David Burling

Computed tomographic colonography versus colonoscopy for investigation of patients with symptoms suggestive of colorectal cancer (SIGGAR): a multicentre randomised trial

BACKGROUND Colonoscopy is the gold-standard test for investigation of symptoms suggestive of colorectal cancer; computed tomographic colonography (CTC) is an alternative, less invasive test. However, additional investigation after CTC is needed to confirm suspected colonic lesions, and this is an important factor in establishing the feasibility of CTC as an alternative to colonoscopy. We aimed to compare rates of additional colonic investigation after CTC or colonoscopy for detection of colorectal cancer or large (≥10 mm) polyps in symptomatic patients in clinical practice. METHODS This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for colonoscopy. Patients were randomly assigned (2:1) to colonoscopy or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-the rate of additional colonic investigation-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. FINDINGS 1610 patients were randomly assigned to receive either colonoscopy (n=1072) or CTC (n=538). 30 patients withdrew consent, leaving for analysis 1047 assigned to colonoscopy and 533 assigned to CTC. 160 (30.0%) patients in the CTC group had additional colonic investigation compared with 86 (8.2%) in the colonoscopy group (relative risk 3.65, 95% CI 2.87-4.65; p<0.0001). Almost half the referrals after CTC were for small (<10 mm) polyps or clinical uncertainty, with low predictive value for large polyps or cancer. Detection rates of colorectal cancer or large polyps in the trial cohort were 11% for both procedures. CTC missed 1 of 29 colorectal cancers and colonoscopy missed none (of 55). Serious adverse events were rare. INTERPRETATION Guidelines are needed to reduce the referral rate after CTC. For most patients, however, CTC provides a similarly sensitive, less invasive alternative to colonoscopy. FUNDING NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.

Significant small-bowel lesions detected by alternative diagnostic modalities after negative capsule endoscopy

BACKGROUND Capsule endoscopy (CE) is considered a first-line investigation for obscure GI bleeding (OGIB) and small-bowel polyp or tumor detection. The reliability of a negative CE in excluding gross small-bowel pathology remains unclear. New imaging modalities, such as double-balloon enteroscopy (DBE), CT enterography (CTE) or magnetic resonance enterography (MRE) now provide complementary roles to CE for these indications. OBJECTIVE We describe our experience of significant small-bowel pathology missed at CE in 5 patients. The lesions were subsequently detected by DBE, CTE, or MRE. DESIGN A retrospective case series. SETTING Single-center academic endoscopy unit in a tertiary-referral hospital. PATIENTS Five patients were evaluated: 4 with a history of OGIB (transfusion dependent in 2) and 1 patient with Peutz-Jeghers syndrome (PJS) under small-bowel surveillance. INTERVENTIONS CE was performed in all patients. Further evaluation via DBE, CTE, or MRE was performed. Definitive treatment was carried out by enteroscopic polypectomy (1 patient), surgical resection (2 patients), and transjugular intrahepatic portosystemic shunt procedure and embolization (1 patient). MAIN OUTCOME MEASUREMENTS Detection of significant small-bowel pathology by using DBE, CT, or MRE after a negative capsule study. RESULTS Significant small-bowel pathology was missed at CE but was detected by alternative modalities in 5 patients. In 4 patients, the lesions were in the proximal small bowel (adenocarcinoma, malignant melanoma, varices, and stromal tumor). The fifth patient had a large PJS polyp in the proximal ileum. LIMITATIONS Retrospective case series with small numbers. CONCLUSIONS Gross pathology may be missed at CE, especially in the proximal small bowel, and a negative CE study does not exclude significant disease. Alternative imaging modalities, such as DBE, CTE, or MRE, should be considered when clinical suspicion persists.

CT colonography: effect of experience and training on reader performance

The purpose of this paper was to investigate the effect of radiologist experience and increasing exposure to CT colonography on reader performance. Three radiologists of differing general experience (consultant, research fellow, trainee) independently analysed 100 CT colonographic datasets. Readers had no prior experience of CT colonography and received feedback and training after the first 50 cases from an independent experienced radiologist. Diagnostic performance and reporting times were compared for the first and second 50 datasets and compared with the results of a radiologist experienced in CT colonography. Before training only the consultant reader achieved statistical equivalence with the reference standard for detection of larger polyps. After training, detection rates ranged between 25 and 58% for larger polyps. Only the trainee significantly improved after training (P=0.007), with performance of other readers unchanged or even worse. Reporting times following training were reduced significantly for the consultant and fellow (P<0.001 and P=0.03, respectively), but increased for the trainee (P<0.001). In comparison to the consultant reader, the odds of detection of larger polyps was 0.36 (CI 0.16, 0.82) for the fellow and 0.36 (CI 0.14, 0.91) for the trainee. There is considerable variation in the ability to report CT colonography. Prior experience in gastrointestinal radiology is a distinct advantage. Competence cannot be assumed even after directed training via a database of 50 cases.

