Introduction

Endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) is emerging as a new and minimally invasive endoscopic treatment method for gastric outlet obstruction (GOO). In EUS-GE, it is important that stents can be safely and reliably deployed and that there is no stent migration. As the optimal method, we have developed the EUS-guided balloon-occluded gastrojejunostomy bypass (EPASS) and have performed it as a clinical study.

Aims & Methods

We retrospectively evaluated the results of EPASS including long-term outcomes. The EPASS procedure was performed under conscious sedation. The endoscope was used to reach the site of obstruction. The stricture was cannulated with a 0.025-inch guidewire and the guidewire was used to negotiate beyond the site of obstruction under endoscopic and fluoroscopic guidance. The double balloon tube was then inserted on the guidewire beyond the duodenal–jejunal flexure using an overtube. The two balloons of the occluder were inflated with 30–40 mL normal saline and constrast. 200–300 mL of methyleneblue-stained saline was then injected to distend the occluded segment of duodenum. A linear echoendoscope was then inserted into the stomach. A site in the posterior wall of the body of the stomach was punctured directly by the delivery system of the lumen apposing metal stent. A 20 x 10 or 15 x 10 mm stent was used. The distal flange of the stent was deployed under EUS guidance, followed by deployment of the proximal flange under endoscopic or EUS guidance. Stent position was confirmed with the drainage of methylene-blue-stained saline, the endoscopic view of the proximal flange and also the fluoroscopic image. Thirty-six consecutive patients with symptomatic GOO who were not refractory to surgical gastrojejunostomy were enrolled in the study. The primary endpoint was technical success rate. Secondary endpoints included procedure time, GOO scoring system (GOOSS) scores at 7 days and 1 month after EPASS, clinical success rate (improvement in GOOSS scores at 7 days after EPASS), procedure-related adverse events (AEs) rate, overall survival (OS) after EPASS in the 23 patients with long-term follow-up, and stent patency rate.

Results

The mean age was 70.6 years (range 47-91), 16 (44%) were female, and the underlying diseases were 18 pancreatic cancer, 9 gastric cancer, 3 duodenal cancer, 4 gallbladder cancer, 1 breast cancer, and 1 chondrosarcoma. The technical success rate was 94.4% (34/36), mean procedure time was 26.9 minutes (range 14-40), mean time to double-balloon tube insertion was 9.8 minutes (range 6-28), mean pre-GOOSS score was 0.42, mean GOOSS score was 2.08 and 2.21 at 7 days and 1 month after EPASS, and the clinical success rate was 88.9% (32/36). The incidence of procedure-related AE was 16.7% (6/36), including 2 cases of fever, 2 cases of abdominal pain, and 2 cases of worsening ascites. The mean overall survival after EPASS was 183.8 days, all patients died of primary disease, and there were no events such as stent occlusion or stent deviation (stent patency was 100%).

Conclusion

EPASS is a safe and reliable EUS-GE method and may be a useful treatment for symptomatic malignant GOO.

References

(1) Tsuchiya T, et al. Tech Innov Gastrointest Endosc. 2020;22:27-32.
(2) Itoi T, et al. J Hepatobiliary Pancreat Sci. 2020;27:791-792.
(3) Itoi T, et al. Gut 2016;65:193-5

Disclosure

Lecture fee : Boston Scientific Japan, Olympus Japan

Introduction

Celiac disease, a chronic autoimmune enteropathy caused by exposure to gluten in genetically predisposed individuals, is characterized by a broad clinical spectrum often with multisystem involvement. Symptoms related to the reproductive system include delayed menarche, early menopause, fertility disorders, miscarriages, and prematurity.

Aims & Methods

To study the impact of celiac disease on fertility in a female Greek population. A retrospective review of all patient records from the celiac disease outpatient clinic at our hospital.

