Introduction

Esophageal stenting (ES) is an important intervention for the management of malignant and benign dysphagia, with migration representing a common drawback. This systematic review with meta-analysis aimed to assess the benefit of ES fixation over non-fixated stenting.

Aims & Methods

A systematic research was performed in MEDLINE, Cochrane, Scopus and ClinicalTrials.gov databases until January 2023 for comparative studies evaluating the migration rates of ES after anchoring or not. The primary outcome included the difference of migration rates for fixated and non-fixated ES, with the rate of adverse events being the secondary outcome. A subgroup analysis was stratified the results based on different fixation techniques; suturing, over the scope clipping (OTSC) and trough the scope clipping (TTSC). Meta-analyses were based on random effects model and the results were reported as odds ratios (OR), with 95% Confidence Intervals (95%CI).

Results

Ten studies (1014 patients) were included to our analysis. The rates of stent migration were significantly lower after fixation [OR=0.20 (95%CI: 0.11-0.37; I²=59%)]. The rates of adverse events were similar between the fixation and control groups [OR=0.65 (95%CI: 0.28-1.52; I²=55%)]. In the subgroup analysis, all anchoring techniques preserved the superiority over non-fixated stents [suturing OR= 0.23 (95%CI: 0.10-0.53); OTSC OR= 0.31 (95%CI: 0.17- 0.58); TTSC OR=0.10 (95%CI: 0.03-0.38)], however only OTSC and TTSC groups achieved non-significant heterogeneity (I²=0%). No difference between techniques was recorded considering the migration rates.

Conclusion

Esophageal stent fixation is associated with significantly lower migration rates compared to the non-fixated stents regardless type and stenting indication.

Introduction

Barrett esophagus (BE) represents a pre-malignant condition of the esophagus and current guidelines favor endoscopic eradication therapy (EET). After endoscopic resection for visible neoplastic lesions, field ablation of the residual BE is advised to mitigate the risk of metachronous neoplasia. Cryoablation was introduced as an endoscopic ablative option for BE during the last decade with growing data on outcomes and interest in potential lower adverse events that established ablative techniques.

Aims & Methods

This systematic review and meta-analysis aimed to summarize the existing data regarding safety and efficacy of Cryoablation on BE treatment. A systematic literature search in Medline, Cochrane and Scopus databases was performed until November 2023 for full papers. Safety was considered as the primary outcome, interpreted as the overall rate of procedure related adverse events. Secondary outcomes included post-Cryoablation stricture development, and the complete eradication rates of intestinal metaplasia (CEIM) and dysplasia (CED). In case of heterogeneity, a sub-analysis based on the used device was performed for the primary outcome. Random effects model was used and the results were reported as percentages for pooled rates with 95% Confidence Intervals (95%CIs).

Results

Ten full-paper studies (471 patients; 80.3% men; mean age 62.2-69) were eligible for analysis. The mean BE length, based on Prague classification, was C0-2M2-5. Regarding the primary outcome, the overall adverse events rate was 19.7% (95%CI: 14-25.4; I²=60.66%), although they were mild in the vast majority. ​Strictures warranting treatment were developed in 30 patients, representing 4.4% (95%CI: 1.8-7.1; I²=61.18%). Four studies provided results on CED, yielding a rate of 94.6% (95%CI: 90.1-99.1; I²=61.06%) whereas CEIM was assessed in six studies, reporting a rate of 90.1% (95%CI: 82.3-97.9; I²=87.92%). Given the high heterogeneity in all outcomes, a sub-analysis including studies on focal Cryoablation was performed, revealing a similar rate of adverse events [16.5% (95%CI: 11.1-21.8)] with lower heterogeneity and non-significant heterogeneity (I²=47.7%).

Conclusion

Cryoablation is a safe procedure with initial data showing a potentially low rate of esophageal strictures and comparable rates of dysplasia and BE eradication when compared to other ablative technologies. High-quality prospective studies including comparisons with established ablation techniques are warranted.

