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World J Gastrointest Pathophysiol. Nov 15, 2014; 5(4): 479-486 Published online Nov 15, 2014. doi: 10.4291/wjgp.v5.i4.479
Evaluation and outcomes of patients with obscure gastrointestinal bleeding
Cositha Santhakumar, Ken Liu
Cositha Santhakumar, Ken Liu, Department of Gastroenterology and Hepatology, Level 1 West, Concord Repatriation General Hospital, Sydney NSW 2139, Australia
ORCID number: $[AuthorORCIDs]
Author contributions: Santhakumar C performed the literature review and composed the initial manuscript; Liu K was involved in editing the manuscript.
Correspondence to: Dr. Cositha Santhakumar, Department of Gastroenterology and Hepatology, Level 1 West, Concord Repatriation General Hospital, Sydney NSW 2139, Australia. email@example.com
Telephone: + 61-2-97675000 Fax: +61-2-97676767
Received: January 28, 2014 Revised: June 30, 2014 Accepted: July 15, 2014 Published online: November 15, 2014
Obscure gastrointestinal bleeding (OGIB) is defined as recurrent or persistent bleeding or presence of iron deficiency anaemia after evaluation with a negative bidirectional endoscopy. OGIB accounts for 5% of gastrointestinal bleeding and presents a diagnostic challenge. Current modalities available for the investigation of OGIB include capsule endoscopy, balloon assisted enteroscopy, spiral enteroscopy and computed tomography enterography. These modalities overcome the limitations of previous techniques. Following a negative bidirectional endoscopy, capsule endoscopy and double balloon enteroscopy remain the cornerstone of investigation in OGIB given their high diagnostic yield. Long-term outcome data in patients with OGIB is limited, but is most promising for capsule endoscopy. This article reviews the current literature and provides an overview of the clinical evaluation of patients with OGIB, available diagnostic and therapeutic modalities and long-term clinical outcomes.
Core tip: This article examines the role of current diagnostic modalities for the investigation of obscure gastrointestinal bleeding (OGIB) and outcomes in patients undergoing these investigations. Capsule endoscopy and double balloon enteroscopy remain the cornerstone of diagnostic and therapeutic management. The diagnostic and therapeutic capabilities of certain modalities are influenced by the nature of bleeding in OGIB. Long-term outcome data in patients with OGIB is limited but is most promising for capsule endoscopy.
Citation: Santhakumar C, Liu K. Evaluation and outcomes of patients with obscure gastrointestinal bleeding. World J Gastrointest Pathophysiol 2014; 5(4): 479-486
Obscure gastrointestinal bleeding (OGIB) is defined as recurrent or persistent bleeding or presence of iron deficiency anaemia (IDA) after negative evaluation with oesophagogastroduodenoscopy (OGD) and colonoscopy. OGIB can be categorised further into overt or occult obscure gastrointestinal (GI) bleeding. Overt GI bleeding refers to patients with clinically evident bleeding (haematemesis, melaena or haematochezia) whereas occult GI bleeding occurs in the setting of persistent IDA or a positive faecal occult blood test.
OGIB accounts for approximately 5% of GI bleeding. In more than 80% of cases, the bleeding arises from the small bowel distal to the Ampulla of Vater and proximal to the ileocaecal valve rendering it relatively inaccessible to traditional endoscopy[2-4]. Patients with OGIB undergo more investigations, have longer duration of hospitalisation, require more blood transfusions and generate higher healthcare expenditures than patients with upper or lower gastrointestinal bleeding. This is largely due to difficulty accessing the small bowel endoscopically which presents a diagnostic challenge.
Current modalities to investigate for OGIB include both endoscopic and radiological techniques. The role of radiological modalities in the evaluation of OGIB has declined substantially as a result of their low diagnostic yield. In this article, we review the clinical evaluation and outcomes of patients presenting with OGIB.
EVALUATION OF OGIB
The clinical history may suggest the possible cause and location of OGIB but it is rarely diagnostic. Endoscopic evaluation remains the cornerstone of diagnosis and management in OGIB. A careful history is key and should include the nature (occult or overt) and clinical presentation of GI bleeding (haematemesis, melaena, haematochezia). Further history regarding other gastrointestinal symptoms (weight loss, obstructive symptoms), medications (anticoagulants, non-steroidal anti-inflammatory drugs), comorbidities (haematological disease, valvular heart disease), prior surgeries (abdominal aortic aneurysm repair, bowel surgery), and family history (inflammatory bowel disease, malignancies, familial telangiectasias) may give clues to the underlying cause. While haematemesis reliably localises the bleeding proximal to the ligament of Treitz, stool colour is a less reliable indicator as it is dependent upon intestinal transit time. Elderly patients, patients with valvular heart disease, renal disease or connective tissue disease are at high risk of vascular lesions. Use of non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of small bowel ulceration. Physical examination may be useful in detecting systemic syndromes such as hereditary haemorrhagic telangiectasias or Coeliac disease.
The most common causes of OGIB vary according to age (Table 1). In patients younger than 40 years of age, small intestinal tumours, Crohn’s disease, Meckel’s diverticulum, polyposis syndromes and angiodysplasias predominate, whereas patients older than 40 years of age are more likely to bleed from vascular causes (e.g., angiodysplasias) and NSAID enteropathy[8,9]. Causes of OGIB are mainly vascular in the Western population and ulcerations or erosions in the Asian population. Patients who present with IDA without gastrointestinal symptoms, may have gastrointestinal diseases that cause iron malabsorption such as Coeliac disease, atrophic gastritis and Helicobacter Pylori gastritis.
