Shraddha Gulati

Vedolizumab in Inflammatory Bowel Disease Associated with Autoimmune Liver Disease Pre- and Postliver Transplantation: A Case Series.

To the Editor: Inflammatory bowel disease (IBD) associated with primary and autoimmune sclerosing cholangitis seems to represent a distinct clinical entity in comparison with “classical” ulcerative colitis and Crohn’s disease. Antitumor necrosis factor (TNF) therapy can be efficacious, but systemic complications remain a real concern, especially after liver transplantation (LT), whereas evidence for other therapeutic interventions is limited to preclinical models and small case series. Vedolizumab (VDZ), a humanized monoclonal antibody directed against the a4b7 integrin, is indicated for induction and maintenance of remission of moderate to severe IBD, either naive or refractory to anti-TNF agents. In this letter, we report our experience of VDZ for 10 patients with primary sclerosing cholangitis/autoimmune sclerosing cholangitis–IBD preand post-LT (n 1⁄4 5, respectively). Table 1 summarizes the disease characteristics and outcomes. Overall, a clinical response was seen in 4/10 patients (40%), 1 of whom achieved clinical remission (sustained to last follow-up). Surgery was required for 1 patient during induction because of acute severe colitis. The median duration of VDZ therapy in the 9 patients who received maintenance was 7.4 (1.4–12.5) months. In responders, a drop in fecal calprotectin (mg/g; median 708 [60–2696] versus 90 [32–960], P 1⁄4 0.03 by Wilcoxon test) and an improvement in quality of life scores were observed (5 [0, 13] versus 13 [8, 16], P 1⁄4 0.03). Abnormalities in liver biochemistry were seen in 2 postLT patients, but both had recurrence of their liver disease before VDZ initiation. No infective complications were attributed to VDZ use. There were no malignancies identified during the follow-up period. This is the first case series of VDZ use in primary sclerosing cholangitis/autoimmune sclerosing cholangitis–IBD patients preand post-LT. Therapy has been well tolerated by all patients, and no safety signals have been identified during the follow-up period despite concomitant immunosuppressants. Even in the context of anti-TNF failure, a good response rate has been documented with improvement in symptoms, objective markers of intestinal inflammation, and quality of life. Followup in this cohort is too short so far to comment on whether VDZ therapy influences the expected rate of pre-LT flares or postLT recurrence of liver disease, but to date, no such events have been recorded. As experience increases, taking into account its potential beneficial effects for autoimmune liver disease and the infectious complications associated with antiTNF use, it seems likely that VDZ will become the treatment of choice for IBD in this group of patients.

Letter: vedolizumab for autoimmune liver disease associated inflammatory bowel disease

1. Everhov AH, Ludvigsson JF, Ol en O. Letter: phenotype and natural history of elderly onset inflammatory bowel disease. Aliment Pharmacol Ther. 2018;47:1420-1421. 2. Ma~ nosa M, Calafat M, de Francisco R, et al. Phenotype and natural history of elderly onset inflammatory bowel disease: a multicentre, case-control study. Aliment Pharmacol Ther. 2018;47:605-614. 3. Everhov AH, Halfvarson J, Myrelid P, et al. Incidence and treatment of patients diagnosed with inflammatory bowel diseases at 60 years or older in Sweden. Gastroenterology. 2017;154:518-528. 4. Lobat on T, Ferrante M, Rutgeerts P, Ballet V, van Assche G, Vermeire S. Efficacy and safety of anti-TNF therapy in elderly patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2015;42: 441-445. 5. Cottone M, Kohn A, Daperno M, et al. Advanced age is an independent risk factor for severe infections and mortality in patients given anti-tumor necrosis factor therapy for inflammatory bowel disease. Clin Gastroenterol Hepatol. 2011;9:30-35. 6. Calafat M, Ma~ nosa M, Ca~ nete F, et al. The initiation of thiopurines in elderly patients with inflammatory bowel disease is associated with an increased risk of adverse effects: a case–control study of the ENEIDA registry. J Crohn’s Colitis. 2018;12:S023S025. 7. Charpentier C, Salleron J, Savoye G, et al. Natural history of elderly onset inflammatory bowel disease: a population-based cohort study. Gut. 2014;63:423. 8. Lakatos PL, David G, Pandur T, et al. IBD in the elderly population: results from a population-based study in Western Hungary, 19772008. J Crohn’s Colitis. 2011;5:5-13. 9. Jeuring SF, van den Heuvel TR, Zeegers MP, et al. Epidemiology and long-term outcome of inflammatory bowel disease diagnosed at elderly age-an increasing distinct entity? Inflamm Bowel Dis. 2016;22:1425-1434. 10. Fries W, Viola A, Manetti N, et al. Disease patterns in late-onset ulcerative colitis: results from the IG-IBD “AGED study”. Dig Liver Dis. 2017;49:17-23.

