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

Endoscopic submucosal dissection (ESD) has become a common treatment method for superficial esophageal cancer, allowing complete resection and accurate postoperative pathological evaluation, especially for relatively larger lesions^{1, 2}. However, resection of larger lesions, especially circumferential lesions, can be time-consuming and challenging. The resected tissue can obstruct the esophageal lumen, leading to limited working space and poor visibility, thereby increasing the risk of adverse events such as perforation and muscular injury³. In recent years, several auxiliary traction techniques have been emerged, including positional adjustment traction, hemostatic clip elastic band traction, snare traction, line traction, and magnet anchor traction, which significantly improve the visibility of the submucosal layer during dissection and enhance the efficiency of the procedure ^4-5. Among these techniques, snare traction allows bidirectional traction through "push and pull" maneuvers, offering flexibility and practicality in clinical practice. However, due to the difficulty and limited cases of circumferential esophageal ESD, there is currently no published literature demonstrating the advantages of snare traction-assisted ESD over traditional ESD techniques.

Aims & Methods

This study aims to investigate the efficacy and safety of snare traction assisted ESD for the management of circumferential superficial esophageal cancer. A total of 68 patients who underwent ESD for circumferential superficial esophageal cancer were included in this study. All the patients were divided into two groups based on whether the snare traction was used or not; the snare traction group (S-ESD, group n=35) and the control group (C-ESD, group n=33).

Results

There was no significant difference in the size of the resected area between the groups [21.98 (18.30, 27.00) cm² vs 24.00 (15.28, 30.72) cm², P=0.976]. The snare traction group had a shorter dissection time [92.00 (74.00, 121.00) min vs 110.00 (92.50, 137.00) min, P=0.017] and a faster resection speed [0.28±0.13 cm²/min vs 0.22±0.11cm²/min, P=0.040] compared to the control group. There were no statistically significant differences between the two groups in terms of hospital stay, cost, en bloc resection rate, R0 resection rate, curative resection rate，bleeding rate, perforation rate, stricture rate, and recurrence rate (P>0.05).

Conclusion

Snare traction-assisted ESD is a safe and efficient approach for the treatment of circumferential superficial esophageal cancer. Its advantages includes shorter procedure so the anesthesia requirement, clear operative filed view, improved mucosal dissection efficiency, simple, and easily accessible equipment.

References

1 Ishihara R, Arima M, Iizuka T et al. Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer. Dig Endosc. 2020; 32: 452-93.
2 Draganov PV, Wang AY, Othman MO, Fukami N. Aga institute clinical practice update: Endoscopic submucosal dissection in the united states. Clin Gastroenterol Hepatol. 2019; 17: 16-25.e1.
3 Zhang W, Zhai Y, Chai N et al. Endoscopic submucosal tunnel dissection and endoscopic submucosal dissection for large superficial esophageal squamous cell neoplasm: Efficacy and safety study to guide future practice. Surg Endosc. 2018; 32: 2814-21.
4 Fukami N. What we want for esd is a second hand! Traction method. Gastrointest Endosc. 2013; 78: 274-6.
5 Jin P, Yu Y, Fu KI, Yu DL, Li AQ, Sheng JQ. A new traction method with use of the snare as a "second hand" during endoscopic submucosal dissection. Endoscopy 2015; 47 Suppl 1 UCTN: E286-7.

Introduction

Oesophageal ulceration (OU) is a frequent finding at oesophago-gastro-duodenoscopy (OGD). Despite limited data on the benefit of a repeat endoscopy, current guidelines recommend a follow-up OGD after six weeks to exclude underlying malignancy¹.