Table 1 Aetiology of obscure gastrointestinal bleeding.
Inflammatory bowel disease
Hereditary Haemorrhagic Telangiectasias
Peptic ulcer disease
Gastrointestinal stromal tumour
Von Willebrand disease
Gastric antral vascular ectasia
Portal hypertensive gastropathy
Henoch Schonlein Purpura
NSAID related gastropathy/enteropathy
NSAID: Non-steroidal anti-inflammatory drugs.
Availability of procedures, patient preferences, physician expertise, costs and risks are important determinants of investigation and management.
Capsule endoscopy (CE) has revolutionised the ability to image the small bowel. It is commonly used as a first-line diagnostic tool for investigation of OGIB. This is due to its non-invasiveness, patient tolerance, high negative predictive value (80%-100%) and high diagnostic yield[3,13,14]. CE enables direct visualisation of the small bowel mucosa and has a high sensitivity for detecting flat lesions, such as angiodysplasias, ulcers and arteriovenous malformations which are not easily detectable on radiological modalities.
The reported diagnostic yield in literature ranges from 58.4% to 86.8%[9,14,16-21]. The wide range is attributable to different definitions of a positive finding on CE. The diagnostic yield is not affected by age, rendering it a useful test across all age groups. However, it is affected by patient factors including ongoing bleeding, low haemoglobin and ongoing transfusion requirements.
Pennazio et al reported that the diagnostic yield of CE was significantly higher in patients with ongoing overt OGIB (92.3%), intermediate in patients with occult OGIB (44.2%) and lowest in patients with previous overt OGIB (12.9%). In the overt OGIB group, the diagnostic yield was inversely proportional to the length of time since the last bleeding episode, as delay in the use of CE allows for healing of the bleeding site. CE thus has its highest diagnostic yield in patients with ongoing and overt bleeding[16,25].
CE has been shown to be superior to other modalities including computed tomography, and small bowel barium studies[26-29]. When compared to push enteroscopy (PE), two meta-analyses have confirmed the superiority of CE, one of which demonstrated a diagnostic yield 30% higher than PE[29,30].
When comparing CE with double balloon enteroscopy (DBE), the literature is inconsistent due to small sample sizes. Teshima et al’s meta-analysis comparing CE and DBE in OGIB revealed a similar diagnostic yield (62% vs 56%), a finding supported by 2 other meta-analyses[31-33]. CE has a higher diagnostic yield than either anterograde or retrograde DBE alone (OR = 1.61, 95%CI: 1.07-2.43) but not when both approaches are used together (OR = 0.12, 95%CI: 0.03-0.52). This highlights the importance of a total enteroscopy in patients with a high clinical suspicion of small bowel pathology. However, the completion rate of DBE is highly variable (16%-86%)[34,35].
CE has other distinct advantages since it allows the patient to remain ambulatory and requires minimal preparation without sedation. Its main limitation is that it is solely a diagnostic tool lacking therapeutic capacity and the ability to obtain histology[37,38]. It has limited effectiveness in detecting small bowel submucosal tumours, with a false-negative rate up to 19%[39,40]. Other limitations include the inability to precisely locate the bleeding lesions and a small (but significant) risk of capsule retention (0.75% to 5.8%)[3,41,42].
PE can visualise the proximal small bowel up to 100cm distal to the ligament of Trietz. It has diagnostic and therapeutic (biopsy, electrocautery, injection, polypectomy) capabilities. An important advantage of PE is that it facilitates a second look for missed lesions within reach of an OGD which is seen in 25%-40% of cases[43,44].
The reported diagnostic yield is between 3%-70%[2,45-47]. The main limitation is its inability to reach lesions beyond the middle jejunum, patient discomfort and its time-consuming nature[4,48]. Complications are rare and include pancreatitis and mucosal injuries. It has largely been replaced by CE for diagnosis and DBE for small bowel endoscopic treatment. Its role mainly lies in the treatment of proximal small bowel lesions found on CE.
Double balloon enteroscopy
Double balloon enteroscopy facilitates examination of the entire small bowel. It is considered the gold standard for therapeutic intervention of many small bowel disorders in OGIB. The diagnostic yield and treatment success of DBE for OGIB in published literature ranges from 60%-81% and 43%-84% respectively[10,50-60]. The variation in diagnostic yield is a result of differences in DBE timing, inclusion criteria and definitions of a significant finding. Like CE, DBE has a higher diagnostic yield in patients with overt-ongoing OGIB than overt previous and occult OGIB, suggesting that the time interval between the last bleeding episode and the DBE examination is a key factor in diagnosing the causative lesion in OGIB.
The approach of a targeted DBE (after a prior CE) has been shown to increase both its diagnostic (73%-93%) and therapeutic yield (53%-73%)[38,62,63]. DBE can change or improve the diagnosis in a significant number of patients in whom CE is performed beforehand. In a study by Kaffes et al, DBE after CE clarified or made a new diagnosis in 20% of patients. A CE guided DBE is likely to diminish the need for total enteroscopy in most patients, as demonstrated by Gay et al who showed a high positive predictive value for CE to correctly predict the DBE approach. The targeted approach is also useful in confirming indeterminate findings from CE. Hence, it is strongly suggested that CE is the initial screening modality in OGIB and that these two investigations should be viewed as complementary[20,64].
