Background and Aim: We aimed to prospectively determine patient burden and patient preference for magnetic resonance enteroclysis, capsule endoscopy and balloon‐assisted enteroscopy in patients with suspected or known Crohn's disease (CD) or occult gastrointestinal bleeding (OGIB). Methods: Consecutive consenting patients with CD or OGIB underwent magnetic resonance enteroclysis, capsule endoscopy and balloon‐assisted enteroscopy. Capsule endoscopy was only performed if magnetic resonance enteroclysis showed no high‐grade small bowel stenosis. Patient preference and burden was evaluated by means of standardized questionnaires at five moments in time. Results: From January 2007 until March 2009, 76 patients were included (M/F 31/45; mean age 46.9 years; range 20.0–78.4 years): 38 patients with OGIB and 38 with suspected or known CD. Seventeen patients did not undergo capsule endoscopy because of high‐grade stenosis. Ninety‐five percent (344/363) of the questionnaires were suitable for evaluation. Capsule endoscopy was significantly favored over magnetic resonance enteroclysis and balloon‐assisted enteroscopy with respect to bowel preparation, swallowing of the capsule (compared to insertion of the tube/scope), burden of the entire examination, duration and accordance with the pre‐study information. Capsule endoscopy and magnetic resonance enteroclysis were significantly preferred over balloon‐assisted enteroscopy for clarity of explanation of the examination, and magnetic resonance enteroclysis was significantly preferred over balloon‐assisted enteroscopy for bowel preparation, painfulness and burden of the entire examination. Balloon‐assisted enteroscopy was significantly favored over magnetic resonance enteroclysis for insertion of the scope and procedure duration. Pre‐ and post‐study the order of preference was capsule endoscopy, magnetic resonance enteroclysis and balloon‐assisted enteroscopy. Conclusion: Capsule endoscopy was preferred to magnetic resonance enteroclysis and balloon‐assisted enteroscopy; it also had the lowest burden. Magnetic resonance enteroclysis was preferred over balloon‐assisted enteroscopy for clarity of explanation of the examination, bowel preparation, painfulness and burden of the entire examination, and balloon‐assisted enteroscopy over magnetic resonance enteroclysis for scope insertion and study duration.     

Obscure gastrointestinal bleeding: role of videocapsule and double-balloon enteroscopy

Capsule endoscopy (CE), which allows the non-invasive visualisation of mucosa throughout the entire small bowel, has revolutionised the exploration of small-bowel diseases, and particularly the evaluation of obscure gastrointestinal bleeding (OGIB) after a negative initial evaluation, including gastroscopy and colonoscopy. CE has a high negative predictive value and a higher diagnostic yield than all other modalities, such as radiology (small-bowel X-rays or computed tomography scan) or push enteroscopy. CE may be the preferred initial diagnostic choice in OGIB because of its non-invasive quality and better tolerance. Double-balloon enteroscopy, also known as push-and-pull enteroscopy, has recently been developed. It has made it possible not only to explore the small bowel but also to carry out therapeutic interventions deep in the small bowel without the need for surgical laparotomy. This exploration should be considered as a second-line exploration for OGIB in patients with a positive finding on CE requiring endoscopic follow-up for histology or intervention, and in patients in whom suspicion of a small-bowel lesion is high despite a negative CE.     

双气囊小肠镜与胶囊内镜在小肠出血应用中的对比研究

目的比较双气囊小肠镜与胶囊内镜在小肠出血中的病变检出率、病因诊断率、耐受性和安全性,初步探讨双气囊小肠镜对小肠出血的内镜下治疗。方法2006年4月至2009年10月烟台毓璜顶医院消化内科收治的可疑小肠出血患者159例,其中81例患者行双气囊小肠镜检查,首选进镜方式分为经口或经肛2种,首选方式检查后未发现病灶者,日后改换进镜方式再行检查。对活动性出血病灶行内镜下止血治疗。另78例患者行胶囊内镜检查。两组患者分别由专门医师独立操作并诊断,最后进行汇总分析,对比双气囊小肠镜与胶囊内镜的临床应用价值。结果双气囊小肠镜组的病变检出率为95.06%,病因诊断率为82.72%,23例检查时见病变活动性出血,行内镜下止血治疗,21例止血成功,内镜止血成功率为91.30%;胶囊内镜组的病变检出率82.05%,病因诊断率为66.67%。双气囊小肠镜组的病因检出率及病因诊断率均显著高于胶囊内镜组,差异有统计学意义(P0.05)。在耐受性方面,胶囊内镜的耐受性最好,双气囊小肠镜的耐受性依次为:全麻下经肛进镜、全麻下经口进镜、非麻醉经肛进镜、非麻醉经口进镜。所有患者均未发生严重并发症。结论双气囊小肠镜对小肠出血的病因诊断明显优于胶囊内镜,并且可行内镜下止血治疗,是一项安全、有效的临床诊疗方法。     

