CLINICAL MANAGEMENT. Obscure-Overt Gastrointestinal Bleeding. Clinical Case. Background

Transcription

1 GASTROENTEROLOGY 2005;128: CLINICAL MANAGEMENT Loren Laine, M.D. Clinical Management Editor University of Southern California Los Angeles, California Obscure-Overt Gastrointestinal Bleeding IAN M. GRALNEK David Geffen School of Medicine at University of California Los Angeles, Veterans Affairs Greater Los Angeles Healthcare System, University of California Los Angeles Center for the Study of Digestive Healthcare Quality and Outcomes, Los Angeles, California Clinical Case A 65-year-old man was admitted for recurrent gastrointestinal (GI) bleeding. The patient, passing dark red blood per rectum, was hospitalized 2 months previously at an outside hospital. He required 2 units of packed red blood cells (RBCs), and there was no further evidence of bleeding by the second day of hospitalization. Upper endoscopy, colonoscopy, and upper GI series with small-bowel follow-through (SBFT) radiography were unrevealing. The patient was discharged home on oral iron therapy and was to be observed. He was again admitted with the same symptoms. He denied abdominal pain, GI history other than the recent episode of bleeding, any family history of GI bleeding, use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin, or heavy alcohol use. He had hypertension, for which he takes a thiazide diuretic and an angiotensin-converting enzyme inhibitor. On admission, his blood pressure was 100/80 mm Hg, and his heart rate was 116 bpm. His abdomen was soft, nondistended, and nontender, and he had normal bowel sounds. He had no cutaneous lesions. Within 12 hours, the patient was hemodynamically stable after resuscitation with intravenous fluids and 3 units of packed RBCs. There is no evidence of ongoing overt GI bleeding. Background Obscure GI bleeding is defined as bleeding from an unknown source that persists or recurs after negative diagnostic evaluation. 1,2 A negative diagnostic evaluation is commonly agreed on as consisting of a negative upper endoscopy and colonoscopy, perhaps with the addition of small-bowel radiographic evaluation (eg, SBFT or enteroclysis). For patients who present with persistent or recurrent hematemesis, a rare presentation of obscure GI bleeding, colonoscopy is not part of the initial diagnostic evaluation. 1 Obscure GI bleeding may be subcategorized as occult or overt. Obscure-overt GI bleeding requires persistent or recurrent visible evidence of bleeding per os or per rectum (hematemesis, hematochezia, or melena), whereas obscure-occult GI bleeding is defined as persistently positive fecal occult blood testing, iron deficiency anemia, or both without evidence of gross GI hemorrhage 1,2 (Table 1). This review focuses exclusively on the clinical management of obscure-overt GI bleeding. There are few published data on the natural history of obscure-overt GI bleeding. As was seen with this patient, the great majority of patients with obscure-overt GI bleeding present with visible evidence of bleeding per rectum (melena or hematochezia); hematemesis is rarely a presenting sign. 1 Moreover, it is estimated that up to 5% of patients with overt GI hemorrhage will have negative upper endoscopy and colonoscopy, and, thus, that a small-bowel source will be suspected for their bleeding. As compared with obscure-occult GI bleeding, patients with obscure-overt GI bleeding are more likely to harbor a significant lesion causing their recurrent symptoms and are at higher risk of morbidity and mortality associated with their ongoing bleeding. Thus, it is very important to pursue a careful, regimented workup that leads to a definitive diagnosis. 3,4 These patients are unique and challenging to treat because they often require recurrent hospitalizations, have symptoms of persistent anemia (eg, fatigue, weakness, and dyspnea), undergo repeated diagnostic studies, require multiple blood transfusions, consume increased health care resources, and have their health-related quality of life significantly Abbreviation used in this paper: SBFT, small-bowel follow-through by the American Gastroenterological Association /05/$30.00 doi: /j.gastro