Results

Medical histories of 231 female patients were reviewed (69% of the total patient population) with a mean age of 44.3 years and a mean age at diagnosis of 35.3 years. The mean age of menarche was 12.7 years. Menstrual irregularities were reported in 27% (20% instability, 7% dysmenorrhea). A total of 28% (65/231) were in menopause, with an average age of menopause onset at 50.7 years. A history of miscarriages was recorded in 15% of all women (35/231), but in 29% of women in menopause (19/65). 82% (53/65) of women in menopause had children, with 98% (52/53) having been pregnant before the diagnosis of the disease. Among all women who gave birth, only 12/113 (11%) had been diagnosed before pregnancy. 56% (63/113) and 44% (50/113) had a vaginal delivery and cesarean section, respectively. Pregnancy complications were recorded in 24 women (18 preterm births, 15 low birth weight infants, 1 intrauterine death).

Conclusion

Women with celiac disease tend to have relatively late menarche and an increased rate of miscarriages. However, the disease does not seem to significantly affect fertility.

References

1.Ehud Galron MD, Rayna Boyarsky MD,Ido Sold MD, Chen Ben David MD,and Eyal Gal MD,Interactions between celiac disease and pregnancy:A literature review, Isr Med Assoc J.2023 Dec;25(12):830-835
2.Giovanni Casella et. Al. Celiac disease and obstetrical-gynecological contribution, Gastroenterol Hepatol Bed Bench. 2016 Autumn; 9(4): 241–249.
3.Stephanie M. Moleski et. Al., Increased rates of pregnancy complications in women with celiac disease, Annals of Gastroenterology (2015) 28, 236-240
4.Nafeesa N. Dhalwani et Al., Women With Celiac Disease Present With Fertility ProblemsNo More Often Than Women in the General Population, Gastroenterology 2014;147:1267–1274

Introduction

Irritable bowel syndrome (IBS) imposes a substantial burden on patients and healthcare systems globally, with diverse gut symptoms. Its pathophysiology involves disorders in gut-brain interaction and gut barrier dysfunction related to diet and stress. Confocal laser endomicroscopy (CLE) can detect barrier dysfunctions in vivo. Multimodal integrative mind-body medicine-based (MBM) therapy, including stress management, exercise, relaxation, and nutrition, may enhance gut barrier function, symptoms and patient well-being.

Aims & Methods

This study aims to screen IBS patients for prevalent and food-induced gut barrier dysfunction via CLE and explore the impact of a multimodal integrative therapy on barrier integrity, IBS-symptom severity, -quality of life and psychological well-being.
Methods: IBS patients (N=119) admitted between 1 February 2021 and 1 July 2023 at a Clinic for Internal and Integrative Medicine for a two-week inpatient stay underwent esophagogastroduodenoscopy with confocal laser endomicroscopy (CLE) and local food challenge (standardized protocol for egg white, soy, milk, yeast or wheat) to test for a primary prevalent (1°CLE+) or secondary food-induced (2°CLE+) duodenal barrier dysfunction – after exclusion of IgE-mediated food allergy and coeliac disease. All IBS patients received a multimodal MBM therapy. Patients with barrier dysfunction were recommended to adhere to an adjuvant preclinically-tested barrier-stabilising therapy with myrrh, chamomile and coffee charcoal (MYRRHINIL INTEST® 3x4 dragées/ day), and exclusion of CLE-identified barrier-disrupting foods until a voluntary follow-up CLE (2^nd CLE). Pre (=1^st CLE) and Post (=2^nd CLE) intervention, IBS-symptom severity (IBS-SSS), IBS-quality of life (IBS-QoL) and psychological well-being via clinically validated questionnaires were additionally assessed.

