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Background

Endoscopic and histologic activity are important therapeutic targets in ulcerative colitis (UC). The Paddington International Virtual ChromoendoScopy ScOre (VCE-PICaSSO)¹ demonstrated that enhanced visualisation of subtle mucosal and vascular inflammatory changes correlated strongly with histology. However, without adequate training, the subjective evaluation of white light (WL) and VCE endoscopic scores varies between observers. We aimed to develop an artificial intelligence (AI) system for objective assessment of endoscopic disease activity and predict histology related to both white light and VCE videos.

Methods

469 endoscopy videos (48512 frames) from 235 patients representative of all grades of inflammation, from our prospective PICaSSO multicentre study¹ were used to develop a convolutional neural network (CNN). 316 videos were divided into training (254) and validation (62) sets. 153 additional videos (78 patients) were used as test cohort. The videos were edited to separate clips with WL and with VCE, and assessed using Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and PICaSSO, respectively. The classification stage of a pre-trained ResNet50 CNN classifier was trained to predict the healing or active inflammation on video frames. One network was trained to predict endoscopic remission (ER) as UCEIS≤1 from WL frames, and a second network was trained to predict PICaSSO≤3 from VCE. Histological remission (HR) was defined as Robarts Histological Index (RHI) ≤3 with no neutrophils in lamina propria or epithelium.

Results

In the validation cohort, our system predicted ER (UCEIS ≤1) in WL videos with 82% sensitivity (Se), 94% specificity (Sp) and an area under the ROC curve (AUROC) of 0.92. For the detection of remission in VCE videos (PICaSSO ≤3) Se was 74%, Sp 95%, and AUROC 0.95. In the testing cohort of independent videos, the diagnostic performance for both cut offs of ER remained similar. Table 1

Our system also had an excellent diagnostic performance for the prediction of HR in the validation set, with Se, Sp, and Accuracy of 92%, 83%, and 85% respectively, using VCE, and 83%, 87%, and 86% respectively, with WL. In the testing set performance declined modestly while remaining good. Of note, the algorithm’s prediction of histology was similar with VCE and WL videos. Table 2

Conclusions 

Our AI system accurately recognize endoscopic remission in videos and predict histological remission equally well. This is the first AI model developed to analyse inflammation and endoscopic remission in VCE through the PICaSSO score, and the first multi-domain system providing a complete endoscopic and histologic assessment.

Reference
1. Iacucci et al. Gastroenterology 2021 

1. To review the goals achieved in Imaging of IBD during the past few years and the new challenges for the next future
2. 1. To understand the future directions of imaging for IBD
3. To have an overview of the current and future role of AI in Imaging of IBD

Educational objectives:

1. Recognize the importance of diet in IBD and the interaction with microbes
2. Diet: not just feeding ourselves
3. ‘Functional foods’: diet as a microbe-altering treatment
4. Discuss what microbe-targeted diet therapy in IBD might look like in the future

Summary:

Both microbes and diet are likely to be involved in the pathogenesis of IBD and some studies suggest that it is the interaction between diet and microbes that offers opportunities for understanding why IBD develops and possibly even offer therapeutic options. Key to this is the recognition that elements in our diet specifically target and influence the microbes and that altering the diet could impact IBD, through effects on microbes.

This talk will focus on how this knowledge and area of research is likely to evolve in the future, highlighting the importance of specific food compounds (such as fibre), the use of complex research tools (including metabolomics), the development of personalized diets, and how this all might impact patient care, and perhaps even disease prevention. While this field is still in very early stages of development, there is much promise that diet will have a major impact on IBD care in the future, through defining impacts on microbes. It is important for both dietitians and those involved in diet research in IBD to be aware of this evolving field.

1) To review the clinical key predictors of poor outcome in IBD
2. To understand the progress made in predicting the future for a given IBD patient
3. To learn how to communicate risk to the patient

IBD is a chronic immune-mediated disease that requires continuous patient care. The frequent contact and the good relationship with the multidisciplinary team (MDT) are essential for improving quality of life (QoL) and medication adherence aiming at treatment success. The aim of the study was to assess the importance of MDT in the view of patients with IBD and its impact on QoL and in medication adherence.