Double balloon enteroscopy and capsule endoscopy for obscure gastrointestinal bleeding: an updated meta-analysis

Background and Aim: Uncertainty remains about the best test to evaluate patients with obscure gastrointestinal bleeding (OGIB). Previous meta‐analyses demonstrated similar diagnostic yields with capsule endoscopy (CE) and double balloon enteroscopy (DBE) but relied primarily on data from abstracts and were not limited to bleeding patients. Many studies have since been published. Therefore, we performed a new meta‐analysis comparing CE and DBE focused specifically on OGIB. Methods: A comprehensive literature search was performed of comparative studies using both CE and DBE in patients with OGIB. Data were extracted and analyzed to determine the weighted pooled diagnostic yields of each method and the odds ratio for the successful localization of a bleeding source. Results: Ten eligible studies were identified. The pooled diagnostic yield for CE was 62% (95% confidence interval [CI] 47.3–76.1) and for DBE was 56% (95% CI 48.9–62.1), with an odds ratio for CE compared with DBE of 1.39 (95% CI 0.88–2.20; P = 0.16). Subgroup analysis demonstrated the yield for DBE performed after a previously positive CE was 75.0% (95% CI 60.1–90.0), with the odds ratio for successful diagnosis with DBE after a positive CE compared with DBE in all patients of 1.79 (95% CI 1.09–2.96; P = 0.02). In contrast, the yield for DBE after a previously negative CE was only 27.5% (95% CI 16.7–37.8). Conclusions: Capsule endoscopy and double balloon enteroscopy provide similar diagnostic yields in patients with OGIB. However, the diagnostic yield of DBE is significantly higher when performed in patients with a positive CE.     

Double-balloon enteroscopy for obscure gastrointestinal bleeding: A single center experience in China

AIM: To evaluate the diagnostic value of double-balloon enteroscopy (DBE) for obscure gastrointestinal bleeding (OGIB). METHODS: The data about 75 OGIB patients who underwent DBE in January 2007-June 2009 in our hospital were retrospectively analyzed. RESULTS: DBE was successfully performed in all 75 patients without complication. Of the 75 patients, 44 (58.7%) had positive DBE findings, 22 had negative DBE findings but had potential bleeding at surgery and capsule endoscopy, etc . These 66 patients were fi...     

Preoperative detection and localization of small bowel hemangioma: Two case reports

Among the various diagnostic modalities for small bowel hemangioma,video capsule endoscopy(VCE)and double-balloon enteroscopy( BE)can be recommended as part of the work-up in patients with obscure gastrointestinal bleeding(OGIB). BE is superior to VCE in the accuracy of diagnosis and therapeutic potential,while in most cases total enteroscopy cannot be achieved through only the antegrade or retrograde BE procedures.As treatment for small bowel bleeding,especially spout bleeding,localization of the lesion for the decision of BE insertion facilitates early treatment,such as endoscopic hemostatic clipping,allowing patients to avoid useless transfusion and the worsening of their disease into life-threatening status.Applying endoscopic India ink marking prior to laparoscopic surgical resection is a particularly useful technique for more minimally invasive treatment.We report two cases of small bowel hemangioma found in examinations for OGIB that were treated with combination of laparoscopic and endoscopic modalities.     

