Introduction

The temporal trend of mortality rates among young individuals with gastric cancer has sparked a contentious debate over the past few decades. Additionally, there remains an ambiguous distribution alteration of disease burden among different countries.

Aims & Methods

​​​​This population-based systematic analysis was conducted to investigate changes in health inequality related to mortality caused by young gastric cancer from 1990 to 2019. We performed a secondary analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 by extracting cross-sectional data on young gastric cancer (<40 years). The age-specific mortality rate was used to determine deaths attributed to young gastric cancer. A prediction of young gastric cancer mortality rate and case number up to 2030 was performed using the Norpred APC model. The slope index of inequality (SII) and the health concentration index were used to quantitatively measure absolute and relative changes in health inequalities, taking into account the socio-demographic indexes (SDI) level. The data was further analysed across different GBD regions and sexes.

Results

The global mortality rate of young gastric cancer declined from 1.61 (95% Uncertainty interval [UI]: 1.49 to 1.72) per 100,000 in 1990 to 0.94 (95% UI: 0.87 to 1.02) per 100,000 in 2019, with an annual rate of change -0.42% (95% Confidence interval (CI): -0.47 to -0.35). The projected data suggests that the number of global mortality case and rate of young gastric cancer would decrease to 24,450 and 0.761 per 100,000 by 2030. Countries belong to the lower 50% of SDI accounted for 49.9% and 52.3% of the global young gastric cancer deaths in 1990 and 2019, respectively. Although the absolute cross-national inequality (SII) of mortality rate fell from 0.133 (95%CI: -0.533 to 0.416) in 1990 to -0.239 (95%CI: -0.432 to -0.046) in 2019, the relative inequality (concentration index) for global young gastric cancer mortality increased from 1990 (−0.058, 95%CI: −0.532 to 0.416) to 2019 (−0.104, 95%CI: −0.526 to 0.317). The observed rise in absolute health inequality was evident in both sexes, but relative health inequality increased in females only. The regions of Sub-Saharan Africa (including Western and Southern), Central Asia, and Central Europe exhibited an increase in both absolute and relative health disparities in young gastric cancer mortality.

Conclusion

Although there has been a decline in the global young gastric cancer mortality rate, health inequality has increased over the past three decades, especially in females and some low SDI countries. It is imperative to prioritize efforts in addressing inequality to further reduce the global burden of young gastric cancer mortality.

Introduction

​Helicobacter pylori is class I carcinogen responsible for 89% of non cardia gastric cancer.

Aims & Methods

Screen and treat application study is ongoing in six EU countries in the asymptomatic age group of citizens from the age of 30 to 34 years. The test-and-treat program is free of charge for all eligible participants. Four different locally validated H. pylori IgG serologies and / or UBT as a test were used. Quadruple bismuth based 14 day, a 10-day regimen with esomeprazole combined with bismuth quadruple therapy in a single-capsule or 14 day tripple eradication therapy were used as the first line therapy. RED Cap IT platform (pretreatment questionnaires, treatment protocols, side effects, compliance,complications…) was used to collect data for quality assurance, monitoring, and evaluation.

Results

The study is still ongoing. Interim results show a wide variation of response rates to the invitation (from 4,1% in Wroclaw to 45,5% in Ljubljana). Seropositivity / UBT rates vary from 13,9% in Ljubljana to 49% in Latvia. The eradication rates are from 88,2% in Dublin to 96,9% in Ljubljana. The use of all three treatment schemes showed encouraging eradication and adherence rates, whereas the incidence of adverse events due to this therapy was within the acceptable range. No serious adverse events have been reported so far. The differences among study sites are in the organisation of invitations, educational campaigns and dissemination activities as well as in the time when study was launched in a certain country.

Conclusion

The screen and treat application study is organised in a way as an organised cancer screening program. Careful study planning: legal, financial, technical, organisational aspect and public awareness campains should be implemented before official lounch of the study.Central data capture system is necessary to implement quality control monitoring. Education and public awareness campaign to increase the participation rate are of crucial importance.