Introduction

Iatrogenic defects of the gastrointestinal (GI) tract represent a challenging indication even for experienced endoscopists, with the optimal approach being often a dilemma. The increase of interventional endoscopic procedures and complex surgical operations have generated the requirement for clear options in the occurrence of a perforation or a leak. Current guidelines recommend self-expandable metal stents (SEMS), over the scope clips (OTSC) and through the scope clips (TTSC) depending on the site and the size of the defect, albeit based on low quality, indirect comparisons between different cohorts.^1,2 This systematic review and meta-analysis aimed to evaluate the available modalities based on comparative quality studies, to elucidate reliably this field.

Aims & Methods

The systematic research was performed in MEDLINE, Cochrane, and Scopus databases until March 2023 for comparative studies evaluating the successful defect closure using SEMS, OTSC, TTSC or endoscopic vacuum therapy (EVT). Any study including at least one comparison was assessed for eligibility. Clinical success was considered as the primary outcome, representing the successful closure of the defect (perforation, leak). Secondary outcomes included overall adverse events were compared among modalities, whereas cumulative rates of the specific complications were also estimated. Meta-analyses were based on random effects model and the results were reported as odds ratios (OR), with 95% Confidence Intervals (95%CI).

Results

Eight studies with an overall number of 744 patients were included in our analysis. In five of them (497 patients) SEMS were compared with alternatives (OTSC and EVT), whereas OTSC and TTSC were assessed in 3 studies (247 patients). SEMS were found to be significantly inferior to alternatives in achieving the primary outcome [OR: 0.38 (95%CI: 0.14-1.01, p=0.05)], however with high heterogeneity (I²=75%). Interestingly, in subgroup analysis, OTSC achieved significantly higher clinical success than SEMS with OR: 2.07 (95%CI: 1.12-3.85, p=0.02) and reduced heterogeneity (I²=19%), whereas the comparison between SEMS and EVT failed to reach statistical significance [OR: 0.42 (95%CI: 0.005-3.19, p=0.4; I²=85%)]. OTSC and TTSC yielded similar rates of successful defect closure [OR: 0.07 (95%CI: 0.03-0.16), p=0.59; I²=0%]. Considering the secondary outcome, SEMS resulted to more adverse events than alternatives [OR: 13.5 (95%CI: 4.57-37.28, p<0.001; I²=63%)], with stent migration been the most common one (81 cases, 26.1%). In the subgroup analysis, both OTSC and ETV provided significantly less complications [OR: 0.07 (95%CI: 0.03-0.16, p<0.001; I²=0%) and OR: 0.09 (95%CI: 0.02-0.44, p=0.003; I²=59%) respectively]. Finally, only one complication was described in the OTSC vs TTSC group.

Conclusion

The success of endoscopic closure of luminal GI defects using SEMS is inferior to alternatives, especially when compared to OTSC, whereas it results to higher rates of adverse events. On the other hand, TTSC and OTSC seemed to be equivalent regarding efficacy and safety.

References

1. Paspatis GA, Arvanitakis M, Dumonceau JM, Barthet M, Saunders B, Turino SY, et al. Diagnosis and management of iatrogenic endoscopic perforations: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement – Update 2020. Endoscopy. 2020 Sep 11;52(09):792–810.
2. Lee JH, Kedia P, Stavropoulos SN, Carr-Locke D. AGA Clinical Practice Update on Endoscopic Management of Perforations in Gastrointestinal Tract: Expert Review. Clinical Gastroenterology and Hepatology. 2021 Nov;19(11):2252-2261.e2.

Introduction

Fully covered self-expandable metal stents (FCSEMS) used for benign and malignant esophageal conditionsare prone to migration, which can impact efficacy but also lead to adverse events. Fixation of proximal end of FCSEMS have shown to reduce stent migration in individual studies. In this systematic review and meta-analysis, we aim to compare rates of stent migration of FCSEMS undergoing fixation (any technique) versus not.

Aims & Methods

PubMed, Embase and Cochrane databases were queried to identify prospective/retrospective studies that compared outcomes of FCSEMS undergoing fixation (FCSEMS-F) versus no fixation (FCSEMS-NF). FCSEMS-F group included use of methods such as sutures, hemoclips and the specific over the scope clip (OTSC). The primary outcome was pooled estimates of the rate of stent migration. Secondary outcomes included clinical success, mean time to stent migration and overall adverse events (chest or abdominal pain, nausea+/-vomiting, tear or perforation, bleeding). Subgroup Analysis was performed to compare stent migration when FCSEMS fixation was performed with endoscopic suturing vs no fixation. Clinical success was defined as resolution of a stricture or closure of a fistula/leak/perforation as documented by clinical and endoscopic/radiological follow-up after stent removal. Odds ratios (RR) with 95% confidence intervals (CI) were calculated for dichotomous variables using the random effects model. Study heterogeneity was assessed using i² statistics.

