Introduction

Bismuth quadruple therapy (BQT) including bismuth, a proton pump inhibitor (PPI) and two antibiotics has been shown to be a very effective treatment for Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. Bismuth prescriptions seem to be increasing in recent years.

Aims & Methods

To describe the use, effectiveness, and safety of BQT in Europe and the evolution of prescriptions as part of the European Registry on Helicobacter pylori management (Hp-EuReg).

All patients who had received BQT in a 9-year period were included. The thirty-one countries participating in the Hp-EuReg been clustered in previous studies in five main regions based both on their geographical situation and the gross domestic product per capita (North, Centre, Est, South-Est, South-West). Data on the prescribed schedules, previous eradication attempts, effectiveness and the incidence of adverse events was analysed. A time trend analysis of the different BQT treatment prescriptions was likewise performed. Effectiveness was defined by a modified intention-to-treat (mITT) analysis. A multivariate analysis was performed to determine the variables predicting treatment effectiveness.

Results

Of the 49,690 patients included in the Hp-EuReg, 15,582 (31%) had received BQT. BQT use increased from 8.6% to 39% during the study period. Forty-six different schedules were used, of which 8 were administered to more than 100 patients. Single-capsule BQT (ScBQT) containing bismuth, metronidazole and tetracycline plus a PPI was the most used therapy (43%). In naïve patients, the following BQTs obtained over 90% effectiveness: those using tetracycline and metronidazole, either drugs prescribed separately for 14 days, or as 10-day ScBQT; and those using amoxicillin either with clarithromycin or metronidazole, both for 14 days. ScBQT was the only schedule achieving optimal cure rates in all the geographical areas. Standard- or high-dose PPIs, prescriptions of 10-14 days and the schedule type are significantly related to higher cure rates in the multivariate analysis.



Table.Predictive factors of treatment effectiveness in multivariate analysis

Conclusion

The use of BQT has increased progressively in the last decade.10-Day ScBQT or 14-day BQT schedules achieved an effectiveness over 90% in Europe.

Disclosure

Prof. J. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen.

Introduction

Computer Aided Detection (CADe) systems may improve detection of (pre-)malignant lesions by endoscopists. Most CADe systems are developed using homogeneous datasets collected by experts, which do not represent the heterogeneous imaging conditions of daily clinical practice. Such heterogeneity is caused by endoscopist-dependent variation (e.g. skill and experience) as well as endoscopist-independent variation (e.g. endoscopy equipment). Recently, we presented a CADe system for Barrett’s neoplasia¹. However, all training and test data originated from expert centers.

Aims & Methods

We aimed to develop an updated CADe system (CADe 2.0) demonstrating more robustness to the varied imaging conditions found in routine patient care.
Our previously published CADe system (CADe 1.0) was trained and internally validated on a high-quality dataset originating from 15 expert centers. The dataset included 6.337 neoplastic (1.362 patients) and 7.695 non-dysplastic images (1.139 patients).
The updated CADe system (CADe 2.0) underwent four improvements. First, we included more heterogeneous training data from our training set patient population. We extracted video frames from videos comprising various quality artefacts (e.g. blurred lenses or insufficient mucosal cleaning). Second, we applied advanced data augmentation methods to address the diversity of post-processing enhancement settings used by modern endoscopy systems. Third, we updated the CADe system with a Vision Transformer architecture², which has shown to improve performance on lower quality endoscopic images³. Finally, we transitioned our pretraining approach from semi-supervised to a self-supervised learning framework⁴.
Both CADe systems were evaluated using three prospectively collected, independent test sets. The first test set represented the true diversity and complexity encountered in daily clinical practice. This dataset comprised all videos captured from all included patients in five referral centers between April 2022 and January 2024 (431 ten-second BE videos from 115 patients). The second test set focused on endoscopist-dependent variation. It included three paired subsets with high, moderate and low-quality images from 122 patients. Quality was determined by factors such as esophageal expansion and mucosal cleaning. The third test set addressed endoscopist-independent variation. It contained 16 paired subsets of 396 images (122 patients). Every subset was based on a different post-processing enhancement setting of the endoscopy system.

Results

For test set 1, CADe 1.0 reached a sensitivity and specificity of 84% and 73%. CADe 2.0 scored 93% and 76%. For test set 2, CADe 2.0 reached higher sensitivity and specificity scores on high-quality images compared to CADe 1.0. In addition, CADe 2.0 performance loss on moderate and low-quality images was smaller. On test set 3 CADe 1.0 scores substantially varied depending on the test sets enhancement setting (82-94% sensitivity, 52-83% specificity). Variation of CADe 2.0 was limited to 91-95% and 81-88%.

Table 1. Results of CADe 1.0 and CADe 2.0

Conclusion

The updated CADe system displayed improved performance for detection of Barrett’s neoplasia in videos. More importantly, this CADe system also displayed less performance loss when exposed to lower image quality and less performance variability when confronted with differing post-processing enhancement settings.

