Introduction

The diagnosis and follow-up of eosinophilic esophagitis (EoE) currently requires an esophagogastroduodenoscopy (EGD) with multiple esophageal biopsies. Since the follow-up of the disease is highly demanding in terms of healthcare resources, non-invasive biomarkers are needed to make the management of EoE less cumbersome.

Aims & Methods

We investigated the utility of serum Eotaxin-1, Eotaxin-2, Eotaxin-3, Interleukin (IL)-4, IL-5, and IL-10 as biomarkers for the diagnosis and monitoring of EoE in a prospective, longitudinal fashion. Consecutive adults (age>18 years) with a new diagnosis of EoE [i.e., esophageal eosinophil counts per high-power field ≥15] were prospectively enrolled. At baseline (T0), patients underwent EGD with six esophageal biopsies to diagnose active EoE, as well as blood sampling immediately after the confirmed histological diagnosis of EoE (within one week from the EGD) while off EoE-directed treatments. Following the diagnosis, EoE-directed treatment was started, and histological response was assessed after 12 weeks of treatment (T1). Serum levels of Eotaxin-1, Eotaxin-2, Eotaxin-3, IL-4, IL-5, and IL-10 were assessed at T0 and at T1. Baseline clinical data were recorded for each EoE patient. Age-, Sex-, and atopy-matched subjects were used as healthy controls (HC). Kruskal-Wallis Rank Sum Test and Pearson’s Chi-squared were used for comparisons as appropriate. ROC curve analysis was used to calculate the diagnostic accuracy (AUC) of the biomarkers. Significance threshold was p<0.05.

Results

We enrolled 25 patients with active EoE and 14 HC, which were comparable in terms of age, sex, and atopy. At baseline (T0), patients with active EoE had significantly higher serum levels of eotaxin-3 compared to HC (501 pg/mL vs 224 pg/mL; p=0.002) and of IL-10 (100 pg/mL vs 56 pg/mL; p=0.01), while other biomarkers were not statistically different between active EoE and HC. Based on ROC curve analysis, a value of 389 pg/mL of etaxin-3 had AUC of 0.80 for the diagnosis of EoE with 93% specificity. A value of 168 pg/mL of IL-10 had AUC of 0.74 for the diagnosis of EoE with 100% specificity. Following treatment (T1), remission of EoE was achieved by 18/25 (72%) of EoE patients taking budesonide orodispersible tablets or PPIs. At T1, patients with EoE in histological remission had significantly lower serum levels of eotaxin-3 (252 pg/mL vs 501 pg/mL; p=0.02) and of IL-10 (67 pg/mL vs 100 pg/mL; p<0.05) compared to T0. A cut-off value of 241 pg/mL of eotaxin-3 had AUC of 0.7, and a cut-off value of 199.5 of IL-10 had AUC of 0.68 for the identification of histological remission at T1 (Table 1).

Conclusion

Serum Eotaxin-3 and IL-10 are promising non-invasive biomarkers for the diagnosis of EoE with high specificity. In addition, Eotaxin-3 and IL-10 can monitor therapeutic response in patients with EoE.

Introduction

The available evidence on the epidemiology of acute pancreatitis (AP) is primarily based on older studies conducted in other countries, limiting its applicability to local settings. This study aims to provide updated data on the clinical characteristics and outcomes of patients with AP in our region thereby improving understanding and management of the disease.

Aims & Methods

A retrospective analysis was conducted on a prospective database comprising a cohort of 526 patients with acute pancreatitis (AP), consecutively included between March 2017 and June 2019 at a tertiary care hospital. Systematic laboratory testing was performed at admission and again at 48 hours. Clinical management followed standard practice guidelines, including routine abdominal ultrasound after admission and abdominal CT scan in cases of diagnostic uncertainty, clinical deterioration, or lack of improvement. Diagnosis and classification were based on the revised 2012 Atlanta classification.