The role of capsule endoscopy in obscure gastrointestinal bleeding

Background and study aimObscure gastrointestinal bleeding is mostly recurrent and originates in the small bowel, which can be only partially examined by conventional endoscopy. Capsule endoscopy has revolutionized the evaluation of obscure gastrointestinal bleeding (OGIB). The diagnostic yield of capsule endoscopy in OGIB was a main concern of many studies. The aim of this study is to assess the diagnostic yield of capsule endoscopy in cases of OGIB. Capsule-related complications and degree of inter-observer variation will be recorded as well.Patients and methods54 consecutive patients suffering from OGIB, whether occult or overt, were subjected to capsule examination and data analysis.ResultsThe majority (74.1%) presented with obscure overt bleeding. Examination was complete in 68.4%. The commonest lesions were angiodysplasias (17.5%). Examinations were negative for lesions in 35.1% and hampered by limitations in 19.3%. The capsule diagnostic yield was 56.1%, while capsule retention occurred in 3.5%. The inter-observer agreement for the cause of bleeding was 91.2%.ConclusionsCapsule endoscopy proved helpful in solving the mystery of OGIB. It succeeded in diagnosing the cause of bleeding and directing further management with good compliance, high proportion of inter-observer agreement and low incidence of complications.     

Investigation of the small bowel in gastrointestinal bleeding--enteroscopy and capsule endoscopy

The last frontier in luminal endoscopy has been conquered. Bleeding lesions in the small intestine can present a frustrating clinical problem, but recent advances have made investigating the small bowel easier and less invasive. Capsule endoscopy and double balloon enteroscopy are two new technologies that promise to lower the barrier to evaluation of the entire small intestine. Recent studies show that capsule endoscopy improves outcomes in patients who have OGIB. Although outcome studies regarding double balloon enteroscopy have not been performed, the opportunity to treat lesions throughout the small bowel without resorting to surgery is a tremendous advance. These improvements suggest that the corner may have been turned in the diagnosis and management of small bowel bleeding. Perhaps to the next generation of gastroenterologists, small bowel bleeding will not be obscure.     

Diagnostic yield of deep enteroscopy techniques for small-bowel bleeding and tumors

Endoscopic evaluation and management with deep enteroscopy techniques have largely replaced the role of intraoperative enteroscopy in the management of small-bowel (SB) disorders. While capsule endoscopy (CE) enables visualization of the entire SB, therapeutic deep enteroscopy techniques (balloon-assisted enteroscopy and spiral enteroscopy) facilitate diagnostic and therapeutic management deep within the SB. CE is currently recommended as the third test of choice in the evaluation of obscure gastrointestinal bleeding after a negative bidirectional endoscopy. The test also has a role in the diagnosis of SB tumors and surveillance of familial polyposis syndromes. Therapeutic deep enteroscopy techniques are mainly used for evaluation and management of CE findings, but they may also have a role in patients with a negative CE but high clinical suspicion for an SB disorder. Because preliminary data suggest a comparable diagnostic and therapeutic yield with double-balloon, single-balloon, and spiral enteroscopy, selection of the enteroscope should be based on availability and the endoscopist's experience with the technique.     

Capsule Endoscopy Versus Push Enteroscopy for Evaluation of Obscure Gastrointestinal Bleeding with 1-Year Outcomes

Because of the low diagnostic yield of standard radiologic tests for identifying sources of obscure gastrointestinal bleeding in the small intestine, we compared wireless video capsule endoscopy with push enteroscopy and small-bowel follow-through. Patients referred to Mayo Clinic, Scottsdale, Arizona, between August and December 2001 for evaluation of obscure gastrointestinal bleeding were potential candidates. Eligible patients had previously inconclusive endoscopy, colonoscopy, small-bowel follow-through, and other radiologic studies. Participants underwent capsule endoscopy and enteroscopy (within 24 hr). The primary end point was localization of any bleeding source, with 1-year telephone follow-up. Capsule endoscopy yielded positive findings in 10 of 20 patients (11 men; mean age, 69 years), 6 of whom had negative enteroscopy and small-bowel follow-through. No patient with negative findings on capsule endoscopy had positive findings on enteroscopy and small-bowel follow-through. At follow-up, 19 patients reported fewer transfusions, gastrointestinal procedures, and hospitalizations. Capsule endoscopy identified more lesions and improved outcomes.Published as an abstract at Digestive Disease Week, San Francisco, California, May 19–22, 2002.     

