Endoscopy 2024; 56(04): 291-301
DOI: 10.1055/a-2232-9630
Original article

High risk stigmata and treatment strategy for acute lower gastrointestinal bleeding: a nationwide study in Japan

Tomonori Aoki
 1   Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Eiji Sadashima
 2   Department of Medical Research Institute, Saga-Ken Medical Centre Koseikan, Saga, Japan
 3   Department of Gastroenterology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
 4   Department of Gastroenterology and Hepatology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan
Atsuo Yamada
 1   Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Jun Omori
 5   Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan
Takashi Ikeya
 6   Department of Gastroenterology, St. Luke's International University, Tokyo, Japan
Taiki Aoyama
 7   Department of Gastroenterology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan
Naoyuki Tominaga
 8   Department of Gastroenterology, Saga-Ken Medical Centre Koseikan, Saga, Japan
Yoshinori Sato
 9   Division of Gastroenterology and Hepatology, Department of Internal Medicine, St Marianna University School of Medicine, Kanagawa, Japan
Takaaki Kishino
10   Department of Gastroenterology and Hepatology, Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan
11   Department of Gastroenterology, Tokyo Shinagawa Hospital, Tokyo, Japan
Tsunaki Sawada
12   Department of Endoscopy, Nagoya University Hospital, Aichi, Japan
Masaki Murata
13   Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
Akinari Takao
14   Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
Kazuhiro Mizukami
15   Department of Gastroenterology, Oita University, Oita, Japan
Ken Kinjo
16   Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
Shunji Fujimori
17   Department of Gastroenterology, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan
Takahiro Uotani
18   Department of Gastroenterology, Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan
Minoru Fujita
19   Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center, Okayama, Japan
20   Division of Gastroenterology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
Yoku Hayakawa
 1   Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
 1   Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Mitsuru Kaise
 5   Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan
Naoyoshi Nagata
21   Department of Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan
22   Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan
CODE BLUE-J Study collaborators
› Author Affiliations
Supported by: the Advanced Research and Development Programs for Medical Innovation (PRIME) from AMED
Supported by: P-CREATE from AMED
Supported by: Smoking Research Foundation http://dx.doi.org/10.13039/501100004330
Supported by: JSPS KAKENHI Grant 20K08366
Supported by: Grants-in-Aid for Research from the National Center for Global Health and Medicine 19A-2015
Supported by: Takeda Science Foundation http://dx.doi.org/10.13039/100007449
Supported by: KAKENHI Grants-in-Aid for Scientific Research from JSPS
Supported by: the Ministry of Health, Labour and Welfare, Japan 19HB1003


Background The rebleeding risks and outcomes of endoscopic treatment for acute lower gastrointestinal bleeding (ALGIB) may differ depending on the bleeding location, type, and etiology of stigmata of recent hemorrhage (SRH) but have yet to be fully investigated. We aimed to identify high risk endoscopic SRH and to propose an optimal endoscopic treatment strategy.

Methods We retrospectively analyzed 2699 ALGIB patients with SRH at 49 hospitals (CODE BLUE-J Study), of whom 88.6 % received endoscopic treatment.

Results 30-day rebleeding rates of untreated SRH significantly differed among locations (left colon 15.5 % vs. right colon 28.6 %) and etiologies (diverticular bleeding 27.5 % vs. others [e. g. ulcerative lesions or angioectasia] 8.9 %), but not among bleeding types. Endoscopic treatment reduced the overall rebleeding rate (adjusted odds ratio [AOR] 0.69; 95 %CI 0.49–0.98), and the treatment effect was significant in right-colon SRH (AOR 0.46; 95 %CI 0.29–0.72) but not in left-colon SRH. The effect was observed in both active and nonactive types, but was not statistically significant. Moreover, the effect was significant for diverticular bleeding (AOR 0.60; 95 %CI 0.41–0.88) but not for other diseases. When focusing on treatment type, the effectiveness was not significantly different between clipping and other modalities for most SRH, whereas ligation was significantly more effective than clipping in right-colon diverticular bleeding.

Conclusions A population-level endoscopy dataset allowed us to identify high risk endoscopic SRH and propose a simple endoscopic treatment strategy for ALGIB. Unlike upper gastrointestinal bleeding, the rebleeding risks for ALGIB depend on colonic location, bleeding etiology, and treatment modality.

Tomonori Aoki and Naoyoshi Nagata contributed equally to this work

Supplementary material

Publication History

Article published online:
14 February 2024

© 2024. Thieme. All rights reserved.

