Scandinavian Journal of Gastroenterology. 2014; 49: 862–870

ORIGINAL ARTICLE

The role of capsule endoscopy in the evaluation and treatment ofobscure-overt gastrointestinal bleeding during daily clinical practice:a prospective multicenter study

PANAGIOTIS KATSINELOS1, GEORGIA LAZARAKI1, ASTERIOS GKAGKALIS2,ANTHI GATOPOULOU3, STAMATINA PATSAVELA2, KOSTAS VARITIMIADIS4,KOSTAS MIMIDIS5, GEORGE PAROUTOGLOU4, ALEXANDROS KOUFOKOTSIOS6,THEOFANIS MARIS7, SOTIRIS TERZOUDIS1, ELENA GIGI1,GRIGORIS CHATZIMAVROUDIS1, CHRISTOS ZAVOS8 & JANNIS KOUNTOURAS8

1Department of Endoscopy andMotility Unit, G.Gennimatas General Hospital, School of Medicine, Aristotle University ofThessaloniki, Thessaloniki, Greece, 2Department of Endoscopy, General Hospital Papageorgiou, Thessaloniki, Greece,32nd Department of Internal Medicine, University Hospital, Dimokrites University of Thrace, Alexandroupoli, Greece,4Department of Gastroenterology, University Hospital of Thessaly, Larissa, Greece, 51st Department of Internal Medicine,University Hospital, Dimokrites University of Thrace, Alexandroupoli, Greece, 6Department of Endoscopy, General Clinic,Thessaloniki, Greece, 7Department of Gastroenterology, George Papanikolaou General Hospital, Thessaloniki, Greece,and 82nd Department of Internal Medicine, Aristotle University, Thessaloniki, Greece

AbstractObjective. Capsule endoscopy (CE) is most commonly performed to evaluate obscure gastrointestinal bleeding (GIB).However, at present the role of CE in patients with obscure-overt GIB especially during daily clinical practice is unknown. Theaim of the present study was to investigate the diagnostic yield and the impact of CE on the management of patients withobscure-overt GIB. Material and methods. Between January 2007 and December 2011 we prospectively included allpatients with obscure-overt GIB who underwent CE after negative bidirectional endoscopy. CE findings revealing the cause ofbleeding, type of therapeutic intervention and clinical variables associated with positive CE and recurrence of GIB wereevaluated. Results. One hundred and eighteen patients with a median age of 66 years (range 8–89 years) were enrolled in thefinal analysis. The overall diagnostic yield of the CE was 66.9%. The most common findings were angiodysplasias (33.1%),followed by ulcer (23.7%), and tumors (6.8%). Age (p = 0.001) and cardiovascular disease (p = 0.007) were significant clinicalvariables predicting the higher incidence of angiodysplasias. Specific therapeutic interventions were undertaken in 54 patientswith positive CE (68.4%). Recurrence of GIB was observed in one patient with negative CE (2.6%) and 16 patients withpositive CE (20.3%). Univariate and multivariate analysis showed high age and no therapeutic intervention as significantfactors associated with recurrent bleeding. Conclusions. CE represents a promising diagnostic method in the investigation ofobscure-overt GIB, with significant impact on its clinical management in daily clinical practice.

Key Words: capsule endoscopy, diagnostic yield, impact, obscure-overt gastrointestinal bleeding

Introduction

Obscure gastrointestinal bleeding (GIB) is defined asbleeding of unknown origin that persists or recurs

after negative initial upper and lower endoscopicevaluation. It can be subclassified as obscure-occultGIB, detected only by positive fecal occult blood testsand/or iron deficiency anemia; and obscure-overt GIB

Correspondence: Panagiotis Katsinelos, MD PhD, Assistant Professor of Gastroenterology, Department of Endoscopy andMotility Unit, G. Gennimatas GeneralHospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. Tel: +30 2310 963341. Fax: +30 2310 963341;E-mail: gchatzimav@yahoo.gr

(Received 1 December 2013; revised 22 January 2014; accepted 23 January 2014)

