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Panel discussion: Motility disorders - Is endoscopy the cure?

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Panel discussion: Motility disorders - Is endoscopy the cure?

Event

UEG Week Vienna 2024

Topics

Endoscopy Neurogastroenterology & Motility Surgery

Session

Motility disorders: Is endoscopy the cure?

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Dietary advice and brain-gut behaviour therapies for IBS: When and for whom?

Laurie Keefer 1, Sanna Nybacka 2

1 Icahn School of Medicine, New York, United States of America

2 University of Gothenburg, Gothenburg, Sweden

Event

UEG Postgraduate Teaching Programme Vienna 2024

Topics

Education & Training Neurogastroenterology & Motility Small Intestine & Nutrition Primary Care

Session

IBS: Tips and tricks for the busy clinician

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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CHARACTERISING THE DUODENAL IMMUNOLOGICAL ENVIRONMENT AND IMMUNOMODULATORY EFFECTS OF HIGH-DOSE PROTON PUMP INHIBITOR THERAPY IN FUNCTIONAL DYSPEPSIA

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Introduction

The pathophysiology of functional dyspepsia (FD) is still incompletely understood, although duodenal immune activation with increased eosinophil and mast cell numbers have been reported¹. However, advanced characterisation of the duodenal immune infiltrate beyond routine histology is largely lacking. Acid suppression with proton pump inhibitors (PPI) is the first line therapy for FD. A routine PPI course was shown to have additional anti-inflammatory effects in the duodenum², although the underlying mechanisms remain to be studied.

Aims & Methods

We aimed to perform the most extensive characterisation of the duodenal immunological environment in FD so far, and assess the immunomodulatory effects of high-dose PPI therapy. Gastroduodenoscopy with duodenal biopsies was performed in Rome IV FD patients before and after 4 weeks PPI (pantoprazole 40mg bid) and healthy controls (HC). Eosinophils and mast cells were quantified via histology and in fresh single cell suspensions by flow cytometry on an LSR Fortessa flow cytometer (BD). Similarly, T cell subsets were characterised by flow cytometry. Gastrointestinal (GI) symptoms were recorded through questionnaires (PAGI-SYM). Cortisol awakening response (CAR), as well as mast cell tryptase and eosinophil derived neurotoxin (EDN) in duodenal biopsy supernatants were measured using ELISA. Data were analysed with Mann-Whitney U tests and paired t tests, or by linear or mixed models in SAS software.

Results

Data from 30 FD patients (25 F, mean ± SD age 32 ± 13 yr.) before and after PPI, and 30 HC (23 F, 30 ± 10 yr.) at baseline were obtained. GI-specific symptoms were higher in FD vs controls and decreased after PPI, while CAR was reduced after PPI (Table). Duodenal tryptase but not EDN release was higher in FD vs. HC. Mast cell numbers were similar at baseline via histology and flow cytometry, but increased after PPI with an increased side scatter profile (P = 0.06) reflecting less degranulation. Eosinophil numbers were not different, although PPI altered their surface marker expression with decreased IL5Rα (P = 0.02) and CD63 (P = 0.08) but increased CD69 (P = 0.03) expression. Cytotoxic T cell maturation was elevated in FD with higher CD45RA- but lower CD45RA+ CD8+ T cells, driven by higher effector memory CD8+ T cells (P = 0.02) and lower TEMRA CD8+ T cells (P = 0.01). CD45RA- and CD45RA+ CD8+ T cell levels tended to normalise after PPI, while naive Tregs increased after therapy.

