Introduction

Transmural defects in the upper gastro-intestinal (GI) tract, e.g. anastomotic leak, Boerhaave syndrome or iatrogenic defects, are associated with severe morbidity. Treatment options include conservative, surgical and endoscopic modalities. Endoscopic vacuum therapy (EVT) has gained a greater role in endoscopic treatment of these defects and is most often applied using endoscopically placed vacuum-sponges. Recently, a vacuum-stent was introduced as a new device to apply EVT, combining the benefits of negative pressure wound therapy and an intraluminal stent, while allowing for oral intake of a soft diet.

Aims & Methods

The aim of this prospective case series was to describe the first experiences with the vacuum-stent for transmural defects in the upper GI tract, between March 2022 and March 2023, in an academic hospital that had experience with EVT using vacuum-sponges since 2018. All patients treated with a vacuum-stent were included. Patients who were already treated with vacuum-sponge and received a vacuum-stent when it became available were also included. All patients signed informed consent for prospective registration of relevant data on treatment and outcomes in a specifically designed database. Outcome measures included successful closure of the defect, adverse events, number of EVT-related endoscopies and treatment duration.

Results

23 patients were included (18 male, median age 65 years). Fourteen patients had anastomotic leakage after esophagectomy, five patients had an iatrogenic perforation and four had Boerhaave syndrome. Twelve patients were treated with vacuum-stent alone and eleven with a combination of vacuum-stent and vacuum-sponge (Table 1), which was mostly due to the later availability of or too little experience with the vacuum-stent. Three Boerhaave patients also underwent surgery for nettoyage of a large mediastinal cavity with decortication of the lung and placement of an intracavitary muscle flap. Successful defect closure was obtained in 91%, requiring a median of 4 (IQR 3-8) EVT-related endoscopies, and median treatment course of 14 (IQR 12-31) days in successful cases. During median 120 (IQR 15-221) days follow-up, four patients developed an anastomotic stricture treated with endoscopic dilation. No other adverse events were observed.

Conclusion

The vacuum-stent combines the benefits of EVT and an intraluminal stent and shows great feasibility and efficacy in treatment of transmural defects in the upper GI tract. More research is necessary, as this device could possibly prevent major (re-)surgery in these patients.

Disclosure

RP is consultant for MicroTech Europe and Medtronic bv., received speaker fee from Pentax and is on the advisory board of EsoCap AG.
MIvBH is consultant for Mylan, Johnson & Johnson, Alesi Surgical, BBraun and Medtronic, and received unrestricted research grants from Stryker. All fees paid to institution.

Clinical Case Summary

Colorectal lymphomas are a rare cause of colonic neoplasia (0.2-0.6% malignant neoplasms of large bowel). Approximately 10% are primary colorectal lymphomas, while the rest correspond to colonic extension of systemic lymphoproliferative diseases.
We present the case of a 66-year-old woman with a history of rectum and pancreas adenocarcinoma (both in remission). During a follow-up CT, a thickening of the cecal pole was identified, with no adenopathy or other relevant findings (Photo1). The patient had no abdominal pain or B symptoms (night sweats, weight loss or fever).
The diagnosis was completed with a PET-CT that showed pathological uptake in the cecum (Photo2), so a colonoscopy was performed, which revealed a large polypoid lesion (30 mm) at the ileocecal level, with nodular areas with small ulcerations and no clear loss of the glandular pattern (Photo 3), from which multiple biopsies were taken.
Biopsies showed lymphoid proliferation with a ‘starry sky’ pattern, mitosis and apoptosis, and positive immunohistochemistry for CD45, CD20, CD10, BCL6, BCL2 and C-MYC, together with a high proliferation index (Ki-67 > 95%), all compatible with high-grade B-lymphoproliferative syndrome with Burkitt morphology (Photo 4).
Burkitt's lymphoma is a rare B-cell lymphoma (15% of GI lymphomas), associated with chromosomal translocation (8:14, 8:22 and 2:8) and overexpression of c-myc oncogene.
There are three clinical variants: endemic (common in Africa and associated with EBV and malaria), HIV-associated and sporadic (20%).
It is common in children and its most frequent symptoms are abdominal pain and weight loss, so diagnosis is often delayed. Although the yield of endoscopic biopsies is low (<20%), it is a key tool in its diagnosis, along with targeted biopsy of abdominal adenopathies.
Despite its aggressiveness, treatment with targeted chemotherapy achieves rates of more than 90%, and early diagnosis is essential to avoid complications and ensure adequate medical treatment.