2 May 2005 IAN M. GRALNEK 1425 Table 1. Definitions of GI Bleeding Bleeding term Overt (visible) bleeding Occult bleeding Obscure bleeding Obscure-occult bleeding Obscure-overt bleeding NOTE. Adapted with modifications. 1 Definition GI bleeding manifest as visible red blood or altered blood (eg, coffee-ground emesis, or melena) per os or per rectum Presentation with iron deficiency anemia or positive fecal occult blood test without overt bleeding Persistent or recurrent bleeding with no source identified on initial evaluation with standard endoscopic or radiographic testing Subcategory of obscure bleeding with iron deficiency anemia or positive fecal occult blood test, no overt bleeding, and no source identified with standard endoscopic or radiographic testing Subcategory of obscure bleeding characterized by overt bleeding with no source identified with standard endoscopic or radiographic testing affected. Their diagnosis is often delayed, which may affect their clinical outcome. 1 5 The differential diagnosis of small-bowel hemorrhage, defined as bleeding from a site between the ligament of Treitz and the ileocecal valve, is extensive. The most common etiology for obscure-overt small-bowel bleeding is, far and away, vascular ectasia. Vascular ectasias may be associated with advanced age, chronic renal failure, valvular heart disease, von Willebrand s disease, CREST syndrome (calcinosis cutis, Raynaud s phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia), or the inherited hereditary hemorrhagic telangiectasia syndrome. In addition, small-bowel tumors including GI stromal tumors (eg, leiomyoma or leiomyosarcoma), adenocarcinoma, lymphoma, carcinoid, Kaposi s sarcoma, and metastatic cancers must be considered. Other potential etiologies of small-bowel bleeding include ulcerations or erosions due to Crohn s disease or NSAID use, and less common causes include aortoenteric fistula, Meckel s diverticulum, polyps, and smallbowel varices. Potential Management Strategies To evaluate patients with obscure-overt GI bleeding, several endoscopic, radiographic, and surgical diagnostic modalities are available to the practicing gastroenterologist. Patient Observation Nonspecific measures, including iron-replacement therapy, correction of existing coagulopathies or platelet abnormalities, and intermittent transfusions with packed RBCs as necessary to maintain adequate hemoglobin levels, can be used in selected patients with obscure GI bleeding. 1 However, these nonspecific measures are usually instituted when blood loss is thought to be very slow or to have resolved or when the risk of further interventional diagnostic modalities outweighs the benefit (eg, frail elderly patients with significant medical comorbidities). Little information is available on the safety and efficacy of this strategy. Repeat Upper Endoscopy As previously noted, it is estimated that up to 5% of patients who present with overt GI bleeding will have an initial nondiagnostic upper endoscopy and colonoscopy. Repeat upper endoscopy and colonoscopy may be helpful in identifying lesions potentially overlooked at the time of the initial endoscopic evaluation. Studies evaluating the value of repeat upper endoscopy or push enteroscopy in obscure GI bleeding report finding a source of hemorrhage within reach of a standard gastroscope 0% 75% of the time. 1,4 6 Lesions commonly missed include gastric or duodenal vascular ectasias, Cameron s erosions or ulcers within a hiatal hernia sac, peptic ulcers, malignancy, Dieulafoy s lesions, isolated gastric varices, and gastric antral vascular ectasias ( watermelon stomach ). Push Enteroscopy Push enteroscopy may be performed directly in this clinical situation instead of repeating upper endoscopy. Push enteroscopy permits evaluation of the esophagus, stomach, and duodenum, as well as the proximal jejunum, to approximately cm beyond the ligament of Treitz. Dedicated videoenteroscopes ( cm long) are available, but if these instruments are not available, then a pediatric or standard adult colonoscope can be used instead. Use of an overtube, backloaded onto the endoscope shaft, may help limit looping of the enteroscope within the stomach and facilitate deeper small-bowel intubation. Diagnostic yield is reported to increase with a greater depth of scope insertion. With a pediatric or adult colonoscope, reported diagnostic yields in the evaluation of GI bleeding range from 13% to 38%. With the use of a dedicated videoenteroscope, reported diagnostic yield rates are 26% to 80%. 5 7 With the development of endoscopic accessories for dedicated videoenteroscopes, including biopsy forceps, polyp snares, thermal probes, and injection needles, push enteroscopy is preferred over SBFT or enteroclysis, not only because of better diagnostic accuracy, but also because of the ability to obtain tissue, perform polypec-

