A survey of patient informational preferences when choosing between medical and surgical therapy for ulcerative colitis: a sub-study from the DISCUSS project.

AIM: People living with ulcerative colitis (UC) have two broad treatment avenues, namely medical or surgical therapy. The choice between these can depend on patient preference as well as the receipt of relevant information. The aim of this study was to define the informational needs of patients with UC. METHOD: A postal survey was designed to capture respondent demographics, treatment experienced within the previous 12 months and informational preferences by rating a long list of items. It was delivered through two hospitals that provide tertiary inflammatory bowel disease services. Descriptive analyses were performed to describe demographics and experiences. Principal component analysis was carried out using a varimax rotation to investigate informational needs. RESULTS: A total of 101 responses were returned (20.1% response rate). The median age of respondents was 45 years and the median time since diagnosis was 10 years. Control preferences skewed towards shared (42.6%) or patient-led but clinician-informed (35.6%). Decision regret was low for the population (median 12.5/100, range 0-100). Key informational needs related to medical therapy were benefits and risks of long-term therapy, burden of hospital attendance, reproductive health, need for steroid treatment and impact on personal life. For surgery, these were stoma information, effect on daily life, effect on sexual and reproductive health, risks and benefits and disruption of life due to surgery. CONCLUSION: This study has identified key areas for discussion when counselling patients about treatment decisions around medical therapy and surgery for UC.

A systematic review and meta-analysis of outcomes after elective surgery for ulcerative colitis.

AIM: Approximately 20%-30% of patients with ulcerative colitis (UC) will undergo surgery during their disease course, the vast majority being elective due to chronic refractory disease. The risks of elective surgery are reported variably. The aim of this systematic review and meta-analysis is to summarize the outcomes after elective surgery for UC. METHODS: A systematic review was conducted that analysed studies reporting outcomes for elective surgery in the modern era (>2002). It was prospectively registered on the PROSPERO database (ref: CRD42018115513). Searches were performed of Embase and MEDLINE on 15 January 2019. Outcomes were split by operation performed. Primary outcome was quality of life; secondary outcomes were early, late and functional outcomes after surgery. Outcomes reported in five or more studies underwent a meta-analysis of incidence using random effects. Heterogeneity is reported with I2 , and publication bias was assessed using Doi plots and the Luis Furuya-Kanamori index. RESULTS: A total of 34 studies were included (11 774 patients). Quality of life was reported in 12 studies, with variable and contrasting results. Thirteen outcomes (eight early surgical complications, five functional outcomes) were included in the formal meta-analysis, all of which were outcomes for ileal pouch-anal anastomosis (IPAA). A further 71 outcomes were reported (50 IPAA, 21 end ileostomy). Only 14 of 84 outcomes received formal definitions, with high inter-study variation of definitions. CONCLUSION: Outcomes after elective surgery for UC are variably defined. This systematic review and meta-analysis highlights the range of reported incidences and provides practical information that facilitates shared decision making in clinical practice.

The informational and decisional preferences of patients undergoing surgery for Crohn's anal fistula: a qualitative study.

AIM: One in three patients with Crohn's disease will develop a perianal fistula, but only a few achieve long-term healing. Treatment is both medical and surgical. Since there is no 'best' surgical procedure, patient preference is important in selecting the appropriate treatment for this condition. The aim of this study was to investigate the informational and decisional preferences of patients when surgical treatment is being considered. METHOD: Patients who had undergone surgery for Crohn's anal fistula underwent face-to-face semi-structured interviews. These explored the experience of treatments for fistula, of receiving information and of participation in decision-making. Transcripts were analysed by two investigators through inductive thematic analysis. Saturation was assessed for at 12 interviews and then after each subsequent interview. RESULTS: Seventeen patients completed interviews, and saturation was achieved. Five themes were identified, of which two (desired information and decision-making) were relevant to this study. Other themes included experience of Crohn's disease, experience of receiving information and procedure-specific comments. Participants wanted to have information on any risks, high-level outcomes (e.g. success), impact on day-to-day life and aftercare. Participants felt they did not always receive the information they needed to select the best treatment option. Participants felt uninvolved in treatment decisions and would have liked to trade off operations to reach their treatment goal. CONCLUSION: Information provided to patients about surgical treatment of Crohn's perianal fistula does not meet their needs. Clinicians should address aftercare, impact on quality of life and the risks and benefits of the any proposed procedure.

