Background and Aims
Methods
Results
Conclusions
Graphical abstract

Abbreviations:
CI (confidence interval), GRADE (Grading of Recommendations Assessment, Development and Evaluation), IV (intravenous), NSAID (nonsteroidal anti-inflammatory drug), PPI (proton pump inhibitor), PUD (peptic ulcer disease), RCT (randomized controlled trial), RR (risk ratio)Methods
Data sources and search strategy

Inclusion and exclusion criteria
Data extraction
Risk of bias assessment
Data synthesis and statistical analysis
Assessment of quality of evidence
Results
Search strategy yield
Study, year | No. of patients | Active bleeding at initial endoscopy n (%) | Endoscopic treatment during first and second endoscopy | Other treatments in both groups | Inclusion criteria | Exclusion criteria | Follow-up |
---|---|---|---|---|---|---|---|
Park et al, 2018 14 | 319 | 130 (40.7) | Hemoclip or thermal coagulation and/or epinephrine or fibrin glue injection therapy. | IV PPI q 12 h | Patients aged 18 y who underwent successful endoscopic hemostasis for bleeding peptic ulcers within 24 h after the admission. | Bleeding not controlled at initial endoscopy, no informed consent, bleeding started while already hospitalized with another illness, bleeding from known carcinoma of the stomach or nonulcerative lesions such as Dieulafoy’s lesion. | 30 days |
Belei et al, 2018 9 | 127 | 52 (41) | Epinephrine injection followed by hemoclips | In second-look endoscopy group, esomeprazole .5 mg/kg q 12 h. In control group, 1 mg/kg IV bolus followed by .1 mg/kg/h continuous infusion. In children ≥40 kg and age ≥12 y, standard adult PPI dose was used. | Patients aged between 2 and 18 y who had undergone successful endoscopic hemostasis for bleeding peptic ulcers. Patients with bleeding peptic ulcers with endoscopic stigmata of active bleeding, nonbleeding visible vessels, or adherent clots were recruited. | If the bleeding could not be controlled during the first endoscopy, no informed consent, known allergy to PPI, bleeding from nonulcer lesions, ASA grade V or VI, patients weighing < 10 kg. | 30 days |
Chiu et al, 2016 8 | 305 | 135 (42) | Epinephrine injection followed by heat probe or hemoclips | In second-look endoscopy group IV omeprazole q 12 h for 72 h. In single endoscopy group, IV omeprazole 80-mg bolus followed by continuous infusion of 8 mg omeprazole per hour for 72 h. | Patients aged 15-90 y who underwent successful endoscopic hemostasis for bleeding peptic ulcers. Patients with bleeding peptic ulcers with endoscopic stigmata of active bleeding, nonbleeding visible vessels, or adherent clots were recruited to the study. | Bleeding could not be controlled during the first endoscopy, no informed consent, pregnant, known allergy to PPIs, bleeding from carcinoma of the stomach or other nonulcer lesions including Dieulafoy’s lesions or angiodysplasia, ASA grade V or VI. | 30 days |