Introduction

In recent years, there has been increased focus on appropriate proton pump inhibitor (PPI) prescribing due to the growing awareness of the prevalence of long-term PPI use globally.1 Rebound acid hypersecretion (RAHS) has been described as potentially contributing to PPI overuse and treatment dependence1 . RAHS is a physiological phenomenon observed following PPI discontinuation after a minimum of 4 – 8-week use. However – despite being first described in 1996 – its clinical relevance, underlying mechanisms, prevalence, and impact on patient outcomes are still not completely understood.

Aims & Methods

The purpose of this rapid review is to assess the current evidence published on RAHS, the potential mechanisms behind the phenomenon, its prevalence and clinical significance in patients discontinuing PPI therapy.
A rapid review of peer-reviewed literature was conducted through Embase and PubMed. Systematic reviews and clinical studies were included if they examined RAHS, reported prevalence, or evaluated patient-reported symptoms post-PPI withdrawal. Key findings were extracted and summarised across three domains: physiological mechanisms, prevalence and severity, and patient impact.

Results

A total of 272 articles – published between 2005 and 2024 – were retrieved, with 7 articles meeting the inclusion criteria for final review. Five of these were clinical studies, whilst the remaining 2 were systematic literature reviews. All, except 1, of the studies included were conducted more than 10 years ago – 3 randomised controlled trials, 1 cross sectional study, and 1 study looked at pre-surgery patients without randomisation. The studies were heterogeneous in design, the study populations varied broadly between 7 and 150 participants, and the prevalence data appeared to be inconsistent. Studies show a physiological basis for RAHS, including upregulation of gastrin and enterochromaffin-like cell hyperplasia, during PPI therapy, leading to transient acid hypersecretion upon PPI withdrawal^2,3,4,5. Symptoms resembling dyspepsia or gastro-oesophageal reflux disease (GORD) recurrence were commonly reported in both healthy volunteers and patients^2,3,6,7. RAHS was transient in most cases^2,3,4 but may drive long-term PPI use due to misinterpretation of symptoms as disease recurrence. However, a small number of studies reviewed in the two systematic literature review papers challenged the existence of clinically meaningful RAHS, particularly after short-term or low-dose therapy^6,8.

Conclusion

There is growing evidence that RAHS is a physiologically plausible and clinically relevant phenomenon in long-term PPI users. It is suggested that RAHS may contribute to symptom recurrence and therapy dependence, resulting in the continuation of unnecessary PPI therapy. With the increasing efforts on PPI deprescribing due to growing concerns over long-term use when there’s a lack of appropriate indication, clinicians need to be aware of the potential for RAHS to act as a roadblock for patients. However, despite discussion about RAHS ongoing for almost 30 years, there is still limited understanding about its impact on patients and the potential contribution to the challenges of PPI deprescription. Most importantly, there’s limited understanding of appropriate management solutions to overcome these challenges. In order to improve education for both clinicians and patients, further research is required on appropriate management solutions for RAHS and to aid PPI deprescribing efforts.

References

1. Savarino E et al., Holistic management of symptomatic reflux: rising to the challenge of proton pump inhibitor overuse. Br J Gen Pract. 2022; 72(724):541-544.
2. Reimer C at el., Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009; 137(1):80-7, 87.e1.
3. Niklasson A et al., Dyspeptic symptom development after discontinuation of a proton pump inhibitor: a double-blind placebo-controlled trial. Am J Gastroenterol. 2010;105(7):1531-7.
4. Fossmark R et al., Rebound acid hypersecretion after long-term inhibition of gastric acid secretion. Aliment Pharmacol Ther. 2005; 21(2):149-54.
5. Helgadóttir H et al., The effects of long-term therapy with proton pump inhibitors on meal stimulated gastrin. Dig Liver Dis. 2014; 46(2):125-30.
6. Lødrup AB et al., Systematic review: symptoms of rebound acid hypersecretion following proton pump inhibitor treatment. Scand J Gastroenterol. 2013; 48(5):515-22.
7. Vales A et al., Randomised clinical trial: the use of alginates during preinvestigation proton pump inhibitor wash-out and their impact on compliance and symptom burden. BMJ Open Gastroenterol. 2023; 10(1):e001026.
8. Hunfeld NG et al., Systematic review: Rebound acid hypersecretion after therapy with proton pump inhibitors. Aliment Pharmacol Ther. 2007 Jan 1;25(1):39-46.