Variable (mean ± SD)	HC	FD	FD vs. HC (p-value)	FD + PPI	FD vs. FD + PPI (p-value)
PAGI-SYM score	0.37±0.41	2.42±0.84	<0.0001	1.76±0.96	0.0002
Cortisol awakening response (ng/mL)	3.94±1.73	3.95±2.58	0.33	2.87±1.97	0.05
Duodenal tryptase (µg/g biopsy)	0.38±0.17	0.60±0.32	0.004	0.53±0.31	0.33
Duodenal EDN (µg/g biopsy)	4.69±2.48	4.81±2.88	0.62	5.28±4.32	0.78
Mast cells (% leukocytes)	2.97±1.38	2.49±1.12	0.16	3.02±1.51	0.04
Eosinophils (% leukocytes)	2.69±1.40	2.39±1.14	0.47	2.33±1.54	0.26
CD45RA+ CD8+ T cells (% CD8+ T cells)	21.37±9.28	15.84±11.77	0.009	18.86±12.62	0.08
CD45RA- CD8+ T cells (% CD8+ T cells)	78.62±9.29	84.16±11.76	0.008	81.14±12.63	0.07
Naïve Treg cells (% CD4+ T cells)	1.23±1.62	1.15±1.40	0.92	1.78±1.55	0.04

Conclusion

High-dose proton pump inhibitors improved symptoms in FD and reduced an objective marker of stress. Interestingly, duodenal tryptase release was increased in FD, although not supported by differences in duodenal mast cells or eosinophils, measured via flow cytometric evaluation. Our data suggest that advanced techniques should complement routine histological evaluation in FD to confirm previously reported immune alterations, which may have overestimated the extent of duodenal immune activation in FD. Lastly, subtle alterations in cytotoxic T cell maturation status were normalised after high-dose PPI therapy, which warrants further investigation.

References

¹ Ceulemans et al. Frontiers in Neuroscience 2022
² Wauters et al. Gastroenterology 2021

CHARACTERISING THE DUODENAL IMMUNOLOGICAL ENVIRONMENT AND IMMUNOMODULATORY EFFECTS OF HIGH-DOSE PROTON PUMP INHIBITOR THERAPY IN FUNCTIONAL DYSPEPSIA

Matthias Ceulemans 1, Pauline Huyghe 1, Joran Toth 1, Inge Jacobs 1, Jonathan Cremer 1, Lucas Wauters 1, Jan Tack 1, Tim Vanuytsel 1

1 KU Leuven, Leuven, Belgium

Event

UEG Week Vienna 2024

Topics

Neurogastroenterology & Motility Stomach & H. Pylori Oesophagus

Submission format

Abstract

Session

Dyspepsia and H.pylori

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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EXPLORING DYNAMIC TRIGGERS OF ABDOMINAL PAIN IN IRRITABLE BOWEL SYNDROME USING THE EXPERIENCE SAMPLING METHOD - PRELIMINARY RESULTS FROM THE MULTICENTER DISCOVERIE STUDY

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Introduction

Real-time symptom assessment provides a detailed understanding of the dynamic interplay between gastrointestinal symptoms in irritable bowel syndrome (IBS) and potential triggers, including affect and environmental factors. This study evaluates the association between abdominal pain and potential triggers over time in IBS patients with and without comorbidities, using the Experience Sampling Method (ESM) as a real-time, ecologically valid measurement method.

Aims & Methods

In this prospective, observational multicenter study, as part of the DISCOvERIE project, we included 215 Rome IV IBS patients (80% female; mean age 42.1) from six European countries, categorized into 103 IBS-alone, 67 IBS-mental (anxiety/depression), 16 IBS-somatic (fibromyalgia/chronic fatigue syndrome), and 29 IBS-multicomorbid patient subgroups. Participants scored abdominal pain and affect using an 11-point Numeric Rating Scale and environmental factors using ESM at up to ten random moments each day over seven consecutive days. Linear mixed-effects models analyzed the associations between abdominal pain and these potential triggers, both concurrently and predictively (trigger scores lagged by one time point, maximum of 90 minutes), in each subgroup.