Review article: pathogenesis of Crohn's perianal fistula-understanding factors impacting on success and failure of treatment strategies.

BACKGROUND: Evidence from groups who have studied fistula aetiology and extrapolation from interventional studies supports a multifactorial hypothesis of Crohn's perianal fistula, with several pathophysiological elements that may contribute to fistula formation, persistence and resistance to treatment. AIM: An evidence synthesis of current understanding of pathophysiological factors underlying Crohn's perianal fistula is presented, exploring the fundamental reasons why some treatments succeed and others fail, as a means of focussing clinical knowledge on improving treatment of Crohn's perianal fistula. METHODS: Evidence to support this review was gathered via the Pubmed database. Studies discussing pathophysiological factors underpinning perianal fistula, particularly in Crohn's disease, were reviewed and cross-referenced for additional reports. RESULTS: Pathophysiological factors that impact on success or failure of interventions for Crohn's perianal fistulae include the high-pressure zone, obliterating the dead space, disconnecting the track from the anus, removing epithelialisation, eradicating sepsis and by-products of bacterial colonisation, correcting abnormalities in wound repair and removing the pro-inflammatory environment which allows fistula persistence. Most current interventions for Crohn's perianal fistulae tend to focus on a single, or at best two, aspects of the pathophysiology of Crohn's anal fistulae; as a result, failure to heal fully is common. CONCLUSIONS: For an intervention or combination of interventions to succeed, multiple factors must be addressed. We hypothesise that correct, timely and complete attention to all of these factors in a multimodal approach represents a new direction that may enable the creation of an effective treatment algorithm for Crohn's anal fistula.

Patients with perianal Crohn's fistulas experience delays in accessing anti-TNF therapy due to slow recognition, diagnosis and integration of specialist services: lessons learned from three referral centres.

AIM: Crohn's anal fistula should be managed by a multidisciplinary team. There is no clearly defined 'patient pathway' from presentation to treatment. The aim of this study was to describe the patient route from presentation with symptomatic Crohn's anal fistula to starting anti-tumour necrosis factor (anti-TNF) therapy. METHOD: Case note review was undertaken at three hospitals with established inflammatory bowel disease services. Patients with Crohn's anal fistula presenting between 2010 and 2015 were identified through clinical coding and local databases. Baseline demographics were captured. Patient records were interrogated to identify route of access, and clinical contacts during the patient pathway. RESULTS: Seventy-nine patients were included in the study, of whom 54 (68%) had an established diagnosis of Crohn's disease (CD). Median time from presentation to anti-TNF therapy was 204 days (174 vs 365 days for existing and new diagnosis of CD, respectively; P = 0.019). The mean number of surgical outpatient attendances, operations and MRI scans per patient was 1.03, 1.71 and 1.03, respectively. Patients attended a mean of 1.49 medical clinics. Seton insertion was the most common procedure, accounting for 48.6% of all operations. Where care episodes ('clinical events per 30 days') were infrequent this correlated with prolongation of the pathway (r = -0.87; P < 0.01). CONCLUSION: This study highlights two key challenges in the treatment pathway: (i) delays in diagnosis of underlying CD in patients with anal fistula and (ii) the pathway to anti-TNF therapy is long, suggesting issues with service design and delivery. These should be addressed to improve patient experience and outcome.

The assessment of online health videos for surgery in Crohn's disease.

AIM: YouTube™ is an open-access, nonpeer-reviewed video-hosting site and is used as a source of publicly available healthcare information. This study aimed to assess the thematic content of the most viewed videos relating to surgery and Crohn's disease and to explore the viewer interactions with these videos. METHOD: A search of YouTube™ was carried out using one search string. The 50 most viewed videos were identified and categorized by source and content themes and assessed for viewer interactions. Video comments were used to describe the usefulness of the video content to viewers. RESULTS: The majority of videos were uploaded by patients (n = 21).The remainder were uploaded by individual healthcare professionals (n = 9), hospital/speciality associations (n = 18) and industry (n = 2). The median number of likes for patient videos was significantly higher than for hospital/speciality association videos (P < 0.001). Patient videos received more comments praising the video content (n = 27) and more comments asking for further information (n = 14). The median number of likes for 'experience of surgery' (P < 0.001) and 'experience of disease' (P = 0.0015) themed videos were significantly higher than for 'disease management' themed videos. CONCLUSION: Crohn's disease patients use YouTube™ as a surgical information source. The content of patient-sourced videos focused on surgical and disease experience, suggesting that these themes are important to patients. Current patient developed videos provide limited information, as reflected by viewers requesting further information. Storytelling patient-centred videos combined with clinical evidence may be a good model for future videos.