Dual camera colon capsule endoscopy increases detection of colorectal lesions

Sir,Colon capsule endoscopy (CCE) was introduced in 2006. A second-generation CCE (Pillcam® COLON 2) is now available for clinical application.[1–3] Recent studies report sensitivity of a second-ge...

Early change in faecal calprotectin predicts primary non-response to anti-TNFα therapy in Crohn's disease.

Abstract Objective: The early identification of primary non-response to anti-TNFα therapy facilitates the timely management of patients with Crohn’s disease (CD). A recent, pilot study to detect prognostic markers of early response to anti-TNFα therapy identified the two genes coding for the calprotectin subunits (S100A8, S100A9) to be among the most highly expressed gene transcripts in non-responders. This study tests the hypothesis that measurements of faecal calprotectin (FCAL) pre- and post-anti-TNFα induction can predict primary non-response. Methods: Retrospective study of 32 CD patients treated over a two-year period. Outcomes were assessed at 6 months based on clinical activity scores and the use of corticosteroids: (a) remission: Harvey–Bradshaw index (HBI) < 5, off corticosteroids >2 months; (b) response: drop in HBI >3, off corticosteroids; (c) non-response: ΔFCAL (and ΔCRP, respectively) was calculated as (FCAL post-induction – FCAL pre-induction) × 100/FCAL pre induction. Results: At 6 months, 23 (72%) patients had responded (median (interquartile range) HBI: 4 (3–5), FCAL: 55 (27–146)), 17 (73%) of whom were in remission [HBI: 3 (2.5–4) and FCAL: 42 (16–115)]. There was a significant difference in the ΔFCAL from baseline to post-induction in the three groups (p < 0.0001). Comparing non-responders to combined response and remission groups, the AUC of ΔFCAL to predict outcome at 6 months was 0.97. Using ROC analysis, a Δ70% returned a sensitivity and specificity of 99% and 96%, respectively (likelihood ratio, LR= 23). ΔCRP did not predict 6 months outcomes. Conclusions: A drop in FCAL <70% after induction predicts primary non-response to anti-TNFα in CD.

OWE-002 Significance of biopsies before large colorectal endoscopic resections and histopathological features of high risk lesions

Introduction Guidelines on endoscopic resection (ER) of colorectal superficial neoplastic lesions (CSNL) recommend against biopsy sampling but many are extensively sampled prior to referral, despite the deleterious effect on ER, to exclude adenocarcinoma or high grade dysplasia (HGD), reflecting a lack of understanding of the incidence and nature of adenocarcinoma or HGD within different morphological sub-types. It is therefore important to define the significance of HGD on biopsy samples and place this in the context of the histopathological characteristics of high risk lesions. Methods ERs of large (≥2 cm) CSNL were included. Sensitivity and specificity of HGD on biopsy and higher risk morphology (laterally spreading tumour (LST) non-granular/LST mixed nodular type/IIc component) for diagnosing covert invasive adenocarcinoma and confirmed HGD after ER were calculated and compared (Mcnemar’s test). In addition, 50 high risk lesions (containing HGD or invasive adenocarcinoma) were subjected to more detailed histopathological analysis. Results Results from prior biopsy sampling were available for 291 lesions (mean size 62.8 mm). Histopathology after ER revealed HGD in 85 (29%) and invasive adenocarcinoma in 26 (9%). Sensitivity and specificity of HGD on biopsy (n=60) for invasive adenocarcinoma were 50% (95% CI 32%–68%) and 82% (95%–CI 77%–86%), and for confirmed HGD after ER were 47% (95% CI 37%–57%) and 90% (95% CI 85%–94%) respectively. Sensitivity and specificity of high risk morphology (n=124) for HGD after ER were 71% (95% CI 60%–79%) and 69% (95% CI 62%75%) respectively. The sensitivity of high risk morphology was significantly higher than HGD on biopsy sampling (p=0.002). Detailed histopathological analysis of high risk lesions revealed invasive adenocarcinoma in 40% but a further 18% had non-invasive areas with cytological and architectural features indistinguishable from invasive adenocarcinoma. HGD was multifocal in 56%. The mean size of the focus of HGD was only 5.6 mm, and of adenocarcinoma was 11.0 mm. Mean lesion size was 53.6 mm. Conclusion Biopsy sampling of large CSNL has no value in excluding high risk lesions and morphology alone has higher sensitivity for high risk lesions. Histopathological analysis of high risk lesions reveals that areas of HGD or adenocarcinoma are very small relative to the lesion size and many contain non-invasive areas which would be cytologically indistinguishable from invasive adenocarcinoma on a biopsy. Despite this, biopsy sampling remains extremely common. Understanding of these findings and improved education regarding accurate lesion assessment may help reduce rates of inappropriate sampling.

