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Background The development of peri-anal fistula mucinous adenocarcinoma (MA) is a presumed rare but recognised event in patients with fistulating peri-anal Crohn’s disease. The true incidence is unknown, with a lack of robust registry data. Fistula mucinous cancers may evade early diagnosis, presenting with locally advanced intra-pelvic disease, necessitating debilitating and morbid exenterative surgery. Given the limitations of endoluminal assessment of this region in the context of an often extra-luminal disease process, MRI studies were reviewed in conjunction with EUA and endoscopic findings. Methods We performed a retrospective analysis of 8 cases of biopsy-proven mucinous adenocarcinoma (MA) that had developed within known Crohn’s related anal fistula. Serial MRI studies pre-dating the diagnosis of malignancy were reviewed in order to establish whether there are early predictive features of MA development within a fistula tract. Demographic, disease and surgical history were collected including the time of fistula diagnosis and histological confirmation of mucinous adenocarcinoma. Results The median time to histological diagnosis of MA from the time of diagnosis of Crohn’s disease was 426 (96–480) months and from diagnosis of fistulating disease 66 (24–156) months. On review of sequential MRI fistula protocol studies, a characteristic ‘budding’ appearance within the T2 high signal ‘sepsis’/fistula tract is noted in all of our MA fistula cancer cases (Fig1 and 2). This finding pre-dates the histological diagnosis of MA by a median of 42(12–156) months. Weight loss was a presenting symptom in 4 of the 8 (50%) patients and all 8 patients reported a new significant peri-anal pain and high volume discharge which prompted reassessment and referral. Metastatic disease was not detected in any of the 8 cases. Potentially curative pelvic exenteration was possible in 7 patients. Conclusion Mucinous adenocarcinoma within this cohort often culminates in exenterative surgery by the time a diagnosis is made. There is an opportunity for early detection on MRI of the development of MA in an anal fistula by recognition of ‘budding’ within the tract. An earlier diagnosis may lessen the magnitude and morbidity of subsequent radical surgery following prolonged growth of these lesions. Long-standing Crohn’s anal fistula should be surveyed with MRI and any finding of ‘budding’ within the tract on T2 sequences should prompt urgent examination under anaesthetic and biopsy.

Background The Lémann index (LI) is the first instrument developed to measure cumulative structural bowel damage in Crohn’s disease (CD).1 We here report its validation. Methods This was an international, multicentre, prospective cross-sectional observational study. At each centre, 10 inclusions, stratified by known or suspected CD location and duration, were planned. Clinical examination and abdominal MRI had to be performed in all patients, and upper endoscopy, colonoscopy, and pelvic MRI according to CD location. Upper tract (UT), small bowel (SB), colon/rectum (CR), and anus (AN) were divided into 3, 20, 6 and 1 segments, respectively. History of previous surgery was collected per segment. For each segment, 1 gastroenterologist and 1 radiologist per centre, identified the presence of predefined stricturing and/or penetrating lesions of maximal severity (grade 1 to 3) at each investigation. They provided a damage evaluation for each non-resected segment ranging from 0 to 10, 10 corresponding to the damage of a completely resected segment. Investigator organ damage evaluation was calculated as the sum of segmental damage evaluations. Finally, investigators provided a global damage evaluation from 0 to 10 for each patient according to the 4 organ damage scores, calculated as a function of investigator organ damage evaluations, resections and a total number of segments. The correlation between the investigator global damage evaluation and the LI was high on the construction sample, since coefficients to derive the LI were estimated by maximising this correlation, and is expected to be lower on data obtained in new patients by new investigators. Thus, the LI would be validated if the linear regression model of investigator global damage evaluation on LI shows a still high correlation. The same applies to investigator damage evaluation of each organ and each organ component of the LI. Results 134 patients were included in 15 centres, 7 to 10 per centre. Correlation coefficients between investigator organ damage evaluation and each organ component of the LI were 0.91, 0.96, 0.95, and 0.81, for UT, SB, CR and AN, respectively. The correlation coefficient between investigator global damage evaluation and the LI was 0.98 (Figure 1). Proportions of the investigator organ damage evaluation variance explained by each organ component of the LI were 82%, 91%, 89%, 65%, for UT, SB, CR, AN, respectively. This proportion was 96% for the investigator global damage evaluation and the LI. Conclusion The Lémann index is now a validated index to assess cumulative bowel damage in CD that can be used in epidemiological studies and disease modification trials. Reference