ISSN 0036-5521 print/ISSN 1502-7708 online � 2014 Informa HealthcareDOI: 10.3109/00365521.2014.889209

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with recurrent or persistent visible episodes of bleed-ing as melena or hematochezia [1]. The majority oflesions causing obscure-overt GIB are located in thesmall bowel and rarely in the colon, stomach, pan-creas or biliary tree [2,3]. These patients may requirenumerous blood transfusions and repeated hospitaladmissions, undergo multiple diagnostic procedures,consume increased health care resources and havetheir quality of life significantly affected [4]. More-over, patients with overt GIB present a higher prob-ability to harbor a significant lesion and this puts themat a higher risk of morbidity and mortality associatedwith GIB [5].Several techniques, including endoscopy, arteriog-

raphy, scintigraphy and barium radiology, can be usedto identify the sourceof bleeding.However, in about 5–10%of cases the bleeding lesion cannot be determined[6,7]. The introduction of capsule endoscopy (CE) in2000 was a revolution in the visualization of the smallintestine; it allows for complete, noninvasive endo-scopic imaging of the small intestine. CE is now themethod of choice for investigation of obscure GIB andseveral studies have shown that a potential source ofsmall bowel bleeding can be identified in 38–93% ofpatients, an improvementover theestablishedmethodslike enteroclysis, radioisotope bleeding scan, angiog-raphy andpush enteroscopy [8].The experience on thediagnostic yield andclinical impactofCEexclusively inpatients with obscure-overtGIB is very limited [9–12],originated mainly from tertiary referral centers. How-ever, the diagnostic yield and clinical impact of CEin the management of patients with obscure-overtGIB during daily clinical practice remain unknown.In the present prospective multicenter study, we

investigated the role of CE in a Greek cohort ofpatients with obscure-overt GIB.

Patients and methods

A prospective observational study was conductedbetween January 2007 and December 2011 in sevencenters of northern (4), central (1) and east (2)Greece to investigate the role of CE in the evaluationand management of obscure-overt GIB in daily clin-ical practice. Of the seven participating centers, onlytwo were tertiary ones; thus patients’ data and man-agement provided information regarding “real world”medicine. The study was conducted in accordancewith good clinical practice, as set forth by the Helsinkiagreements and their later amendments. The studywas approved by our hospitals’ Ethics Committeesand informed consent was obtained from all patients.Obscure-overt GIB was defined according to the

published American Gastroenterological Association(AGA) position statement [13]: patients were defined

as having obscure-overt GIB when they had a bleedingepisodemarkedbymelena, hematocheziaorhematem-esis and nondiagnostic upper and lower endoscopy.Patients excluded from participation in the study werethosewith severeGIhemorrhagedefinedby the clinicalcriteria of hemorrhagic shock or hemodynamic insta-bility (systemic arterial pressure <100 mmHg andtachycardia with pulse rate >100 bpm) that persistedor recurred, despite appropriate volume resuscitationand blood transfusions. Moreover, patients wereexcluded from the study in cases of suspected ileus,small bowel obstruction and presence of cardiacpacemakeror other implantable electromedical device.Clinical and laboratory data were collected, includ-

ing age, gender, underlying diseases (liver cirrhosis,chronic renal failure and heart disease), application ofanti-coagulation, nonsteroidal antiinflammatorydrugs(NSAIDs) and antiplatelet drugs, hematologicalprofile (hemoglobin, hematocrit and platelet count),symptoms of obscure-overt GIB (melena, hematoche-zia, hematemesis), time interval between the last bleed-ing episode and CE (early: £6 days, late: >7 days,respectively) and number of transfused blood units.In addition, the findings of upper and lower endoscopyand prior radiographic examination (small bowelfollow-through, abdominal CT and MRI), or otherdiagnostic modalities (angiography, 99Tc-pertechnatescan) were recorded. Liver cirrhosis was diagnosedbased on the laboratory tests, liver biopsy and mor-phologic characteristics under CT scan or fibroscan ofthe liver. Chronic renal failure was defined whenpatients were under regular hemodialysis or peritonealdialysis. Thedefinition of heart disease included severeaortic valvular disease, congestive heart failure andcoronary artery disease. Moreover, comorbiditieswere recorded. Preparation for CE was defined asexcellent (no debris, complete visualization of themucosa), good (some debris), fair (several areas withincomplete visualization) or poor (large amounts ofdebris that compromised the results). In case of incom-plete visualization due to fair or poor preparation of thesmall intestine,CEwas repeatedwithin thenext 5days.CE (Pillcam SB, Given Imaging, Athens) was per-

