Introduction

CD is a chronic progressive disease associated with bowel damage and disability and with a globally increasing prevalence. Contemporary reports on the clinical presentation, disease outcomes, and treatment choices in newly diagnosed patients across Europe are important to inform physicians.

Aims & Methods

To describe the clinical characteristics in a contemporary European cohort of recently diagnosed CD patients. The Crohn´s Disease Cohort (CROCO) is an ongoing multicentre, European, prospective cohort study of recently diagnosed CD patients (within 12 months following diagnosis) intended to characterize bowel damage progression and disability. Herin, we report on the characteristics of CD-patients at inclusion in the study.

Results

Between Aug/21-April/24, 316 patients (58% male, 47% smoker or ex-smokers) with a median age at diagnosis of 34.4 (IQR 24.8; 49.6), were recruited from 17 centres. The median delay between symptoms onset and diagnosis was 6.5 months (IQR 2; 17.5); median disease duration at the time of inclusion was 3.9 months (IQR 1.6; 7.6); Ileal involvement (L1/L3) was reported in 86%. Overall, 15% had perianal disease and 28% had extra-intestinal manifestations, the most frequent being arthritis/arthralgia. One-third (32%) had evidence of either stricturing (B2) (17%) or penetrating (B3) (15%) phenotype; 7% had an intestinal-related surgery, and 2% perianal surgery. Fifty-nine (21%%) patients had at least one CD-related hospitalization. Median faecal calprotectin was was 236µg/g (IQR 75; 731) and median C-reactive protein was 4mg/L (IQR 1.2; 11). Regarding the therapies receiveid from diagnosis to inclusion, 54% of the patients had received systemic steroids, 18% 5ASA, 10% IM monotherapy, and 43% started biological therapy (126 anti-TNF, 6 anti-IL 12/23 and 3 anti-integrin).

Conclusion

In this prospective cohort of newly diagnosed CD-patients, more than one-third of the patients presented with a complicated phenotype despite a short delay between onset of symptoms and diagnosis. Steroids remain frequently used, however early and effective therapy was started in approximately in 40% of patients, highlighting the changing paradigm in CD treatment.

Disclosure

JB: Reports grants and personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring, personal fees from Galapagos, outside the submitted work. NA: received speaker fees from Ferring and Janssen. PE: educational grants Jannsen; SV: Speaker fees from Abbvie, Ferring, Janssen Takeda. IR-L: has received financial support for travelling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Celltrion, Chiesi, Danone, Dr. Falk Pharma, Ferring, Faes Farma Janssen, Galapagos, MSD, Otsuka Pharmaceutical, Pfizer, Roche, Takeda, and Tillotts Pharma. IO: has served as speaker and/or consultant and has received educational funding from MSD, Abbvie, Pfizer, Takeda, Janssen, Faes Farma and Chiesi, and has received research funding from Abbvie and Faes Farma. DD: Lecture fee/consultancy from: Takeda, Pfizer, Janssen, Ferring, AbbVie, Eli-Lilly. SS: received consulting fees and advisory board fees from Takeda, AbbVie, Merck, Ferring, Pharmacocosmos, Warner Chilcott, Janssen, Falk Pharma, Biohit, TriGenix, Celgene, and Tillots Pharma; speaker honoraria from AbbVie, Takeda, Celltrion, Pfizer, Biogen, AbbVie, Janssen, Merck, Warner Chilcott, and Falk Pharma. VH: Has served as consultant, has served as speaker, has received travel support or research funding from MSD, AbbVie, Ferring, Dr. Falk Pharma, Tillotts Pharma, Pfizer, Takeda, Janssen, KernPharma Biologics, Adacyte, Sandoz, Biogen, Fresenius-Kabi, FAES Farma and Galapagos. MN: received board membership, consultancy, or lecture fees from Abbvie, Amgen, Biogen, Celltrion, Ferring, Fresenius-Kabi, Galapagos, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Pfizer, Takeda, Viatris. MF: Lecture and consulting fees from Abbvie, Pfizer, Tillots, Takeda, Gilead, Arena, Sandoz, Celltrion, Galapagos, Celgene, Boehringer, Biogen, Viatris, Amgen, Fresenius, Celltrion, CTMA, Ferring and Janssen. MA: Speaker and consulting fees from Abbvie, Pfizer, Ferring and Janssen. BB: Speaker and consulting fees from Janssen, Takeda, Sofar, Alfasigma, Doxapharma. BB: Speaker and consulting fees from Janssen, Takeda, Sofar, Alfasigma, Doxapharma. RCU: has received consulting and/or advisory board fees from AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Lilly, Pfizer, Roivant, Takeda. JC: receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Anaptysbio, Allergan, Inc. Ferring Pharmaceuticals, Shire, and Takeda; receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Galxo Smith Kline, Japan Gastroenterological Endoscopy Society, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microba, Morgan, Lewis & Bockius LLP, Novartis, Otsuka Pharmaceutical Development PBM Capital, Pfizer, Protagonist Therapeutics Sanofi, Takeda, TiGenix, Vifor; and hold stock options in Intestinal Biotech Development. JT: Grant - AbbVie, Janssen Personal Fees - Pfizer, Janssen, Abbvie, sandoz.

