Colitis Surveillance Research Articles

Target biopsy or step biopsy? Optimal surveillance for ulcerative colitis: a Japanese nationwide randomized controlled trial

Colorectal cancer is one of the complications of ulcerative colitis (UC) and the risk of cancer increases as the duration of the disease becomes longer. Surveillance colonoscopy has been considered to be important for the early detection and early treatment of colorectal cancer, especially in longstanding UC. Because it is not always easy to detect neoplastic lesions in UC endoscopically, guidelines recommend the use of step biopsy in surveillance, in which either 4 biopsy specimens for every 10 cm or a total of 33 or more biopsy specimens are obtained. However, it has been pointed out that a step biopsy obtaining several tens of biopsy specimens may not be an ideal method in terms of invasiveness to the patient or medical cost. Instead of step biopsy, recent studies report the usefulness of target biopsy, in which biopsy tissues are obtained only from regions suspected of neoplasia. Therefore, the Research Group for Intractable Inflammatory Bowel Disease of the Ministry of Health, Labour and Welfare of Japan has initiated a randomized controlled study to compare the efficacy of step biopsy and target biopsy. The present article gives an introduction to this ongoing randomized controlled trial in Japan.

Surveillance programmes for neoplasia in colitis

Patients with longstanding extensive colitis, both ulcerative colitis and Crohn's colitis, have an increased risk of developing colorectal cancer. Because of this risk, colonoscopic surveillance for neoplasia is recommended by most authorities. Although there has been no randomised controlled trial to demonstrate surveillance effectiveness, there are several retrospective comparative studies, which suggest that surveillance reduces colorectal cancer mortality. Over the past decade there have been a number of developments in our understanding of colitis cancer. We have discovered that the severity of colorectal inflammation is an important risk factor, in addition to other known risk factors such as the extent and duration of colitis, primary sclerosing cholangitis and a family history of colorectal cancer. Endoscopic techniques have also improved and evidence now demonstrates that pancolonic chromoendoscopy yields significantly more intraepithelial neoplasia than random biopsies. Endoscopic resection of well-circumscribed lesions is now also recognised as being an appropriate strategy, potentially reducing the number of patients requiring colectomy. It is hoped that such developments will further improve the effectiveness of colitis surveillance.

Prevalence of Colorectal Cancer Surveillance for Ulcerative Colitis in an Integrated Health Care Delivery System

The absence of grade A supporting evidence for surveillance colonoscopy in patients with ulcerative colitis (UC) has led to controversy regarding its benefit, yet it is routinely recommended in practice guidelines. Limited data are available on rates of colonoscopy surveillance and factors associated with surveillance. A retrospective study of UC patients receiving care between 2006 and 2007 with ≥ 8 years history of UC was conducted. Primary outcome was the proportion of patients who underwent surveillance during this 2-year study period. Sociodemographic and disease factors were identified a priori from variables recorded electronically in the medical record; multivariable associations with surveillance were estimated using logistic regression. Of 771 patients with ≥ 8 years history of UC, 24.6% of patients underwent at least 1 surveillance colonoscopy within the 2-year study period, with a maximum of 38.5% observed among patients with primary sclerosing cholangitis. In a multivariable analysis, gender, age, race, and education were not associated with surveillance. Factors associated with increasing surveillance included lack of significant comorbidity (Charlson-Deyo index 0 vs 1+: odds ratio [OR], 1.7; 95% confidence interval: 1.1-2.5), > 3 inflammatory bowel disease-related outpatient visits (OR, 2.0; 95% CI: 1.4-3.0), and use of mesalamine (OR, 2.8; 95% CI: 1.7-4.4). Utilization of surveillance colonoscopy in a 2-year period was low, even among high-risk patients. Although specific factors recorded in computerized data were identified to be associated with surveillance, a greater understanding of how patients and physicians decide on surveillance is needed.

