Adler, Douglas G.

Abstract Background and Objectives Gastric varices (GVs) are associated with a higher risk of uncontrolled bleeding and death when compared with esophageal varices. While endoscopic glue injection therapy has been traditionally used for secondary prophylaxis in GV, data regarding primary prophylaxis continue to emerge. Recently, EUS–guided therapies have been used in GV bleeding. Methods We conducted a comprehensive search of several major databases from inception to June 2022. Our primary goals were to estimate the pooled rates of treatment efficacy, GV obliteration, GV recurrence, and rebleeding with EUS-guided therapy in primary and secondary prophylaxis. Overall adverse events and technical failures were assessed. Random-effects model was used for our meta-analysis, and heterogeneity was assessed using the I 2 % statistics. Results Eighteen studies with 604 patients were included. In primary prophylaxis, pooled rate of GV obliteration was 90.2% (confidence interval [CI], 81.1–95.2; I 2 = 0). With combination EUS–glue and coil therapy, the rate was 95.4% (CI, 86.7%–98.5%; I 2 = 0). Pooled rate of posttherapy GV bleeding was 4.9% (CI, 1.8%–12.4%; I 2 = 0). In secondary prophylaxis, pooled rate of treatment efficacy was 91.9% (CI, 86.8%–95.2%; I 2 = 12). With EUS-glue, EUS-coil, and combination EUS–glue and coil, the rates were 94.3% (CI, 88.9%–97.1%; I 2 = 0), 95.5% (CI, 80.3%–99.1%; I 2 = 0), and 88.7% (CI, 76%–95.1%; I 2 = 14), respectively. Pooled rate of GV obliteration was 83.6% (CI, 71.5%–91.2%; I 2 = 74). With EUS-glue, EUS-coil, and combination EUS–glue and coil, the rates were 84.6% (CI, 75.9%–90.6%; I 2 = 31), 92.3% (CI, 81.1%–97.1%; I 2 = 0), and 84.5% (CI, 50.8%–96.7%; I 2 = 75), respectively. Pooled rates of GV rebleeding and recurrence were 18.1% (CI, 13.1%–24.3%; I 2 = 16) and 20.6% (CI, 9.3%–39.5%; I 2 = 66), respectively. Conclusion Our analysis shows that EUS-guided therapy for GVs is technically feasible and clinically successful in both primary and secondary prophylaxis of GV.

Abstract Background and Aims: Recent systematic reviews and meta-analyses (SRMAs) have shown inconsistent effectiveness of FMT among IBD patients. This study aimed to appraise the evidence for clinically relevant outcomes with FMT in IBD patients using published SRMAs. Methods: We searched major databases from inception through Nov 2023 to identify SRMAs assessing the effectiveness of FMT in IBD patients. Primary outcomes included clinical remission, clinical response, endoscopic remission/response, a composite endpoint, and adverse effects. We included SRMAs investigating FMT's effect in IBD patients using RCTs and observational studies data. Methodological quality and evidence certainty were assessed using AMSTAR 2 and GRADE. Results: Out of 106 citations, 16 SRMAs were included with varying study sizes (2 to 60 primary studies) and participants (112 to 1169 per SRMA). Five SRMAs assessed FMT in IBD, while 11 focused on Ulcerative Colitis (UC). Seven SRMAs included RCTs only, and nine included both RCTs and observational studies. Methodological quality was critically low in 9 SRMAs (56%) and low in 7 studies (44%). FMT showed clinical remission benefit in all 16 SRMAs, with varying certainty: 3 high, 4 moderate, 4 low, and 5 very low. Endoscopic remission/response was reported in 5 meta-analyses on UC, with 1 high, 3 moderate, and 1 very low certainty. Combined clinical remission and endoscopic response were reported in 3 SRMAs on UC, with 1 low and 2 moderate certainty. Adverse events were reported in 6 SRMAs, with 1 high, 3 moderate, 1 low, and 1 very low certainty. Conclusion: Current evidence shows potential benefits of FMT in IBD, particularly UC, supported by significant associations in 16 meta-analyses. However, poor methodological quality and variability in evidence certainty call for high-quality RCTs to strengthen the evidence.

