Cost-effectiveness analysis of management strategies for obscure GI bleeding

ORIGINAL ARTICLE: Clinical Endoscopy

Cost-effectiveness analysis of management strategiesfor obscure GI bleeding

Lauren Gerson, MD, MSc, Ahmad Kamal, MD, MSc

Stanford, California, USA

Background and Aims: Of patients who are seen with GI hemorrhage, approximately 5% will have a small-bowel source. Management of these patients entails considerable expense. We performed a decision analysisto explore the optimal management strategy for obscure GI hemorrhage.

Methods: We used a cost-effectiveness analysis to compare no therapy (reference arm) to 5 competing modal-ities for a 50-year-old patient with obscure overt bleeding: (1) push enteroscopy, (2) intraoperative enteroscopy,(3) angiography, (4) initial anterograde double-balloon enteroscopy (DBE) followed by retrograde DBE if thepatient had ongoing bleeding, and (5) small-bowel capsule endoscopy (CE) followed by DBE guided by theCE findings. The model included prevalence rates for small-bowel lesions, sensitivity for each intervention,and the probability of spontaneous bleeding cessation. We examined total costs and quality-adjusted life years(QALY) over a 1-year time period.

Results: An initial DBE was the most cost-effective approach. The no-therapy arm cost $532 and was associatedwith 0.870 QALYs compared with $2407 and 0.956 QALYs for the DBE approach, which resulted in an incremen-tal cost-effectiveness ratio of $20,833 per QALY gained. Compared to the DBE approach, an initial CE was morecostly and less effective. The initial DBE arm resulted in an 86% bleeding cessation rate compared to 76% for theCE arm and 59% for the no-therapy arm. The model results were robust to a wide range of sensitivity analyses.

Limitations: The short time horizon of the model, because of the lack of long-term data about the naturalhistory of rebleeding from small-intestinal lesions.

Conclusions: An initial DBE is a cost-effective approach for patients with obscure bleeding. However, capsule-directed DBE may be associated with better long-term outcomes because of the potential for fewer complica-tions and decreased utilization of endoscopic resources. (Gastrointest Endosc 2008;68:920-36.)

Approximately 5% of patients who are seen with GIhemorrhage have no source found by an upper endos-copy and a colonoscopy.1 In approximately 75% of thesepatients, responsible lesions can be detected in thesmall bowel.2-4 Small-bowel arteriovenous malformations(AVMs) are the most common finding in 20% to 40% of pa-tients who are seen with obscure overt bleeding (defined asthe presence of recurrent melena or hematochezia withnormal evaluation by upper endoscopy and colonoscopy).5

Other potential causes of bleeding, in order of frequency,include ulcerations; primary or metastatic tumors and

Abbreviations: AVM, arteriovenous malformation; CE, capsule endos-

copy; CPT, current procedural terminology code; DBE, double-balloon

enteroscopy; ICER, incremental cost-effectiveness ratio; QALY, quality-

adjusted life year; QOL, quality of life; RBC, red blood cell.

Copyright ª 2008 by the American Society for Gastrointestinal Endoscopy

0016-5107/$34.00

doi:10.1016/j.gie.2008.01.035

920 GASTROINTESTINAL ENDOSCOPY Volume 68, No. 5 : 2008

vascular lesions, including Dieulafoy’s lesions; or hemor-rhage associated with portal hypertension. The natural his-tory of bleeding from AVMs remains poorly understood.There appears to be a spontaneous cessation rate fromAVMs of approximately 40% per year.6,7

Current options for the diagnosis and managementof small-bowel lesions include push enteroscopy, capsuleendoscopy (CE), intraoperative enteroscopy, and double-balloon enteroscopy (DBE). Sonde enteroscopy, a tech-nique that involves the peroral placement of a long(3 m) enteroscope, with a distal balloon that is propelledby peristaltic activity into the distal small bowel has beenlargely abandoned because of the long duration of the ex-amination (mean 7 hours), patient discomfort, the needfor additional endoscopy staff, and the inability to performtherapeutic procedures.8 The diagnostic yield of push en-teroscopy in patients with obscure overt bleeding rangesfrom 3% to 70%, with AVMs as the most common lesionsidentified in 7% to 60% of examinations.2,9,10 Although

www.giejournal.org

Gerson & Kamal Management strategies for obscure GI bleeding

a CE does not offer therapeutic potential for small-bowellesions, multiple studies to date demonstrated a 25% to55% higher diagnostic yield of CE compared with push en-teroscopy in patients who were seen with obscure GIhemorrhage.11,12 Intraoperative enteroscopy, which in-volved the insertion of an endoscope through an incisionin the mid small intestine (enterotomy), is associated witha diagnostic yield between 58% and 84%.13,14 Although thesuccess rate of reaching the ileum approaches 90%, theuse of intraoperative enteroscopy does not appear to beassociated with lower rates of recurrent GI bleeding andcarries a significant risk for postoperative complications,including mortality in up to 2% to 4% of cases. DBE, firstdescribed by Yamamoto et al15 in 2001, allows completevisualization of the small intestine by using a 200-cm en-teroscope (Fujinon Inc, Saitama, Japan) equipped witha 140-cm overtube. In the major studies published onDBE to date, obscure bleeding was the indication forthe DBE in approximately 36% to 100% of examinations,and the overall diagnostic yield from DBE ranged from43% to 80%.16-18 Diagnostic or therapeutic success wasreached in 55% to 75% of examinations, comparablewith other diagnostic modalities for the small bowel.

Recently, the International Conference on Capsule En-doscopy produced a consensus statement on obscure GIbleeding and concluded that ‘‘capsule endoscopy wasthe preferred test for mucosal imaging of the entire smallintestine and should be part of the initial evaluation in pa-tients with obscure bleeding.’’19 The proposed algorithmfrom this consensus conference proposed an initial CE fol-lowed by other potential diagnostic tests, including a DBE,angiography, or intraoperative enteroscopy, if there werepositive findings on a CE. Although a CE allows for visual-ization of the entire small bowel in a noninvasive fashion,disadvantages associated with the use of a CE include thepotential for missed lesions20 and an inability to performtherapeutic intervention. We, therefore, used decisionanalysis to estimate the potential cost-effectiveness of aninitial CE compared with other diagnostic modalities,including DBE, push enteroscopy, angiography, or intrao-perative enteroscopy, for patients with bleeding fromsmall-bowel lesions.

PATIENTS AND METHODS

Cost-effectiveness analysis is a quantitative methodused to evaluate the outcomes and costs of interventionsdesigned to improve health.21 We used decision analysissoftware (TreeAge Pro 2005 Suite; TreeAge Software, Bos-ton, Mass) to create a decision tree to compare no therapy(reference arm) to 5 competing modalities for a 50-year-old patient with obscure overt bleeding: (1) push entero-scopy, (2) intraoperative enteroscopy, (3) angiography, (4)initial anterograde DBE, followed by a retrograde DBE ifthe patient had ongoing bleeding, and (5) small-bowel

www.giejournal.org

Capsule Summary

What is already known on this topic

d Double balloon enteroscopy (DBE) allows for diagnosticimaging and endoscopic therapy in the small bowel butis time consuming and expensive.

What this study adds to our knowledge

d In a decision analysis that compared the cost-effectiveness of an initial DBE to other imagingmodalities for obscure bleeding, the DBE approach wasa cost-effective approach, but an initial capsuleendoscopy reduced the number of DBE procedures andhad fewer associated complications.

CE followed by a DBE guided by the CE findings. Patientsin the CE arm would only proceed to a DBE if they hadpersistent obscure bleeding after the CE examination.Patients with normal CE examinations and ongoing GIhemorrhage would undergo an initial anterograde DBE,with the assumption that a lesion might have been missedon the prior CE examination. We performed our analysisfrom a third-party–payer perspective over a 1-year timehorizon by using 1-month cycles for probabilities of hem-orrhage, bleeding cessation, and alterations in health-related quality of life (QOL).

Base-case patientThe base-case patient was a 50-year-old man with

a 6-month history of recurrent melena and associatediron-deficiency anemia. The patient had a prior normal up-per endoscopic examination, including retroflexed views ofthe gastric cardia and the fundus, a colonoscopy, anda small-bowel series. He required approximately 2 unitsof packed red blood cells (RBC) per month for ongoingGI bleeding. He denied the use of aspirin, nonsteroidalanti-inflammatory agents, or warfarin. There was no per-sonal history of malignancy or prior surgeries, except fora routine appendectomy. The patient was considered tobe a candidate for a CE, as well as endoscopic or surgicaltherapy, for presumed small-bowel sources of the bleeding.

Competing strategiesA truncated version of the decision tree is depicted in

Figure 1. A patient who is seen with obscure GI bleedingwould initially undergo a diagnostic upper endoscopy,a colonoscopy, and a small-bowel series that would benondiagnostic for a potential bleeding source. Obscurebleeding would continue, and the patient would thenenter the decision tree, at which time the followingtherapeutic options outlined above could be undertaken.We did not model the possibility of obtaining additionaldiagnostic or therapeutic interventions if the patient con-tinued to bleed after an initial procedure. The exception

Volume 68, No. 5 : 2008 GASTROINTESTINAL ENDOSCOPY 921

Management strategies for obscure GI bleeding Gerson & Kamal

Figure 1. The model schema. Patients with small-intestinal bleeding from AVMs may enter the no-therapy arm (supportive blood transfusions, refer-

ence arm) or 1 of 5 treatment arms, including push enteroscopy, intraoperative enteroscopy, angiography, initial oral DBE, or CE followed by DBE if

patients continued to bleed after CE. Patients with normal capsule examinations and who were ongoing bleeding underwent subsequent anterograde

DBE. For each arm, the probability of spontaneous cessation, cessation after endoscopic therapy, and procedural complications were modeled.

to this was in the CE arm, in which patients who hadpositive findings on a CE and ongoing bleeding wouldproceed to DBE examination, with the route determinedby the location of the lesion during the CE. A DBEwould subsequently be performed by the opposite ap-proach only if the patient had persistent bleeding afterthe initial DBE. Our model assumed that there couldbe single or multiple small-bowel lesions and that the di-agnostic test would locate and treat multiple lesions ifpresent in the area of small bowel examined. For exam-ple, we modeled the probability that patients could con-tinue to bleed from distal AVMs after an anterogradeDBE located and treated multiple proximal small-bowellesions.