S1950 A New Methylation Markers Panel to Improve Cancer Surveillance in Inflammatory Bowel Disease

S1950 A New Methylation Markers Panel to Improve Cancer Surveillance in Inflammatory Bowel Disease

M1937 The Efficacy of Colorectal Cancer Surveillance in Crohn's Colitis

M1937 The Efficacy of Colorectal Cancer Surveillance in Crohn's Colitis

The role of endoscopy in the management of patients with diarrhea

The role of endoscopy in the management of patients with diarrhea

Leitlinienorientierte endoskopisch-bioptische Diagnostik, Überwachung und Therapie von Magen-Darm-Erkrankungen

The present review summarises the detailed recommendations for an optimal endoscopic-bioptic diagnostic procedure, endoscopic surveillance of and therapy for gastrointestinal diseases. The recommendations are mainly based on the S 3-guidelines and have been developed by histopathologists and gastroenterologists in interdisciplinary work. The material has been arranged according to topographic regions of the gastrointestinal tract and clinical problems. The focus is placed on diagnostic and surveillance of Barrett's oesophagus, therapy and postoperative treatment for early gastrointestinal carcinoma, management of colon polyps and endoscopic surveillance of inflammatory bowel disease. Treatment recommendations for both ulcerative colitis and Crohn's disease as well as low-grade and high-grade intraepithelial neoplasia and polypoid neoplasia are currently being intensively discussed. Thus we examine this controversial discussion in detail. Furthermore, the recent guidelines for Helicobacter pylori (H. pylori) and gastric MALT-lymphoma diagnostics are included in this survey. To allow the gastroenterologist a time-sparing overview during practical work, most of the recommendations are presented in itemised form and summarised in tables and figures at the end of the discussion.

Endoscopic surveillance in colitis in 2010: time for a change?

Endoscopic surveillance in colitis in 2010: time for a change?

Application of virtual microscopy in consultation practice of gastrointestinal and liver pathology: From the 1st Digital Pathology Summit, New Frontiers in Digital Pathology, University of Nebraska Medical Center, Omaha, Nebraska 14-15 May 2010

For several years now, virtual microscopy has been utilized in medical teaching, research, proficiency testing, American Board of Pathology examinations, pathology meetings and conferences, and quality assurance programs. In diagnostic practice, it is most widely and routinely used in image analysis. Some practices are beginning to use it internally (within their group) for frozen section intraoperative consultations and subspecialty consultations due to geographic and time constrains. Although diagnostic consultation for expert second opinion is a well-established practice in pathology for glass slides, similar consultation via virtual microscopy poses multiple controversial issues such as licensing, liability, security, reimbursement, and scanning quality and its validation. Regulations and standardization are not yet in place that pathologists can use to allay these fears. Nevertheless, if the virtual microscopy scans are of optimal quality, these can be simply substituted for glass slides and a microscope while maintaining all other practice guidelines for second opinion consultation. Additionally, the cost and maintenance of scanning equipment is not currently affordable to most practitioners and consultants. A practice model that offers tertiary consultation in gastrointestinal (GI) and liver pathology is presented that eliminates the cost and maintenance of scanners by the consultants and clients, minimizes the need for review of glass slides, facilitates clinicopathological and radiological correlation and serves the need of clients who need timely help with challenging liver and GI cases and to obtain expert opinion for dysplasia in Barrett’s and ulcerative colitis surveillance biopsies required by the American Gastroenterology Association (AGA). This model has been practiced for 3 years and applied to over 2000 cases by small pathology practices in the 50 United States and a single consultant GI and liver pathologist.

Positive Association Between Helicobacter pylori and Gastroesophageal Reflux Disease in Children