Results

Of the 119 IBS patients included in the study, 62% (n=74) showed duodenal barrier dysfunction [1°CLE+: n=27 (23%); 2°CLE+: n=47 (39%)]. Of those, N=35 IBS patients (47%) with barrier dysfunction at 1^st CLE returned for a voluntary 2^nd CLE after 6.3 ± 3.0 months [at 1^st CLE: 1°CLE+: n=15 (43%), 2°CLE+: n=20 (57%); n=25 (71%) female; age 42.9 ± 15.4 yrs, diagnosis age 32.1 ± 15.0 yrs; disease duration 11.1 ± 11.2 yrs]. Of returned IBS patients, n=25 (71%) showed an improved gut barrier integrity, of whom 16 (46%) achieved complete stabilisation of the gut barrier (CLE-).
Pre-intervention, IBS patients were clinically characterized by severe IBS symptom severity (IBS-SSS 304.8 ± 83.4), severely impaired IBS-related quality of life (IBS-QoL 42.7 ± 16.6) and concomitant severe level of anxiety and depression (HADS 19.2 ± 7.7), fatigue (MFI-20 66.8 ± 13.1) and perceived stress (PSS-10 31.3 ± 7.7). Post-intervention, patients exhibited significant and clinically relevant (MCID) improvement in all of these clinical outcomes (IBS-SSS p=<.001, IBS-QoL p=<.001, HADS p=<.001, MFI-20 p=<.001, PSS-10 p=0.004), even allowing the severity score level to be reduced from severe to moderate. Patients reported particular improvement in abdominal pain, change in stool frequency and consistency, abdominal cramps and nausea assessed via 5-point Likert scale.

Conclusion

IBS patients have a high prevalence of existing and food-induced duodenal barrier dysfunction (62%). A multimodal integrative therapy showed a stabilisation of the gut barrier in 71% of IBS patients in a 2^nd CLE as well as significant and clinically relevant improvement in IBS-related symptom severity, quality of life and psychological well-being.

References

1) Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology. 2021;160(1):99-114.e3. doi:10.1053/j.gastro.2020.04.014
2) Martin CR, Osadchiy V, Kalani A, Mayer EA. The Brain-Gut-Microbiome Axis. Cell Mol Gastroenterol Hepatol. 2018 Apr 12;6(2):133-148. doi: 10.1016/j.jcmgh.2018.04.003.
4) Hanning N, Edwinson AL, Ceuleers H, Peters SA, De Man JG, Hassett LC, De Winter BY, Grover M. Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review. Therap Adv Gastroenterol. 2021 Feb 24;14:1756284821993586. doi: 10.1177/1756284821993586.
5) Fritscher-Ravens A, Pflaum T, Mösinger M, Ruchay Z, Röcken C, Milla PJ, Das M, Böttner M, Wedel T, Schuppan D. Many Patients With Irritable Bowel Syndrome Have Atypical Food Allergies Not Associated With Immunoglobulin E. Gastroenterology. 2019 Jul;157(1):109-118.e5. doi: 10.1053/j.gastro.2019.03.046. Epub 2019 May 15.
6) Fritscher-Ravens A, Schuppan D, Ellrichmann M, Schoch S, Röcken C, Brasch J, Bethge J, Böttner M, Klose J, Milla PJ. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2014 Nov;147(5):1012-20.e4. doi: 10.1053/j.gastro.2014.07.046. Epub 2014 Jul 30.
7) Rosenthal R. et al. Myrrh exerts barrier-stabilising and –protective effects in HT-29/B6 and Caco-2 intestinal epithelial cells. Int J Colorectal Dis (2016)

Disclosure

Jost Langhorst
Fees and lecturing: Falk Foundation; Repha GmbH biological medicines; Dr. Willmar Schwabe; Medice Arzneimittel, Galapagos Pharma, Takeda Pharmaceutical, Janssen Cilag, Dr. Pfleger Arzneimittel
Research funding: Steigerwald Arzneimittelwerke GmbH, Falk Foundation, TechLab, Inc., Dr. Willmar Schwabe, Repha GmbH biological medicines,
Other financial or non-financial benefits: none
Consulting and expert activities: Medical Publishers Stuttgart; Steigerwald Arzneimittelwerke GmbH; Repha GmbH; Ferring Arzneimittel GmbH; Dr. Willmar Schwabe
Corporate investments: none
Other conflicts of interest: None