Results

ESM assessment completion rate was 63%. Regarding affect triggers, abdominal pain was significantly correlated with concurrent positive and negative affect in all IBS groups (p<0.02), while significant lagged associations were only found within IBS-mental for positive affect (p=0.02) and within IBS-alone and IBS-multicomorbid for negative affect (p<0.001). Regarding environmental triggers, abdominal pain was significantly associated with concurrent ‘feeling comfortable in situation’ within IBS-alone, IBS-mental and IBS-multicomorbid (p<0.001), concurrent ‘feeling of pleasantness of company’ (p=0.01) and being alone (versus with somebody, p=0.01) within IBS-alone, and eating since the last ESM-assessment within IBS-alone (p=0.04) and IBS-multicomorbid (p=0.002). No significant lagged associations or correlations with location, activity, alcohol consumption, and nicotine use were found.

Conclusion

Our results demonstrate that in IBS patients, real-time abdominal pain is significantly associated with environmental and affect triggers, with both positive and negative affect correlating with abdominal pain irrespective of mental comorbidities. Moreover, fewer triggers predict abdominal pain over time, underscoring the importance of in-the-moment assessments. This study highlights the value of ESM in accurately identifying symptom triggers, thereby enhancing personalized healthcare in IBS.

Disclosure

MB, LV, MH, IM, SM, MRB, and DD declare no conflicts of interests. DJ has received research funding from public-private partnership grants of Top Knowledge Institute (TKI) Agri&Food and Health Holland, by the Carbokinetics program as part of the NWO-CCC Partnership Program, and by Organic A2BV/Mothersfinest BV. DK has received research funding from ZonMw, MLDS, UEG, Rome Foundation, Horizon Europe, Horizon 2020, Grunenthal, Allergan and speaker’s fee from Dr Falk (paid to host institute).

EXPLORING DYNAMIC TRIGGERS OF ABDOMINAL PAIN IN IRRITABLE BOWEL SYNDROME USING THE EXPERIENCE SAMPLING METHOD - PRELIMINARY RESULTS FROM THE MULTICENTER DISCOVERIE STUDY

Michelle Bosman 1, Lisa Vork 1, Maaike Van Den Houte 2, Irina Midenfjord 3, Silvia Muñoz 4, Maria Raffaella Barbaro 5, Dan Lucian Dumitrascu 6, Daisy Mae Jonkers 1, Daniel Keszthelyi 1

1 Department of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands

2 Laboratory for Brain-Gut Axis Studies, Translational Research in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases & Metabolism, KU Leuven, Leuven, Belgium

3 Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

4 Psychiatry, Mental Health and Addictions Research Group, Vall d’Hebron Institute of Research (VHIR), Barcelona, Spain

5 IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, Bologna, Italy

6 Second Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania

Event

UEG Week Vienna 2024

Topics

Neurogastroenterology & Motility Primary Care Colorectal

Submission format

Abstract

Session

IBS: Emerging evidence for treatment

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Poster

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Clinical Case Summary

Introduction: Gastric siderosis (GS) refers to the abnormal deposition of iron within the gastric mucosa, a condition that can be associated with various underlying pathologies. Our case depicts a case of gastric siderosis with iron deposition in the stomach in association with excessive oral iron intake, presenting unusually with chronic diarrhea. Such association has been mentioned previously in the literature but not established.
Case: A 70-year-old lady with a history of iron deficiency anemia and chronic kidney disease presented with 3 weeks of progressively worsening diarrhea. Home medicines included iron pills. She denied any blood in stool, abdominal pain, recent travel, or antibiotic use. Her vitals and her abdominal exam were unremarkable. Stool studies, including stool parasite, C. difficile toxin, calprotectin, and bacterial PCR, were negative.
Colonoscopy showed a normal macroscopic appearance with random biopsies negative for microscopic colitis. An upper endoscopy was performed demonstrating normal esophagus but pitted brown spots mucosa in the gastric body, and antrum. Biopsies were taken, with antral ones demonstrating antral mucosa with iron deposition in the glands and lamina propria concerning gastric siderosis. Oral iron was discontinued and the patient endorsed improvement in symptoms upon outpatient follow-up with endoscopic resolution at 6 months.
Discussion: Iron deposition in gastric mucosa induces a highly oxidative state, producing injury. However, siderosis due to oral iron use is less commonly associated with mucosal injury, with cases seen with changes ranging from erythema to mucosal erosions. Our patient had pattern B on biopsy involving stroma, whereas A involves macrophages in gastric inflammation, and C involves glands in hemochromatosis. No association with the duration or amount of exposure is associated with differences in symptoms. Non-bloody diarrhea occurs without active ulceration being reported, making our patient unique.

