Introduction

Recent advances in endoscopic imaging have improved the diagnostic accuracy for superficial non- ampullary duodenal epithelial tumors (SNADETs). Endoscopic resection is the treatment of choice for these lesions and endoscopic mucosal resection (EMR) is the commonly used technique. Endoscopic resection with the use of a specific distal attachment (cap-assisted EMR (CEMR)) has been reported as a safe and effective method for SNADETs.¹ However, there is limited data on the technical aspects of the same. Duodenal resections have a high risk of delayed bleeding and perforation probably due to direct exposure of ulcer to biliary and pancreatic juices. Hence, appropriate closure is absolutely essential. We have previously reported safety of closure of duodenal endoscopic resections using over-the-scope and conventional clips.² We now report on the safety and efficacy of using only hemoclips for defect closure of CEMR of SNADETs.

Aims & Methods

This prospective study aimed to evaluate the safety and efficacy of using only hemoclips for closure of SNADETs resected by CEMR. 21 patients from December, 2022 to March, 2023 who underwent the procedure at our center for lesions <10mm in size were included in the study. The pimary outcome was post procedural adverse events that included the rate of delayed bleeding and perforation, and ulcer dehiscence. The secondary outcomes were en bloc and R0 resection rates, complete closure rate, number of clips used, total procedure time, and duration of hospital stay. Descriptive statistics were used to summarize the outcomes.

Results

16 males and 5 females with median age of 59(38-75) years underwent CEMR for SNADETs and closure with hemoclips only. Paris classification morphology of 67.7% lesions was 0-IIa and 33.3% lesions was 0-IIc. All lesions of median size 4(2-6) mm were successfully resected en bloc. The median specimen size was 14(12-25) mm and the median number of hemoclips used for complete closure were 7(5-11). The mean resection and closure times were 5.7+1.8 and 9.3+3.9 minutes respectively. The mean total procedure time was 14.9+4.9 minutes. Complete closure rate was 100% with no dehiscence seen on check endoscopy (done one day post index procedure). Pathology revealed 42.9% of the lesions having low grade dysplasia and 57.1% having high grade dysplasia with R0 resection rate being 100%. There was no delayed bleeding or perforation. The mean duration of post procedure hospitalization was 2.2+0.9 days.

Outcomes of closure of CEMR for SNADETs with hemoclips only

Conclusion

Our single center study is the first to demonstrate an excellent safety profile for the use of only hemoclips in closing post CEMR defects of SNADETs. It is easy to perform, requires no additional accessories, and reduces procedure time and cost compared to other available methods of closure. Furthermore, in lesions under 10mm, CEMR was effective at en-bloc resection with favorable procedure time and duration of post procedural hospital stay. Larger scale studies may be warranted to confirm this method of resection for SNADETs and safety of closure technique.

References

1. Jamil LH, Kashani A, Peter N, et al. Safety and efficacy of cap-assisted EMR for sporadic nonampullary duodenal adenomas. Gastrointest Endosc 2017; 86:666-72.
2. Ohata K, Sakai E, Suzuki Y et al. Risk factors of delayed bleeding after endoscopic resection of superficial non-ampullary duodenal epithelial tumors and prevention by over-the-scope and conventional clipping. Dig Endosc 2021; 33: 390–8.

Introduction

Upper gastrointestinal bleeding (UGIB) is associated with an unfavorable prognosis in cancer patients. In biliary tract cancers (BTCs), little is known about the occurrence of UGIB and its prognostic relevance for the course of the disease.

Aims & Methods

The aim of this study was to analyze the prevalence of UGIB in BTC patients, compare therapeutic approaches for efficacy, and identify parameters associated with survival and recurrence rates. This retrospective observational study included all patients with BTCs and UGIB, that were treated in our tertiary care hospital between 2010 and 2023.

Results

A total of 1033 patients with BTC were analyzed. 41 (4.0%) of these patients had a total of 60 bleeding events. At the time of the bleeding event, 30.8% of patients displayed symptoms of shock, and 67.5% received red blood cell transfusions. The most common causes of bleeding were tumor infiltration (24.4%), variceal bleeding (19.5%), or ulcer bleeding (14.6%). At the time of presentation, 56.4% of patients had stage IV cancer. Most patients had perihilar (39.0%) or intrahepatic (34.1%) cholangiocarcinoma. At index bleeding, endoscopic treatment was performed in 41,5% of cases, while conservative measures (53,7%) or interventional radiological procedures (4.9%) were used in the remaining cases. In cases of bleeding caused by tumor infiltration, endoscopic hemostasis was usually performed using hemostatic powder (18.8%) or clip application (12.5%). Admission to an intermediate or intensive care unit (odds ratio 6.7; 95% CI 1.5 – 33.9) as well as symptoms of shock at the time of the bleeding event (odds ratio 2.6; 95% CI 0.5 – 15.6) were risk factors of rebleeding within 14 days. In patients with UGIB due to tumor infiltration, bleeding recurred after endoscopic therapy in 33.3% of cases. With conservative therapy, the recurrence rate was 28.6%. Survival of Patients with UGIB due to tumor infiltration was significantly shorter compared with patients having non-tumor-associated UGIB (median survival 0.93 vs. 6.5 months, log-rank test p = 0.018).