Results

We identified 9 studies of FCSEMS placement comparing fixation versus no-fixation methods including a total 727 patients with 899 stent procedures: FCSEMS-F group (269 patient, 291 stents, mean age 60.4 years) and FCSEMS-NF group (458 patients, 608 stents, mean age 61.7 years). The stent migration rate for all procedures was 16.1% in FCSEMS-F group compared to 32.8% in FCSEMS-NF group (9 studies, OR 0.36, 95% CI 0.20 -0.64,i²= 53%). Clinical success was achieved in 68.9% procedures in FCSEMS-F group compared to 56.1% in FCSEMS-NF group (3 studies, OR 1.94, 95% CI 1.10 – 3.41, i²=0%). Mean time to stent migration was longer for FCSEMS-F (29.4 +/- 11.2 days) compared to FCSEMS-NF (21.6 +/- 11days) with a mean difference of 7.8 days (95% CI 5.4 – 10.2; SE 1.2, p< 0.0001). There was no difference in overall adverse events between the 2 groups. In a sub-group analysis for FCSEMS patients undergoing fixation with endoscopic suturing versus no fixation, the rate of stent migration was significantly lower in the sutured group (16.3% vs 32.8%, OR 0.37,95% CI 0.19 – 0.72, i²= 55%).

Conclusion

Fixation of FCSEMS (sutured in particular) offer significant advantages in terms of lower stent migration rates, longer duration to stent migration and higher clinical success without any difference in adverse events when compared to esophageal stents not undergoing fixation. Randomized studies comparing various fixation methods is needed to further guide the exact method for stent fixation.

Disclosure

No Relevant Financial Disclosures

Introduction

Zenker’s diverticulum is associated with a significant burden on quality of life and morbidity, predisposing to dysphagia, regurgitation and aspiration pneumonia. This is often a condition that affects senior patients and access to interventions is limited. Surgery has been the preferred option historically due to a lack of alternative options but remains invasive with major potential complications in an already high-risk patient group. Endoscopic approaches offer a minimally invasive alternative treatment option including rigid and flexible diverticulotomy, and the emerging Zenker per-oral endoscopic myotomy (Z-POEM), albeit no superiority has been demonstrated among these techniques.

Aims & Methods

This systematic review and meta-analysis aimed to summarize the efficacy and safety of these endoscopic techniques.A systematic search in Medline, Cochrane and Scopus databases was performed until November 2023. The primary outcome was technical success, defined as the completion of diverticulotomy/myotomy in one session. Secondary outcomes included clinical success which corresponded to the complete resolution of dysphagia or a post-procedure Dakkak and Bennett score ≤ 1. Moreover, the recurrence rates and the overall adverse events were recorded. Subgroup analyses per outcome were performed to discriminate the results depending on the endoscopic approach (Rigid, flexible diverticulotomy and Z-POEM), whereas the comparative studies were meta-analyzed to compare Z-POEM with alternatives. We used a random effects model and the results were reported as percentages for pooled rates and odds ratios (OR) for comparative data with 95% Confidence Intervals (95%CIs).

Results

From 2004 to 2023 twenty-three studies (1357 patients; 40% female; mean age 43-80) were included in our analysis. The cumulative technical success rate was 97.7% (95%CI: 96.9-98.5) with null heterogeneity (I²=0%), and this outcome was preserved in all subgroups. Considering clinical success, the overall pooled rate was 84.8% (95%CI: 80.8-88.8; I²=79.15%) with Z-POEM yielding higher rate [90.4% (95%CI: 87.8-93.1)] with low heterogeneity (I²=11%), in contrast to the alternatives. 8.6% (95%CI: 6.0-11.3; I²: 63.6%) of cases experienced recurrence, with those post-Z-POEM having the lowest rates [5.7% (95%CI: 2.3-9.1; I²:55.68%)] and post-flexible myotomy the highest ones [12.1% (95%CI: 8.0-16.2; I²=36.09%)]. Finally, complications occurred in 8.7% (95%CI: 6.0-11.4; I2=78.08%) with no changes in subgroup analysis. Five studies (759 patients) provided comparative data for Z-POEM and alternatives. Technical success and recurrence rates were similar between comparators [OR:1.38 (95%CI: 0.59-3.23, p=0.5; I2=0%) and OR:0.69 (95%CI: 0.29-1.51, p=0.39; I²=48.71%), respectively], whereas Z-POEM achieved higher clinical success rates [OR:2.38 (95%CI: 1.54-3.68, p<0.001; I²=0%)]

