Long-term rebleeding rate and predictive factors of rebleeding after capsule endoscopy in patients with obscure GI bleeding

      Background and Aims

      The incidence of rebleeding in obscure GI bleeding (OGIB) remains unclear. This study used capsule endoscopy (CE) to determine the long-term rebleeding rate and predictive factors for rebleeding in patients with OGIB.


      This single-center, observational study enrolled consecutive patients with OGIB who underwent CE as the first small intestinal examination between March 2004 and December 2015 and were followed up through medical records or letters.


      Three hundred eighty-nine patients were included in the analysis. Survival curve analysis showed that the overall cumulative rebleeding rate in OGIB during the 5 years was 41.7%. Multivariate analysis using the Cox proportional hazards model revealed that overt OGIB (hazard ratio [HR], 2.017; 95% confidence interval [CI], 1.299-3.131; P = .002), anticoagulants (HR, 1.930; 95% CI, 1.093-3.410; P = .023), positive balloon-assisted enteroscopy findings after CE (HR, 2.927; 95% CI, 1.791-4.783; P < .001), and iron supplements without therapeutic intervention (HR, 2.202; 95% CI, 1.386-3.498; P = .001) were associated with rebleeding, whereas a higher minimum hemoglobin level (HR, .902; 95% CI, .834-.975; P = .009) and therapeutic intervention (HR, .288; 95% CI, .145-.570; P < .001) significantly reduced the risk of rebleeding. Among the Charlson Comorbidity Index components, liver cirrhosis was an independent predictor associated with rebleeding in patients with OGIB (HR, 4.362; 95% CI, 2.622-7.259; P < .001) and in patients with negative CE findings (HR, 8.961; 95% CI, 4.424-18.150; P < .001).


      Rebleeding is common during the long-term follow-up of patients with OGIB. Careful follow-up is required for patients with liver cirrhosis or previous massive bleeding.

