Introduction

Several factors are known to affect the clinical presentation of Helicobacter pylori (H. pylori) infection including bacterial virulence factors, intensity of the immune response of the host, host’s genetic factors, as well as different environmental factors. Complex interactions between H. pylori and the host’s immunological response result in the production of various cytokines (interferon-γ, tumor-necrosis factor α, interleukin-1β, and interleukin-8) and reactive oxygen species (ROS) which lead to prolonged inflammation and subsequent damage to the gastric mucosa. Various inflammation mechanisms have been studied in H. pylori infection, including those related to the NF-κB signaling pathway, ROS, and more recently NLRP3 inflammasome. When it comes to the multifunctional family of glutathione transferase enzymes, glutathione S-transferase omega (GSTO) and pi (GSTP) are known for their antioxidant, as well as signaling activity. Specifically, the regulatory effects of GSTO and GSTP1, on NLRP3 inflammasome and NF-κB signaling pathway, respectively, have been extensively studied.

Aims & Methods

Based on the known catalytic and signaling functions of GSTO and GSTP and their effect on both redox homeostasis and inflammation, we proposed a possible modifying role of GSTO and GSTP1 polymorphisms in the individual susceptibility towards the development of H. pylori infection. The distribution of polymorphisms in GSTO1 (rs4925), GSTO2 (rs156697), and GSTP1 (rs1695 and rs1138272) were assessed in 101 H.pylori-positive and 107 H.pylori-negative patients, emphasizing their individual and haplotype effects on disease development. Polymorphisms were determined by the appropriate qPCR method.

Results

The obtained results showed no influence of GSTO1 (rs4925) and GSTO2 (rs156697) polymorphisms on H.pylori infection development in both individual and haplotype analyses (p>0.05). However, individuals carrying variant GSTP1 (rs1695 and rs1138272) genotypes exhibit up to three times higher odds of H.pylori infection development, compared to those carrying referent alleles (Table 1). These findings are confirmed by further haplotype analysis. Carriers of H3 haplotype, comprising GSTP1*G and GSTP1*T variant alleles were at more than a 3-fold increased risk of H. pylori infection development (p=0.012).
Table1. Distribution of GSTP1 genotypes in H. pylori-positive and H. pylori-negative patients.

GSTP1 rs1695 genotype	HP negative, n (%)	HP positive, n (%)	OR (95% CI)	p
*A/A	47 (44)	35 (35)	1a
*A/G	53 (50)	50 (49)	1.27 (0.71-2.27)	0.427
*G/G	7 (6)	16 (16)	3.07 (1.14-8.26)	0.026
*A/G + *G/G	60 (56)	66 (65)	1.47 (0.84-2.58)	0.172
GSTP1 rs1138272 genotype
*C/C	92 (87)	74 (73)	1a
*C/T	14 (13)	22 (22)	1.95 (0.93-4.08)	0.075
*T/T	0 (0)	5 (5)	/	/
*C/T + *T/T	14 (13)	27 (27)	2.39 (1.17-4.89)	0.016

HP – Helicobacter pylori; OR – odds ratio; CI – confidence interval;

Conclusion

GSTP1 polymorphisms modify susceptibility to developing H. pylori infection. Further studies are needed to clarify the specific roles of glutathione transferases in innate and acquired immune response in the context of H. pylori infection development and maintenance.

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

Low grade dysplasia (LGD) is a key risk factor for development of high grade dysplasia (HGD) and colorectal cancer (CRC), in individuals with inflammatory bowel disease (IBD). Current clinical guidelines recommend that the detection of LGD should guide decision making, often leading to intensified surveillance or, in some cases, colectomy. As such, the detection of LGD in IBD imposes a considerable burden on both affected individuals and healthcare systems. The incidence, prevalence and treatment of IBD are continuously evolving. This may have influenced the incidence of IBD-related LGD and potentially its progression to HGD and CRC. Despite these developments, limited literature describes temporal trends in the incidence of IBD-related LGD, HGD and CRC, especially over the past decade, a period marked by the widespread use of biological therapies. Therefore, we aimed to utilize nationwide Danish health registers to describe trends over time in the incidence of IBD-related LGD, HGD and CRC.