Lee et al, 2005 15 | 143 | NA | Epinephrine injection followed by hemoclips | NA | Patients with bleeding gastric or duodenal ulcers admitted to Kyungpook National University Hospital. | NA | 30 days |
Chiu et al, 2003 16 | 194 | 89 (45.8) | Epinephrine injection followed by heater probe | IV PPI q 12 h | Patients aged 15-90 y who underwent successful endoscopic hemostasis for bleeding peptic ulcers within 24 h after admission. | Bleeding not controlled at primary endoscopy, no informed consent, bleeding from carcinoma of the stomach or other nonulcer lesions such as Dieulafoy lesions, patients with ASA grade V. | 30 days |
Messmann et al, 1998 17 | 105 | 46 (43.8) | Epinephrine injection followed by fibrin glue injection | IV PPI q 12 h for 48 h | Patients who presented with upper GI bleed and endoscopy showed peptic ulcer with active bleeding or signs of recent bleeding. | Failed initial endoscopy treatment, malignant disease, severe coagulopathy, age <18 y, no informed consent. | 4 weeks |
Saeed et al, 1996 18 | 40 | 27 (67.5) | Heat probe ± epinephrine injection | IV ranitidine | High-risk patients (Baylor bleeding score >5) in whom endoscopic hemostasis was achieved. | Low-risk patients (Baylor bleeding score <5), high-risk patients in whom endoscopic therapy was not indicated, and if initial endoscopic hemostasis was not successful. | Until discharge |
Lin et al 1996 11 | 115 | NA | Epinephrine injection | Ranitidine. Route and dose not available | Patients with bleeding ulcer of upper GI tract were enrolled after endoscopic injection therapy with .01% epinephrine. | Patients with terminal cancer or multiple-organ failure. | NA |
Villanueva et al, 1994 10 | 104 | 40 (38.4) | Epinephrine injection | IV ranitidine | Patients presenting with upper GI bleed in whom endoscopy revealed a peptic ulcer with active bleeding or nonbleeding visible vessel. | Patients age <18 y, no informed consent. |
Study, year | Groups | No. of patients in each group | Recurrent bleeding | Need for surgery | Mortality | Units of blood transfused | Size of ulcer | Length of stay |
---|---|---|---|---|---|---|---|---|
Park et al, 2018 14 | Second-look EGD | 158 | 16 | 0 | 2 | 2.4 ± 1.7 | NA | 6 (0-57) |
Single EGD | 161 | 9 | 1 | 2 | 2.2 ± 1.6 | 5 (0-62) | ||
Belei et al, 2018 9 | Second-look EGD | 63 | 4 | 2 | NA | NA | .8 ± .6 | NA |
Single EGD | 64 | 3 | 1 | 1 ± .5 | ||||
Chiu et al, 2016 8 | Second-look EGD | 152 | 12 | 3 | 3 | 1.9 ± 2.4 | 1 ± .6 | 3 (1-49) |
Single EGD | 153 | 10 | 6 | 8 | 2.2 ± 2.7 | 1.2 ± .8 | 2 (2-35) | |
Lee et al, 2005 15 | Second-look EGD | 70 | 7 | NA | NA | NA | NA | 5 |
Single EGD | 73 | 12 | 7 | |||||
Chiu et al, 2003 16 | Second-look EGD | 100 | 5 | 1 | 2 | 1.9 ± 1.7 | 1 ± .5 | 4 (2-24) |
Single EGD | 94 | 13 | 6 | 2 | 2.1 ± 2.3 | .9 ± .5 | 4 (2-24) | |
Messmann et al, 1998 17 | Second-look EGD | 52 | 11 | 3 | 3 | 3.5 | 1.3 ± .4 | 14 |
Single EGD | 53 | 9 | 2 | 2 | 3.1 | 1.1 ± .3 | 12 | |