      Graphical abstract


      BAE (balloon-assisted enteroscopy), CCI (Charlson Comorbidity Index), CE (capsule endoscopy), CI (confidence interval), CKD (chronic kidney disease), HR (hazard ratio), OGIB (obscure GI bleeding)
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      1. American Gastroenterological Association medical position statement: evaluation and management of occult and obscure gastrointestinal bleeding.
        Gastroenterology. 2000; 118: 197-201
        • Raju G.S.
        • Gerson L.
        • Das A.
        • et al.
        American Gastroenterological Association (AGA) Institute technical review on obscure gastrointestinal bleeding.
        Gastroenterology. 2007; 133: 1697-1717
        • Yamamoto H.
        • Sekine Y.
        • Sato Y.
        • et al.
        Total enteroscopy with a nonsurgical steerable double-balloon method.
        Gastrointest Endosc. 2001; 53: 216-220
        • Iddan G.
        • Meron G.
        • Glukhovsky A.
        • et al.
        Wireless capsule endoscopy.
        Nature. 2000; 405: 417
        • Handa O.
        • Naito Y.
        • Okayama T.
        • et al.
        Endoscopic diagnosis of small intestinal diseases.
        Clin J Gastroenterol. 2013; 6: 94-98
        • Gerson L.B.
        • Fidler J.L.
        • Cave D.R.
        • et al.
        ACG clinical guideline: diagnosis and management of small bowel bleeding.
        Am J Gastroenterol. 2015; 110 (quiz 1288): 1265-1287
        • 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: 643-653
        • Selby W.
        Can clinical features predict the likelihood of finding abnormalities when using capsule endoscopy in patients with GI bleeding of obscure origin?.
        Gastrointest Endosc. 2004; 59: 782-787
        • Redondo-Cerezo E.
        • Perez-Vigara G.
        • Perez-Sola A.
        • et al.
        Diagnostic yield and impact of capsule endoscopy on management of patients with gastrointestinal bleeding of obscure origin.
        Dig Dis Sci. 2007; 52: 1376-1381
        • Teshima C.W.
        • Kuipers E.J.
        • van Zanten S.V.
        • et al.
        Double balloon enteroscopy and capsule endoscopy for obscure gastrointestinal bleeding: an updated meta-analysis.
        J Gastroenterol Hepatol. 2011; 26: 796-801
        • Cortegoso Valdivia P.
        • Skonieczna-Zydecka K.
        • Pennazio M.
        • et al.
        Capsule endoscopy transit-related indicators in choosing the insertion route for double-balloon enteroscopy: a systematic review.
        Endosc Int Open. 2021; 9: E163-E170
        • Otani K.
        • Watanabe T.
        • Shimada S.
        • et al.
        Clinical utility of capsule endoscopy and double-balloon enteroscopy in the management of obscure gastrointestinal bleeding.
        Digestion. 2018; 97: 52-58
        • Shahidi N.C.
        • Ou G.
        • Svarta S.
        • et al.
        Factors associated with positive findings from capsule endoscopy in patients with obscure gastrointestinal bleeding.
        Clin Gastroenterol Hepatol. 2012; 10: 1381-1385
        • Charlson M.E.
        • Pompei P.
        • Ales K.L.
        • et al.
        A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
        J Chronic Dis. 1987; 40: 373-383
        • Shimada S.
        • Watanabe T.
        • Nadatani Y.
        • et al.
        Clinical factors associated with positive capsule endoscopy findings in patients with obscure gastrointestinal bleeding: a single-center study.
        Scand J Gastroenterol. 2017; 52: 1219-1223
        • Katsinelos P.
        • Chatzimavroudis G.
        • Terzoudis S.
        • et al.
        Diagnostic yield and clinical impact of capsule endoscopy in obscure gastrointestinal bleeding during routine clinical practice: a single-center experience.
        Med Princ Pract. 2011; 20: 60-65
        • Saurin J.C.
        • Delvaux M.
        • Gaudin J.L.
        • et al.
        Diagnostic value of endoscopic capsule in patients with obscure digestive bleeding: blinded comparison with video push-enteroscopy.
        Endoscopy. 2003; 35: 576-584
        • Korman L.Y.
        • Delvaux M.
        • Gay G.
        • et al.
        Capsule endoscopy structured terminology (CEST): proposal of a standardized and structured terminology for reporting capsule endoscopy procedures.
        Endoscopy. 2005; 37: 951-959
        • Yung D.E.
        • Koulaouzidis A.
        • Avni T.
        • et al.
        Clinical outcomes of negative small-bowel capsule endoscopy for small-bowel bleeding: a systematic review and meta-analysis.
        Gastrointest Endosc. 2017; 85: 305-317
        • Shin J.K.
        • Cheon J.H.
        • Lim J.S.
        • et al.
        Long-term outcomes of obscure gastrointestinal bleeding after CT enterography: Does negative CT enterography predict lower long-term rebleeding rate?.
        J Gastroenterol Hepatol. 2011; 26: 901-907
        • Macdonald J.
        • Porter V.
        • McNamara D.
        Negative capsule endoscopy in patients with obscure GI bleeding predicts low rebleeding rates.
        Gastrointest Endosc. 2008; 68: 1122-1127
        • Wetwittayakhlang P.
        • Wonglhow J.
        • Netinatsunton N.
        • et al.
        Re-bleeding and its predictors after capsule endoscopy in patients with obscure gastrointestinal bleeding in long-term follow-up.
        BMC Gastroenterol. 2019; 19: 216
        • von Elm E.
        • Altman D.G.
        • Egger M.
        • et al.
        The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
        Int J Surg. 2014; 12: 1495-1499
        • Jutabha R.
        • Jensen D.M.
        Management of upper gastrointestinal bleeding in the patient with chronic liver disease.
        Med Clin North Am. 1996; 80: 1035-1068
        • Arakawa D.
        • Ohmiya N.
        • Nakamura M.
        • et al.
        Outcome after enteroscopy for patients with obscure GI bleeding: diagnostic comparison between double-balloon endoscopy and video capsule endoscopy.
        Gastrointest Endosc. 2009; 69: 866-874
        • Chalasani N.
        • Cotsonis G.
        • Wilcox C.M.
        Upper gastrointestinal bleeding in patients with chronic renal failure: role of vascular ectasia.
        Am J Gastroenterol. 1996; 91: 2329-2332
        • Harada A.
        • Torisu T.
        • Okamoto Y.
        • et al.
        Predictive factors for rebleeding after negative capsule endoscopy among patients with overt obscure gastrointestinal bleeding.
        Digestion. 2020; 101: 129-136
        • Tan W.
        • Ge Z.Z.
        • Gao Y.J.
        • et al.
        Long-term outcome in patients with obscure gastrointestinal bleeding after capsule endoscopy.
        J Dig Dis. 2015; 16: 125-134
        • Lai L.H.
        • Wong G.L.
        • Chow D.K.
        • et al.
        Long-term follow-up of patients with obscure gastrointestinal bleeding after negative capsule endoscopy.
        Am J Gastroenterol. 2006; 101: 1224-1228
        • Park J.J.
        • Cheon J.H.
        • Kim H.M.
        • et al.
        Negative capsule endoscopy without subsequent enteroscopy does not predict lower long-term rebleeding rates in patients with obscure GI bleeding.
        Gastrointest Endosc. 2010; 71: 990-997
        • Silva J.C.
        • Pinho R.
        • Ponte A.
        • et al.
        Predicting the risk of rebleeding after capsule endoscopy in obscure gastrointestinal bleeding—external validation of the RHEMITT score.
        Dig Dis. Epub 2020 Jul 8;
        • Iwamoto J.
        • Mizokami Y.
        • Shimokobe K.
        • et al.
        The clinical outcome of capsule endoscopy in patients with obscure gastrointestinal bleeding.
        Hepatogastroenterology. 2011; 58: 301-305
        • Harada A.
        • Torisu T.
        • Fujioka S.
        • et al.
        Risk of rebleeding in patients with small bowel vascular lesions.
        Intern Med. 2021; 60: 3663-3669
        • Endo H.
        • Matsuhashi N.
        • Inamori M.
        • et al.
        Rebleeding rate after interventional therapy directed by capsule endoscopy in patients with obscure gastrointestinal bleeding.
        BMC Gastroenterol. 2008; 8: 12
        • Otani K.
        • Watanabe T.
        • Shimada S.
        • et al.
        Usefulness of small bowel reexamination in obscure gastrointestinal bleeding patients with negative capsule endoscopy findings: comparison of repeat capsule endoscopy and double-balloon enteroscopy.
        United Eur Gastroenterol J. 2018; 6: 879-887
        • Metzger Y.C.
        • Adler S.N.
        • Shitrit A.B.-G.
        • et al.
        Comparison of a new PillCam™ SB2 video capsule versus the standard PillCam™ SB for detection of small bowel disease.
        Rep Med Imag. 2009; 2: 7-11