The role of Helicobacter pylori (H pylori) in gastroesophageal reflux disease (GERD) remains controversial, particularly in children, because there are limited published data. Adult studies suggested that H pylori infection may protect against GERD by causing atrophic gastritis, which leads to reduced gastric acid secretion. The objective of our study was to determine the role of H pylori infection in the development of GERD in a pediatric population. A retrospective analysis of 420 patients (M:F = 214:206) who underwent esophagogastroduodenoscopy (EGD) with biopsies between January 2000 and April 2006 was conducted. Patient demographics, clinical indications for EGD and the prevalence of reflux esophagitis (RE), the biomarker for GERD, in 2 groups, H pylori positive and H pylori negative, were reviewed. The prevalence of RE in the H pylori-positive and H pylori-negative groups was further analyzed on the basis of sex and age (<1 year, 1-10 years, >10 years). The mean age of the study population was 8.2 years (range 0-20 years). The clinical indications for EGD were as follows: recurrent abdominal pain (n = 186, 44%), malabsorption (n = 80, 19%), persistent vomiting (n = 80, 19%), suspected eosinophilic gastrointestinal disorders (n = 63, 15%), and others such as upper gastrointestinal bleeding or inflammatory bowel disease surveillance (n = 11, 3%). Statistical analysis was performed by using chi test, Fisher exact test, and multivariate logistical regression analysis. Among the 420 patients, 16 patients (3.8%) were positive for H pylori and 167 patients (39.8%) were found to have RE. Thirteen patients with H pylori were found to have histologic evidence of RE. The prevalence of RE in the H pylori-positive population was 81.3% compared with 38.1% in the H pylori-negative population (P < or = 0.05). There were no patients with H pylori in the youngest age group. In the second age group (1-10 years), 100% of the H pylori-positive patients had RE, whereas 44.6% of the H pylori-negative patients had RE (P < or = 0.05). Both male and female patients with H pylori had a higher prevalence of RE, 77.8% and 85.7%, respectively. On a multivariate logistical regression, for the overall study cohort, H pylori-positive patients had an odds ratio of 5.79 of developing RE compared with H pylori-negative patients (P < or = 0.05). Our study results indicate that there is a significantly higher prevalence of RE in an H pylori-infected cohort independent of age or sex. The findings suggest that H pylori infection in children is positively associated with RE.

Modelling dysplasia detection in ulcerative colitis: clinical implications of surveillance intensity

Background:Endoscopic surveillance of chronic colitis uses random biopsies to find dysplastic fields. Enhanced endoscopic methods are more sensitive for dysplasia detection, but their specificity for colorectal cancer risk is unknown.Aims:To...

Analysis of mutations in TP53, APC, K-ras, and DCC genes in the non-dysplastic mucosa of patients with inflammatory bowel disease

Patients with ulcerative colitis (UC) and Crohn's disease (CD) have a high risk for colorectal cancer (CRC). To understand the molecular basis of colitis-associated CRC, we analyzed alterations in TP53, APC, K-ras, and DCC genes in the non-dysplastic UC and CD colon. Endoscopic biopsies were collected from six predefined colon sites of 35 UC and 12 CD patients for DNA extraction and genetic analysis. A mutation was found in codon 1141 of the APC gene of two CD patients, being somatic in one and germinative in the other. The mutation seen in both patients was a base exchange of thymine for cytosine, resulting in an exchange of leucine for serine. We did not detect any mutations in the other samples analyzed. Mutations in APC gene may occur in the non-dysplastic CD mucosa of patients with disease for more than 10 years. The follow-up of these patients will show the likelihood of mutant APC progressing to CRC in CD. Further analysis will be required for evaluating the impact of these findings in the context of cancer surveillance in inflammatory bowel disease.

Cost Effectiveness of Ulcerative Colitis Surveillance in the Setting of 5-Aminosalicylates

