Introduction

Previous epidemiological studies have examined the association between Helicobacter pylori and gastroesophageal reflux disease (GERD) but the findings were inconsistent This study aimed to explore the causal relation between Helicobacter pylori IgG and six specific antibody levels and risk of GERD using mendelian randomization analysis.

Aims & Methods

We used summary-level data from two large genome-wide association studies (GWAS), i.e. the FinnGen research project and the UK biobank cohort. Eighteen single nucleotide polymorphisms (SNPs) associated with levels of IgG and six Helicobacter pylori specific antibodies (UreA, CagA, VacA, Catalase, OMP, and GroEL) were used as instrument variables to predict levels of these markers for Helicobacter pylori infection. Associations between these SNPs and GERD risk were examined primarily using the inverse variance weighted method, and secondly using MR-Egger, weighted median, simple mode, and weighted mode methods. We further conducted multivariable mendelian randomization analysis on the association between levels of the six specific antibodies and risk of GERD.

Results

Genetically predicted Helicobacter pylori lgG antibody levels were not associated with risk of GERD in either FinnGen (odds ratio [OR]=0.992, 95% confidence interval [CI] 0.961-1.025) or UK Biobank (OR=0.999, 95%CI 0.998-1.001). Genetically predicted levels of the six Helicobacter pylori specific antibodies were not associated with risk of GERD, except for UreA antibody levels in MR-Egger method only (OR=1.138; 95%CI 1.005-1.289) for which pleiotropy was indicated (MR-Egger intercept -0.029, P=0.048). Multivariate MR also found no associations between levels of Helicobacter pylori specific antibodies and risk of GERD.

Conclusion

This Mendelian randomization study found no evidence for a causal relation between Helicobacter pylori infection and the risk of GERD.

Introduction

Gastroesophageal reflux is responsible for various extresophageal symptoms that are commonly labelled as laryngopharyngeal reflux (LPR). These mostly include cough, throat clearing, globus sensation and hoarseness. The pathophysiological link between reflux and symptoms likely includes direct effect of the refluxate on the upper airways epithelium and reflex that is initiated by stimulation of the afferent nociceptive fibres in the distal esophagus by acidic gastroesophageal reflux. Arguably, the relationship between reflux and laryngopharyngeal symptoms might involve other, yet not well explored mechanisms. In our previous research we found that LPR patients have impaired mucociliary clearance of the respiratory epithelium of the upper airways. This could contribute to the inflammation persistence and the presence of symptoms. We therefore aimed to determine whether any parameter of the reflux burden as detected by 24-hour pH/impedance correlates with ciliary beat frequency (CBF), the major quantifiable aspect of mucociliary clearance.

Aims & Methods

Consecutive patients with LPR confirmed by off PPI 24-hour pH/impedance had a sample of the ciliated epithelium obtained from the nose using a cytology brush. Nasal CBF was analysed using a digital high‐speed video microscope and the dedicated software application Ciliary Analysis (NI LabVIEW). Healthy volunteers without either esophageal or extraesophageal reflux symptoms served as a control group. Both patients’ and healthy volunteers’ group were without any airway inflammation at least 3 months prior to the evaluation and were at least 10 days of PPI therapy. Maximal, minimal, and the median value of the CBF (Hz) was obtained. We performed correlation analyses between the acid exposure time (AET), number of reflux episodes, mean nocturnal baseline impedance (MNBI) in all impedance segments (Z1-Z6) and CBF values.