References

1. Fockens N, Jong MR, Jukema JB, Pouw RE, Duits LC, Van Munster SN, et al. A deep learning system for detection of early Barrett's neoplasia: a model development and validation study. The Lancet Digit Health. 2023;5:905-21.
2. Yu W, Si C, Zhou P, Luo M, Zhou Y, Feng J, et al. MetaFormer Baselines for Vision2022 October 01, 2022:[arXiv:2210.13452 p.]. Available from: https://ui.adsabs.harvard.edu/abs/2022arXiv221013452Y.
3. Kusters CHJ, Boers TGW, Jaspers TJM, Jukema JB, Jong MR, Fockens KN, et al., editors. CNNs vs. Transformers: Performance and Robustness in Endoscopic Image Analysis. Applications of Medical Artificial Intelligence; 2024 2024//; Cham: Springer Nature Switzerland.
4. Caron M, Touvron H, Misra I, Jégou H, Mairal J, Bojanowski P, et al. Emerging Properties in Self-Supervised Vision Transformers2021 April 01, 2021:[arXiv:2104.14294 p.]. Available from: https://ui.adsabs.harvard.edu/abs/2021arXiv210414294C.

Introduction

Endoscopic or percutaneous bile duct brushing is often performed as first step to differentiate between benign and malignant biliary strictures. Although brush cytology has a high specificity (95-100%), the sensitivity for detection of malignancy has been reported to be poor (41-67%).(1-4) This results in repeated diagnostic procedures with potential treatment delay, adverse events, and additional costs.

Aims & Methods

Aim of this study was to evaluate a change in protocol for brush cytology with optimization of handling and rating, Next Generation Sequencing (NGS), and the use of two brushes plus intraductal biopsies in patients with suspected perihilar or intrahepatic cholangiocarcinoma (pCCA/iCCA). Patients with suspicion of pCCA or iCCA were prospectively included between June 2021 and December 2023. Preferably two brushes and 2-4 intraductal fluoroscopy guided biopsies were taken during the initial procedure. Cells were dislodged in a Cytolyt container within 30 seconds of which two ''thin prep'' slides were prepared. Double reading was routinely performed by at least two expert cytopathologists. NGS was performed in samples with an uncertain diagnosis of atypia. A historical cohort (January 2017-June 2021) was used as control. In this cohort a single brush was performed without intraductal biopsies. The obtained cells were preserved in a Roswell Park Memorial Institute (RPMI) 1640 medium of which four cytospins were done. Double reading and NGS were not routinely performed. In both cohorts morphological diagnosis was assessed according to the Papanicolau society of cytopathology system for reporting pancreatobiliary cytology. Both the diagnostic category ‘suspicious for malignancy’ and ‘malignant’ were classified as results compatible with malignant disease. Final diagnosis was confirmed by either histological proof of malignancy or in case unavailable, follow-up compatible with malignant disease. Primary endpoint was the sensitivity before and after implementation of the protocol; secondary endpoints were the sensitivity of the individual steps of the modified protocol in the prospective cohort e.g. the sensitivity of only the first brush and additional value of NGS, the second brush, and intraductal biopsies.

Results

In this study, a total of 167 patients were evaluated (51 prospectively and 116 historical controls). The final diagnosis was malignant disease in 153 patients (91.6%). After implementation of the protocol, the sensitivity rose to 86% (95%CI, 72.6-93.7%) versus 48.5% (95%CI, 38.7-58.5%) prior to implementation (difference 37.5%; 95%CI, 22.3-52.6%). Specificity was 100% in both groups (1/1 vs 13/13). Sensitivity of the first brush in the prospective cohort was 76% (95%CI, 61.5-86.5%). NGS was of additional diagnostic value in 3 patients with uncertain brush cytology results, increasing the sensitivity to 82% (95%CI, 68.1-91%). A second brush was performed in 37 patients; in one of these patients, the second brush had additional diagnostic value over the first brush. Intraductal biopsies were performed in 26 patients (4 benign, 9 suspicious of malignancy, 13 malignant), leading to a malignant diagnosis in 2 out of 12 patients with false-negative brush cytology.

Conclusion

A modification in the handling of cytopathology, led to a significant improvement in the sensitivity of bile duct brushes to 76% for patients with suspected pCCA or iCCA. Furthermore, adding NGS, use of two brushes, and intraductal biopsies in the initial procedure could further increase sensitivity to 86%.

References

1. Mehmood S, Loya A, Yusuf MA. Biliary Brush Cytology Revisited. Acta Cytol. 2016;60(2):167-72.
2. Kobayashi M, Ryozawa S, Araki R, Nagata K, Tanisaka Y, Fujita A, et al. Investigation of Factors Affecting the Sensitivity of Bile Duct Brush Cytology. Internal Medicine. 2019;58(3):329-35.
3. Volmar KE, Vollmer RT, Routbort MJ, Creager AJ. Pancreatic and bile duct brushing cytology in 1000 cases: review of findings and comparison of preparation methods. Cancer. 2006;108(4):231-8.
4. Weber A, von Weyhern C, Fend F, Schneider J, Neu B, Meining A, et al. Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma. World J Gastroenterol. 2008;14(7):1097-101.

