Introduction

Acute severe flares occur in 15% of patients with ulcerative colitis (UC). Intravenous corticosteroids induce clinical remission in up to 50-60% of cases. Infliximab (IFX) and cyclosporin (CsA) are the only evidence-based alternatives to colectomy in steroid-refractory acute severe UC (SRASUC), with a similar efficacy. It has been suggested that a more aggressive induction regimen of IFX might decrease the rate of colectomy.

Aims & Methods

To evaluate the short and mid-term outcomes of patients with SRASUC treated with IFX regarding the used induction regimen.
Methods: Retrospective, observational study including adult patients included in the ENEIDA registry supported by GETECCU, treated with IFX (at least two doses) due to SRASUC and available follow-up of at least 3 months or until colectomy or death. Dates and dosing of the first three IFX infusions, dose-escalation or treatment discontinuation, colectomy and date were collected. Induction regimens were grouped as follows: CONVENTIONAL (IFX 5mg/kg at 0, 2 and 6 weeks), ESCALATED (any of the first three infusions >5mg/kg) and ACCELERATED (second infusion administered before 11 days of the first one, or third infusion administered before 21 days of the second one).

Results

A total of 339 patients were included, 59% with extensive UC and 34% previously exposed to thiopurines. At the time of the first IFX infusion, median partial Mayo score was 7 (IQR, 6-8), median Mayo endoscopic subscore 3 (IQR, 2-3) and median C-reactive protein 49 mg/L (IQR, 18-99). IFX was started after a median of 7 days (IQR, 6-8) on iv steroids, with concomitant thiopurines in 51% of the cases. The induction regimen was conventional in 207 patients (61%), escalated in 81 (24%), and accelerated in 99 (29%), although 48 (14%) used escalated and accelerated regimens together. Partial Mayo score, Mayo endoscopic subscore and C-reactive protein levels at the time of the first IFX infusion were not significantly different between those patients following conventional regimen and those who did not; baseline serum albumin levels (29.9±0.7 vs 32.3±0.9 g/L; P=0.002) and prior exposure to thiopurines (38.2% vs 25.9%; P=0.022) were significantly lower in patients who followed escalated or accelerated regimens. One hundred and thirty-three patients (39%) discontinued IFX within the first year due to failure (no response or partial response) in 72 (21%), adverse event in 45 (13%), complete remission in 9 (3%) and patient’s willingness in 5 (2%).
The colectomy rate at 30 days, 90 days and 12 months in the whole series was 6%, 8% and 13%, respectively. Patients who followed a full conventional regimen had significantly lower rates of colectomy at 30 (1.5% vs 12.9%; p<0.0001), 90 days (3.9% vs 15.2%; p<0.0001) and 1 year (9.6% vs 20.9%; p=0.004). In the logistic regression analysis, following a conventional induction regimen was the only protective factor of colectomy at 30 (OR 0.08 95%CI 0.02-0.36) and 90 days (OR 0.19 95%CI 0.07-0.54).
No differences were observed among conventional and intensified induction regimens in terms of steroid reintroduction and IFX discontinuation within the first year.

Conclusion

In clinical practice, accelerated and/or escalated induction regimens of IFX are used in almost half of the patients with SRASUC. Accelerated and escalated induction regimens were associated with significantly higher rates of colectomy at one and three months. Therefore, no benefit of using these modified induction regimens was found on the basis of current clinical practice decision-making criteria.

Disclosure

Eugeni Domènech has served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Galapagos, Gilead, GoodGut, Imidomics, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, Tillots.

Introduction

Despite new therapeutic strategies, substantial proportion of patients with ulcerative colitis (UC) undergo colectomy at some point. Restorative proctocolectomy with ileal pouch ano anastomosis (IPAA) is regarded as intervention of choice in these patients. However, the disease conversion to Crohn´s disease (CD) is reported in up to one third of these patients who necessitate immune suppressive treatment after IPAA. Considering the life-long need for immune suppressive therapy in these patients, ileo-rectal anastomosis (IRA) would represent a good alternative to IPAA in this specific group of patients. Todate, no data are available to predict the UC-CD conversion. One of the possibility to reduce the risk of performing IPAA in patients developing CD in pouch is to use the modified two-stage proctocolectomy approach and identify patients who develop CD endoscopically between colectomy and the restoration of continuity.