formed on an outpatient/inpatient basis after bowelpreparation (oral intake of 4 l of polyethylene glycolsolution). Patients were allowed to drink clear fluids2 h after capsule ingestion and were instructed tomaintain their normal activities during CE. Theyreturned to the hospital 8 h after capsule ingestionand then the registration device and the antennas werecollected. Seven endoscopists with a diverse level ofexperience in the interpretation of CE findingsreviewed CE recordings.The reviewers were not blinded to the type of

obscure-overt GIB and patients’ data; lesions were

Capsule endoscopy and obscure-overt GI bleeding 863

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interpreted and characterized at the time of reading ina similar fashion to the CE structured terminology(CEST), previously described and reported in 2005[14]. Clinically significant findings of CE includedtumors, large ulcerations, angiodysplasias, hemangio-mas, varices, multiple erosions, Dieulafoy’s lesionsand aorto-enteric fistulas. Findings inconsistent topotential bleeding included red spots, small isolatederosions, nonbleeding diverticulae and noduleswithout mucosal breaks. CE findings were commu-nicated to the referring physician (PK); patients’management was carried out at the discretion ofthe referring physician and included endoscopic inter-vention (argon plasma coagulation), operation, ces-sation of medication (NSAIDs, aspirin, clopidogrel,oral anticoagulant) and pharmaceutical treatment(misoprostol, propranolol, thalidomide, long actingreleased somatostatin or bevacizumab).Recurrence was defined as having a new bleeding

episode marked by melena, hematochezia or hema-temesis. In case of recurrence, supportive treatmentmeasures and/or interventional management (endo-scopic/surgical) were employed as appropriate, ineach case.Following capsule ingestion, phone call wasmade to

all patients once daily for seven consecutive days, toinquire about any symptoms and to confirm capsule

expellation. As the major complication of CE iscapsule retention or impaction, all patients wereinstructed to contact the study team if they presentedwith anyGI symptomsduring or afterCE.At the endofDecember 2011, all patientswere followed-up either inoutpatient clinic or by telephone call, to record clinicaloutcome according to theCEfindings and endoscopic,pharmaceutical and surgical interventions.The primary end point of the study was to identify

small intestinal lesions as causes of obscure-overtGIB, while secondary end point was the impact ofCE findings on the management and clinical course ofpatients during the follow-up period.

Statistical analysis

Data were analyzed using the SPSS Windowsprogram (version 10.0, SPSS, Chicago, IL, USA).Continuous variables were expressed with theirmedian (range). Analysis of variance (ANOVA) wasused to calculate the significance of differences, andMann–Whitney U-test for the nonparametric values.Qualitative data were examined using the chi-squaredor Fisher’s exact test, as appropriate. Statisticalsignificance was set at p £ 0.05. The clinicalcharacteristics and treatment interventions, foundto be statistically associated with recurrence of

Studypopulation

n = 118

Melenan = 85

Positiven = 59

Pharmaceuticaln = 24

Endoscopicn = 9

Pharmaceuticaln = 9

Endoscopicn = 1

Surgicaln = 9

Nonen = 17

Surgicaln = 2

Nonen = 8

Positiven = 20

Therapeuticintervention

Therapeuticintervention

Recurrence ofbleeding n = 1

Recurrencen = 4

Recurrencen = 0

Recurrencen = 0

Recurrencen = 9

Recurrencen = 1

Recurrencen = 0

Recurrencen = 0

Recurrencen = 2

Recurrence ofbleeding n = 0

Negativen = 36

Negativen = 13

Hematochezian = 33

Figure 1. Flow chart showing the study population by presentation, CE results, therapeutic intervention and recurrence of bleeding.