3 1426 OBSCURE OVERT GASTROINTESTINAL BLEEDING GASTROENTEROLOGY Vol. 128, No. 5 tomy or hemostasis if necessary, and mark the bleeding location with India ink tattoo However, push enteroscopy does not allow for visualization of the entire small bowel, and complications (eg, perforation and mucosal laceration) have been reported with use of an overtube. With the advent of wireless capsule endoscopy (described later in this review), Sonde enteroscopy is now a historical footnote and should not be considered part of the workup of obscure GI bleeding. Repeat Colonoscopy Repeat colonoscopy with intubation of the ileocecal valve and retrograde examination of the terminal ileum may be performed as part of the evaluation of a patient with obscure-overt GI bleeding unless hematemesis is a presenting symptom. Colonic lesions missed at initial colonoscopy have been reported in up to 3% of patients with obscure GI bleeding. Missed lesions include vascular ectasias, neoplasms, and diverticular disease. Diverticula are very common in elderly patients, and because we rarely see active bleeding emanating from a diverticulum or peridiverticular stigmata of recent hemorrhage (eg, nonbleeding visible vessel), a definitive diagnosis of diverticular hemorrhage is difficult. Documentation of cecal intubation, the quality of the bowel preparation, and whether the terminal ileum was evaluated and commented on at the initial colonoscopy all should be considered when deciding whether to repeat the colonoscopy. Small-Bowel Contrast Radiography An upper GI series with SBFT is often used in evaluating obscure GI bleeding either preceding push enteroscopy or after a negative push enteroscopy examination. SBFT is commonly used because it is simple, readily available, and well tolerated by patients. The problem with SBFT is its poor sensitivity (reported diagnostic yields of 0% 6%) in identifying definitive lesions in obscure bleeding and its inability to diagnose flat mucosal and subepithelial lesions (eg, vascular ectasias). 1,5,6 Small-bowel enteroclysis, a radiographic procedure that involves the instillation of barium, methylcellulose, and air through a nasogastric tube directly into the duodenum, has been shown to have greater diagnostic sensitivity, compared with SBFT, in patients with obscure GI bleeding. However, when enteroclysis is used for the diagnosis of obscure GI bleeding, its yield is still only approximately 10% 25%. 1,2 In addition to its limited diagnostic sensitivity in obscure GI bleeding, enteroclysis can be uncomfortable for the patient (eg, gagging and retching), involves more radiation exposure than SBFT, and is less readily available than SBFT in radiology departments. Nuclear Medicine Tagged Red Blood Cell Scan Tagged RBC scans are safe, are readily available, and may be helpful when there is evidence of active bleeding. The technetium-99m labeled RBC scan is the most common method of radionuclide scanning because the long half-life of technetium allows for delayed scans to be performed for up to 24 hours. However, data on its utility in the evaluation of obscure GI bleeding are quite limited. The overall rate of positive tagged RBC scans for lower GI bleeding is 45% (range, 26% 78%). 1 Early scans (eg, up to 4 hours after injection) may be helpful in gross localization of bleeding when the rate of blood loss exceeds ml/min. 3 There are, however, several shortcomings to delayed tagged RBC scans (eg, scans obtained hours after injection), including pooling of blood in the bowel remote from the actual bleeding site, that may result in a false-positive scan with mistaken localization of bleeding. Moreover, there is also a high rate of false-negative bleeding scans because of the intermittent nature of GI hemorrhage. Because of the high false-positive and -negative rates, assessment with other diagnostic modalities such as angiography, endoscopy, or surgery is necessary after tagged RBC scan. Thus, the utility of tagged RBC scans in the evaluation of patients with obscure-overt GI bleeding is limited, and the test is not generally recommended. Angiography As found with tagged RBC scanning, there are limited data evaluating angiography in the specific clinical setting of obscure GI bleeding. In all patients with acute lower GI bleeding (not just those with obscure GI bleeding), the overall positive yields of angiography range from 27% to 77%. 1 This increases to 61% 72% in patients thought to be actively bleeding, as determined by hemodynamic instability, ongoing blood transfusion requirements, and positive early findings at tagged RBC scan. As compared with tagged RBC scans, mesenteric angiography is more likely to document the specific site of bleeding, yet the rate of bleeding must be 0.5 ml/min, and this technique is more invasive. Angiography also can identify lesions that are not actively bleeding because of demonstration of typical vascular features seen in vascular ectasias (eg, slow-filling vein that persists, vascular tuft seen in the arterial phase of the test, and early-filling vein) and tumors. 1,5,6 Moreover, interventional radiologists are able to administer embolization therapy if an amenable lesion is detected.