Abstract Background and study aims Hemospray (TC-325) is a mineral powder with adsorptive properties designed for use in various gastrointestinal bleeding (GIB) scenarios. We conducted a systematic review & meta-analysis of randomized controlled trials (RCTs) comparing TC-325 to standard endoscopic therapy (SET) for non-variceal GIB (NVGIB). Methods Multiple databases were searched through October 2022. Meta-analysis was performed using a random-effects model to determine pooled relative risk (RR) and proportions with 95 % confidence intervals (CI) for primary hemostasis, hemostasis failure, 30-day rebleeding, length of stay (LOS), and need for rescue interventions. Heterogeneity was assessed using I2%. Results Five RCTs with 362 patients (TC-325 178, SET 184) – 123 females and 239 males with a mean age 65 ± 16 years). The most common etiologies were peptic ulcer disease (48 %), malignancies (35 %), and others (17 %). Bleeding was characterized as Forrest IA (7 %), IB (73 %), IIA (3 %), and IIB (1 %). SET included epinephrine injection, electrocautery, hemoclips, or a combination. No statistical difference in primary hemostasis between TC-325 compared to SET, RR 1.09 (CI 0.95–1.25; I2 43), P = 0.2, including patients with oozing/spurting hemorrhage, RR 1.13 (CI 0.98–1.3; I2 35), P = 0.08. Failure to achieve hemostasis was higher in SET compared to TC-325, RR 0.30 (CI 0.12–0.77, I2 0), P = 0.01, including patients with oozing/spurting hemorrhage, RR 0.24 (CI 0.09 – 0.63, I2 0), P = 0.004. We found no difference between the two interventions in terms of rebleeding, RR 1.13 (CI 0.62–2.07, I2 26), P = 0.8 and LOS, standardized mean difference (SMD) 0.27 (CI, –0.20–0.74; I2 62), P = 0.3. Finally, pooled rate of rescue interventions (angiography) was statistically higher in SET compared to TC-325, RR 0.68 (CI 0.5–0.94; I2 0), P = 0.02. Conclusions Our analysis shows that for acute NV GIB, including oozing/spurting hemorrhage, TC-325 does not result in higher rates of primary hemostasis compared to SET. However, lower rates of failures were seen with TC-325 than SET. In addition, there was no difference in the two modalities when comparing rates of rebleeding and LOS.

Abstract Background and study aims Refractory and recurrent esophageal variceal (EV) bleeding can be life threatening. Self-expanding metal stents (SEMS) have been used as a “bridge” therapy. However, their role in the treatment protocol is not established due to paucity in data. Methods We searched multiple databases from inception through May 2019 to identify studies that reported on SEMS and TIPS in refractory EV hemorrhage. Our primary goals were to analyze and compare the pooled all-cause mortality, immediate bleeding control and rebleeding rates. Results Five hundred forty-seven patients from 21 studies were analyzed (SEMS: 12 studies, 176 patients; TIPS: 9 studies, 398 patients). The pooled rate of all-cause mortality with SEMS was 43.6 % (95 % CI 28.6–59.8, I2 = 38) and with TIPS was 27.9 % (95 % CI 16.3–43.6, I2 = 91). The pooled rate of immediate bleeding control with SEMS was 84.5 % (95 % CI 74–91.2, I2 = 40) and with TIPS was 97.9 % (95 % CI 87.7–99.7, I2 = 0). The pooled rate of rebleeding with SEMS was 19.4 % (95 % CI 11.9–30.4, I2 = 32) and with TIPS was 8.8 % (95 % CI 4.8–15.7, I2 = 40). Conclusion Use of SEMS in refractory EV hemorrhage demonstrates acceptable immediate bleeding control with good technical success rate. Mortality and rebleeding rates were lesser with TIPS, however, its superiority and/ or inferiority cannot be validated due to limitations in the comparison methodology.

Abstract Background Gastric variceal bleeding carries significant mortality in the setting of portal hypertension. Among the endoscopic treatment options, endoscopic ultrasound (EUS)-guided glue and/or coil injection is a novel approach, but its role in the treatment of gastric varices is not established due to a lack of robust data. Methods We conducted a comprehensive search of several databases (inception to June 2019) to identify studies evaluating EUS in the treatment of gastric varices. Our primary goals were to estimate the pooled rates of treatment efficacy, obliteration and recurrence of gastric varices, early and late rebleeding, and adverse events with EUS-guided therapy in gastric varices. We also searched for studies that evaluated direct endoscopic glue (END-glue) injection for treatment of gastric varices, and used the pooled rates as comparators. Results 23 studies (851 patients) evaluating EUS-guided therapy were included. The pooled treatment efficacy was 93.7 % (95 % confidence interval [CI] 89.5 – 96.3, I 2 = 53.7), gastric varices obliteration was 84.4 % (95 %CI 74.8 – 90.9, I 2 = 77), gastric varices recurrence was 9.1 % (95 %CI 5.2 – 15.7, I 2 = 32), early rebleeding was 7.0 % (95 %CI 4.6 – 10.7, I 2 = 0), and late rebleeding was 11.6 % (95 %CI 8.8 – 15.1, I 2 = 22). The rates were comparable to END-glue therapy (28 studies, 3467 patients) except for obliteration, which was significantly better with EUS-guided therapy. On subgroup analysis, EUS-coil/glue combination showed superior outcomes. Conclusions EUS-guided therapy demonstrated clinical efficacy for treatment of gastric varices in terms of obliteration, recurrence, and long-term rebleeding, and may be superior to END-glue.