Not surprisingly, when compared with PE, a controlled prospective trial on patients with suspected small bowel bleeding, confirmed that anterograde DBE is significantly superior to PE in regards to the detection of pathological lesions (63% vs 44%) and the length of small bowel visualised (230 cm vs 80 cm).
DBE is restricted by its limited availability, prolonged procedural times and sedation requirements. The complication rate is 0.8% for diagnostic procedures and up to 4% for therapeutics such as polypectomy, electrocautery or dilatation. Complications include bleeding, ileus, intestinal perforation, pancreatitis or those related to sedation. For these reasons, DBE is a second-line investigation in OGIB, reserved for patients with a positive CE who require therapeutic intervention or biopsy.
Current guidelines recommend CE as the preferred initial modality in OGIB given its diagnostic yield, outcome data, safety and non-invasive nature. DBE should be viewed as a complementary procedure. It plays an important therapeutic role following diagnostic CE and diagnostic role following negative CE in patients with ongoing bleeding or high suspicion of small bowel pathology. Other scenarios for initial use of DBE are where CE is not available or affordable and in patients with overt OGIB who may benefit from early DBE. More prospective randomised controlled clinical studies are required to determine the most efficient and cost effective use of CE and DBE.
Spiral enteroscopy utilises a spiral shaped overtube with a raised helix at the distal end. It allows for advancement and withdrawal of the enteroscope through the small bowel by using clockwise and anticlockwise movements respectively. It offers the same diagnostic and therapeutic capabilities as DBE. Initial studies comparing DBE and spiral enteroscopy have suggested that the two procedures have similar diagnostic yields[66-68]. Further studies comparing spiral enteroscopy to other modalities such as CE and DBE are required.
Intraoperative enteroscopy (IOE) was previously considered the gold standard of small intestinal imaging. It has the highest sensitivity in detecting bleeding small bowel lesions with a diagnostic yield of 80%-100%[69,70]. This is at the expense of extreme invasiveness making this modality a last resort in the investigation OGIB. Indications of IOE include when small bowel lesions cannot be managed by angiographic embolisation or endoscopic treatment or when surgery is required.
REPEAT UPPER AND LOWER ENDOSCOPY
Bleeding sources within reach of upper and lower endoscopy may be missed as a result of small size, atypical location, inadequate endoscopy investigation, slow or intermittent bleeding, or compromised visualisation (due to presence of blood or poor colonic preparation).
Numerous studies demonstrate that a significant proportion of patients with negative initial investigations have a bleeding source on repeat OGD in 35%-75% or repeat colonoscopy in 6% of cases[45,71-76]. Thus a re-look endoscopy may be recommended as a cost-effective first step before further evaluation. Factors associated with increased yield on repeat OGD include large hiatus hernias, history of NSAID use, and haematemesis.
Common missed lesions include colonic angiodysplasias, peptic ulcers, Cameron’s lesions, gastric antral vascular ectasia and radiation proctitis.
The American Gastroenterological Association recommend repeating OGD and colonoscopy if there is suspicion of an overlooked lesion before proceeding to CE or DBE. Repeat OGD and/or colonoscopy should also be considered if suboptimal equipment was used or in the setting of inadequate mucosal visualisation secondary to poor bowel preparation.
COMPUTED TOMOGRAPHY ENTEROGRAPHY
Computed tomography enterography (CTE) is a readily available, non-invasive, operator independent method for visualising the small bowel. It can detect extraluminal pathology which is not possible with CE. The overall sensitivity of CTE is low (50%), however it is effective for detecting small bowel tumours (sensitivity exceeding 90%)[77-79]. The diagnostic yield of CE following negative CTE is high, 57% in one study. Small bowel ulcers are the most commonly missed lesions with CTE which are readily detected by CE. However, in patients less than 40 years of age where small bowel tumours are the most common cause of OGIB, CTE should be strongly considered given the aforementioned false negative rate of CE for detecting small bowel neoplasms[80,81].
Although many studies demonstrate a high diagnostic yield of CE for detecting a cause of OGIB, its impact on patient outcomes is more important. With regards to rebleeding rates, Endo et al found that among patients with significant CE findings, the rebleeding rate at a mean of 11.6 mo follow up of the patients who underwent therapeutic intervention was significantly lower than that of those without intervention (9.5% vs 40.0%, P = 0.046). This is supported by other studies[83,84]. Hence, aggressive intervention of patients with significant CE findings reduces risk of rebleeding. Patients with insignificant findings (erosions, small ulcers, red spots, small polyps) or a negative CE, had a significantly higher rate of re-bleeding than those with significant findings on CE. These patients should have careful follow up, whilst being mindful that the bleeding may not be originating from the small bowel. Viazis et al found that 65% of patients with a negative initial CE continued to have OGIB after a mean follow up period of 24 mo. Development of overt bleeding and a haemoglobin drop of 4 g/dL or more were significant predictive factors for a diagnostic repeat CE. Similar to its influence on diagnostic yield, the nature of bleeding in OGIB also impacts on rebleeding rates. In the Pennazio et al study, complete resolution of bleeding occurred significantly more often in patients with ongoing overt and occult OGIB than with previous OGIB.