After each intervention, we modeled the probability ofcessation or continuation of bleeding after endoscopictherapy as shown by a circular ‘‘chance node.’’ Patientswho were undergoing diagnostic and potentially thera-peutic procedures were also modeled to sustain a chanceof complication related to the intervention, includinghemorrhage, perforation, and/or death from the complica-tion. Patients with lesions missed by the examination weremodeled to have either spontaneous cessation of bleedingfrom the lesion or ongoing GI hemorrhage that resulted inongoing transfusions and a possibility of death fromongoing hemorrhage (Fig. 2). We did not model repeatedor alternative procedures if the patients continued to ex-perience GI bleeding.


Potential lesions in the small bowel that accounted forbleeding included AVMs (prevalence of 40%), ulcerations(20%), neoplasms (5%), and other vascular lesions(20%), including Dieulafoy’s lesions of the small bowel.We also assumed that 15% of the patients would havemissed lesions in the stomach or the colon, including Ca-meron’s lesions, gastric antral vascular ectasia, and AVMsof the colon and/or malignancies. For each of theselesions, we modeled the prevalence of each lesion andthe sensitivity of each intervention for the diagnosis ofthe lesion based on a comprehensive literature review.Given the limitations of the published literature, weassumed 100% specificity for each test.

Limited long-term data exist about the recurrence ofAVMs after therapeutic intervention and rates of spontane-ous cessation for these lesions over time. We, therefore,limited our analysis to a 1-year time horizon based onthe current evidence from the available medical literature.

No-therapy armWe modeled that patients in the no-therapy arm would

not undergo any endoscopic interventions. AVMs areectatic blood vessels that consist of thin walls with orwithout endothelial lining. The factors that trigger bleed-ing from AVMs and the natural history of vascular lesionsin the small bowel have not been well characterized. Esti-mates about the spontaneous cessation rate were de-rived primarily from clinical trials that compared

www.giejournal.org


Patients Without Bleeding Patients With Obscure Bleeding

Intervention

Death

Complication

Surgery

Figure 2. A Markov state diagram for patients with obscure GI bleeding. Patients enter the model with obscure bleeding. During each 3-month cycle,

patients can either remain in a state of bleeding (recursive arrow) or progress to a new health state, as demonstrated by a straight arrow. Patients may

stop bleeding spontaneously or via an endoscopic or surgical intervention. Transition rates between health states were derived from the literature (see

Table 1).

hormonal therapy with a placebo for the treatment ofAVMs in the GI tract. The spontaneous cessation ratein these patients was reported to range from 40% to50% per year (Table 1).6,7 For example, in a 1992 studyby Lewis et al,7 44% of 34 patients with small bowelAVMs who were untreated did not receive any transfu-sions over a mean follow-up period of 13.4 months.We, therefore, assumed that the rate of spontaneous ces-sation of bleeding from AVMs would be 45% per year. Wemodeled that patients enrolled in the no-therapy armwould receive approximately 2 units of packed RBCsper month. This estimate was based on data froma 1996 retrospective study,22 in which 83 patients whohad GI bleeding from small-bowel AVMs demonstratedon both push enteroscopy and Sonde enteroscopywere observed for outcomes after their examinations.Of these patients, 55 (66%) underwent electrocauteryof their AVMs, whereas 28 (34%) received only medicaltherapy. Follow-up assessments of these patientsrevealed that, over a mean (�SD) of 26 months, thenoncauterized group continued to bleed, which required2.2 � 3.9 units of packed RBC per month, which did notchange significantly after diagnosis, whereas the cauter-ized group significantly improved from 2.4 � 3 unitsper month pretreatment to 0.32 � 0.91 units per monthafter cauterization (P ! .001). There has been a paucity

www.giejournal.org

of published literature about the natural history of bleed-ing from small-bowel AVMs in patients who do not re-ceive endoscopic or medical therapy. We did not modelthe administration of medical therapy for the treatmentof AVMs, because studies to date have not demonstratedbenefit of hormonal therapy compared with a placebo.23

Although there is likely to be formation of additionalAVMs over time, we did not model this occurrence be-cause of the short time horizon of 1 year and the factthat no data are available about the rate of thisphenomenon.

For patients with small-bowel ulcerations, we assumedthat these patients would receive 8 weeks of proton pumpinhibitor therapy and that most of the lesions would becaused by aspirin or other anti-inflammatory agents.24

We did not model the possibility or treatment of infectiousetiologies (such as tuberculosis) as an etiology for small-bowel ulcerations. We also did not model the probabilityor management of ulcerations that were caused by inflam-matory bowel disease.

Based on a prospective study by Lai et al,25 in 2006, inwhich 49 patients were observed for 19 months after a CEwas performed for obscure bleeding, we modeled that therebleeding rate would approximate 25% for small-bowelulcerations and 50% for patients with active bleedingseen without an identifiable cause (most likely vascular



TABLE 1. Baseline probabilities for the model*

Probability Base-case estimate Range in sensitivity analysis Sensitivity Reference

Findings in patients with obscure GI

bleeding*

AVM

Overall prevalence 40% 20%-60%

Detection rates

Push enteroscopy 18% 4%-49% 45% 2-4,9-12,28-42

Intraoperative enteroscopy 36% 19%-48% 90% 13,14,30,53-57,84

Angiography 15% 10%-52% 38% 59,60,85

DBE 33% 5%-56% 83% 24,66,67

CE 35% 16%-64% 87% 56,66,67

Probability that AVM will be within reach

of DBE anterograde approach

80% 50%-100% 24

Malignancy



Angiography 4% 4%-10% 45%, 78% 61,86,87

Intraoperative enteroscopy 5% 7%-17% 100% 13,14,30,53-57

CE 4% 0%-13% 80% 11,12,35,36,38,41-43,56,61

DBE 4% 4%-20% 80% 24,67,81,88-90

Ulcerations



Angiography 4% 0%-6% 20%, 60% 61,86,87


CE 11% 5%-26% 55% 11,12,35,36,38,41-43,56,61

DBE 13% 0%-56% 65% 24,67,81,88-90

Other vascular lesions

Prevalence 20% 0%-20%


Angiography 6% 0%-43% 30% 61,86,87


CE 10% 0%-40% 50% 11,12,35,36,38,41-43,56,61

DBE 10% 0%-19% 50% 13,14,30,53-57

Missed lesions on upper or lower

endoscopyy15% 5%-20% 44,91,92

(continued on next page)

924 GASTROINTESTINAL ENDOSCOPY Volume 68, No. 5 : 2008 www.giejournal.org


TABLE 1 (continued )

Probability Base-case estimate Range in sensitivity analysis Sensitivity Reference

Rebleeding rates

Without endoscopic therapy

AVM 0.55 0.22-0.80 25,38,46

Ulceration 0.25 0.10-0.40 25

Tumor 0.90 0.0-0.10 25

Other, including vascular 0.50 0.25-0.80 25,46

Spontaneous cessation rate bleeding

AVMs

0.45 0.10-0.80 6,7

Postendoscopic therapy

AVM 0.20 0.10-0.40 25,46

Ulceration 0.10 0.05-0.25 93-95

Other vascular lesions 0.25 0.0-0.50 96-99

Complication rates

Mortality, GI hemorrhage 0.10 0.04-0.45 100-102

Complication after endoscopyz 0.0001 0.0013-0.000009 7,12,28,29

Complication after DBEz 0.02 0.002-0.02 65

Retention after CE 0.01 0-0.21 42,103-106

Success in capsule retrieval by DBE after

retention

0.50 0.25-0.75 71,72

Mortality after endoscopic complication 0.00005 0.000021-0.00009 7,12,28,29

Morbidity after intraoperative

enteroscopy

0.20 0.01-0.57 13,14,30,53-57

Mortality after intraoperative

enteroscopy

0.05 0-0.20 13,14,30,53-57

Complication after angiography 0.05 0.01-0.20 62,63

Mortality after angiography 0.0005 0.0002-0.0010 62,63

QOL estimates

No bleeding 1.0 0.9-1.0 Definition

GI hemorrhage 0.80 0.70-1.0 75,76

Hospitalization 0.75 0.40-0.81 77,78

Return to normal QOL after bleeding

cessation

1 mo 0-3 mo Expert opinion

Return to normal QOL after perforation 3 mo 0-6 mo 79

xIncludes reported cases of perforation after DBE; pancreatitis and abdominal pain were not included.*Includes weighted averages from the literature. See

Patients and Methods section for more details.

yIncludes missed lesions found in the upper-GI tract that would be in reach of a standard endoscope, including AVMs, ulcerations, hiatal hernia with

ulcerations (Cameron’s erosions), and other vascular lesions (Dieulafoy’s lesions); missed lesions in the colon, including diverticula, AVMs, and other vascular

lesions; and lesions in the small bowel, including Dieulafoy’s lesions, diverticula, radiation enteritis, or vasculitis. We assumed that both a push enteroscopy and

a DBE would be 75% effective in identification and treatment of missed lesions. CE and angiography would detect missed lesions 50% of the time, whereas

they would not be detected during intraoperative enteroscopy.

zComplications after a push enteroscopy or a DBE, including perforation, hemorrhage, cardiopulmonary complications, and adverse effects caused by

medication.

www.giejournal.org Volume 68, No. 5 : 2008 GASTROINTESTINAL ENDOSCOPY 925


lesions) and that there would not be any rebleeding fortumors that were identified and resected.