Results

32 patients with LPR confirmed by 24-hour pH/impedance that had positive reflux symptom index (RSI>13) were included in the final analysis. Of them, 12 patients had confirmed by positive acid exposure time (AET>6%) and/or abnormal number of reflux episodes (>80). Firstly, we confirmed our previous observations that LPR patients had lower CB frequency (median value) compared to the healthy individuals (6,37±2,17 vs. 10,9±1,9; p<0.0001). Separate analysis of patients with proven GERD showed no CBF difference from the remaining (pH negative patients) (6,26±2,53 vs. 6,43±1,94; p=0,42). Secondly, we performed correlation analysis between AET/number of reflux episodes and CBF. We found no significant correlation between reflux burden and median value of CBF (N=32, R=-0.18, p=NS and R=0.05, p=NS for AET and number of refluxes, resp.). Thirdly, we performed correlation analyses between CBF and MNBI values of all impedance segments. Indeed, correlation analysis between median CBF and MNBI Z1-Z6 showed no significant correlations (N=32, R=-0.16, 0.09, 0.28, 0.01, 0.14 for Z1, Z2, Z3, Z4, Z5, Z6, resp., resulting in p=NS in all segments).

Conclusion

pH positive LPR patients had no difference in CBF values from the remaining (pH negative) patients. Reflux burden in the esophagus as determined by pH recording does not seem to be related to ciliary beat frequency. We observed no significant correlation between the MNBI values in any impedance segment and the median CBF value. Further research should be performed to determine the putative mechanism between the impairment of CBF and reflux.
Supported by: VEGA 1/0060/23

Introduction

The enteric nervous system (ENS) is situated deep in the intestinal wall. Full-thickness biopsies may be used to assess damage to the neurons, i.e., enteric neuropathy. The ENS is difficult to examine in conventional histological sections of 3-5 µm, due to the complex spatial organization and large size of neurons.

Aims & Methods

The aim of the present study was to assess the volume and thickness of the ENS in human ileum full-thickness biopsies using X-ray phase-contrast micro-computed tomography. Full-thickness ileum biopsies from five controls and six patients clinically diagnosed with gastrointestinal dysmotility and neuropathy were included. Punch biopsies of 1-mm diameter (up to 1 cm in length), centered on the myenteric plexus, were extracted from the paraffin blocks, placed into a polyimide tube, and subsequently scanned with x-ray phase-contrast micro-CT. Quantitative volumetric analysis was performed from the reconstructed data.

Results

The architecture of both ganglia and fascicles was well visible. The connections between different parts of the ENS could be followed. The volume and thickness of the neural tissue could be determined in 3D in all samples. The neural tissue volume/total tissue volume was higher in controls (4.57 (3.61-5.26)) compared with the patients with enteric neuropathy (3.07 (2.57-3.76)) (p=0.013). The patient with the longest disease duration had the lowest ratio overall (2.51).

Conclusion

3D analysis may be used to determine the thickness and volume of the ENS over larger areas of the gastrointestinal tract than available in light microscopy. The assessment can be performed in an objective, standardized way, without prior staining or preparaiton, to ensure reproducibility and comparison between health and disease. Further evaluation is needed to examine the role of this method in the diagnosis of enteric neuropathy.

References

Peruzzi N, et al. 3D analysis of the myenteric plexus of the human bowel by X-ray phase-contrast tomography - a future method? Scand J Gastroenterol 2020;55:1261–1267.

Introduction

Pancreatic cystic lesions (PCL) represent an increasingly diagnosed condition with significant burden to patients’ lives and medical resources. Endoscopic ultrasound (EUS)-ablation techniques have been utilized to treat focal pancreatic lesions. This systematic review with meta-analysis aims to assess the efficacy of EUS-ablation on PCL in terms of complete or partial response and safety.

Aims & Methods

A systematic search in Medline, Cochrane and Scopus databases was performed until April 2023 for studies assessing the performance of the various EUS-ablation techniques. The primary outcome was complete cyst resolution, defined as cyst disappearance in follow-up imaging. Secondary outcomes included partial resolution (reduction in PCL size), and adverse events rate. A subgroup analysis was planned to evaluate the impact of the available ablation techniques (ethanol, ethanol/paclitaxel, radiofrequency ablation (RFA), lauromacrogol) on the results. Meta-analyses using a random effects model were conducted and the results were reported as percentages with 95% Confidence Intervals (95%CI).