Background Current evidence demonstrates that anti-TNF therapies lead to clinical response rates >50% have been reported in the short-term. These remission rates decrease to about a third of patients who initially achieved remission, after three years. Options are limited in cases refractory to biologic therapy, and there is limited knowledge of disease course in these cases, in part due to limited disease states characterised for Crohn’s perianal fistula in the absence of cure. This study applies recently described disease states within the context of Crohn’s perianal fistula to determine the fate of patients refractory to initial biologic therapy and quantitatively evaluate the health resource impact of the loss of response to treatment in this cohort. Methods Retrospective review of records from patients undergoing anti-TNF treatment for Crohn’s perianal fistula at St Mark’s Hospital between January 2007–December 2016, identified those refractory to treatment. We applied disease states defined from a recent vignette study of the general public and CD patients in the UK, and also obtained data on length of time patients spent in each disease state and subsequent disease states they transitioned to and created a Markov model to assess transition probabilities. We also collected data on healthcare resource utilisation (MRI, hospital interactions, surgical/medical therapy) within each disease state. Results Eight fistula disease states (including proctectomy, defunctioning surgery, remission and symptomatic states) were retrospectively ascribed to all clinical records/visits where documentation was available. The majority of refractory patients were switched on to alternate anti-TNF therapy and most reside in a ‘mild chronic symptomatic fistula’ disease state with a minority of patients subsequently transitioning into a severe disease state or remission state. Successful proctectomy disease state accounted for the longest period of continuous length of time in any one disease state (mean 4.4 years). The overall remission rate (of any duration) for our study cohort of 78 patients was 46%; however, sustained (1year or more) remission rate was 27%. Some 19% patients underwent proctectomy. There was considerable healthcare resource utilisation amongst all disease states particularly with biologic therapy (most expensive healthcare resource). Conclusion Whereas most patients reside in a mild chronic state following failure of at least one biologic therapy, a fifth of patients refractory to treatment undergo proctectomy which, when successful, accounts for the longest continuous length of time patients spend in a single disease state. There remains considerable healthcare resource utilisation and better treatment options are needed in refractory patients.

Background: Magnetic Resonance Imaging (MRI) is the tool used to assess response to medical therapy for the treatment of perianal Crohn’s fistulae. Quantifying fistula volumes would be more beneficial than relying on subjective MRI reports. We aim to use computer software and MRI segmentation to design 3D models of fistula tracks and measure baseline and post-biologics treatment fistula volumes. Methods: Ten baseline and post-biologics MRI images of Crohn’s perianal fistulae were randomly selected. Three-Dimensional fistula models were independently created by a surgeon and radiologist • Manual fistula volumes were calculated for each patient and the results compared • Data were obtained on Perianal Disease Activity Index (PDAI) scores, clinical and radiological healing for these patients. Data were analysed using Spearman’s correlation to determine whether a change in fistula volume over a one-year period correlated with a change in PDAI score over the same time period. Fistula volumes and PDAI score were also correlated with degrees of clinical healing. Results: Baseline volumes for the surgeon showed a median of 9766mm3 (IQR 4636, 30980). Post-biologics volumes had a median of 4200mm3 (IQR 2720, 20070). A change in baseline and post-treatment volumes was also observed by the radiologist; the median volume was 9207mm3 (IQR 5132, 21710) for the baseline MRIs and 2872mm3 (IQR 1827, 18830) for the post-treatment ones.