Brian P. Saunders

Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002)

The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned this update of the 2002 guidance. The aim, as before, is to provide guidance on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer. This guidance provides some new recommendations for those with inflammatory bowel disease and for those at moderate risk resulting from a family history of colorectal cancer. In other areas guidance is relatively unchanged, but the recent literature was reviewed and is included where appropriate.

Pancolonic indigo carmine dye spraying for the detection of dysplasia in ulcerative colitis

Background and aims: Colonoscopic surveillance for cancer in longstanding extensive ulcerative colitis relies heavily on non-targeted mucosal biopsies. Chromoendoscopy can aid detection of subtle mucosal abnormalities. We hypothesised that routine pancolonic indigo carmine dye spraying would improve the macroscopic detection of dysplasia and reduce the dependence on non-targeted biopsies. Patients and methods: One hundred patients with longstanding extensive ulcerative colitis attending for colonoscopic surveillance underwent “back to back” colonoscopies. During the first examination, visible abnormalities were biopsied, and quadrantic non-targeted biopsies were taken every 10 cm. Pancolonic indigo carmine (0.1%) was used during the second colonoscopic examination, and any additional visible abnormalities were biopsied. Results: Median extubation times for the first and second colonoscopies were 11 and 10 minutes, respectively. The non-targeted biopsy protocol detected no dysplasia in 2904 biopsies. Forty three mucosal abnormalities (20 patients) were detected during the pre-dye spray colonoscopy of which two (two patients) were dysplastic: both were considered to be dysplasia associated lesions/masses. A total of 114 additional abnormalities (55 patients) were detected following dye spraying, of which seven (five patients) were dysplastic: all were considered to be adenomas. There was a strong trend towards statistically increased dysplasia detection following dye spraying (p = 0.06, paired exact test). The targeted biopsy protocol detected dysplasia in significantly more patients than the non-targeted protocol (p = 0.02, paired exact test). Conclusions: No dysplasia was detected in 2904 non-targeted biopsies. In comparison, a targeted biopsy protocol with pancolonic chromoendoscopy required fewer biopsies (157) yet detected nine dysplastic lesions, seven of which were only visible after indigo carmine application. Careful mucosal examination aided by pancolonic chromoendoscopy and targeted biopsies of suspicious lesions may be a more effective surveillance methodology than taking multiple non-targeted biopsies.

A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis

Background: Non-selective cyclooxygenase (COX) inhibitors (non-steroidal anti-inflammatory drugs) inhibit large bowel carcinogenesis in patients with familial adenomatous polyposis (FAP). Their role in the duodenum of these patients is less certain. The disease modifying activity of specific COX-2 inhibitors has not been explored in humans. Patients and methods: This was a randomised, double blind, placebo controlled study of celecoxib (100 mg twice daily (n=34) or 400 mg twice daily (n=32)) versus placebo (n=17), given orally twice daily for six months to patients with FAP. Efficacy was assessed qualitatively by blinded review of shuffled endoscopy videotapes comparing the extent of duodenal polyposis at entry and at six months and quantitatively by measurement of the percentage change in duodenal area covered by discrete and plaque-like adenomas from photographs of high and low density polyposis. Results: Shuffled and blinded video review showed a statistically significant effect of 400 mg twice daily celecoxib compared with placebo treatment (p=0.033) with all five independent observers scoring a beneficial effect. Overall, patients taking celecoxib 400 mg twice daily showed a 14.5% reduction in involved areas compared with a 1.4% for placebo (p=0.436). However, patients with clinically significant disease at baseline (greater than 5% covered by polyps) showed a 31% reduction in involved areas with celecoxib 400 mg twice daily compared with 8% on placebo (p=0.049). Conclusions: A panel of five endoscopists found a significant reduction in duodenal polyposis after six months of treatment with celecoxib 400 mg twice daily. COX-2 inhibition may help this otherwise untreatable condition.

Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk

Background and aims: The risk of colorectal cancer is increased in ulcerative colitis (UC). Patients with UC have diverse colonoscopic appearances. Determining colonoscopic markers for cancer risk could allow patient risk stratification. Patients and methods: Following on from an earlier study which demonstrated a correlation between inflammation severity and neoplasia risk, a case control study was performed to look for colonoscopic markers of colorectal neoplasia risk in UC. Each patient with neoplasia detected between 1988 and 2002 was matched with two non-dysplastic colitic controls. Data were collected on post-inflammatory polyps, scarring, strictures, backwash ileitis, a shortened, tubular, or featureless colon, severe inflammation, and normal looking surveillance colonoscopies. Results: Cases (n = 68) and controls (n = 136) were well matched. On univariate analysis, cases were significantly more likely to have post-inflammatory polyps (odds ratio (OR) 2.14 (95% confidence interval 1.24–3.70)), strictures (OR 4.22; 1.08–15.54), shortened colons (OR 10.0; 1.17–85.6), tubular colons (OR 2.03; 1.00–4.08), or segments of severe inflammation (OR 3.38; 1.41–10.13), and less likely to have had a macroscopically normal looking colonoscopy (OR 0.40; 0.21–0.74). After multivariate analysis, a macroscopically normal looking colonoscopy (OR 0.38; 0.19–0.73), post-inflammatory polyps (2.29; 1.28–4.11), and strictures (4.62; 1.03–20.8) remained significant. The five year risk of colorectal cancer following a normal looking colonoscopy was no different from that of matched general population controls. Conclusions: Macroscopic colonoscopic features help predict neoplasia risk in UC. Features of previous/ongoing inflammation signify an increased risk. A macroscopically normal looking colonoscopy returns the cancer risk to that of the general population: it should be possible to reduce surveillance frequency to five years in this cohort.

Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study

Background: Duodenal cancer is one of the leading causes of death in familial adenomatous polyposis (FAP) patients. An endoscopic surveillance programme was therefore initiated in 1988, the outcome of which is described in this paper. Methods: We report the 10 year follow up of 114 patients with FAP who were prospectively screened for the presence and severity of duodenal adenomas. Results: Six of 114 patients (median age 67 years) developed duodenal adenocarcinoma. Four of these were from 11 patients who originally had Spigelman stage IV disease (advanced duodenal polyposis), which gives a 36% risk within this group of developing cancer. One case of duodenal cancer arose from 41 patients who originally had stage III disease (2%) and one cancer arose from 44 patients with original stage II disease (2%). All six patients have died: five were inoperable and one had recurrence three years after a pancreaticoduodenectomy. There was no association between duodenal cancer and site of germline mutation of the APC gene. Conclusions: Surveillance for duodenal adenocarcinoma and subsequent early referral for curative surgery has not been effective. Selection of patients with advanced but benign (Spigelman stage IV) duodenal polyposis for prophylactic pancreaticoduodenectomy should therefore be considered and can now be justified on the basis of these results. More comprehensive endoscopic surveillance of high risk (stage III and IV) patients is needed in an attempt to avoid underestimating the severity of duodenal polyposis, and to evaluate the role of endoscopic therapy in preventing advanced disease.

Optical diagnosis of small colorectal polyps at routine colonoscopy (Detect InSpect ChAracterise Resect and Discard; DISCARD trial): a prospective cohort study