References

1. Marginean EC, Bennick M, et al. Gastric siderosis: patterns and significance. Am J Surg Pathol. 2006 Apr;30(4):514-20. doi: 10.1097/00000478-200604000-00013. PMID: 16625099.
2. Abraham SC, Yardley JH, Wu TT. Erosive injury to the upper gastrointestinal tract in patients receiving iron medication: an underrecognized entity. Am J Surg Pathol. 1999 Oct;23(10):1241-7. doi: 10.1097/00000478-199910000-00009. PMID: 10524525.
3. Siah CW, Ombiga et al. Normal iron metabolism and the pathophysiology of iron overload disorders. Clin Biochem Rev. 2006 Feb;27(1):5-16. PMID: 16886043; PMCID: PMC1390789.
4. Idoate Gastearena MA, et al. A comparative study on the gastroduodenal tolerance of different antianaemic preparations. Hum Exp Toxicol. 2003 Mar;22(3):137-41. doi: 10.1191/0960327103ht330oa. PMID: 12723894.
5. Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J. 2011 Mar 15;434(3):365-81. doi: 10.1042/BJ20101825. PMID: 21348856; PMCID: PMC3048577.
6. Hattori H. High prevalence of haemosiderin accumulation in the cytoplasm of gastric glands in patients with liver cirrhosis. J Clin Pathol. 2004 Jun;57(6):621-4. doi: 10.1136/jcp.2003.010405. PMID: 15166268; PMCID: PMC1770335.
7. De Petris G, Gatius Caldero S, et al. Histopathological changes in the gastrointestinal tract due to drugs: an update for the surgical pathologist (part I of II). Int J Surg Pathol. 2014 Apr;22(2):120-8. doi: 10.1177/1066896913502229. Epub 2013 Sep 10. PMID: 24021899.

GASTRIC SIDEROSIS IN THE SETTING OF ORAL IRON INTAKE

Bipneet Singh 1, Mohammad Zarrar Khan 2, Palak Patel Rodrigues 3, Palak Grover 1, Gurleen Kaur 4

1 Henry Ford Allegiance, Jackson, United States

2 Henry Ford Detroit, Detroit, United States

3 Henry Ford, Detroit, United States

4 Government Medical College, Amritsar, India

Conference

UEG Week Berlin 2025

Topics

Oesophagus

Submission format

Clinical Case

Session

CLINICAL CASES (Posters)