A cross-sectional study was carried out, including 114 patients from an IBD reference center in Brazil. The relevance of MDT was assessed through a questionnaire that included the importance of physicians, nurses, nutritionists and psychologists in the patient care. QoL was assessed by IBDQ. Treatment adherence and knowledge about the disease were assessed using the Morisky and CCKNOW questionnaires, respectively.

:In total, 69 (60.53%) patients with CD and 45 (39.47%) patients with UC were included. The mean age was 39.16 (±13.50) years and 58.77% were female. The disease duration was 9.88 (±7.35) years. Presence of comorbidities was observed in 52.63% patients. About 57 (82.61%) patients with CD use biological therapy, with a statistical difference (p <0.0001) when compared to patients with UC (37.78%). The gastroenterologist was considered very important by 91.23% of patients, coloproctologist by 62.07% of patients, nurse by 65.05% of patients, nutritionist by 50% of patients and psychologist by 47.25% of patients. In the analysis of QoL, 24 (21.05%) patients had excellent QoL, 52 (45.61%) had good QoL, 29 (25.44%) had regular QoL and 9 (7.89%) had poor QoL, with no difference between patients who followed with nurses or other MDT professionals (Table 1). Medication adherence was low in 58.88% of patients. Knowledge about the disease was low (6.21 ± 3.99 points), being higher among patients with CD (p = 0.01). Patients identify the doctor as the main provider of care for their health, but about 10% leave with doubts from their appointments. 10% of patients think that more care with the nurse is necessary and less than 10% of patients are clarified by the nurse about QoL, ostomies, fecal incontinence, disease activity, biological therapy and sexuality.

Patients considered doctors as the most important professionals in their care. Although the service has a multidisciplinary team, not all patients had the opportunity to consult with all professionals, mainly do the Covid pandemic in 2020 and 2021. The lack of contact with the entire team, especially with the nurse, may have contributed to low medication adherence and low knowledge of the disease, impacting disease control and QoL.

Data regarding the influence of prednisolone tapering on clinical outcomes among patients with ulcerative colitis (UC) are limited. We aimed to investigate the influence of different prednisolone tapering algorithms on the effectiveness of infliximab (IFX) among patients with UC.

This Danish retrospective single-center study included all patients with UC who were treated with IFX between 2009 and 2019 at Herlev University Hospital. The patients were grouped according to the prednisolone tapering: standard (≤5 mg/week), fast (>5 mg/week), or direct discontinuation after an initial course of less than one week. Finally, we included a control group of patients treated with IFX monotherapy. The primary outcome was corticosteroid-free clinical remission at weeks 14 and 52 defined as a partial Mayo score ≤1. Variables with a p-value ≤0.20 in univariable regression analysis were included in multivariable analysis. A subgroup analysis containing patients with acute severe ulcerative colitis (ASUC) treated with at least 40 mg of prednisolone at initiation of IFX was performed.

The study included 148 patients with UC of whom 81 (54.7%) were treated with prednisolone at the initiation of IFX. No association between prednisolone tapering and corticosteroid-free clinical remission with IFX at weeks 14 or 52 was observed (Figure 1 and Table 2). However, a higher proportion of patients in the standard tapering group achieved a C-reactive protein (CRP) level less than 5 mg/L at week 14 as compared with the fast-tapering group (23/23 (100%) vs. 14/18 (77.8%); p=0.03) and directly discontinuation group (6/10 (60%); p=0.03). This difference was not explained by prednisolone usage. In addition, none of the patients within the standard tapering regime (0/24; 0%) had severe activity at week 14 whereas this was seen in 4/19 (21.1%) in the fast tapering regime (p=0.03). In the subgroup analysis of 33 patients with ASUC, the standard tapering algorithm was associated with higher clinical remission as compared with the fast tapering regime at week 14 (9/14 (64.3%) vs. 5/19 (27.8%); p=0.02) and clinical response or remission at week 52 (12/14 (85.7%) vs. 7/19 (36.8%); p=0.01, Figure 2).