In regards to other outcome measures, Leighton et al demonstrated significant reductions in the requirement for blood transfusions, gastrointestinal procedures and hospitalisation as well as significant improvements in haemoglobin levels at 1 year follow-up of 20 patients undergoing CE for investigation of OGIB. Hindryckx et al also confirmed favourable outcomes in 66.3% of their patients after CE guided therapy which led to a decrease in the need for blood transfusions and significantly higher haemoglobin levels after a mean follow up of 635.5 d.
Kaffes et al reported significant reductions in further bleeding (80%), blood transfusions and iron requirements in a prospective cohort study of 60 patients with positive CE findings undergoing DBE treatment after 10 ± 5.2 mo follow up. Seventy-seven percent of patients maintained a normal haemoglobin. Hsu et al similarly found significantly less rebleeding in patients who were treated for an identified lesion when compared to patients in whom no lesion was found (20% vs 80%).
Byeon et al found that repeat DBE in the same direction may detect a source of bleeding in 53% of recurrent OGIB patients, particularly in patients with a previous positive DBE (81% yield). Angiodysplasias were the most common cause of OGIB in both DBEs. Angiodysplasia has been identified as a common source of rebleeding in studies exploring outcome in patients with OGIB after PE, CE and or DBE[88,89].
Most studies follow up patients for up to 12 mo. Larger prospective studies with longer follow up are required to evaluate long term outcomes of OGIB patients following DBE.
Several small studies suggest that patient outcomes are improved after PE. In one study of 105 patients with OGIB with a mean follow up of 29 mo, resolution of bleeding occurred in 69% of patients. PE impacts upon clinical management in 40%-50% of patients with OGIB[74,91]. Decreased transfusion requirements and improvement in functional status one year post treatment have been found with PE.
There are limited data on outcomes of OGIB patients after investigation with other modalities. However, similar to data from CE, DBE and PE, patients who underwent endoscopic treatment for an identified lesion had better outcomes than those without treatment.
Williamson et al followed up 61 patients undergoing spiral enteroscopy for OGIB. The mean time to recurrent overt bleeding was 10.4 months. Patients who had endoscopic treatment for bleeding lesions during spiral enteroscopy were significantly less likely to have further overt bleeding (26% vs 64%). Increased haemoglobin levels and reduced requirements for blood transfusions, iron supplementation and additional procedures were all observed after spiral enteroscopy.
A retrospective study of IOE demonstrated, at 32 mo follow up, bleeding had resolved in 52% of patients with OGIB in whom a lesion was detected and treated during IOE. Bleeding persisted in 20% and recurred in 8% of patients. Angiodysplasias were responsible for the majority of patients with ongoing bleeding.
In a retrospective study, Shin et al showed that CTE discovered the source of bleeding in only 26.7% of patients with OGIB. The overall re-bleeding rate was 21.7% during a mean follow up of 17.6 mo. Again, patients with positive CTE who were treated endoscopically had significantly reduced rebleeding rates. A negative CTE did not predict lower long term rebleeding, and thus these patients should be closely observed and have further diagnostic work up (such as with CE or DBE) if there is a high clinical suspicion of small bowel bleeding.
Obscure gastrointestinal bleeding is a common problem and remains a diagnostic challenge to gastroenterologists. Various endoscopic, radiological and surgical modalities exist for the investigation of OGIB each with their own advantages, disadvantages and indications in which they should be used. Both CE and DBE remain the cornerstone of investigation and management of OGIB, with other modalities assuming a more selective role. Ultimately patient factors and resource availability determine the modality used. The short-term outcomes of OGIB patients with a treated lesion are good; however rebleeding is common especially in patients where no source of bleeding was found. Further studies are required to evaluate long-term outcomes. With ongoing development and experience in new techniques, the clinical conundrum that is OGIB may no longer be so obscure.
P- Reviewer: Aisa AP, Cho YS, Yang MH S- Editor: Wen LL L- Editor: A E- Editor: Wang CH
Shin JK, Cheon JH, Lim JS, Park JJ, Moon CM, Jeon SM, Lee JH, Hong SP, Kim TI, Kim WH. Long-term outcomes of obscure gastrointestinal bleeding after CT enterography: does negative CT enterography predict lower long-term rebleeding rate?J Gastroenterol Hepatol. 2011;26:901-907.
Raju GS, Gerson L, Das A, Lewis B. American Gastroenterological Association (AGA) Institute technical review on obscure gastrointestinal bleeding.Gastroenterology. 2007;133:1697-1717.
Keum B, Chun HJ. Capsule endoscopy and double balloon enteroscopy for obscure gastrointestinal bleeding: which is better?J Gastroenterol Hepatol. 2011;26:794-795.
Carey EJ, Fleischer DE. Investigation of the small bowel in gastrointestinal bleeding--enteroscopy and capsule endoscopy.Gastroenterol Clin North Am. 2005;34:719-734.
Pasha SF, Hara AK, Leighton JA. Diagnostic evaluation and management of obscure gastrointestinal bleeding: a changing paradigm.Gastroenterol Hepatol (N Y). 2009;5:839-850.