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  • References

  • 1 Strate LL, Gralnek IM. ACG Clinical Guideline: Management of patients with acute lower gastrointestinal bleeding. Am J Gastroenterol 2016; 111: 459-474
  • 2 Triantafyllou K, Gkolfakis P, Gralnek IM. et al. Diagnosis and management of acute lower gastrointestinal bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2021; 53: 850-868
  • 3 Nagata N, Ishii N, Manabe N. et al. Guidelines for colonic diverticular bleeding and colonic diverticulitis: Japan Gastroenterological Association. Digestion 2019; 99 (Suppl. 01) 1-26
  • 4 Laine L, Barkun AN, Saltzman JR. et al. ACG Clinical Guideline: Upper gastrointestinal and ulcer bleeding. Am J Gastroenterol 2021; 116: 899-917
  • 5 Gralnek IM, Stanley AJ, Morris AJ. et al. Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2021. Endoscopy 2021; 53: 300-332
  • 6 Forrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastrointestinal bleeding. Lancet 1974; 2: 394-397
  • 7 Chiorean EG, Nandakumar G, Fadelu T. et al. Treatment of patients with late-stage colorectal cancer: ASCO resource-stratified guideline. JCO Glob Oncol 2020; 6: 414-438
  • 8 Spadaccini M, Albéniz E, Pohl H. et al. Prophylactic clipping after colorectal endoscopic resection prevents bleeding of large, proximal polyps: meta-analysis of randomized trials. Gastroenterology 2020; 159: 148-158.e11
  • 9 Brandt LJ, Feuerstadt P, Blaszka MC. Anatomic patterns, patient characteristics, and clinical outcomes in ischemic colitis: a study of 313 cases supported by histology. Am J Gastroenterol 2010; 105: 2245-2252
  • 10 Kobayashi K, Nagata N, Furumoto Y. et al. Effectiveness and adverse events of endoscopic clipping versus band ligation for colonic diverticular hemorrhage: a large-scale multicenter cohort study. Endoscopy 2022; 54: 735-744
  • 11 Kishino T, Nagata N, Kobayashi K. et al. Endoscopic direct clipping versus indirect clipping for colonic diverticular bleeding: a large multicenter cohort study. United European Gastroenterol J 2022; 10: 93-103
  • 12 Gobinet-Suguro M, Nagata N, Kobayashi K. et al. Treatment strategies for reducing early and late recurrence of colonic diverticular bleeding based on stigmata of recent hemorrhage: a large multicenter study. Gastrointest Endosc 2022; 95: 1210-1222
  • 13 Nagata N, Kobayashi K, Yamauchi A. et al. Identifying bleeding etiologies by endoscopy affected outcomes in 10,342 cases with hematochezia: CODE BLUE-J Study. Am J Gastroenterol 2021; 116: 2222-2234
  • 14 Nagata N, Kobayashi K, Yamauchi A. et al. Nationwide large-scale data of acute lower gastrointestinal bleeding in Japan uncover detailed etiologies and relevant outcomes: CODE BLUE J-Study. medRxiv 2021; DOI: 10.1101/2021.01.18.21250035.
  • 15 Charlson ME, Pompei P, Ales KL. et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373-383
  • 16 Jensen DM, Ohning GV, Kovacs TOG. et al. Natural history of definitive diverticular hemorrhage based on stigmata of recent hemorrhage and colonoscopic Doppler blood flow monitoring for risk stratification and definitive hemostasis. Gastrointest Endosc 2016; 83: 416-423
  • 17 Kaltenbach T, Watson R, Shah J. et al. Colonoscopy with clipping is useful in the diagnosis and treatment of diverticular bleeding. Clin Gastroenterol Hepatol 2012; 10: 131-137
  • 18 Strate LL, Orav EJ, Syngal S. Early predictors of severity in acute lower intestinal tract bleeding. Arch Intern Med 2003; 163: 838-843
  • 19 Strate LL, Ayanian JZ, Kotler G. et al. Risk factors for mortality in lower intestinal bleeding. Clin Gastroenterol Hepatol 2008; 6: 1004-1010
  • 20 VanderWeele TJ. Principles of confounder selection. Eur J Epidemiol 2019; 34: 211-219
  • 21 Peduzzi P, Concato J, Kemper E. et al. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol 1996; 49: 1373-1379
  • 22 Elze MC, Gregson J, Baber U. et al. Comparison of propensity score methods and covariate adjustment: evaluation in 4 cardiovascular studies. J Am Coll Cardiol 2017; 69: 345-357
  • 23 Peery AF, Keil A, Jicha K. et al. Association of obesity with colonic diverticulosis in women. Clin Gastroenterol Hepatol 2020; 18: 107-114.e1
  • 24 Sugihara K, Muto T, Morioka Y. Motility study in right sided diverticular disease of the colon. Gut 1983; 24: 1130-1134
  • 25 Niikura R, Nagata N, Shimbo T. et al. Colonoscopy can miss diverticula of the left colon identified by barium enema. World J Gastroenterol 2013; 19: 2362-2367
  • 26 Sadahiro S, Ohmura T, Yamada Y. et al. Analysis of length and surface area of each segment of the large intestine according to age, sex and physique. Surg Radiol Anat 1992; 14: 251-257
  • 27 Motomura Y, Akahoshi K, Matsui N. et al. Clinical and endoscopic characteristics of acute haemorrhagic rectal ulcer, and endoscopic haemostatic treatment: a retrospective study of 95 patients. Colorectal Dis 2010; 12: e320-e325
  • 28 Nishimura N, Mizuno M, Shimodate Y. et al. Risk factors for active bleeding from colonic angiodysplasia confirmed by colonoscopic observation. Int J Colorectal Dis 2016; 31: 1869-1873