Miriam Bittel
Fees and lecturing: Falk Foundation; Weber & Weber GmbH
Research funding: Deutsche Morbus Crohn/Colitis ulcerosa Vereinigung (DCCV)
Other financial or non-financial benefits: none
Consulting and expert activities: Weber & Weber GmbH
Corporate investments: none
Other conflicts of interest: None

The other co-authors: no conflicts of interest

Introduction

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals, characterized by small intestinal inflammation and villous atrophy. Microbial agents such as Helicobacter pylori (H. pylori) may influence autoimmune disorders, including CD, through immune modulation. However, the relationship remains controversial.This study aimed to assess the association between CD and H. pylori infection by comparing the prevalence of H. pylori in patients with and without CD.

Aims & Methods

We conducted a retrospective study from January 2019 to December 2024. Two groups were analyzed: patients with biopsy-confirmed CD and controls without CD who underwent upper endoscopy for dyspeptic or non-specific gastrointestinal symptoms. Exclusion criteria included prior H. pylori eradication, recent use of PPIs, antibiotics, or bismuth compounds, other autoimmune disorders, and incomplete data.

Results

A total of 231 patients were included: 103 with CD (19.4% male, mean age 28.8 ± 12.6 years) and 128 controls (28.1% male, mean age 33.9 ± 11.9 years).
No significant differences were observed in age (p = 0.73) or sex distribution (p = 0.167) between groups.
H. pylori was detected in 67% of CD patients and 50% of controls, with a significantly higher prevalence in the CD group (p = 0.014).

Conclusion

Contrary to some previous reports suggesting a protective effect, this study found a significantly higher prevalence of H. pylori in patients with CD compared to controls.
These findings highlight the need for further investigations into the potential impact of H. pylori on the clinical presentation and management of celiac disease.

Introduction

Current evidence suggests that joint complaints without any underlying rheumatic condition are common in patients with celiac disease. This important clinical aspect of non-rheumatic joint complaints has not systematically been investigated and the prevalence of joint complaints is not known.

Aims & Methods

The aim of this study was to estimate the prevalence of joint complaints in patients with celiac disease through a systematic review and meta-analysis of existing literature. We searched Medline, Embase, Cochrane, and Web of Science databases for studies reporting joint complaints in patients with celiac disease between January 1, 1990 and November 26, 2024. Search results were screened by two independent reviewers. The quality of included studies was appraised and meta-regression analysis performed. A study protocol was pre-registered in the PROSPERO database and results were reported according to the PRISMA guidelines.

Results

A total of 7,414 publications were identified in the search. Of these, 226 were reviewed in full-text and 27 included in the meta-analysis. Among 6,901 patients with celiac disease, 530 had joint complaints, yielding a weighted pooled prevalence of 10.7% (95 % CI 6.9-15.1). Stratified by adults (n=17 studies) vs. children (n=13 studies), the pooled prevalence was 16.8% (95% CI 9.0-26.3) in adults compared with 6.4% (95% CI 3.4-10.1) in children. In comparison by region, studies in South and North America (n=5) showed the highest weighted pooled estimate (12.9%; 95% CI 8.7-17.8). Europe (n=15) had the second highest (12.4%; 95% CI 6.8-19.4, and Asia (n=3) the lowest prevalence (5.2%; 95% CI 0.0-18.3). In meta-regression analysis, no association between the prevalence of joint complaints and study characteristics or demographics was found.

Conclusion

One in 10 patients with celiac disease suffers from joint complaints that are not directly associated with any specific rheumatic comorbidity. This indicates that joint complaints are extraintestinal manifestations in patients with celiac disease, occurring more frequently than commonly thought. Increased awareness of joint complaints is warranted to improve the clinical care of patients with celiac disease.