Aims & Methods

Aims: We aimed to explore the utility of a follow-up endoscopy after a diagnosis of oesophageal ulcer and identify predictors of oesophageal malignancy and dysplasia. Secondary aims were to estimate the environmental and financial impact of a follow-up endoscopy.
Methods: We collected demographic, endoscopy, and histology data from patients diagnosed with OU over a 5-year period (from 1^st January 2016 to 31^st December 2020 inclusive) at Leeds Teaching Hospitals NHS Trust. We collected data from the index OGD, follow-up OGD, and from their medical records up to 3 years after a diagnosis of OU at their index OGD. We examined the proportion of patients who were diagnosed with dysplasia or malignancy at follow-up or up to 3 years after their index OGD. Binary logistic regression was performed to identify predictors of oesophageal malignancy or dysplasia at index OGD, follow-up OGD, or 3 years after the index OGD. NHS national cost data for OGD, and carbon dioxide (CO2) emissions were estimated for all unnecessary follow-up OGDs^2,3.

Results

In total, 409 patients were diagnosed with OU. Of these, 33 patients were diagnosed with oesophageal cancer or dysplasia, with 30 diagnoses (90.9%) made at the index OGD and the remaining 3 (9.1%) at either the follow-up OGD or within 3 years of the index OGD. Of those 3 patients, one was diagnosed with oesophageal carcinoma, one with low grade dysplasia, and one with high grade dysplasia, all within a segment of Barrett’s oesophagus already diagnosed at the index OGD. Those who were diagnosed with oesophageal malignancy or dysplasia, compared to those who were not, were more likely to have larger ulcers (mean size (SD), mm, 15.9 (17.2) vs 9.50 (11.1), P = 0.003), endoscopic features suspicious for malignancy (69.7% vs 8.0%, P < 0.001), Barrett’s oesophagus (54.5% vs 14.4%, P < 0.001), and biopsies taken at index OGD (100% vs 64.1%, P < 0.001), and less likely to have a proton pump inhibitor prescribed (57.6% vs 86.4%, P < 0.001) after the index OGD. Following logistic regression controlling for all data, those with endoscopic features suspicious for malignancy (OR = 45.9; 95% CI 10.3 to 204) and those with Barrett’s oesophagus at index OGD (OR = 5.29; 95% CI 1.56 to 18.0) were more likely to be diagnosed with oesophageal cancer or dysplasia up to 3 years after the index OGD. A total of 376 unnecessary OGDs were undertaken over a 5-year period, the costs of which were estimated at £140, 248 and 10.6 tonnes of CO2 emissions.

Conclusion

Repeat OGD to exclude underlying malignancy following a diagnosis of oesophageal ulcer may only be required in those with endoscopic features suspicious for malignancy and those with Barrett’s oesophagus. Larger prospective multi-centre studies, with cost and carbon footprint analyses, are required to confirm our results and to inform guidelines.

References

1. Beg S. et al. (2017). Quality standards in upper gastrointestinal endoscopy: a position statement of the British Society of Gastroenterology (BSG) and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS), Gut, 66(11):1886-1899. DOI: 10.1136/gutjnl-2017-314109
2. NHS (2023): National tariff payment system documents, annexes and supporting documents. Available at: https://www.england.nhs.uk/publication/national-tariff-payment-system-documents-annexes-and-supporting-documents/
3. Lacroute, J. et al. (2023), The carbon footprint of ambulatory gastrointestinal endoscopy, Endoscopy, 55(10): 918–926. DOI: 10.1055/a-2088-4062

Introduction

Oesophageal squamous cell carcinoma (OSCC) represents approximately 90% of the nearly half-million annual cases of oesophageal cancer globally. The invasiveness and high costs associated with traditional upper endoscopy limit its use in the routine surveillance of at-risk populations, including individuals with a history of head and neck cancer (HNC). Previous data suggest that copy number abnormalities (CNAs) are a feature of OSCC development.

Aims & Methods

This study explored the efficacy of shallow whole-genome sequencing (sWGS) to detect genome-wide CNAs in cells collected using a non-endoscopic sponge pan-oesophageal sampling device. Our objective was to develop and validate a predictive model for the early detection of oesophageal squamous dysplasia and neoplasia, aiming to improve disease prognosis through timely intervention.
We prospectively collected oesophageal specimens from 178 participants using the Cytosponge device as part of the EDEN and OSCAR projects: OSCC (n = 24), high-risk individuals (n = 61), and healthy controls with dyspeptic symptoms (n = 93). The samples underwent 1.5-2x sWGS as well as H&E staining for atypia assessment and p53 immunohistochemistry (IHC) which were performed by two gastrointestinal (GI) pathologists who were blinded to the reference endoscopic diagnoses. Through penalised regression analysis, we identified significant CNAs indicative of dysplasia or early neoplasia. These critical genomic insights were then used to develop and refine a logistic regression model aimed at predicting dysplasia or early neoplasia in cytosponge-derived specimens. The predictive accuracy of the model was subsequently confirmed through validation against sWGS in microdissected ESD samples which represented known pathological states.