Disclosure

Clinical Case Summary

Introduction: Cap polyposis is a rare benign inflammatory condition characterized by inflammatory polyps covered with a fibrinopurulent exudate. It is more commonly observed in women and the elderly, although it can present at any age. The disease typically affects the rectum and sigmoid colon. The most frequent symptoms include mucous diarrhea and rectal bleeding. It has been associated with mucosal prolapse due to altered intestinal motility, Helicobacter pylori infection, and even intestinal dysbiosis.
Endoscopy: A 46-year-old male with no relevant personal or family medical history presented with altered bowel habits, characterized by increased stool frequency, decreased consistency, and the presence of mucus and blood, along with tenesmus and urgency. H. pylori testing was negative. Colonoscopy revealed numerous sessile and pedunculated polyps with an inflammatory appearance distributed throughout the colon, predominantly in the sigmoid and rectum. Most polyps were covered at their apex by a fibrinopurulent exudate (Figures 1–4). The colonic mucosa adjacent to the polyps appeared normal. Multiple biopsies were taken, confirming inflammatory polyps. A first therapeutic colonoscopy was performed, during which multiple polyps consistent with cap polyps were resected (Figure 5). Additional sessions were scheduled to complete polyp resection. Furthermore, a molecular study was performed using next-generation sequencing (NGS) with a multigene panel including genes associated with polyposis, with negative results.
Conclusions: The clinical course of cap polyposis remains unclear. The need for and timing of colonoscopy should be individualized based on the number of polyps and symptom severity. Initial treatment should be conservative, focusing on resolving constipation and eradicating H. pylori. In cases with persistent symptoms, endoscopic resection of the lesions should be considered.

Introduction

Gut microbiome has been suggested to play a role in the etiology of autism. Specifically, recent studies have pointed toward altered gut microbiome compositions, resulting in overgrowth of particular bacteria that have been linked to autism symptom severity, increased repetitive behavior, and gastrointestinal problems. However, how variations in the gut microbiome relate to autistic behavioral difficulties remains sparse. Recent autism research points towards alterations in the oxytocinergic system in autistic individuals (1), which have been implicated to form a major mediator of the gut microbiome and his impact on behavior. However, there have been no studies to date directly addressing whether stimulation of the oxytocinergic system could modulate gut microbiome compositions in autistic children. Furthermore, it is largely unknown how potentially confounding factors may impact the results of this intervention.

Aims & Methods

In the current study we analysed gut microbiome from a previous clinical trial (2). We examined diagnosis-related differences in gut microbiome compositions in autistic versus non-autistic children (8-12 years), and the effects of a 4-week intranasal oxytocin administration on gut microbiome compositions, taking into account confounding variables.
This double-blind randomized placebo-controlled trial consisted of a double-blind phase followed by a 4-week single-blind phase during which all participants received intranasal oxytocin. Effects of oxytocin (12 IU, twice daily) on gut microbiome compositions and behavioral difficulties were assessed immediately after the administration period and 4 weeks after the last administration. Eighty autistic children and 40 typically developing peers were recruited. Note that the collection of stool samples were optional, resulting in 52 autistic children and 27 non-autistic children included in the gut microbiome part of this study. Behavioral difficulties were assessed using the Social Responsiveness Scale, the Repetitive Behavior Scale-Revised, and the child- and parent-reported version of the Screen for Anxiety Related Emotional Disorders. Gut microbiome was analysed by 16S rRNA sequencing.