Automated Insufflation of Carbon Dioxide for MDCT Colonography: Distension and Patient Experience Compared with Manual Insufflation

OBJECTIVE The purpose of our study was to compare the effects of automated and manual carbon dioxide insufflation before CT colonography on distention and patient acceptance. SUBJECTS AND METHODS One hundred forty-one symptomatic subjects underwent CT colonography using either an automated device (n = 47) or a manual method (n = 94) for carbon dioxide insufflation. CT data sets were assessed retrospectively in consensus by two blinded observers who graded distention for six colonic segments using a 4-point scale. An additional assessment of the overall clinical adequacy of distention (yes/no) was also made, and any learning curve was sought. Each patient completed a validated 24-point patient questionnaire reflecting patient satisfaction and discomfort. Distention scores, clinical adequacy, and questionnaire responses were analyzed using ordered logistic regression, Fishers exact test, and the Mann-Whitney test statistic, respectively. RESULTS Automated insufflation significantly improved distention overall (p = 0.001). For individual segments, distention was significantly improved in the sigmoid (p = 0.007) and descending (p < 0.001) colons when the patient was supine; and in the sigmoid (p = 0.02), descending (p = 0.001), and transverse (p = 0.02) colons when supine and prone positions were combined. No significant difference was seen in the clinical adequacy of distention, nor was there evidence of any learning curve for either insufflation method. Subjects were more weary after automated insufflation (p = 0.03), but no significant difference was seen for the remaining 23 questionnaire items or for feelings of bloating or discomfort. CONCLUSION Automated carbon dioxide insufflation significantly improves colonic distention compared with manual insufflation. Benefit is greatest in the left colon, particularly when the patient is supine. Patient acceptance is similar to that for manual insufflation.

Prospective Evaluation of Anti-Tumor Necrosis Factor Therapy Guided by Magnetic Resonance Imaging for Crohn ' s Perineal Fistulas

OBJECTIVES:Anti-tumor necrosis factor (TNF) therapy heals Crohns fistulas clinically, but the rate, extent, and duration to achieve fistula track healing are unknown.METHODS:We sought to monitor deep healing, as indicated by magnetic resonance imaging (MRI), and to use this to determine treatment duration. Clinical and MRI fistula healing (at 6, 12, and 18 months), Crohns Disease Activity Index (CDAI), Perianal Crohns Disease Activity Index (PDAI), and the Inflammatory Bowel Disease Questionnaire were prospectively assessed.RESULTS:Thirty-four consecutive patients with perineal fistulas were treated with infliximab (19), adalimumab (7; all infliximab failures) and thalidomide (8). Median follow-up was 110 weeks (range, 74–161). Baseline MRI: 38% ⩾2 tracks, 21% anolabial/rectovaginal. At latest follow-up, clinical fistula ‘response’ and ‘closure’ were seen in 50 and 46% of antibody-treated patients, respectively. All patients stopped thalidomide early due to side effects. Of 26 antibody-treated patients, at 6 (n=25), 12 (n=25), and 18 (n=20) months, respectively, MRI showed complete healing (20, 28, and 30%, respectively), improvement (68, 72, and 65%), no change (12, 0, and 0%) or worsening (0, 0, and 5%). MRI healing at 6 months (n=5) persisted at 12 and 18 months, including in two patients who stopped treatment at 6 months. Fistula history length and complexity did not influence the outcome. The only surgical intervention was seton insertion in one patient. The PDAI and CDAI scores decreased, and quality of life improved significantly at last follow-up.CONCLUSIONS:MRI fistula resolution was variable and slower than clinical healing. Prolonged treatment is often required for internal track resolution. Preliminary data suggest once MRI healing has occurred fistulas remain healed, while remaining on, or stopping anti-TNFα therapy. The use of a second antibody is clinically valuable.