Conclusion

UGIB is a rare but serious complication in patients with BTC. Patients with major bleeding episodes should be closely monitored for short-term rebleeding. The occurrence of UGIB due to tumor infiltration is associated with adverse outcomes and significantly shortened survival time.

Introduction

Among patients with celiac disease (CeD), following a gluten-free diet after diagnosis is expected to reduce symptom burden. Using a large US claims database, we compared symptoms in individuals with CeD pre- and post-diagnosis with those in matched individuals without CeD to evaluate the burden of CeD.

Aims & Methods

This case-control study was conducted among individuals of all ages enrolled in MarketScan from 2002 to 2023. CeD diagnosis (index date) was defined as ≥1 inpatient or ≥2 outpatient International Classification of Diseases (ICD)-9/-10 diagnostic codes; controls were matched (1:5 ratio) for age, sex, region, and diagnosis year. All individuals had continuous medical and pharmacy enrolment for 2 years pre- and post-index. Core CeD symptoms (abdominal pain, diarrhoea, joint pain, bloating, fatigue, and nausea) were defined as ≥1 inpatient or ≥2 outpatient ICD-9/-10 codes during each 2-year period. Unadjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression comparing CeD cases versus controls.

Results

During the 21 years of data coverage, we identified 39 814 patients with CeD and 198 961 matched individuals without CeD with similar age and sex distribution (mean age 41.6 years [standard deviation 20.1]; 70.5% female). The burden of CeD symptoms pre-diagnosis was significantly higher among patients with CeD versus controls, particularly for diarrhoea, bloating, and abdominal pain. The pre-diagnosis OR (95% CI) for abdominal pain was 5.37 (5.22, 5.52), joint pain 1.87 (1.81, 1.93), diarrhoea 11.64 (11.10, 12.20), bloating 8.64 (7.86, 9.51), fatigue 3.63 (3.48, 3.79), and nausea 5.78 (5.36, 6.24). As expected, symptom burden decreased post-diagnosis, however all symptoms (except joint pain) had an approximately twofold greater burden compared with controls, 2 years post-diagnosis: OR (95% CI) abdominal pain 2.43 (2.57, 2.30), joint pain 1.61 (1.51, 1.71), diarrhoea 2.47 (2.21, 2.76), bloating 2.47 (1.86, 3.27), fatigue 2.17 (1.98, 2.38), and nausea 2.24 (1.83, 2.74). When we evaluated symptoms only among individuals with CeD, on average symptom persistence 2 years after diagnosis occurred in 29.7% of patients while an average of 6.3% had new-onset symptoms (most commonly abdominal pain; 17.0%).

Conclusion

Claims databases were able to capture CeD symptom burden and demonstrated that patients with CeD continue to experience symptoms (including new-onset) post-diagnosis. Although a gluten-free diet might control some symptoms, there is still considerable remaining burden and some unresolved symptoms (e.g. joint pain and fatigue) or new-onset symptoms.

Disclosure

MA, SM, VG, SG, RS, DAL, IP, and NC are employees and shareholders of Takeda. BL has nothing to disclose. FZ served as a speaker for Werfen and a consultant for Takeda.

Introduction

Inflammatory bowel disease (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation of the intestines. This is accompanied by oxidative stress, which plays an important role in the pathophysiology of IBD. Oxidative stress-related biomarkers can serve as potential biomarkers for disease activity monitoring. Systemic free thiols (FT) are found to accurately reflect oxidative stress brought on by inflammation and have shown promise as a biomarker for inflammatory disease activity in IBD. However, the clinical significance of this marker warrants validation. This prospective diagnostic study aimed to compare FT to other validated biomarkers and investigate the link between FT and endoscopic disease activity in patients with IBD.

Aims & Methods

An interim analysis was conducted in 52 patients. FT were measured using a colorimetric detection method. Clinical disease activity was quantified by the Harvey-Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC. Biochemical disease activity was determined by measuring blood C-reactive protein [CRP] and fecal calprotectin [fCal] levels. Endoscopic disease activity was quantified with the Mayo endoscopic sub score for UC and the Simple Endoscopic Score (SES-CD) for CD. Serum FT levels were assessed for correlations with disease activity parameters using linear and logistic regression analyses. Discriminative capacity of FT as biomarker was assessed by calculating receiver operating characteristics (ROC) statistics.