Results

No difference in gut microbiome major confounder transit time (Bristol Stool Scale) was observed between autistic and non-autistic children. Diagnosis-related difference analyses in alpha-diversity revealed a significant lower observed richness (Z = 2.476, p = .013) and a higher microbial evenness (Z = -2.377; p = .017) in autistic vs non-autistic children after Benjamini-Hochberg correction (BH-correction). Moreover, no significant differences in (CLR-transformed) abundances of bacterial genera were found between the autistic and non-autistic children after BH-correction. However, examining the overall associations with behavioral difficulties, a significant positive association (q-value (p-value after BH-correction) <.25) was evident between Romboutsia and parent-reported anxiety-like behavior (Coeff. = 0.048, q = .06).
Ongoing analyses will unveil initial findings on oxytocin's effect on the gut microbiome in association to clinical responses at UEG 2024.

Conclusion

Gut microbiome differs modestly between autistic and non-autistic children. The anticipated outcomes of the intervention will allow to advance our understanding of the intricate interplay between the oxytocinergic system and the gut microbiome, offering a foundation for the development of targeted therapeutic interventions.

References

1. Evenepoel M, Moerkerke M, Daniels N, Chubar V, Claes S, Turner J, et al. Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation. Transl Psychiatry [Internet]. 2023 Jun 30 [cited 2023 Jul 3];13(1):235. Available from: https://pubmed.ncbi.nlm.nih.gov/37391413/
2. Daniels N, Moerkerke M, Steyaert J, Bamps A, Debbaut E, Prinsen J, et al. Effects of multiple-dose intranasal oxytocin administration on social responsiveness in children with autism: a randomized, placebo-controlled trial. Mol Autism [Internet]. 2023 Dec 1 [cited 2023 Oct 23];14(1). Available from: https://pubmed.ncbi.nlm.nih.gov/37081454/

Introduction

Food is often reported as a trigger for symptoms in patients with irritable bowel syndrome (IBS). One of the proposed pathophysiological mechanisms is a local immune response to food antigens, triggered by a preceding infection¹.

Aims & Methods

This study aimed to investigate rectal mucosal reactions to food in patients with IBS. Therefore, patients with IBS and food-related symptoms were included. Allergies to the food items that were tested during the colonoscopic antigen provocation (COLAP) were excluded by an allergologist. The COLAP was started in the absence of macroscopic abnormalities during sigmoidoscopy. A 200 μL solution of each food antigen (wheat, gluten, soy, and milk; administered in a randomized order and blinded), a negative control (NaCl 0.9%), and a positive control (histamine) were injected in the rectal mucosa, with a positive reaction defined as mucosal edema 12 minutes after injection and judged based on a previously used semiquantitative scale ². The reaction was independently judged by two endoscopists, resulting in a positive or negative reaction when they agreed and doubtful when they did not.

Results

Data from ten patients were available for this interim analysis. Nine were female, with a median age of 45 [range 24-58] years, and a median IBS symptom severity score of 356 [range 197-416], i.e. in the moderate to severe range. Six patients had predominant constipation, one predominant diarrhea, and three mixed bowel habits. COLAP was positive in seven patients, with a positive reaction for one food antigen in three patients and for two food antigens in four patients. In the other three patients, the test was only doubtful for one of the food antigens (n=2), or negative for all (n=1). A positive reaction to gluten was observed in five patients, to soy in three, to wheat in two, and to milk in one (Table). The reaction to histamine was positive in eight patients, with no positive reaction after injection of the negative control in all.

Conclusion

A local intestinal reaction to food antigens was seen in a subset of patients with IBS. Further research will focus on underlying pathophysiological mechanisms and clinical relevance of these findings.

References

1. Aguilera-Lizarraga J, Florens MV, Viola MF, Jain P, Decraecker L, Appeltans I, et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature. 2021;590(7844):151-6.
2. Bischoff SC, Mayer J, Wedemeyer J, Meier PN, Zeck-Kapp G, Wedi B, et al. Colonoscopic allergen provocation (COLAP): a new diagnostic approach for gastrointestinal food allergy. Gut. 1997;40(6):745-53.