Aims & Methods

The aim of the present study was to assess the UC-CD conversion rate identified prior IPAA via ileoscopy.
All patients with UC operated in one tertiary IBD center between 2016 and 2021 were identified in medical records. The main outcome was CD detected at ileoscopy between the first stage operation, i.e. total colectomy with terminal ileostomy and the restoration of continuity either via IPAA or IRA. The ileoscopy was performed between three to six months after colectomy. The secondary outcome was the rate of conversion to CD after IPAA or IRA.

Results

Sixty patients underwent total colectomy (mean age 41 years, range 22-77; 62% were men); seven patients were lost to follow-up, finally the data from 53 patients were analysed. The majority of these patients (36 - 68%) underwent colectomy for therapy resistent chronically active UC, 9 (17%) patients for acute severe UC, 2 patients had benign colonic stenosis, 5 had high-grade dysplasia or colorectal cancer detected at surveillance colonoscopy and one patient had extensive pseudopolyposis.
All resection specimen were reviewed and no histopathological features of CD were found. Three out of the 53 (6%) ileoscopically assessed patients prior IPAA or IRA were diagnosed with CD in prestomal terminal ileum. During the further follow-up, additional 4 patients developped CD, two after IPAA, one with definitive ileostomy in prestomal ileum and one in neoterminal ileum after IRA.
In total 7 out of 53 patients in this cohort developped CD (13%). Using the two stage approach with ileoscopy between colectomy and restoration of continuity, three out of these seven patients with CD convertion in this cohort were detected prior the decision on the type of second-stage operation.

Conclusion

The conversion from ulcerative colitis to Crohn`s disease occurs in a significant proportion of IBD patients after colectomy. Ileoscopy performed between the two stages of restorative proctolectomy is helpfull in detecting these patients and guiding the decision on the type of surgical intervention to restore continuity.

Disclosure

Nothing to disclose.

Introduction

The evolution of therapy in Inflammatory Bowel Disease (IBD) has included multiple biologics and small molecule options in recent years. Despite this, treatment failure remains high. Combination immune therapies targeting different targets may improve outcomes. Safety profile of combination biologic therapies require further evaluation with a paucity of real-world use currently available.

Aims & Methods

Aim: To review dual biologic efficacy, safety and long-term outcomes in patients with refractory IBD.
Method: All patients with IBD receiving combination immune therapies, mainly biologics in two IBD centres and academic teaching hospitals in South of Ireland were reviewed. Eligible patients had confirmed IBD on combination biologic therapies. Efficacy outcomes were clinical, biomarker, endoscopic and histological response. Long-term outcomes included IBD flare, steroid use, change in therapy for disease activity, hospitalisation and colectomy.

Results

61 patients were treated with dual biologic therapies. 64% were Crohn’s disease (n=39), the median age at initiation of combination was 33y (range 17-84), median time since diagnosis and initiation of combination therapy was 7y (range 0-26). Indications for combination therapy included refractory IBD (94%), Active Extra-intestinal manifestations (EIM) (4%) and Active IBD and EIM (3%). Previous biologic or oral synthetic drug exposure was as follows; anti-TNF (100%), Vedolizumab (28%), Ustekinumab (36%) and Tofacitinib (8%). Median duration of follow-up was 10 months (range;1-42).Full data available for 6 months, clinical response within 12 weeks was observed in 52%. We performed sub-group analysis as per combination groups; Vedolizumab-Ustekinumab, Vedolizumab-Other(Infliximab, Adaliumab, Tofacitinib, filgotinib), Ustekinumab-Other and Miscellaneous for 6 months follow up as detailed in Table 1.
The 3 groups were similar in FCP and CRP( Kruskall Wallis test).

