Clinical Case Summary

A 3-year-old child was admitted with the chief complaint of vomiting and dysphagia. The child underwent laparoscopic pyloric myotomy at the age of 27 days. After a 7-month course with normal feeding and weight gain, projectile vomiting reoccurred. Then the child was fed by parents at home, but overall growth was not good. When the child was 3 years old, he came to our hospital for treatment, with height of 90 cm [−1.8 standard deviation score (SDS)], weight of 13 kg (−1.1 SDS).
The upper gastrointestinal contrast radiography showed that the obstruction of the pylorus and cardia. Achalasia was subsequently confirmed by high-resolution manometry with elevated integrated relaxation pressure and 100% failed peristalsis during liquid swallows.
The patient underwent peroral endoscopic myotomy combined with gastric peroral endoscopic myotomy. The patient remained asymptomatic and gained weight during the follow-up period.
The combination of HPS and cardia of achalasia is very rare, however there are few reports of HPS associated with esophageal achalasia^[1-4]. Ono S et al^[4] showed that endoscopic pyloroplasty technique can be a less-invasive therapeutic alternative to surgery for adult patients with HPS， while not mentioned the processing mode to cope with the esophageal achalasia. A Castro et al^[1] reported endoscopic ballon a juvenile with HPS and cardia of achalasia, extramucosal pyloromyotomy at the age of 3-week-old and endoscopic forceful dilatation at the age of 11-year-old successfully resolve the stenosis of tract. We reported the first case of POEM combined with G-POEM dual tunnel therapy in pediatric population.

References

[1] Castro A., Mearin F., Gil-Vernet J.M., et al. Infantile hypertrophic pyloric stenosis and achalasia: NO-related or non-related conditions? [J]. Digestion, 1997, 58(6): 596-8.
[2] Blades B., Adkins P.C., Gwathmey O. Combined surgical treatment of achalasia of the esophagus and hypertrophic pyloric stenosis; report of a case [J]. Med Ann Dist Columbia, 1957, 26(4): 180-2; passim.
[3] Cataliotti F., Livoti G., Di Pace M.R. Esophageal achalasia and hypertrophic pyloric stenosis associated with a phytobezoar in an adolescent [J]. J Pediatr Surg, 2002, 37(9): 1363-4.
[4] Ono S., Yano F., Hoshino M., et al. Endoscopic pyloroplasty for adult hypertrophic pyloric stenosis associated with esophageal achalasia [J]. VideoGIE, 2018, 3(1): 17-9.

Introduction

Irritable bowel syndrome (IBS) is a heterogeneous disorder of gut-brain interactions characterised by pain and altered bowel habits¹. The low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet is efficacious for improving symptoms and quality of life (QoL)², however not all individuals will have a therapeutic response resulting in adequate symptom relief³. Behavioural, emotional and cognitive predictors of response have been explored in psychological therapies, but not in dietary treatments of IBS⁴.

Aims & Methods

The aim of this study was to identify psychological predictors of treatment response to the low FODMAP diet. Participants underwent a three-phase dietitian-led low FODMAP diet between August 2018 and July 2021. Participants completed questionnaires to obtain scores for psychological factors and symptoms (predictor variables). Data on depression, anxiety, gastrointestinal (GI) specific anxiety, somatic symptoms, illness perceptions, behavioural avoidance, treatment beliefs and expectations, symptom severity and QoL was collected at five time points; pre dietitian (week 0), post dietitian (week 1), post FODMAP restriction (week 5), post FODMAP reintroduction (week 13) and personalisation (week 25). Linear mixed models (LMM) were used to test the effect of baseline psychological scores on IBS symptoms and QoL over time. Cross lag panel models (CLPM) were used to identify directional relationships between predictor variables on the one hand, and IBS symptoms and QoL on the other.

Results

112 participants, (89% female, median age 30 ± 17 years) were included. LMM showed that higher treatment beliefs predicted a stronger initial symptom response (effect on linear slope p=0.036). Of the illness perceptions, lower emotional representations predicted a stronger initial and later QoL response (effect on linear (p=0.006) and quadratic (p=0.049) slopes). Increased cyclical time beliefs predicted poorer initial and later QoL response (effect on linear (p=0.015) and quadratic (p=0.029) slopes). CLPM showed that lower GI specific anxiety predicted a stronger reduction in symptoms from week 0 to 25. Of the illness perceptions, positive perceptions relating to higher personal and treatment control predicted a stronger reduction in symptoms from week 0 to week 25. Increased QoL predicted reductions in GI specific anxiety and stress from week 0 to week 25 and week 1 to week 25, respectively. Increased personal and treatment control predicted improved QoL across all time points.