Results

The most frequent etiology of AP in our setting was biliary lithiasis (65.9%), followed by idiopathic (15.4%) and alcohol-related causes (8.4%). Severe AP accounted for 9% of cases, while 14.3% were classified as moderately severe. Up to 20.2% of patients developed local complications; however, only 4.9% presented with pancreatic necrosis. SIRS was observed in 18.7% of patients at admission, decreasing to 8.7% at 48 hours. Only 3.7% of patients required ICU admission (Table 1). Factors such as smoking, ERCP, antibiotic therapy, acute cholangitis, and SIRS showed significant differences across different etiological groups.

Conclusion

Acute pancreatitis (AP) is a common condition that imposes a significant healthcare burden. Determining the etiology of AP at admission is important not only from an epidemiological standpoint but also due to its profound implications for patient prognosis.
Contrary to what has been reported in the literature, the second most frequent cause of AP in our cohort was idiopathic, surpassing alcohol-related cases. In line with other studies, we observed significant differences between biliary and alcohol-related etiologies regarding smoking habits, development of acute cholangitis, need for ERCP, and use of antibiotic therapy. Patients with alcohol-related AP were significantly more likely to present with SIRS at admission. However, we did not find statistically significant differences in other key clinical outcomes, although patients with alcohol-related AP appeared to have a higher, but not statistically significant, risk of developing local complications, pancreatic necrosis, and SIRS at 48 hours.
This study highlights the importance of tailoring management strategies according to etiology to optimize clinical outcomes.

References

1. Wang, G. J., Gao, C. F., Wei, D., Wang, C., & Ding, S. Q. (2009). Acute pancreatitis: etiology and common pathogenesis. World journal of gastroenterology, 15(12), 1427–1430.
2. Petrov, M. S., & Yadav, D. (2019). Global epidemiology and holistic prevention of pancreatitis. Nature reviews. Gastroenterology & hepatology, 16(3), 175–184.
3. Iannuzzi, J. P., King, J. A., Leong, J. H., Quan, J., Windsor, J. W., Tanyingoh, D., Coward, S., Forbes, N., Heitman, S. J., Shaheen, A. A., Swain, M., Buie, M., Underwood, F. E., & Kaplan, G. G. (2022). Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis. Gastroenterology, 162(1), 122–134.

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

Accurate estimation of cancer risk in patients with Barrett’s esophagus (BE) and low-grade dysplasia (LGD) or indefinite for dysplasia (ID) is difficult, leading to potential under- and over-treatment. We aimed to evaluate the utility of machine learning (ML) and copy number alterations (CNAs) assessed by shallow whole genome sequencing (sWGS) on standard formalin-fixed paraffin-embedded (FFPE) samples for precise risk stratification in this group of BE patients.

Aims & Methods

We conducted a retrospective analysis on a cohort of 164 BE patients encompassing 990 tissue samples with sWGS (~0.4X) data from 2001-2018. These included 215 samples with LGD or ID from 64 patients, of which 38 progressed to high-grade dysplasia (HGD) or cancer at later timepoints (P), and 26 who did not progress (NP). CNAs were quantified using QDNASeq, and outlier bins were determined by Tukey's fences. Subsequently, the CNAs of 64 esophageal cancer driver genes were compared between P and NP groups using t-tests and ranked by p-values. A random forest (RF) ML model was developed on the CNAs of the 64 genes, employing nested 5-fold cross-validation split by patients and iterated 100 times to mitigate bias. The model's performance was compared against routine p53 immunohistochemistry (IHC), a decision tree that incorporates p53 followed by the ML model, and the current ESGE clinical guideline recommending treatment after LGD is identified in two endoscopies. Both the model and model+p53 were assessed across 100 test sets derived from the cross-validation. The guideline's performance was evaluated using a historical extended cohort comprising 253 LGD patients, of which 32 progressed, and underwent at least one surveillance endoscopy after LGD diagnosis and before HGD/cancer diagnosis. According to the guideline, two occurrences of LGD result in a positive prediction.