	Vedo-UST	Vedo-Other	UST-Other	Misc(IFX-Tofa)
Number of pts	26	29	13	1 – colectomy
Clinical response at 12 wks	11	17	6	0
Clinical remission at 6mo	5 ( n=10)	6 (n=22)	6 (n=6)	NA
FCP baseline (median)	1800	899	476	1900
FCP 6mo (median)	608 (n=13)	725 (n=22)	317 (n=6)	NA
CRP baseline(median)	20.0	5.0	9.65	1
CRP 6mo (median)	6.95 (n=13)	3 (n=22)	9.2 (n=6)	NA

Of 24 patients who completed 1- year follow-up, 66% achieved clinical remission within 1 year. For 2 year follow-ups (n=11) clinical remission was achieved in 36%, with median FCP of 307 and 3-year data (n=6) demonstrated clinical and endoscopic remission in 33% and median FCP of 378.
Adverse events were documented in 10 cases (16%). 7 hospitalisations due to worsening disease or complications: 3 IBD flare, 2 perianal sepsis, 1 hyponatraemia, and 1 influenza, with a median length of stay of 4 days. The remaining adverse events were non-serious infections; URTI, LRTI and gastroenteritis. There were no reports of malignancy during study follow-up. Four patients underwent surgery; 1 colectomy,1 EUA perianal abscess and 2 ileocolic resections. 18 patients (26%) discontinued combination therapy during study follow-up; 11 switched to alternative combination biologic therapy, 5 de-escalated to monotherapy and 2 underwent surgery.

Conclusion

Our real-world study suggests efficacy in achieving clinical improvement in difficult-to-treat cohort of patients. Our study did not demonstrate new serious/opportunistic infections or new/recurrent malignancies on combination therapy. Dual therapy may be an option for refractory IBD patients with limited therapeutic options.

Introduction

Despite the increasing incidence of Crohn’s disease (CD), its early immune disturbances have not been described yet. The preclinical period provides an opportunity to gain insight into the initial processes involved in the pathogenesis of the disease.

Aims & Methods

The main aim of our study was to describe how the subclinical inflammatory process is modifying the individual’s immunologic environment while the patient is still on preclinical period. We analysed scRNASeq data from peripheral blood mononuclear cells (PBMC) of patients with incidentally-diagnosed CD according to ECCO criteria during the colorectal cancer screening programme, after histologic confirmation. Their gene expression profile was compared to healthy individuals acquired from publicly available datasets. The analytical pipeline included merging of the datasets followed by batch correction concerning integration from different studies, quality control and filtering, and finally cell-type annotation and differential gene expression analysis.

Results

Two patients with CD (mean age 53,5 years) and 2 healthy controls were included. We observed distinct transcriptomic profile in preclinical patients compared to controls, with small intragroup differences. The cell-type annotation identified B cells (B), CD4+ and CD8+ T-cells (CD4T, CD8T), dendritic cells (DC), monocytes (Mono) and natural killer cells (NK). The analytical pipeline included 17,021 cells (B:3,274, CD4T:5,798, CD8T:3,476, DC:315, 2, Mono:928, NK:3,230) and 3000 quantified genes. Considering each cell type individually, we identified 49 differentially expressed genes (DEG) between CD patients and controls (B:39, CD4T:37, CD8T:41, DC:42, Mono:37, NK:37), from which 30 were DEGs in all cell types.
Building on the list of 49 detected DEGs, we report three insights into the preclinical period of the disease.
First, pathway analysis revealed significant enrichment of the pathway that is related to immunoregulatory interactions between lymphoid and non-lymphoid cells, and functional annotation analysis identified gene products that are related to immunological defense. Second, we identified significant transcriptomic alterations in genes that have previously been related to the symptomatic phase of IBD, or reported as potential biomarkers. Third, after performing principal component analysis we observed greater separation between the patients groups in the CD8T cells compared to the other cell-types.