Aims & Methods

We conducted a nationwide cohort study using data from Danish national health registers from 1990 to 2022. All Danish residents with a first-time diagnosis of either IBD, IBD-related LGD, HGD or CRC during this period were included. IBD-relation was established when a diagnosis of dysplasia or CRC was recorded within 180 days prior to, or at any time after, a first IBD diagnosis. HGD and/or CRC was defined as a composite endpoint, with the date assigned to the first occurring diagnosis if both were present. Incidence rates for IBD, IBD-related LGD, and HGD/CRC were calculated per 100,000 person years. Annual incidence rates and incidence rate ratios (IRRs) with 95 percent confidence intervals (CIs) were calculated using a Poisson approximation.

Results

During the study period, a total of 92,717 new cases of IBD, 8,406 cases of LGD, and 2,480 cases of HGD/CRC were identified.
The incidence of IBD per 100,000 person years increased markedly over time, rising from 30.36 in 1990 (95% CI: 28.89 to 31.91) to 59.71 in 2020 (95% CI: 57.76 to 61.73). A similar trend was observed for IBD-related LGD, with the incidence increasing from 0.33 (95% CI: 0.21 to 0.53) in 1990 to 10.41 (95% CI: 9.61 to 11.27) in 2020. For IBD-related HGD/CRC, the incidence rose from 0.12 (95% CI: 0.05 to 0.26) to 0.81 (95% CI: 0.61 to 1.07) in the same period. In the yearly incidence curves, the increase for both IBD and HGD/CRC appeared steady over time until a plateau was reached around 2008, whereas a distinct spike in LGD incidence was observed in 2014. This spike coincided with the introduction of a national CRC screening program in Denmark. Notably, the overall increase in IBD-related LGD far exceeded that of advanced dysplasia, with an IRR between 1990 and 2020 of 31.44 (95% CI: 28.01 to 35.28) for LGD, compared to 3.59 (95% CI: 3.35 to 3.85) for HGD/CRC.

Conclusion

The incidence of IBD, IBD related LGD, and IBD-related HGD/CRC has increased substantially in Denmark over the past 30 years. We observed a plateau in the incidence of IBD and IBD-related HGD/CRC within the last decade. Notably the overall increase in incidence was far more pronounced for IBD-related LGD, where we also observed a very notable spike in 2014, temporally aligned with the introduction of CRC screening in Denmark, this was not mirrored in the incidence of IBD-related HGD/CRC.

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

Oesophageal food bolus impaction [OFBI] is a common presentation to emergency room [ER] and often requires endoscopic intervention. We aimed to describe the incidence of OFBI in Canterbury, New Zealand and examine factors predicting the need for endoscopic intervention and complications in the population-based cohort.

Aims & Methods

All ER presentations of OFBI in Canterbury between October 2018 and August 2023 were included. Population data for the Canterbury population was obtained from Statistics NZ. Ethnicity was defined according to hospital records based on patients’ self-identification. Endoscopic intervention was defined as the presence of bolus during the endoscopy requiring any endoscopic manoeuvre for clearance. Complications were defined as unsuccessful attempts requiring a repeat procedure or procedure-related injuries.

	Total (n = 187)
Age (years)	Mean 55 Median 54.9
Gender - Male (%) : Female (%)	113 (60.4) : 74 (39.6)
Ethnicity - European (%) : Non-European (%)	163 (87.2) : 24 (12.8)
Cause of oesophageal impaction (%)	EoE 42 (22.5) Stricture 43 (23)£ Other 15 (8)* Idiopathic/unknown 87 (46.5)¥
Food type (%)	Meat 141 (86.5) Non-meat 46 (24.5)
Spontaneous clearance of food bolus clinically, without endoscopy performed (inpatient or outpatient) (%)	42 (22.5)
Spontaneous clearance of food bolus diagnosed on endoscopy as an inpatient (%)	37 (19.8)
Inpatient endoscopic intervention required (%)	92 (49.2)
Total complications (%)	8 (4.3)

£ cause of impaction from Schatzi ring or benign esophageal stricture
* cause of impaction from severe reflux oesophagitis (Los Angeles Grade C or D), esophageal dysmotility, malignant stricture, or esophageal candidiasis
¥ no cause for impaction found; either no endoscopy performed as an inpatient or outpatient or no pathology found on endoscopy

Results

There were 187 ER presentations of OFBI between October 2018 and August 2023. Clinical characteristics of the population-based cohort are presented in Table 1.
The average annual incidence of ER presentations of OFBI in Canterbury region between 2019 – 2022 was 5.82 per 100,000 population (95% CI 3.96-7.68/100,000). The incidence of ER presentations of OFBI in Europeans and non-Europeans over the same period was 8 per 100,000 European population (95% CI 5.27-10.73/100,000) and 1.94 per 100,000 non-European population (95% CI 0.15-3.73/100,000).
A total of 92 cases (49%) required endoscopic intervention. Factors predicting the need for endoscopic intervention were meat bolus [p= 0.01], stricture [p<0.01], and early endoscopy performed <12hrs [p<0.01]. There were only 8 complications. Predictors with a trend associated with complications were after-hours presentation [p=0.06] and early endoscopy performed <6hrs [p=0.06].

Conclusion

Our population-based cohort showed a significantly higher incidence of ER presentations of OFBI in Europeans than in non-European ethnic groups. Factors predicting the need for endoscopic intervention were meat bolus, stricture and early endoscopy. After-hours presentation and early endoscopy <6hrs showed a trend towards a higher risk of complications. The results suggest that a delayed approach may be associated with a higher chance of spontaneous clearance and a lower risk of complications, although further study is needed.

Disclosure

Not applicable

Introduction

As many as 40% of IBD patients do not respond to targeted therapies¹. Enhancing the efficacy of these therapies is a key priority, and defective host-microbe interplay is often thought to underpin a proportion of mechanistic therapeutic failure. Interactions of macrophages with the microbial-derived SCFAs (Butyrate, Propionate and Acetate) in particular; may be critical for disease remission. Therefore, we examined the manner that macrophages interacted with, and changed their behaviour according to exposure to SCFAs in order to identify new therapeutic targets.

Aims & Methods

This study aimed to explore phenotypic changes of macrophages upon sensing of SCFAs in the context of IBD. We hypothesised that SCFAs would alter the inflammatory signature of macrophages, and that de-orphanized transmembrane G-protein receptor Free-fatty acid receptor 3 (FFA3) expressed by immune cells in GI tract would be critical for this process, and furthermore that effective sensing of SCFAs would be necessary for shaping macrophage phenotype. THP-1 and monocyte-derived macrophage models were developed for exploring inflammatory signatures in the presence of 1mM or 4mM of each SCFA (Butyrate/Propionate/Acetate). By using a pharmacological activator of FFA3 (AR420626) we aimed to identify whether this receptor play an important role in directing macrophage phenotype. Secretion of (type-I Interferon) IFN-I and pro-inflammatory cytokines were measured using ELISA. Expression of Interferon-stimulated genes (ISGs) was quantified using RT-PCR. Subsequent experiments aimed to validate our findings with a knock-down model of FFA3.

Results

We demonstrated that polarisation of macrophages with LPS & IFN-γ rapidly led to the induction of type-I interferon responses and release of pro-inflammatory cytokines. This heightened secretion of IFN-I was almost entirely muted in the presence of butyrate and propionate (1mM and 4mM). As IFN-I drives the expression of ISGs though activation of IFNAR1-JAK/STAT axis, we quantified expression of the ISGs MX1 and IFIT1 as an indirect measure of bioactive IFN. Induction of MX1 and IFIT1, were strongly repressed by butyrate and propionate. Based on these observations, we determined that these responses to both SCFAs were being mediated by FFA3. Intriguingly, our results were closely mimicked by pharmacological intervention with AR420626 in a dose-dependent manner (10 – 50 μM), suggesting that IFN-I secretion could be attenuated through activation of FFA3. Introducing a knock-down to our model, we validated our findings, and macrophages displayed impaired sensing of SCFA in the absence of FFA3.

Conclusion

We identified that macrophages reduce IFN-I release in the presence of butyrate and propionate, which is partly mediated through FFA3, and FFA3 ligands may be helpful for dampening inflammation in the gut mucosa in IBD.

References

(1). Ben-Horin, S., Kopylov, U. & Chowers, Y. Optimizing anti-TNF treatments in inflammatory bowel disease. Autoimmun. Rev. 13, 24–30 (2014).

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

	FVT (n=20)	FMT (n=20)	P value for difference
Age, Mean (SD)	63.4 (15.7)	63.1 (18.7)	0.95
Gender, Females, n (%)	12 (60)	13 (65)	1
Number of CDI episodes, Mean (SD)	2.55 (0.5)	2.45 (0.5)	0.54
Charlson comorbidity index, Mean (SD)	3.1 (2.2)	3.7 (2.8)	0.46
Previous treatment of CDI: Vancomycin Vancomycin and Fidaxomycin Vancomycin and FMT	17 2 1	20 0 0

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.