Results

Significant variance was observed in the distribution of relative CNAs across genomic bins between P- and NP-LGD/ID samples, with the proportions of outliers at 2.15% (95% CI: 1.88%, 2.42%) vs. 1.35% (95% CI: 1.26%, 1.44%). The most divergent genes included TP53, ABCB1, MET, BRAF, and SIN3A, exhibiting higher CNAs in progressed samples. Among the 215 samples, the RF model achieved an average sensitivity of 73.4% and specificity of 80.2%. Of these, 160 samples were tested for p53 IHC staining, where p53 alone showed a sensitivity of 22.1% and specificity of 100%, and a combined analysis of p53 and model increased the sensitivity of model alone (81.5% vs. 78.1%, p<0.001) while maintaining the same specificity at 78.9%. As a benchmark, the performance of the current ESGE guideline on biopsy diagnosed LGD patients demonstrated a sensitivity of 75.0% and specificity of 59.6%.

Conclusion

Our findings affirm the utility of ML and CNAs in predicting progression in BE patients with LGD or ID. Incorporating p53 followed by ML can further improve the performance. Molecular biomarkers would allow anticipation of intervention in high-risk cases and reduction of overtreatment in low-risk cases.

Disclosure

Nothing to disclosure.

Introduction

Globally, there is no standardized approach to sedation during endoscopic procedures, leading to variability in practices both regionally and across institutions. Sedation plays a crucial role in alleviating patient discomfort and ensuring the safety of endoscopic examinations and treatments. However, it occasionally leads to paradoxical reaction, which can adversely affect the outcomes of these procedures. As of 2023, in Japan, choice of sedatives and frequency of their use, and the incidence and management of paradoxical reaction during upper gastrointestinal endoscopy remain unclear.

Aims & Methods

This study is aimed to delineate the frequency and types of sedatives used in upper gastrointestinal endoscopy across different medical facilities in Japan and to investigate the extent of anesthesiologist involvement and the incidence and handling of paradoxical reactions. An anonymous online survey was distributed from November 28 to December 13, 2023, through mailing lists reaching about 2,500 gastroenterologists and endoscopists.

Results

The survey received responses from 635 participants including 418 hospital-based endoscopists, 118 clinic-based endoscopists, and screening 29 facility-based endoscopists. Sedation performed by anesthesiologists was found to be rare, with only 3.5% of examinations and 7.1% of treatments being managed by anesthesiologists once a week or more. 87% of respondents reported not using anesthesiologistsmanaged sedation at all for examinations, and 61% reported the same for treatments. Regarding the frequency of sedation use during examinations, 9.8% of respondents reported using sedation in over 95% of cases, and 53% reported using it in more than half of the cases. 6.6%, reported not using sedation at all. In treatments, 86% of respondents used sedation in over 95% of cases, and 96% used it in more than half of their cases.

Midazolam was the most common sedative for examinations (n=593), chosen in over 80% of cases by 54% of respondents, while only 9.9% never selected it. Meperidine was frequently used by 10% of respondents in similar proportions. Other sedatives like flunitrazepam, diazepam, and propofol were selected by 5.0%, 3.5%, and 2.5% of respondents, respectively.

For treatments (n=401), midazolam was again the most frequently chosen, selected in over 80% of cases by 72% of respondents. Other commonly used sedatives were meperidine and pentazocine, selected in over 80% of cases by 29% of respondents, with propofol and dexmedetomidine each chosen by 12%.

64% of endoscopists who use sedative drugs experienced difficult cases to continue procedures due to paradoxical reactions, with a median incidence of 5% of cases and median of two cases are required to discontinue procedures. Midazolam was the most common cause, reported by 91% of respondents, followed by flunitrazepam (13%), diazepam (8.8%), and propofol (8.3%). The typical response involved physically restraining the patient with multiple staff members' assistance. Eighteen percent of respondents did not use antagonist drugs for examinations, and 22% for treatments.

Conclusion

In Japan, over half of upper gastrointestinal procedures used sedation, with 53% in diagnostics and 96% in treatments predominantly using midazolam. Additionally, 64% of physicians experience difficulties with paradoxical reactions during procedures under sedation by themselves.. These reactions are recognized as significant challenges that must be addressed in the management of sedation for upper gastrointestinal endoscopy.

