Ulcerative Colitis: Thomson M

Smith LA, Tiffin N, Thomson M, Cross SS, Hurlstone DP. · The General Infirmary, Leeds, Yorkshire, UK. · J Gastroenterol Hepatol. · Pubmed #18557799 No free full text.

Abstract: Advances in imaging technology and engineering have now permitted functional integration of a confocal endomicroscope into the distal tip of a conventional video colonoscope enabling imaging of the surface epithelium and the underlying lamina propria during ongoing video endoscopy. For the first time, the endoscopist is now able to resolve the surface and subsurface mucosa at cellular resolution in vivo and in real time. A new era in endoscopic imaging has therefore begun - histoendoscopy. In addition to providing a high-accuracy in vivo optical biopsy tool for the differentiation between benign hyperplasia, intra-epithelial neoplasia and carcinoma in sporadic cohorts, endomicroscopy with targeted biopsies has now been shown to increase the yield of intra-epithelial neoplasia complicating ulcerative colitis. Furthermore, recent data examining endomicroscopic molecular ex vivo imaging using anti-CD44v6 antibody has identified aberrant crypt foci based on their surface molecular expression. Receptor overexpression in vivo in humans may, in the near future, be exploited for the diagnosis of inflammation, neoplasia and in predicting targeted molecular therapy. Endomicroscopy will be key to this immuno-imaging interface. Within the present review, we discuss the current clinical evidence in support of confocal endomicroscopy and explore the new diagnostic possibilities for this technology.

Hurlstone DP, Tiffin N, Brown SR, Baraza W, Thomson M, Cross SS. · Gastroenterology and Liver Unit at the Royal Hallamshire Hospital, Sheffield, UK. · Histopathology. · Pubmed #17903203 No free full text.

Abstract: Recently, miniaturization of a novel confocal laser endomicroscope (Optiscan Pty, Notting Hill, Victoria, Australia) has permitted functional integration into the distal tip of a conventional video colonoscope (Pentax EC3870K; Pentax, Tokyo, Japan) enabling imaging of the surface epithelium and the underlying lamina propria during ongoing video endoscopy. Using endomicroscopy and intravenous sodium fluorescein as a contrast agent, 'virtual histology' can be created, which allows visualization of both the surface epithelium, and some of the lamina propria (down to a quarter of a millimetre), including the microvasculature. Confocal endomicroscopy may have major implications in the future of colonoscopy as uniquely it allows in vivo diagnosis of colonic intraepithelial neoplasia and carcinoma enabling 'smart' biopsy targeting and hence potentially influencing 'on table' management decisions. Initial pilot data have now shown that confocal imaging in vivo using the newly developed EC3870K has high overall accuracy for the immediate diagnosis of intraepithelial neoplasia and carcinoma in sporadic screened cohorts, but also has a role in the detection of intraepithelial neoplasia detection in chronic ulcerative colitis cancer screening when used in conjunction with methylene blue chromoscopy. We discuss the current evidence in support of confocal endomicroscopy in the colorectum and explore the new diagnostic possibilities for this technology.

Hurlstone DP, Thomson M, Brown S, Tiffin N, Cross SS, Hunter MD. · Gastroenterology and Liver Unit, Royal Hallamshire Hospital, Sheffield, UK. · Clin Gastroenterol Hepatol. · Pubmed #17690019 No free full text.