Conclusion

Negative illness perceptions were associated with poorer symptom and QoL response, whereas positive illness perceptions and treatment beliefs predicted better QoL and symptom responses to the low FODMAP diet in adults with IBS. Illness perceptions and treatment beliefs can be easily assessed in clinical practice and should be considered when determining if the low FODMAP diet is a suitable treatment, and may serve as targets to enhance treatment response.

References

¹Camileri, M & Dilmaghani, S. (2023). Update on treatment of abdominal pain in irritable bowel syndrome: a narrative review. Pharmacology and therapeutics, 245, 108400-108400. http://doi.org/10.1016/j.pharmthera.2023.108400
²van Lanen, A.S., de Bree, A & Greyling, A. (2021). Efficacy of a low FODMAP diet in adult irritable bowel syndrome: a systematic review and meta-analysis. Eur J Nutr, 60(6), 3505-3522. doi:10.1007/s00394-020-02437-0
³Wilson, B., Cox, S.R. & Whelan, K. (2021). Challenges of the low FODMAP diet for managing irritable bowel syndrome and approaches to their minimisation and mitigation. Proc Nutr Soc, 80(1), 19-8. doi:10.1017/s0029665120006990
⁴ Radu, M., Moldovan, R., Pintea, S., Baban, A & Dumitrascu. (2018). Predictors of outcome in cognitive and behavioural interventions for irritable bowel syndrome. A meta-analysis. Journal of Gastrointestinal and Liver Diseases, 27(3), 257-263. http://dx.doi.org/10.15403/jgld.2014.1121.273.bab

Introduction

Etrasimod is an investigational, oral, once-daily, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). In ELEVATE UC 52 (NCT03945188), etrasimod was superior to placebo (PBO) in achieving Week (Wk) 52 corticosteroid (CS)-free clinical remission (CR).¹

Aims & Methods

This post hoc analysis reports CS-free efficacy and safety in patients (pts) on baseline (BL) CS. Pts were randomised 2:1 to once-daily etrasimod 2 mg or PBO using a treat-through design (12-wk induction and 40-wk maintenance period). At entry, pts could receive concomitant CS (prednisone [≤ 20 mg/day], budesonide [≤ 9 mg/day] or equivalent) if on a stable dose ≥ 4 wks immediately before screening endoscopy; from Wk 12, CS tapering was recommended. CS-free was defined as withdrawal of CS ≥ 12 wks prior to assessment timepoint. CS-free outcomes assessed were CS-free CR at Wk 52, CS-free endoscopic improvement (EI) at Wk 52, and CR at Wk 12 + CS-free CR at Wk 52. From Wk 12, 4-wk CS‑free symptomatic remission (SR; 4 wk in contrast to ≥ 12-wks CS free) was analysed at each visit. Logistic regressions examined associations with CS-free efficacy at Wk 52. Safety was assessed.

Results

At BL, 32.2% (93/289) and 29.2% (42/144) of etrasimod and PBO pts received CS; of these, significantly more etrasimod vs PBO pts achieved CS-free CR at Wk 52, CS-free EI at Wk 52 and CR at Wk 12 + CS-free CR at Wk 52 (all p<0.05; Table). At Wks 40–52, there were significant differences (16.6–26.6%; p<0.05) in 4-wk CS-free SR between etrasimod and PBO. In this subpopulation, being biologic/Janus kinase inhibitor-naïve was not a significant predictor of 12-wk CS-free CR at Wk 52 (odds ratio [OR]: 3.61; 95% confidence interval [CI] 0.91, 14.39; p=0.07); age, per 10-year increase, was significantly associated (OR: 1.51; 95% CI 1.03, 2.22; p=0.04). Etrasimod vs PBO pts with concomitant CS at BL experienced slightly more adverse events (AEs; not exposure adjusted) (71.0% [66/93] vs 61.9% [26/42]) but fewer serious AEs (6.5% [6/93] vs 14.3% [6/42]), including serious infections (0% [0/93] vs 7.1% [3/42]).

Conclusion

More etrasimod vs PBO pts who received CS at BL met CS‑free efficacy endpoints. Four-wk CS-free SR with etrasimod was superior to PBO from Wk 40. Concomitant CS use at BL had no notable negative effect on the safety of etrasimod, consistent with the overall ELEVATE UC 52 population.¹