Computed tomographic colonography versus barium enema for diagnosis of colorectal cancer or large polyps in symptomatic patients (SIGGAR): a multicentre randomised trial

BACKGROUND Barium enema (BE) is widely available for diagnosis of colorectal cancer despite concerns about its accuracy and acceptability. Computed tomographic colonography (CTC) might be a more sensitive and acceptable alternative. We aimed to compare CTC and BE for diagnosis of colorectal cancer or large polyps in symptomatic patients in clinical practice. METHODS This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for radiological investigation of the colon. Patients were randomly assigned (2:1) to BE or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-diagnosis of colorectal cancer or large (≥10 mm) polyps-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. FINDINGS 3838 patients were randomly assigned to receive either BE (n=2553) or CTC (n=1285). 34 patients withdrew consent, leaving for analysis 2527 assigned to BE and 1277 assigned to CTC. The detection rate of colorectal cancer or large polyps was significantly higher in patients assigned to CTC than in those assigned to BE (93 [7.3%] of 1277 vs 141 [5.6%] of 2527, relative risk 1.31, 95% CI 1.01-1.68; p=0.0390). CTC missed three of 45 colorectal cancers and BE missed 12 of 85. The rate of additional colonic investigation was higher after CTC than after BE (283 [23.5%] of 1206 CTC patients had additional investigation vs 422 [18.3%] of 2300 BE patients; p=0.0003), due mainly to a higher polyp detection rate. Serious adverse events were rare. INTERPRETATION CTC is a more sensitive test than BE. Our results suggest that CTC should be the preferred radiological test for patients with symptoms suggestive of colorectal cancer. FUNDING NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.

A diagnostic accuracy meta-analysis of endoanal ultrasound and MRI for perianal fistula assessment.

BACKGROUND: Imaging modalities such as endoanal ultrasound or MRI can be useful preoperative adjuncts before the appropriate surgical intervention for perianal fistulas. OBJECTIVES: We present a systematic review of published literature comparing endoanal ultrasound with MRI for the assessment of idiopathic and Crohn’s perianal fistulas. DESIGN: A meta-analysis was performed to obtain pooled values for specificity and sensitivity. SETTINGS: Electronic databases were searched from January 1970 to October 2010 for published studies. PATIENTS AND INTERVENTIONS: Four studies were used in our analysis. There were 241 fistulas in the ultrasound group and 240 in the magnetic resonance group. RESULTS: The combined sensitivity and specificity of magnetic resonance for fistula detection were 0.87 (95% CI: 0.63-0.96) and 0.69 (95% CI: 0.51-0.82). There was a high degree of heterogeneity between studies reporting on MRI sensitivity (df = 3, I2 = 93%). This compares to a sensitivity and specificity for endoanal ultrasound of 0.87 (95% CI: 0.70-0.95) and 0.43 (95% CI: 0.21-0.69). There was a high degree of heterogeneity between studies reporting on endoanal ultrasound sensitivity (df = 3, I2 = 92%). CONCLUSIONS: From the available literature, the summarized performance characteristics for MRI and endoanal ultrasound demonstrate comparable sensitivities at detecting perianal fistulas, although the specificity for MRI was higher than that for endoanal ultrasound. Both specificity values are considered to be diagnostically poor, however. The high degree of data heterogeneity and the shortage of applicable studies precludes any firm conclusions being made for clinical practice. Future trials with improved study design (including prospective data collection and consideration of verification bias) may help to further clarify the role of MRI in the assessment and treatment response monitoring of perianal fistulas (particularly in patients with Crohn’s disease).

Effective dilation of small-bowel strictures by double-balloon enteroscopy in patients with symptomatic Crohn's disease (with video)

BACKGROUND Crohns disease (CD)-related small-bowel strictures remain a major cause of morbidity, frequently requiring surgery. OBJECTIVE Assessment of the feasibility and effectiveness of CD small-bowel stricture dilation by DBE. DESIGN Prospective case series. SETTINGS Single, tertiary referral center. METHODS Outcome data on cases of DBE-assisted CD small-bowel stricture dilation were prospectively collected from 2005. Dilation was performed by using controlled radial expansion balloon dilators. A 10-cm visual analogue scale (VAS) was used to assess obstructive symptoms and dietary restriction before DBE stricture dilation and at follow-up. RESULTS A total of 13 DBEs were performed in 11 consecutive patients (mean +/- SD age 46.4 +/- 7.8 years). Eighteen small-bowel stricture dilations were performed in 9 of 11 patients. The mean dilation diameter was 15.4 mm (range 12-20 mm). In 2 cases, stricture dilation was not performed because adhesions made reaching the strictures impossible. One case was complicated by a delayed perforation. In the other 8 patients, stricture dilation was successful; VAS scores improved dramatically and none of the patients has required surgery (mean follow-up 20.5 months; range 2-41 months). During follow-up, 2 patients required repeated dilation (at 6.5 and 13 months, respectively) because of symptom recurrence. Clinical improvements in before and after VAS scores were significant (mean 8.8 vs 1.8, respectively; P < .001). LIMITATIONS Small case series; single tertiary referral center. CONCLUSION DBE-assisted small-bowel stricture dilation for selected patients with CD is potentially of significant benefit and should be considered as a useful and effective alternative to surgery. Larger studies are required to confirm this benefit.