Abstract: BACKGROUND & AIMS: The management of dysplasia-associated lesional mass (DALM) and adenoma-like mass (ALM) in chronic ulcerative colitis (CUC) differs radically, involving total pan-proctocolectomy vs endoscopic resection and surveillance. Such lesions cannot be reliably differentiated using conventional colonoscopy. Confocal laser scanning imaging enables in vivo surface and subsurface cellular resolution imaging during ongoing video endoscopy. The aim of this study was to prospectively assess the clinical applicability and predictive power of the Pentax EC3870K endomicroscope for the in vivo differentiation of ALM and DALM in CUC during ongoing videocolonoscopy. METHODS: Patients were recruited who had a diagnosis of ALM or DALM within the previous 16 weeks. Confocal laser endomicroscopic (CLE) imaging of the circumscribed lesion and 4 adjacent mucosal segments was performed. Targeted biopsy with and without tissue sampling with endoscopic mucosal resection was performed and compared with conventional histopathology as the gold standard. RESULTS: Thirty-six patients with 36 lesions fulfilled the study entry criteria. Using modified Mainz criteria for the in vivo diagnosis of ALM and DALM, the kappa coefficient of agreement between CLE and histopathologic evaluation was 0.91, and accuracy was 97% (95% confidence interval = 86%-99%). CONCLUSIONS: This is the first study addressing the novel application of the Pentax EC3870K endomicroscopy system for the in vivo differentiation of ALM and DALM during ongoing video colonoscopy in CUC. We have shown that ALM and DALM can be differentiated with a high overall accuracy, enabling the safe selection of patients suitable for endoluminal resection versus immediate referral for pan-proctocolectomy.

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.

Castellaneta SP, Afzal NA, Greenberg M, Deere H, Davies S, Murch SH, Walker-Smith JA, Thomson M, Srivistrava A. · University Department of Paediatric Gastroenterology, Department of Histopathology, Royal Free Hospital, London, UK. · J Pediatr Gastroenterol Nutr. · Pubmed #15319625 No free full text.

Abstract: BACKGROUND: Discrimination between ulcerative colitis (UC) and Crohn disease (CD) may be difficult on ileo-colonoscopy alone because of a lack of definitive lesions. Retrospective studies show upper gastrointestinal endoscopy may be helpful in confirming diagnosis in such cases. AIMS: To prospectively determine importance of upper gastrointestinal endoscopy in diagnosis of inflammatory bowel disease (IBD) and assess factors predictive of upper gastrointestinal involvement in IBD. METHODS: All pediatric patients were enrolled prospectively and consecutively over a 2-year period and investigated with an ileo-colonoscopy and barium meal follow-through. Children with procto-sigmoiditis, later confirmed histologically to be typical of UC, were excluded from the study. The remainder underwent upper gastrointestinal endoscopy. The protocol and methodology were determined a priori. RESULTS: 65 children suspected of IBD underwent colonoscopy. Of the total, 11 had recto-sigmoiditis with typical macroscopic appearances of UC; once this was confirmed on histology these patients were excluded from the study. Of the 54 children (males, 31; median age, 11.1 years) remaining, 23 were initially diagnosed with CD on ileo-colonoscopy and 18 (33%) were diagnosed with UC. The diagnosis remained ambiguous in 13 (six colonic, four ileo-colonic, three normal colon) on clinical, radiologic and histologic grounds. Upper GI endoscopy helped to confirm CD in a further 11 (20.4%). Two patients were diagnosed with indeterminate colitis.Upper gastrointestinal inflammation was seen in 29 of 54 (22 CD; 7 UC ). Epigastric and abdominal pain, nausea and vomiting, weight loss and pan-ileocolitis were predictive of upper gastrointestinal involvement (P < 0.05). However, 9 children with upper gastrointestinal involvement were asymptomatic at presentation (31%). Overall upper gastrointestinal tract inflammation was most common in the stomach (67%), followed by the esophagus (54%) and duodenum (22%). CONCLUSIONS: Upper gastrointestinal tract endoscopy should be part of the first-line investigation in all new cases suspected of IBD. Absence of specific upper gastrointestinal symptoms do not preclude presence of upper gastrointestinal inflammation.

Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S, O'Leary JJ, Berelowitz M, Walker-Smith JA. · University Department of Medicine, Royal Free and University College Medical School, London, United Kingdom. · Am J Gastroenterol. · Pubmed #11007230 No free full text.