References

1. Sandborn W et al. Lancet 2023: Epub ahead of print.

Disclosure

BES: grants/research: Arena, Janssen; speaker: BMS, Janssen, Lilly, Pfizer, Takeda; consultancy/advisory board: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, BMS, Celltrion, Fresenius Kabi, Genentech, GSK, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D; stock: Ventyx Biosciences; non-financial support: Janssen, Lilly, Pfizer, Takeda.
YL: speaker: Pfizer Inc, Takeda, Abbvie, Jannsen; Consultancy, Advisory Committee/Board Member: Pfizer Inc, BMS, Takeda, Abbvie, Amgen BioJamp, Lilly.
DTR: grant support: Takeda, Helmsley Charitable Trust, GastroIntestinal Research Foundation; consultancy fees/is a member of advisory boards: AbbVie, AltruBio, ASLAN Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chronicles, Syneos, ClostraBio, Connect Biopharma, EcoR1, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen Pharmaceuticals, Kaleido Biosciences, Eli Lilly, Pfizer Inc, Prometheus, Reistone, Seres Therapeutics, Takeda, Target RWE, Trellus Health; is on the Board of Trustees for Crohn’s & Colitis Foundation and Cornerstones Health, Inc; holds stock options in Alike Health, AltruBio, Datos Health and Iterative Health.
KBG: research support: Celltrion, Galapagos, Pfizer Inc; speaker honoraria and/or consulting fees: AbbVie, Celltrion, Ferring Pharmaceuticals, Immunic Therapeutics, Janssen, Novartis, Pfizer Inc, Samsung Bioepis, Takeda, Tillotts.
JP: personal: AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celltrion, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, GSK, Immunic, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer Inc, Progenity, Revolo, Takeda, Theravance Biopharma and Wassermann; grant support: AbbVie, Pfizer Inc.
MG: employee & shareholder of Pfizer AG.
WW, KS, JCW, CCS: employees & shareholders of Pfizer Inc.
KW: employee & shareholder of Pfizer Canada Inc.
SS: speaker: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Fresenius, Janssen, MSD, Pfizer Inc, Takeda; consultancy/advisory: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Fresenius, Gilead Sciences, IMAB, Janssen, MSD, Mylan, Pfizer Inc, Protagonist, Provention Bio, Takeda, Theravance.

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 low fermentable oligosaccharide, disaccharide, monosaccharide and polyol diet (LFD) has been purported as a first line therapeutic treatment for the management of irritable bowel syndrome (IBS)^1,2. Despite the extensive research supporting the efficacy of the LFD^{3 4}, there are few studies exploring the lived experience of people with IBS undertaking a dietitian-led three-phase LFD.

Aims & Methods

This study aimed to explore people’s expectations of and experience with each phase of the LFD, and identify barriers and enablers to successfully completing each phase. A descriptive, qualitative design employed semi-structured interviews with adults with IBS who undertook all or part of a dietitian-led research study on predictors of response to a LFD. Participants underwent LFD restriction, reintroduction and personalisation between October 2020 and April 2022. Interviews examined expectations and experiences of the LFD process, and barriers and enablers to undertaking and completing each phase. Sociodemographic and IBS characteristics were also collected. Thematic analysis summarised key themes.

Results

Seventeen people (32%, 17/53 response rate) aged 37.5 ± 14 years (88% female) completed interviews, of whom 76% (13/17) completed all three phases of the LFD. Duration of experiencing IBS symptoms ranged from one to 40 years with 76% experiencing diarrhoea as the most predominant symptom. Four themes emerged from the data. Firstly, people presented with different IBS and healthcare experiences, and expectations of what the LFD would provide. Previous unsuccessful treatments (pre- and probiotics, gluten elimination, herbal medicine) motivated people to undertake the LFD. Secondly, people’s expectations of outcomes within each phase varied and was related to their symptom response. People expected symptom resolution during the restriction phase and were disappointed that symptoms were not entirely alleviated. Symptoms during the reintroduction phase were a barrier to continuing challenges for some but others felt that symptoms assisted in identifying trigger foods. Despite overall reductions in symptoms during each phase, a residual frustration was felt as symptoms were not eliminated on completion of personalisation. Thirdly, the three-phase process required significant planning, effort and self-efficacy. Ability to adhere to personal tolerance levels of fermentable carbohydrates was an enabler to successful completion of the reintroduction and personalisation phase. Environmental barriers included eating out, multi-person households and altering meals to suit family mealtimes. Personal barriers included perceptions of food triggers, apprehension to try foods that had long been avoided and experiencing symptoms during the reintroduction phase. Lastly, most people incorporated learning and experiences from the LFD into daily life after reintroduction. Those with symptom improvement identified strategies to circumvent FODMAP intake in daily life and were understanding of the interplay between food, the environment and psychological factors on symptoms. Some used the LFD restriction to manage symptom exacerbations.

Conclusion

The LFD process is complex, and personal beliefs, experiences and expectations impact on adherence and completion of each phase. Further personalisation of the LFD to individual circumstances is fundamental to improving the experience and outcome of this therapeutic management strategy in people with IBS. These findings will be used to inform improved implementation to optimise peoples experience and success with the LFD.