Colorectal cancer (CRC) is a feared complication of chronic ulcerative colitis (UC). Annual endoscopic surveillance is recommended for the detection of early neoplasia. 5-Aminosalicylates (5-ASAs) may prevent some UC-associated CRC. Therefore, in patients prescribed 5-ASAs for maintenance of remission, annual surveillance might be overly burdensome and inefficient. We aimed to determine the ideal frequency of surveillance in patients with UC maintained on 5-ASAs. We performed systematic reviews of the literature, and created a Markov computer model simulating a cohort of 35-year-old men with chronic UC, followed until the age of 90 years. Twenty-two strategies were modeled: natural history (no 5-ASA or surveillance), surveillance without 5-ASA at intervals of 1-10 years, 5-ASA plus surveillance every 1-10 years, and 5-ASA alone. The primary outcome was the ideal interval of surveillance in the setting of 5-ASA maintenance, assuming a third-party payer was willing to pay $100,000 for each quality-adjusted life-year (QALY) gained. In the natural history strategy, the CRC incidence was 30%. Without 5-ASA, annual surveillance was the ideal strategy, preventing 89% of CRC and costing $69,100 per QALY gained compared with surveillance every 2 years. 5-ASA alone prevented 49% of CRC. In the setting of 5-ASA, surveillance every 3 years was ideal, preventing 87% of CRC. 5-ASA with surveillance every 2 years cost an additional $147,500 per QALY gained, and 5-ASA with annual surveillance cost nearly $1 million additional per QALY gained compared with every 2 years. In Monte Carlo simulations, surveillance every 2 years or less often was ideal in 95% of simulations. If 5-ASA is efficacious chemoprevention for UC-associated CRC, endoscopic surveillance might be safely performed every 2 years or less often. Such practice could decrease burdens to patients and on endoscopic resources with a minimal decrease in quality-adjusted length of life, because 5-ASA with annual surveillance may cost nearly $1 million per additional QALY gained.

Appropriateness of colonoscopy in Europe (EPAGE II) – Chronic diarrhea and known inflammatory bowel disease

To summarize the published literature on assessment of appropriateness of colonoscopy for investigation of chronic diarrhea, management of patients with known inflammatory bowel disease (IBD), and for colorectal cancer (CRC) surveillance in such patients, and to report report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. A systematic search of guidelines, systematic reviews, and primary studies regarding the evaluation of chronic diarrhea, the management of IBD, and colorectal cancer surveillance in IBD was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. According to the literature, colonoscopic evaluation may be justified for patients aged > 50 years with recent-onset chronic diarrhea or with alarm symptoms. Surveillance colonoscopy for CRC should be offered to all patients with extensive ulcerative colitis or colonic Crohn's disease of 8 years' duration, and to all patients with less extensive disease of 15 years' duration. Intervals for surveillance colonoscopy depend on duration of evolution, initial diagnosis, and histological findings. The EPAGE II criteria also confirmed the appropriateness of diagnostic colonoscopy for diarrhea of > 4 weeks' duration. They also suggest that, in addition to assessing extent of IBD by colonoscopy, further colonoscopic examination is appropriate in the face of persistent or worsening symptoms. Surveillance colonoscopy in IBD patients was generally appropriate after a lapse of 2 years. In the presence of dysplasia at previous colonoscopy, it was not only appropriate but necessary. Despite or perhaps because of the limitations of the available published studies, the panel-based EPAGE II (http://www.epage.ch) criteria can help guide appropriate colonoscopy use in the absence of strong evidence from the literature.

Repeat Endoscopy Affects Patient Management in Pediatric Inflammatory Bowel Disease

OBJECTIVES: Endoscopy is commonly performed in the diagnosis of children with inflammatory bowel disease (IBD). The utility of repeat endoscopy for the management of pediatric IBD has not been subject to investigation. The frequency and determinants of changes in medical management resulting from endoscopy are unknown. METHODS: We conducted a cross-sectional cohort study to assess the frequency and determinants of management change in all children (0-21 years) who underwent endoscopy for the surveillance or evaluation of established IBD between July 2002 and July 2006 at 2 referral centers in the United States. Patients were sampled from the Pediatric Endoscopy Database System Clinical Outcomes Research Initiative, and a chart review was performed to identify demographic features (age, gender), blood work (hemoglobin, albumin, erythrocyte sedimentation rate, C-reactive protein), and endoscopy results (endoscopic and histologic). An endoscopic score was used to assess mucosal injury. Subjects were divided into two groups for comparative analysis: (i) patients with management changes based on endoscopic or histologic findings, and (ii) patients without changes. RESULTS: We analyzed 285 endoscopic procedures (137 colonoscopies, 109 esophagogastroduodenoscopy (EGD) with colonoscopy, 25 sigmoidoscopies, 8 EGDs, 6 EGDs with sigmoidoscopy) performed in 230 children (mean age 14.5) with established IBD, including 147 with Crohn's disease, 80 with ulcerative colitis, and 3 with indeterminant colitis. Management changes were documented in 119 (42%) procedures, including 58 (20%) immediately after endoscopy, 52 (18%) after histology review, and 9 (3%) after both. Management changes included new medications in 86 cases, discontinuation of a medication in 3 cases, hospital admission in 11, and surgical consult in 14. No significant differences between groups occurred with regard to age, gender, endoscopy type, or infliximab use. The presence of anemia, hypoalbuminemia, or elevated markers of inflammation (ESR, CRP) did not correlate with management outcome. Management changes after endoscopy were more frequent in patients with Crohn's disease as compared to patients with ulcerative colitis. Patients with mucosal injury were more likely to have a management change than those with mucosal healing (80% vs. 20%;P<0.001). CONCLUSIONS: The overall rate of management change after endoscopic evaluation in children with IBD is approximately 42%. Addition of a new medication is the most common intervention. Blood work and patient symptoms before the procedure did not predict management outcome; however, mucosal healing may be an important end point. Our findings suggest that endoscopy is valuable for the evaluation of children with IBD.