Published

2025

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Clinical Case Summary

We present the case of a 50-year-old man with six months of persistent, non-bloody watery diarrhea (8–10 episodes/day), unresponsive to antibiotics and probiotics. His past medical history was unremarkable, he took no home medications, and denied raw meat or fish consumption. Notably, he had recently started working in an animal feed production facility one month before symptom onset. Initial labs showed mild leukocytosis (10.04 x 10³/µL; ULN: 8.77) and mildly elevated CRP (7.5 mg/L; ULN: 3.4). Extensive infectious workup, including CMV serology, Quantiferon, stool cultures for Salmonella, and tests for fungi and parasites (e.g., Giardia), fecal elastase, rectal swabs for Klebsiella pneumoniae carbapenemase and Clostridium difficile returned negative. Colonoscopy and upper GI endoscopy were normal, and biopsies from all intestinal segments showed no pathological findings. He was discharged with partial improvement (3–4 bowel movements/day) and normalized CRP, but was readmitted a week later for worsening symptoms. Repeat blood work, thyroid function, serum calcitonin and inflammatory markers were within normal limits. Intestinal ultrasound showed a tubular descending colon suggestive of nonspecific left-sided colitis; other bowel segments were normal. Stool tests remained negative.Urine toxicology was positive for cannabinoids. Upon further questioning, the patient admitted to regular use over the past eight months, including during both hospitalisations (CUDIT-R score = 12). After cessation of cannabinoid use, diarrhea resolved completely. At 3-month follow-up, he was asymptomatic, with normal bowel habits and labs. He reported only sporadic cannabinoid use at present (CUDIT-R score 7). This case illustrates the potential for chronic cannabinoid use to induce persistent diarrhea mimicking infectious or inflammatory disease. Screening for substance use should be considered in chronic unexplained diarrhea.

CHRONIC DIARRHEA LINKED TO CANNABINOID USE: A CASE REPORT

Francesco Savino 1, Emanuela Stano 1, Antonella Contaldo 1, Mariabeatrice Rita Daniela Principi 1

1 Università degli Studi di Bari "Aldo Moro", Bari, Italy

Conference

UEG Week Berlin 2025

Topics

Colorectal

Submission format

Clinical Case

Session

CLINICAL CASES (Posters)

Published

2025

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INCREASED DISEASE BURDEN IN IRRITABLE BOWEL SYNDROME WITH COMORBIDITIES

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Introduction

Irritable bowel syndrome patients frequently suffer from comorbid mental (anxiety or depression) or somatic (fibromyalgia or chronic fatigue) conditions. In this pan-European project (the DISCOvERIE project), IBS patients with and without comorbidities were compared with disease controls and healthy controls, to further elucidate the effect of comorbid conditions in IBS on the disease burden.

Aims & Methods

We included participants from nine different European centers – IBS patients according to Rome IV criteria, disease controls (patients with comorbid conditions; i.e. fulfilling diagnostic criteria for anxiety, depression, fibromyalgia and/or chronic fatigue, but no IBS) and healthy controls. The participants were further divided into eight groups based on presence or absence of comorbitidies: IBS with no/ mental/ somatic/ mental and somatic comorbidity, disease controls with mental/ somatic/ mental and somatic comorbidity, and healthy controls. The severity of IBS symptoms (IBS-SSS), depression (PHQ-9), anxiety (GAD-7), somatic symptoms (PHQ-15), fibromyalgia symptoms (FIQ) and general and mental fatigue (MFI) were compared between these groups.

Results

In total, 849 participants (median age 44 years) were included. A majority were females (76%), with the most pronounced female predominance (83%-86%) in the IBS groups with comorbidities. The most severe IBS symptoms were noted among IBS with both mental and somatic comorbidity and IBS with somatic comorbidity (Table 1). In IBS, the severity of IBS symptoms increased gradually with increasing number of comorbidities (partial eta squared: 0.053, p<0.001), as did severity of anxiety, depression, somatic symptoms and general fatigue (partial eta squared: 0.214, 0.247, 0.240, 0.239, respectively, all p<0.001). The groups with both mental and somatic comorbidity had the highest levels of anxiety, depression and mental fatigue. Somatic symptoms and general fatigue were most severe among IBS and disease controls with somatic comorbidity or both somatic and mental comorbidity. Fibromyalgia symptoms were most severe in IBS and disease controls with somatic comorbidity.

Table 1: Symptom severity of the study groups.