Saeed et al, 1996 18 | Second-look EGD | 19 | 0 | 0 | 1 | 3 | NA | NA |
Single EGD | 21 | 5 | 0 | 2 | 2 | |||
Lin et al, 1996 11 | Second-look EGD | 60 | 4 | NA | NA | NA | NA | NA |
Single EGD | 55 | 12 | ||||||
Villanueva et al, 1994 10 | Second-look EGD | 52 | 11 | 4 | 1 | 1.7 ± 1.9 | NA | 9.3 ± 8.6 |
Single EGD | 52 | 15 | 8 | 2 | 2.5 ± 2.5 | 11.8 ± 10.8 |
Meta-analysis
Recurrent bleeding

Need for surgery

Mortality

Blood transfusion

Discussion
Appendix

Study, year | Groups | No. of patients | No. (%) of male patients | Mean age | Forest classification Class, n (%) | Ulcer location n (%) | Mean size of ulcer (cm) | Hemodynamic instability n (%) | Mean hemoglobin at presentation | Use of nonsteroidal anti-inflammatory drugs n (%) | Helicobacter pylori infection n (%) | Comorbidity indices |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Park et al, 2018 14 | Second-look endoscopy | 158 | 124 (78.5) | 58.4 ± 16.6 | Ia=17(10.7), Ib=49 (31), IIa=68 (43), IIb= 24 (15.1) | Gastric = 92 (58.2), Duodenal= 66 (41.8) | NA | NA | 9.5 ± 1.7 | 56 (35.4) | 63 (39.9) | Rockall score = 5.3 ± 1.7 Charlson comorbidity index = 1.8 ± 1.4 |
Control | 161 | 120 (74.5) | 58.7 ± 18.3 | Ia=15 (9.3), Ib=50 (31), IIa=75 (46.6), IIb= 21 (13) | Gastric= 101 (62.7) Duodenal= 60 (37.3) | 9.8 ± 1.8 | 57 (35.4) | 52 (32.3) | Rockall score = 5.1 ± 1.8 Charlson comorbidity index = 1.6 ± 1.4 | |||
Belei et al, 2018 9 | Second-look endoscopy | 63 | 24 (38) | 9.7 ± 1.5 | Ia=5(7.9) , Ib=21(33.3), IIa=17(27) , IIb= 20 (31.2) | Gastric=15(23.8) duodenal= 48 (76.2) | 0.8 (.6) | 7 (11.1) | 9.5 ± 2.3 | 28 (44.4) | 35 (55.5) | ASA = 2 (1-3) |
Control | 64 | 23 (35.9) | 10.5 ± 1.2 | Ia=6(9.3), Ib=20(31.2), IIa=19(29.6), IIb= 19(29.6) | Gastric= 13 (20.3) Duodenal= 51 (79. 7) | 1 (.5) | 6 (9.3) | 9.1 ± 2.4 | 25 (39) | 32 (50) | ASA = 2 (1-3) | |
Chiu et al, 2016 8 | Second-look endoscopy | 152 | 114 (75) | 67.4 | Ia=14(9.2), Ib=51(33.5), IIa=42(27.6), IIb= 45(29.6) | Gastric= NA Duodenal= 91(59.8) Anastomotic =6 (3.9) | 1 (.6) | 17 (11.2) | 9.6 (2.6) | 54 (35.5) | 67 (44.1) | ASA= 2 (1-3) Comorbidities, median= 2 (1-3) |
Control | 153 | 117 (76.4) | 67.1 | Ia=8 (5.2), Ib=62 (40.5), IIa=41 (26.8), IIb= 42 (27.4) | Gastric= NA Duodenal= 91(59.8) Anastomotic= 5 (3.3) | 1.2 (.8) | 14 (9.2) | 9.4 (2.8) | 60 (39.2) | 66 (43.1) | ASA = 2 (1-3) Comorbidities, median = 2 (0-7) | |
Lee et al, 2005 15 | Second-look endoscopy | 70 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
Control | 73 | |||||||||||
Chiu et al, 2003 16 | Second-look endoscopy | 100 | 70 (70) | 68.7 ± 13.9 | Ia=10 (10), Ib=33 (33), IIa=37(37), IIb= 20 (20) | Gastric= 44 (44), Duodenal= 56 (56) | 1 (.5) | 48 (48) | 8.9 (2.6) | 12 (12) | 56 (56) | Coexisting illnesses= 65%, ASA I=44, ASA II=30, ASA III=23, ASA IV=3 |