Introduction

Histopathological assessment remains the gold standard for evaluating diminutive colorectal polyps, despite the potential of optical diagnosis (OD) to reduce colonoscopy-associated costs (1). However, implementing OD strategies remains limited in clinical practice (2). This study aimed to evaluate patient acceptance of truly replacing pathology evaluation of diminutive polyps with resect and discard (RD) and diagnose and leave (DL) strategies using computer-aided polyp diagnosis (CADx).

Aims & Methods

In this prospective clinical pilot study at the Montreal University Hospital Center, 102 patients undergoing colonoscopy were invited to participate in the study. Patients received information on CADx, RD, DL and were informed that if they agree to participate in the study, we will diagnose all polyps using CADx during the colonoscopy, but polyps will be discarded or left in place and no pathology exams will be performed. For consenting patients, blue light imaging (BLI)-assisted CADx was used and endoscopists made the final histology determination and rated their confidence level (high vs. low) in the OD. Endoscopists also determined if high-risk features were present before using RD or DL strategies. Then all diminutive polyps optically diagnosed with high confidence as adenomas were resected and discarded and all diminutive rectosigmoid polyps optically diagnosed as hyperplastic with high confidence were left in situ. All polyps >5mm, with disagreement between endoscopists and CADx OD, low-confidence OD, or high-risk features (JNET 2b or higher) were sent for pathology evaluation. All cases were video recorded, and a quality review of the diagnoses performed with two expert endoscopists (DR and HP).

Results

Among the 102 patients approached, 97 (95%) accepted participating and utilization of CADx instead of pathology. Three stated that they did not want to participate in any research, and two patients stated that they did not trust OD or CADx as the reason for refusal. Overall, 164 diminutive polyps were removed in 97 patients (mean age=67.2 years), of which 36% were in the rectosigmoid and 64% in the proximal colon. CADx-assisted OD was performed on 97% of the polyps. The proportion of polyps with a low-confidence OD or disagreement between endoscopists' and CADx-based OD was 19/159 (11.9%). Overall, 98/159 (61.6%) polyps underwent the RD strategy, of which 4 polyps were discarded by the endoscopist's discretion despite disagreement between endoscopists and CADx OD. One of these 4 polyps had to undergo the DL strategy but was RD because of serrated features. One polyp in the proximal colon was resected and retrieved because of serrated features. 40 polyps were DL in the rectosigmoid, of which 1 polyp was neoplastic based on CADx and endoscopist's OD.

Conclusion

We observed a very high patient acceptance for truly replacing diminutive polyp histopathology with CADx-assisted OD. CADx-based OD was used to RD 98/159 (61.6%) or DL 40/159 (25.2%) diminutive polyps found in the cohort.