4 May 2005 IAN M. GRALNEK 1427 Provocative angiography using anticoagulants, vasodilators, or thrombolytic agents may increase the likelihood that a source of bleeding can be identified and has been advocated by some investigators. A retrospective study reported a doubling in the proportion of patients with extravasation identified at angiography, from 32% to 65%, with the use of provocative agents, although nonbleeding lesions were more commonly identified in the group not given pharmacological agents (40% vs 19%). 11 The risk of inducing uncontrolled bleeding limits this technique. Again, as noted with tagged RBC scans, the utility of mesenteric angiography in the evaluation of patients with obscureovert GI bleeding is limited and not commonly recommended. Meckel s Scan Meckel s diverticulum is the most common congenital anomaly of the gut (1% 3% prevalence in autopsy studies) and results from failure of the vitelline duct to completely obliterate. However, Meckel s diverticulum is a rare presentation of obscure-overt bleeding in adults. Technetium-99m pertechnetate scintigraphy (Meckel s scan) can be used to show heterotopic gastric mucosa in a Meckel s diverticulum. 12 This test has a sensitivity of 75% 100% in children with bleeding. 12 In patients with bleeding because of a Meckel s diverticulum, surgical resection of the diverticulum is the treatment of choice. Capsule Endoscopy Capsule endoscopy is a new technology able to obtain images from the entire small bowel. Because this technology is still very recent, there are limited data, in small numbers of patients, on its effectiveness in evaluating obscure GI bleeding In a prospective study that compared SBFT with capsule endoscopy in a subset of 13 patients with obscure-overt GI bleeding, capsule endoscopy made a definitive diagnosis in 4 (31%), vs 1 (8%) with SBFT. 13 In an uncontrolled pilot study of 21 patients with obscure bleeding (overt, n 9; occult, n 12), Lewis and Swain 14 reported that capsule endoscopy identified a lesion in 7 of 21 (33%) patients with obscure GI bleeding, as compared with 6 of 21 (29%) with push enteroscopy. An additional 4 patients also had fresh blood identified without a bleeding site at capsule endoscopy. 14 Another study of 32 patients with obscure GI bleeding showed superiority of capsule endoscopy over push enteroscopy 15 : the yield of capsule endoscopy was 66%, as compared with 28% with push enteroscopy. Adler et al. 16 reported on 20 patients with obscure GI bleeding (overt, n 11; occult, n 9) and found definitive bleeding sites in 6 of 20 (30%) with capsule endoscopy and 2 of 20 (10%) with push enteroscopy. Finally, a recent study of capsule endoscopy in 100 patients with obscure bleeding identified a positive site of bleeding in 42% of patients. When stratified by type of bleeding, a positive site of bleeding or active bleeding was seen in 24 of 26 (92%) patients with ongoing obscure-overt bleeding, 4 of 31 (13%) patients with obscure-overt bleeding in the past year, and 19 of 43 (44%) patients with obscure-occult bleeding. 17 Therefore, capsule endoscopy seems to have its highest diagnostic yield in patients with ongoing overt GI bleeding. A well-done experimental study using implantable beads in a canine model showed that push enteroscopy performed better than capsule endoscopy in detecting beads within reach of the enteroscope: the sensitivity of push enteroscopy was 94%, vs 53% for capsule endoscopy. 18 However, overall, the sensitivity of capsule endoscopy in detecting beads throughout the small bowel was higher than that of push enteroscopy (64% vs 37%, respectively). There are limitations with capsule endoscopy, including that at the present time neither biopsy, nor hemostatic therapy, nor endoscopic marking (eg, India ink tattoo) is possible, all of the intestinal mucosa is not visualized, luminal debris is not able to be cleared, the capsule s imaging cannot be controlled and is not viewed in real time, not all examinations reach the ileocecal valve, the precise location of lesions cannot be determined, some patients may not be suitable candidates for capsule examination (eg, patients with cardiac pacemakers or defibrillators or those with potential GI tract obstruction), the capsule infrequently does not pass naturally, and a bowel preparation is commonly used. Furthermore, it is unclear how often the results of a capsule endoscopy will alter the subsequent treatment of a patient. In a patient with recurrent, transfusion-requiring, obscure-overt bleeding, intraoperative endoscopy would likely be planned if the capsule endoscopy is negative or if it shows a treatable lesion such as a vascular ectasia or tumor. Identification of a missed lesion within reach of a standard enteroscope amenable to endoscopic therapy would obviate the need for surgery. In addition, identification of a process that does not require surgical or endoscopic therapy might prevent the need for intraoperative endoscopy, although such findings (eg, Crohn s disease or an NSAID ulcer) might still be resected in an otherwise healthy patient who required repeated hospitalizations and transfusions. To obtain an optimal capsule examination, especially when looking for a source of obscure GI bleeding, preparation of the bowel is suggested. We have patients stop any iron supplements for 7 days preceding capsule ex-