Control | 94 | 62 (66) | 67.5 ± 12.6 | Ia=14 (14.8), Ib=32 (34), IIa=27 (28.7), IIb= 21 (22.3) | Gastric= 40 (42.5) Duodenal= 54 (50.7) | .9 (.5) | 44 (46.8) | 9.4 (2.7) | 6 (6.4) | 44 (46.8) | Coexisting illnesses= 69.1%, ASA I= 43, ASA II= 37, ASA III=15, ASA IV= 1 | |
Messmann et al, 1998 17 | Second-look endoscopy | 52 | 29 (55.7) | 63.1 ± 6.2 | Ia=9 (17.3), Ib=16 (30.7), IIa=16(30.7),IIb= 11 (21) | Gastric=22 (42.3) Duodenal= 30 (57.7) | 1.3 ± 0.4 | 31 (60) | 10.3 ± 1.2 | 24 (47) | NA | NA |
Control | 53 | 34 (64.2) | 60.9 ± 5.9 | Ia=7 (13.2), Ib=14 (26.4), IIa=17 (32), IIb= 15(28.3) | Gastric=24 (45.3) Duodenal= 29 (54.7) | 1.1 ± .3 | 29 (53) | 9.8 ± 2.1 | 27 (53) | |||
Saeed et al, 1996 18 | Second-look endoscopy | 19 | NA | 62 (23-75) | Ia and Ib= 13 (68), IIb= 3 (16) | Gastric= 6 (32) Duodenal= 11 (58) Esophageal= 2 (10) | NA | NA | NA | 7 (39) | NA | NA |
Control | 21 | 70 (51-94) | Ia and Ib= 14 (67) IIb= 1 (5) | Gastric= 12 (57) Duodenal=9 (43) Esophageal= 0 | 9 (42) | |||||||
Lin et al 1996 11 | Second-look endoscopy | 60 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
Control | 55 | |||||||||||
Villanueva et al, 1994 10 | Second-look endoscopy | 52 | 39 (75) | 62.4 ± 16.4 | Ia=1 (2), Ib=16 (30.7), IIa=35 (67.3) | Gastric=15 (29), Duodenal= 34 (65) Stomal= 1 (2) Pyloric=2 (4) | NA | NA | 10 (2.6) | 21 (44) | NA | Associated diseases: 23 (44) |
Control | 52 | 33 (63.4) | 66.5 ± 13.5 | Ia=3 (5.7), Ib=20 (38.4), IIa=29 (55.7) | Gastric: 12 (23) Duodenal: 33 (63) Stomal: 4 (8) Pyloric: 3 (6) | 9.5 (2.3) | 31 (59) | Associated diseases: 31 (59) |
Study | Random sequence generation | Allocation concealment | Performance bias | Detection bias | Attrition bias | Reporting bias |
---|---|---|---|---|---|---|
Belei et al 9 | Low | Unclear | Low | Low | Low | Low |
Lin et al 11 | Unclear | Unclear | Unclear | Unclear | Low | Unclear |
Chiu et al 16 | Low | Low | Low | Low | Low | Low |
Chiu et al 8 | Low | Low | Low | Low | Low | Low |
Lee et al 15 | Unclear | Unclear | Unclear | Unclear | Low | Unclear |
Messmann et al 17 | Low | Low | Low | Low | Low | Low |
Park et al 14 | Low | Low | Low | Low | Low | Low |
Saeed et al 18 | Low | Low | Low | Low | Low | Low |
Villanueva et al 10 | Low | Low | Low | Low | Low | Low |
Outcomes | Risk of bias | Indirectness | Inconsistency | Imprecision | Publication bias | Quality of evidence |
---|---|---|---|---|---|---|
Rebleeding | Low | No serious indirectness | Moderate heterogeneity | Serious imprecision | Not detected | Low (because of Inconsistency and imprecision) |
Need for surgery | Low | No serious indirectness | Low heterogeneity | Serious imprecision | Not detected | Moderate (because of imprecision) |
Mortality | Low | No serious indirectness | Low heterogeneity | Serious imprecision | Not detected | Moderate (because of imprecision) |
Search number | PubMed search query | Results |
---|---|---|
1 | (Esophagoduodenoscop∗ OR EGD OR esophagogastroduodenoscop∗ OR esophago-gastro-duodenoscop∗ OR oesophagogastroduodenoscop∗ OR endoscop∗ OR gastroscop∗ OR duodenoscop∗ OR esophagoscop∗)OR "Endoscopy, Gastrointestinal"[Mesh]) | 296,129 |