Lin S, Rockey DC. Obscure gastrointestinal bleeding.Gastroenterol Clin North Am. 2005;34:679-698.
Mujica VR, Barkin JS. Occult gastrointestinal bleeding. General overview and approach.Gastrointest Endosc Clin N Am. 1996;6:833-845.
Estévez E, González-Conde B, Vázquez-Iglesias JL, de Los Angeles Vázquez-Millán M, Pértega S, Alonso PA, Clofent J, Santos E, Ulla JL, Sánchez E. Diagnostic yield and clinical outcomes after capsule endoscopy in 100 consecutive patients with obscure gastrointestinal bleeding.Eur J Gastroenterol Hepatol. 2006;18:881-888.
Tanaka S, Mitsui K, Yamada Y, Ehara A, Kobayashi T, Seo T, Tatsuguchi A, Fujimori S, Gudis K, Sakamoto C. Diagnostic yield of double-balloon endoscopy in patients with obscure GI bleeding.Gastrointest Endosc. 2008;68:683-691.
Annibale B, Capurso G, Chistolini A, D’Ambra G, DiGiulio E, Monarca B, DelleFave G. Gastrointestinal causes of refractory iron deficiency anemia in patients without gastrointestinal symptoms.Am J Med. 2001;111:439-445.
Rondonotti E, Marmo R, Petracchini M, de Franchis R, Pennazio M. The American Society for Gastrointestinal Endoscopy (ASGE) diagnostic algorithm for obscure gastrointestinal bleeding: eight burning questions from everyday clinical practice.Dig Liver Dis. 2013;45:179-185.
Delvaux M, Fassler I, Gay G. Clinical usefulness of the endoscopic video capsule as the initial intestinal investigation in patients with obscure digestive bleeding: validation of a diagnostic strategy based on the patient outcome after 12 months.Endoscopy. 2004;36:1067-1073.
Hartmann D, Schmidt H, Bolz G, Schilling D, Kinzel F, Eickhoff A, Huschner W, Möller K, Jakobs R, Reitzig P. A prospective two-center study comparing wireless capsule endoscopy with intraoperative enteroscopy in patients with obscure GI bleeding.Gastrointest Endosc. 2005;61:826-832.
Soyer P. Obscure gastrointestinal bleeding: difficulties in comparing CT enterography and video capsule endoscopy.Eur Radiol. 2012;22:1167-1171.
Pennazio M, Santucci R, Rondonotti E, Abbiati C, Beccari G, Rossini FP, De Franchis R. Outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy: report of 100 consecutive cases.Gastroenterology. 2004;126:643-653.
Apostolopoulos P, Liatsos C, Gralnek IM, Kalantzis C, Giannakoulopoulou E, Alexandrakis G, Tsibouris P, Kalafatis E, Kalantzis N. Evaluation of capsule endoscopy in active, mild-to-moderate, overt, obscure GI bleeding.Gastrointest Endosc. 2007;66:1174-1181.
Endo H, Matsuhashi N, Inamori M, Akimoto K, Ohya T, Yanagawa T, Asayama M, Hisatomi K, Teratani T, Fujita K. Rebleeding rate after interventional therapy directed by capsule endoscopy in patients with obscure gastrointestinal bleeding.BMC Gastroenterol. 2008;8:12.
Kim JB, Ye BD, Song Y, Yang DH, Jung KW, Kim KJ, Byeon JS, Myung SJ, Yang SK, Kim JH. Frequency of rebleeding events in obscure gastrointestinal bleeding with negative capsule endoscopy.J Gastroenterol Hepatol. 2013;28:834-840.
Li X, Dai J, Lu H, Gao Y, Chen H, Ge Z. A prospective study on evaluating the diagnostic yield of video capsule endoscopy followed by directed double-balloon enteroscopy in patients with obscure gastrointestinal bleeding.Dig Dis Sci. 2010;55:1704-1710.
Zakaria MS, El-Serafy MA, Hamza IM, Zachariah KS, El-Baz TM, Tacheci JB. The role of capsule endoscopy in obscure gastrointestinal bleeding.Arab J Gastroenterol. 2009;10:57–62.
Orlando G, Luppino IM, Lerose MA, Gervasi R, Amato B, Silecchia G, Puzziello A. Feasibility of capsule endoscopy in elderly patients with obscure gastrointestinal bleeding. An up-to-date report.BMC Surg. 2012;12 Suppl 1:S30.
Rockey DC. Occult and obscure gastrointestinal bleeding: causes and clinical management.Nat Rev Gastroenterol Hepatol. 2010;7:265-279.
Esaki M, Matsumoto T, Yada S, Yanaru-Fujisawa R, Kudo T, Yanai S, Nakamura S, Iida M. Factors associated with the clinical impact of capsule endoscopy in patients with overt obscure gastrointestinal bleeding.Dig Dis Sci. 2010;55:2294-2301.
Heo HM, Park CH, Lim JS, Lee JH, Kim BK, Cheon JH, Kim TI, Kim WH, Hong SP. The role of capsule endoscopy after negative CT enterography in patients with obscure gastrointestinal bleeding.Eur Radiol. 2012;22:1159-1166.