This study demonstrated no overall impact of prednisolone tapering algorithms on short and long-term effectiveness of IFX in patients with UC. However, standard tapering resulted in lower CRP levels and fewer cases of severe disease activity in the overall cohort and higher rate of short and long-term clinical response among ASUC patients, as compared with fast tapering regimes. Taken together, the data indicate that longer corticosteroid exposure in patients with high disease burden might improve IFX responses.

Educational objectives

1-    To understand that IBD are associated with worse quality of life and high rates of depression, beyond symptoms alone.

2-    To consider the role of psychological components on postoperative outcomes

3-    To understand the rationale and results of our study

4-    To understand the rationale for preoperative psychological support in IBD patients

Summary

Background: Inflammatory bowel diseases lead to increased rates of depression and reduced quality of life (QoL), beyond intestinal symptoms alone. QoL seems to improve at 1 year after surgery, but not in the short term. No studies have explored the potential role of psychological components (mindfulness in particular) on postoperative outcomes. 

Aim: the aim of this pilot-study was to explore the correlation between a set of psychological predictors, QoL and surgical outcomes.

Methods: psychological questionnaires were administered before surgery. QoL questionnaires were administered both preoperatively and at 30- 90 days and 6 months after surgery. Length of stay (LOS), postoperative pain and complications were also evaluated. 

Results: 30 patients were enrolled(56% Crohn’s - CD, 44% ulcerative colitis - UC). 67% were males. Mean age was 43,5, mean BMI 22,6. Most patients were ASA 2(70%). Smoke habit was reported in 17%. Charlson Comorbidity Index was 0 in 54% of patients, 1 in 23%, 2 in 17%, 3 in 3% and > 5 in 3%. Index procedure was ileocecal resection in 47% of cases, total colectomy in 13% and restorative proctectomy in 40%. Mean operative time was 186 minutes. In 53% of patients a temporary stoma was performed. No differences in baseline psychological characteristics were found between CD and UC patients. Higher levels of stress(PSS) (P=0.0008), anxiety(HADS-A)(P=0.028) and depression (HADS-D)(P=0.028)were correlated with worse preoperative QoL. No correlation was found between preoperative psychological predictors and LOS, postoperative pain and functional recovery (time to 1° bowel movement). However, the logistic regression model found a correlation between postoperative complications and Anxiety(HADS-A). Patients experienced a significant increase in QoL after surgery(30 days, P=0.008; 90 days, P=0.005). Patients with higher QoL and Cognitive Flexibility Scale scores at baseline had more probabilities to experience a significant improvement 30 and 90 days after surgery(P<0.0001; P=0.04).

Conclusions: stress, anxiety and depression impacted on preoperative QoL. Anxiety correlated with postoperative adverse outcomes. Cognitive flexibility had a positive effect on QoL improvement at 30 and 90 days after surgery. Patients with higher baseline QoL were more susceptible to improve their QoL over time after surgery. 

-          To review the frequency and type of pancreatic manifestations in IBD

-          To have an overview of the morphological features of chronic and autoimmune pancreatitis

-          To emphasise the role of histopathology in the diagnosis of pancreatic manifestations in IBD

Pancreatic changes are present in up to 50% of IBD patients, but symptomatic disease is rare and mostly related to acute pancreatitis, chronic pancreatitis or autoimmune pancreatitis.

Acute pancreatitis in patients with IBD is usually related to gallstones or drugs (thiopurines, mesalamine) and is more common in Crohn’s disease (CD) than in ulcerative colitis (UC).

Chronic pancreatitis is quite rare and thought to be idiopathic or possibly related to obstruction, e.g. in patients with primary sclerosing cholangitis. There is no possibility to specifically diagnose IBD-associated chronic pancreatitis, and diagnosis is usually one of exclusion.

Autoimmune pancreatitis (AIP) is more frequent in IBD patients than in the general population, but it remains a rare disease. IBD, and especially UC, are most frequently associated with type 2 (= non IgG4-related) AIP and this association is characterized by an active and more aggressive disease with higher rates of colectomies. There are definite histopathologic criteria for the diagnosis of AIP, which can be successfully applied on biopsy material. Therefore, if AIP is suspected in IBD patients, a pancreatic biopsy can be useful to confirm the diagnosis and direct therapy.