2 | (Upper-gastrointestinal-bleed∗ OR upper-GI-bleed∗ OR upper-Gastrointestinal-Hemorrhage OR upper-digestive-haemorrhage OR upper-digestive-hemorrhage OR upper-digestive-tract-haemorrhage OR upper-digestive-tract-hemorrhage OR Upper-gastrointestinal-tract-bleed∗ OR upper-GI-tract-bleed∗ OR esophagogastroduodenal-bleed∗ OR esophagogastroduodenal-hemorrhage∗ OR esophagogastroduodenal-haemorrhage∗ OR ("Gastrointestinal Hemorrhage"[Mesh] AND (gastric∗ OR gastro∗ OR stomach OR esophagi∗ OR duoden∗))) | 50,754 |
3 | Second-look∗ OR "Second-Look Surgery"[Mesh] | 5132 |
4 | #1 AND #3 | 430 |
5 | #2 AND #4 | 103 |
6 | (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR placebo[tiab] OR drug therapy[sh] OR randomly[tiab] OR trial[tiab] OR groups[tiab] NOT (animals [mh] NOT humans [mh])) | 4,220,476∗ |
7 | #5 AND #6 | 49 |
8 | #7 NOT ("editorial"[Publication Type] OR "guideline"[Publication Type] OR "introductory journal article"[Publication Type] OR "review"[Publication Type] OR "meta analysis"[Publication Type] OR "systematic review"[Publication Type]) | 32 |
∗Search terms for randomized controlled trials from Cochrane: https://work.cochrane.org/pubmed (Sensitivity-maximizing version) | ||
No. | Embase query | Results |
1 | 'second look∗' OR 'second look surgery'/exp OR '2nd look∗' | 7982 |
2 | esophagoduodenoscop∗ OR egd OR esophagogastroduodenoscop∗ OR 'esophago gastro duodenoscop∗' OR oesophagogastroduodenoscop∗ OR endoscop∗ OR gastroscop∗ OR duodenoscop∗ OR esophagoscop∗ OR 'esophagogastroduodenoscopy'/exp | 521,125 |
3 | #1 AND #2 | 964 |
4 | 'upper gastrointestinal bleed∗' OR 'upper gi bleed∗' OR 'upper gastrointestinal hemorrhage' OR 'upper digestive haemorrhage' OR 'upper digestive hemorrhage' OR 'upper digestive tract haemorrhage' OR 'upper digestive tract hemorrhage' OR 'upper gastrointestinal tract bleed∗' OR 'upper gi tract bleed∗' OR 'esophagogastroduodenal bleed∗' OR 'esophagogastroduodenal hemorrhage∗' OR 'esophagogastroduodenal haemorrhage∗' OR 'upper gastrointestinal bleeding'/exp OR 'gastrointestinal hemorrhage'/exp OR 'peptic ulcer bleeding'/exp | 117,602 |
5 | #3 AND #4 | 243 |
6 | random∗ OR factorial∗ OR crossover∗ OR 'cross over' OR placebo∗ OR (doubl∗ NEXT/2 blind∗) OR (singl∗ NEXT/2 blind∗) OR assign∗ OR allocat∗ OR volunteer∗ OR 'crossover procedure'/exp OR 'double-blind procedure'/exp OR 'randomized controlled trial'/exp OR 'single-blind procedure'/exp | 2,623,171 |
7 | #5 AND #6 | 76 |
8 | #7 NOT ('conference review'/it OR 'editorial'/it OR 'review'/it) | 59 |
9 | #8 NOT ('meta analysis'/de OR 'practice guideline'/de OR 'systematic review'/de) | 44 |
Cochrane Central Register of Controlled Trials | ||
Issue 9 of 12, September 2020 | ||
21 Trials matching | ||
Second-look∗ in Title Abstract Keyword | ||
AND | ||