Assessing internet-based information used to aid patient decision-making about surgery for perianal Crohn's fistula.

BACKGROUND: Decision-making in perianal Crohn's fistula (pCD) is preference sensitive. Patients use the internet to access healthcare information. The aim of this study was to assess the online information and patient decision aids relating to surgery for pCD. METHODS: A search of Google™ and the Decision Aids Library Inventory (DALI) was performed using a predefined search strategy. Patient-focussed sources providing information about pCD surgery were included in the analysis. Written health information was assessed using the International Patient Decision Aids Standards (IPDAS) and DISCERN criteria. The readability of the source content was assessed using the Flesch-Kincaid score. RESULTS: Of the 201 sources found, 187 were excluded, leaving 14 sources for analysis. Three sources were dedicated to pCD, and six sources mentioned pCD-specific outcomes. The most common surgical intervention reported was seton insertion (n = 13). The least common surgical intervention reported was proctectomy (n = 1). The mean IPDAS and DISCERN scores were 4.43 ± 1.65 out of 12 (range = 2-8) and 2.93 ± 0.73 out of 5 (range = 1-5), respectively. The mean reading ease was US college standard. CONCLUSIONS: We found no patient decision aids relating to surgery for pCD. The online sources relating to surgery for pCD are few, and their quality is poor, as seen in the low IPDAS and DISCERN scores. Less than half of the sources mentioned pCD-specific outcomes, and three sources were solely dedicated to providing information on pCD. Healthcare professionals should look to create a patient tool to assist decision-making in pCD.

Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn's disease in established remission.

BACKGROUND AND AIMS: Outcomes of cessation of anti-TNF therapy for Crohn's disease (CD) in clinical and/or endoscopic remission in routine clinical practice is uncertain. This study aimed to evaluate clinical outcomes and factors associated with relapse in CD patients following formal disease assessment and elective anti-TNF withdrawal. METHODS: Prospective observational study of CD patients in whom anti-TNF therapy was stopped electively after ≥12months and follow-up of ≥6months. Investigations at assessment prior to cessation included ≥1 of clinical assessment, endoscopic and/or imaging. Relapse was defined as recurrent symptoms of CD requiring medical or surgical therapy. RESULTS: Eighty-six patients received anti-TNF for a median duration of 23 (12-80) months for severe active luminal (70%), fistulating perianal (25.5%) and other fistulating disease (4.5%). Relapse rates at 90,180 and 365days were 4.7%, 18.6% and 36%, respectively. If anti-TNF dose escalation occurred 6months prior to withdrawal, 88% (7/8) relapsed. Based on multivariate analysis, risk factors for relapse include ileocolonic disease at diagnosis and previous anti-TNF therapy. An elevated faecal calprotectin (FC) is likely to predict relapse (p=0.02), with a PPV of 66.7% at >50µg/g. Of 36 patients who relapsed, 31 were retreated with anti-TNF, with an overall recapture rate of 93%. CONCLUSION: Relapse rates at 1year following elective withdrawal of anti-TNF are 36%, with high retreatment response rate. Predictors of relapse include ileocolonic involvement, previous anti-TNF therapy and raised FC. Endoscopic/radiologic assessment prior to cessation of therapy does not appear to predict those at lower risk of relapse.

Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients.

BACKGROUND: Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors. AIM: To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse. METHODS: This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively. RESULTS: 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4-8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007). CONCLUSION: Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.

Combined modality treatment for complex fistulating perianal Crohn's disease.