References

1) Rex, Douglas K. It’s not lack of evidence holding back resect and discard. Gastrointestinal Endoscopy, Volume 96, Issue 6, 1033 - 1035.
2) Willems P, Djinbachian R, Ditisheim S, Orkut S, Pohl H, Barkun A, Bouin M, Faulques B, von Renteln D. Uptake and barriers for implementation of the resect and discard strategy: an international survey. Endosc Int Open. 2020 May;8(5):E684-E692.

Disclosure

Dr Rex is a consultant for Olympus Corporation, Boston Scientific, Aries Pharmaceutical, Braintree Laboratories, Lumendi Ltd., Norgine, Endokey, GI Supply,
Medtronic, and Acacia Pharmaceuticals; the recipient of research support from EndoAid, Olympus Corporation, Medivators, Erbe USA Inc, and Braintree Laboratories; and a shareholder in Satisfai Health. Dr Pohl has received research funding from Steris, Cosmo, and is an advisory board member of InterVenn. Dr von Renteln has received research funding from ERBE Elektromedizin GmbH, Ventage, Pendopharm, Fujifilm, and Pentax and has received consultant or speaker fees from Boston Scientific Inc, ERBE Elektromedizin GmbH, and Pendopharm. The remaining authors disclose no conflicts.

Introduction

The distinction between eosinophilic esophagitis (EoE) and other causes of dysphagia in clinical practice can be difficult without histology. In addition, failure to collect esophageal biopsies represents one of the reasons for a delayed diagnosis in patients with EoE. Current guidelines recommend multiple esophageal biopsies in all patients reporting dysphagia although this may not be cost-effective.

Aims & Methods

To optimize resources allocation in the diagnostic workup of EoE, we developed and thereafter validated on an independent cohort of patients two point-of-care machine learning (ML) tools to predict a diagnosis of EoE: 1) based on clinical history data alone and 2) based on clinical-endoscopic findings, prior to the results of esophageal biopsies. This was a two-step multi-center international study conducted in three European tertiary referral centers for EoE (London, Pisa, and Padua). We build predictive ML models based on retrospectively extracted clinical data alone (age at diagnosis, sex, presence or absence of heartburn, chest pain, postprandial nausea/dyspepsia, history of food impaction requiring endoscopic removal, allergic rhinitis, asthma, nasal polyposis) and on clinical and upper endoscopy (EGDS) (exudates, rings, edema, furrows, stricture) data collected from 273 EoE and 55 non-EoE dysphagia (NED) patients in London. We performed an external validation of the models on an independent cohort of 93 prospectively enrolled patients reporting dysphagia at Pisa and Padua University Hospitals. The performance of the models was described with area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). We then developed a freely downloadable software for use in clinical practice at the point-of-care.

Results

The machine learning model trained on clinical data alone showed AUC of 0.82, and sensitivity, specificity, PPV, and NPV of 0.75, 0.82, 0.82, 0.75, respectively, for the diagnosis of EoE in the external validation cohort. Among clinical data alone, the patients’ age at diagnosis and sex had the highest predictive ability. The machine learning model trained on a combination of clinical and endoscopic data showed AUC of 0.93, and sensitivity, specificity, PPV, and NPV of 0.88, 0.95, 0.95, 0.87, respectively, in the external validation cohort. Among clinical and endoscopic data, the patients’ age at diagnosis, esophageal rings at endoscopy, and sex had the highest predictive ability. The models’ performance in the development and external validation cohorts is reported in Table 1.

Conclusion

The international external validation of our ML tools, as well as the freely available software, allow generalizability of our findings to other settings. Our software can be easily used at the point-of-care to optimize resources allocation in the diagnostic workup of EoE and 1) Support the clinical suspicion of EoE even in the absence of endoscopic findings, 2) Support decision making in performing repeat EGDS in patients in whom biopsies had been omitted, 3) Support decision making in performing repeat EGDS in patients with persistent EoE symptoms who had non-diagnostic levels of eosinophils at a previous EGDS performed while on proton-pump inhibitors, 4) Avoid unnecessary biopsies in very low-risk patients.