Repeat Endoscopy Affects Patient Management in Pediatric Inflammatory Bowel Disease

Endoscopy is commonly performed in the diagnosis of children with inflammatory bowel disease (IBD). The utility of repeat endoscopy for the management of pediatric IBD has not been subject to investigation. The frequency and determinants of changes in medical management resulting from endoscopy are unknown. We conducted a cross-sectional cohort study to assess the frequency and determinants of management change in all children (0-21 years) who underwent endoscopy for the surveillance or evaluation of established IBD between July 2002 and July 2006 at 2 referral centers in the United States. Patients were sampled from the Pediatric Endoscopy Database System Clinical Outcomes Research Initiative and a chart review was performed to identify demographic features (age, gender), blood work (hemoglobin, albumin, erythrocyte sedimentation rate, C-reactive protein), and endoscopy results (endoscopic and histologic). An endoscopic score was used to assess mucosal injury. Subjects were divided into two groups for comparative analysis: (i) patients with management changes based on endoscopic or histologic findings, and (ii) patients without changes. We analyzed 285 endoscopic procedures (137 colonoscopies, 109 esophagogastroduodenoscopy (EGD) with colonoscopy, 25 sigmoidoscopies, 8 EGDs, 6 EGDs with sigmoidoscopy) performed in 230 children (mean age 14.5) with established IBD, including 147 with Crohn's disease, 80 with ulcerative colitis, and 3 with indeterminant colitis. Management changes were documented in 119 (42%) procedures, including 58 (20%) immediately after endoscopy, 52 (18%) after histology review, and 9 (3%) after both. Management changes included new medications in 86 cases, discontinuation of a medication in 3 cases, hospital admission in 11, and surgical consult in 14. No significant differences between groups occurred with regard to age, gender, endoscopy type, or infliximab use. The presence of anemia, hypoalbuminemia, or elevated markers of inflammation (ESR, CRP) did not correlate with management outcome. Management changes after endoscopy were more frequent in patients with Crohn's disease as compared to patients with ulcerative colitis. Patients with mucosal injury were more likely to have a management change than those with mucosal healing (80% vs. 20%; P<0.001). The overall rate of management change after endoscopic evaluation in children with IBD is approximately 42%. Addition of a new medication is the most common intervention. Blood work and patient symptoms before the procedure did not predict management outcome; however, mucosal healing may be an important end point. Our findings suggest that endoscopy is valuable for the evaluation of children with IBD.

