Diagnostic and therapeutic yields of early capsule endoscopy and device-assisted enteroscopy in the setting of overt GI bleeding: a systematic review with meta-analysis
Gastrointestinal Endoscopy. 2022;95(4):610-625.e9
BACKGROUND AND AIMS Small-bowel capsule endoscopy (SBCE) and device-assisted enteroscopy (DAE) are essential in obscure GI bleeding (OGIB) management. However, the best timing for such procedures remains unknown. This meta-analysis aimed to compare, for the first time, diagnostic and therapeutic yields, detection of active bleeding and vascular lesions, recurrent bleeding, and mortality of "early" versus "nonearly" SBCE and DAE. METHODS MEDLINE, ScienceDirect, and Cochrane Central Register of Controlled Trials were searched to identify studies comparing early versus nonearly SBCE and DAE. Random-effects meta-analysis was performed; reporting quality was assessed. RESULTS From 1974 records, 39 were included (4825 patients). Time intervals for the early approach varied, within 14 days in SBCE and 72 hours in DAE. The pooled diagnostic and therapeutic yields of early DAE were superior to those of SBCE (7.97% and 20.89%, respectively; P < .05). The odds for active bleeding (odds ratio [OR], 5.09; I(2) = 53%), positive diagnosis (OR, 3.99; I(2) = 45%), and therapeutic intervention (OR, 3.86; I(2) = 67%) were higher in the early group for SBCE and DAE (P < .01). Subgroup effects in diagnostic yield were only identified for the early group sample size. Our study failed to identify differences when studies were classified according to time intervals for early DAE (I(2) < 5%), but the analysis was limited because of a lack of data availability. Lower recurrent bleeding in early SBCE and DAE was observed (OR, .40; P < .01; I(2) = 0%). CONCLUSIONS The role of small-bowel studies in the early evaluation of OGIB is unquestionable, impacting diagnosis, therapeutic intervention, and prognosis. Comparative studies are still needed to identify optimal timing.
Prophylactic transcatheter arterial embolization reduces rebleeding in non-variceal upper gastrointestinal bleeding: A meta-analysis
World Journal of Gastroenterology. 2021;27(40):6985-6999
BACKGROUND Despite the improvement in the endoscopic hemostasis of non-variceal upper gastrointestinal bleeding (NVUGIB), rebleeding remains a major concern. AIM: To assess the role of prophylactic transcatheter arterial embolization (PTAE) added to successful hemostatic treatment among NVUGIB patients. METHODS We searched three databases from inception through October 19(th), 2020. Randomized controlled trials (RCTs) and observational cohort studies were eligible. Studies compared patients with NVUGIB receiving PTAE to those who did not get PTAE. Investigated outcomes were rebleeding, mortality, reintervention, need for surgery and transfusion, length of hospital (LOH), and intensive care unit (ICU) stay. In the quantitative synthesis, odds ratios (ORs) and weighted mean differences (WMDs) were calculated with the random-effects model and interpreted with 95% confidence intervals (CIs). RESULTS We included a total of 3 RCTs and 9 observational studies with a total of 1329 patients, with 486 in the intervention group. PTAE was associated with lower odds of rebleeding (OR = 0.48, 95%CI: 0.29-0.78). There was no difference in the 30-d mortality rates (OR = 0.82, 95%CI: 0.39-1.72) between the PTAE and control groups. Patients who underwent PTAE treatment had a lower chance for reintervention (OR = 0.48, 95%CI: 0.31-0.76) or rescue surgery (OR = 0.35, 95%CI: 0.14-0.92). The LOH and ICU stay was shorter in the PTAE group, but the difference was non-significant [WMD = -3.77, 95%CI: (-8.00)-0.45; WMD = -1.33, 95%CI: (-2.84)-0.18, respectively]. CONCLUSION PTAE is associated with lower odds of rebleeding and any reintervention in NVUGIB. However, further RCTs are needed to have a higher level of evidence.