Introduction

Terminal ileitis is the endoscopic manifestation of a wide range of diseases: inflammatory, infectious, vasculitic, ischemic, drug-induced and malignancy. When it comes to asymptomatic terminal ileitis, it is incidentally found on screening ileo-colonoscopy. The prevalence of this entity was not well established and is found in few studies with heterogenous results.

Aims & Methods

We conducted this study to define the prevalence and histopathologic characteristics of asymptomatic terminal ileitis. This is a cross-sectional study. The study population is composed of all the patients that underwent a colonoscopy between September 2020 and March 2023. Selection bias were avoided by excluding patients with inflammatory bowel disease (IBD), sacroiliitis, chronic diarrhea, elevated calprotectin, medical history of ileitis diagnosed either on previous colonoscopy or on imaging showing wall thickening, and those with altered anatomy (colectomy with ileo-colic anastomosis).

Results

A total of 3901 colonoscopies were realized in a single center between September 2020 and March 2023; 3035 met our inclusion criteria based on medical history and the indication of the colonoscopy that excluded the above-mentioned reasons. Ileal intubation was performed in 91.4% (n=2773) of these cases, representing the final study population. Terminal ileitis was found in 5% (n=139) of patients, of whom 58.3% (n=81) were men and 41.7% (n=58) were women. The median age at diagnosis was 50 and and the mean age was 49.43 +/-15.5. The three main indications for colonoscopy were: colorectal cancer screening in 57.5% (n=80) of cases, gastrointestinal red flag symptoms including bleeding, anemia, and weight loss in 28.8% (n=40) of cases, and abdominal pain in 13.7% (n=19) of cases. Biopsies were performed in 90.6% (n=126) of ileo-colonoscopies and showed, regardless of the indication, normal histology, erosive and ulcerated ileitis, and non specific and other findings in 12.7% (n=16), 36.5% (n=46) and 44.4% (n=56) of samples respectively. Definitive Crohn’s disease diagnosis was found in 5.75% (n=8) of asymptomatic ileitis patients.

Conclusion

The prevalence of asymptomatic terminal ileitis was 5% in our population. This finding was not associated with the indication of the colonoscopy, namely colorectal cancer screening, gastrointestinal red flag symptoms including bleeding, anemia, and weight loss and abdominal pain. The clinical significance of this finding requires longitudinal follow-up studies to assess the incidence of IBD or other conditions.

Introduction

The 6-minute withdrawal time for colonoscopy is widely considered the standard of care. However, there may not be appropriate if the 6-minute is equally divided into various colon segments. Since the adenoma detection in each colon segment is not the same, there may be differences with the withdrawal time in different colon segments.

Aims & Methods

Our objective was to evaluate the relationships between adenoma detection rate (ADR) and respective withdrawal time in different colon segments. Outpatients, age range 18-75 years, undertaking complete colonoscopy were enrolled in this study from November 2019 to November 2020 in the digestive endoscopy center. The entire colon was divided into four different segments: ascending colon, transverse colon, descending colon and rectosigmoid colon. The respective withdrawal time and ADR in each colon segment were recorded respectively.