References

- Photo 1: Thickening of the cecal pole seen in CT-Scan.
- Photo 2: Pathological uptake in the caecal area as seen on PET-CT Scan.
- Photo 3: Polypoid lesion in ileocecal area at colonoscopy
- Photo 4: Pathological anatomy of endoscopic biopsies: starry sky imaging and immunohistochemistry of Bcl-2 and C-myc

Introduction

Swallowed topical corticosteroids (STC) are a treatment option for eosinophilic esophagitis (EoE); however, they are associated with side effects and some patients (pts) may not respond. Dupilumab demonstrated improvements in histologic, symptomatic, and endoscopic features in adult and adolescent pts with EoE over 24 weeks (Phase 3 LIBERTY EoE TREET study, NCT03633617) and is approved in the US and EU for the treatment of EoE. Here we assess the effect of long-term dupilumab on histologic, symptomatic, and endoscopic aspects of EoE in pts with/without prior use of STC and with/without prior inadequate response, intolerance, or contraindication to STC.

Aims & Methods

In Part B, pts received dupilumab 300 mg or placebo weekly (qw) for 24 weeks (W24). Eligible pts who completed Part B entered Part C and received dupilumab 300 mg qw for 28 weeks (W52). Clinicians categorized pts as with/without prior STC use and with/without prior inadequate response, intolerance, or contraindication to STC at screening. Assessed outcomes were: proportion of pts achieving ≤6 and <15 eosinophils per high-power field (eos/hpf), absolute change in Dysphagia Symptom Questionnaire (DSQ) score, mean change in Endoscopic Reference Score (EREFS), and Histologic Scoring System (HSS) grade/stage scores.

Results

In Part B, 80 pts received dupilumab and 79 placebo; in Part C, 74 continued dupilumab and 37 switched from placebo to dupilumab. Among pts who enrolled in Part C from Part B, 70% (78/111) had prior STC use. At W24, dupilumab improved vs placebo proportion of pts achieving ≤6 eos/hpf (with prior STC use 69% vs 7%, without 57% vs 0%), <15 eos/hpf (92% vs 11%, 83% vs 0%), and DSQ score (absolute mean [SD] change -27.3 [-15.8] vs -13.6 [12.5], -23.1 [15.6] vs -19.6 [15.0]). Pts continuing dupilumab in Part C further improved at W52: proportion achieving ≤6 eos/hpf (with prior STC use 86%, without 81%) and DSQ score (absolute mean [SD] change ‑31.4 [15.8], ‑27.7 [14.6]); all pts achieved <15 eos/hpf regardless of prior STC use. Pts switching from placebo to dupilumab at W24 improved at W52: proportion achieving ≤6 eos/hpf (with 70%, without 60%), <15 eos/hpf (82%, 70%), and DSQ score (‑26.1 [12.6], ‑29.9 [8.4]). At W52, EREFS and HSS grade/stage scores further improved or were maintained in pts continuing dupilumab and improved in pts switching to dupilumab (Table). Similar results were observed in pts with/without prior inadequate response, intolerance, or contraindication to STC.

Table. Peak eosinophil count in patients with or without prior swallowed topical corticosteroid use to Week 52

Conclusion

Dupilumab 300 mg qw for 52 weeks led to histologic remission (<6 eos/hpf) and sustained improvements in histologic, symptomatic, and endoscopic aspects of EoE, regardless of prior use or inadequate response, intolerance, or contraindication to STC.

Disclosure

AJB: Dr Falk Pharma, Norgine, Nutricia, Sanofi, SST, and Thelial – research funding; Alimentiv, Aqilion, AstraZeneca, Dr. Falk Pharma, Laborie, Medtronic, Regeneron Pharmaceuticals Inc., and Sanofi – consulting fees.
ESD: Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Celgene/Receptos/BMS, GSK, Meritage, Miraca, Nutricia, Regeneron Pharmaceuticals Inc., Revolo, Shire/Takeda – research funding; Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, Gossamer Bio, GSK, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nextstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron Pharmaceuticals Inc., Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio – consulting fees; Allakos, Holoclara, and Invea – educational funding.
IH: Allakos, AstraZeneca, Calyx/Parexel, Eli Lilly, Ellodi/Adare Pharma, EsoCap, Gossamer Bio, GSK, Nextstone, Pfizer/Arena Pharmaceuticals, Phathom, Receptos/BMS, Sanofi/Regeneron Pharmaceuticals Inc., and Shire/Takeda – consulting fees; Allakos, Ellodi/Adare Pharma Solutions, Receptos/BMS, Regeneron Pharmaceuticals Inc., and Shire/Takada – research funding.
AJL: Dr Falk Pharma and EsoCap – consulting fees; Dr Falk Pharma, Ellodi Pharmaceuticals, Regeneron Pharmaceuticals Inc. – research funding.
CS: Adare Pharmaceuticals Inc., AstraZeneca, Calypso, Dr. Falk Pharma, EsoCap, GmbH, and Regeneron Pharmaceuticals Inc. – consulting fees.
AS, EM, JM, and XS: employees of Regeneron Pharmaceuticals Inc. and may hold stock and/or stock options in the company.
EL and LG: employees of Sanofi and may hold stock and/or stock options in the company.