	IBS alone (N=268)	IBS comorbid mental (N=173)	IBS comorbid somatic (N=48)	IBS multicomorbid (N=124)	Disease control mental (N=58)	Disease control somatic (N=51)	Disease control mental + somatic (N=52)	Healthy controls (N=75)	P-value between all groups	p-value between IBS groups
IBS-SSS	226 [170-298]	259 [184-320]	296 [200-358]	300 [239-375]	100 [59-160]	119 [80-188]	114 [82-213]	4 [0-33]	<0.001	<0.001
PHQ-9	4 [1-7]	8 [4-13]	8 [6-10]	12 [8-18]	11 [6-16]	9 [5-11]	12 [8-17]	1 [0-3]	<0.001	<0.001
GAD-7	3 [1-7]	7 [4-11]	4 [2-8]	11 [7-15]	8 [6-9]	6 [3-10]	12 [7-14]	1 [0-3]	<0.001	<0.001
PHQ-15	10 [7-13]	12 [9-15]	16 [13-19]	17 [14-23]	11 [7-14]	15 [11-17]	16 [12-20]	3 [1-4]	<0.001	<0.001
FIQ	23 [9-44]	20 [7-38]	39 [14-56]	24 [10-48]	38 [23-47]	48 [28-67]	41 [20-57]	22 [7-48]	<0.001	0.004
MFI general fatigue	11 [7-15]	15 [11-17]	18 [15-19]	18 [16-20]	14 [12-17]	17 [16-19]	18 [15-20]	8 [6-10]	<0.001	<0.001
MFI mental fatigue	9 [6-12]	13 [9-16]	13 [10-18]	16 [13-18]	13 [10-16]	13 [10-16]	15 [13-17]	8 [5-11]	<0.001	<0.001

Numbers presented as medians with interquartile range. Groups compared through Kruskal-Wallis tests with Holm’s correction.

Conclusion

This large European multicenter study strengthens the importance of the impact of mental and somatic comorbid conditions and symptoms in IBS, and their influence on outcomes and disease burden.

Disclosure

Hans Törnblom: Consultant or advisory board member for Allergan, Cinclus Pharma, Medifactia, and VIPUN and as a speaker for Tillotts, Takeda, and Shire.

Daisy Jonkers: Part of the work of DJ, outside the submitted work has been financed by public-private partnership grants of Top Knowledge Institute (TKI) Agri&Food and Health Holland, by the Carbokinetics program as part of the NWO-CCC Partnership Program, by Organic A2BV/Mothersfinest BV.

INCREASED DISEASE BURDEN IN IRRITABLE BOWEL SYNDROME WITH COMORBIDITIES

Irina Midenfjord 1, Elias Sundelin 1, Inês A. Trindade 1, Mahrukh Khadija 1, Hans Törnblom 1, Javier Santos 2, Danique Mulder 3, Alejandro Arias-Vasquez 3, Georgy Ruesing 4, Andreas Reif 4, Mareike Aichholzer 4, Maaike Van Den Houte 5, Lukas Van Oudenhove 5, Maria Chiara Matteucci 6, Giovanni Barbara 6, Michelle Bosman 7, Daisy Mae Jonkers 7, Josep Antoni Ramos-Quiroga 2, Éva Jekkel 8, István Bitter 8, Andrei Pop 9, Dan Lucian Dumitrascu 9, Carmen Alonso-Cotoner 2, Amanda Rodriguez 2, Magnus Simrén 1

1 University of Gothenburg, Gothenburg, Sweden

2 Vall d'Hebron Hospital Universitari, Barcelona, Spain

3 Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands

4 Johann Wolfgang Goethe- Universitat Frankfurt Am Main, Frankfurt, Germany

5 Katholieke Universiteit Leuven, Leuven, Belgium

6 University of Bologna and IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy

7 Maastricht University Medical Center, Maastricht, Netherlands

8 Semmelweis University, Budapest, Hungary

9 'Iuliu Hatieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania

Event

UEG Week Vienna 2024

Topics

Neurogastroenterology & Motility Primary Care Colorectal

Submission format

Abstract

Session

IBS: Emerging evidence for treatment

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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