Results

Key genomic indicators for oesophageal squamous dysplasia and early neoplasia were identified, including significant CNAs in chromosome arms chr2q, chr3q, chr9p, and chr11q along with the Genome-Wide Instability Score (GWIS), a percentage-based metric quantifying genomic instability across the genome. Our logistic regression model, which integrated these genomic biomarkers, achieved an Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.947, with sensitivity and specificity rates of 89% and 88.2%, respectively. This model outperformed another that utilised only pathological data (definite squamous atypia and p53 IHC), which achieved an AUROC of 0.880, with a sensitivity and specificity of 83.6% and 84.6%, respectively. However, when pathological data were combined with the genomic indicators, the diagnostic performance of our model improved significantly, resulting in an AUROC of 0.969 with enhanced sensitivity and specificity of 95.9% and 90.5%, respectively. Further validation of the genomic model against microdissected ESD samples with known pathological states reinforced its robustness, achieving an AUROC of 0.879, which improved to 0.905 when low grade dysplasia (LGD) samples were excluded, highlighting the diagnostic challenges and variability in LGD classification.

Conclusion

The integration of shallow whole-genome sequencing with non-endoscopic sponge sampling has the potential for the early detection of OSCC. This approach is particularly valuable in high-risk populations and settings where traditional endoscopy is impractical.

Introduction

Crohn’s disease (CD), a variant of inflammatory bowel disease, is a complex, debilitating, chronic and relapsing disorder of the gastrointestinal tract. If poorly controlled, patients are at risk of intestinal obstruction and infection due to the formation of strictures, fistulae and narrowing of the intestinal lumen, often requiring surgical intervention. As the precise aetiology remains unclear, current treatments for CD are limited. An altered composition of native gut microbiota may play a role in CD pathogenesis, with recent faecal microbiota transplantation (FMT) studies revealing variable therapeutic efficacy in CD management. Orally administered Emu Oil, derived from Emu adipose tissue, has demonstrated anti-inflammatory and reparative properties in models of intestinal disease.

Aims & Methods

The current study aimed to determine whether Emu Oil-modulated FMT could reduce disease severity and modulate the gut microbiota in a mouse model of trinitrobenzene sulfonic acid (TNBS)-induced Crohn’s-like colitis. Female ARC(s) mice were assigned to FMT donor (n=5/group) and recipient (n=10/group) groups. Donor mice were orally administered either Water (80μl), Olive Oil (OO) or Emu Oil (160μl) daily (days -7 to 0); fresh faeces were collected (days -1 to 3) and pooled per group. Recipient mice were administered TNBS (3mg; day 0) and donor faecal supernatant (120μl; day 3) intrarectally and euthanised on day 6. Daily bodyweight and disease activity index (DAI), colonoscopically-assessed disease severity, organ weights, intestinal permeability (fluorescein isothiocyanate [FITC]-dextran uptake), histologically-assessed colonic damage (disease severity, crypt depth), intestinal barrier function (mucin-secreting cells), acute inflammation (myeloperoxidase [MPO]) and faecal microbiome (16S rRNA amplicon sequencing) were assessed. p<0.05 was considered statistically significant.