Results

A total of 586 outpatients (279 males, 307 females) enrolled in this study and the general ADR was 38.2%. The positive withdrawal time (adenomas detected) was longer than negative withdrawal time (non-adenomas detected) (334.04±24.21 secs vs 303.65±5.20 secs, t=1.26, P<0.001). ADR in ascending colon, transverse colon, descending colon and rectosigmoid colon were respectively 30.5%, 2.9%, 3.1% and 7.5%. While all of their positive withdrawal time were longer than negative withdrawal time (94.34±33.76 secs vs 70.40±41.84 secs, t=3.31, P=0.001; 85.40±49.76 secs vs 71.66±36.87 secs, t=1.95, P=0.025; 80.29±39.85 secs vs 69.73±35.96 secs, t=1.40, P=0.016;100.95±55.92 secs vs 80.96±42.87 secs, t=3.61; P<0.001, respectively). The withdrawal time threshold in the ascending colon, transverse colon, descending colon, rectosigmoid colon determined by receiver operating characteristic (ROC) curve were 77s, 61s, 56s and 109s, respectively. In the ascending colon, ADR was significantly higher (47.0% vs 33.1%, P < 0 .001) when the colonoscopy withdrawal time was ≥77s. When the withdrawal time was ≥61s in the transverse colon (42.7% vs 32.7%, P = 0.013), ≥59s in the descending colon (42.3% vs 29.9%, P=0.004) and ≥109s in rectosigmoid colon (52.2% vs 33.9%, P < 0 .001), ADR was also significantly higher. After adjusting for age, sex and BMI, Logistic regression analysis showed that withdrawal time ≥ 77s in the ascending colon (OR, 1.796; 95% CI, 1.273-2.532; P < 0 .001), ≥ 61s in the transverse colon (OR, 1.535; 95% CI, 1.094-2.155; P = 0.013), ≥56s in the descending colon (OR, 1.722; 95%CI, 1.193-2.486; P =0.004) and ≥109s in the rectosigmoid colon (OR, 2.134; 95% CI, 1.446-2.350; P < 0.001) were independent risk factors for the increase of ADR.

Conclusion

ADR and withdrawal time are all various in individual colon segments. During the operation of colonoscopy, withdrawal time in the ascending colon may be shortened appropriately. The adenomas in the rectosigmoid colon are more likely to be detected and do not take longer withdrawal times. We need to choose the appropriate time according to different colon segments.

References

[1] Sung H, Ferlay J, Siegel R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians 2021;71(3): 209-249.
[2] Shaukat A, Kahi C J, Burke C A, et al. ACG clinical guidelines: colorectal cancer screening 2021. Official journal of the American College of Gastroenterology ACG 2021;116(3): 458-479.
[3] Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol 2021;14(10):101174.
[4] Araghi M, Soerjomataram I, Bardot A, et al. Changes in colorectal cancer incidence in seven high-income countries: a population-based study. The lancet Gastroenterology & hepatology 2019;4(7): 511-518.
[5] Siegel RL, Torre LA, Soerjomataram I, et al. Global patterns and trends in colorectal cancer incidence in young adults. Gut 2019;68(12):2179-2185.
[6] Kaminski MF, Robertson DJ, Senore C, et al. Optimizing the Quality of Colorectal Cancer Screening Worldwide. Gastroenterology 2020;158(2):404-417.
[7] Lee JK, Jensen CD, Levin TR, et al. Long-term Risk of Colorectal Cancer and Related Deaths After a Colonoscopy With Normal Findings. JAMA Intern Med 2019;179(2):153-160.
[8] Ladabaum U, Dominitz JA, Kahi C, et al. Strategies for colorectal cancer screening. Gastroenterology 2020;158(2):418-432.

Introduction

The Updated Sydney System recommends reporting the severity of both glandular atrophy (GA) and intestinal metaplasia (IM) as two independent parameters. However, the OLGA system assesses both GA and IM together as part of the same entity which should be reported as an average severity. The OLGIM system is based on the IM severity recommended by the updated Sydney system. Thus, the final OLGIM score can be estimated by any clinician. Currently, no system addresses the severity of both GA and IM as they are reported following the updated Sydney recommendation.