Introduction

Surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). Present risk stratification strategies do not discriminate sufficiently between risk groups. We aimed to develop and validate a dynamic multivariable prediction model for advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD.

Aims & Methods

We pooled data from six existing surveillance cohort studies (two unpublished).^1-3 Patients with IBD and an indication for CRC surveillance were included if they underwent at least one follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictors were selected based on the results of a recent meta-analysis,⁴ frequency, and data availability: extensive disease, prior dysplasia (indefinite for dysplasia or low-grade dysplasia), primary sclerosing cholangitis, male sex, IBD type, post-inflammatory polyps, age, and maximal endoscopic inflammation. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modelling.⁵ Model performance was assessed with Harrell’s c-statistic and by calibration curves, adjusted for optimism by internal cross-validation. In a sensitivity analysis model performance was assessed in data ≥2010 only (internal validation). Generalizability across the surveillance cohorts was evaluated by internal-external cross-validation.

Results

The surveillance cohorts encompassed time periods 1973-2021 and comprised 3,731 patients (54% male sex; 75% ulcerative colitis or IBD-unclassified and 25% Crohn’s disease) with a median follow-up of 5.7 years (interquartile interval 3.3-9.6; 26,336 patient-years of follow-up); 146 individuals were diagnosed with aCRN (see table 1 for patient characteristics). The final model contained eight predictors, with a cross-validation median c-statistic of 0.74 and 0.75 and calibration slope of 0.77 and 0.83 for, respectively, a 5- and 10-year prediction window in overall analyses. Calibration plots showed good calibration. Ninety percent of 10-year predicted aCRN risks were between 0.9 and 18.7%. Model discrimination improved in data ≥2010 and calibration results remained unchanged (48% of all procedures ≥2010). Internal-external cross-validation results showed medium discrimination and reasonable to good calibration.

Conclusion

We generated a model based on clinical factors that predicts future aCRN risk, with moderate to good model discrimination and good calibration. However, generalizability results vary and are impacted by varying cohort sizes and should be interpreted with caution. Future research should focus on formal external validation, relate predicted aCRN risks to surveillance intervals, and investigate the impact of this new model in daily clinic prior to clinical application.

References

1. Choi CR, Al Bakir I, Ding NJ, et al. Cumulative burden of inflammation predicts colorectal neoplasia risk in ulcerative colitis: a large single-centre study. Gut 2019;68:414-422.
2. Mahmoud R, Shah SC, Ten Hove JR, et al. No Association Between Pseudopolyps and Colorectal Neoplasia in Patients With Inflammatory Bowel Diseases. Gastroenterology 2019;156:1333-1344 e3.
3. Ten Hove JR, Shah SC, Shaffer SR, et al. Consecutive negative findings on colonoscopy during surveillance predict a low risk of advanced neoplasia in patients with inflammatory bowel disease with long-standing colitis: results of a 15-year multicentre, multinational cohort study. Gut 2019;68:615-622.
4. Wijnands AM, de Jong ME, Lutgens M, et al. Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis. Gastroenterology 2021;160:1584-1598.
5. van Houwelingen, H., & Putter, H. (2012). Dynamic Prediction in Clinical Survival Analysis (1st ed.). CRC Press. https://doi.org/10.1201/b11311:

Disclosure

Laurent Beaugerie: Research grants: Biogen, Celltrion, Takeda, Ferring, Celltrion, Viatris; Personal fees: Takeda, Nordic Pharma, Janssen, BMS, and Viatris.
Charles N. Bernstein: Dr Bernstein is supported by the Bingham Chair in Gastroenterology. Dr. Bernstein has served on advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb Canada, Eli Lilly Canada, Roche Canada, Janssen Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada; Educational grants from Abbvie Canada, Amgen Canada, Bristol Myers Squibb Canada, Ferring Canada, Organon Canada, Pfizer Canada, Takeda Canada, and Janssen Canada. Speaker’s panel for Abbvie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from Abbvie Canada, Amgen Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada.
Steven H. Itzkowitz: Dr Itzkowitz has served on Advisory Board for Exact Sciences Corporation and a consultant for Geneoscopy. He has received research support from Exact Sciences Corporation and Freenome.
Julien Kirchgesner: Lecture fees from Janssen and Lilly, and consulting fees from Roche, Gilead, Pfizer, Janssen, Celltrion, Lilly, Takeda, and Abbvie.
Cyriel Y. Ponsioen: Received grant support from Gilead and Perspectum and speaker’s fees from Tillotts

