Introduction

Infliximab is used to treat inflammatory bowel disease (IBD) but may be associated with adverse events such as infections. We describe hospitalization and emergency department (ED) visits among IBD patients using infliximab bio-originator (INF-O) or biosimilar (INF-B).

Aims & Methods

We used data from Canadian IBD Research Consortium (CIRC) cohorts contributing to CAN-AIM’s biosimilar registry, a pan-Canadian clinical registry of biosimilar/bio-originator users. We included people diagnosed with IBD who initiated infliximab between 2019-2023. Our outcome was self-reported hospitalization or ED visits, any time from INF initiation until outcome, treatment discontinuation or last information available. Categorical variables are presented as absolute numbers (percentage) and continuous as median (interquartile range, IQR). Kaplan-Meier curves with log-rank test and Cox regression model were used for time to event analyses for first hospitalization or ED - adjusted for sex and age at INF initiation.

Results

Of 158 individuals (78% INF-B), 53% had Crohn’s and 47% ulcerative colitis. Individuals were 54% male, 85% Caucasian, age at INF initiation at 37 years; 28% were using prednisone at enrolment. 16% were hospitalized at least once (first hospitalization within a median follow-up of 17 months (IQR 7-25) and 25% had at least one ED visit (first ED occurred at a median of 13 months, IQR 5-26). A total of 45 hospitalizations and 61 EDs were recorded. Most ED visits were due to IBD flare (n=33), infections (n=9), and other reasons (n=15). Most hospitalizations were for IBD-related surgery (n=19), IBD flare (n=16), and infections (n=7). Time from treatment initiation to first hospitalization or first ED was similar for INF-B and INF-O. Compared to INF-O, aHR for first hospitalization was 0.64 (95%CI 0.27-1.50) and ED was 0.72 (0.36-1.43) for INF-B.

Conclusion

In this real-world dataset, almost one-third of infliximab users for IBD had hospitalization or ED visits, often due to IBD flare, IBD-related surgery, and infections. We noted no clear differences between biosimilars and bio-originators, though limited sample size precluded precision.

Disclosure

Author disclosures (speaker, advisory board and/or grants): WA (Abbvie, Amgen, BMS, Dynacare, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, Prometheus, Sandoz, Sanofi, Takeda); NN (Janssen, Abbvie, Takeda, Pfizer, Merck, Sandoz, Novartis, Fresinius Kabi, Amgen, Celltrion, Viatris, Innomar Strategies, Iterative Health, and Ferring); YL: (BMS; Janssen, Abbvie, Frenius Kabus; Amgen; Takeda, Pfizer, Lily, Pendopharm; BioJamp); HS (Amgen Canada, Roche Canada, Sandoz Canada, Takeda Canada, Pendopharm Inc and Guardant Health, Inc); MGB, LL, AN, LW, SB: nothing to disclose.

Introduction

Fecal Microbiota Transplantation (FMT) delivered through capsules is an effective therapy against recurrent Clostrdioides difficile infections (rCDI). Studies suggests that the viral part (mainly represented by bacteriophages) of donor stool plays an important role in FMT treatment effect[1]. Through filtration steps the viral fraction of donor stool can be separated from the bacterial part to produce material that can be capsulized and delivered as fecal virome transplantation (FVT) through capsules[2].
The goal of this study was to compare the effect of FVT capsules against FMT capsules as treatment of rCDI in a randomized controlled pilot trial.

Aims & Methods

In the VISION study treatment with FVT capsules was compared to the standard treatment of FMT capsules in 40 patients with first or second recurrence of C. difficile infection.
Participants were randomized 1:1 to receive either one dose of FMT or FVT capsule treatment preceded by approximately 10 days of Vancomycin 125 mg x 4 daily or Fidaxomycin 200 mg x 2 daily. The same four fecal donors were used to produce FMT and FVT material. The primary endpoint was clinical resolution defined as resolution of diarrhea with ≤ 3 daily bowel movements or persistent diarrhea with a negative C. difficile test result, eight weeks following treatment. Patients receiving antibiotics as treatment of other infections were treated with concurrent Vancomycin and were defined as treatment failures in the Intention-to-treat analysis but were excluded from the per-protocol analysis.

Results

Forty patients were randomized and received FMT or FVT capsule treatment with no significant difference between groups in baseline characteristics (Table 1). The primary outcome was achieved by 70 % (14/20) in the FVT group and 75% (15/20) in the FMT group with no significant difference between groups (p = 1). Three patients were omitted from the per-protocol analysis. Here the primary outcome was achieved by 73.7 % (14/19) in the FVT group and 83.3 % (15/18) in the FMT group with no significant difference between groups (p = 0.69).