Push enteroscopyVideo push enteroscopy, by using adult or pediatric

colonoscopes, is commonly used in the diagnosis andmanagement of obscure bleeding. Dedicated push entero-scopes were developed with working lengths of 220 to250 cm. For patients enrolled in the push enteroscopyarm, we assumed that push enteroscopy, by using a tradi-tional small-bowel video enteroscope, would be perfor-med with the patient under conscious sedation. Weassumed that the extent of the examination would be 50to 150 cm of visualized small bowel distal to the proximalduodenum and that an overtube would be used, based ondata that the use of an overtube to prevent looping corre-lates with significantly greater depth of insertion in 2 case-control studies.26,27

Although the overall yield for any pathologic lesions inpatients with obscure overt bleeding ranges from 3% to70% on push enteroscopy, we calculated, by usingweighted averages from prior clinical trials, that AVMswould be identified in approximately 18% of push enteros-copies.2-4,9-12,28-43 Once AVMs were identified, endoscopictherapy would be administered. We assumed that the effi-cacy for endoscopic treatment would be equivalent, re-gardless of whether ablation occurred when usingelectrocoagulation, laser therapy, or argon plasma coagu-lation.9,28,29,31,32,39-42,44,45 We modeled that cessation ofbleeding would be associated with improved patient out-comes, including a decreased probability of death fromhemorrhage and a decreased cost associated with transfu-sions. To calculate the probability that a patient wouldstop bleeding after a push enteroscopy, we used informa-tion from clinical trials of endoscopic therapy for small-bowel lesions and cessation rates.9,28,29,31,32,39-42,44,45

Based on the literature, we modeled that there wouldbe a 20% rebleeding rate in a patient who received endo-scopic therapy for AVMs, whereas AVMs that were nottreated would have a rebleeding rate of 55%.25,46 Wealso modeled that bleeding AVMs that were not treatedwould have a spontaneous cessation rate of 45%.6,7

The model included the possibility of a complicationassociated with push endoscopy of approximately 1 per10,000 examinations,47 with an associated mortality of0.005%. We assumed that a perforation that required sur-gical repair would occur in 50% of the patients witha complication and that hemorrhage that required hospi-talization with emergent endoscopic examination wouldoccur in the remaining 50% of patients.48,49 We assumedthat all patients with complications would present within1 to 7 days after the endoscopic procedure.48

Intraoperative enteroscopyIntraoperative enteroscopy, which involves insertion of

an endoscope through an incision in the mid small intes-


tine (enterotomy), was initially performed in the 1950swith a sterile rigid sigmoidoscope50 and then, in the1970s, with fiberoptic endoscopes.51 In the 1980s, intrao-perative enteroscopy was subsequently performed bypassing a fiberoptic colonoscope first orally and thenanally while the surgeon would manually telescope thebowel over the tip of the endoscope,30,52 which allowedpassage of the enteroscope to the terminal ileum in themajority of cases, while decreasing morbidity associatedwith an enterotomy.

Traditionally, the criterion standard for comparison ofthe efficacy of an intraoperative enteroscopy was surgicalresection, with histopathologic documentation of the pa-thology. For patients with GI bleeding of obscure origin,the overall diagnostic yield of intraoperative enteroscopywas between 58% and 84%.13,14,30,53-57 The performancecharacteristics for intraoperative enteroscopy are shownin Table 1. By using weighted probabilities from prior stud-ies, we calculated that the prevalence of AVMs was approx-imately 36% on an intraoperative enteroscopy, witha sensitivity of 90%. The study by Hartmann et al56 com-pared a CE with an intraoperative enteroscopy in 47 pa-tients. A CE detected definitive multiple or bleedingangiectasias in 22 of 47 patients (47%). An intraoperativeenteroscopy confirmed AVMs in all of these patients(100%). One patient had an AVM found on intraoperativeenteroscopy that was not seen on CE. Based on the litera-ture, intraoperative enteroscopy had the lowest miss ratefor small-bowel lesions compared with the other diagnosticmodalities (Table 1). The calculated postoperative morbid-ity rate associated with an intraoperative enteroscopy was20%, with a mortality rate of 5%.13,14,30,53-57

AngiographyAngiographic therapy is most successful when patients

have acutely bleeding lesions and are bleeding at least 1.0mL/min. Tagged RBC scans are usually initially attempted,because detection of bleeding sites can occur with bleed-ing rates of 5 mL/min. Because our base-case patient hadobscure bleeding, we did not model initial testing withtagged RBC scans but instead proceeded directly to selec-tive mesenteric angiographic examination, and we as-sumed that a detected lesion would be treated withselective embolotherapy with either microcoils, gelatinsponge pledgets, or polyvinyl alcohol embolospheres.58

To identify the probability of finding a known AVM whenusing angiography, we examined prior studies in whichsubsequent surgical resection was the criterion standard.Because most of these prior studies included small num-bers of patients, we used weighted averages to obtainour base-case probability. Based on these studies, the abil-ity of angiography to detect AVMs ranged from 10% to52%, with a weighted average of 20%.59,60 An angiographyhad a lower detection rate for AVMs compared with a CE,DBE, and intraoperative enteroscopy, and, similarly,a higher miss rate for other small-bowel lesions that

www.giejournal.org


TABLE 2. Published studies of DBE in patients with obscure GI bleeding

Study

Patients with bleeding/DBE

examinations

Diagnostic

yield (%)

Diagnostic or treatment

success (%)

Total

DBE(%)*

Rebleed

rate Complications

Yamamoto et al,90

2004

66/178 (37%) 76 61 86 N/A Perforation: 1 (0.6%)

May et al,81 2005 90/248 (36%) 80 76 35 N/A None

Ell et al,17 2005 64/147 (44%) 72 62 16 N/A None

Di Caro et al,88 2005 33/89 (37%) 80 42 44 N/A None

Mehdizadeh et al,66

2006

130/237 (55%) 43 60 0 N/A Perforation: 1 (0.4%)

Hadithi et al,67 2006 35/35 (100%) 60 77 20 20% None

Heine et al,24 2006 168/275 (61%) 73 55 42 N/A Pancreatitis: 3 (1%)

Kaffes et al,89 2006 32/40 (80%) 48 75 0 N/A Perforation: 1 (2.5%)

Monkemuller et al,18

2006

29/70 (41%) 67 57 30 0% Polypectomy bleed:

1 (1.4%)

Manabe et al,107

2006

31/31 (100%) 74 74 29 0% None

Nakamura et al,108

2006

28/28 (100%) 41 43 63 6% Perforation: 1 (3.6%)

Akahoshi et al,109

2006

20/103 (19%) 43 43 40 N/A None

Totalsy 726 Patients; 1481

examinations

63 60 34 Perforation: 4 (0.3%);

pancreatitis: 3 (0.2%)

N/A, Not available.

*Defined as initial DBE in one direction, with a tattoo at the most distal insertion point, followed by a DBE from the opposite direction with the prior tattoo site

identified.

yCalculated averages for diagnostic yield, treatment success, and total DBE rates.

were not actively bleeding.61 The complication rate froman angiography, including access-site thrombosis or hem-orrhage, contrast reactions, and injury to the target ves-sels, specifically, the superior mesenteric artery, inferiormesenteric artery, and celiac artery, including dissectionand distal embolization, approximates 5%, althoughsome centers reported rates as high as 11%.62,63

DBEDBE, first described by Yamamoto et al15 in 2001, allows

complete visualization of the small intestine by usinga 200-mL enteroscope with an outer diameter of 8.5 mmand equipped with a 140-cm overtube with an outer diame-ter of 12 mm (Fujinon). Latex balloons at the tip of theenteroscope and the overtube are inflated and deflatedwith air from a pressure-controlled pump system. By inflat-ing the overtube balloon enough to grip the intestinal wall(which can occur at a balloon pressure of 45 mm Hg), theendoscope can be inserted further without forming redun-dant loops in the small intestine. The overtube can then beinserted while the endoscope balloon is inflated. Thismethod allows for insertion of the endoscope deep intothe small intestine.

www.giejournal.org

Except for rare instances, a total enteroscopy with cecalintubation by the antegrade approach alone is notfeasible. In patients without prior imaging modalities tosuggest the location of lesions, it is reasonable to investi-gate the patient who has obscure bleeding initially by us-ing the anterograde approach, because the majority of thelesions would be expected to be located in the proximal tomid small bowel.24 We modeled that an oral DBE wouldoccur if the CE suggested a lesion located within the initial75% of the small-bowel transit time.64 The majority of pa-tients do not require retrograde DBE after a successfuloral procedure.66 A total enteroscopy, defined as an initialDBE procedure, with tattooing of the most distal extent ofthe examination, followed by a DBE from the oppositeapproach that identifies the prior tattoo site, can beattempted on different days to minimize the patientdiscomfort and bowel distension.

