Ulcerative Colitis: Sanders DS

Hurlstone DP, Sanders DS. · Royal Hallamshire Hospital, Room BD 82/B Floor Endoscopy, Sheffield, South Yorkshire, United Kingdom. · Curr Gastroenterol Rep. · Pubmed #16968609 No free full text.

Abstract: The basic rationale for secondary prevention of colorectal carcinoma is by endoscopic polypectomy. New technologies in the form of high-magnification or "zoom" colonoscopy complemented by chromoscopic agents permit early detection of neoplastic colorectal lesions, particularly flat and depressed types. Detailed morphologic characteristics of the surface crypt or "pit pattern" can be obtained with these techniques, enabling an in vivo "optical biopsy" and staging tool. Establishing suitability for endoscopic resection or surgical excision can be enhanced using these techniques. Furthermore, chromoscopic colonoscopy may have a role in routine endoscopic colorectal cancer surveillance programs in patients at high risk for colorectal neoplasia, such as those with long-standing ulcerative colitis and familial colorectal cancer syndromes. This review summarizes recent data regarding the prevalence and histopathologic characteristics of flat and depressed colorectal lesions in Western cohorts and describes how their detection and management can be improved by chromoscopy and magnification technology. We outline these techniques from a clinical perspective and describe the basic principles of endoscopic mucosal resection.

Bourreille A, Ignjatovic A, Aabakken L, Loftus EV, Eliakim R, Pennazio M, Bouhnik Y, Seidman E, Keuchel M, Albert JG, Ardizzone S, Bar-Meir S, Bisschops R, Despott EJ, Fortun PF, Heuschkel R, Kammermeier J, Leighton JA, Mantzaris GJ, Moussata D, Lo S, Paulsen V, Panés J, Radford-Smith G, Reinisch W, Rondonotti E, Sanders DS, Swoger JM, Yamamoto H, Travis S, Colombel JF, Van Gossum A, Anonymous00249. · Institut des Maladies de l'Appareil Digestif, CHU, Université de Nantes, Nantes, France. · Endoscopy. · Pubmed #19588292 No free full text.

Abstract: Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

Leeds JS, Höroldt BS, Sidhu R, Hopper AD, Robinson K, Toulson B, Dixon L, Lobo AJ, McAlindon ME, Hurlstone DP, Sanders DS. · Gastroenterology and Liver Unit, Royal Hallamshire Hospital, Sheffield, UK. · Scand J Gastroenterol. · Pubmed #17918008 No free full text.

Abstract: OBJECTIVE: The relationship between coeliac disease and inflammatory bowel disease (IBD) is controversial. The aim of this study was to determine the prevalence of coeliac disease in IBD and the prevalence of IBD in coeliac disease. MATERIAL AND METHODS: Patients were enrolled from specialist IBD and coeliac clinics. Antigliadins, endomysial, tissue transglutaminase antibody and total IgA levels were measured in IBD patients. Patients with positive antibodies were offered a duodenal biopsy. The notes on coeliac patients were reviewed for colonoscopic and biopsy findings. Controls were recruited from the local population. RESULTS: The study included 305 patients with coeliac disease, 354 with IBD and 601 healthy controls. The IBD group comprised 154 ulcerative colitis (UC) cases, 173 Crohn's disease, 18 indeterminate colitis and 9 cases of microscopic colitis. Forty-seven patients had positive antibodies and 3 had villous atrophy on biopsy. All three patients had positive anti-tissue transglutaminase antibodies but only two were endomysial antibody (EMA) positive. Ten coeliac patients had IBD (5 UC and 5 lymphocytic colitis). Five controls had coeliac disease and 2 had IBD (1 Crohn's disease and 1 UC). Stepwise multiple logistic regression showed only antibody positivity as being significant (p<0.0001). CONCLUSIONS: The prevalence of IBD in coeliac disease was increased 10-fold compared with that in controls (odds ratio 9.98, 95% CI 2.8-45.9, p=0.0006), while the prevalence of coeliac disease in IBD was comparable with that in controls (odds ratio 1.02, 95% CI, 0.24-4.29, p=1.0).

Hurlstone DP, Sanders DS, McAlindon ME, Thomson M, Cross SS. · Gastroenterology and Liver Unit, Royal Hallamshire Hospital, Sheffield, UK. · Endoscopy. · Pubmed #17163321 No free full text.