Role of routine second-look endoscopy in patients with acute peptic ulcer bleeding: meta-analysis of randomized controlled trials
Gastrointestinal Endoscopy. 2021;93(6):1228-1237.e5
BACKGROUND AND AIMS Studies evaluating the role of routine second-look endoscopy in patients with acute upper GI bleed because of peptic ulcer disease (PUD) have reported conflicting results. This meta-analysis evaluates the usefulness of routine second-look endoscopy in these patients. METHODS We reviewed several databases from inception to September 15, 2020 to identify randomized controlled trials (RCTs) that compared routine second-look endoscopy with no planned second-look endoscopy in patients with acute upper GI bleed because of PUD. Our outcomes of interest were recurrent bleeding, mortality, need for surgery, and mean number of units of blood transfused. For categorical variables, we calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs); for continuous variables, we calculated standardized mean difference with 95% CIs. Data were analyzed using a random effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to ascertain the quality of evidence. RESULTS We included 9 RTCs comprising 1452 patients; 726 patients underwent planned/routine second-look endoscopy and 726 did not. We found no significant difference in recurrent bleeding (RR, .79; 95% CI, .51-1.23), need for surgery (RR, .58; 95% CI, .29-1.15), mortality (RR, .69; 95% CI, .33-1.45), or mean number of units of blood transfused (standardized mean difference, -.06; 95% CI, -.19 to .07). Quality of evidence ranged from low to moderate based on the GRADE framework. CONCLUSIONS Single endoscopy with complete endoscopic hemostasis is not inferior to routine second-look endoscopy in reducing the risk of recurrent bleeding, mortality, or need for surgery in patients with acute upper GI bleed because of PUD.
Comparison of a Hemostatic Powder and Standard Treatment in the Control of Active Bleeding From Upper Nonvariceal Lesions : A Multicenter, Noninferiority, Randomized Trial
Annals of internal medicine. 2021
BACKGROUND The effectiveness of the hemostatic powder TC-325 as a single endoscopic treatment for acute nonvariceal upper gastrointestinal bleeding is uncertain. OBJECTIVE To compare TC-325 with standard endoscopic hemostatic treatments in the control of active bleeding from nonvariceal upper gastrointestinal causes. DESIGN One-sided, noninferiority, randomized, controlled trial. (ClinicalTrials.gov: NCT02534571). SETTING University teaching hospitals in the Asia-Pacific region. PATIENTS 224 adult patients with acute bleeding from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION TC-325 (n = 111) or standard hemostatic treatment (n = 113). MEASUREMENTS The primary outcome was control of bleeding within 30 days. Other outcomes included failure to control bleeding during index endoscopy, recurrent bleeding after initial hemostasis, further interventions, blood transfusion, hospitalization, and death. RESULTS 224 patients were enrolled (136 with gastroduodenal ulcers [60.7%], 33 with tumors [14.7%], and 55 with other causes of bleeding [24.6%]). Bleeding was controlled within 30 days in 100 of 111 patients (90.1%) in the TC-325 group and 92 of 113 (81.4%) in the standard treatment group (risk difference, 8.7 percentage points [1-sided 95% CI, 0.95 percentage point]). There were fewer failures of hemostasis during index endoscopy with TC-325 (3 [2.7%] vs. 11 [9.7%]; odds ratio, 0.26 [CI, 0.07 to 0.95]). Recurrent bleeding within 30 days did not differ between groups (9 [8.1%] vs. 10 [8.8%]). The need for further interventions also did not differ between groups (further endoscopic treatment: 8 [7.2%] vs. 10 [8.8%]; angiography: 2 [1.8%] vs. 4 [3.5%]; surgery: 1 [0.9%] vs. 0). There were 14 deaths in each group (12.6% vs. 12.4%). LIMITATION Clinicians were not blinded to treatment. CONCLUSION TC-325 is not inferior to standard treatment in the endoscopic control of bleeding from nonvariceal upper gastrointestinal causes. PRIMARY FUNDING SOURCE General Research Fund to the University Grants Committee, Hong Kong SAR Government.