Conclusion

This study reveals the initial transcriptomic profiles and the main pathways that precede the onset of symptomatic inflammatory bowel disease. Our findings may help in identifying potential targets for early disease intervention.

Introduction

Recently, artificial intelligence-based computer-aided detection (CADe) for colonoscopy is garnering significant attention due to its effectiveness in increasing adenoma detection rate (ADR). However, theoretically, CADe system cannot decrease exposure error which polyps obscured by an object. In this regard, computer-aided quality improvement (CAQ) which expects to induce the meticulous mucosal inspection and leading to a reduction of blind spot area. In this study, we developed and evaluated CAQ for colonoscopy.

Aims & Methods

This was a single center, retrospective study from period April 1, 2022 to February 25, 2023. We randomly extracted colonoscopy videos and created 18,922 training images. Quadrant images were made from one image and three endoscopists annotated the following scores; i) appropriateness for mucosal inspection, ii) appropriate distance, and iii) presence of blind area in the field of view (e.g., fold or flexure). We conducted supervised machine learning using annotated images. The CAQ deployed multi-head deep convolutional neural network model which can output multiclass prediction from one image. Consequently, the CAQ system outputs aforementioned score from whole colonoscopy video. To validate its performance, we retrospectively analyzed colonoscopy procedures performed by seven endoscopists using the CAQ. We compared calculated CAQ model scores and expertise of endoscopists.

Results

29 videos were included as validation samples (8 videos were performed by non-expert endoscopists) As a result, there was a significant difference in the proportion of appropriate images during the examination between experts and non-experts (median 56% vs. 49%, p=0.005, Mann–Whitney U test) and there was also a significant difference in the evaluation score of the distance between the colon mucosa and the endoscope (median 4.2 vs. 3.2, p=0.0004, Mann–Whitney U test). In addition, there was a significant difference in the scores evaluating the presence of blind areas in the field of view (median 1.6 vs. 1.2, p=0.0007, Mann-Whitney U test).

Conclusion

In this study, developed CAQ system could quantify the skill of the endoscopists. Such CAQ would be expected to standardize the observation technique of colonoscopy.

Introduction

Endoscopic submucosal dissection (ESD) is the preferred method for the treatment of superficial gastric neoplasms. In cases of curative resection, the outcome is excellent with recurrence rates of less than 5% and disease-free survival rates greater than 95%. However, surgical resection is indicated in cases of non-curative resection, although recent studies suggest that this strategy may have an unfavorable risk/benefit ratio.

Aims & Methods

The aim of this study is to analyze the evolution of patients with non-curative resection in our center. Patients who did not meet the criteria for cure after ESD of superficial gastric neoplasms were prospectively evaluated. Clinical (before and after ESD), endoscopic (location, size, and morphology of the lesion), pathological (tumor size, degree of dysplasia, vertical and horizontal margins, vascular, lymphatic, and perineural invasion), and surgical (type of intervention, pathological characteristics of the specimen) data were collected and analyzed.

Results

Of the 203 patients who underwent ESD of upper digestive tract lesions, 20 patients with non-curative resection of gastric neoplasms were identified (median age 70 years, 65% of whom female). The mean size of the lesions was 20 ± 9 mm, and 40% were depressed (Paris Classification 0-IIa+c [n = 6] and 0-IIb+c [n = 2]). Resection was R1 in five cases, nine had submucosal invasion greater than 500μm, nine had lymphatic invasion, and four had vascular invasion. Of these, 15 patients underwent surgical resection (75%), mostly partial gastrectomy (n = 12). In the remaining cases, surveillance (n = 3) or pending multidisciplinary discussion (n = 2) was opted for. Pathological evaluation revealed a "white" specimen in 10 cases (2/3). The clinical characteristics and histological data of the ESD specimen (including the eCura score [Hatta et al., 2017]) were not statistically different in patients with and without residual neoplasia in the operative specimen (p>0.05).