AIM: Perianal disease affects 33% (range 8-90%) of patients with Crohn's disease. Fistulae are often complex and their management is often difficult and unsatisfactory. This study was a retrospective assessment of a combination of surgical treatment with a standardized protocol of infliximab (IFX) therapy. METHOD: A consecutive series of patients with complex perianal Crohn's disease, presenting between January 2003 and June 2008, were included. Acute sepsis was initially treated with antibiotics and/or surgical drainage (MRI guided when appropriate) and loose seton insertion. IFX was given at 5 mg/kg, at 0, 2 and 6 weeks. End-points were complete, partial or no response. Setons were empirically removed after the second cycle of IFX. RESULTS: Forty-eight patients, average age 46 (range 24-82)years, with perianal Crohn's disease were identified. Three patients stopped IFX after the second infusion, either because of allergy (two patients) or for failure to respond (one patient). Fourteen patients were given maintenance IFX at 8-weekly intervals. Results were recorded for 48 patients, of whom 14 (29%) had a complete response, 20 (42%) had a partial response and 14 (29%) had no response to treatment. Outpatient follow-up was for a median of 20 months. CONCLUSION: Combining surgical procedures with IFX resulted in complete and partial remission in 29% and 42% of patients, respectively. No serious side effects occurred. Using a combined, intensive medico-surgical approach, good initial control of perianal disease was achieved safely.

Prodromal irritable bowel syndrome may be responsible for delays in diagnosis in patients presenting with unrecognized Crohn's disease and celiac disease, but not ulcerative colitis.

INTRODUCTION: We aimed to determine the prevalence and duration of prodromal periods in patients with celiac disease and inflammatory bowel disease (Crohn's disease and ulcerative colitis). Furthermore, we explored to what extent vague abdominal symptoms consistent with both disorders were attributed to irritable bowel syndrome (IBS) and if the presence of prodromal IBS (P-IBS) had an impact on prodrome duration. METHODS: In the study, 683 biopsy-proven patients (celiac n = 225, ulcerative colitis n = 228, Crohn's disease n = 230) completed a postal survey including an assessment of prodromal periods and IBS symptoms during both the prodrome and at present (achieved by completion of the ROME II criteria). Results were compared to age/sex-matched controls (n = 348). RESULTS: Crohn's disease patients had the highest prevalence of prodromes (94%) in comparison to ulcerative colitis (48%) and celiac disease (44%). However, Crohn's disease patients have the lowest prevalence of P-IBS (29%) in comparison to ulcerative colitis (38%) and celiac disease (67%). Prodrome duration in patients with P-IBS Crohn's disease was 4 years in comparison to 2 years without (p = 0.018). Prodrome duration in P-IBS celiac disease was 10 years in comparison to 7 years without (p = 0.046). Prodrome duration in patients with ulcerative colitis was not affected by P-IBS (p ≥ 0.05). Age and sex were not confounding factors. CONCLUSIONS: This is the first study to make direct comparisons of prodrome periods between celiac disease and IBD. Prodrome duration in celiac disease is significantly longer and more often characterized by P-IBS than IBD. In celiac disease and CD, P-IBS increases prodrome duration. This may represent a failure to understand the overlap between IBS and celiac disease/IBD.

Variations in the reporting of endoscopies by different endoscopists.

All gastroscopies and colonoscopies performed in two U.K. teaching hospitals over a period of one year were audited to investigate whether endoscopic reporting of gastroscopies and colonoscopies by different endoscopists is consistent. Endoscopic diagnoses were retrieved from the hospitals' endoscopy databases. The results of 1814 colonoscopies and 2127 gastroscopies were analysed using chi2 (Chi squared). The frequency of reporting common diagnoses was variable and the differences between specialist endoscopists were highly significant, including for important conditions such as peptic ulceration (range 2-10%, p = 0.001) and colonic polyps (16-45%, p < 0.001). There is a large variation in the frequency of the diagnoses reported by different endoscopists. This is unlikely to be explained by casemix or chance. This may have major implications for the health of patients. More emphasis must be placed during training on the correct interpretation of endoscopies.

Endoscopic mucosal resection for flat neoplasia in chronic ulcerative colitis: can we change the endoscopic management paradigm?

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.

Indigo carmine-assisted high-magnification chromoscopic colonoscopy for the detection and characterisation of intraepithelial neoplasia in ulcerative colitis: a prospective evaluation.

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.

Endoscopic morphological anticipation of submucosal invasion in flat and depressed colorectal lesions: clinical implications and subtype analysis of the kudo type V pit pattern using high-magnification-chromoscopic colonoscopy.