Table 1. Baseline characteristics

Conclusion

FVT capsules were effective as treatment of rCDI and were non-inferior to FMT capsules. Larger trials are needed to further explore the efficacy of FVT capsules as treatment of rCDI.

References

[1] Liu Q, Xu Z, Dai M, Su Q, Leung Chan FK, Ng SC. Faecal microbiota transplantations and the role of bacteriophages. Clinical Microbiology and Infection 2023;29:689–94. https://doi.org/10.1016/j.cmi.2022.11.012.
[2] Rasmussen TS, Mao X, Forster S, Larsen SB, Von Münchow A, Tranæs KD, et al. Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments. Microbiome 2024;12:119. https://doi.org/10.1186/s40168-024-01820-1.

Disclosure

Frederik Cold declares support for attending meeting and/or travel from AbbVie and Orion Pharma, Andreas Munk Petersen declares support for attending meeting and/or travel from AbbVie, grants or contracts from Chr. Hansen A/S part of Novonesis and consulting fee from Genfit, Hengameh Chloe Mirsepasi-Lauridsen, Torben Sølbeck Rasmussen, Lars Hestbjerg Hansen, Sofie Ingdam Halkjær, Dennis Sandris Nielsen and Morten Helms declares no conflicts of interest.

Introduction

Duodenal stump fistula (DSF) represents a significant complication that can arise following gastrectomy, with a prevalence ranging from 1.0% to 2.5%. This condition is characterised by a high mortality risk (12.5% to 28%) and a high morbidity rate (75%). In instances where conservative management has proven ineffective, percutaneous transhepatic biliary drainage (PTBD) emerges as a valuable intervention. This procedure involves the aspiration of bile, thereby reducing duodenal pressure and diminishing fistula output. However, it is important to note that PTBD does necessitate a prolonged healing period and frequently requires subsequent treatments, such as percutaneous or endoscopic injection of glue. The prolonged hospitalization is also to be considered in these patients, in which the resolution of the fistula generally requires a period of between 60 and 240 days.
The objective of this study was to ascertain the viability and effectiveness of a pioneering technique involving percutaneous DFS embolization with ethylene vinyl alcohol copolymer (EVOH) in combination with an occlusion balloon, utilised in the management of DSF following gastrectomy for malignant or benign indications.

Aims & Methods

The present study encompassed patients with a diagnosis of DSF, as determined by the presence of duodenal juice in the surgical drainage or its leakage through the abdominal wall. This diagnosis was confirmed through surgical approach and/or a computerised tomography (CT) scan. A retrospective analysis was conducted on 15 consecutive patients who underwent PTB-A embolization with Ethylene-Vinyl Alcohol Copolymer (EVOH) as a treatment for DSF, following the failure of medical, surgical, or endoscopic interventions.
An analysis was conducted of clinical and technical success, morbidity and mortality.

Results

The population under scrutiny comprised 10 female and 5 male subjects. Furthermore, it is noteworthy that 74% of patients underwent surgery for a malignant lesion. In the present study, a total of 13 patients underwent subtotal gastrectomy. In all cases, technical success was achieved. A positive outcome was achieved in 11 out of 15 patients following a single treatment. In 4 cases, patients required further treatment to achieve complete fistula healing. In the course of treatment, it was observed that a single patient required four treatment sessions to achieve complete healing. No procedure-related complications or mortalities were recorded. No recurrence of the fistula was observed in the population under study. Radiological follow-up was conducted at one or three months following the procedure for a total of 11 patients. 2 patients expired prior to the scheduled follow-up due to unrelated causes, while 2 patients failed to attend the control appointment.

Conclusion

PTB-A embolization with EVOH of duodenal stump fistula seems to be an effective treatment for DSF, with prompt recovery, no mortality and short hospitalization after the procedure.

References

1. Orsenigo E,et al. Duodenal stump fistula after gastric surgery for malignancies: a retrospective analysis of risk factors in a single centre experience. Gastric Cancer. 2014 Oct;17(4):733-44. doi: 10.1007/s10120-013-0327-x.

2. Paik HJ, et al. Duodenal stump fistula after gastrectomy for gastric cancer: risk factors, prevention, and management. Ann Surg Treat Res. 2016 Mar;90(3):157-63. doi: 10.4174/astr.2016.90.3.157.

3. Gu L, et al. Risk Factors for Duodenal Stump Leakage after Laparoscopic Gastrectomy for Gastric Cancer. J Gastric Cancer. 2020 Mar;20(1):81-94. doi: 10.5230/jgc.2020.20.e4.

4. Naito R, et al. Retrograde drainage for duodenal stump leakage using ileal decompression tube guided by double-balloon endoscopy: a novel case report. Surg Case Rep. 2024 Feb 18;10(1):44. doi: 10.1186/s40792-024-01842-9.