Effectiveness of hemostatic powders in lower gastrointestinal bleeding: a systematic review and meta-analysis
Endoscopy international open. 2021;9(8):E1283-e1290
Background and study aims There is limited evidence on the effectiveness of hemostatic powders in the management of lower gastrointestinal bleeding (LGIB). We aimed to provide a pooled estimate of their effectiveness and safety based on the current literature. Patients and methods Literature review was based on computerized bibliographic search of the main databases through to December 2020. Immediate hemostasis, rebleeding rate, adverse events, and mortality were the outcomes of the analysis. Pooled effects were calculated using a random-effects model. Results A total of 9 studies with 194 patients were included in the meta-analysis. Immediate hemostasis was achieved in 95 % of patients (95 % confidence interval [CI] 91.6 %-98.5 %), with no difference based on treatment strategy or bleeding etiology. Pooled 7- and 30-day rebleeding rates were 10.9 % (95 %CI 4.2 %-17.6 %) and 14.3 % (95 %CI 7.3 %-21.2 %), respectively. Need for embolization and surgery were 1.7 % (95 %CI 0 %-3.5 %) and 2.4 % (95 %CI 0.3 %-4.6 %), respectively. Overall, two patients (1.9 %, 95 %CI 0 %-3.8 %) experienced mild abdominal pain after powder application, and three bleeding-related deaths (2.3 %, 95 %CI 0.2 %-4.3 %) were registered in the included studies. Conclusion Novel hemostatic powders represent a user-friendly and effective tool in the management of lower gastrointestinal bleeding.
Efficacy of Hemospray in non-variceal upper gastrointestinal bleeding: a systematic review with meta-analysis
Annals of gastroenterology. 2020;33(2):145-154
Background: Recently, amongst other hemostatic modalities, Hemospray (TC-325) has emerged as an effective method for managing patients with non-variceal upper gastrointestinal bleeding (GIB). We conducted this systematic review and meta-analysis to assess the efficacy of Hemospray in patients with non-variceal upper GIB. Methods: Our primary outcomes were clinical and technical success; secondary outcomes were aggregate rebleeding, early rebleeding, delayed rebleeding, refractory bleeding, mortality, and treatment failure. A meta-analysis of proportions was conducted for all reported primary and secondary outcomes. A relative risk meta-analysis was conducted for studies reporting direct comparisons between Hemospray and other hemostatic measures. Results: A total of 20 studies with 1280 patients were included in the final analysis. Technical success of Hemospray was seen in 97% of cases (95% confidence interval [CI] 94-98%, I (2)=52.89%) and a significant trend towards increasing technical success was seen during publication years 2011-2019. Clinical success of Hemospray was seen in 91% of cases (95%CI 88-94%, I (2)=47.72%), compared to 87% (95%CI 75-94%, I (2)=0.00%) for other hemostatic measures. The secondary outcomes of aggregate rebleeding, early rebleeding, delayed rebleeding, refractory rebleeding, mortality and treatment failure following the use of Hemospray were seen in 27%, 20%, 9%, 8%, 8%, and 31% of cases, respectively. Conclusion: Hemospray is safe, effective and non-inferior to traditional hemostatic measures for the management of non-variceal upper GIB, and can thus be used as an alternative option.