Abstract: BACKGROUND AND STUDY AIMS: Colonoscopy with mucosal biopsy is currently considered to be the "gold standard" investigation for the evaluation of disease activity and disease extent in ulcerative colitis. Conventional colonoscopic criteria are inadequate for assessing disease extent and for predicting clinical relapse, however. Histopathological markers of relapse, such as microscopic crypt abscess formation and mucin depletion cannot be identified using conventional endoscopy. The aim of this study was to evaluate the efficacy of high-magnification chromoscopic colonoscopy for the in vivo assessment of histopathological inflammation and disease extent using standardised endoscopic and histopathological criteria. PATIENTS AND METHODS: Total colonoscopy using the Olympus CF240Z magnifying colonoscope was performed prospectively in 325 consecutive patients with a known diagnosis of ulcerative colitis. A "biphasic" examination of all five colonic segments and the rectum was performed with conventional endoscopy followed by magnification imaging and biopsy. Disease activity was documented using Baron's classification, modified Saitoh criteria for magnification imaging, and Matts' histopathological grading. RESULTS: A total of 1800 images from 300 patients were analyzed (25 patients were excluded). The kappa coefficients of agreement between Saitoh's magnification criteria grades 1/2, 3/4, and 5/6 and Matts' histopathological grades 1/2, 3a/b, and 4/5 were 0.96, 0.62, and 0.51, respectively. Mild, moderate, and severe histopathological disease (Matts' grades 1/2, 3a - 4, and 5) were represented more accurately using Saitoh's criteria than by conventional Baron scores for all clinical parameters ( R = 0.976; P < 0.001). Magnification imaging was significantly better than conventional colonoscopy for predicting disease extent in vivo ( P < 0.0001). CONCLUSIONS: This is the largest prospective study and the only Western group to report on this application of magnification imaging. High-magnification imaging provides a sensitive and specific in vivo "virtual biopsy" in ulcerative colitis and so an instant biomarker for disease relapse, while accurately predicting disease extent. High-accuracy optical biopsy can limit the number of biopsies required, with significant cost savings for pathology services.

Hurlstone DP, Sanders DS, Atkinson R, Hunter MD, McAlindon ME, Lobo AJ, Cross SS, Thomson M. · Gastroenterology and Liver Unit at the Royal Hallamshire Hospital, Sheffield, UK. · Gut. · Pubmed #17135310 No free full text.

Abstract: BACKGROUND: The potential of endoscopic mucosal resection (EMR) for treating flat dysplastic lesions in chronic ulcerative colitis (CUC) has not been addressed so far. Historically, such lesions were referred for colectomy. Furthermore, there are only limited data to support endoscopic resection of exophytic adenoma-like mass (ALM) lesions in colitis. AIMS: To evaluate the safety and clinical outcomes of patients with colitis undergoing EMR for Paris class 0-II and class I ALM compared with sporadic controls. Secondary aims were to re-evaluate the prevalence, anatomical "mapping" and histopathological characteristics of both Paris class 0-II and class I lesions in the context of CUC. METHODS: Prospective clinical, pathological and outcome data of patients with colitis-associated Paris class 0-II and Paris class I ALM treated with EMR (primary end points being colorectal cancer development, resection efficacy, metachronous lesion rates and post-resection recurrence rates) were compared with those of sporadic controls. RESULTS: 204 lesions were diagnosed in 169 patients during the study period: 167 (82%) diagnosed at "entry" colonoscopy, and 36 (18%) diagnosed at follow-up. 170 ALMs, 18 dysplasia-associated lesion masses (DALMs) and 16 cancers were diagnosed. A total of 4316 colonoscopies were performed throughout the study period (median per patient: 6; range: 1-8). The median follow-up period for the complete cohort was 4.1 years (range: 3.6-5.21). 1675 controls were included from our prospective database of patients without CUC who had undergone EMR for sporadic Paris class 0-II and snare polypectomy of Paris type I lesions from 1998 onwards, and were considered to be at moderate to high lifetime risk of colorectal cancer. 3792 colonoscopies were performed throughout the study period in this group (median per patient: 4; range: 1-7). The median follow-up period was 4.8 years (range: 2.9-5.2). No statistically significant differences were observed between the CUC study group and controls with respect to age, sex, median number of colonoscopies per patient, median follow-up duration, post-resection complications, median lesional diameter or interval cancer rates. However, there was a significant between-group difference regarding the prevalence of Paris class 0-II lesions in the CUC group (82/155 (61%)) compared with controls (285/801 (35%); chi(2) = 31.13; p<0.001). Furthermore, recurrence rates of lateral spreading tumours were higher in the colitis cohort (1/7 (14%)) than among controls (0/10 (0%); p = 0.048 (95% CI 11.64% to 40.21%)). CONCLUSIONS: Flat DALM, similarly to Paris class I ALM, can be managed safely by EMR in CUC. A change in management paradigm to include EMR for the resection of flat dysplastic lesions in selected cases is proposed.

Hurlstone DP, Sanders DS, Lobo AJ, McAlindon ME, Cross SS. · Gastroenterology and Liver Unit, The Royal Hallamshire Hospital, Sheffield, United Kingdom. · Endoscopy. · Pubmed #16329015 No free full text.