References

¹ Clinical Decision Support Tool: IBS Treatment. (2022). Gastroenterology 163(1): 152-152 http://doi.org./10.1053/S0016-5085(22)00536-4
² Vasant, D.H., Paine, P.A., Black, C.J., Houghton, L.A., Everitt, H.A., Corsetti, M., Agrawal, A., Aziz, I., Farmer, A.D., Eugenicos, M.P, Moss-Morris, R., Yiannakou, Y & Ford, A, C. (2021). British Society of Gastroenterology guidelines on the management of irritable bowel syndrome Gut, 70(7), 1214-1240.http://doi.org/10.1136/gutjn-2021-324598
³ Black, C.J., Staudacher, H.M & Ford, A.C. (2022). Efficacy of a low FODMAP diet in irritable bowel syndrome: systematic review and network meta-analysis. Gut, 71(6), 1117-1126. doi:10.1136/gutjnl-2021-325214
⁴ Wang, J., Yang, P., Zhang, L and Hou, X. (2021). A low FODMAP diet improves the global symptoms and bowel habits of adult IBS patients: A systematic review and meta-analysis. Frontiers in nutrition, 8. http://doi.org/10.3389/fnut2021.683191

Introduction

Gastro-esophageal reflux disease (GERD) is a multifactorial disease that manifests in patients with different degrees of anti-reflux barrier impairment. GERD significantly impacts quality of life despite the fact that symptom burden may not always correlate with disease severity. Precise pathophysiologic evaluation can identify patients with actionable GERD who may benefit from anti-reflux surgery or escalation of medical therapy. The Milan Score, a novel high-resolution manometry (HRM) metric, numerically quantifies the degree of anti-reflux barrier disruption¹. While the Milan Score has been proven to predict pathologic GERD, its ability to distinguish non-severe from severe GERD and to identify patients with a higher grade of anti-reflux barrier disruption requires further study.

Aims & Methods

A database of prospectively collected data from a cohort of patients undergoing HRM and pH-study for persistent GERD symptoms was queried. Using Lyon 2.0 consensus, pathologic GERD was defined as AET >6%, grade B-C-D esophagitis or Barrett’s esophagus on endoscopy. Severe reflux was defined as AET >12%, DeMeester score >50, grade C-D esophagitis or Barrett’s esophagus². Demographic, HRM and pH data were extracted, classified and compared between groups with varying GERD severity (no GERD, non-severe GERD, severe GERD). The Milan Score integrates the main manometric parameters related with the pathophysiology of GERD (ineffective esophageal motility, esophago-gastric junction (EGJ) contractile integral, EGJ morphology and straight leg raise maneuver response). In order to simplify the use of the Milan Score, risk rates have been classified into six categories, from extremely unlikely to extremely likely. A cumulative odds ordinal logistic regression was run to determine the independent effect of HRM variables on reflux severity. The ability of the Milan Score to predict severe reflux was assessed, as well as its association with the pH-study criteria proposed by Lyon 2.0 as adjunctive evidence for pathologic GERD (>80 reflux episodes, mean nocturnal baseline impedance (MNBI) <1500 W or positive reflux-symptom association).

Results

Among 603 patients enrolled (median age 49.9 years, median body mass index (BMI) 25.3 Kg/m², 50.5% males), 124 (20.6%) had non-severe and 142 (23.5%) had severe GERD. Non-severe and severe GERD patients had similar demographic and clinical characteristics, but were significantly different from the no-GERD group (Table). On univariate analysis, presence and size of hiatal hernia, Milan Score and Milan Score categories were significantly different among the groups (p <0.001). On ordinal logistic regression, hiatal hernia size and Milan Score category were found to be independent predictors of GERD severity (OR 1.28, 95% CI, 1.04-1.57, p=0.018 and OR 2.92, 95% CI, 2.47-4.45, p=<0.001 respectively). A significantly higher Milan Score (p <0.001) was found in patients with >80 reflux episodes, MNBI <1500 W, positive reflux-symptom association and any criteria of severe GERD.

Conclusion

Hiatal hernia size and Milan Score assessed at HRM are independent factors associated with severe GERD. The Milan Score is significantly higher in patients with pathologic adjunctive pH-impedance metrics and in patients with severe GERD.

References

1. Siboni S, Sozzi M, Kristo I et al. The Milan score: A novel manometric tool for a more efficient diagnosis of gastro-esophageal reflux disease. United European Gastroenterol J. 2024 Mar 27. doi: 10.1002/ueg2.12565. Epub ahead of print. PMID: 38536701.
2. Horvath KD, Jobe BA, Herron DM et al. Laparoscopic Toupet fundoplication is an inadequate procedure for patients with severe reflux disease. J Gastrointest Surg. 1999 Nov-Dec;3(6):583-91. doi: 10.1016/s1091-255x(99)80079-1. PMID: 10554364.

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.