Voderholzer WA, Ortner M, Rogalla P, Beinhölzl J, Lochs H. Diagnostic yield of wireless capsule enteroscopy in comparison with computed tomography enteroclysis.Endoscopy. 2003;35:1009-1014.
Voderholzer WA, Beinhoelzl J, Rogalla P, Murrer S, Schachschal G, Lochs H, Ortner MA. Small bowel involvement in Crohn’s disease: a prospective comparison of wireless capsule endoscopy and computed tomography enteroclysis.Gut. 2005;54:369-373.
Hara AK, Leighton JA, Sharma VK, Fleischer DE. Small bowel: preliminary comparison of capsule endoscopy with barium study and CT.Radiology. 2004;230:260-265.
Triester SL, Leighton JA, Leontiadis GI, Fleischer DE, Hara AK, Heigh RI, Shiff AD, Sharma VK. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with obscure gastrointestinal bleeding.Am J Gastroenterol. 2005;100:2407-2418.
Leighton JA, Triester SL, Sharma VK. Capsule endoscopy: a meta-analysis for use with obscure gastrointestinal bleeding and Crohn’s disease.Gastrointest Endosc Clin N Am. 2006;16:229-250.
Teshima CW, Kuipers EJ, van Zanten SV, Mensink PB. Double balloon enteroscopy and capsule endoscopy for obscure gastrointestinal bleeding: an updated meta-analysis.J Gastroenterol Hepatol. 2011;26:796-801.
Pasha SF, Leighton JA, Das A, Harrison ME, Decker GA, Fleischer DE, Sharma VK. Double-balloon enteroscopy and capsule endoscopy have comparable diagnostic yield in small-bowel disease: a meta-analysis.Clin Gastroenterol Hepatol. 2008;6:671-676.
Chen X, Ran ZH, Tong JL. A meta-analysis of the yield of capsule endoscopy compared to double-balloon enteroscopy in patients with small bowel diseases.World J Gastroenterol. 2007;13:4372-4378.
Gross SA, Stark ME. Initial experience with double-balloon enteroscopy at a U.S. center.Gastrointest Endosc. 2008;67:890-897.
Yamamoto H, Sekine Y, Sato Y, Higashizawa T, Miyata T, Iino S, Ido K, Sugano K. Total enteroscopy with a nonsurgical steerable double-balloon method.Gastrointest Endosc. 2001;53:216-220.
Leighton JA, Sharma VK, Hentz JG, Musil D, Malikowski MJ, McWane TL, Fleischer DE. Capsule endoscopy versus push enteroscopy for evaluation of obscure gastrointestinal bleeding with 1-year outcomes.Dig Dis Sci. 2006;51:891-899.
Williamson JB, Judah JR, Gaidos JK, Collins DP, Wagh MS, Chauhan SS, Zoeb S, Buscaglia JM, Yan H, Hou W. Prospective evaluation of the long-term outcomes after deep small-bowel spiral enteroscopy in patients with obscure GI bleeding.Gastrointest Endosc. 2012;76:771-778.
Kaffes AJ, Siah C, Koo JH. Clinical outcomes after double-balloon enteroscopy in patients with obscure GI bleeding and a positive capsule endoscopy.Gastrointest Endosc. 2007;66:304-309.
Lewis BS, Eisen GM, Friedman S. A pooled analysis to evaluate results of capsule endoscopy trials.Endoscopy. 2005;37:960-965.
Pennazio M, Rondonotti E, de Franchis R. Capsule endoscopy in neoplastic diseases.World J Gastroenterol. 2008;14:5245-5253.
Barkin JS, Friedman S. Wireless capsule endoscopy requiring surgical intervention: the world’s experience [abstract].Am J Gastroenterol. 2002;97:A83.
Sears DM, Avots-Avotins A, Culp K, Gavin MW. Frequency and clinical outcome of capsule retention during capsule endoscopy for GI bleeding of obscure origin.Gastrointest Endosc. 2004;60:822-827.
Berner JS, Mauer K, Lewis BS. Push and sonde enteroscopy for the diagnosis of obscure gastrointestinal bleeding.Am J Gastroenterol. 1994;89:2139-2142.
Parry SD, Welfare MR, Cobden I, Barton JR. Push enteroscopy in a UK district general hospital: experience of 51 cases over 2 years.Eur J Gastroenterol Hepatol. 2002;14:305-309.
Chak A, Koehler MK, Sundaram SN, Cooper GS, Canto MI, Sivak MV. Diagnostic and therapeutic impact of push enteroscopy: analysis of factors associated with positive findings.Gastrointest Endosc. 1998;47:18-22.
Lin S, Branch MS, Shetzline M. The importance of indication in the diagnostic value of push enteroscopy.Endoscopy. 2003;35:315-321.
Chak A, Cooper GS, Canto MI, Pollack BJ, Sivak MV. Enteroscopy for the initial evaluation of iron deficiency.Gastrointest Endosc. 1998;47:144-148.
Ge ZZ, Chen HY, Gao YJ, Hu YB, Xiao SD. Best candidates for capsule endoscopy for obscure gastrointestinal bleeding.J Gastroenterol Hepatol. 2007;22:2076-2080.
Fry LC, Bellutti M, Neumann H, Malfertheiner P, Mönkemüller K. Incidence of bleeding lesions within reach of conventional upper and lower endoscopes in patients undergoing double-balloon enteroscopy for obscure gastrointestinal bleeding.Aliment Pharmacol Ther. 2009;29:342-349.