PTH-044 Risk of stenosis and outcomes following endoscopic resection of large colorectal lesions involving more than 75% of the luminal circumference

Introduction Little is known about the risk of stenosis and outcomes following endoscopic resection of colorectal lesions which leave extensive mucosal defects. A limited number of studies suggest significant stenosis rates, although reported outcomes and suggested management are conflicting. We determined the risk of stenosis and outcomes of endoscopic resection leaving mucosal defects≥75% of the circumference. Method Patients who underwent endoscopic resection using endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD) and hybrid techniques of colorectal lesions≥2 cm were included. Patients were grouped according to circumferential extent of the mucosal defect. Surveillance colonoscopy was performed at 3 and 12 months. Clinicopathological characteristics and outcomes were compared between groups. Results 435 lesions≥2 cm were resected using EMR (n=342), ESD (n=45) or hybrid techniques (n=48). Circumferential extent of the mucosal defect was ≥75% in 41 patients. 8 were fully circumferential: 1 caecal lesion and the rest in the recto-sigmoid and rectum. 3 circumferential lesions contained deeply invasive adenocarcinoma and 1 benign lesion ultimately required surgery. 41 lesions with a mucosal defect ≥75% of the circumference had a mean size of 100.5 mm vs 49.0 mm for other lesions (p<0.001). These patients had significantly more complications (16.7% vs 4.7%, p<0.001), including a higher rate of perforation (8.3% vs 2.3%, p=0.02), although none required surgery, and a significantly higher rate of recurrence (44.8% vs 9.2%, p<0.001). 79% of patients without cancer were free from recurrence and had avoided surgery at last follow up compared to 97% with mucosal defects<75% (p<0.001). Stenosis occurred in 7 patients: 4 lesions extensively involving the rectum and recto-sigmoid and 2 lesions involving the sigmoid extending to the rectosigmoid. 1 of these involved a mucosal defect of only 50% of the circumference and 3 were fully circumferential. 1 patient had a symptomatic anorectal stenosis requiring dilatation under anaesthesia, 1 patient was asymptomatic but underwent early dilatation after the first surveillance endoscopy. The remaining patients were asymptomatic and managed expectantly. In all these latter cases spontaneous improvement in the stricture was noted at the subsequent surveillance colonoscopy. Conclusion The majority of patients with these extensive complex lesions can successfully be treated with endoscopic resection and avoid surgery. However, these patients have a significantly greater risk of complications and recurrence and should be managed in a tertiary institution. Although there is a significant risk of stenosis, it appears that most cases are asymptomatic and spontaneously improve with expectant management. Disclosure of Interest None Declared

PTH-042 Outcomes of endoscopic resection of recurrent colorectal lesions treated at a uk tertiary referral centre

Introduction Endoscopic resection of large colorectal lesions, especially by piecemeal EMR, carries a significant risk of recurrence. Although several series examine the outcomes and risk of recurrence following endoscopic resection, few focus on the outcomes of patients being treated for recurrence after initial expert resection, and these mostly focus on one technique to deal with recurrence. We evaluated the outcomes after recurrence of colorectal lesions after apparent successful endoscopic resection in a specialised UK tertiary institution employing a range of resection techniques. Method Consecutive patients who underwent endoscopic resection of colorectal lesions≥2 cm were included. All lesions were assessed with magnification chromoendoscopy supplemented by colonoscopic ultrasound in selected cases. A lesion specific approach was used to decide on resection technique. Outcomes were evaluated for patients treated for recurrent lesions. Results Of 396 colorectal lesions≥2 cm successfully resected at our institution, recurrence occurred in 50. 36% of these patients had already had a mean of 1.6 previous failed attempts at resection prior to referral to our institution, and 66% had had either a failed attempt at resection or extensive sampling involving ≥6 biopsies or tattoo placed under the lesion. 69% of patients were successfully treated with further endoscopic resection and avoided surgery. 27 patients had endoscopic resection of a recurrence larger than 20 mm, with a mean lesion size of 48.3+/-19.1 mm. Techniques used were EMR (n=16), ESD (n=2), Hybrid ESD and EMR (n=9). The remaining lesions<2 cm were resected using EMR. A mean of 1.4+/-0.75 procedures were required to achieve successful endoscopic treatment of recurrence. 24 patients who were ultimately successfully treated with endoscopic resection required a single further endoscopic resection after recurrence, 10 patients required 2 or more further resections. 8 patients required surgery, 4 as a result of developing invasive adenocarcinoma with the recurrence. There were no perforations as a result of endoscopic resection of recurrent lesions and only 1 patient was readmitted with post-procedural bleeding which was managed conservatively. Conclusion These data demonstrate the challenges of an advanced endoscopic resection service in much of western practice where patients with recurrent lesions represent a particularly complex cohort, most of whom have already had extensive prior manipulation or attempts at resection. Familiarity with a range of resection techniques and appropriate equipment is essential to successfully treat recurrent lesions in this group with endoscopic resection, which can be achieved in the majority of patients without significant complications. Disclosure of Interest None Declared