Educational objectives:

• To discuss the therapeutic options for paediatric patients with inflammatory bowel disease (IBD) refractory to standard medical therapy
• To review the current evidence for segmental resection for patients with Crohn’s disease (CD)
• To review the evidence for “out of the box” treatments such as tacrolimus for both diseases, thalidomide for CD, granulocyte- monocyte apheresis, fecal microbial transplantation, mesenchymal stromal or adipose cell therapy for refractory perianal fistulas, dual biologics and autologous hematopoietic stem cell transplant.

Presentation outline:

When patients with IBD fail standard medical therapies there are limited therapeutic options. The first step should be to optimize biologic therapy (based on therapeutic drug monitoring in anti-TNF treated patients or empiric escalation in patients treated with vedolizumab or ustekinumab). Tofacitinib should be considered for patients with ulcerative colitis (UC).

Surgical resection has an established benefit in segmental CD even in the colon.

The edition of nutritional therapy as a combination treatment with biologics may be considered for selected cases.

Tacrolimus was shown efficacious in UC and may serve as a bridge to other therapies such as vedolizumab or even in combination at low doses with vedolizumab.

Thalidomide was studies in CD but treatment is limited by adverse events in high rate and rarely sustainable.

Granulocyte- monocyte apheresis has a limited effect (mainly in UC). Fecal microbial transplantation has emerged a promising treatment with negligible side effects. However, studies using different techniques have yielded limited short-term benefit only.

Autologous hematopoietic stem cell transplant is regarded as a “last resort” option for patients with refractory CD but was studied so far only in adults with promising results though carrying a very high rate of adverse events.

Finally, in the last 2-3 years evidence accumulate on combination of different biologics. Though expensive, such combination may provide relief in refractory cases but more research is needed.

Direct health care costs have shifted towards drug-related expenditures in patients with inflammatory bowel disease (IBD). Frequently, patients will have to switch to a second- or third-line biological therapy due to no response or loss of response. The aim of this study was to describe the use and efficacy of biological therapy in a tertiary centre during a 10-year period and investigate the need for surgery.

The study population consisted of all bio-naïve IBD patients who initiated biological therapy between January 1, 2010 and February 19, 2020 at the Gastro unit, Hvidovre Hospital, Denmark. The electronic medical records were reviewed, and data were systematically registered. Failure of the biological therapy as no response and loss of response was defined by the need for surgery, steroid or shift in biological therapy.

The study population consisted of 291 (46.9%) patients with ulcerative colitis (UC), 327 (52.7%) with Crohn’s disease (CD) and 3 with (0.5%) IBD Unclassified (IBDU), who initiated biological therapy with a median follow-up of 3 (IQR=2-5) years from initiation of therapy. The annual number of patients who initiated biological therapy was increasing throughout the study period.

Most patients (457, 73.6%) received one biological drug, 126 (20.3%) received two, and 38 (6.1%) received three or more different types of biological drugs during the study period. Systemic steroid was required in 99 patients (15.9%) and the 5-year surgery-free survival was 76.5% (120 patients with surgery). 302 patients (54.3%) had effect of the first biological therapy at one year follow-up.

In multivariate Cox-regression analyses, concurrent treatment with thiopurines decreased the risk of failure of the first biological therapy in UC patients (hazard ratio (HR) 0.745, 95% CI: 0.559-0.992) but not in CD patients (HR 0.969, 95% CI: 0.722-1.300). Male gender decreased the risk of failure (HR: 0.677, 95% CI: 0.505-0.908) while higher age at initiation of biological therapy increased the risk (HR: 1.0152, 95% CI: 1.004-1.027) in CD patients. These factors had no impact in UC patients. Prior surgery, disease duration and location were not associated with increased risk of failure of first biological therapy.

In conclusion, an increasing number of IBD patients received biological therapy during the 10-year period at our tertiary centre. A considerable part of IBD patients in biological therapy will require surgery, additional steroids, or second line biological therapy. Our findings suggest a beneficial role of thiopurine in combination with biological therapy. Improved identification of patients not responding to first line biological therapy is of great importance.