5 1428 OBSCURE OVERT GASTROINTESTINAL BLEEDING GASTROENTEROLOGY Vol. 128, No. 5 amination. We then use 2 L of a polyethylene glycol solution the evening before capsule endoscopy and allow nothing by mouth thereafter except for a single 10-mg oral dose of metoclopramide minutes immediately preceding the examination. Simethicone is generally not given. Double-Balloon Enteroscopy Yamamoto et al 19 recently reported on a new insertion technique of enteroscopy, the double-balloon technique, in an attempt to improve on currently available endoscopic insertion methods to evaluate the entire small bowel. Double-balloon enteroscopy uses a dedicated videoendoscope with 2 balloons: one attached to the tip of the endoscope and the other attached at the distal end of a flexible overtube. The balloons grip the wall of the bowel, thus allowing the endoscope to be advanced without looping. The procedure is performed under fluoroscopic guidance. The enteroscope can be performed via an oral or anal approach. Double-balloon enteroscopy has been shown to allow visualization of the entire small bowel and allows for biopsy and therapeutic interventions. 20 At this time, there is very limited clinical experience with this endoscopic technique, and, thus, it is not ready for prime-time use. Ongoing concerns about the endoscopic learning curve, potential need for endoscopy on 2 separate days (oral and then anal route), potential limitations in visualizing the entire small bowel, miss rates for subepithelial lesions due to insufflation issues, potential complications, and the need for anesthesia all require further evaluation before this procedure can be recommended in patients with obscure GI bleeding. Exploratory Laparotomy With Intraoperative Enteroscopy Intraoperative enteroscopy has been used since the 1980s and is an important diagnostic and potentially therapeutic endoscopic modality in suspected smallbowel bleeding. It is considered to be the ultimate endoscopic evaluation of the small bowel. Intraoperative enteroscopy has been reported to identify small-bowel sources of obscure bleeding 50% 100% of the time. 1,5,6,21 Moreover, intraoperative enteroscopy allows for hemostatic therapy, as well as identification of lesions for definitive surgical resection. By use of an orally passed colonoscope or, better yet, a dedicated small-bowel videoenteroscope (eg, 220 cm long), the endoscope is advanced beyond the ligament of Treitz into the proximal jejunum. At that point, the surgeon gently telescopes the small bowel, section by section, over the shaft of the endoscope, with careful inspection of the mucosa. Small-bowel evaluation should be performed in a careful anterograde manner, because telescoping of the small bowel over the endoscope often leads to mucosal trauma (artifacts) that can be confused with vascular ectasias at the time of withdrawal. Dimming the operating room lights facilitates endoscopic visualization, as well as extrinsic examination of the bowel by the surgeon. Lesions identified endoscopically can be marked for resection by the surgeon with a suture on the serosal side of the bowel. After completion of the enteroscopy and withdrawal of the endoscope, the marked sites can be resected. Alternative approaches to intraoperative enteroscopy involve insertion of a sterilized endoscope through a single enterotomy or multiple surgically created enterotomies, rectal insertion, or laparoscopy-assisted enteroscopy. Reported complications associated with intraoperative enteroscopy include mucosal lacerations, perforations, prolonged ileus, abdominal abscess, and bowel ischemia. 1,21 Therefore, because of its invasive nature and potential complications, the decision to perform intraoperative enteroscopy must not be taken lightly. All risks and benefits need to be fully considered, and this procedure should be performed only by experienced endoscopists and surgeons. Intraoperative enteroscopy should be considered in a patient whose bleeding source has not been identified after extensive evaluation, when there is an ongoing requirement for blood transfusions, or when the risk of continued bleeding outweighs the risk of laparotomy. 