Published studies that examined outcomes associatedwith a DBE that were used for the model are shown inTable 2. Summary statistics based on these 726 patientswho underwent a total of 1481 DBE examinations demon-strated an average diagnostic yield of 63% and diagnosticor treatment success of 60%. Obscure bleeding was the



indication for the DBE in approximately 36% to 100% ofexaminations, and the overall diagnostic yield from DBEranged from 43% to 80%. Diagnostic or therapeutic suc-cess was reached in 55% to 75% of examinations, whichis comparable with other diagnostic modalities for thesmall bowel. Patients with obscure bleeding as an indica-tion for a DBE had higher pathology detection rates. Nodeaths have been reported to date after a DBE. Intestinalperforation occurred in 4 of 1481 procedures (0.3%). Mildpancreatitis, possibly a sequela of duodenal hypertensionfrom double-balloon inflation, was reported in 3 of the pa-tients (0.2%). A recent multicenter survey study, including2367 DBE procedures from 10 centers, demonstrated thatthe perforation rate was 0.3%.65

For patients enrolled in the DBE arm, we modeled thatthe patients would undergo an empiric anterograde DBEas the initial diagnostic test. We derived the probabilityof finding lesions based on comparative studies in whichpatients had undergone prior CE examinations. Threestudies to date described results in patients who were un-dergoing a DBE after a CE.24,66,67 In the study by Heineet al,24 in which 275 patients underwent a DBE, small-bowel AVMs were the indication for DBE in 60 patients(22%) based on a prior CE. The diagnostic yield fora DBE was 48% when an oral DBE was performed aloneand 70% when both oral and rectal approaches were per-formed. In the U.S. multicenter trial,66 CE suggested AVMsin 42 patients (36%) of which 24 (57%) were confirmed bya DBE. In the study by Hadithi et al,67 AVMs were detectedduring 19 of 35 CE examinations (54%) (primarily locatedin the jejunum), and DBE diagnosed AVMs in 16 of these19 patients (84%). By using the weighted probabilitiesfrom these studies, we calculated that the probability offinding an AVM on a DBE was 33%. The probability ofAVM detection on a DBE was lower than with a CE be-cause a CE allows for complete small-bowel imaging in ad-dition to the possibility of false-positive lesions that maybe identified on a CE and classified as nonspecific redspots or other lesions that may not represent true AVMs.For tumors and ulcerations, prior studies showed excel-lent agreement between CE and DBE that ranged from96% to 100%.24,66

Although most lesions will be located within the prox-imal two thirds of the small bowel, it is also possible thatpatients might be bleeding from isolated or multiplelesions in the distal bowel. To calculate this probability,we used data from the study by Heine et al,24 in whichthe probability of finding a lesion on rectal DBE if anoral examination was normal was approximately 20%.

Information regarding outcomes after endoscopic ther-apy for AVMs have not been widely published. In a clinicaltrial by Hadithi et al67 that included 35 patients with ob-scure GI bleeding, AVMs were present and treated in 16of the patients (45%). Over a mean follow-up of 5 months(range 2-12 months), 80% of the patients did not reportany subsequent GI bleeding. We modeled that the


rebleeding rate after therapy for AVMs would approach20%. After completion of both anterograde and retrogradeDBE, the probability of recurrent bleeding decreased to5%.67 We modeled the probability of complications anddeath associated with endoscopic complications for DBEby using a rate of 0.3% for a perforation based on the avail-able medical literature (Table 2) and a large study fromMensink et al.65

Capsule-directed DBECE, developed by Given Imaging (Given Imaging Ltd,

Yoqneam, Israel), involves swallowing a 11 � 26 mm cap-sule that subsequently obtains images throughout the GItract and transmits the data during an 8-hour recordingperiod via radio frequency to a recording device wornabout the patient’s waist. Multiple studies demonstratedthe superiority of CE compared with push enteroscopyfor patients with obscure GI bleeding. The yield of CEranged from 55% to 75%,11,12,35,36,38,41-43,56,61 with a 25%to 50% higher yield compared with a push enteroscopy.A recent meta-analysis that examined 14 trials comparingCE to push enteroscopy for obscure bleeding demon-strated a 63% yield for CE compared to 28% for push en-teroscopy.68 In a recent pooled analysis of raw data frommanufacturer-sponsored trials, CE was shown to be supe-rior to push enteroscopy, small-bowel series, and colono-scopy with ileal intubation.69 In this analysis, CE identifiedpathology in approximately 70% of the 530 pooledexaminations.

We assumed that patients would undergo a small-bowelCE after a bowel preparation. After the initial CE examina-tion, we modeled a spontaneous cessation rate of hemor-rhage for AVMs, ulcerations, tumors, and other vascularlesions according to the published literature.6,7,25,46 Ifthe patients continued to experience bleeding, thena DBE would be performed, with an oral approach initi-ated if the CE findings occurred within the initial 75% ofthe examination time, and rectal approach for lesionswithin the distal 25% of the transit time.64 Patients witha normal CE and ongoing bleeding would undergoempiric DBE via the oral approach.

Although up to 1% of patients may not be able to swal-low the capsule70 and will require endoscopic placement,we assumed, in the decision analysis, that all patientscould ingest the capsule. We did assume that capsule re-tention would occur in 1% of patients and that a DBEwould be successful in retrieval of the capsule in 50% ofcases.71,72 Patients who undergo surgical removal of theCE after retention could undergo subsequent DBE ifthey continued to bleed.

OutcomesThe primary focus of our analysis was cost per quality-

adjusted life years (QALY). The guidelines on cost-effec-tiveness analyses suggest that QALYs are the mostappropriate health-economic unit for decision analytic

www.giejournal.org


models.73 Patients with acute GI bleeding were previouslyshown to have associated diminished health-related QOLwhen using generalized health surveys, such as the ShortForm Medical Outcomes Survey 36.74 Health-state utilitiesare preference-weighted measures required for cost-effec-tiveness analyses. Utility measurements are designed toprovide a numerical indicator of symptom severity basedon a scale of 0 to 1.0, in which 0 represents death or a stateequivalent to death, and 1.0 represents ideal health, ora state without a particular disease. A paucity of utilitydata exists for the state of GI hemorrhage. In a decisionanalysis that examined anticoagulant therapy to preventa stroke in patients with atrial fibrillation, the mean utilityof GI hemorrhage was 0.84 when derived hypotheticallyfrom elderly patients with atrial fibrillation who wereasked about a theoretical situation of GI hemorrhage.75

In a 1995 decision analysis that examined the cost-effec-tiveness of warfarin and aspirin for prophylaxis of strokein patients with nonvalvular atrial fibrillation,76 74 elderlyveterans with atrial fibrillation were interviewed abouta hypothetical scenario of GI hemorrhage; the meantime trade-off value was 0.76. Therefore, hypothetical esti-mates for the utility state associated with the state of acuteGI bleeding ranged between 0.76 and 0.84. We assumedthat patients without bleeding would have a perfect utilityscore of 1.0, whereas patients with ongoing bleedingwould have a QALY score of 0.80.75,76 We modeled thatthe QALY associated with hospitalization for perforationwould approximate 0.7577,78 and that patients would re-turn to their usual state of health within 1 month afterbleeding.79

In patients with obscure bleeding, other important out-comes include costs associated with diagnostic testing andmanagement. Prior studies showed that most patientswith obscure GI bleeding undergo a large number of diag-nostic tests and hospitalizations before a diagnosis is es-tablished and treatment is initiated. In one study, of 39patients with obscure bleeding, there were a total of 277diagnostic tests performed before study entry, with anaverage of 7.3 tests per patient, and 49% of patients con-tinued to have an unknown bleeding source after push en-teroscopy.28 In another study, of 14 patients with obscurebleeding who were undergoing intraoperative entero-scopy, there was an average of 5 hospital admissions and46 units of blood transfused per patient before theexamination.80

Data sourcesWe performed a thorough search of published articles

between 1960 and 2006 from the MEDLINE database toidentify relevant English-language publications that per-tain to AVMs, push enteroscopy, intraoperative entero-scopy, angiography, CE, and DBE. Studies published onlyas abstracts were excluded. For assessment of proceduraloutcomes, case series were not included. Because therewas a large variation in the number of patients enrolled

www.giejournal.org

in clinical trials, we used weighted averages of the avail-able probabilities to estimate the base-case probabilityfor the model. To calculate yearly probabilities, theformula P Z 1 � e (�rt) was used, where P Z probability,r Z rate, and t Z time.

Estimation of model costsWe estimated the costs associated with push entero-

scopy, intraoperative enteroscopy, angiography, and CEfrom the perspective of a third-party payer (Table 3). Weonly considered direct health care costs and did not ac-count for costs because of non–health care expenditures,such as transportation and/or time lost from work. Weused facility and professional fees based on Medicare-allowable payments in 2005 to derive costs for endoscopicprocedures, GI hemorrhage, and perforation after an en-doscopic procedure. We derived an average cost basedon Medicare payments for rural and urban areas for 4 ma-jor states in the United States (California, Illinois, NewYork, and Georgia). The costs of inpatient hospitalservices were obtained by using the 2005 Medicare Pro-spective Payment System diagnosis related group. Wedid not include costs of cardiopulmonary complicationsfrom conscious sedation, because these complicationsare rare and are treated by prompt drug reversal. Dis-counting of costs was not performed because of the shorttime horizon of the analysis.

Because a DBE is a relatively new procedure, havingbeen initiated into the United States in approximately Sep-tember 2004, current procedural terminology code (CPT)codes are not yet available. The average procedural timeper procedure is typically 75 to 80 minutes.81 Currently,most physicians who perform DBE use the CPT code of44376 for diagnostic anterograde procedures (small-intes-tinal endoscopy, enteroscopy beyond second portion ofduodenum, including ileum; diagnostic, with or withoutcollection of a specimen or specimens by brushing orwashing). We estimated that the cost for the DBE wouldbe twice the cost of the 44376 CPT code based on the pro-cedural time. For DBE procedures performed via the rec-tal approach, most physicians currently use an unlistedCPT code of 44799. However, for the purposes of thisdecision analysis, we estimated the cost for a rectal DBEexamination by combining the cost for a diagnostic colo-noscopy (CPT code 44378) with the cost for a small-bowelexamination of the ileum and distal jejunum (CPT code44376). We widely varied the costs for the DBE examina-tions in the sensitivity analyses.