Disclosure

Drs. Poddighe, Galiyeva, Zhubanova and Mussina declare no conflicts of interest. Dr. Forss has served as a speaker and an advisory board member for Janssen Cilag AB and Tillotts Pharma.

Introduction

Barrett’s esophagus (BE), the major precursor of esophageal adenocarcinoma (EAC), is a condition where the normal stratified squamous esophageal epithelium undergoes transdifferentiation into the specialized, intestinal-like epithelium. This reprogramming, also termed ‘paligenosis’, is predominantly caused by gastroesophageal reflux disease (GERD)¹. On the other hand, hydrogen sulfide (H₂S) next to carbon monixide (CO) is an important endogenous gaseous mediator. H₂S is biosynthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH). Both, H₂S and CO have been shown to maintain gastrointestinal (GI) integrity^2,3,4. However, the contribution of gaseous mediators signaling to esophageal transdifferentiation process is overlooked.

Aims & Methods

Thus, in this study we aimed to explore the role of H₂S bioavailability in mTOR-dependent paligenosis induced by chronic epithelial injury. Furthermore, we evaluated the relationship between GERD, the barrier function of cultured cells, and the pattern of selected components involved in the formation of the tight junctions (TJs) and responsible for epithelial barrier integrity.
We implemented an animal model of GERD, based on Male Wistar rats with esophagogastroduodenal anastomosis (EGDA) treated i.g. for 8 weeks with vehicle or with H₂S- releasing chemicals: GYY4137 (5.0 mg/kg)/NaHS (1.0 mg/kg) or CTH/CBS inhibitors: PAG (15 mg/kg)/AOAA (11 mg/kg). In parallel, we employed optimized in-vitro GERD model based on human-derived esophageal epithelial (EPC2) cells +/- CRISPR-Cas9-induced knockout of H₂S-producing enzymes that were treated with acidified bile mixture (BM) or with GYY4137/NaHS (100 µM). We evaluated activation of AKT/mTOR pathway by multiplex microbeads fluorescent assay and an expression of TJ-associated protein (ZO-1) and occludin by capillary immunoblotting. The barrier function of cultured cells was evaluated by measurement of transepithelial electrical resistance (TER).

Results

We observed that either chronic reflux in EGDA-rats and/or treatment of human esophageal cells with BM led to a slight or a significant activation of AKT/mTOR signaling pathway and its down-stream effector - p70S6K. Additionally, we observed that pharmacologically-derived H₂S reversed this effect, while inhibition of endogenous H₂S biosynthesis (pharmacological or induced by knockout of H₂S-producing enzymes) had either no effect or increased GERD-induced phosphorylation of AKT/mTOR pathway components. Moreover, we showed that ZO-1 is highly expressed in BM treated EPC2 cells and this was reflected by the increase in TER measurment. Level of occludin remained unchanged. We did not observe any changes in expression of ZO-1 and occludin after GYY4137 treatment; however, TER measurment decreased in comparison to BM treated cells. Selective knockout of H₂S-producing enzymes led to a decrease in ZO-1 protein content in comparison to wild-type cells.

Conclusion

We conclude that interventional enhancing or decreasing of H₂S bioavailability in esophageal epithelium respectively delay or accelerate the GERD-induced paligenosis process via regulation of the mTOR pathway. H₂S-prodrugs may provide a protective effect on the esophageal epithelium by substituting the phisiological defensive response of the tissue against GERD, which is reflected by an increase in the expression of ZO-1 and tightening of the cellular barrier.