864 P. Katsinelos et al.

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bleeding on univariate analysis, were entered into abinary logistic regression model, to identify factorsindependently predicting the relapse of bleeding.

Results

Between January 2007 and December 2011, 132patients were referred to our departments for CEdue to obscure-overt GIB. Of these, 118 patients(68 men, 50 women; median age: 66 years, range:8–89 years) fulfilled the inclusion criteria and wereenrolled in the final analysis. The remaining14 patients were excluded for various reasons (threerefused to participate in the study, five had incompleteCE examination of small intestine, while in sixpatients data were insufficient). From 118 patientsincluded in the final analysis, 85 patients (72%)presented with melena and 33 patients (28%) withhematochezia (Figure 1). Baseline characteristics areshown in Table I. The follow-up period ranged from

5 to 52 months (median follow-up: 13 months)(Table I). The most common comorbid diseasesincluded cardiovascular diseases (n = 61 patients;51.7%), followed by muscle-skeletal diseases (n =21 patients; 18.1%), hematological diseases (n = 7patients; 6.0%), cerebrovascular diseases (n = 8patients; 6.9%), chronic renal failure (n = 5 patients;4.3%) and portal hypertension (n = 3 patients; 2.6%)(Table I). There was a history of oral anticoagulants,aspirin, clopidogrel, clopidogrel-plus aspirin andNSAIDs intake in 12 (10.2%), 13 (11%), 18(15.3%), 18 (15.3%) and 19 patients (16.1%), respec-tively (Table I). Previous investigations to identify theetiology of bleeding were available in 39 patients.These included small bowel contrast radiology in12 patients, abdominal CT in 12 patients, MRI ofthe abdomen in 4 patients, red blood cell scan in5 patients and angiography in 6 patients (Table I). Ofthe 39 patients, all but 2 had negative findings. Twopatients underwent red blood cell scan, which showedactive hemorrhage in the jejunum. The hemoglobinlevels during the bleeding episodes ranged from 5.7 to12.7 g/dl (median: 9.35 g/dl) and 64 patients (54.2%)had been treated by blood transfusion prior to CE; thenumber of blood units transfused ranged from 1 to7 (median: 2 units) (Table I).The overall diagnostic yield of CE was 66.9%

(n = 79) (Table II). Comparison of diagnostic yieldof CE according to the time interval from the bleedingepisode, showed that when CE was performed within6 days from the last bleeding episode, its diagnosticyield was 37.3% (n = 44), and when performed after6 days the yield was 29.7% (n = 35), a difference notstatistically significant (p = 0.244) (Table III). Themost common findings were angiodysplasias(Figure 2), diagnosed in 39 patients (33.1%), fol-lowed by ulcer (Figure 3) in 28 patients (23.7%)and tumors in 8 patients (6.8%) (Table II). Patientswith angiodysplasias presented with higher incidenceof cardiovascular disease (p = 0.007; Figure 4) andclopidogrel intake (p = 0.033). Moreover, intestinalulcers were observed more often in patients withNSAIDS (p = 0.01) or aspirin (p = 0.03) intake. Usingthe post hoc analysis, the Scheffe’s test showed thatpatients with small intestinal tumors were youngerthan those with angiodysplasias (p < 0.001) or ulcers(p = 0.012) (Figure 5). Of the 79 patients with positiveCE findings, therapeutic interventions were applied in54 patients (68.35%); the intervention includedendoscopic management, and more specifically,argon plasma coagulation in 10 patients (18.52%),surgical treatment in 11 patients (20.37%) andpharmaceutical treatment (misoprostol 14, propran-olol 3, thalidomide 4, long-acting release somatostatin10, bevacizumab 2) in 33 patients (61.11%).