Disclosure

Jeska A. Fritzsche, Esmée Smit, Otto M. van Delden, Frederike Dijk, Arantza Farina Sarasqueta, Sybren L. Meijer, Anne M. Uyterlinde, Mattheus C.B. Wielenga, IJsbrand A.J. Zijlstra, and Joanne Verheij have no conflicts of interest or financial ties to disclose.
Paul Fockens performed as a consultant for Olympus and Cook Endoscopy.
Geert Kazemier reports research support and travel fees from SAS Analytics and research grants from KWF, ZonMw, Cancer Center Amsterdam Foundation, and Bennink Foundation outside the submitted research.
Heinz-Josef Klümpen performed in advisory board for Janssen, Astra-Zeneca and IPSEN, and received Speaker’s fees from CCO and MedTalks.
Cyriel Y. Ponsioen reports research grants from Gilead and Perspectum, performed as a consultant for Pliant, Takeda and Shire, and received speaker’s fees from Tillotts.
Roy L.J. van Wanrooij performed as a consultant for Boston Scientific.
Rogier P. Voermans reports research grants from Boston Scientific and Prion Medical, performed as a consultant for Boston Scientific, and received speaker’s fee from Mylan and Zambon.
All outside the submitted work.

Introduction

Eosinophilic esophagitis (EoE) is a complex disease that often coexists with different conditions. Given the complexity of this pathology, a multidisciplinary approach, with gastroenterologist, allergist, dietitian, psychologist, and endoscopist may benefit to diagnosis and management of patients, reducing time to diagnosis as well.

Aims & Methods

To evaluate impact of multidisciplinary team in diagnosis and management of eosinophilic esophagitis disease. A retrospective study was conducted to include all patients referred to Fondazione Policlinico Universitario A. Gemelli between September 2016 and April 2023. Prevalence of allergic, nutritional, and psychological disturbs was evaluated. Referral for each patient was reviewed. Diagnostic delay (time interval between first occurrence of EoE symptoms and confirmed diagnosis with endoscopy) was analyzed in patients with suspected eosinophilic esophagitis and diagnosis made in our center, compared to data reported in literature. Publications from 2014 to 2023 were reviewed.

Results

A total of 98 patients, 76 males and 22 females, with a mean age at diagnosis of 25 years, were included in the study. For all patients, each visit was conducted in team with gastroenterologist, allergist, dietitian, and psychologist. 81 patients presented allergic diseases (82 %), 51 patients (52 %) needed nutritional support by a dietitian and 63 patients (64 %) presented psychological implication by the disease to necessitate clinical support. 42 patients (43%) were referred by team members. 13 patients (13%) presented to our center with suspect eosinophilic esophagitis. For these patients, ab initio evaluated with multidisciplinary approach, mean time to diagnosis was 2.25 months. Diagnostic delay reported in literature was 3 years.

Conclusion

Multidisciplinary team is needed to manage patients with eosinophilic esophagitis because its several associated diseases. In fact, most of our patients presented allergic, nutritional, and psychological disturbs. This approach assures more appropriate medical management through shared decision making. Almost half of patients was referred by team members. Thank to awareness of each physician of the team and his early referral, we assisted in a reduction of diagnostic delay in our center compared to data reported in literature.

References

Lenti MV, Savarino E, Mauro A, Penagini R, Racca F, Ghisa M, Laserra G, Merli S, Arsiè E, Longoni V, de Bortoli N, Sostilio A, Marabotto E, Ziola S, Vanoli A, Zingone F, Barberio B, Tolone S, Docimo L, Pellegatta G, Paoletti G, Ribolsi M, Repici A, Klersy C, Di Sabatino A. Diagnostic delay and misdiagnosis in eosinophilic oesophagitis. Dig Liver Dis. 2021 Dec;53(12):1632-1639. doi: 10.1016/j.dld.2021.05.017. Epub 2021 Jun 8. PMID: 34116974
Sauer BG, West A, McGowan EC. Multidisciplinary Eosinophilic Esophagitis Care: A Model for Comprehensive Patient-Centered Care Through Shared Decision Making Between Gastroenterology, Allergy, and Nutrition. Clin Gastroenterol Hepatol. 2021 Nov;19(11):2226-2229. doi: 10.1016/j.cgh.2021.07.025. Epub 2021 Jul 16. PMID: 34280551.
Murray FR, Kreienbuehl AS, Greuter T, Nennstiel S, Safroneeva E, Saner C, Schindler V, Schlag C, Schoepfer AM, Schreiner P, Straumann A, Biedermann L. Diagnostic Delay in Patients With Eosinophilic Esophagitis Has Not Changed Since the First Description 30 Years Ago: Diagnostic Delay in Eosinophilic Esophagitis. Am J Gastroenterol. 2022 Nov 1;117(11):1772-1779. doi: 10.14309/ajg.0000000000001950. Epub 2022 Aug 12. PMID: 35971224.