Hadithi M, Heine GD, Jacobs MA, van Bodegraven AA, Mulder CJ. A prospective study comparing video capsule endoscopy with double-balloon enteroscopy in patients with obscure gastrointestinal bleeding.Am J Gastroenterol. 2006;101:52-57.
Arakawa D, Ohmiya N, Nakamura M, Honda W, Shirai O, Itoh A, Hirooka Y, Niwa Y, Maeda O, Ando T. Outcome after enteroscopy for patients with obscure GI bleeding: diagnostic comparison between double-balloon endoscopy and videocapsule endoscopy.Gastrointest Endosc. 2009;69:866-874.
Yamamoto H, Kita H, Sunada K, Hayashi Y, Sato H, Yano T, Iwamoto M, Sekine Y, Miyata T, Kuno A. Clinical outcomes of double-balloon endoscopy for the diagnosis and treatment of small-intestinal diseases.Clin Gastroenterol Hepatol. 2004;2:1010-1016.
Di Caro S, May A, Heine DG, Fini L, Landi B, Petruzziello L, Cellier C, Mulder CJ, Costamagna G, Ell C. The European experience with double-balloon enteroscopy: indications, methodology, safety, and clinical impact.Gastrointest Endosc. 2005;62:545-550.
May A, Nachbar L, Ell C. Double-balloon enteroscopy (push-and-pull enteroscopy) of the small bowel: feasibility and diagnostic and therapeutic yield in patients with suspected small bowel disease.Gastrointest Endosc. 2005;62:62-70.
Heine GD, Hadithi M, Groenen MJ, Kuipers EJ, Jacobs MA, Mulder CJ. Double-balloon enteroscopy: indications, diagnostic yield, and complications in a series of 275 patients with suspected small-bowel disease.Endoscopy. 2006;38:42-48.
Zhong J, Ma T, Zhang C, Sun B, Chen S, Cao Y, Wu Y. A retrospective study of the application on double-balloon enteroscopy in 378 patients with suspected small-bowel diseases.Endoscopy. 2007;39:208-215.
Byeon JS, Chung JW, Choi KD, Choi KS, Kim B, Myung SJ, Yang SK, Kim JH. Clinical features predicting the detection of abnormalities by double balloon endoscopy in patients with suspected small bowel bleeding.J Gastroenterol Hepatol. 2008;23:1051-1055.
Choi H, Choi KY, Eun CS, Jang HJ, Park DI, Chang DK, Kim JO, Ko BM, Lee MS, Huh KC. Korean experience with double balloon endoscopy: Korean Association for the Study of Intestinal Diseases multi-center study.Gastrointest Endosc. 2007;66:S22-S25.
Hsu CM, Chiu CT, Su MY, Lin WP, Chen PC, Chen CH. The outcome assessment of double-balloon enteroscopy for diagnosing and managing patients with obscure gastrointestinal bleeding.Dig Dis Sci. 2007;52:162-166.
Manabe N, Tanaka S, Fukumoto A, Nakao M, Kamino D, Chayama K. Double-balloon enteroscopy in patients with GI bleeding of obscure origin.Gastrointest Endosc. 2006;64:135-140.
Pennazio M. Diagnostic and Therapeutic Utility of Double-Balloon Endoscopy in Small-Bowel Bleeding.Tech Gastrointest Endosc. 2008;10:77-82.
Gay G, Delvaux M, Fassler I. Outcome of capsule endoscopy in determining indication and route for push-and-pull enteroscopy.Endoscopy. 2006;38:49-58.
Hendel JW, Vilmann P, Jensen T. Double-balloon endoscopy: who needs it?Scand J Gastroenterol. 2008;43:363-367.
John S, Appleyard M. Role of double balloon enteroscopy in obscure gastrointestinal bleeding.J Gastroenterol Hepatol. 2008;23:994-996.
May A, Nachbar L, Schneider M, Ell C. Prospective comparison of push enteroscopy and push-and-pull enteroscopy in patients with suspected small-bowel bleeding.Am J Gastroenterol. 2006;101:2016-2024.
Messer I, May A, Manner H, Ell C. Prospective, randomized, single-center trial comparing double-balloon enteroscopy and spiral enteroscopy in patients with suspected small-bowel disorders.Gastrointest Endosc. 2013;77:241-249.
Frieling T, Heise J, Sassenrath W, Hülsdonk A, Kreysel C. Prospective comparison between double-balloon enteroscopy and spiral enteroscopy.Endoscopy. 2010;42:885-888.
Rahmi G, Samaha E, Vahedi K, Ponchon T, Fumex F, Filoche B, Gay G, Delvaux M, Lorenceau-Savale C, Malamut G. Multicenter comparison of double-balloon enteroscopy and spiral enteroscopy.J Gastroenterol Hepatol. 2013;28:992-998.
Swain P, Fritscher-Ravens A. Role of video endoscopy in managing small bowel disease.Gut. 2004;53:1866-1875.
Bonnet S, Douard R, Malamut G, Cellier C, Wind P. Intraoperative enteroscopy in the management of obscure gastrointestinal bleeding.Dig Liver Dis. 2013;45:277-284.