OBJECTIVE: Focal submucosal invasive colorectal cancers (submucosa-sm1) can be managed by endoscopic mucosal resection (EMR) as local lymph node metastasis (LNM) are rare. Lesions are usually flat, depressed or mixed. In deeper vertical submucosal invasion (sm2-3) LNM rates exceed 10-15%. EMR within this group can be complicated by perforation, noncurative resection and may leave LNM untreated. It is therefore essential to differentiate accurately focal sm1 disease from submucosal sm2/3 disease. The aim of this study was to evaluate the relationship between the invasive type V pit pattern using high-magnification-chromoscopic-colonoscopy (HMCC) and submucosal invasive depth for flat and depressed colorectal lesions. METHODS: Total colonoscopy was performed by a highly selected single endoscopist using the Olympus C240Z on 850 patients between January 2001 and July 2003. Kudo type V pits were identified using 0.05% crystal violet (CV) applied directly to the lesion using a steel tipped catheter. Type V pits were graded into class V(n)A-C as described by Nagata. Morphology was documented using the Japanese Research Society classification (JRSC). Histological sections, with reference to mucosal invasive characteristics, acquired using EMR or surgical excision were then compared with the pit pattern. RESULTS: Fifty-one lesions showed a type V pit pattern. The kappa coefficient of agreement between pit the type V pit pattern and histologically confirmed submucosal invasion was 0.51 (95% CI). Following resection, 97% of lesions were correctly anticipated to have sm2 + invasion using pit type Vn(B) and Vn(C) as clinical indicators of invasive disease. Specificity was low at 50% with an accuracy of 78%. CONCLUSIONS: The type V pit pattern is useful for the in vivo staging of submucosal invasive depth in flat and depressed colorectal lesions and is as sensitive as conventional 7.5 MHz EUS. There was a tendency to over-stage lesions and hence the technique is limited by its low overall specificity.

Colonoscopic resection of lateral spreading tumours: a prospective analysis of endoscopic mucosal resection.

BACKGROUND: Lateral spreading tumours are superficial spreading neoplasms now increasingly diagnosed using chromoscopic colonoscopy. The clinicopathological features and safety of endoscopic mucosal resection for lateral spreading tumours (G-type "aggregate" and F-type "flat") has yet to be clarified in Western cohorts. METHODS: Eighty two patients underwent magnification chromoscopic colonoscopy using the Olympus CF240Z by a single endoscopist. All patients had received a previous colonoscopy where an endoscopic diagnosis of lateral spreading tumour was made. All lesions were examined initially using indigo carmine chromoscopy to delineate contour followed by crystal violet for magnification crypt pattern analysis. A 20 MHz "mini probe" ultrasound was used if T2 disease was suspected. Following endoscopic mucosal resection, patients were followed up at 3, 6, 12, and 24 months using total colonoscopy. RESULTS: Eighty two lateral spreading tumours were diagnosed in 80 patients (32% (26/82) F-type and 68% (56/82) G-type). G-type lesions were larger than F-type (G-type mean 42 (SD 14) mm v F-type 24 (6.4) mm; p<0.01). F-type lesions were more common in the right colon (F-type 77% (20/26) compared with G-type 39% (22/56); p<0.01) and more often associated with invasive disease (stage T2) (66% (10/15) v 33% (5/15); p<0.001). Fifty eight lesions underwent endoscopic mucosal resection (G-type 64% (37/58)/F-type 36% (21/58)). Local recurrent disease was detected in 17% of patients (10/58), all within six months of the index resection. Piecemeal resection and G-type morphology were significantly associated with recurrent disease (p<0.1). Overall "cure" rates for lateral spreading tumours using endoscopic mucosal resection at two years of follow-up was 96% (56/58). CONCLUSIONS: Endoscopic mucosal resection for lateral spreading tumours, staged as T1, is a safe and effective treatment despite their large size. Endoscopic mucosal resection may be an alternative to surgery in selected patients.

Clinical significance of azathioprine active metabolite concentrations in inflammatory bowel disease.

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.

An evaluation of colorectal endoscopic mucosal resection using high-magnification chromoscopic colonoscopy: a prospective study of 1000 colonoscopies.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection provides an alternative to surgery for resection of sessile and flat colorectal lesions. High-magnification chromoscopic colonoscopy may allow early detection and anticipate histological diagnosis by identifying colonic crypt patterns. The aim of the present study was to assess the efficacy and safety of en-bloc endoscopic mucosal resection with high-magnification chromoendoscopy in the management of sessile and flat colorectal lesions