Results

TNBS induced bodyweight loss in all groups, which normalised to day 0 values on the final day of the experimental period. Daily DAI remained elevated throughout the trial in all groups; only Emu Oil FMT normalised DAI on day 6 compared with day 0 (p<0.05). TNBS increased colonoscopically-assessed disease severity scores (p<0.05), with no significant Emu Oil nor OO FMT effect. Emu Oil FMT decreased liver weights and increased small intestinal weights relative to bodyweight, reduced histologically assessed disease severity and increased colonic mucin counts compared with Water and OO FMT (p<0.05). The most abundant genera across all groups were Muribaculaceae, Eisenbergiella and Bacteroides; while alpha and beta diversity, taxonomic profiles, FITC-dextran, crypt depth and MPO activity remained unchanged in all treatment groups (p>0.05).

Conclusion

Emu Oil-modulated FMT improved histologically-assessed indicators of intestinal disease and barrier function, compared with Water FMT and OO FMT. Interestingly, Emu Oil-modulated FMT affected liver and small intestinal organs weights, suggesting a systemic effect in this setting of disease. Importantly, key genera across taxonomic profiles were identified, however, the microbiome and remaining disease indicators were largely unchanged between treatments. Overall, Emu Oil-modulated FMT demonstrates therapeutic potential in CD management. Future studies would benefit from a deeper assessment of the gastrointestinal microbiome through long-read whole genome sequencing to further determine the role of the microbiome in EO FMT efficacy compared with conventional FMT.

Introduction

The interplay of race and gender significantly influences the manifestation of Gastroesophageal Reflux Disease (GERD) symptoms following Helicobacter pylori (H. pylori) treatment. This multifaceted relationship, deeply rooted in biological, cultural, and socioeconomic factors, presents a complex medical challenge. Understanding these disparities is crucial for tailoring effective treatment strategies, ensuring equitable healthcare outcomes, and advancing personalized medicine in managing GERD symptoms in diverse populations post-H. pylori eradication

Aims & Methods

Our research, spanning 2009 to 2023, retrospectively analyzed patients treated for H. Pylori, ensuring a minimum one-year follow-up. We collected data encompassing comorbidities, insurance status, and socioeconomic factors, particularly targeting the emergence of GERD symptoms, Esophagitis, and duodenal ulcers, identified using CPT and ICD codes. Initially, we employed a Chi-square test of independence to evaluate the association between race and GERD symptoms. We conducted a post-hoc analysis with adjusted standardized residuals to delve deeper, pinpointing specific races with notably higher or lower GERD symptom frequencies than expected. We performed pairwise race comparisons via Chi-square tests, applying a Bonferroni correction for multiple comparisons.

Results

Between 2009 and 2023, 4,205 patients received H. Pylori treatment, with 3,329 qualifying for our study after excluding those lost to follow-up. The average age was 54.5 years, with 64% female (2,134) and 48% Caucasian (1,664). The Chi-square test revealed a significant association between Race and GERD symptoms (Chi sq stat:8.69 p-value <0.01). In-depth post-hoc pairwise comparisons showed that the Hispanic race had significantly higher rates of GERD symptoms when compared to other races Other races (p <0.01), White (p <0.01), Black (p <0.01), and Asian races (<0.01). Adjusted residual analysis further confirmed that the Hispanic race (5.54, p<0.023) showed a higher-than-expected number of GERD symptom cases. Among the Hispanic races, Patients with low socioeconomic status showed increased GERD symptoms (Chi. Sq: 7.65, P<0.01). Gender does not significantly impact GERD symptoms (Chi. sq: 0.831, P = 0.512)

Conclusion

Our study, analyzing data from 2009 to 2023 on patients treated for H. Pylori, underscores the significant influence of race and gender on GERD symptoms post-treatment. Notably, the Hispanic population exhibited a higher incidence of GERD symptoms compared to other races, with socioeconomic status further intensifying this trend. These findings highlight the need for more personalized, culturally sensitive approaches in healthcare, emphasizing the importance of considering race, gender, and socioeconomic factors in the treatment and management of GERD following H. Pylori eradication.

References

Lai Y, Shi H, Wang Z, Feng Y, Bao Y, Li Y, Li J, Wu A. Incidence trends and disparities in Helicobacter pylori related malignancy among US adults, 2000-2019. Front Public Health. 2022 Nov 28;10:1056157. doi: 10.3389/fpubh.2022.1056157. PMID: 36518580; PMCID: PMC9743990.