Results

Serum FT levels demonstrated a significant inverse correlation with clinical parameters, such as the HBI (r=-0.53, p<0.05). Additionally, other inflammatory biomarkers, including CRP, exhibited a negative correlation with serum FT levels (r=-0.43, p<0.05), which were decreased in patients with active IBD . Discrimination between clinically quiescent (HBI<5) and active disease based on serum FT levels was accurate (AUC=0.80, p=0.02) with a value numerically higher than that of fCal (AUC=0.55, p=0.83). Serum FT levels did not significantly differ between biochemically quiescent and active disease based on CRP (AUC=0.69, p=0.20). Both endoscopic scores demonstrated a tendency toward negative associations with serum FT levels. Patients with moderate and severe disease activity had lower FT levels compared to those with mild disease activity (estimated marginal means [EMM] 497.2 vs 529.5 µM, p=0.43) and 447.1 vs 529.5µM , p=0.06, respectively).

Conclusion

The interim analysis of this study indicates that plasma FT levels inversely correlate with IBD activity and may surpass traditional markers like fCal in detecting disease states. Plasma FT demonstrates potential as a sensitive biomarker for both clinical and endoscopic disease activity in IBD. Further patient inclusion and longitudinal data are essential to validate FT's utility fully. Continued research could establish FT as a key tool for personalized treatment strategies, improving patient outcomes in IBD management.

Disclosure

S. Geertsema, A.R. Bourgonje., H. van Goor, G. Dijkstra, and K.N. Faber are supported by a research grant from Janssen Research & Development LLC. A.R. Bourgonje received speaker fees from AbbVie. G. Dijkstra received research grants from Royal DSM, Takeda, and Janssen Pharmaceuticals and speaker fees from AbbVie, Pfizer, Takeda, and Janssen Pharmaceuticals.

Introduction

Potential therapeutic effects of natural compounds, such as grape polyphenols, have been suggested in the prevention and treatment of mucositis induced by radiotherapy or bacterial infections. Lipopolysaccharide (LPS) significantly increases the paracellular permeability of gut epithelium downregulating the expression of tight junctions. In this study, the protective effect of proanthocyanidin-rich grape seed extract (GSE) was investigated on epithelial barrier damage and ROS production induced by LPS and ionizing radiations in an in vitro model.

Aims & Methods

GSE chemical analysis was performed by high-performance liquid chromatography (HPLC-DAD) and nuclear magnetic resonance (NMR).
Human intestinal epithelial cell line Caco-2, previously treated with LPS [10 µg/m] (pathogenic strain of Escherichia Coli 0111:B4) [1], GSE [6,25 mg/ml] and LPS + GSE, were irradiated with 10 Gy subdivided in 5 daily fractions using TrueBeam™ radiotherapy system by Varian Medical System. Epithelial barrier integrity was investigated measuring the paracellular flux of fluorescein isothiocyanate-dextran (FD-4) [1] and ROS production was assessed by adding 2′,7′-dichlorodihydrofluorescein diacetate (H2-DCF-DA) [3] using a multiplate reader (Tecan). Each experiment was performed twice in triplicates with independent controls among the three conditions.

Results

HPLC-DAD and NMR revealed a 70% content of total procyanidins in both the extract obtained from the virgin hydroalcoholic mixture and quantify 24 metabolites classified as amino acids, organic acids, classified as amino acids, organic acids, carbohydrates and miscellaneous molecules. Among them, it is interesting the presence of ascorbate, procyanidin B1 and polymeric procyanidins.
Our in vitro experiments showed a significant increased permeability was observed in LPS-treated cells over time compared to control (5.215 vs 0.3418; p<0.05), which is prevented by co-treatment with GSE (5.215 vs 0.3407; p<0.05). Irradiation significantly increased intestinal permeability over time and in a dose dependent manner compared to control both in Caco2 cells without LPS treatment (at day 5 with maximal dose of 10 Gy: 3.64 vs 0.441; p<0.05) and in LPS-treated cells (25.5 vs 2.42; p<0.05). GSE treatment significantly reduced this damage in both conditions (25.5 vs 2.04; p<0.05 and 38.87 vs 2.675; p<0.05 respectively). Moreover, LPS significantly increased ROS production in Caco2 cells (12,9 vs 104; p<0.0001) and GSE treatment significantly prevented this damage (104 vs 11.3; p<0.0001). Irradiation increased ROS production in LPS-treated cells (3056 vs 362; p<0.0001) and also in this case GSE treatment was able to reduce ROS production due to irradiation (502 vs 357; p<0.0001). this beneficial effect was observed also in LPS treated cells and then exposed to irradiation (3056 vs 681; p<0.0001).