Conclusion

Endoscopic treatment offers high technical success and symptom resolution in patients with Zenker diverticulum, with relatively low prevalence of adverse events and recurrence. Z-POEM offers higher clinical success rates compared to alternatives with optimal homogeneity.

Introduction

Esophageal Squamous Cell Carcinoma (ESCC) remains a significant global health problem with few therapeutic options and poor prognosis. Camrelizumab, an anti-PD-1 immune checkpoint inhibitor, has been shown in clinical trials to be of potential value in the treatment of advanced or metastatic ESCC as monotherapy or in combination with chemotherapy or anti-angiogenic therapy.

Aims & Methods

The aim of this study is to evaluate the clinical efficacy and safety profile of Camrelizumab in patients with esophageal squamous cell carcinoma, with the main outcomes being progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events.
We conducted a comprehensive search of PubMed, Scopus, Web of Science, Embase, and Cochrane from their inception to April 2025, focusing on randomized controlled trials (RCTs) and observational studies evaluating Camrelizumab for the treatment of esophageal squamous cell carcinoma. Meta-analyses utilized a random-effects model to calculate odds ratios, mean differences, and 95% confidence intervals for adverse events and total patients.

Results

Out of 1,563 studies initially screened, 15 studies met the inclusion criteria for our meta-analysis, comprising adult patients. Meta-analysis established a median progression-free survival (PFS) of 7.60 months (95% CI: 6.00–9.19). The major pathological response rate (MPR) was 0.42 (95% CI: 0.37–0.48), and the objective response rate (ORR) was 0.53 (95% CI: 0.38–0.68). The R0 resection rate was also remarkably high at 0.98 (95% CI: 0.96–1), and the disease control rate (DCR) was 0.87 (95% CI: 0.64–1). The pathological complete response rate (pCR) was 0.31 (95% CI: 0.20–0.43).
Regarding safety, the most common treatment-related adverse events were leukopenia 0.45 (95% CI: 0.23–0.68), neutropenia 0.30 (95% CI: 0.19–0.41), anemia 0.14 (95% CI: 0.03–0.29), thrombocytopenia 0.09 (95% CI: 0.03–0.17), and elevated transaminases 0.06 (95% CI: 0.02–0.12). Pneumonia 0.17 (95% CI: 0.11-0.23) and hypertension 0.12 (95% CI: 0.06-0.19) were the other immune-related adverse events. The majority of these events were tolerable and within safe parameters.

Conclusion

Camrelizumab demonstrates promising efficacy in the treatment of esophageal squamous cell carcinoma with satisfactory rates of ORR, MPR, and R0 resection. The safety profile is acceptable with controllable adverse effects. These findings support the potential therapeutic value of camrelizumab as a significant treatment strategy in multimodal treatment of esophageal squamous cell carcinoma and the need for further research to optimize its clinical use.

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory and progressive fibrotic condition of the esophagus characterized by the infiltration of eosinophils into the esophageal mucosa and esophageal dysfunction. There remain limited treatment options for EoE and accordingly, a substantial unmet need for effective and safe medical therapies. Drug development in EoE has been hampered by heterogeneous placebo response rates, especially for clinical outcomes, and uncertainty regarding appropriate endpoint configurations. Accurate characterization of placebo response in EoE randomized controlled trials (RCTs) will help inform more future efficient trial designs.