Computer-Assisted Reader Software Versus Expert Reviewers for Polyp Detection on CT Colonography

OBJECTIVE The purpose of our study was to assess the sensitivity of computer-assisted reader (CAR) software for polyp detection compared with the performance of expert reviewers. MATERIALS AND METHODS A library of colonoscopically validated CT colonography cases were collated and separated into training and test sets according to the time of accrual. Training data sets were annotated in consensus by three expert radiologists who were aware of the colonoscopy report. A subset of 45 training cases containing 100 polyps underwent batch analysis using ColonCAR version 1.2 software to determine the optimum polyp enhancement filter settings for polyp detection. Twenty-five consecutive positive test data sets were subsequently interpreted individually by each expert, who was unaware of the endoscopy report, and before generation of the annotated reference via an unblinded consensus interpretation. ColonCAR version 1.2 software was applied to the test cases, at optimized polyp enhancement filter settings, to determine diagnostic performance. False-positive findings were classified according to importance. RESULTS The 25 test cases contained 32 nondiminutive polyps ranging from 6 to 35 mm in diameter. The ColonCAR version 1.2 software identified 26 (81%) of 32 polyps compared with an average sensitivity of 70% for the expert reviewers. Eleven (92%) of 12 polyps > or = 10 mm were detected by ColonCAR version 1.2. All polyps missed by experts 1 (n = 4) and 2 (n = 3) and 12 (86%) of 14 polyps missed by expert 3 were detected by ColonCAR version 1.2. The median number of false-positive highlights per case was 13, of which 91% were easily dismissed. CONCLUSION ColonCAR version 1.2 is sensitive for polyp detection, with a clinically acceptable false-positive rate. ColonCAR version 1.2 has a synergistic effect to the reviewer alone, and its standalone performance may exceed even that of experts.

A Prospective Study of MR Enterography Versus Capsule Endoscopy for the Surveillance of Adult Patients With Peutz-Jeghers Syndrome

OBJECTIVE The objective of our study was to assess the utility of MR enterography compared with capsule endoscopy for the detection of small-bowel polyps in patients with Peutz-Jeghers syndrome (PJS). SUBJECTS AND METHODS Adult patients with PJS scheduled for surveillance capsule endoscopy were prospectively recruited and underwent MR enterography and capsule endoscopy. Polyps > 10 mm were regarded as clinically relevant. When appropriate, large polyps (> 15 mm) were removed at enteroscopy, enabling correlation with MR enterography and capsule endoscopy findings. Interobserver agreement for MR enterography and capsule endoscopy was calculated. Patient comfort, convenience, and test preference were assessed. RESULTS Nineteen patients (median age, 39.6 years) underwent both procedures. There was no significant difference between techniques for the detection of polyps > 10 mm (18 vs 23 polyps at capsule endoscopy and MR enterography, respectively; p = 0.35) or in the number of patients in whom > 10 mm polyps were detected (eight vs 11 patients at capsule endoscopy and MR enterography, respectively; p = 0.38). However, in three patients, large polyps (> 15 mm) detected on MR enterography were not detected on capsule endoscopy; large polyps were seen in six patients at capsule endoscopy and in nine patients at MR enterography (p = 0.25). Interobserver agreement was high for MR enterography but was only fair for capsule endoscopy (kappa = 0.81 and 0.27, respectively). Size assessments of large polyps (> 15 mm) appeared more reproducible with MR enterography than with capsule endoscopy. Patients rated capsule endoscopy as more comfortable than MR enterography. There was no significant difference between the techniques with regard to patient convenience or preference. CONCLUSION MR enterography is a promising alternative to capsule endoscopy for small-bowel surveillance in adults with PJS. Although our results suggest that capsule endoscopy is more comfortable for the patient, MR enterography may be less prone to missing large polyps and may be more reliable in their size assessment.