BACKGROUND Accurate optical diagnosis of small (<10 mm) colorectal polyps in vivo, without formal histopathology, could make colonoscopy more efficient and cost effective. The aim of this study was to assess whether optical diagnosis of small polyps is feasible and safe in routine clinical practice. METHODS Consecutive patients with a positive faecal occult blood test or previous adenomas undergoing surveillance at St Marks Hospital (London, UK), from June 19, 2008, to June 16, 2009, were included in this prospective study. Four colonoscopists with different levels of experience predicted polyp histology using optical diagnosis with high-definition white light, followed by narrow-band imaging without magnification and chromoendoscopy, as required. The primary outcome was accuracy of polyp characterisation using optical diagnosis compared with histopathology, the current gold standard. Accuracy of optical diagnosis to predict the next surveillance interval was also assessed and compared with surveillance intervals predicted by current guidelines using histopathology. This study is registered with ClinicalTrials.gov, NCT00888771. FINDINGS 363 polyps smaller than 10 mm were detected in 130 patients, of which 278 polyps had both optical and histopathological diagnosis. By histology, 198 of these polyps were adenomas and 80 were non-neoplastic lesions (of which 62 were hyperplastic). Optical diagnosis accurately diagnosed 186 of 198 adenomas (sensitivity 0.94; 95% CI 0.90-0.97) and 55 of 62 hyperplastic polyps (specificity 0.89; 0.78-0.95), with an overall accuracy of 241 of 260 (0.93, 0.89-0.96) for polyp characterisation. Using optical diagnosis alone, 82 of 130 patients could be given a surveillance interval immediately after colonoscopy, and the same interval was found after formal histopathology in 80 patients (98%) using British guidelines and in 78 patients (95%) using US multisociety guidelines. INTERPRETATION For polyps less than 10 mm in size, in-vivo optical diagnosis seems to be an acceptable strategy to assess polyp histopathology and future surveillance intervals. Dispensing with formal histopathology for most small polyps found at colonoscopy could improve the efficiency of the procedure and lead to substantial savings in time and cost. FUNDING Leigh Family Trust, London, UK.

Total colonic dye-spray increases the detection of diminutive adenomas during routine colonoscopy: A randomized controlled trial

BACKGROUND Small adenomas may be missed during colonoscopy, but chromoscopy has been reported to enhance detection. The aim of this randomized-controlled trial was to determine the effect of total colonic dye spray on adenoma detection during routine colonoscopy. METHODS Consecutive outpatients undergoing routine colonoscopy were randomized to a dye-spray group (0.1% indigo carmine used to coat the entire colon during withdrawal from the cecum) or control group (no dye). RESULTS Two hundred fifty-nine patients were randomized, 124 to the dye-spray and 135 to the control group; demographics, indication for colonoscopy, and quality of the preparation were similar between the groups. Extubation from the cecum took a median of 9:05 minutes (range: 2:48-24:44 min) in the dye-spray group versus 4:52 minutes (range: 1:42-15:21 min) in the control group (p < 0.0001). The proportion of patients with at least 1 adenoma and the total number of adenomas were not different between groups. However, in the dye-spray group significantly more diminutive adenomas (<5 mm) were detected proximal to the sigmoid colon (p = 0.026) and more patients were identified with 3 or more adenomas (p = 0.002). More non-neoplastic polyps were detected throughout the colon in the dye-spray group (p = 0.003). There were no complications. CONCLUSIONS Dye-spray increases the detection of small adenomas in the proximal colon and patients with multiple adenomas, but long-term outcomes should be studied to determine the clinical value of these findings.