(Esophagoduodenoscop∗ OR EGD OR esophagogastroduodenoscop∗ OR esophago-gastro-duodenoscop∗ OR oesophagogastroduodenoscop∗ OR endoscop∗ OR gastroscop∗ OR duodenoscop∗ OR esophagoscop∗) in Title Abstract Keyword | ||
AND | ||
(Upper-gastrointestinal-bleed∗ OR upper-GI-bleed∗ OR upper-Gastrointestinal-Hemorrhage OR upper-digestive-haemorrhage OR upper-digestive-hemorrhage OR upper-digestive-tract-haemorrhage OR upper-digestive-tract-hemorrhage OR Upper-gastrointestinal-tract-bleed∗ OR upper-GI-tract-bleed∗ OR esophagogastroduodenal-bleed∗ OR esophagogastroduodenal-hemorrhage∗ OR esophagogastroduodenal-haemorrhage∗) OR ((bleed∗ OR hemorrhag∗) AND (gastric∗ OR gastro∗ OR stomach OR esophagi∗ OR duoden∗)) in Title Abstract Keyword | ||
AND | ||
"randomized controlled trial" in Publication Type | ||
Query from Web of Science Core Collection | ||
You searched for: | ||
TOPIC: (Second-look∗ OR 2nd-look∗ OR second-therapeutic∗) | ||
AND | ||
TOPIC: ((Esophagoduodenoscop∗ OR EGD OR esophagogastroduodenoscop∗ OR esophago-gastro-duodenoscop∗ OR oesophagogastroduodenoscop∗ OR endoscop∗ OR gastroscop∗ OR duodenoscop∗ OR esophagoscop∗)) | ||
AND | ||
TOPIC: ((Upper-gastrointestinal-bleed∗ OR upper-GI-bleed∗ OR upper-Gastrointestinal-Hemorrhage OR upper-digestive-haemorrhage OR upper-digestive-hemorrhage OR upper-digestive-tract-haemorrhage OR upper-digestive-tract-hemorrhage OR Upper-gastrointestinal-tract-bleed∗ OR upper-GI-tract-bleed∗ OR esophagogastroduodenal-bleed∗ OR esophagogastroduodenal-hemorrhage∗ OR esophagogastroduodenal-haemorrhage∗) OR ((bleed∗ OR hemorrhag∗) AND (gastric∗ OR gastro∗ OR stomach OR esophagi∗ OR duoden∗))) | ||
AND | ||
TOPIC: (random∗ OR factorial∗ OR crossover∗ OR cross-over OR placebo∗ OR (doubl∗ NEAR/2 blind∗) OR (singl∗ NEAR/2 blind∗) OR assign∗ OR allocat∗ OR volunteer∗ OR "crossover procedure" OR "double-blind procedure" OR "randomized controlled trial" OR "single-blind procedure") | ||
Timespan: All years. Indexes: SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, ESCI. | ||
Results: 76 |
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DISCLOSURE: All authors disclosed no financial relationships.
See CME section, p. 1421.
If you would like to chat with an author of this article, you may contact Dr Kamal at [email protected].
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- Strategies to pre-empt recurrent bleeding after endoscopic hemostasisGastrointestinal EndoscopyVol. 93Issue 6
- PreviewIn the management of bleeding peptic ulcers, endoscopic hemostasis and adjunctive use of acid suppression are the criterion standard.1,2 Despite these treatments, bleeding recurs in a significant proportion of patients. In the United Kingdom audit, 13% of patients experienced recurrent bleeding.3 The mortality in those who required surgery was 29%.3 It is therefore of paramount importance that recurrent bleeding is forestalled.
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