6 Recommended Management Strategy A recommended management strategy for this case is summarized in Figure 1. The patient in the case outlined previously has now been readmitted to the hospital with recurrent overt GI bleeding and has required repeat blood transfusions. The findings from the previous esophagogastroduodenoscopy, colonoscopy, and SBFT were reviewed. At the time of previous colonoscopy, there was a moderate amount of liquid brown stool in the cecum and ascending colon that limited visibility, and there was no documentation that the terminal ileum had been intubated. My recommended management strategy to further evaluate this patient with obscureovert GI bleeding would be to go directly to push enteroscopy, ideally with a dedicated videoenteroscope, followed by repeat colonoscopy with retrograde examination of the terminal ileum if enteroscopy is unremarkable for a definitive cause of bleeding. These 2 procedures can be performed at the same time to minimize patient

6 May 2005 IAN M. GRALNEK 1429 ligament of Treitz. The examination, including careful evaluation of the GI tract proximal to the ligament of Treitz, did not identify any etiology for recurrent hemorrhage. The patient also underwent repeat colonoscopy with retrograde examination of the terminal ileum, which was normal. No blood was found in the colon or terminal ileum. The patient had no further bleeding while in the hospital, his hemoglobin stabilized, and he was discharged home again without a definitive diagnosis. The patient had capsule endoscopy performed as an outpatient several days after hospital discharge that showed a possible ulcerated mass lesion in the distal jejunum vs the proximal ileum. The patient then underwent an intraoperative enteroscopy in which a 1.5-cm mass lesion with an ulcerated area oozing blood was discovered. This area was surgically resected, including sampling of the surrounding lymph nodes. Histopathology was consistent with carcinoid tumor, without evidence of metastatic disease. The patient has done well since then, with no further episodes of GI bleeding and with a stable hemoglobin. Figure 1. Recommended management strategy for patients with recurrent obscure-overt GI bleeding. EGD, esophagogastroduodenoscopy. exposure to conscious sedation. If these endoscopic examinations are inconclusive for determining a source of bleeding, then the patient should undergo capsule endoscopy. Tagged RBC scanning and mesenteric angiography are unlikely to be useful here because this patient was hemodynamically stable and not thought to be actively bleeding at the time of presentation and because the overall diagnostic yield with these interventions is limited. If capsule endoscopy is negative, I would then proceed to intraoperative enteroscopy because this patient has recurrent overt bleeding, required rehospitalization, and needed repeat blood transfusions. Some would consider a Meckel s scan, although very low yield, before surgery, because of its ease and safety, and, even if there is no active bleeding, an angiography also may be considered to look for evidence of vascular ectasias or tumors. These patients require aggressive diagnostic evaluation, because they usually harbor a definitive cause for their bleeding, and delayed diagnosis can lead to increased morbidity and mortality. Evolution of the Case During hospitalization, the patient underwent push enteroscopy with a dedicated 220-cm small-bowel videoenteroscope to approximately 90 cm beyond the Conclusions Obscure GI bleeding is defined as bleeding from an unknown source that persists or recurs after negative diagnostic evaluation and may be further subcategorized as occult or overt. It is estimated that up to 5% of patients with overt GI hemorrhage will have negative upper endoscopy and colonoscopy and therefore be suspected of a small-bowel source for their bleeding. As compared with obscure-occult GI bleeding, patients with obscure-overt GI bleeding are more likely to harbor a significant lesion causing their recurrent symptoms and are at higher risk of morbidity and mortality associated with their ongoing bleeding. Thus, these patients are unique and challenging to the gastroenterologist, and it is important to pursue a regimented workup that will lead to a definitive diagnosis. Although there is no single uniform diagnostic approach to the patient with obscure GI bleeding, a careful sequential workup that includes push enteroscopy, repeat colonoscopy with retrograde evaluation of the terminal ileum, capsule endoscopy, and possible exploratory laparotomy with intraoperative endoscopy is often warranted. Upper GI series with SBFT, enteroclysis, tagged RBC scan, Meckel s scan, and mesenteric angiography have a limited role in the diagnostic evaluation of obscure GI bleeding. Finally, future technological advances such as double-balloon enteroscopy remain to be fully evaluated, and their future place in the diagnostic algorithm of obscure GI bleeding is unclear.