5. Aurello P, et al. Management of duodenal stump fistula after gastrectomy for gastric cancer: Systematic review. World J Gastroenterol. 2015 Jun 28;21(24):7571-6. doi: 10.3748/wjg.v21.i24.7571.

6. Zizzo M, et al. Management of duodenal stump fistula after gastrectomy for malignant disease: a systematic review of the literature. BMC Surg. 2019 May 28;19(1):55. doi: 10.1186/s12893-019-0520-x.

7. Cozzaglio L, et al. Percutaneous transhepatic biliary drainage and occlusion balloon in the management of duodenal stump fistula. J Gastrointest Surg. 2011 Nov;15(11):1977-81. doi: 10.1007/s11605-011-1668-6.

Introduction

Early detection of gastric neoplasms in esophagogastroduodenoscopy (EGD) remains challenging due to the subtle and indistinct appearance of the lesions. In addition to white light imaging (WLI), image-enhanced endoscopy techniques, such as linked color imaging (LCI), are commonly used to detect such lesions. Recently, a computer-aided detection (CADe) system compatible with WLI and LCI (CAD EYE; Fujifilm Co., Tokyo, Japan) has been developed. However, evidence of its effectiveness in real-world clinical settings remains limited.

Aims & Methods

We conducted a multicenter, non-randomized confirmatory trial to evaluate the performance of CAD EYE in detecting gastric neoplasms. Between July 2023 and January 2024, patients undergoing EGD for known early gastric neoplasms were recruited at four institutions in Japan. While systematically observing the entire stomach with WLI and LCI, we investigated whether these lesions were detected by CAD EYE. The primary outcome was the sensitivity of CAD EYE (WLI-CADe and LCI-CADe) in detecting tumors. Secondary outcomes included identifying tumor characteristics and factors associated with missed detections by CAD EYE. To determine the sample size, we presumed the sensitivity of CAD EYE to be 95% based on pre-approval data, with a threshold set at 90%. The number of lesions required was calculated to be 150, ensuring that the lower limit of the 95% confidence interval (CI) exceeded the threshold of 90%. Assuming one lesion per patient and accounting for a 5% dropout rate, we recruited a total of 160 patients.

Results

A total of 174 lesions from 162 patients (mean age: 73.7±9.5 years, male: 69.7%) were analyzed. Current or past history of Helicobacter pylori (H. pylori) infection was observed in 158 patients (97.5%). The mean tumor diameter was 15.1 ± 11.3 mm, and the morphology consisted of 6 protruded, 51 flat elevated, and 117 flat types. Histology included 151 differentiated adenocarcinoma, 20 undifferentiated adenocarcinoma, 2 adenocarcinoma of fundic-gland type, and 1 tubular adenoma. The sensitivities of WLI-CADe and LCI-CADe in detecting tumors were 92.0% (95% CI: 86.9%–95.5%) and 96.5% (95% CI: 92.6%–98.7%), respectively. The sensitivity of LCI-CADe met expectations, as the lower limit of the 95% CI exceeded the threshold of 90%; however, WLI-CADe failed to meet the same standard. In WLI-CADe, lesions located on the anterior/posterior wall were missed significantly more often than those on the greater/lesser curvature (13.9% [11 of 79] vs. 3.2% [3 of 95]; P = 0.020); whereas no difference was observed in LCI-CADe. Other factors, such as H. pylori infection status, tumor morphology, location, and histology, showed no differences between lesions detected and missed by WLI-CADe and LCI-CADe.

Conclusion

The use of CADe with LCI demonstrated satisfactory sensitivity in detecting gastric neoplasms in real-world clinical settings, suggesting its potential to assist endoscopists in tumor detection. However, CADe with WLI did not meet the expected standards, possibly due to limitations, such as detecting lesions located on the anterior/posterior wall.

Disclosure

CAD EYE was temporarily provided by Fujifilm Co. Osamu Dohi has received a research grant, not related to this study, from Fujifilm Co. The remaining authors declare no conflicts of interest.