Multimodal Endoscopic Evaluation Guides Treatment Decisions for Early Rectal Cancers and Complex Rectal Neoplasms

Introduction There is wide variation in the treatment of early rectal cancers and complex rectal neoplasms. With increasing emphasis on minimally invasive techniques and organ preservation, we aimed to evaluate the utility of a standardised, structured and rational assessment of rectal tumours to inform decision making for patients referred to a tertiary unit specialising in early rectal cancer. Method Since 2012, our unit has employed a standard approach to the assessment of rectal lesions which includes multimodal endoscopic assessment of all lesions using white light, magnification chromoendoscopy and colonoscopic high frequency miniprobe ultrasound to inform treatment decisions. Patients can then be allowed a fully informed decision regarding treatment options, which include advanced endoscopic resection, minimally invasive transanal endoscopic microsurgery (TEMS) or laparoscopic segmental oncological resection, all of which are offered by our unit. Results 191 patients (mean age 71 years) with rectal tumours were referred to our unit for an assessment regarding suitability for local resection. Multimodal endoscopic evaluation assessed 128 lesions as benign and 63 as malignant. 125 lesions with a mean size of 70.9 mm were treated with endoscopic resection: 108 adenomas, 9 adenocarcinomas and 5 neurendocrine tumours. 92% were performed without general anaesthesia and 78% as day cases. There were 2 small perforations treated endoscopically with clips with no adverse sequelae. The recurrence rate was 10%, all managed endoscopically. At last surveillance 97% of patients were free from recurrence. None required a major resection. 37 patients underwent TEMS as curative treatment or for patients unfit for, or refusing major resection. Only 3 patients with benign neoplasms had TEMS. The few remaining patients were either directed to major surgical resection, palliative options or declined treatment. Conclusion A standardised rational approach employing multimodal endoscopic evaluation for assessing complex rectal neoplasms results in high rates of safe, effective organ preserving treatment with almost no patients with benign disease subjected to a surgical procedure. Disclosure of Interest None Declared

Colorectal endoscopic submucosal dissection: patient selection and special considerations

Endoscopic submucosal dissection (ESD) enables en bloc resection of large complex colorectal superficial neoplastic lesions, resulting in very low rates of local recurrence, high-quality pathologic specimens for accurate histopathologic diagnosis and potentially curative treatment of early adenocarcinoma without resorting to major surgical resection. The safety and efficacy of the technique, which was pioneered in the upper gastrointestinal tract, has been established by the consistently impressive outcomes from expert centers in Japan and some other eastern countries. However, ESD is challenging to perform in the colorectum and there is a significant risk of complications, particularly in the early stages of the learning curve. Early studies from western centers raised concerns about the high complication rates, and the impressive results from Japanese centers were not replicated. As a result, many western endoscopists are skeptical about the role of ESD and few centers have incorporated the technique into their practice. Nevertheless, although the distribution of expertise, referral centers and modes of practice may differ in Japan and western countries, ESD has an important role and can be safely and effectively incorporated into western practice. Key to achieving this is meticulous lesion assessment and selection, appropriate referral to centers with the necessary expertise and experience and application of the appropriate technique individualized to the patient. This review discusses the advantages, risks and benefits of ESD to treat colorectal lesions and the importance of preprocedure lesion assessment and in vivo diagnosis and outlines a pragmatic rationale for appropriate lesion selection as well as the patient, technical and institutional factors that should be considered.

Peroral endoscopic myotomy: a literature review and the first UK case series

ABSTRACT Peroral endoscopic myotomy (POEM) is an established treatment for primary achalasia. It has gained endorsement from the American Society for Gastrointestinal Endoscopy with increasing clinical acceptance since the first procedure, performed in Japan in 2008. The first successful POEM in the UK was performed in November 2013 at King’s College Hospital and this article presents the first UK case series. Prospective data were collected at 3 and 12–24 months for consecutive patients undergoing POEM. Post-POEM gastro-oesophageal reflux health-related quality of life scale (GORD-HRQoL) score was recorded. Statistical comparisons were made using paired non-parametric testing. In an initial series of 33 consecutive prospectively followed patients (12 female; 49.5±13 years; median follow-up 9 (3–28) months; 58% having had previous intervention), a 91% success rate has been achieved at 3 months. To date, 16 patients have reached the 12-month time point, with 13 (81%) sustaining response. This case series compares well with international cohorts and demonstrates excellent long-term safety and favourable efficacy.