Table I. Characteristics of the study population.

No. of patients 118Gender (M/F) 68/50 (57.6%/42.4%)Median age (range)(years) 66 (8–89)Associated comorbiditiesCardiovascular diseases 61 (51.7%)Coronary artery disease 44 (37.3%)Valvular heart disease 6 (5.1%)Congestive heart failure 9 (7.6%)Atrial fibrillation 11 (9.3%)Cerebrovascular diseases 8 (6.9%)Muscle-skeletal diseases 21 (18.1%)Respiratory diseases 1 (0.9%)Hematological diseases 7 (6.0%)Chronic renal failure 5 (4.3%)Portal hypertension 3 (2.6%)

Medications usedNSAIDs 19 (16.1%)Antiplatelets 49 (41.5%)Aspirin 13 (11 %)Clopidogrel 18 (15.3 %)Aspirin+ clopidogrel 18 (15.3 %)Oral anticoagulants 12 (10.2%)

Type of bleedingMelena 85 (72%)Hematochezia 33 (28%)Ongoing bleeding 20 (16.9%)

Other imaging modalities usedEnteroclysis 12 (10%)Scintigraphy 5 (4.2%)Angiography 8 (6.8%)Abdominal CT 12 (10%)Abdominal MRI 4 (3.4%)

Lower median (range)hemoglobin concentration (g/dl)observed during bleeding

9.35 (5.7–12/7)

Median follow-up after CE (range)(months) 13 (5–52)

Abbreviations: NSAIDs = Nonsteroid antiinflammatory drugs;M = male; F = female.

Capsule endoscopy and obscure-overt GI bleeding 865

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Moreover, cessation of medication (NSAIDs, aspirin,clopidogrel, oral anticoagulant) was ordered in 15 of79 patients (19%) with positive CE findings. Tenpatients (12.7%) did not receive any intervention;all these patients suffered from angiodysplasias.Balloon enteroscopy with therapeutic interventionin a tertiary center was offered to them as an option,but they declined.Recurrence of bleeding occurred in one patient

(2.6%) with negative CE. Among patients withpositive CE, recurrence of bleeding was observed in16 patients (20.3%) (Figure1); only 5 (31.3%) of themhadundergone therapeutic intervention andmore spe-cifically pharmaceutical treatment (Figure 1). All ofthemwere successfully treatedwith argonplasmacoag-ulation. Of the remaining 11 patients, 6 finally under-went argon plasma coagulation with success, while5 patients refused any type of intervention.Both univariate and multivariate analysis showed

that the absence of any therapeutic intervention(endoscopic, pharmaceutical, surgical) and the highage were the two significant clinical variables for therecurrence of GIB (Table IV).

Discussion

CE is a first-line noninvasive procedure for examiningthe entire small intestine, and is recommended by theAmerican Gastrointestinal Association (AGA) [13]

and European Society for Gastrointestinal Endoscopy(ESGE) [15] as the method of choice in the evaluationof patients with obscure GIB after negative findingson bidirectional endoscopy. The role of CE in theevaluation of patients with obscure-overt GIB isevolving, because there are only four studies [9–12]in the literature investigating the impact of CE in thediagnosis and treatment of patients with purelyobscure-overt GIB. Three of these studies were

Table II. Diagnosis of obscure-overt GIB by CE.

Vascular disease 40 (34.2%)Angiodysplasias 39 (33.1%)Portal enteropathy 1 (0.8%)Ulcers 28 (23.7%)NSAIDs-induced injury 3 (1.6%)Aspirin 14 (11.9)

Radiation injury 1 (0.8%)Tumors 8 (6.8%)GIST 5 (4.2%)Adenocarcinoma 2 (1.7%)Juvenile polyposis 1 (0.8%)

Other 2 (1.7%)Bleeding diverticulum 2 (1.7%)

Undiagnosed 39 (33,1%)

Abbreviations: GIB = Gastrointestinal bleeding;GIST = Gastrointestinal stromal tumor.