Abstract: OBJECTIVE: Intestinal pathology, i.e., ileocolonic lymphoid nodular hyperplasia (LNH) and mucosal inflammation, has been described in children with developmental disorders. This study describes some of the endoscopic and pathological characteristics in a group of children with developmental disorders (affected children) that are associated with behavioral regression and bowel symptoms, and compares them with pediatric controls. METHODS: Ileocolonoscopy and biopsy were performed on 60 affected children (median age 6 yr, range 3-16; 53 male). Developmental diagnoses were autism (50 patients), Asperger's syndrome (five), disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD) (one), schizophrenia (one), and dyslexia (one). Severity of ileal LNH was graded (0-3) in both affected children and 37 developmentally normal controls (median age 11 yr, range 2-13 yr) who were investigated for possible inflammatory bowel disease (IBD). Tissue sections were reviewed by three pathologists and scored on a standard proforma. Data were compared with ileocolonic biopsies from 22 histologically normal children (controls) and 20 children with ulcerative colitis (UC), scored in an identical manner. Gut pathogens were sought routinely. RESULTS: Ileal LNH was present in 54 of 58 (93%) affected children and in five of 35 (14.3%) controls (p < 0.001). Colonic LNH was present in 18 of 60 (30%) affected children and in two of 37 (5.4%) controls (p < 0.01). Histologically, reactive follicular hyperplasia was present in 46 of 52 (88.5%) ileal biopsies from affected children and in four of 14 (29%) with UC, but not in non-IBD controls (p < 0.01). Active ileitis was present in four of 51 (8%) affected children but not in controls. Chronic colitis was identified in 53 of 60 (88%) affected children compared with one of 22 (4.5%) controls and in 20 of 20 (100%) with UC. Scores of frequency and severity of inflammation were significantly greater in both affected children and those with UC, compared with controls (p < 0.001). CONCLUSIONS: A new variant of inflammatory bowel disease is present in this group of children with developmental disorders.

Hurlstone DP, Kiesslich R, Thomson M, Atkinson R, Cross SS. · Gastroenterology and Liver Unit at the Royal Hallamshire Hospital Sheffield/The Sheffield Hallam University Academy of Endomicroscopy, Sheffield, UK. · Gut. · Pubmed #18192453 No free full text.

Abstract: BACKGROUND: The diagnosis of intraepithelial neoplasia is pivotal for ongoing clinical management decisions in ulcerative colitis. Previous studies have compared the diagnostic yield of endomicroscopy with conventional "white light" endoscopy and hence the overall objective increase of endomicroscopy targeted biopsies as compared to chromoscopy guided alone is not apparent. AIMS: We performed a prospective randomised controlled study to compare the diagnostic yield of intraepithelial neoplasia and cancer in patients undergoing ulcerative colitis screening using chromoscopy assisted endomicroscopy (group A) versus pan-colonic chromoscopy assisted colonoscopy (group B). METHODS: Patients were randomised in a 1:1 ratio to undergo screening colonoscopy using either chromoscopic endomicroscopy or chromoscopy alone with targeted biopsies. Circumscribed lesions were characterised using endomicroscopy and chromoscopy with pit pattern analysis. Targeted biopsies in addition to conventional 10 cm quadrantic biopsies were taken. Primary outcome addressed the number of intraepithelial neoplasias detected in each group. RESULTS: Endomicroscopy targeted biopsies significantly increased the yield of intraepithelial neoplasia as compared to pan-chromoscopy and biopsy alone (p<0.001) and also increased the yield of high-grade dysplastic lesions (p<0.001). Endomicroscopy targeted biopsies increased the diagnostic yield of intraepithelial neoplasia as compared to chromoscopy guided biopsies alone by 2.5-fold. CONCLUSIONS: This is the first randomised controlled study to show the true clinical benefit of endomicroscopy for the in vivo detection and characterisation of intraepithelial neoplasia in chronic ulcerative colitis surveillance colonoscopy. Endomicroscopy with targeted biopsy may potentially be the "gold standard" for the detection of intraepithelial neoplasia in ulcerative colitis.