Introduction

Eosinophilic esophagitis (EoE) is a chronic, type-2 inflammation-driven esophageal disease causing dysphagia and esophageal dysfunction. Patients with inflammatory bowel disease (IBD) or other type-2 inflammatory disorders may have an increased risk of EoE, but prevalence data are limited. This study examines the prevalence of dysphagia and EoE in patients with type-2 inflammatory diseases or IBD.

Aims & Methods

In this prospective, multicentric, questionnaire-based screening study, patients from the departments of gastroenterology, pulmonology, dermatology, and otolaryngology at the Medical University of Vienna, as well as from the Allergy Center Floridsdorf, were screened for dysphagia using the validated brief esophageal dysphagia questionnaire (BEDQ). The primary endpoint was the prevalence of clinically relevant dysphagia, defined as a BEDQ score ≥10 or a history of bolus impaction in the past year. Endoscopy was offered to symptomatic patients without recent biopsies. Patient characteristics and differences in absolute eosinophil count, eosinophilic cationic protein (ECP), and IgE levels were analyzed using independent-samples T-tests.

Results

A total of 690 patients (45.7% female, mean age 54.5 years) were screened; 54.4% had IBD, 20.2% allergic rhinitis, 16.4% asthma, 8.7% atopic dermatitis, 6.4% chronic rhinosinusitis with nasal polyps (CRSwNP), and 5.2% IgE-mediated food allergy with multiple diagnoses possible. Overall, 5.1% (n=35) exhibited clinically relevant dysphagia. EoE was previously diagnosed in 2.0% (n=14), including four patients with clinically relevant dysphagia. Among the remaining 31 patients, eight had prior endoscopies ruling out EoE, seven underwent endoscopy revealing two new EoE cases, and 16 are still awaiting gastroscopy. No significant differences in IgE, eosinophilic count, or ECP were found between patients with EoE, those with dysphagia, and asymptomatic individuals.

Conclusion

Patients with IBD and type-2 inflammatory diseases exhibit a high prevalence of dysphagia. While EoE is more common than in the general population, most dysphagia remains unexplained. Systematic dysphagia screening in this high-risk population may reduce diagnostic delay.

Introduction

Currently there is no single strategy that has a clear benefit as primary therapy for Eosinophilic Esophagitis (EoE). Because of the continuous emergence of randomized clinical trials on various pharmacological and nonpharmacological approaches, we conducted a network meta-analysis in order to evaluate the efficacy and safety of available treatments for EoE in adult patients.

Aims & Methods

Histologic remission, clinical and endoscopic response, and serious adverse events (SAEs) were evaluated. Direct and indirect comparisons between treatments (proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), monoclonal antibodies (mAb), placebo) were performed. Results are expressed as risk ratio (RR) and 95% confidence interval (CI).

Results

A total of eight eligible randomized controlled trials (1057 patients) were included in the meta-analysis. When the three interventions were compared with each other, none was significantly more effective in terms of histologic remission (STC vs mAb RR 5.03, 95% CI 0.96-26.24, PPI vs mAb RR 0.87, 95% CI 0.41-3.12, PPI vs STC RR 0,75, 95% CI 0.60-5.09) while all three interventions were significantly superior to placebo (mAb vs placebo RR 31, 95% CI 10.91-88, STC vs placebo RR 54.26, 95% CI 12.1-241.83, PPI vs placebo RR 10.78, 95% CI 5.33-21.78). STC and mAB resulted as the best interventions (SUCRA 0.93 and 0.78, respectively) followed by PPI (SUCRA 0.38). None of the interventions tested resulted in a significant increase in SAE rate compared with placebo (mAb vs placebo RR 3.41, 95% CI 0.61-19.12, STC vs placebo RR 1.28, 95% CI 0.25-6.44). As a consequence, placebo ranked as the safest treatment (SUCRA 0.73), followed by STC (SUCRA 0.63) and mAb (SUCRA 0.51).

Conclusion

The results of this network meta-analysis show that mAb and STC were the most effective treatments among those available for EoE as assessed by histologic remission, both with a relatively low rate of serious adverse events.