Table III. Comparison of diagnostic yield of CE according to thetime interval from bleeding episode (days).

Timeinterval

Positive(no patients)

Negative(no patients) Total

£6 days 44 (37.3%) 17 (14.4%) 61 (51.7%)>6 days 35 (29.7%) 22 (18.6%) 57 (48.3%)Total 79 (66.9%) 39 (33.1%) 118 Figure 3. CE view showing a large circumscribed ulceration cov-

ered by a thick white adherent exudate, in the distal ileum.

Figure 2. Two large jejunal angiodysplasias with active bleeding.

866 P. Katsinelos et al.

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retrospective and only one was prospective and per-formed in tertiary referral centers. To our knowledge,the present study is the largest prospective, and thefirst investigating the diagnostic yield of CE inobscure-overt GIB, the therapeutic interventionsused according to the CE findings, and the clinicaloutcome of patients during the follow-up in dailyclinical practice.An important finding of our study is the relatively

small number of other imaging modalities (CT, MRI,

angiography, red blood cell scan) (Table I) that usedin the investigation of patients with obscure-overtGIB, which led to total cost reduction. In this regard,other comparable studies reported that, when com-pared with other imaging procedures, CE appears tobe a cost-saving approach in the evaluation of patientswith obscure GIB; overall, 58.4% of patients hadpositive findings with CE compared to 28.0% withother imaging procedures (p < 0.001) and the meancost of a positive diagnosis with CE was e2090.76 and

1112

16

28

7

30

20

10

0

Type of lession

Nu

mb

er o

f p

atie

nts

Angiodysplasias Ulcer Tumor

No

Yes

CVD

Figure 4. Correlation of CE findings with patients’ associated comorbidities.

Angiodysplasias Ulcer Tumor

Ag

e o

f p

atie

nts

Type of lession

100

80

60

40

20

0

N- 39 28 8

Figure 5. Association of patients’ age according to CE findings.

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that of other procedures was e3828.83 with a meancost saving of e1738.07 (p < 0.001) for one positivediagnosis [16].In our series, the overall diagnostic yield of CE

was 66.9%, which is in accordance with other studies[9–12]. We observed no statistical difference in diag-nostic yield of CE performed within 6 days frombleeding episode, and after that time interval. Thisfinding was surprising because most experts in CEsuggest that the best approach to maximize the yield ofCE is to perform the examination as close to thebleeding episode as possible [17–19]; earlier timingof CE achieves a higher diagnostic yield for patientswith obscure-overt GIB and consequently results in ahigher intervention rate [20]. This discrepancybetween our results and the results of other studiesis probably explained by the fact that 20 of 61 patientswho underwent CE within 6 days from the bleedingepisode had active bleeding during the examination;the presence of blood in the intestinal lumen obscuredthe capsule view in 12 patients leading to lowerdiagnostic yield of CE.In our study population, a significant percentage of

patients were taking antiplatelets (41.5%) or antic-oagulants (10.2%), leading to increased risk of bleed-ing. This is not surprising because anticoagulants andantiplatelets are well-recognized risk factors for bleed-ing peptic ulcers [21], as well as post-polypectomy[22], and endoscopic post-sphincterotomy bleeding[23], and it is likely that they have the same effects andmode of action in patients with small intestinal lesionssuch as angiodysplasias.Angiodysplasias (33.1%) were the leading cause of

bleeding, followed by ulcers (23.7%) and tumors(6.8%). Our findings do not differ from other studies[9–12], which have shown the presence of small bowelangiodysplasias in 20–40% of patients with obscure-overt GIB, followed by ulcers, primary or metastatictumors, and other vascular lesions (hemangioma,Dieulafoy’s lesions and portal hypertension). More-over, our study showed a correlation of angiodyspla-sias with advanced age and cardiovascular diseases,

while intestinal tumors were found in youngerpatients, findings, which are concordant with otherpublished studies [9–12,24,25].The clinical impact of CE on diagnosis and ther-