Conclusion

In an in vitro model, GSE is able to prevent the intestinal epithelium permeability damage and ROS production induced by LPS and by ionizing radiations suggesting a potential therapeutic effect. Further studies are needed to better understand the mechanism underlying radiation-induced mucositis and the antioxidant effect of GSE in its prevention and management.

References

[1] Gori M, Altomare A, Cocca S, Solida E, Ribolsi M, Carotti S, Rainer A, Francesconi M, Morini S, Cicala M, Guarino MPL. Palmitic Acid Affects Intestinal Epithelial Barrier Integrity and Permeability In Vitro. Antioxidants (Basel). 2020 May 13;9(5):417
[2] Calabriso N, Massaro M, Scoditti E, Verri T, Barca A, Gerardi C, Giovinazzo G, Carluccio MA. Grape Pomace Extract Attenuates Inflammatory Response in Intestinal Epithelial and Endothelial Cells: Potential Health-Promoting Properties in Bowel Inflammation. Nutrients. 2022 Mar 11;14(6):1175

Introduction

The use of artificial intelligence (AI) systems for decision support has recently gained great popularity in the medicine.¹ However, recent studies have shown possible limitations emerging from the interaction between humans and AI. Among these, the term “automation bias (AB)” refers to human errors deriving from over-relying on AI’s false alarms such that the human changes a correct initial interpretation.² AB is poorly investigated in the medical field and was never tested in the gastroenterological setting.

Aims & Methods

The aim of the study was to investigate the impact of AI on human diagnostic performance in gastrointestinal endoscopy, including AB.
Ninety high-quality endoscopic videoclips (16 seconds) extracted from small bowel (SB) capsule endoscopy (N=60) and proctosigmoidoscopy (N=30) were edited with the addition of a mock AI system designed with diagnostic accuracy, sensitivity and specificity of 80%, 86% and 75%. The ground truth was settled on the agreement of 9 established experts about the presence of SB lesions with significant hemorrhagic potential according to the Saurin classification (30 videoclips), inflammatory lesions relevant for the diagnosis of SB Crohn's disease according to the Lewis score (30 videoclips) and assessing the Ulcerative Colitis (UC) Endoscopic Index of Severity (30 videos). The videoclips were randomly divided into three sessions and submitted around Europe to fully trained endoscopist, trainees and endoscopic technicians. Participants were instructed to the accuracy measures of AI annotations and scored each videoclip first without, then with AI support. Participants’ performances with and without AI were calculated. Subgroup analyses were made after stratification by participants’ experience level in each endoscopic setting and test performances.

Results

A total of 12.660 videoclips (both with and without AI) were visualized in 422 sessions (182, 118 and 122 participants completed the first, second and third session, respectively). A strong and significant difference between the respondents' performance (N=281) when they were unaided by AI (average accuracy (M)=0.78, [0.77, 0.79] and when they were supported by the AI (M=0.81, [0.80, 0.82], paired t-test, t(276)=11.2, p<0.001) was found. Size effect and the evidence in favour of a significant positive effect of AI were large, 0.67 (Cohen's D) and very large (Bayes Factor>100), respectively. Interestingly, no significant difference between trainees and specialists both in regard to their performance, either unaided, M=0.77 [0.74, 0.79] vs M=0.78, [0.77, 0.79] or aided M=0.80 [0.78, 0.82] vs M=0.81 [0.80, 0.82] and their accuracy improvement (M=0.03, [0.02, 0.05] vs M=0.03, [0.02, 0.04] (unaided t-value=-0.89, p=0.37; aided t-value=-0.69, p=0.49, difference t-value=0.54, p=0.59) were found. A strong leveller effect emerged, with low-performers improving their accuracy much more than top-performers (average improvement 5%, [0.04, 0.06] vs 1%, [0.00, 0.02], paired T test, t=6.53, p<0.001). Nine percent of the final decisions involved disregarding correct AI advice in favour of incorrect human judgment, while AB occurred in 2% of cases.

Conclusion

In this study, the application of AI to assess SB bleeding, SB inflammatory lesions, and UC activity brings significant improvement in diagnostic accuracy, with the benefit appearing to be greater in the low-performers. However, in rare cases, AI may induce diagnostic errors due to AB. Future studies directly evaluating the impact of AI in real-life clinical settings are needed to confirm these data.

References

1. Cabitza F, Campagner A, Angius R, Natali C, Reverberi C. 2023. AI Shall Have No Dominion: on How to Measure Technology Dominance in AI-supported Human decision-making. In Proceedings of the 2023 CHI Conference on Human Factors in Computing Systems (CHI '23). Association for Computing Machinery, New York, NY, USA, Article 354, 1–20. https://doi.org/10.1145/3544548.3581095
2. Reverberi, C., Rigon, T., Solari, A. et al. Experimental evidence of effective human–AI collaboration in medical decision-making. Sci Rep 12, 14952 (2022). https://doi.org/10.1038/s41598-022-18751-2