Abstract: BACKGROUND AND STUDY AIMS: Recent data suggest that panchromoscopy using methylene blue can improve the detection of intraepithelial neoplastic lesions in the context of surveillance colonoscopy for patients with chronic ulcerative colitis. This method has also been shown to provide a more accurate diagnosis of the extent of disease and inflammatory activity. Interval cancers are known to occur in patients with chronic ulcerative colitis despite the adoption of currently accepted surveillance biopsy protocols. We hypothesised that targeted chromoscopy alone, with high-magnification imaging, may increase the total number of intraepithelial neoplastic lesions detected, compared with conventional colonoscopy and biopsy surveillance according to current protocols. PATIENTS AND METHODS: A total of 350 patients with long-standing ulcerative colitis (>or=8 years) underwent surveillance colonoscopy using high-magnification chromoscopic colonoscopy (HMCC). Quadrantic biopsies at 10-cm intervals were taken on extubation in addition to targeted biopsies of abnormal mucosal areas. Defined lesions were further evaluated using modified Kudo crypt pattern analysis. These data were compared with data from 350 disease duration- and disease extent-matched control patients who had undergone conventional colonoscopic surveillance between January 2001 and April 2005. RESULTS: Significantly more intraepithelial neoplastic lesions were detected in the magnification chromoscopy group compared with controls (69 vs. 24, P<0.0001). Intraepithelial neoplasia was observed in 67 lesions, of which 53 (79%) were detected using magnification chromoscopy alone. Chromoscopy increased the number of flat lesions with intraepithelial neoplasia detected compared with controls (P<0.001). Twenty intraepithelial neoplastic lesions were detected from 12,850 non-targeted biopsies in the HMCC group (0.16%), while 49 intraepithelial neoplastic lesions were detected from the 644 targeted biopsies in the HMCC group (8%). From 12,482 non-targeted biopsies taken in the control group patients, 18 (0.14%) showed intraepithelial neoplasia. The yield of intraepithelial neoplastic lesions from targeted biopsies in the control group (i. e. without HMCC imaging), however, was only modestly improved at 1.6% (6/369). Using modified Kudo criteria, the sensitivity and specificity for differentiating neoplastic from non-neoplastic lesions using HMCC were 93% and 88% respectively. The total procedure time was significantly longer in the HMCC group compared with controls (P<0.02). CONCLUSIONS: Magnification chromoscopy improves the detection of intraepithelial neoplasia in the endoscopic screening of patients with chronic ulcerative colitis. Neoplastic and non-neoplastic mucosal change can be predicted with a high overall accuracy using magnification techniques. These adjunctive endoscopic techniques have important clinical implications and may lead to changes in current practice guidelines.

Hurlstone DP, Sanders DS, Lobo AJ, McAlindon ME, Cross SS. · Gastroenterology and Liver Unit, The Royal Hallamshire Hospital, Sheffield, UK. · Eur J Gastroenterol Hepatol. · Pubmed #16292085 No free full text.

Abstract: BACKGROUND: High-frequency mini-probe ultrasound imaging permits trans-mural cross-sectional imaging of the colorectal wall. In ulcerative colitis, prognosis is dependent on the severity of mucosal inflammatory change where accurate assessment of disease activity is required to optimize medical therapy. Furthermore, predicting relapse of disease using conventional endoscopic, histopathological and clinical criteria has not proven reliable. AIM: To evaluate the correlation of high-frequency mini-probe imaging with standardized measures of clinical, endoscopic and histopathological severity. METHODS: High-frequency ultrasound images were obtained from the caecum to rectum in 200 patients. Tsuga colorectal ultrasound criteria were then compared to the endoscopic Baron score, Seo activity score and Matts histopathological grade. RESULTS: For rectal disease, the kappa coefficient between Tsuga criteria I/II and Matts grade 1/2 was 0.78 (95% CI, 0.67-0.89), 0.57 (95% CI, 0.46-0.68) and 0.48 (95% CI, 0.34-0.62) for Tsuga class IIIa/b, IVa/b and Matts grade 3a/b and 4, respectively. Colonic imaging showed a kappa coefficient between Tsuga class I/II and Matts grade1/2 of 0.76 (95% CI, 0.72-0.8). Tsuga class IIIa-IIIb/IVa-IVb as compared to Matts grade 3a-3b/4 yielded kappa coefficients of 0.49 (95% CI, 0.43-0.55) and 0.62 (95% CI, 0.56-0.69), respectively. In the rectum both the total wall thickness, mucosa and submucosa were significantly thicker in Matts grade 3b and 4 disease as compared to Matts grade 1/2 (P < 0.02) for all parameters. A significant increase in colonic total wall thickness was observed between Matts score 4 and Tsuga grade 1-3a disease (P < 0.001). CONCLUSIONS: High-frequency ultrasound is a valid adjunctive 'tool' for the trans-mural assessment of the colorectal wall in ulcerative colitis. This technique may aid in the initial diagnosis, and ongoing chronic management of disease.