apeutic intervention has been extensively discussed inobscure-occult GIB [17,19,26]; however, in purelyobscure-overt GIB it has to yet be determined. In ourseries, 68.4% of patients underwent a therapeuticintervention (endoscopic, surgical, pharmaceutical)based on CE findings thus demonstrating a significantimpact of CE on obscure-overt GIB. Unfortunately,our experience demonstrates that therapeutic inter-vention is dependent on the availability of experiencedendoscopists in double or single balloon enteroscopy;among the seven participating centers in our study,therapeutic small bowel endoscopy could be per-formed only in two, emphasizing the differencebetween the real world of daily clinical practice andtertiary referral centers. On the other hand, despitethe availability and reliability of surgical treatment, itsinvasiveness is related with significant morbidity andmortality, especially in patients with comorbidities.Therefore, we believe that endoscopic treatment(first-line or repeat) is considered preferable tosurgery and should be performed, if available.Intestinal ulcers induced by the use of NSAIDs or

aspirin typically resolve upon withdrawal of the med-ications in most cases [27–29]. In our study, norebleeding developed after withdrawal of NSAIDsand aspirin, and in five patients the administrationof misoprostol led to healing of intestinal ulcers, eventhough aspirin was continued in patients withcoronary disease and drug-eluding stents.The cumulative risk of recurrence of hemorrhage in

our patients with positive CE after therapeutic inter-vention was significantly lower than those without anyintervention [5/54 (9%) vs. 11/25 (44%), respectively;p < 0.001].In 39 patients (33.1%) of the present study, CE was

unable to identify lesions related to bleeding for thefollowing possible reasons: CE may have missed anintestinal lesion responsible for hemorrhage; CE wasperformed relatively late after the bleeding episode,thus allowing time for some of the lesions (NSAID- oraspirin-associated ulcers) to heal; the presence ofblood in the intestinal lumen obscured the lesionsresponsible for bleeding; and the experience of inves-tigator. Contrary to the report of Esaki et al. [11], therate of rebleeding in our CE-negative patients was low(2.6% vs. 28%) and in accordance with the report byLai et al. [30] (5.6%).Themanagementofpatientswithobscure-overtGIB

and nonsignificant findings onCE remains undefined.In a recent study, Viazis et al. [31] demonstrated that amarked drop in hemoglobin value (‡4 g/dl) and a

Table IV. Univariate and multivariate analysis of factors predictingrecurrence of bleeding in patients with obscure-overt GIB whounderwent CE.

Multivariate analysis

FactorsUnivariateanalysis

95% C.I.for EXP(B)

p-Value p-Value Exp(B) Lower Upper

Age 0.041 0.027 1.061 1.007 1.119Therapeuticintervention

< 0.001 < 0.001 9.562 2.804 32.614

868 P. Katsinelos et al.

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change of bleeding pattern were predictive factors ofpositive findings during a repeat CE. We believe thattaking into account the low rebleeding rate in negativeCE, and that CE is a relatively expensive and time-consuming examination, the selection of appropriatemanagement in the future should be based onclinical symptoms, laboratory data and availability ofendoscopic modalities.The current study has several advantages. First, a

large number of patients were included; further, it isprospective with complete data and follow-up ofpatients, and represents a combination of tertiaryreferral centers (2) and centers (5) with no experiencein advanced therapeutic enteroscopy depicting moreaccurately the real world of daily clinical practice. Themain limitations of the present work are the diverselevel of experience of the participating endoscopists inthe interpretation of CE findings and the inability toperform advanced therapeutic enteroscopy in five ofthe seven participated centers, which influenced therate of diagnostic yield of CE therapeutic interventionand the rate of rebleeding episodes.In conclusion, our study confirmed the leading

role of CE in the investigation of obscure-overtGIB and its considerable impact on the subsequenttherapeutic strategy in daily clinical practice despitethe absence of therapeutic enteroscopy in manycenters.

Declaration of interest: The authors report noconflicts of interest. The authors alone are responsiblefor the content and writing of the paper.

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