胶囊内镜对不明原因消化道出血诊断价值的评估

背景：对于不明原因消化道出血（OGIB），胶囊内镜是一种有价值的诊断方法。但迄今为止，该技术在OGIB诊断中应用的研究多限于小样本病例。目的：评价胶囊内镜对OGIB的诊断价值，确定其敏感性，特异性，阳性，阴性预测值和总诊断率。方法：2002年5月-2005年1月，对连续选取的91例OGIB患者行胶囊内镜检查94次，对胶囊排出时间，再检查，治疗，再出血，依从性和并发症等情况进行随访观察。结果：胶囊内镜检查的阳性率为74.7%，疑诊率为11.0%，阴性率为14.3%。其诊断OGIB的敏感性，特异性以及阳性，阴性预测值分别为94.6%、88.9%和80.0%，总诊断率为93.8%。检查过程中仅1例（1.1%）患者发生胶囊滞留，后经手术取出并证实为克罗恩病所致的肠腔狭窄。结论：胶囊内镜对于OGIB是一种有效而安全的检查手段，迟早行胶囊内镜检查可使患者早日明确诊断并得到及时治疗，从而改善预后。     

Assessment of multi-modality evaluations of obscure gastrointestinal bleeding

AIM To determine the frequency of bleeding source detection in patients with obscure gastrointestinal bleeding(OGIB) who underwent double balloon enteroscopy(DBE) after pre-procedure imaging [multiphase computed tomography enterography(MPCTE), video capsule endoscopy(VCE), or both] and assess the impact of imaging on DBE diagnostic yield.METHODS Retrospective cohort study using a prospectively maintained database of all adult patients presenting with OGIB who underwent DBE from September 1~(st), 2002 to June 30~(th), 2013 at a single tertiary center.RESULTS Four hundred and ninety five patients(52% females; median age 68 years) underwent DBE for OGIB. AVCE and/or MPCTE performed within 1 year prior to DBE(in 441 patients) increased the diagnostic yield of DBE(67.1% with preceding imaging vs 59.5% without). Using DBE as the gold standard, VCE and MPCTE had a diagnostic yield of 72.7% and 32.5% respectively. There were no increased odds of finding a bleeding site at DBE compared to VCE(OR = 1.3, P = 0.150). There were increased odds of finding a bleeding site at DBE compared to MPCTE(OR = 5.9, P 0.001). In inpatients with overt OGIB, diagnostic yield of DBE was not affected by preceding imaging.CONCLUSION DBE is a safe and well-tolerated procedure for the diagnosis and treatment of OGIB, with a diagnostic yield that may be increased after obtaining a preceding VCE or MPCTE. However, inpatients with active ongoing bleeding may benefit from proceeding directly to antegrade DBE.     

Continuing challenges in the diagnosis and management of obscure gastrointestinal bleeding

The diagnosis and management of obscure gastrointestinal bleeding(OGIB) have changed dramatically since the introduction of video capsule endoscopy(VCE) followed by deep enteroscopy and other imaging technologies in the last decade. Significant advances have been made, yet there remains room for improvement in our diagnostic yield and treatment capabilities for recurrent OGIB. In this review, we will summarize the latest technologies for the diagnosis of OGIB, limitations of VCE, technological enhancement in VCE, and different management options for OGIB.     

双气囊小肠镜与胶囊内镜诊断小肠出血病因比较

目的比较双气囊小肠镜和胶囊内镜在小肠出血中的诊断准确率和实用价值。方法24例原因不明的可疑小肠出血患者分别接受双气囊小肠镜和胶囊内镜检查。双气囊小肠镜首选进镜方式分为经口或经肛2种，首选方式检查后未发现病灶者，日后改换进镜方式再行检查。胶囊内镜采用以色列GIVEN公司产品。2种检查方法分别由专门医师独立操作并诊断，最后进行汇总比较。结果24例患者中21例通过小肠镜检查发现病灶，总检出率为87．5％。24例患者行胶囊内镜检查后，有阳性发现者11例(45．8％)，另13例无异常发现。双气囊小肠镜检查发现的阳性病灶均经活检病理和手术探查证实，其病因诊断准确率为87．5％，胶囊内镜诊断准确率为25％。在耐受性评估方面，胶囊内镜和全麻下经口进镜的耐受性最佳，以后依次为非麻醉经肛方式和非麻醉经口方式。所有小肠镜和胶囊内镜检查者中未见操作相关的严重不良反应。结论①经口和经肛方式结合能使双气囊小肠镜完成对全小肠的检查。②双气囊小肠镜在不明原因小肠出血的病因诊断方面明显优于胶囊内镜检查。③胶囊内镜在小肠多节段病变和长段病变的诊断上仍有一定价值。④胶囊内镜和全麻下经口双气囊小肠镜检查是一项易为患者接受的、安全的检查方法。     