Colorectal cancer surveillance in inflammatory bowel disease: The search continues

Patients with inflammatory bowel disease (IBD) are at increased risk for colorectal cancer (CRC). Risk factors for the development of CRC in the setting of IBD include disease duration, anatomic extent of disease, age at time of diagnosis, severity of inflammation, family history of colon cancer, and concomitant primary sclerosing cholangitis. The current surveillance strategy of surveillance colonoscopy with multiple random biopsies most likely reduces morbidity and mortality associated with IBD-related CRC. Unfortunately, surveillance colonoscopy also has severe limitations including high cost, sampling error at time of biopsy, and interobserver disagreement in histologically grading dysplasia. Furthermore, once dysplasia is detected there is disagreement about its management. Advances in endoscopic imaging techniques are already underway, and may potentially aid in dysplasia detection and improve overall surveillance outcomes. Management of dysplasia depends predominantly on the degree and focality of dysplasia, with the mainstay of management involving either proctocolectomy or continued colonoscopic surveillance. Lastly, continued research into additional chemopreventive agents may increase our arsenal in attempting to reduce the incidence of IBD-associated CRC.

Controversy in surveillance for ulcerative colitis

Controversy in surveillance for ulcerative colitis

Adherence to surveillance guidelines for dysplasia and colorectal carcinoma in ulcerative and Crohn’s colitis patients in the Netherlands

To study adherence to the widely accepted surveillance guidelines for patients with long-standing colitis in The Netherlands. A questionnaire was sent to all 244 gastroenterologists in The Netherlands. The response rate was 63%. Of all gastroenterologists, 95% performed endoscopic surveillance in ulcerative colitis (UC) patients and 65% in patients with Crohn's colitis. The American Gastroenterological Association (AGA) guidelines were followed by 27%, while 27% and 46% followed their local hospital protocol or no specific protocol, respectively. The surveillance was correctly initiated in cases of pancolitis by 53%, and in cases of left-sided colitis by 44% of the gastroenterologists. Although guidelines recommend 4 biopsies every 10 cm, less than 30 biopsies per colonoscopy were taken by 73% of the responders. Only 31%, 68% and 58% of the gastroenterologists referred patients for colectomy when low-grade dysplasia, high-grade dysplasia (HGD) or Dysplasia Associated Lesion or Mass (DALM) was present, respectively. Most Dutch gastroenterologists perform endoscopic surveillance without following international recommended guidelines. This practice potentially leads to a decreased sensitivity for dysplasia, rendering screening for colorectal cancer in this population highly ineffective.

Correlations among total colonoscopic findings, clinical symptoms, and laboratory markers in ulcerative colitis

Colonoscopy plays an integral role in the diagnosis, management and surveillance of ulcerative colitis (UC). In the present study we assessed the relationship between endoscopic and histological findings, clinical symptoms, and laboratory data. We performed total colonoscopy examinations in 54 consecutive patients with UC. Seven segments (appendiceal region, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum) were scored for endoscopic and histological activity. The patients were also evaluated using a symptom-activity index and laboratory markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) and platelet (plt) counts. There was a significant positive correlation between endoscopic and histological scores (r(s)=0.738), and between symptom activity score, endoscopic score (r(s)=0.444), and histological score (r(s)=0.557). Although the endoscopic and histological scores of distal colonic lesions (rectum-sigmoid, endoscopic: r(s)=0.515, histological: r(s)=0.624) correlated with clinical symptoms, there was no similar correlation for the proximal colon (appendiceal region-descending; endoscopic, r(s)=0.268, histological, r(s)=0.329). CRP, ESR, and WBC count also correlated with the sum of endoscopic and histological scores (CRP, r(s)=0.447, r(s)=0.369; ESR, r(s)=0.483, r(s)=0.589; WBC, r(s)=0.338, r(s)=0.330), whereas platelet count did not (r(s)=0.171, r(s)=0.210). In particular, CRP and ESR were well correlated with the activity of proximal colonic lesions (CRP, r(s) = 0.474, r(s)=0.480; ESR, r(s) = 0.423, r(s)=0.529) rather than with that of distal lesions (CRP, r(s)=0.236, r(s)=0.212; ESR, r(s)=0.368, r(s)=0.497). In this study, clinical symptoms reflected the activity of distal colonic lesions, whereas CRP and ESR reflected the activity of proximal lesions. Therefore, total colonoscopy may be indicated when CRP or ESR is elevated in UC patients in clinical remission.