7 1430 OBSCURE OVERT GASTROINTESTINAL BLEEDING GASTROENTEROLOGY Vol. 128, No. 5 References 1. Zuckerman GR, Prakash C, Askin MP, Lewis BS. AGA technical review on the evaluation and management of occult and obscure gastrointestinal bleeding. Gastroenterology 2000;118: Mitchell SH, Schaefer DC, Dubagunta S. A new view of occult and obscure gastrointestinal bleeding. Am Fam Physician 2004;69: Dulai G, Jensen D. Severe GI bleeding of obscure origin. Gastrointest Endosc Clin North Am 2004;14: Dulai G, Jensen D, Cave D, Bini E, Kimmey M, Farris K, Gerson L. Diagnostic yield of capsule endoscopy in patients with recurrent, overt GI bleeding of obscure origin (abstr). J Invest Med 2003; 51(Suppl 2):S Lewis B, Goldfarb N. Review article: the advent of capsule endoscopy a not so-futuristic approach to obscure gastrointestinal bleeding. Aliment Pharmacol Ther 2003;17: Kovacs TO, Jensen DM. Recent advances in the endoscopic diagnosis and therapy of upper gastrointestinal, small intestinal and colonic bleeding. Med Clin North Am 2002;86: Eisen GM, Dominitz JA, Faigel DO. Enteroscopy. Gastrointest Endosc 2001;53: Taylor ACF, Buttigieg RJ, McDonald IG, Desmond PV. Prospective assessment of the diagnostic and therapeutic impact of smallbowel push enteroscopy. Endoscopy 2003;35: Pennazio M. Small-bowel endoscopy. Endoscopy 2004;36: 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: Koval G, Benner KG, Rosch J, Kozak BE. Aggressive angiographic diagnosis in acute lower gastrointestinal hemorrhage. Dig Dis Sci 1987;32: Gralnek IM, Jensen DM. Lower gastrointestinal tract bleeding. In: McNally PR, ed. GI/liver secrets. 2nd ed. Philadelphia: Hanley & Belfus, 2001: Costamagna G, Shah S, Riccioni M, et al. A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease. Gastroenterology 2002;123: Lewis B, Swain P. Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: results of a pilot study. Gastrointest Endosc 2002;56: Ell C, Remke S, May A, et al. The first prospective controlled trial comparing wireless capsule endoscopy with push enteroscopy in chronic gastrointestinal bleeding. Endoscopy 2002;34: Adler DG, Knipschield M, Gostout C. A prospective comparison of capsule endoscopy and push enteroscopy in patients with GI bleeding of obscure origin. Gastrointest Endosc 2004;59: 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: Appleyard M, Fireman Z, Glukhovsky A, Jacob H, Shreiver R, Kadirkamanathian S, Lavy A, Lewkowicz S, Scapa E, Shofti R, Swain P, Zaretsky A. A randomized trial comparing wireless capsule endoscopy with push enteroscopy for the detection of smallbowel lesions. Gastroenterology 2000;119: Yamamoto H, Sekine Y, Sato Y, Toshihiko H, Miyata T, Lino S, Ido K, Sugano K, et al. Total enteroscopy with a nonsurgical steerable double-balloon method. Gastrointest Endosc 2001;53: Ohmiya N, Taguchi A, Shirai K, Mabuchi N, Arakawa D, Kanazawa H, Ozeki M, Yamada M, Nakamura M, Itoh A, Hirooka Y, Niwa Y, Nagasaka T, Ito M, Ohashi S, Okamura S, Goto H. Endoscopic resection of Peutz-Jeghers polyps throughout the small intestine at double-balloon enteroscopy without laparotomy. Gastrointest Endosc 2005;61: Zaman A, Sheppard B, Katon RM. Total peroral intraoperative enteroscopy for obscure GI bleeding using a dedicated push enteroscope: diagnostic yield and patient outcome. Gastrointest Endosc 1999;50: Address requests for reprints to: Ian M. Gralnek, MD, MSHS, Wilshire Blvd, CURE Bldg 115, Room 215, Los Angeles, California igralnek@mednet.ucla.edu; fax: (310)