Clinical Case Summary

A 64-year-old woman with a prior diagnosis of type I achalasia underwent Heller myotomy with Dor fundoplication in 2015, which resulted in the resolution of dysphagia and regurgitation. However, she kept experiencing chest pain, which partially improved with nitro-glycerine. In 2018, due to worsening pain, she underwent high-resolution oesophageal manometry (HROM), which demonstrated absent peristalsis without oesophageal pressurization. Also, upper endoscopy was unremarkable, and timed barium swallow (TBS) revealed some tertiary contractions. By 2019, the patient received botulinum toxin injections with partial improvement. Another TBS performed in 2023 showed tertiary contractions in the distal third of the oesophagus, contributing to mild oesophageal emptying delay but without stasis. In 2024, repeat HROM revealed pan-oesophageal pressurization, except in the distal-most centimetres of the oesophagus. During rapid drink challenge, the patient reported pain. Given these findings, she was proposed for peroral endoscopic myotomy (POEM) to extend the myotomy proximally. In August 2024, she underwent a complete distal oesophageal myotomy, including the lower oesophageal sphincter and cardia. Endoscopic assessment in November showed no evidence of stasis, esophagitis, or resistance at the cardia. Latest clinical evaluation in March 2025 confirmed complete resolution of chest pain.
Conclusion: Non-cardiac chest pain is a less common yet challenging symptom to manage in achalasia. Its persistence after disease-directed treatment has been described in the literature, with its primary risk factor being its presence preoperatively¹. However, comparative data on different therapeutic approaches for achalasia-related chest pain remain limited. To our knowledge, only two similar cases have been reported in which pain persisted after Heller myotomy but improved following POEM, probably linked to the inadequate or incomplete myotomy of the oesophageal muscle layer^2,3.

References

1. Olvera-Prado H, et al. Predictive factors associated with the persistence of chest pain in post-laparoscopic myotomy and fundoplication in patients with achalasia. Front Med (Lausanne). 2022 Oct 14;9:941581.
2. Miftahussurur M, Tandan M, Makmun D, Nabi Z. Peroral Endoscopic Myotomy in a Patient with Achalasia Cardia with Prior Heller's Myotomy. Case Rep Gastroenterol. 2020 Jan 22;14(1):48-55.
3. Sato C, et al. Salvage therapy for postoperative residual chest pain due to esophageal achalasia. SAGES 2017 Annual Meeting in Houston [Abstract], https://www.sages.org/meetings/annual-meeting/abstracts-archive/salvage-therapy-for-postoperative-residual-chest-pain-due-to-esophageal-achalasia/

Introduction

H. pylori eradication therapy induces significant alterations in the gut microbiome. While probiotics have been extensively studied as a potential strategy to mitigate microbiota-related consequences of antibiotics, their efficacy remains a subject of debate.

Aims & Methods

The aim of our study was to evaluate the influence of butyric acid+inulin supplements on gut microbiota changes (including gut microbiota taxonomic composition, functional potential, and gut resistome) induced by H.pylori eradication therapy. A total of 22 H. pylori-positive patients aged 19 to 64 years were enrolled in the study. Patients were randomized into two H. pylori eradication regimens: 1) ECAB-14: esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, orally, for 14 days. 2) ECAB-Z-14: esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, along with butyric acid+inulin (Zacofalk) supplementation (two tablets daily, each containing 250 mg of butyric acid and 250 mg of inulin), orally, for 14 days. Stool samples were collected from each subject at three time points: prior to eradication therapy (I), after therapy completion (II), and one month post-therapy (III). Total DNA from fecal samples was isolated for whole genome sequencing using the Illumina NextSeq 500 platform.

Results

Gut Microbiota Alpha Diversity (Shannon Index): Immediately after eradication therapy, both the ECAB-14 and ECAB-Z-14 groups experienced a significant decrease in gut microbiota alpha diversity compared to the initial level: (2.46 ± 1.06) vs. (3.75 ± 0.342), p = 0.0029, and (3.22 ± 0.73) vs. (3.82 ± 0.30), p = 0.037, respectively. After one month, the Shannon index was restored to the baseline level in the ECAB-Z-14 treatment group: no statistically significant differences were identified between time points III and I [(3.71 ± 0.33) vs. (3.82 ± 0.30), p = 0.206]. However, even a month after therapy, the ECAB-14 treatment group still exhibited a lower Shannon index than the baseline level [(3.27 ± 0.39) vs. (3.75 ± 0.342), p = 0.019].
Functional Potential Alterations: In the ECAB-Z-14 treatment group, less pronounced alterations in gut microbiota functional potential were observed. Specifically, 72 metabolic pathways changed immediately after eradication therapy. In contrast, the ECAB-14 group showed impact on 112 signaling pathways.
Butyrate Production Genes: The abundance of genes associated with butyrate production decreased only in the ECAB-14 treatment group. However, in the ECAB-Z-14 treatment group, the abundance of genes responsible for butyrate production remained stable.
Antibiotic Resistance Genes: The prevalence of gut microbiota antibiotic resistance genes increased significantly in both treatment groups immediately after eradication. Notably, more severe alterations were observed in the ECAB-14 treatment group, where the abundance of 73 antibiotic resistance genes significantly increased. Meanwhile, the ECAB-Z-14 group showed an increase in only 50 antibiotic resistance genes immediately after eradication therapy.

Conclusion

H. pylori eradication therapy significantly affects gut microbiota composition, functional potential, and increases the abundance of antibiotic resistance genes. However, the addition of butyric acid+inulin supplements to the H. pylori eradication regime may mitigate these effects.