Wireless capsule endoscopy: a comparison with push enteroscopy in patients with gastroscopy and colonoscopy negative gastrointestinal bleeding

BACKGROUND: The development of wireless capsule endoscopy allows painless imaging of the small intestine. Its clinical use is not yet defined. The aim of this study was to compare the clinical efficacy and technical performance of capsule endoscopy and push enteroscopy in a series of 50 patients with colonoscopy and gastroscopy negative gastrointestinal bleeding. METHODS: A wireless capsule endoscope was used containing a CMOS colour video imager, transmitter, and batteries. Approximately 50,000 transmitted images are received by eight abdominal aerials and stored on a portable solid state recorder, which is carried on a belt. Push enteroscopy was performed using a 240 cm Olympus video enteroscope. RESULTS: Studies in 14 healthy volunteers gave information on normal anatomical appearances and preparation. In 50 patients with gastrointestinal bleeding and negative colonoscopy and gastroscopy, push enteroscopy was compared with capsule endoscopy. A bleeding source was discovered in the small intestine in 34 of 50 patients (68%). These included angiodysplasia (16), focal fresh bleeding (eight), apthous ulceration suggestive of Crohn's disease (three), tumour (two), Meckel's diverticulum (two), ileal ulcer (one), jejunitis (one), and ulcer due to intussusception (one). One additional intestinal diagnosis was made by enteroscopy. The yield of push enteroscopy in evaluating obscure bleeding was 32% (16/50). The capsule identified significantly more small intestinal bleeding sources than push enteroscopy (p<0.05). Patients preferred capsule endoscopy to push enteroscopy (p<0.001). CONCLUSIONS: In this study capsule endoscopy was superior to push enteroscopy in the diagnosis of recurrent bleeding in patients who had a negative gastroscopy and colonoscopy. It was safe and well tolerated.     

The patient with recidivent obscure gastrointestinal bleeding

Obscure gastrointestinal (GI) bleeding is defined as visible or invisible GI blood loss, the source of which can not be identified by standard endoscopy (oesophagogastroduodenoscopy and colonoscopy). Nowadays, GI bleeding is divided into upper, mid- and lower bleeding. Mid-GI bleeding covers the section from the Treitz ligament to the ileocaecal valve. The new diagnostic methods of capsule endoscopy and double balloon enteroscopy have revolutionised the diagnostic approach in recent years. As a result, previous radiological and nuclear medicine techniques (small bowel X-ray, scintigraphy and angiography), but also endoscopic techniques, such as the push enteroscopy and intraoperative endoscopy, are becoming less important. After standard endoscopy and persistent blood loss it is advisable to first have these procedures repeated by an experienced examiner under optimal conditions. Nevertheless, no source of bleeding is identified by this method in 5% of cases. It is then recommended to use capsule endoscopy and, depending on the findings, double balloon enteroscopy with the option of intervention. In patients with unstable circulation an invasive procedure (intraoperative endoscopy) may be required.     

Clinical Practice Guideline for Enteroscopy

Management of small bowel diseases has evolved since the advent of capsule endoscopy (CE) and balloon‐assisted enteroscopy (BAE). One of the most common indications for enteroscopy is obscure gastrointestinal bleeding (OGIB), followed by small bowel stenosis, tumors, and inflammatory bowel disease. Although enteroscopes have been regarded as useful tools, correct guidelines are required to ensure that we manipulate these enteroscopes safely and efficiently in clinical practice. Herein, the Japanese Gastroenterological Endoscopy Society has developed ‘Clinical Practice Guidelines for Enteroscopy’ in collaboration with the Japanese Society of Gastroenterology, the Japanese Gastroenterological Association, and the Japanese Association for Capsule Endoscopy. These guidelines are based on the evidence available until now, but small bowel endoscopy is a relatively new technology, so the guidelines include recommendations based on a consensus reached among experts when the evidence has not been considered sufficient. These guidelines were not designed to be disease‐based, but focus on how we should use small bowel CE and BAE in everyday clinical practice.