Aims & Methods

This study aimed to assess the utility of a new system, OLGIMA (Operative Link on Gastric IM and GA assessment), as a tool to identify patients at higher risk for GC in daily practice.
Consecutive diagnostic UGI endoscopies performed for any indications in patients older than 18 years old were recorded prospectively in 21 Spanish hospitals between April 2021 and July 2023. Protocolized gastric biopsies were taken according to the Updated Sydney consensus. We excluded patients with dysplasia, any malignancy, suspicion of autoimmune chronic atrophic gastritis, and lack of histological data. The severity of both GA and IM was assessed in the antrum (including incisura) and corpus following the updated Sydney system. After that, we considered the most advanced severity (none:0; mild:1; moderate:2; marked:3) provided for any of them in each of the two topographical areas. Then, the OLGIMA staging was done according to the same methodology used by the OLGA and OLGIM systems.

Results

A total of 998 patients were included. The median age was 57 (IQR 46 - 67), and 64% were women. Hp infection was identified in 334 (35%) patients (19% active infection and 16% eradicated). GA was identified in 192 (19.2%) patients which was limited to the antrum in 113 (11.3%) cases and extensive in 79 (7.9%). IM was identified in 159 (15.9%) patients which was limited to the antrum in 114 (11.4%) cases and extensive in 45 (4.5%). According to IM severity, 27 (2.7%) patients were OLGIM III/IV. According to GA severity, 22 (2.2%) patients were significantly extensive. The OLGIM system would have missed 12 (1.2%) patients with GA at higher risk. Considering both criteria, we would have detected 39 (3.9%) patients at higher risk in total (17 OLGIM III-IV, 12 extensive significative GA, and 10 both OLGIM III-IV and extensive significative GA). The new OLGIMA system categorized all 39 (3.9%) patients, OLGIM III-IV and significantly extensive GA, in the high-risk group (OLGIMA III/IV).

Conclusion

The new OLGIMA system (based on the severity of IM and GA recommended by the updated Sydney system) was able to detect patients at higher risk including all cases of OLGIM III/IV and also with advanced GA. The OLGIMA staging is much simpler and it can be estimated by any clinician regardless of whether the biopsy from incisura was taken.

References

Rugge M, Meggio A, Pennelli G et al. Gastritis staging in clinical practice: the OLGA staging system. Gut. 2007;56:631-6
Capelle LG, de Vries AC, Haringsma J et al. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010;71:1150-8
Pimentel-Nunes P, Libânio D, Marcos-Pinto R et al. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy. 2019;51:365-388.

Introduction

In Australian patients receiving intravenous (IV) infliximab (IFX) treatment, 44% of patients do not respond to standard regimen and require dose escalation within a year. The REMSWITCH (6-month evaluation) and REMSWITCH-LT (18-months evaluation) investigated the effectiveness of switching from IV to subcutaneous (SC) IFX in patients with inflammatory bowel disease (IBD) who received standard and dose-escalated IV regimen. The two studies concluded that a fixed dose of 120 mg Q2W is feasible, safe and well-accepted leading to a low risk of long-term relapse in patients with escalated IV doses except for those on 10mg/kg/4weeks regimen. In this study, we developed a model to estimate the financial implications of switching.

Aims & Methods

Clinical efficacy parameters were derived from the REMSWITCH and REMSWITCH-LT studies and applied to the Australian context. Number of Australian patients who are on IFX, the proportion of patients on dose escalated regimen, and cost parameters were identified from the published literature or publicly available resources. A financial model was developed based on the assumption that a cohort of patients will receive either IV or SC IFX, and the analysis concluded with the cost difference.

Results

The model assumes that a total of 5.6K patients are receiving IV IFX, with 44.2% of them receiving dose escalation and/or shortened interval of IV IFX. The model produced 6 months and 12 months results, suggesting savings between 582 and 882 AUD per patient, respectively, and equates to a yearly societal savings of 5 million AUD.

Conclusion

IFX SC deserves premium over IFX IV, given that the novel formulation offers tangible and intangible benefits that originator Remicade and biosimilars cannot provide. There is a concern regarding the affordability of SC IFX because it is generally priced higher than IV IFX, which has many biosimilars on the market. However, this study asserts that fixed dosing of 120mg of IFX is cost-saving for society, considering highly prevalent practice of dose escalation and/or shortened intervals of IFX regimen.