Results

Fifteen studies (840 patients) were eligible for analysis. Complete cyst resolution after EUS-ablation was achieved in 44% (95%CI: 31-57; 352/767; I2=93.7%), and the respective partial response rate was 30% (95%CI:20-39; 206/767; I2=86.1%). Adverse events were recorded in 14% (95%CI: 8-20; 164/840; I2=87.2%) of cases, rated as mild in 10% [(95%CI: 5-15); 128/840; I2=86.7%]; and severe in 4% (95%CI: 3-5; 36/840; I2=0%). The subgroup analysis for the primary outcome revealed rates of 70% (95%CI: 64-76; I2=42.3%) for ethanol/paclitaxel, 44% (95%CI: 33-54; I2= 0%) for lauromacrogol, 32% (95%CI: 27-36; I2=88.4%) for ethanol and 13% (95%CI: 4-22; I2=95.8%) for RFA. Considering adverse events, the ethanol-based sub-group rated the highest percentage [16% (95%CI: 13-20; I2:91.0%)].

Conclusion

EUS-ablation of pancreatic cysts provides acceptable rates of complete resolution and low incidence of severe adverse events, with chemoablative agents yielding higher performance rates.

Disclosure

Nothing to declare

Introduction

Corpus Atrophic Gastritis (CAG) is a precancerous inflammatory condition of the oxyntic mucosa. Up today, two types of CAG are distinguished: 1) autoimmune (corpus-restricted), defined for CAG sparing the antrum 2) Helicobacter pylori (Hp)-related (multifocal), which involves antrum too.
Antrum involvement/sparing is crucial for both CAG definition as autoimmune and gastric cancer risk level, which is increased in case of pan-atrophy/pan-metaplasia, according to OLGA and OLGIM scores. CAG natural history is still poorly known, especially regarding antrum evolution. In cases with previous antral involvement, possible antrum healing after cure of Hp infection was formerly described. So, given the importance of the criterium antrum-sparing, we aimed to assess antral mucosa changes at long-term follow-up(FU) beside baseline in a cohort of CAG patients.

Aims & Methods

Given the importance of the criterium antrum-spared, we aimed to assess antral mucosa changes at long-term follow-up(FU) beside baseline in a cohort of CAG patients.
We performed a retrospective study on 130 patients with CAG and antrum involvement according to updated Sydney System. Mean time of FU gastroscopy was 40.6(range 4-192) months. In 13 patients corpus atrophy was not confirmed at FU, so were excluded. At baseline, among the remaining 117 patients [mean age 63 (range 20-87) years; F 67.5%], 47 (40.2%) had antral non-atrophic and 70 (59.8%) had antral atrophic gastritis, metaplastic in 84.3%. Histologically diagnosed Hp infection was present in 27.3% of patients, all receiving eradication therapy, anti-parietal cells antibodies (APCA) were positive in 53.8%.

Results

At FU 29/117(24.8%) of patients with tout-court involved antrum showed a complete restitutio ad integrum of antral mucosa. In particular, on 70 cases with antral atrophy at baseline, atrophy regressed in 15 (21.4%). Hp infection at baseline was present in 38% of patients who reported complete antral healing at FU, cured in all but one. Both antral healing and atrophy regression were found to be similar in Hp-cured and not-cured/negatives (p>0.05). In 8 patients (6.8%) a worsening of antral histology at FU was reported: 5 developed antral atrophy, not present at baseline, and 3 antral atrophic patients developed intestinal metaplasia.

Conclusion

Nearly 25% of CAG patients with antral involvement showed complete antrum healing, with regression of baseline antral atrophy in 21.4%. Antral healing occurred also in patients without history of Hp infection and/or eradication. These data suggest that in CAG natural history, concomitant antral involvement may regress irrespective of Hp cure, implying cancer risk reduction and raising queries about histology as sole criteria diagnostic for autoimmune gastritis.

References

1. Lahner et al. Dig LIver Dis 2019
2. Sipponen P et al. Gastroenterology clinics of North America 2000
3. Annibale B Helicobacter 1997