Hurlstone DP, Shorthouse AJ, Cross SS, Brown S, Sanders DS, Lobo AJ. · Gastroenterology and Liver Unit, Royal Hallamshire Hospital, Sheffield, South Yorkshire S10, UK. · Tech Coloproctol. · Pubmed #15654525 No free full text.

Abstract: BACKGROUND: Persistence of underlying disease in the residual rectal mucosa and anal transition zone (ATZ) following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis and familial adenomatous polyposis provides a site for potential malignancy. For this reason endoscopic surveillance is performed, although conventional assessment may be unreliable. We hypothesized that the novel technique of high-magnification chromoscopic pouchoscopy (HMCP) may permit accurate anatomical localization of this high risk zone in vivo and permit improved biopsy accuracy. PATIENTS AND METHODS: We studied 132 patients with IPAA using HMCP. Three distinct zones were defined using magnification endoscopy: ATZ, appearing as a linear cellular marix; columnar cuff, identifiable by a type I crypt pattern; and ileal pouch body, appearing as villous projections. Quadrantic biopsies of these zones were taken in addition to biopsies of any other lesions noted. RESULTS: A total of 1586 biopsies were taken from zones 1-3 (median, 12; range, 5-16 per patient). Overall biopsy-targeting accuracies using magnification guidance as compared with histopathology were 82%, 73% and 91% for the ATZ, cuff and pouch body, respectively. No dysplasia was identified in the quadrantic surveillance biopsies. Histologically confirmed columnar metaplasia was visualized in vivo using magnification chromoscopy. Patients with IPAA >3 years' duration were more likely to have pouch reservoir columnar metaplasia as compared to those <3 years (p<0.01). Pouch reservoir metaplasia was associated with a pre-morbid diagnosis of high-grade dysplasia or carcinoma within the premorbid colectomy specimen (p<0.001). CONCLUSIONS: This is the first study to evaluate this novel application of high magnification chromoscopy. Magnification pouchoscopy is a valid predictor of ATZ and cuff anatomy, permitting accurate biopsy targeting. Further randomized studies validating this technique with an emphasis on dysplasia detection in larger cohorts are required.

Karmo M, Goh J, Boulton R, Sanders DS. · Birmingham Heartlands Hospital, 1 Sandy Way, Edgbaston, Birmingham B15 1EQ, UK. · Gut. · Pubmed #15591507 links to  free full text

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Wright S, Sanders DS, Lobo AJ, Lennard L. · University of Sheffield, School of Medicine and Biomedical Sciences, Academic Unit of Molecular and Clinical Pharmacology, The Royal Hallamshire Hospital, Sheffield, UK. · Gut. · Pubmed #15247179 links to  free full text

Abstract: BACKGROUND AND AIMS: There are conflicting reports on the role of azathioprine (AZA) thioguanine nucleotide (TGN) metabolites in optimising therapy for inflammatory bowel disease (IBD). The aim of this study was to investigate TGN intrapatient variation, and the relationship between TGN concentrations and disease activity in IBD patients taking long term constant dose AZA. METHODS: TGN and methylmercaptopurine nucleotide (MeMPN) concentrations were measured at intervals over a two year period. Disease activity was assessed at each clinic visit using the Crohn's disease activity index or Walmsley simple index for ulcerative colitis. RESULTS: Serial TGNs were measured in 159 patients (3-14 TGN assays, median 6). Intrapatient variation in TGN concentrations was 1-5-fold (median 1.6); the incidence of non-compliance was 13%. At the end of two years, 131 patients were evaluable at TGN steady state. Of this group, patients who remained in remission had significantly higher mean TGN concentrations than those patients who developed active disease (median TGNs 236 v 175, respectively; median difference 44 pmol (95% confidence interval 1-92); p = 0.04). MeMPN concentrations were not related to AZA efficacy or toxicity. CONCLUSIONS: This study has shown that lower TGN concentrations were linked to the development of active disease, and that TGNs may act as useful markers of compliance. However, it is clear that repeat TGN measurements are required for an unambiguous index of active metabolite exposure. In view of the high intrapatient variability in TGN production over time, TGN measurements may not be currently advocated for routine clinical use.

Hurlstone DP, McAlindon ME, Sanders DS, Koegh R, Lobo AJ, Cross SS. · The Gastroenterology and Liver Unit, Royal Hallamshire Hospital, Sheffield, England. · Gastroenterology. · Pubmed #14753220 No free full text.

This publication has no abstract.