BRECHT HENS (VUB, UZ Brussel) : Improved detection of dysplasia and colorectal carcinoma in inflammatory bowel disease
Patients with colonic inflammatory bowel disease (IBD) are at increased risk for the development of colorectal cancer (CRC), accounting for 10% of the mortality in IBD. It is unclear how novel treatments may have an impact on cancer risk. European guidelines recommend endoscopic surveillance of patients with IBD based on individual risk profile and disease duration, which, however, is flawed due to a lack of standardisation and the difficult discrimination between inflammatory and neoplastic changes in chronically active colitis. Early dysplastic lesions are often flat and subtle and hence difficult to detect, contributing to the higher rate of CRC diagnosed within 3-5 years after colonoscopy in patients with IBD compared to non-IBD patients. An estimated 50% of CAC are considered so-called interval carcinomas.
This large number of colonoscopies pose a significant strain on IBD-patients and -clinics, but currently constitute the sole screening method for CAC. In contrast, screening for CRC in the general population is optimized by using non-invasive faecal blood testing to identify high-risk individuals, limiting colonoscopies mainly to patients with an abnormal stool test result.
The main objectives of this joint research project with Amsterdam UMC are 1) to develop biomarkers for early detection of colorectal dysplasia and carcinoma in order to non-invasively identify individuals at high risk, and 2) to develop an AI algorithm for endoscopic identification of dysplastic colorectal lesions to improve colonoscopic accuracy and yield. These techniques might ultimately reduce the need of frequent surveillance colonoscopies and ameliorate the detection of early dysplasia, resulting in improved patient outcome and quality of life
INE DE GREEF (KU Leuven) : Identification of mesentric triggers of early post-operative Crohn's recurrence
The chronic uncontrolled inflammation in Crohn’s disease may lead to tissue remodelling and fibrosis, and is the main reason why more than 50% of Crohn’s disease patients will ever need surgery, of which 70% will develop new lesions in the intestine as early as weeks to months after surgery. The triggers that play a role in this post-operative recurrence are not yet completely unravelled. At the external side of the small intestine, the phenomenon “creeping fat” is observed, which is mesenteric fat – a structure that connects the intestines and holds them in place - migrating to the sites of intestinal inflammation. This is solely seen in Crohn’s disease, but whether creeping fat has a pathological or protective role is still not clear.
In this project, state-of-the-art technologies will be used to characterize the cellular and molecular composition of creeping fat, and link these new insights to the post-operative outcome 6 months after surgery. The results of this study will lead to (1) a better understanding of the underlying disease biology and etiology; (2) identification of pointers for new therapies or repurposing of existing drugs; (3) identification of predictive markers for post-operative Crohn’s disease recurrence so that medical treatment can be initiated quickly in order to prevent Crohn’s lesions to recur after surgery
MATTHIAS LENFANT (KU Leuven) : Role of histological remission and mucosal healing as new targets for IBD
Crohn’s disease (CD) and ulcerative colitis(UC) are chronic inflammatory bowel diseases (IBD). A better understanding of disease course and the introduction of biologics has led to a shift from conventional symptom control to a treat-to-target approach. The most recent STRIDE-II consensus established endoscopic remission in addition to steroid-free clinical remission as suitable targets based on current evidence.
Histopathology has an important role in IBD management with regards to (1) diagnosis, (2) assessing disease severity, (3) evaluation of complications, and (4) evaluation of treatment response. Endoscopic and histological healing are not synonymous: histological evaluation of IBD patients has demonstrated the presence of histological signs of disease activity regardless of clinical and endoscopic remission.
Histologic remission may be a better predictor of the clinical course. In UC, histologic remission has been associated with a reduced risk of clinical relapse, corticosteroid use, hospitalization, and colorectal carcinoma. The data in CD are scarcer though some studies suggest a reduced risk of therapy failure, drug escalation and corticosteroid use in the presence of histologic remission.
The depth of healing necessary for long-term remission remains unclear, and it is uncertain if this should be evaluated by endoscopy, by histology, or both. Incorporating molecular profiling of IBD patients using transcriptomic analyses may further improve understanding and classification of deep remission.
The general objective of this research project is to gain further insight into the role of histological remission and mucosal healing in CD and UC using a combination of classical H&E histological analyses combined with molecular transcriptomic RNA-Seq approaches. Furthermore, we hope to identify molecular differences in patients with quiescent disease, which could identify a patient subgroup at risk of recurrence and help optimize treatment strategies in the future.
The first part of the grant will be awarded thanks to a legacy received through the King Boudewijn foundation.