Aims & Methods

To conduct a systematic review and meta-analysis to characterize symptomatic, endoscopic, and histologic placebo response rates in placebo controlled EoE RCTs.
Electronic database (CENTRAL, MEDLINE, EMBASE) searching (inception to 1 JAN 2024) identified placebo controlled RCTs evaluating medical therapies for adults with EoE. Studies were screened independently by 2 reviewers (AR and SA), and full texts were then reviewed for eligibility. The proportion of clinical, endoscopic, and histologic responders (improvement and remission) assigned to placebo were pooled using a random-effect model. The Stuart-Ord inverse double arcsine square root transformation method was used to compute 95% confidence intervals (CI) for point estimates of placebo response. Heterogeneity was evaluated using the I² method. Analyses were conducted in StatsDirect 3.3.6.

Results

A total of 25 placebo-controlled RCTs (placebo sample size range: N = 4–105) were included. The pooled proportion of patients receiving placebo who achieved clinical response was 41.0% (n = 11; 95% CI 29.7%, 52.8%) with substantial heterogeneity (I² = 74.9%%). Definitions of clinical response varied between studies. The pooled proportion for histologic remission (peak eosinophil count [PEC] ≤6 eos per high power field [hpf]) was 4.3% (n = 20; 95% CI 2.6%, 6.2%) with low heterogeneity (I² = 23.6%), while a more stringent definition of histologic remission (PEC ≤1 eos/hpf) yielded a pooled placebo remission rate of 1.3% (n = 18; 95% CI 0.5%, 2.5%) with low heterogeneity (I² = 0%). The pooled histologic improvement rate was 6.2% (n = 15; 95% CI 3.3%, 10.0%) with substantial heterogeneity (I² = 50.6%). Limited studies reported on endoscopic improvement and remission (Table 1).

Conclusion

More than 1 in 3 patients assigned to placebo in EoE RCTs will achieve clinical response (substantial heterogeneity detected), while less than 1 in 10 of these patients will achieve histologic remission (low heterogeneity detected). These findings highlight 1) the need to develop validated and responsive patient-reported outcome measures, which may be difficult due to the episodic nature of symptoms in EoE; and 2) the challenge of using a coprimary clinical and histologic outcome in EoE RCTs, given the discordance between symptoms and objective disease activity measures.

Table 1. Pooled proportion of placebo patients achieving measured outcomes in EoE studies

Disclosure

AR: No conflicts of interest
SA: No conflicts of interest
YY: No conflicts of interest
AQ: Is an employee of Alimentiv Inc.
DBO: Is an employee of Alimentiv Inc.
BGF: consulting fees from AbbVie, Abivax, Adiso, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Arena Pharma, Avoro Capital Advisors, Atomwise,, BioJamp, Biora Therapeutics, Blackbird Laboratories,Boehringer-Ingelheim, Boxer Capital, Celsius Therapeutics, Celgene/BMS, Celltrion, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, Forbion, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer Pharma, GSK, Hinge Bio, Index Pharma, Imhotex, Immunic Therapeutics, Intercept, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Klick Health, Landos Biopharma, Lenczner Slaght, LifeSci Capital, Lument AB, Mage Biologics, Mestag, Millennium, MiroBio, Monte Rose Tx, Morgan Lewis, Morphic Therapeutics, Mylan, Nexys Therapeutics, Nimbus Therapeutics, OM Pharma, OrbiMed Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics (Merck), Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Roivant/Televant, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Sobi, Spyre Therapeutics, Surrozen Inc., Sun Pharma, Synedgen, Takeda, Teva, Thelium, Tigenix, Tillotts, Triastek, TR1X Inc. Ventyx Biosciences, Zagbio, Zealand Pharma. Speaker fees from AbbVie, Janssen, Takeda.
VJ: consulting/advisory board fees from AbbVie, Alimentiv, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Anaptyis Bio, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Synedgen, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; and speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi.
AJB: AJB received research funding from Nutricia, Thelial, Sanofi/Regeneron, SST, and Dr. Falk Pharma and received speaker and/or consulting fees from Laborie, Medtronic, BMS, Dr. Falk Pharma, Calypso Biotech, Eupraxia, Aqilion, Alimentiv, Sanofi/Regeneron, Reckitt and AstraZeneca
ESD: Research funding: Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda
Consultant: Abbott, Abbvie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Apollo, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Dr. Falk Pharma, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio
Educational grant: Allakos, Aqilion, Holoclara, Invea
CM: consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer.