Introduction

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease with unknown causes. Patients experience periods with active disease and symptoms such as diarrhoea, pain and weight loss. Little is known about environmental factors that trigger flare-ups, including the effects of commonly used medications. Recent studies suggest a link between microbial factors and IBD, making it important to investigate the impact of antibiotics on flare-ups.

Aims & Methods

We aimed to investigate whether certain antibiotics increase the risk of flares in patients with IBD. We utilized a previously described¹ cohort of all patients with IBD in Denmark between 1974 and 2018. The cohort is based on the Danish Nationwide Patient Registry, which registers all healthcare related visits, treatments and procedure on an individual level. We utilized data between 1994 and 2018 and two distinct cohorts was created for the purpose of identifying flares. The first cohort was characterized by having an IBD-related hospital stay. The second cohort was characterized by experiencing a flare of IBD in need of systemic steroids. Patient were matched 1:5 using K-nearest neighbour. Antibiotics were grouped into the 3rd level of the Anatomical Therapeutic Chemical (ATC) classification system, with anthelmintics grouped into the 2nd level due to low numbers and all given within 60 days before the outcome. Logistic regression analysis was used to calculate odds ratios (ORs) with a 95% confidence interval (95% CI), with adjusting variables including year of remission/flare, sex, age at diagnosis, year of diagnosis, type of IBD, socioeconomic status², use of 5-ASA, use of budesonide, use of immunosuppressants, and use of subtypes of biologics.

Results

There were in total 69,908 IBD patients in the original cohort. After applying the abovementioned algorithm, a total of 15,636 and 5,178 patients were included in the cohort for hospitalisation and steroid use, respectively.
Using a multivariate logistic regression model, both cohorts observed a significant increase in odds ratios for certain antibiotics in relation to hospitalization and steroid course. Specifically, for the need of a course of steroids, quinolones (OR 3.83 (95% CI: 2.73-5.35)), antimycotics (OR 2.30 (95% CI: 1.53-3.40)), agents against amoebiasis and protozoal (OR 2.06 (95% CI: 1.39-3.01)), betalactam antibiotics (OR 1.35 (95% CI: 1.10-1.66)), and intestinal anti-infectives (OR 2.12 (95% CI: 1.08-3.98)) were associated with an increased risk for a flare requiring steroids.
Regarding the need for an IBD-related hospitalization, agents against amoebiasis and protozoal (OR 3.48 (95% CI: 2.72-4.44)), quinolones (OR 3.10 (95% CI: 2.48-3.86)), intestinal anti-infectives (OR 2.42 (95% CI: 1.54-3.76)) and antimycotics (OR 1.58 (95% CI: 1.17-2.12)) were all found to be significantly associated.

Conclusion

This study provides evidence that certain types of antibiotics increase the risk of flare-ups in patients with IBD. Quinolones, antimycotics, agents against amoebiasis and protozoal, betalactam, and intestinal anti-infectives were all associated with increased odds ratios for hospitalization and a need for a course of steroids. These findings highlight the importance of carefully considering the use of antibiotics in IBD patients and the need for further research on the effects of different antibiotics on disease progression.

References

¹ Lo B, Zhao M, Burisch J. Identifying patients with inflammatory bowel disease in the Danish National Patient Register. Dan Med J. 2023 Mar 27;70(4):A07220458. PMID: 36999818.
² https://www.dst.dk/en/Statistik/dokumentation/nomenklaturer/socio

Disclosure

An unrestricted grant was received from the Aage og Johanne Louis-Hansens Fond to support this study.

Introduction

To prevent stent migration during EUS-HGS, intra-scope channel release technique is important, but are unfamiliar to non-expert hands. The self-expandable metal stent (SEMS) is an additional factor to prevent stent migration. However, no comparative studies of laser-cut and braided types during EUS-HGS have been reported.

Aims & Methods

The aim of this study was to compare the distance between the intrahepatic bile duct and stomach wall after EUS-HGS among laser-cut- and braided-type SEMS. To evaluate stent anchoring function, we measured the distance between the hepatic parenchyma and stomach wall before EUS-HGS, one day after EUS-HGS, and 7 days after EUS-HGS.　Also, propensity score matching was performed to create a propensity score for using Laser cut type group and Braided group with a logistic regression model.

Results

A total 144 patients were enrolled in this study. Among them, 24 patients underwent EUS-HGS using a laser-cut-type SEMS, and 118 patients underwent EUS-HGS using a braided-type SEMS. EUS-HGS using the laser-cut-type SEMS was mainly performed by non-expert endoscopists (n=21). However, EUS-HGS using braided-type SEMS was mainly performed by expert endoscopists (n=98), showing a significant difference. The distance after 1 day was significantly shorter with the laser-cut-type group (2.91 ± 1.88 mm) compared with the braided-type group (8.19 ± 6.07 mm). In addition, this distance remained significantly shorter in the laser-cut type group compared with the braided-type group after 7 days.　Although these results were similar after propensity score matching analysis, the distance between hepatic parenchyma and stomach after 7 days was increased 4mm compared with the distance after 1 day in Braided group. On the other hand, in Laser cut type group, the distance after 1 day and 7 days was almost same.

Conclusion

In conclusion, EUS-HGS using a laser-cut-type SEMS may be safe to prevent stent migration, even in non-expert hands, compared with a braided-type SEMS, although a randomized trial is warranted.

Disclosure

None

Introduction

Balloon dilation and plastic stent deployment have been performed as hepaticojejunostomy stricture (HJS) treatment techniques by PTBD or under DB-ERCP guidance. Although these techniques have shown favorable clinical results, the treatment period can be long because stent deployment is required. In addition, HJS may recur even after treatment because the scar tissue itself remains. To overcome these challenges, we developed an transluminal antegrade piecemeal dilation technique (TAPD) for treating HJS. The aim of this study was to evaluate the technical feasibility and safety of this technique in terms of the pre- and post-cholangioscopic findings.

Aims & Methods

This retrospective study included consecutive patients who were complicated with symptomatic HJS between November and February 2022. The primary outcome of this study was the technical success rate of TAPD using a drill dilator. Technical success was defined as resolution of the HJS, based on the cholangioscopic findings. The secondary outcome was adverse events associated with TAPD such as bleeding or perforation.

Results

TAPD was attempted at around 11 days after EUS-HGS in 19 patients. Among the 19 patients, passage of the guidewire across the HJS into the intestine was unsuccessful in 4 patients, and the technical success rate of this procedure was 78.9%. TAPD was successful in all 15 patients in whom passage of the guidewire was achieved. After TAPD, cholangioscopy identified no bleeding or perforation in any patient. During the follow-up period, no recurrence of HJS was observed in any patient who underwent TAPD.

Conclusion

In conclusion, TAPD appears to be technically feasible and safe. Although it is necessary to conduct a randomized trial in comparison with other methods, with long-term follow up, TAPD may be a useful option for the treatment of HJS.

Introduction

Despite new therapeutic strategies, substantial proportion of patients with ulcerative colitis (UC) undergo colectomy at some point. Restorative proctocolectomy with ileal pouch ano anastomosis (IPAA) is regarded as intervention of choice in these patients. However, the disease conversion to Crohn´s disease (CD) is reported in up to one third of these patients who necessitate immune suppressive treatment after IPAA. Considering the life-long need for immune suppressive therapy in these patients, ileo-rectal anastomosis (IRA) would represent a good alternative to IPAA in this specific group of patients. Todate, no data are available to predict the UC-CD conversion. One of the possibility to reduce the risk of performing IPAA in patients developing CD in pouch is to use the modified two-stage proctocolectomy approach and identify patients who develop CD endoscopically between colectomy and the restoration of continuity.

Aims & Methods

The aim of the present study was to assess the UC-CD conversion rate identified prior IPAA via ileoscopy.
All patients with UC operated in one tertiary IBD center between 2016 and 2021 were identified in medical records. The main outcome was CD detected at ileoscopy between the first stage operation, i.e. total colectomy with terminal ileostomy and the restoration of continuity either via IPAA or IRA. The ileoscopy was performed between three to six months after colectomy. The secondary outcome was the rate of conversion to CD after IPAA or IRA.

Results

Sixty patients underwent total colectomy (mean age 41 years, range 22-77; 62% were men); seven patients were lost to follow-up, finally the data from 53 patients were analysed. The majority of these patients (36 - 68%) underwent colectomy for therapy resistent chronically active UC, 9 (17%) patients for acute severe UC, 2 patients had benign colonic stenosis, 5 had high-grade dysplasia or colorectal cancer detected at surveillance colonoscopy and one patient had extensive pseudopolyposis.
All resection specimen were reviewed and no histopathological features of CD were found. Three out of the 53 (6%) ileoscopically assessed patients prior IPAA or IRA were diagnosed with CD in prestomal terminal ileum. During the further follow-up, additional 4 patients developped CD, two after IPAA, one with definitive ileostomy in prestomal ileum and one in neoterminal ileum after IRA.
In total 7 out of 53 patients in this cohort developped CD (13%). Using the two stage approach with ileoscopy between colectomy and restoration of continuity, three out of these seven patients with CD convertion in this cohort were detected prior the decision on the type of second-stage operation.

Conclusion

The conversion from ulcerative colitis to Crohn`s disease occurs in a significant proportion of IBD patients after colectomy. Ileoscopy performed between the two stages of restorative proctolectomy is helpfull in detecting these patients and guiding the decision on the type of surgical intervention to restore continuity.

Disclosure

Nothing to disclose.

Introduction

Autoimmune atrophic gastritis (AAG) leads to significant changes in the gastric mucosa, including hypo-achlorhydria and increased gastrin (G) levels, providing proliferative stimuli on the gastric mucosa (1-5).

Aims & Methods

The aim of our study is to evaluate the occurrence and characteristics of gastric polyps in AAG patients across six tertiary centers in Italy. We conducted a multicentric, cross-sectional study from January to June 2023, prospectively enrolling consecutive patients diagnosed with AAG, from January 2000 to June 2023, who underwent at least one endoscopy. Data on demographics, clinical history, biochemical profiles, serological data, and endoscopic and histopathological findings were collected.

Results

Among 612 AAG patients (73.9% female, median age 66) followed up for a median of 4 (IQR 2-7.5) years, 222 (36.3%) had at least one gastric polyp. Non-endocrine polyps (214) were found in 162 patients, including 151 (70.5%) inflammatory, 29 (13.6%) adenomatous, 18 (8.4%) fundic gland polyps, 13 (6.1%) adenocarcinomas, and one MALT lymphoma. Additionally, 108 patients (48.6% of the population with polyps and 17.6% of the overall AAG patients) presented with gastric neuroendocrine neoplasms (gNENs), 48 of whom also had non-endocrine polyps. The median polyp size was 4 (IQR 2-7) mm. Older age, smoking prevalence, and higher levels of G and chromogranin A (CgA) were associated with polyp presence. No significant differences in OLGA/OLGIM stages or H. pylori status were noted between patients with and without polyps.

Conclusion

This study represents the largest multicentric cohort of AAG patients, highlighting the significant presence of gastric polyps, including gNENs and various non-endocrine types including a not negligible proportion of patients who showed gastric adenocarcinoma. These results emphasize the importance of proactive endoscopic monitoring and comprehensive histopathological evaluation in patients with AAG, to effectively identify and manage these different gastric lesions.

References

1. Zhang H, Jin Z, Cui R, Ding S, Huang Y, Zhou L. Autoimmune metaplastic atrophic gastritis in chinese: a study of 320 patients at a large tertiary medical center. Scand J Gastroenterol. 2017;52(2):150-6.
2. Krasinskas AM, Abraham SC, Metz DC, Furth EE. Oxyntic mucosa pseudopolyps: a presentation of atrophic autoimmune gastritis. Am J Surg Pathol. 2003;27(2):236-41.
3. Kishino M, Nonaka K. Endoscopic Features of Autoimmune Gastritis: Focus on Typical Images and Early Images. J Clin Med. 2022;11(12).
4. Park JY, Cornish TC, Lam-Himlin D, Shi C, Montgomery E. Gastric lesions in patients with autoimmune metaplastic atrophic gastritis (AMAG) in a tertiary care setting. Am J Surg Pathol. 2010;34(11):1591-8.
5. Massironi S, Elvevi A, Gallo C, Laffusa A, Tortorella A, Invernizzi P. Exploring the spectrum of incidental gastric polyps in autoimmune gastritis. Dig Liver Dis. 2023.

Introduction

Inflammatory cells and cytokines play an instrumental role in the pathogenesis and disease course of ulcerative colitis (UC) and are thus accepted therapeutic targets. NX-13 is a first-in-class, orally active, once-daily, gut-selective NLRX1 agonist in development for UC. NLRX1 is a mitochondrial associated protein with a novel, bimodal, immunometabolic mechanism which upregulates mitochondrial metabolism, reduces oxidative stress, and decreases pro-inflammatory cell differentiation and cytokine release broadly in mouse models of IBD¹. NX-13 was well tolerated and showed gut selectivity with low systemic drug exposure in Phase 1 studies reported previously^2,3. We now present data from the phase 1b study describing changes in tissue cytokine levels and related to clinical response.

Aims & Methods

In this double-blind phase 1B trial (NCT04862741)³, 36 patients with active UC (Total Mayo Score 4-10; Mayo endoscopic subscore 2-3) were randomly assigned to NX-13 250mg Immediate Release (IR), 500mg IR, 500mg Delayed Release (DR) or Placebo QD for 4 weeks. Protein levels of IFNγ, IL-10, IL-12(p40), IL-17, IL-4, IL-6, IL-8, MCP1, and TNFα in colonic tissue from NX-13 treated patients collected at screening (baseline) and week 4 of treatment were determined by Human Cytokine/Chemokine Panel – Immunology Multiplex Assay (Millipore Sigma) normalized to total protein concentrations. Patients from all NX-13 dose groups with paired baseline and week 4 samples (n=18) were included in this analysis. Mann-Whitney U testing was used for comparisons between responders (Resp) and non-responders (NR).

Results

Baseline cytokines levels were not different between Resp (change from baseline of at least –3, or –30% in total Mayo Score) and NR. NX-13 treatment resulted in a decrease of multiple proinflammatory cytokines at week 4 compared to baseline in most patients, and especially in Resp. compared to NR at week 4 (Table 1). Primarily, the reduction (% change from baseline) of Th1 cytokines IL-12(p40) and IFNγ was greater in NX-13 treated patients with clinical response compared to NR, resulting in significantly lower values in Resp compared to NR at the end of the 4-week study. Similarly, IL-6 also tended to be lower among Resp. after 4 weeks of treatment with NX-13. Additionally, Th2 cytokine IL-4 values were significantly lower after 4 weeks of NX-13 in patients in clinical response compared to NR. Myeloid cell recruitment may also have been affected by cytokine changes induced by NX-13 as IL-8 and MCP levels were lower in clinical Resp. Reduced myeloid cell recruitment is consistent with higher levels of histologic remission in NX-13 treated patients³.

Conclusion

Broad changes in tissue cytokine expression were specifically observed in patients that responded to NX-13- after 4 weeks of treatment, compared to non-responders. These changes mirror those seen in preclinical mouse colitis models where a broad array of cytokines is reduced¹. The early onset of cytokine shifts associated with clinical response to NX-13 at week 4 is notable and will be assessed in the ongoing phase 2 NEXUS study in patients with moderate to severe UC (NCT05785715).

References

¹Leber, et al. J Immunol 203(12); ²Leber, et al. UEGW J 9(Supp); ³Verstockt, et al. JCC epub 11NOV2023

Disclosure

BS has received grant support from Pfizer (to institution); served as a consultant (served as a representative of Charité) for AbbVie, Arena, BMS, Boehringer, Celgene, Endpoint Health, Falk, Galapagos, Janssen, Landos, Lilly, Pfizer, PredictImmune, and Takeda; and has received speaker’s fees (served as a representative of Charité) from AbbVie, CED Service GmbH, Falk, Ferring, Galapagos, Janssen, Lilly, Pfizer, and Takeda; support for attending meetings/travel from Falk; and served as president of ECCO. | SV has received grants from AbbVie, J&J, Pfizer, Takeda, and Galapagos; consulting and/or speaking fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG, and Zealand Pharma. | AY reports consulting fees from Takeda, Prometheus Labs, Arena Pharmaceuticals, and Bristol Myers Squibb; and speaker bureau fees from Bristol Myers Squibb. | SS has received personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Dr Falk Pharma, Ferring, Fresenius, Galapagos, Genentech, GSK, Gilead, I-MAB Biopharma, Janssen, Lilly, Merck, Novartis-Sandoz, Pfizer, Protagonist, Takeda, and Theravance. | SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB Inc., and Vifor; he reports lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, and Takeda. | RM is an employee of Landos. | FC is an employee of Landos. | BV has received grants from Abbvie, Biora Therapeutics, Landos, Pfizer, Sossei Heptares, and Takeda; Speaker’s fees from Abbvie, Biogen, Bristol Myers Squibb, Celltrion, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, Truvion and Viatris. Consultancy fees from Abbvie, Alimentiv, Applied Strategic, Atheneum, Biora Therapeutics, Bristol Myers Squibb, Galapagos, Guidepoint, Landos, Mylan, Inotrem, Ipsos, Janssen, Progenity, Sandoz, Sosei Heptares, Takeda, Tillots Pharma and Viatris. | MCD reports consulting fees from AbbVie, Arena, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, Gilead, Janssen, Pfizer, Prometheus Labs, and Takeda; and is founder and a shareholder of Trellus Health.

Introduction

Pancreatic duct (PD) stones frequently occur in chronic calcifying pancreatitis (CCP) and are a main factor contributing to pain onset and exacerbation as well as impaired quality of life (QOL). In these patients endoscopic intervention with removal of obstructing pancreatic duct (PD) calculi and regaining pancreatic duct drainage should be performed. In this regard, digital single operator video pancreatoscopy (d-SOVP) is still under investigation for the treatment of PD stones but seems to be an emerging alternative to standard endoscopic procedures with reported success rates between 43%-100%, based on small retrospective studies. However, while reported short term success rates seem very promising, there is still poor evidence for long-term clinical success and benefit for patients` quality of life.

Aims & Methods

Aims: To investigate the role of d-SOVP guided PD-stone lithotripsy in patients with CCP on clinical success and QOL in a long-term follow-up (FU).
Methods: Patients with CCP undergoing d-SOVP (SpyGlass DS) guided lithotripsy of PD stones with initial technical and clinical success were recruited in this retrospective analysis. Persistence of technical success (ductal clearance) and clinical success (defined as pain reduction >50 % in numerical rating scale (NRS)) as well as postinterventional QOL were evaluated by database analysis and a systematic questionnaire (based on SF-12) regarding pain intensity and incidence, painkiller intake and impact on QOL every 6 months obtained in the respective outpatient clinic. Data are presented as mean±SD.

Results

A total of 32 patients was evaluated during long-term FU of 40.8±8.3 months (range 32 – 57 months). 81% of patients (26/32) reported a significant and lasting decrease in pain and symptom burden with mean decrease of NRS from 6.1±0.55 (preinterventionally) to 1.6±0.35 at last reported visit of FU, p<0.01. In 4 patients (12.5%) subsequent pancreatic duct stenting was required due to persistent PD strictures, no recurrent intraductal stones were observed. 3 patients (9.4%) reported persistent pain, with 2 of these being eligible for partial pancreatectomy. QOL criteria significantly improved in 81% of patients defined by major improvements of their general health status and everyday life performance. Two patients were lost to follow-up, 3 patients (9.4%) died during follow up.

Conclusion

D-SOVP guided lithotripsy is safe and effective, achieving high rates of initial technical and clinical success rates as defined by complete ductal clearance and QOL. Beneficial effects on symptom control and QOL persist in the majority of CCP patients after approximately 41 months of FU. Therefore, we suggest d-SOVP to become the intervention of choice in these complex patients. Nevertheless, further prospective trials are warranted to prove these results.

Disclosure

Mark Ellrichmann, Horst Neuhaus, Torsten Beyna and Christian Gerges received lecture from Boston Scientific.