Cost-effectiveness and sensitivity analysesThe main outcomes evaluated included overall costs

per model arm, QALYs, the number of patients with cessa-tion of bleeding, the frequency of endoscopic complica-tions, and the overall mortality. We estimated theprobability of death over the course of the year basedon age-specific death rates from 2003 U.S. life tables82 in



TABLE 3. Costs based on 2007 CPT codes and 2005 Medicare rates*

CPT or DRG code Cost item Cost, $ ($ range in sensitivity analysis)

91110 CEy 1120 (500-1500)

44360 Push enteroscopy, diagnostic 160 (100-1000)

44366 With hemostasis 282 (100-1200)

DBEz

Anterograde approach

44376 Diagnostic 577 (200-2000)

44378 With hemostasis 780 (400-2000)

Rectal approach

45378 þ 44376 Diagnostic 1264 (400-2500)

45378 þ 44378 With hemostasis 1568 (400-3000)

Intraoperative enteroscopy 14,799 (7000-30,000)

49000 Exploratory laparotomy 805

44378 Small intestinal endoscopy with hemostasis 412

00840 Anesthesia 252

174,175 Hospitalizationx 13310

37204 Transcatheter embolization, angiography 1097 (500-3000)

36430 Monthly blood transfusionsk 122 (60-500)

Small-bowel resection 14710 (10,000-30,000)

44120 Enterectomy 1148



Endoscopic complication 27,562 (13,000-52,000)

GI hemorrhage 13,652

99283 Emergency department visit 70

44378 DBE with hemostasis 412

174, 175 HospitalizationV 13310

Perforation 41,191

99283 Emergency department visit 70

44605 Repair of perforation 1212



Omeprazole OTC 20 mg daily for 8 weeks{ 48 (20-200)

*Sources: American Medical Association. Current Procedural Terminology Code Book for CPT codes. 2005. Available at: http://www.ama-assn.org/ama/pub

(accessed February 26, 2008). Agency for Healthcare Research and Quality(AHRQ) Web site for 2003 Diagnosis Related Group charges. Available at: http://

hcup.ahrq.gov/HCUPnet (accessed February 26, 2008). The costs shown are the sum of included costs, based on an average of 4 different carrier localities for

each CPT code to derive a national average.

yCost of the capsule ($450) plus physician interpretation.

zCPT code for a DBE is not yet established. For an anterograde DBE, the cost estimated was with the CPT code of 44376, previously used for Sonde enteroscopy

including the ileum. The current procedural times average is 75-80 minutes for DBE examinations. The DBE cost was obtained by doubling the reimbursement

for the 44376 code. For a retrograde approach, the currently recommended code is the unlisted code of 44799. However, for the model, we estimated costs of

diagnostic colonoscopy (CPT code 45378 or $453) plus small-bowel examination (44376 or 44378 if hemostasis was performed).

xHospitalization charges were based on an average of charges for hospitalizations with and without complications. The cost for an endoscopic complication

was calculated by assuming that 50% would experience hemorrhage and 50% perforation.

kThe cost of blood transfusions was $61 per unit. When assuming that the bleeding patient receives 2 units per month, the cost of transfusional therapy was

$1464 per year.

{Omeprazole over the counter based on retail price of $11 for 14 capsules. Available at: http://www.drugstore.com (accessed February 26, 2008).

930 GASTROINTESTINAL ENDOSCOPY Volume 68, No. 5 : 2008 www.giejournal.org

http://www.ama-assn.org/ama/pub

http://hcup.ahrq.gov/HCUPnet

http://hcup.ahrq.gov/HCUPnet

http://www.drugstore.com


TABLE 4. Base-case results

Model arm

Average

cost ($)* Effectivenessy Incremental cost-effectivenessz

No therapy 532 0.870 Base case

Push enteroscopy 1025 0.888 -

DBE 2407 0.956 $20,833 per QALY

Angiography 3215 0.899

Capsule-directed DBE 4309 0.942 -

Intraoperative

enteroscopy

21263 0.939 -

*Average cost per patient.

yQALYs gained per year.

zIncremental cost per additional QALY gained compared with no therapy.

addition to the probability of death resulting from endo-scopic procedural complications.

We calculated the incremental cost-effectiveness ratio(ICER) between the no treatment arm and the most effec-tive strategy. For this model, the ICER represented the ad-ditional cost accrued to gain the greatest fraction of QALYswhen adopting the more expensive yet more effectivestrategy. If one of the arms was less costly and more effec-tive than the other arm, then that strategy was said to bedominant. We performed 1-way, 2-way, and multivariablesensitivity analyses to evaluate the effects from varyingcosts and probabilities over ranges derived from thereview of the medical literature.

RESULTS

By using the base-case probabilities shown in Table 1,the no-therapy arm was the least expensive and was asso-ciated with the lowest fraction of QALYs. The initial DBEarm was the most effective but more expensive than theno-therapy arm, whereas all of the other strategies (exceptfor a push enteroscopy, which was less costly) were lesseffective than the DBE arm and more expensive. The no-therapy arm cost $532 and was associated with 0.870 QA-LYs, whereas the DBE arm cost $2407 and was associatedwith 0.956 QALYs, which resulted in an incremental cost-effectiveness ratio of $20,833 per QALY gained (Table 4).Compared with a DBE, an initial CE was more costlyand less effective. Based on these results, approximately86.5% of patients would experience cessation of hemor-rhage over the course of a year in the DBE arm comparedwith 76% in the CE arm and 59% in the no-therapy arm(Table 5).

A tornado analysis revealed that the variables with themost impact on the cost-effectiveness ratio (in descendingorder) were the QOL associated with the well state, the

www.giejournal.org

QOL associated with bleeding, the probability of an AVM,the mortality rate associated with hemorrhage, the proba-bility of missed lesions on upper and lower endoscopies,the DBE complication rate, and the DBE cost.

We performed 1-way sensitivity analyses on all parame-ters of the model. When the QALY of the well state was!0.53, the no-therapy arm was the preferred approach.When this value ranged between 0.6 and 0.8, the initialCE approach was preferred. The effectiveness of the CEarms and the DBE arms were equivalent when (a) theQALY state associated with bleeding O0.875, (b) themiss rate for lesions on upper and/or lower endoscopiesexceeded 23%, and (c) when the DBE complication ratewas O30%. However, despite equal effectiveness, theDBE arm was less expensive and, therefore, was preferredby extended dominance. When the cost of yearly transfu-sions exceed $10,000, the DBE arm cost less than the no-therapy arm but remained more effective. When the costof DBE exceeded $5925, the CE arm cost less than the

TABLE 5. Base-case results per 1000 patients

Model arm

No. patients

still bleeding

No. patients

with bleeding

cessation

No.

deaths

No therapy 388 590 22

Push enteroscopy 324 656 19

Angiography 297 684 18

Capsule-directed

DBE

235 760 5

Intraoperative

enteroscopy

158 821 21

DBE 125 865 10



DBE arm but remained less effective. At a probability ofAVM !5%, the no-therapy arm was preferred.

We performed a Monte Carlo simulation to simulta-neously vary all of the key variables identified during thetornado analysis. We assumed a triangular distributionfor each parameter entered into the simulation. Themean ICER of these 1000 trials (Fig. 3) was $28,600 perQALY (2.5 and 97.5 percentiles, $27,871 and $41,680, re-spectively). The percentage of trials that resulted in lessthan the $50,000 and $100,000 willingness-to-pay thresh-olds were 86% and 99%. For example, if a third-party payerwere willing to pay $50,000 per patient with bleeding ces-sation for the use of DBE, then 86% of the patients in thissimulation would be within the budget.

A major limitation of our model was the short time ho-rizon of 1 year. We extended the time frame of our analysisto determine the impact on the current model, with pa-tients remaining in their current states after receiving theirinitial course of treatment. After 5 years, the results of theanalysis did not change. However, after 7 years, the CEarm and DBE arm were equally effective, which resultedin 5.3 QALYs per arm. This exercise was limited, however,by a lack of knowledge about the long-term probabilitiesof bleeding cessation and the potential recurrence ofsmall-bowel lesions.

Because a DBE is a time-consuming and difficult proce-dure, we also examined the number of DBE proceduresrequired in the initial DBE strategy compared with the ini-tial CE strategy. By assuming a cohort of 1000 patients, allwould require an initial oral DBE and then approximately130 would require subsequent rectal DBE procedures be-cause of ongoing bleeding. In the initial CE arm, all 1000patients would undergo a CE; approximately 237 patients

Figure 3. Probabilistic sensitivity analysis by using 1000 trials. This anal-

ysis simultaneously varied all parameters over the full range of plausible

values. Each point represents the ICER generated by 1 trial through the

simulation. The bold line represents the median ICER of $20,833 per

QALY. By definition, 50% of the trials fall on either side of the line. The

remaining 2 diagonal lines represent willingness-to-pay thresholds. If

a third-party payer was willing to pay $50,000 per patient with cessation

of bleeding, then 86% of the patients would fall within the budget.


would require a DBE after the CE examination because ofongoing bleeding, and, subsequently, 47 patients wouldexperience ongoing bleeding and require a DBE via theopposite approach. Therefore, an initial CE was associatedwith a decreased DBE workload and potential for endo-scopic complications, since only patients with ongoingbleeding would undergo subsequent DBE examination.

