Introduction

In patients with disorders of the gut-brain interaction abdominal bloating is a visceral sensation (sensation of pressure/fullness), whereas visible abdominal distension is a somatic manifestation with abnormal postural tone (abdominophrenic dyssynergia, i.e., diaphragmatic push and abdominal wall relaxation). Abdominophrenic dyssynergia can be corrected by a simple non-instrumental technique, and our aim was to determine the relation of distension and bloating responses over time.

Aims & Methods

In a randomized, placebo-controlled, parallel trial (ClincalTrials.gov number NCT06150638) 40 consecutive patients (34 women, 6 men; age range 18–58 years) with disorders of gut-brain interaction complaining of visible abdominal distension were randomized to receive biofeedback or placebo. Patients in the biofeedback group were explained the mechanism of distension, and were taught to relax the diaphragm and contract the abdominal wall, using an original audiovisual support and hands-on guidance by a trained operator. In the placebo group, sham measurements of abdominal and thoracic motion were performed, and a pill of placebo was administered. Three 30-min sessions were performed over a 4-week intervention period, with instructions to perform daily exercises (biofeedback group) or to take placebo three times a day (control group) at home. After the intervention, patients allocated to the placebo group were offered biofeedback treatment. After receiving biofeedback treatment, patients in both groups were instructed to continue practicing these same exercises over time, and were followed up: visible abdominal distension and sensation of abdominal pressure/fullness (bloating) were measured at 1 and 3 months using 10-cm scales for 7 consecutive days, and the mean values (±SE) were calculated.

Results

After undergoing the three treatment sessions, abdominal distension improved in the biofeedback group (n=19; by 24±7 %), but not in the placebo group (n=20; 8±3 % change; p=0.025 vs feedback group). In the 20 patients randomized to placebo, subsequent biofeedback treatment improved abdominal distension (by 35±7 %). Follow-up in all patients after biofeedback (n=36) showed a sustained improvement in abdominal distension and bloating sensation at 1 month (by 39±5 % and 36±7 %, respectively; p<0.001 vs before treatment for both), and at 3 months (by 37±5 % and 34±8 %, respectively; p<0.003 vs before treatment for both).

Conclusion

In patients with disorders of gut-brain interaction, correction of abdominophrenic dyssynergia by a simple, non-instrumental technique, produces a sustained improvement of visible abdominal distension, associated with a concomitant improvement of bloating sensation.

Disclosure

I have the following Conflict of Interest to declare: Coloplast, Schwabe

Introduction

Hypergastrinemia, caused by chronic atrophic gastritis or Helicobacter pylori (H. pylori) associated pangastritis, is associated with an increased risk of non-cardia gastric cancer. Recent studies have also found an increased risk of gastric cancer in long-term proton pump inhibitor (PPI) users. Patients with chronic atrophic gastritis also have an increased risk of neuroendocrine neoplasms (NEN) due to hypergastrinemia. However, whether long-term PPI use increases the risk of gastric NEN has not been assessed in the general population.

Aims & Methods

The aim of the present study was to assess the risk of gastric NEN among long-term PPI users in a multinational population-based study from the Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). The study was based on the Nordic Gastric and Esophageal Tumor Study (NordGETS), which is a population-based multinational sex, age, calendar year, and country matched case-control study including all adults (≥18 years of age) with a diagnosis of gastric or esophageal tumor in the Nordic countries. In the present study, the cases were incident gastric NEN identified in the cancer registries and the exposure was long-term use of PPI categorised into three equal-sized groups (tertiles) of defined daily doses (DDDs) from the medication registries of the Nordic countries between 1996 and 2020. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for chronic atrophic gastritis, NEN in the duodenum or pancreas, and H. pylori infection identified in the patient registries and medication registries.

Results

In total, 1,790 gastric NEN case patients were compared to 17,897 control participants. After a one-year run-in period, the median follow-up was 11.8 years. The risk of incident gastric NEN increased in PPI users compared to non-users in a dose-dependent manner. The adjusted OR for incident gastric NEN was 1.83 (95% CI 1.56 to 2.15) in the highest tertile of PPI use (>385 DDDs, entire drug history) compared to no PPI use (Table). The risk was higher in the younger age group (<65 years) than the older age group (≥65 years) and the estimates were consistent when excluding individuals with chronic atrophic gastritis, other NENs, and H. pylori.

Conclusion

In this population-based study from the five Nordic countries the risk of gastric NEN was increased in PPI users compared to non-users of PPI in a seemingly dose-dependent manner. The risk was higher in younger age groups of PPI users compared to older age groups.

Disclosure

No conflicts of interest

Introduction

Spasmolytic polypeptide expressing metaplasia (SPEM) is a cell repair lineage and is a very important phenotype of gastric mucosal injury and precancerous lesion.
Previously, parietal cells loss is considered as the first step and followed with chief cells transdiffernation to induce SPEM. But whether chief cells initial loss cause SPEM
needs to be further investigation. Acidic mammalian chitinase (CHIA) belongs to the 18 glycosidase family and is highly expressed in the chief cells. Our previous study showed that CHIA deficiency in the chief cells is the key event to induce SPME to progress to gastric cancer (Liu et al., DDW 2023 and 2024). However, the molecular role of CHIA in the development of SPEM is need further investigated.

Aims & Methods

Electron microscopy, qRT-PCR and single-cell sequencing (scRNA-seq) technology, as well as histopathological and immunofluorescence (IF) stainning with specific markers were performed in chief cells specific CHIA knockout mouse model (CHIA^rox/rox-GIF-Dre) and wild-type mice(CHIA^rox/rox), and in CHIA over - expression mice (CHIA ^rox/rox - GIF - Dre + rAAv - CHIA) and the control group (CHIA ^rox/rox - GIF - Dre + rAAv - control).

Results

Compared with CHIA^rox/rox mice, histological analysis and scRNA-seq technology data showed that loss of chief cells with increased M2 macrophage infiltration and final SPEM formation, but remaining of parietal cells in CHIA^rox/rox-GIF-Dre mice. Electron microscopy showed CHIA deficiency in mice resulted in endoplasmic reticulum was dilated and swollen, as well as the mitochondrial membrane was discontinuous of chief cells, followed with the accumulation of endoplasmic reticulum stress marker, including PERK, XBP-1, eIF2α/P-eIF2α, and GRP78, together with upregulation of pyroptosis-related marker, including NLRP3, ACS, GSDMD, NEK7, Caspase1, Caspase11, IL-1β, and IL-18, which was detected by qRT-PCR. These data indicating that target CHIA deletion caused chief cells pyroptosis. Furthermore, qRT-PCR analysis showed that CHIA deficiency caused the activation of IL33/IL-13 circuit in the mucosa of mice. Moreover, double immunofluorescence staining confirmed that upregulation and colocalization of IL-33 induced M2 macrophage polarization markers, including F4/80 and CD163⁺ with NLRP3 in the base of gastric mucosal of CHIA^rox/rox-GIF-Dre mice when compared with CHIA^rox/rox mice.Notably, CHIA ^rox/rox - GIF - Dre + rAvv - CHIA mice reversed the above process compared with controls.

Conclusion

Chief cells specific CHIA deficiency resulted in endoplasmic reticulum stress mediate NLRP3 inflammasome activation to induce chief cells proptosis.
Chief cells initial loss is sufficient and the key step to activate IL-33/ST2-M2 macrophage polarization axis to induce SPEM, which is independent of parietal cells loss.