Optimal endoscopy timing in patients with acute variceal bleeding: A systematic review and meta-analysis
Scientific reports. 2020;10(1):4046
Although current guidelines recommend performing endoscopy within 12 hours for acute variceal bleeding (AVB), the optimal timing remains controversial. This study aimed to assess the effect of endoscopy timing on the mortality and rebleeding rates in AVB through a systematic review and meta-analysis of all eligible studies. PubMed, Cochrane Library, and Embase were searched for relevant publications up to January 2019. Overall mortality, rebleeding rate, and other clinical outcomes were determined. For the non-randomized studies, the risk of bias assessment tool was used to assess the methodological quality of the included publications. The Mantel-Haenszel random-effects model of the RevMan software (Cochrane) and the inverse variance method were used to analyse binary end points and continuous outcomes, respectively. This meta-analysis included five studies with 854 and 453 participants who underwent urgent (≤12 hours) and non-urgent endoscopies (>12 hours), respectively. All the included studies were retrospective in nature, because of obvious ethical issues. No significant differences in the severity indexes were found between the urgent and non-urgent groups. Three studies showed 6-week mortality and the others in-hospital mortality as main outcomes. No significant difference in overall mortality rate was found between the groups (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.36-1.45, p = 0.36). The rebleeding rate was similar between the two groups (OR: 1.21, 95% CI: 0.76-1.93, p = 0.41). Other outcomes such as successful haemostasis, need for salvage therapy, length of hospital stay, and number of blood transfusions were also similar between the groups. We demonstrated that endoscopy timing does not affect the mortality or rebleeding rate of patients with AVB. Therefore, an appropriate timing of endoscopy would be more important than an urgent endoscopy depending on each patient's condition.
Endoscopic Ultrasound-Guided Treatments for Non-Variceal Upper GI Bleeding: A Review of the Literature
J Clin Med. 2020;9(3)
Endoscopic injection of glues, clotting factors, or sclerosing agents is a well-known therapy for the treatment of non-variceal upper gastrointestinal bleeding (NVUGIB), but less is known about endoscopic ultrasound (EUS)-guided treatments. In this setting, literature data are scarce, and no randomized controlled trials are available. We performed a review of the existing literature in order to evaluate the role of EUS-guided therapies in the management of NVUGIB. The most common treated lesions were Dieulafoy's lesions, pancreatic pseudoaneurysms, and gastrointestinal stromal tumors (GISTs). Mostly, the treatments were performed as a salvage option after failure of conventional endoscopic hemostatic attempts, showing good efficacy and a good safety profile, also documented by Doppler monitoring of treated lesions. EUS-guided therapies may be an effective option in the treatment of refractory NVUGIB, thus avoiding radiological or surgical management. Nevertheless, available literature still lacks robust data.
Band ligation versus no intervention for primary prevention of upper gastrointestinal bleeding in adults with cirrhosis and oesophageal varices
The Cochrane database of systematic reviews. 2019;6:Cd012673
BACKGROUND The presence of oesophageal varices is associated with the risk of upper gastrointestinal bleeding. Endoscopic variceal ligation is used to prevent this occurrence but the ligation procedure may be associated with complications. OBJECTIVES To assess the beneficial and harmful effects of band ligation versus no intervention for primary prevention of upper gastrointestinal bleeding in adults with cirrhosis and oesophageal varices. SEARCH METHODS We combined searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and Science Citation Index with manual searches. The last search update was 9 February 2019. SELECTION CRITERIA We included randomised clinical trials comparing band ligation verus no intervention regardless of publication status, blinding, or language in the analyses of benefits and harms, and observational studies in the assessment of harms. Included participants had cirrhosis and oesophageal varices with no previous history of variceal bleeding. DATA COLLECTION AND ANALYSIS Three review authors extracted data independently. The primary outcome measures were all-cause mortality, upper gastrointestinal bleeding, and serious adverse events. We