DISCUSSION

Approximately 5% of patients with GI bleeding willhave a source localized to the small intestine. Before theadvent of CE, the primary tools available for diagnosisand treatment of small-bowel lesions included pushenteroscopy, which could primarily detect lesions just dis-tal to the ligament of Treitz, or intraoperative enteroscopy,which had a high success rate for treatment of small-bowellesions but also carried a high morbidity and mortalityrate. With the advent of CE in 2000, the entire small bowelwas able to be visualized by using a noninvasive method-ology that was associated with a 25% to 50% higher yieldcompared with small-bowel radiography or push entero-scopy. The major disadvantages associated with CE in-clude a lack of therapeutic options, the potential formissed lesions because of tumbling of the capsule, anda field of view of approximately 140 degrees. The adventof DBE in 2000 and then the introduction of DBE intothe United States in 2004 allowed for therapeutic potentialin the small bowel without the need for an intraoperativeenteroscopy, except in circumstances in which bowel ad-hesions or other technical factors prevent advancementof the enteroscope. A DBE can be performed in theendoscopy suite with the patient under conscious seda-tion but generally requires additional staff to help withovertube positioning and, on average, 60 to 80 minutesper procedure. By using a systematic approach to estimatethe depth of insertion by advancement cycles, at least240 cm of small-bowel mucosa can be reached from theoral approach and 140 cm from the ileocecal valve.81

The retrograde approach is more challenging because ofthe need for adequate colonic preparation, the potentialfor looping in the colon, and the difficulty with intubationof the ileocecal valve, particularly in a patient with prioradhesions. Even with considerable experience, the failurerates for rectal procedures remain at 20% because of thepresence of adhesions from prior pelvic and abdominalsurgeries and poor preparation that prevented intubationof the ileocecal valve.83 However, the majority of small-bowel lesions would be expected to be located withinthe proximal small bowel and within reach of an oralDBE. Although a CE is not associated with any potentialfor therapeutic maneuvers and can miss lesions, the disad-vantages associated with DBE include the long duration ofthe procedure, potential for complications, the need foradditional staffing, and difficulty in missing lesions in the

www.giejournal.org


mid small bowel where access is often challenging. None-theless, our decision analysis suggests that, in patientswith obscure bleeding, DBE would be a cost-effective ap-proach because of the ability to identify and treat lesionsduring the initial small-bowel examination.

Currently, the cost for a DBE is not known. It is antici-pated that CPT codes will be established for a DBE withinthe near future. Many hospital billing departments arerecommending that providers use the CPT code 44799(unlisted procedure small intestine). The long associatedprocedural time may discourage gastroenterologists fromperforming this procedure. We found that a DBE re-mained a cost-effective approach, regardless of the costfor the examination, because patients did not incur theadditional costs of the capsule examination, and therapeu-tic interventions could be performed. However, thelimitation of these conclusions is the current lack of avail-ability of a DBE in most centers. An initial DBE would sig-nificantly increase the endoscopy workload (includingprocedural time) for gastroenterologists and would leadto a higher rate of endoscopic complications comparedwith initial usage of a CE. Benefits of performing an initialCE would include a reduction in the number of subse-quent DBE procedures, and localization of small-bowel le-sions to the proximal or distal small bowel. Therefore, inhospitals where a DBE is not available, an initial CE wouldremain a cost-effective approach compared with the otherdiagnostic modalities included in our model.

There are several limitations to our analysis. We derivedthe probabilities for the model from prior clinical trials,most that included small numbers of patients. Outcomesdata about cessation of bleeding after endoscopic therapy,particularly a DBE, are not yet available but are needed toperform an analysis over a longer time period. In addition,the prevalence of small-bowel lesions is likely to be differ-ent, depending upon the age of the patient. In patientsbelow the age of 40 years and with obscure GI bleeding,more common etiologies for obscure bleeding wouldinclude tumors, Meckel’s diverticulum, Crohn’s disease,or a Dieulafoy’s lesion. In this population, a CE may bemore effective in the identification of pathology locatedin the mid small bowel, although a DBE could offerboth diagnostic and therapeutic potential. In patientsover the age of 40 years, in whom small-bowel AVMs aremore likely to be causal, an initial DBE appears to becost effective in that diagnosis and management can occurduring the same examination.

Given the published rates in the literature, we wereable to calculate the sensitivity of each test for each typeof small-bowel lesion but not the specificity. We, therefore,assumed 100% specificity of each modality. In the prelim-inary multicenter U.S. DBE study, miss rates for a CE anda DBE for small-bowel lesions were between 20% and30%.65 It would be expected that higher false-positiverates for lesions on a CE would lead to increased utiliza-tion and costs attributable to a DBE and that higher

www.giejournal.org

false-positive rates on any test would lead to higher com-plication rates. Future studies that derive sensitivity andspecificity of each modality for each type of small-bowellesion are warranted to refine future cost-effectivenessanalyses in this area. To derive these probabilities, subjectswould be required to undergo comparative diagnostictesting.

Additional limitations of our model include the shorttime horizon of 1 year. As DBE becomes more widely prac-ticed, patients who have undergone the procedure withendoscopic therapy for AVMs could be followed overtime to determine the long-term duration of endoscopictherapy. We were able to demonstrate equal effectivenessfor the capsule and DBE arms at 7 years. As shown inTable 5, the DBE arm had a 0.5% absolute increase indeaths compared with CE because of procedural compli-cations. If the base-case 50-year-old male patient wasexpected to live approximately 20 more years, then thatdifference alone would amount to a 0.1 absolute yearadvantage over a lifetime for CE, an amount that wouldexceed the initial 0.014 benefit in QALYs produced byDBE during the 1-year time horizon of the current model.

Although we focused our analysis on the impact ofbleeding on QOL, a paucity of information exists aboutthe impact of chronic GI bleeding on QOL. To date,health-state utility values exist only for patients with acuteGI bleeding, and these values were derived from hypo-thetical situations.73,74 Because obscure GI bleeding isusually a chronic process, it would be expected that thehealth-related QOL might be lower in this population,and future studies are warranted in this area.

We did not model indirect costs to the patient, such astime lost from work. Although most patients lose a day ofwork for any endoscopic procedure, a CE does not requiresedation and, therefore, could be performed during a work-ing day if needed. This would be unlikely to impact thecurrent decision analysis. However, more information re-garding work productivity and chronic bleeding is needed.

In summary, we demonstrated that an initial DBE is a cost-effective approach for patients with obscure bleeding. How-ever, a capsule-directed DBE may be associated with betterlong-term outcomes because of the potential for fewer com-plications and decreased utilization of endoscopic re-sources. Future research is warranted to understand thenatural history of bleeding from these lesions and the im-pact of obscure bleeding on health-related QOL.

DISCLOSURE

The following author reports no disclosures relevantto this publication: A. Kamal. The following author hasdisclosed actual or potential conflicts: L. Gerson has re-ceived research support, equipment, and honorariumfrom Fujinon, and has received honorarium from GivenImaging Inc.



REFERENCES

1. Szold A, Katz LB, Lewis BS. Surgical approach to occult gastrointesti-

nal bleeding. Am J Surg 1992;163:90-2, discussion 92–3.

2. Pennazio M, Arrigoni A, Risio M, et al. Clinical evaluation of push-type

enteroscopy. Endoscopy 1995;27:164-70.

3. Chong J, Tagle M, Barkin JS, et al. Small bowel push-type fiberoptic

enteroscopy for patients with occult gastrointestinal bleeding or sus-

pected small bowel pathology. Am J Gastroenterol 1994;89:2143-6.

4. Davies GR, Benson MJ, Gertner DJ, et al. Diagnostic and therapeutic

push type enteroscopy in clinical use. Gut 1995;37:346-52.

5. Thompson JN, Hemingway AP, McPherson GA, et al. Obscure gastro-

intestinal haemorrhage of small-bowel origin. Br Med J (Clin Res Ed)

1984;288:1663-5.

6. Junquera F, Feu F, Papo M, et al. A multicenter, randomized, clinical

trial of hormonal therapy in the prevention of rebleeding from gas-

trointestinal angiodysplasia. Gastroenterology 2001;121:1073-9.

7. Lewis BS, Salomon P, Rivera-MacMurray S, et al. Does hormonal ther-

apy have any benefit for bleeding angiodysplasia? J Clin Gastro-

enterol 1992;15:99-103.

8. Gostout CJ. Sonde enteroscopy. Technique, depth of insertion, and

yield of lesions. Gastrointest Endosc Clin N Am 1996;6:777-92.

9. Schmit A, Gay F, Adler M, et al. Diagnostic efficacy of push-entero-

scopy and long-term follow-up of patients with small bowel angio-

dysplasias. Dig Dis Sci 1996;41:2348-52.

10. Descamps C, Schmit A, Van Gossum A. ‘‘Missed’’ upper gastrointestinal

tract lesions may explain ‘‘occult’’ bleeding. Endoscopy 1999;31:452-5.

11. Ell C, Remke S, May A, et al. The first prospective controlled trial com-

paring wireless capsule endoscopy with push enteroscopy in chronic

gastrointestinal bleeding. Endoscopy 2002;34:685-9.

12. Mata A, Bordas JM, Feu F, et al. Wireless capsule endoscopy in pa-

tients with obscure gastrointestinal bleeding: a comparative study

with push enteroscopy. Aliment Pharmacol Ther 2004;20:189-94.

13. Desa LA, Ohri SK, Hutton KA, et al. Role of intraoperative enteroscopy

in obscure gastrointestinal bleeding of small bowel origin. Br J Surg

1991;78:192-5.

14. Ress AM, Benacci JC, Sarr MG. Efficacy of intraoperative enteroscopy

in diagnosis and prevention of recurrent, occult gastrointestinal

bleeding. Am J Surg 1992;163:94-8, discussion 98–9.

15. Yamamoto H, Sekine Y, Sato Y, et al. Total enteroscopy with a nonsur-

gical steerable double-balloon method. Gastrointest Endosc 2001;53:

216-20.

16. May A, Wardak A, Nachbar L, et al. Influence of patient selection on

the outcome of capsule endoscopy in patients with chronic gastro-

intestinal bleeding. J Clin Gastroenterol 2005;39:684-8.

17. Ell C, May A, Nachbar L, et al. Push-and-pull enteroscopy in the small

bowel using the double-balloon technique: results of a prospective

European multicenter study. Endoscopy 2005;37:613-6.

18. Monkemuller K, Weigt J, Treiber G, et al. Diagnostic and therapeutic

impact of double-balloon enteroscopy. Endoscopy 2006;38:67-72.