Descamps C, Schmit A, Van Gossum A. “Missed” upper gastrointestinal tract lesions may explain “occult” bleeding.Endoscopy. 1999;31:452-455.
Zuckerman GR, Prakash C. Acute lower intestinal bleeding. Part II: etiology, therapy, and outcomes.Gastrointest Endosc. 1999;49:228-238.
Zaman A, Katon RM. Push enteroscopy for obscure gastrointestinal bleeding yields a high incidence of proximal lesions within reach of a standard endoscope.Gastrointest Endosc. 1998;47:372-376.
Hayat M, Axon AT, O’Mahony S. Diagnostic yield and effect on clinical outcomes of push enteroscopy in suspected small-bowel bleeding.Endoscopy. 2000;32:369-372.
Spiller RC, Parkins RA. Recurrent gastrointestinal bleeding of obscure origin: report of 17 cases and a guide to logical management.Br J Surg. 1983;70:489-493.
Leaper M, Johnston MJ, Barclay M, Dobbs BR, Frizelle FA. Reasons for failure to diagnose colorectal carcinoma at colonoscopy.Endoscopy. 2004;36:499-503.
Huprich JE. Multi-phase CT enterography in obscure GI bleeding.Abdom Imaging. 2009;34:303-309.
Lee SS, Oh TS, Kim HJ, Chung JW, Park SH, Kim AY, Ha HK. Obscure gastrointestinal bleeding: diagnostic performance of multidetector CT enterography.Radiology. 2011;259:739-748.
Hakim FA, Alexander JA, Huprich JE, Grover M, Enders FT. CT-enterography may identify small bowel tumors not detected by capsule endoscopy: eight years experience at Mayo Clinic Rochester.Dig Dis Sci. 2011;56:2914-2919.
Soyer P, Boudiaf M, Fishman EK, Hoeffel C, Dray X, Manfredi R, Marteau P. Imaging of malignant neoplasms of the mesenteric small bowel: new trends and perspectives.Crit Rev Oncol Hematol. 2011;80:10-30.
Filippone A, Cianci R, Milano A, Valeriano S, Di Mizio V, Storto ML. Obscure gastrointestinal bleeding and small bowel pathology: comparison between wireless capsule endoscopy and multidetector-row CT enteroclysis.Abdom Imaging. 2008;33:398-406.
Mazzarolo S, Brady P. Small bowel capsule endoscopy: a systematic review.South Med J. 2007;100:274-280.
García-Compean D, Armenta JA, Marrufo C, Gonzalez JA, Maldonado H. Impact of therapeutic interventions induced by capsule endoscopy on long term outcome in chronic obscure GI bleeding.Gastroenterol Clin Biol. 2007;31:806-811.
Park JJ, Cheon JH, Kim HM, Park HS, Moon CM, Lee JH, Hong SP, Kim TI, Kim WH. Negative capsule endoscopy without subsequent enteroscopy does not predict lower long-term rebleeding rates in patients with obscure GI bleeding.Gastrointest Endosc. 2010;71:990-997.
Viazis N, Papaxoinis K, Vlachogiannakos J, Efthymiou A, Theodoropoulos I, Karamanolis DG. Is there a role for second-look capsule endoscopy in patients with obscure GI bleeding after a nondiagnostic first test?Gastrointest Endosc. 2009;69:850-856.
Hindryckx P, Botelberge T, De Vos M, De Looze D. Clinical impact of capsule endoscopy on further strategy and long-term clinical outcome in patients with obscure bleeding.Gastrointest Endosc. 2008;68:98-104.
Byeon JS, Mann NK, Jamil LH, Lo SK. Is a repeat double balloon endoscopy in the same direction useful in patients with recurrent obscure gastrointestinal bleeding?J Clin Gastroenterol. 2013;47:496-500.
Gerson LB, Batenic MA, Newsom SL, Ross A, Semrad CE. Long-term outcomes after double-balloon enteroscopy for obscure gastrointestinal bleeding.Clin Gastroenterol Hepatol. 2009;7:664-669.
May A, Friesing-Sosnik T, Manner H, Pohl J, Ell C. Long-term outcome after argon plasma coagulation of small-bowel lesions using double-balloon enteroscopy in patients with mid-gastrointestinal bleeding.Endoscopy. 2011;43:759-765.
Landi B, Cellier C, Gaudric M, Demont H, Guimbaud R, Cuillerier E, Couturier D, Barbier JP, Marteau P. Long-term outcome of patients with gastrointestinal bleeding of obscure origin explored by push enteroscopy.Endoscopy. 2002;34:355-359.
Bezet A, Cuillerier E, Landi B, Marteau P, Cellier C. Clinical impact of push enteroscopy in patients with gastrointestinal bleeding of unknown origin.Clin Gastroenterol Hepatol. 2004;2:921-927.
Vakil N, Huilgol V, Khan I. Effect of push enteroscopy on transfusion requirements and quality of life in patients with unexplained gastrointestinal bleeding.Am J Gastroenterol. 1997;92:425-428.
Kendrick ML, Buttar NS, Anderson MA, Lutzke LS, Peia D, Wang KK, Sarr MG. Contribution of intraoperative enteroscopy in the management of obscure gastrointestinal bleeding.J Gastrointest Surg. 2001;5:162-167.