undertook meta-analyses and presented results using risk ratios (RRs) with 95% confidence intervals (CIs) and I(2) values as a marker of heterogeneity. In addition, we calculated the number needed to treat to benefit (NNTTB) for the primary outcomes . We assessed bias control using the Cochrane Hepato-Biliary domains; determined the certainty of the evidence using GRADE; and conducted sensitivity analyses including Trial Sequential Analysis. MAIN RESULTS Six randomised clinical trials involving 637 participants fulfilled our inclusion criteria. One of the trials included an additional small number of participants (< 10% of the total) with non-cirrhotic portal hypertension/portal vein block. We classified one trial as at low risk of bias for the outcome, mortality and high risk of bias for the remaining outcomes; the five remaining trials were at high risk of bias for all outcomes. We downgraded the evidence to moderate certainty due to the bias risk. We gathered data on all primary outcomes from all trials. Seventy-one of 320 participants allocated to band ligation compared to 129 of 317 participants allocated to no intervention died (RR 0.55, 95% CI 0.43 to 0.70; I(2) = 0%; NNTTB = 6 persons). In addition, band ligation was associated with reduced risks of upper gastrointestinal bleeding (RR 0.44, 95% CI 0.28 to 0.72; 6 trials, 637 participants; I(2) = 61%; NNTTB = 5 persons), serious adverse events (RR 0.55, 95% CI 0.43 to 0.70; 6 trials, 637 participants; I(2) = 44%; NNTTB = 4 persons), and variceal bleeding (RR 0.43, 95% CI 0.27 to 0.69; 6 trials, 637 participants; I(2) = 56%; NNTTB = 5 persons). The non-serious adverse events reported in association with band ligation included oesophageal ulceration, dysphagia, odynophagia, retrosternal and throat pain, heartburn, and fever, and in the one trial involving participants with either small or large varices, the incidence of non-serious side effects in the banding group was much higher in those with small varices, namely ulcers: small versus large varices 30.5% versus 8.7%; heartburn 39.2% versus 17.4%. No trials reported on health-related quality of life.Two trials did not receive support from pharmaceutical companies; the remaining four trials did not provide information on this issue. AUTHORS' CONCLUSIONS This review found moderate-certainty evidence that, in patients with cirrhosis, band ligation of oesophageal varices reduces mortality, upper gastrointestinal bleeding, variceal bleeding, and serious adverse events compared to no intervention. It is unlikely that further trials of band ligation versus no intervention would be considered ethical.
Carvedilol vs endoscopic band ligation for the prevention of variceal bleeding: a meta-analysis
Therapeutics and clinical risk management. 2019;15:191-200
Objective: Variceal hemorrhage is the primary driver of mortality in patients with portal hypertension. Recent guidelines recommended that patients with esophageal varices should receive endoscopic band ligation (EBL) or carvedilol as prophylaxis of variceal bleeding. Several clinical trials have compared carvedilol use with EBL intervention, yielding controversial results. The present study aimed to perform a meta-analysis of randomized controlled trials (RCTs) evaluating the benefits and harms of carvedilol vs EBL for the prevention of variceal bleeding. Methods: Studies were searched on Pubmed, Embase, Medline, and Cochrane library databases up to August 2018. Main outcomes in selected studies (variceal bleeding, all-cause deaths, bleeding-related deaths, and adverse events) were pooled into a meta-analysis. Results: Seven RCTs were identified in this meta-analysis, including a total of 703 patients. A total of 359 patients were randomized to carvedilol group and 354 were randomized to EBL group. No significant difference in variceal bleeding was observed between carvedilol use and EBL groups (relative ratio [RR] =0.86, 95% CI =0.60-1.23, I (2)=11%), without publication bias. No significant difference was found neither for all-cause deaths (RR =0.82, 95% CI =0.44-1.53, I (2)=66%) nor for bleeding-related deaths (RR =0.85, 95% CI =0.39-1.87, I (2)=42%) in four included studies. Moreover, no reduced trend was observed toward adverse events in carvedilol group compared with that in EBL group (RR =1.32, 95% CI =0.75-2.31, I (2)=81%). Conclusion: There is no significant difference between carvedilol use and EBL intervention for the prophylaxis of variceal bleeding in patient with esophageal varices. Large-scale clinical trials are further needed to make a confirmed conclusion.