19. Pennazio M, Eisen G, Goldfarb N. ICCE consensus for obscure gastro-

intestinal bleeding. Endoscopy 2005;37:1046-50.

20. Appleyard M, Fireman Z, Glukhovsky A, et al. A randomized trial com-

paring wireless capsule endoscopy with push enteroscopy for the

detection of small-bowel lesions. Gastroenterology 2000;119:1431-8.

21. Russell LB, Gold MR, Siegel JE, et al. The role of cost-effectiveness

analysis in health and medicine. Panel on Cost-Effectiveness in Health

and Medicine. JAMA 1996;276:1172-7.

22. Askin MP, Lewis BS. Push enteroscopic cauterization: long-term fol-

low-up of 83 patients with bleeding small intestinal angiodysplasia.

Gastrointest Endosc 1996;43:580-3.

23. Hodgson H. Hormonal therapy for gastrointestinal angiodysplasia.

Lancet 2002;359:1630-1.

24. Heine GD, Hadithi M, Groenen MJ, et al. Double-balloon enteroscopy:

indications, diagnostic yield, and complications in a series of 275 pa-

tients with suspected small-bowel disease. Endoscopy 2006;38:42-8.


25. Lai LH, Wong GL, Chow DK, et al. Long-term follow-up of patients

with obscure gastrointestinal bleeding after negative capsule endos-

copy. Am J Gastroenterol 2006;101:1224-8.

26. Benz C, Jakobs R, Riemann JF. Do we need the overtube for push-en-

teroscopy? Endoscopy 2001;33:658-61.

27. Taylor AC, Chen RY, Desmond PV. Use of an overtube for entero-

scopy: does it increase depth of insertion? A prospective study of en-

teroscopy with and without an overtube. Endoscopy 2001;33:227-30.

28. Foutch PG, Sawyer R, Sanowski RA. Push-enteroscopy for diagnosis

of patients with gastrointestinal bleeding of obscure origin. Gastro-

intest Endosc 1990;36:337-41.

29. Adrain AL, Dabezies MA, Krevsky B. Enteroscopy improves the clinical

outcome in patients with obscure gastrointestinal bleeding. J Lapa-

roendosc Adv Surg Tech A 1998;8:279-84.

30. Zaman A, Sheppard B, Katon RM. Total peroral intraoperative entero-

scopy for obscure GI bleeding using a dedicated push enteroscope:

diagnostic yield and patient outcome. Gastrointest Endosc 1999;50:

506-10.

31. Shackel NA, Bowen DG, Selby WS. Video push enteroscopy in the in-

vestigation of small bowel disease: defining clinical indications and

outcomes. Aust N Z J Med 1998;28:198-203.

32. Hayat M, Axon AT, O’Mahony S. Diagnostic yield and effect on clinical

outcomes of push enteroscopy in suspected small-bowel bleeding.

Endoscopy 2000;32:369-72.

33. Sharma BC, Bhasin DK, Makharia G, et al. Diagnostic value of push-

type enteroscopy: a report from India. Am J Gastroenterol 2000;95:

137-40.

34. Landi B, Cellier C, Gaudric M, et al. Long-term outcome of patients

with gastrointestinal bleeding of obscure origin explored by push

enteroscopy. Endoscopy 2002;34:355-9.

35. Lewis BS, Swain P. Capsule endoscopy in the evaluation of patients

with suspected small intestinal bleeding: results of a pilot study. Gas-

trointest Endosc 2002;56:349-53.

36. Mylonaki M, Fritscher-Ravens A, Swain P. Wireless capsule endos-

copy: a comparison with push enteroscopy in patients with gastros-

copy and colonoscopy negative gastrointestinal bleeding. Gut

2003;52:1122-6.

37. Saurin JC, Delvaux M, Gaudin JL, et al. Diagnostic value of endoscopic

capsule in patients with obscure digestive bleeding: blinded compar-

ison with video push-enteroscopy. Endoscopy 2003;35:576-84.

38. Saurin JC, Delvaux M, Vahedi K, et al. Clinical impact of capsule

endoscopy compared to push enteroscopy: 1-year follow-up study.

Endoscopy 2005;37:318-23.

39. Keizman D, Brill S, Umansky M, et al. Diagnostic yield of routine push

enteroscopy with a graded-stiffness enteroscope without overtube.

Gastrointest Endosc 2003;57:877-81.

40. Romelaer C, Le Rhun M, Beaugerie L, et al. Push enteroscopy for gas-

trointestinal bleeding: diagnostic yield and long-term follow-up. Gas-

troenterol Clin Biol 2004;28:1061-6.

41. Adler DG, Knipschield M, Gostout C. A prospective comparison of

capsule endoscopy and push enteroscopy in patients with GI bleed-

ing of obscure origin. Gastrointest Endosc 2004;59:492-8.

42. Pennazio M, Santucci R, Rondonotti E, et al. Outcome of patients with

obscure gastrointestinal bleeding after capsule endoscopy: report of

100 consecutive cases. Gastroenterology 2004;126:643-53.

43. Hartmann D, Schilling D, Bolz G, et al. Capsule endoscopy versus

push enteroscopy in patients with occult gastrointestinal bleeding.

Z Gastroenterol 2003;41:377-82.

44. 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;47:372-6.

45. Landi B, Tkoub M, Gaudric M, et al. Diagnostic yield of push-type en-

teroscopy in relation to indication. Gut 1998;42:421-5.

46. Hsu CM, Chiu CT, Su MY, et al. The outcome assessment of double-

balloon enteroscopy for diagnosing and managing patients with ob-

scure gastrointestinal bleeding. Dig Dis Sci 2007;52:162-6.

www.giejournal.org


47. Clarke GA, Jacobson BC, Hammett RJ, et al. The indications, utiliza-

tion and safety of gastrointestinal endoscopy in an extremely elderly

patient cohort. Endoscopy 2001;33:580-4.

48. Sieg A, Hachmoeller-Eisenbach U, Eisenbach T. Prospective evalua-

tion of complications in outpatient GI endoscopy: a survey among

German gastroenterologists. Gastrointest Endosc 2001;53:620-7.

49. Schauer PR, Schwesinger WH, Page CP, et al. Complications of surgi-

cal endoscopy. A decade of experience from a surgical residency

training program. Surg Endosc 1997;11:8-11.

50. Strodel WE, Eckhauser FE, Knol JA, et al. Intraoperative fiberoptic en-

doscopy. Am Surg 1984;50:340-4.

51. Greenberg GR, Phillips MJ, Tovee EB, et al. Fiberoptic endoscopy dur-

ing laparotomy in the diagnosis of small intestinal bleeding. Gastro-

enterology 1976;71:133-5.

52. Bowden TA Jr, Hooks VH 3rd, Teeslink CR, et al. Occult gastrointesti-

nal bleeding: locating the cause. Am Surg 1980;46:80-7.

53. Lopez MJ, Cooley JS, Petros JG, et al. Complete intraoperative small-

bowel endoscopy in the evaluation of occult gastrointestinal bleed-

ing using the Sonde enteroscope. Arch Surg 1996;131:272-7.

54. Douard R, Wind P, Panis Y, et al. Intraoperative enteroscopy for diag-

nosis and management of unexplained gastrointestinal bleeding. Am

J Surg 2000;180:181-4.

55. Kendrick ML, Buttar NS, Anderson MA, et al. Contribution of intrao-

perative enteroscopy in the management of obscure gastrointestinal

bleeding. J Gastrointest Surg 2001;5:162-7.

56. Hartmann D, Schmidt H, Bolz G, et al. A prospective two-center study

comparing wireless capsule endoscopy with intraoperative entero-

scopy in patients with obscure GI bleeding. Gastrointest Endosc

2005;61:826-32.

57. Jakobs R, Hartmann D, Benz C, et al. Diagnosis of obscure gastroin-

testinal bleeding by intra-operative enteroscopy in 81 consecutive

patients. World J Gastroenterol 2006;12:313-6.

58. d’Othee BJ, Surapaneni P, Rabkin D, et al. Microcoil embolization for

acute lower gastrointestinal bleeding. Cardiovasc Intervent Radiol

2006;29:49-58.

59. Richardson JD, Max MH, Flint LM Jr, et al. Bleeding vascular malfor-

mations of the intestine. Surgery 1978;84:430-6.

60. Rollins ES, Picus D, Hicks ME, et al. Angiography is useful in detecting

the source of chronic gastrointestinal bleeding of obscure origin. AJR

Am J Roentgenol 1991;156:385-8.

61. Saperas E, Dot J, Videla S, et al. Capsule endoscopy versus computed

tomographic or standard angiography for the diagnosis of obscure

gastrointestinal bleeding. Am J Gastroenterol 2007;102:731-7.

62. Aina R, Oliva VL, Therasse E, et al. Arterial embolotherapy for upper

gastrointestinal hemorrhage: outcome assessment. J Vasc Interv Ra-

diol 2001;12:195-200.

63. Cohn SM, Moller BA, Zieg PM, et al. Angiography for preoperative

evaluation in patients with lower gastrointestinal bleeding: are the

benefits worth the risks? Arch Surg 1998;133:50-5.

64. Gay G, Delvaux M, Fassler I. Outcome of capsule endoscopy in deter-

mining indication and route for push-and-pull enteroscopy. Endos-

copy 2006;38:49-58.

65. Mensink PB, Haringsma J, Kucharzik T, et al. Complications of double

balloon enteroscopy: a multicenter survey. Endoscopy 2007;39:613-5.

66. Mehdizadeh S, Ross AS, Gerson L, et al. What is the learning curve

associated with double-balloon enteroscopy? Technical details and

early experience in 6 U.S. tertiary care centers. Gastrointest Endosc

2006;64:740-50.