Conclusion

Despite the small sample size, this series suggests the need to identify better predictors of "clinically significant non-curative resection," in which disease persistence after ESD is more likely.

References

Hatta W, Gotoda T, Oyama T, et al. A Scoring System to Stratify Curability after Endoscopic Submucosal Dissection for Early Gastric Cancer: "eCura system" [published correction appears in Am J Gastroenterol. 2019 Dec;114(12):1925-1926]. Am J Gastroenterol. 2017;112(6):874-881.

Introduction

Climate change is responsible for increasing global health consequences and healthcare-related expenses. Despite efforts to address these issues, the healthcare sector remains a significant contributor to the world's carbon footprint due to increasing greenhouse gas emissions, compromising its own sustainability. Particularly, endoscopy stands out as the second highest waste generator per clinical procedure, largely attributed to its resource-intensive processes and extensive use of single-use devices. This study aimed to assess the waste carbon footprint generated at a high-volume tertiary endoscopy center both before and after implementing a targeted sustainability intervention. Additionally, we assessed the intervention's impact on the daily workflow of the endoscopy staff.

Aims & Methods

A 3-stage prospective interventional study was conducted from December 2023 until March 2024. Pre-intervention: four-week observational audit, during which daily endoscopic waste (landfill, regulated medical waste (RMW), and recycled paper and plastic) was weighed in both endoscopy rooms and recovery areas. Intervention: following data collection, a dedicated training session was conducted for the endoscopy staff. The session included a presentation of the collected data and outlined key sustainability strategies aimed at enhancing waste segregation. Additionally, recycling streams were established with placement of dedicated bins in assessment areas. Post-intervention: four-week period during which daily endoscopic waste was weighed in both endoscopy rooms and recovery areas.
Weighing was conducted using an engineer-calibrated scale. For the purpose of this study, waste carbon footprint calculations were based on the equivalence of 1kg of landfill waste to 1kgCO_2e and 1kg of RMW to 3kgCO_2e.
Upon conclusion of the study, an anonymous survey was distributed to all staff members to assess the impact of the study on the daily work routine.

Results

Total waste carbon footprint was reduced by 28.2%. In endoscopy rooms, waste carbon footprint decreased 20.4% (pre- vs. post-intervention: 1472.8kgCO_2e vs. 1173.7kgCO_2e, p=0.552). RMW was reduced by 24.4% (pre- vs. post-intervention: 462.8kgvs. 336.3kg, p=0.020), whereas landfill waste (pre- vs. post-intervention: 72.2 vs. 151.1, p<0.001) and recycling waste increased (paper – pre- vs. post-intervention: 0 vs. 21, p<0.001; plastic – pre- vs. post-intervention: 0 vs. 33.6, p<0.001). Mean endoscopy load was similar (pre- vs. post-intervention: 517 vs. 541, p=0.48).
In recovery areas, waste carbon footprint decreased 58.3% (pre- vs. post-intervention: 386.7kgCO_2e vs. 161.1kgCO_2e, p=0.002). RMW was reduced by 42.1% (pre- vs. post-intervention: 109.4kgvs. 28kg, p<0.001), whereas landfill waste (pre- vs. post-intervention: 58.4 vs. 77.2, p=0.040) and recycling waste increased (paper – pre- vs. post-intervention: 0 vs. 6, p<0.001; plastic – pre- vs. post-intervention: 0 vs. 9.9, p<0.001).
All staff members agreed the project did not disrupt their daily work routine, emerging as a valuable asset for promoting further sustainable practices.

Conclusion

Our study demonstrated that reducing RMW and implementing daily recycling in endoscopy rooms and recovery areas are attainable objectives that do not hinder endoscopy productivity. As a result, a yearly reduction of 2104kgCO_2e could be achieved in our endoscopy unit. Additionally, this study highlighted the effectiveness of educational initiatives in raising awareness towards more sustainable endoscopy practices.