Introduction

High-risk human papillomavirus (hr-HPV) has been associated with a subset of Barrett’s dysplasia (BD) and oesophageal adenocarcinoma (OAC).^1,2,3,4 The L1 major capsid protein has been closely linked to disease regression and is a prognostic factor in HPV driven cancers of the cervix and anus.​^5,6​​​​ The progression of cervical intraepithelial neoplasia to invasive cancer is accompanied by a loss of viral L1 capsid protein expression.

Aims & Methods

Thus, in a retrospective, cross-sectional study, we investigated L1 protein expression in HPV-positive patients representing the oesophageal squamous (controls) [Group1]-Barrett’s metaplasia [Group 2]-low-grade dysplasia [Group 3]-high-grade dysplasia [Group 4]-adenocarcinoma [Group 5] sequence. L1 protein immuno-histochemical staining was correlated with p16 overexpression and E6/E7 mRNA in-situ hybridization. The association between the 5 patient groupings and L1 expression was analysed using the Chi-square test. Multivariable logistic regression was undertaken to investigate the above association with adjustment of potential confounders (age, gender, BMI, ever smoked and excess alcohol). Adjusted odds ratio (95% CI) was calculated.​​​​​

Results

^​​​​​​Of 116 HPV DNA-positive patients [(age range: 19-90, mean (SD), 63.2 (13.5)], 88 males and 28 females), 73 (62.9%) were genotype 16, 37 (31.9%) genotype 18 and 6 (5.2%) were genotype 6. L1 nuclear staining was observed in 64 individuals. L1 expression was detected in 84.9% (28/33) of controls; 94.1% (16/17) of BO patients; 50% (7/14) of LGD subjects; 38.1% (8/21) of HGD individuals and 16.1% (5/31) of OAC patients; [adjusted P < 0.0001]. Conversely, p16 was present in 9.1% (3/33) of controls, 17.7% of BO (3/17), 57.1% (8/14) in LGD individuals, 61.9% (13/21) of HGD patients and 64.5% (20/31) of OAC subjects [p<0.0001]. Corresponding figures for E6/E7 mRNA positivity was 6.1% (2/33), 23.5% (4/17), 28.6% (4/14), 38.1% (8/21) and 45.2% (14/31) respectively [p=0.008]. Expression of HPV-L1 and p16 or L1 and E6/E7 mRNA was largely mutually exclusive.

Conclusion

HPV L1 capsid expression is incrementally lost with increasing oesophageal disease severity as in viral driven anal and cervical lesions. Utility of L1 alone or in combination with p16/E6/E7 mRNA in stratifying HPV-positive oesophageal lesions for treatment should be further explored.

References

1. Rajendra S, Wang B, Snow ET, et al. Transcriptionally active human papillomavirus is strongly associated with Barrett’s dysplasia and esophageal adenocarcinoma. Am J Gastroenterol 2013;108:1082–1093.
2. Rajendra S, Yang T, Xuan W, et al. Active human papillomavirus involvement in Barrett's dysplasia and oesophageal adenocarcinoma is characterized by wild-type p53 and aberrations of the retinoblastoma protein pathway. Int J Cancer. 2017;141(10):2037-2049.
3. Li X, Gao C, Yang Y, et al. Systematic review with meta-analysis: the association between human papillomavirus infection and oesophageal cancer. Aliment Pharmacol Ther. 2014;39(3):270-281.
4. Rajendra, S., W. Xuan, N. Merrett, et al. Survival Rates for Patients With Barrett High-grade Dysplasia and Esophageal Adenocarcinoma With or Without Human Papillomavirus Infection. JAMA Netw Open. 2018; 1: e181054.
5. Choi YS, Kang WD, Kim SM, et al. Human papillomavirus L1 capsid protein and human papillomavirus type 16 as prognostic markers in cervical intraepithelial neoplasia 1. Int J Gynecol Cancer 2010;20(2):288-293.
6. Hernandez J, Elahi A, Siegel E, Coppola D, Riggs B, Shibata D. HPV L1 capsid protein detection and progression of anal squamous neoplasia Am J Clin Pathol 2011; 135: 436-41.

Disclosure

None