67. Hadithi M, Heine GD, Jacobs MA, et al. A prospective study compar-

ing video capsule endoscopy with double-balloon enteroscopy in

patients with obscure gastrointestinal bleeding. Am J Gastroenterol

2006;101:52-7.

68. Triester SL, Leighton JA, Leontiadis GI, et al. A meta-analysis of the

yield of capsule endoscopy compared to other diagnostic modalities

in patients with non-stricturing small bowel Crohn’s disease. Am J

Gastroenterol 2006;101:954-64.

www.giejournal.org

69. Lewis BS, Eisen GM, Friedman S. A pooled analysis to evaluate results

of capsule endoscopy trials. Endoscopy 2005;37:960-5.

70. Lapalus MG, Dumortier J, Fumex F, et al. Esophageal capsule endos-

copy versus esophagogastroduodenoscopy for evaluating portal hy-

pertension: a prospective comparative study of performance and

tolerance. Endoscopy 2006;38:36-41.

71. Baichi MM, Arifuddin RM, Mantry PS. What we have learned from 5

cases of permanent capsule retention. Gastrointest Endosc 2006;64:

283-7.

72. Rondonotti E, Herrerias JM, Pennazio M, et al. Complications, limita-

tions, and failures of capsule endoscopy: a review of 733 cases. Gas-

trointest Endosc 2005;62:712-6, quiz 752, 754.

73. Gold MR, Siegel JE, Russell LB, et al. Cost-effectiveness in health and

medicine. Oxford: Oxford University Press; 1996.

74. Fryback DG, Dasbach EJ, Klein R, et al. The Beaver Dam Health Out-

comes Study: initial catalog of health-state quality factors. Med Decis

Making 1993;13:89-102.

75. Thomson R, Parkin D, Eccles M, et al. Decision analysis and guidelines

for anticoagulant therapy to prevent stroke in patients with atrial fi-

brillation. Lancet 2000;355:956-62.

76. Gage BF, Cardinalli AB, Albers GW, et al. Cost-effectiveness of warfa-

rin and aspirin for prophylaxis of stroke in patients with nonvalvular

atrial fibrillation. JAMA 1995;274:1839-45.

77. Tsevat J, Cook EF, Green ML, et al. Health values of the seriously ill.

SUPPORT investigators. Ann Intern Med 1995;122:514-20.

78. Tsevat J, Dawson NV, Wu AW, et al. Health values of hospitalized

patients 80 years or older. HELP investigators. Hospitalized Elderly

Longitudinal Project. JAMA 1998;279:371-5.

79. Joneja JS, Sharma DB, Sharma D, et al. Quality of life after peptic per-

foration. J Assoc Physicians India 2004;52:207-9.

80. Flickinger EG, Stanforth AC, Sinar DR, et al. Intraoperative video pan-

endoscopy for diagnosing sites of chronic intestinal bleeding. Am

J Surg 1989;157:137-44.

81. May A, Nachbar L, Ell C. Double-balloon enteroscopy (push-and-pull

enteroscopy) of the small bowel: feasibility and diagnostic and ther-

apeutic yield in patients with suspected small bowel disease. Gastro-

intest Endosc 2005;62:62-70.

82. Arias E. United States life tables, 2003. Natl Vital Stat Rep 2006;54:

1-40.

83. Mehdizadeh S, Han NJ, Cheng DW, et al. Success rate of retrograde

double-balloon enteroscopy. Gastrointest Endosc 2007;65:633-9.

84. Lewis BS, Wenger JS, Waye JD. Small bowel enteroscopy and intrao-

perative enteroscopy for obscure gastrointestinal bleeding. Am

J Gastroenterol 1991;86:171-4.

85. Marx FW Jr, Gray RK, Duncan AM, et al. Angiodysplasia as a source of

intestinal bleeding. Am J Surg 1977;134:125-30.

86. Ettorre GC, Francioso G, Garribba AP, et al. Helical CT angiography in

gastrointestinal bleeding of obscure origin. AJR Am J Roentgenol

1997;168:727-31.

87. Lau WY, Ngan H, Chu KW, et al. Repeat selective visceral angiography

in patients with gastrointestinal bleeding of obscure origin. Br J Surg

1989;76:226-9.

88. Di Caro S, May A, Heine DG, et al. The European experience with dou-

ble-balloon enteroscopy: indications, methodology, safety, and clini-

cal impact. Gastrointest Endosc 2005;62:545-50.

89. Kaffes AJ, Koo JH, Meredith C. Double-balloon enteroscopy in the

diagnosis and the management of small-bowel diseases: an initial

experience in 40 patients. Gastrointest Endosc 2006;63:81-6.

90. Yamamoto H, Kita H, Sunada K, et al. Clinical outcomes of double-

balloon endoscopy for the diagnosis and treatment of small-intesti-

nal diseases. Clin Gastroenterol Hepatol 2004;2:1010-6.

91. Chak A, Koehler MK, Sundaram SN, et al. Diagnostic and therapeutic

impact of push enteroscopy: analysis of factors associated with pos-

itive findings. Gastrointest Endosc 1998;47:18-22.

92. O’Mahony S, Morris AJ, Straiton M, et al. Push enteroscopy in the in-

vestigation of small-intestinal disease. QJM 1996;89:685-90.



93. Kim JI, Cheung DY, Cho SH, et al. Oral proton pump inhibitors are as

effective as endoscopic treatment for bleeding peptic ulcer: a pro-

spective, randomized, controlled trial. Dig Dis Sci 2007;52:3371-6.

94. Lo CC, Hsu PI, Lo GH, et al. Comparison of hemostatic efficacy for epi-

nephrine injection alone and injection combined with hemoclip ther-

apy in treating high-risk bleeding ulcers. Gastrointest Endosc

2006;63:767-73.

95. Chung IK, Ham JS, Kim HS, et al. Comparison of the hemostatic

efficacy of the endoscopic hemoclip method with hypertonic

saline-epinephrine injection and a combination of the two for the

management of bleeding peptic ulcers. Gastrointest Endosc

1999;49:13-8.

96. Sone Y, Kumada T, Toyoda H, et al. Endoscopic management and fol-

low up of Dieulafoy lesion in the upper gastrointestinal tract. Endos-

copy 2005;37:449-53.

97. Park CH, Sohn YH, Lee WS, et al. The usefulness of endoscopic

hemoclipping for bleeding Dieulafoy lesions. Endoscopy 2003;35:

388-92.

98. Parra-Blanco A, Takahashi H, Mendez Jerez PV, et al. Endoscopic man-

agement of Dieulafoy lesions of the stomach: a case study of 26 pa-

tients. Endoscopy 1997;29:834-9.

99. Kwan V, Bourke MJ, Williams SJ, et al. C. Argon plasma coagulation in

the management of symptomatic gastrointestinal vascular lesions:

experience in 100 consecutive patients with long-term follow-up.

Am J Gastroenterol 2006;101:58-63.

100. Christensen S, Riis A, Norgaard M, et al. Short-term mortality after

perforated or bleeding peptic ulcer among elderly patients: a popula-

tion-based cohort study. BMC Geriatr 2007;7:8-15.

101. Lecleire S, Di Fiore F, Merle V, et al. Acute upper gastrointestinal

bleeding in patients with liver cirrhosis and in noncirrhotic patients:

epidemiology and predictive factors of mortality in a prospective

multicenter population-based study. J Clin Gastroenterol 2005;39:

321-7.

102. Klebl F, Bregenzer N, Schofer L, et al. Risk factors for mortality in se-

vere upper gastrointestinal bleeding. Int J Colorectal Dis 2005;20:

49-56.


103. Barkin JS, O’Loughlin C. Capsule endoscopy contraindications: com-

plications and how to avoid their occurrence. Gastrointest Endosc

Clin N Am 2004;14:61-5.

104. Eliakim R, Fischer D, Suissa A, et al. Wireless capsule video endoscopy

is a superior diagnostic tool in comparison to barium follow-through

and computerized tomography in patients with suspected Crohn’s

disease. Eur J Gastroenterol Hepatol 2003;15:363-7.

105. Fireman Z, Mahajna E, Broide E, et al. Diagnosing small bowel

Crohn’s disease with wireless capsule endoscopy. Gut 2003;52:

390-2.

106. Kastin DA, Buchman AL, Barrett T, et al. Strictures from Crohn’s dis-

ease diagnosed by video capsule endoscopy. J Clin Gastroenterol

2004;38:346-9.

107. Manabe N, Tanaka S, Fukumoto A, et al. Double-balloon enteroscopy

in patients with GI bleeding of obscure origin. Gastrointest Endosc

2006;64:135-40.

108. Nakamura M, Niwa Y, Ohmiya N, et al. Preliminary comparison of cap-

sule endoscopy and double-balloon enteroscopy in patients with

suspected small-bowel bleeding. Endoscopy 2006;38:59-66.

109. Akahoshi K, Kubokawa M, Matsumoto M, et al. Double-balloon en-

doscopy in the diagnosis and management of GI tract diseases:

methodology, indications, safety, and clinical impact. World J Gastro-

enterol 2006;12:7654-9.

Received July 18, 2007. Accepted January 17, 2008.

Current affiliations: Division of Gastroenterology and Hepatology Stanford

University School of Medicine, Stanford, California, USA.

Presented at American Society for Gastrointestinal Endoscopy, Digestive

Disease Week, May 21-24, 2006, Los Angeles, California (Gastrointest

Endosc 2006;63:AB90).

Reprint requests: Lauren B. Gerson, MD, Division of Gastroenterology and

Hepatology, Stanford University Medical Center, A149, 300 Pasteur Dr,

Stanford, CA 94305-5202.

www.giejournal.org

Cost-effectiveness analysis of management strategies for obscure GI bleeding

Documents

Transcript of Cost-effectiveness analysis of management strategies for obscure GI bleeding