References

1. Souza RF, Spechler SJ. Mechanisms and pathophysiology of Barrett oesophagus. Nat Rev Gastroenterol Hepatol 2022.
2. Fiorucci S, Distrutti E, Cirino G, Wallace JL. The emerging roles of hydrogen sulfide in the gastrointestinal tract and liver. Gastroenterology 2006.
3. Magierowska K, Korbut E, Wójcik-Grzybek D, Bakalarz D, Sliwowski Z, Cieszkowski J, Szetela M, Torregrossa R, Whiteman M, Magierowski M. Mitochondria-targeted hydrogen sulfide donors versus acute oxidative gastric mucosal injury. J Control Release 2022.
4. Magierowska K, Brzozowski T , Magierowski M. Emerging role of carbon monoxide in regulation of cellular pathways and in the maintenance of gastric mucosal integrity. Pharmacol Res 2018.

[Funding: National Science Centre, Poland (UMO-2016/23/D/NZ4/01913, UMO-2019/33/B/NZ4/00616) and Statutory Grant (N41/DBS/000874), Jagiellonian University Medical College].

Introduction

IBS patients are often high healthcare utilizers. Symptom frequency, as well as psychological factors like neuroticism, anxiety, and depression, impact healthcare seeking. Bothersomeness, i.e., how distressing or disruptive symptoms are to a person’s daily life, is a potential treatment-seeking motivator in IBS. We aimed to evaluate symptom bothersomeness in IBS and its potential influence on healthcare utilization.

Aims & Methods

Adults in 9 countries (Canada, China, Germany, Japan, Mexico, Poland, Romania, Spain, United States) completed an online survey that included IBS Rome IV Diagnostic Questions, lifetime healthcare utilization (HCU) for IBS (Yes/No); depression and anxiety; negative emotionality/neuroticism (NE), or a person’s tendency to experience anxiety, anger, frustration, pessimism, or depressed mood; demographic questions and the question “Is the [symptom] bothersome to you?” (yes/no) for each: abdominal pain, hard/lumpy stools, and soft/mushy stools. Three separate binary logistic regression models assessed the symptom's frequency, depression, anxiety, NE, sex, and age as predictors of bothersomeness for each of the key IBS symptoms. Three additional regression models evaluated each symptom's bothersomeness and frequency, depression, anxiety, NE, sex, and age as predictors of HCU.

Results

Of 17,663 participants, 1,389 (7.9%) met Rome IV criteria for IBS (mean age 41.6 (SD 14.7) years, 62.3% female; IBS sub-types: 32% C, 29% D, 36% M, 4% U). Of those with IBS, 65.7% had ever visited a doctor because of bowel problems. Abdominal pain was rated bothersome by 93% of people with IBS, hard stools by 80%, and mushy/watery stools by 78%, with no sex differences. Older people (ages 65+) reported only hard stools as more bothersome (t(1236) = -3.40, 95%CI: -5.54 to -1.49, p<.001) than people of ages 18-39 or 40-64. Bothersomeness (yes/no) was predicted in regression analyses by higher frequencies of abdominal pain [Odds Ratio (OR) and 95% CI: 2.00 (1.46-2.74)], hard stools [1.33 (1.24-1.43)], and mushy stools [(1.24 (1.16-1.31)], but not by age, sex, or psychological variables. People with IBS were significantly more likely (χ²) to have ever visited a doctor for bowel problems if they rated their pain (p = .003), hard stools (p = .020), and mushy stools (p < .001), as bothersome. Finding pain and mushy stools bothersome (yes/no) increased the odds of HCU for pain and mushy stools, but not for hard stools in the regression models (Table 1). Higher frequency of pain and hard stools (but not mushy stools) also increased HCU odds, and older people were more likely to consult for all 3 symptoms. Psychological variables and sex were not significant predictors of HCU.

Table 1. Binary regression analyses for predicting IBS lifetime doctor consulting for bowel symptoms

Conclusion

For persons with IBS, subjective experience of how bothersome symptoms are is strongly associated with symptom reporting and a driving factor to HCU regardless of gender, psychological distress, or negative emotionality. Providers need to assess symptom bothersomeness in their clinical decision-making.