Surveillance guidelines after removal of colorectal adenomatous polyps

Most colon cancers are assumed to have a premalignant adenomatous polyp phase, therefore colonoscopic detection and polypectomy provides the opportunity for cancer prevention. Some patients who have undergone colonoscopy and have had adenomas removed are at increased risk of developing colorectal cancer (CRC) in the future, and therefore might benefit from colonoscopic surveillance. However, it is important to appreciate that colonoscopy is an invasive and costly procedure with some associated morbidity. It is also an under-resourced procedure in the UK, with a serious lack of fully trained endoscopists. Around one third of the population will develop an adenoma by age 60. Most adenomas are asymptomatic and remain undiagnosed. If colorectal screening is introduced this situation will change dramatically. There are few data on the benefits of colonoscopic surveillance in preventing colorectal cancer after a baseline clearing colonoscopy. It is therefore important that this practice is applied judiciously, balancing the risks and benefits in each individual case. Using published evidence, this guideline recommends appropriate surveillance after adenoma removal. The decision to perform each follow up colonoscopy should also depend on the patient’s wishes, the presence of comorbidity, the patient’s age, and the presence of other risk factors. ### Risk of colorectal cancer and adenomas with advanced pathology (≥1 cm or severely dysplastic) (see fig 1) Figure 1 Surveillance after adenoma removal. Risk can be stratified according to findings at baseline and refined at each subsequent surveillance examination. (Recommendation Grade B) #### Low risk Patients with only 1–2, small (<1 cm) adenomas. Recommendation: no follow up or five yearly until one negative examination . #### Intermediate risk Patients with 3–4 small adenomas or at least one >1 cm Recommendation: three yearly until two consecutive negative examinations . #### High risk If either of the following are detected at any single examination (at baseline or follow up): ≥5 adenomas or ≥3 adenomas at least one of which is ≥1 cm. Recommendation: An extra examination should be undertaken at 12 months before returning …

Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

BACKGROUND AND AIM This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the choice amongst regimens available for cleansing the colon in preparation for colonoscopy. METHODS This Guideline is based on a targeted literature search to evaluate the evidence supporting the use of bowel preparation for colonoscopy. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence. RESULTS The main recommendations are as follows. (1) The ESGE recommends a low-fiber diet on the day preceding colonoscopy (weak recommendation, moderate quality evidence). (2) The ESGE recommends a split regimen of 4 L of polyethylene glycol (PEG) solution (or a same-day regimen in the case of afternoon colonoscopy) for routine bowel preparation. A split regimen (or same-day regimen in the case of afternoon colonoscopy) of 2 L PEG plus ascorbate or of sodium picosulphate plus magnesium citrate may be valid alternatives, in particular for elective outpatient colonoscopy (strong recommendation, high quality evidence). In patients with renal failure, PEG is the only recommended bowel preparation. The delay between the last dose of bowel preparation and colonoscopy should be minimized and no longer than 4 hours (strong recommendation, moderate quality evidence). (3) The ESGE advises against the routine use of sodium phosphate for bowel preparation because of safety concerns (strong recommendation, low quality evidence).

Validation of a Simple Classification System for Endoscopic Diagnosis of Small Colorectal Polyps Using Narrow-Band Imaging

BACKGROUND & AIMS Almost all colorectal polyps ≤ 5 mm are benign, yet current practice requires costly pathologic analysis. We aimed to develop and evaluate the validity of a simple narrow-band imaging (NBI)-based classification system for differentiating hyperplastic from adenomatous polyps. METHODS The study was conducted in 4 phases: (1) evaluation of accuracy and reliability of histologic prediction by NBI-experienced colonoscopists; (2) development of a classification based on color, vessels, and surface pattern criteria, using a modified Delphi method; (3) validation of the component criteria by people not experienced in endoscopy or NBI analysis (25 medical students, 19 gastroenterology fellows) using 118 high-definition colorectal polyp images of known histology; and (4) validation of the classification system by NBI-trained gastroenterology fellows, using still images. We performed a pilot evaluation during real-time colonoscopy. RESULTS We developed a classification system for the endoscopic diagnosis of colorectal polyp histology and established its predictive validity. When all 3 criteria were used, the specificity ranged from 94.9% to 100% and the combined sensitivity ranged from 8.5% to 61.0%. The specificities of the individual criteria were lower although the sensitivities were higher. During real-time colonoscopy, endoscopists made diagnoses with high confidence for 75% of consecutive small colorectal polyps, with 89% accuracy, 98% sensitivity, and 95% negative predictive values. CONCLUSIONS We developed and established the validity of an NBI classification system that can be used to diagnose colorectal polyps. In preliminary real-time evaluation, the system allowed endoscopic diagnoses of colorectal polyp histology.