Outcomes Post Beyond Total Mesorectal Excision Plane Resections Following Setting up Complex Colorectal Cancer Service in a District General Hospital.

Background: This study aims to validate the feasibility of a hub-and-spoke model for pelvic exenteration (PE) surgery while upholding favorable patient outcomes. Methods: A retrospective analysis of patients undergoing PE at our trust October 2017 and December 2023 was conducted. Descriptive statistics and Kaplan-Meier survival analysis were employed. Results: Sixty-seven patients underwent PE during the study period, mainly for locally advanced colorectal cancer (n=61, 91.04%). Minimally invasive surgery was performed in 16 cases (Robotic 3, 4.47% / Laparoscopic 13, 19.40) while the rest of patients 51 had open surgery (75.11%). Median hospital stay was 12 days (range:8-20). While 24 patients (35.82%) developed major complications (CD III-IV) post-surgery, there were no mortalities associated with pelvic exenteration in this study. Of the 67 patients undergoing surgery with curative intent, negative margins (R0 resection) were achieved in 57 patients (85.12%). This is comparable to outcomes reported by the PelvEx collaborative (85.07% versus 79.8%). At a median follow-up of 22 months, 15 patient (22.38%) recurred with 10.44% local recurrence rate. The 2 years overall and disease-free survival were 85.31% and 77.0.36%, respectively. Conclusion: Our study suggests that a nascent PE service, supported by specialist expertise and resources, can achieve good surgical outcomes within a district general hospital.

Faecal immunochemical testing (FIT) in patients with signs or symptoms of suspected colorectal cancer (CRC): a joint guideline from the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the British Society of Gastroenterology (BSG).

Faecal immunochemical testing (FIT) has a high sensitivity for the detection of colorectal cancer (CRC). In a symptomatic population FIT may identify those patients who require colorectal investigation with the highest priority. FIT offers considerable advantages over the use of symptoms alone, as an objective measure of risk with a vastly superior positive predictive value for CRC, while conversely identifying a truly low risk cohort of patients. The aim of this guideline was to provide a clear strategy for the use of FIT in the diagnostic pathway of people with signs or symptoms of a suspected diagnosis of CRC. The guideline was jointly developed by the Association of Coloproctology of Great Britain and Ireland/British Society of Gastroenterology, specifically by a 21-member multidisciplinary guideline development group (GDG). A systematic review of 13 535 publications was undertaken to develop 23 evidence and expert opinion-based recommendations for the triage of people with symptoms of a suspected CRC diagnosis in primary care. In order to achieve consensus among a broad group of key stakeholders, we completed an extended Delphi of the GDG, and also 61 other individuals across the UK and Ireland, including by members of the public, charities and primary and secondary care. Seventeen research recommendations were also prioritised to inform clinical management.

Colorectal Cancer: Performance and Evaluation for CT Colonography Screening- A Multicenter Cluster-randomized Controlled Trial.

Background Most radiologists reporting CT colonography (CTC) do not undergo compulsory performance accreditation, potentially lowering diagnostic sensitivity. Purpose To determine whether 1-day individualized training in CTC reporting improves diagnostic sensitivity of experienced radiologists for 6-mm or larger lesions, the durability of any improvement, and any associated factors. Materials and Methods This prospective, multicenter cluster-randomized controlled trial was performed in National Health Service hospitals in England and Wales between April 2017 and January 2020. CTC services were cluster randomized into intervention (1-day training plus feedback) or control (no training or feedback) arms. Radiologists in the intervention arm attended a 1-day workshop focusing on CTC reporting pitfalls with individualized feedback. Radiologists in the control group received no training. Sensitivity for 6-mm or larger lesions was tested at baseline and 1, 6, and 12 months thereafter via interpretation of 10 CTC scans at each time point. The primary outcome was the mean difference in per-lesion sensitivity between arms at 1 month, analyzed using multilevel regression after adjustment for baseline sensitivity. Secondary outcomes included per-lesion sensitivity at 6- and 12-month follow-up, sensitivity for flat neoplasia, and effect of prior CTC experience. Results A total of 69 hospitals were randomly assigned to the intervention (31 clusters, 80 radiologists) or control (38 clusters, 59 radiologists) arm. Radiologists were experienced (median, 500-999 CTC scans interpreted) and reported CTC scans routinely (median, 151-200 scans per year). One-month sensitivity improved after intervention (66.4% [659 of 992]) compared with sensitivity in the control group (42.4% [278 of 655]; difference = 20.8%; 95% CI: 14.6, 27.0; P < .001). Improvements were maintained at 6 (66.4% [572 of 861] vs 50.5% [283 of 560]; difference = 13.0%; 95% CI: 7.4, 18.5; P < .001) and 12 (63.7% [310 of 487] vs 44.4% [187 of 421]; difference = 16.7%; 95% CI: 10.3, 23.1; P < .001) months. This beneficial effect applied to flat lesions (difference = 22.7%; 95% CI: 15.5, 29.9; P < .001) and was independent of career experience (≥1500 CTC scans: odds ratio = 1.09; 95% CI: 0.88, 1.36; P = .22). Conclusion For radiologists evaluating CT colonography studies, a 1-day training intervention yielded sustained improvement in detection of clinically relevant colorectal neoplasia, independent of previous career experience. Clinical trial registration no. NCT02892721 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Pickhardt in this issue. An earlier incorrect version appeared online and in print. This article was corrected on February 28, 2022.

Imaging alternatives to colonoscopy: CT colonography and colon capsule. European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline - Update 2020.

MAIN RECOMMENDATIONS: 1. ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia. Strong recommendation, high quality evidence. ESGE/ESGAR do not recommend barium enema in this setting. Strong recommendation, high quality evidence.2. ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. The timing depends on an interdisciplinary decision including endoscopic and radiological factors. Strong recommendation, low quality evidence. ESGE/ESGAR suggests that, in centers with expertise in and availability of colon capsule endoscopy (CCE), CCE preferably the same or the next day may be considered if colonoscopy is incomplete. Weak recommendation, low quality evidence.3. When colonoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with alarm symptoms. Strong recommendation, high quality evidence. Because of lack of direct evidence, ESGE/ESGAR do not recommend CCE in this situation. Very low quality evidence. ESGE/ESGAR recommend CTC as an acceptable alternative to colonoscopy for patients with non-alarm symptoms. Strong recommendation, high quality evidence. In centers with availability, ESGE/ESGAR suggests that CCE may be considered in patients with non-alarm symptoms. Weak recommendation, low quality evidence.4. Where there is no organized fecal immunochemical test (FIT)-based population colorectal screening program, ESGE/ESGAR recommend CTC as an option for colorectal cancer screening, providing the screenee is adequately informed about test characteristics, benefits, and risks, and depending on local service- and patient-related factors. Strong recommendation, high quality evidence. ESGE/ESGAR do not suggest CCE as a first-line screening test for colorectal cancer. Weak recommendation, low quality evidence.5. ESGE/ESGAR recommend CTC in the case of a positive fecal occult blood test (FOBT) or FIT with incomplete or unfeasible colonoscopy, within organized population screening programs. Strong recommendation, moderate quality evidence. ESGE/ESGAR also suggest the use of CCE in this setting based on availability. Weak recommendation, moderate quality evidence.6. ESGE/ESGAR suggest CTC with intravenous contrast medium injection for surveillance after curative-intent resection of colorectal cancer only in patients in whom colonoscopy is contraindicated or unfeasible. Weak recommendation, low quality evidence. There is insufficient evidence to recommend CCE in this setting. Very low quality evidence.7. ESGE/ESGAR suggest CTC in patients with high risk polyps undergoing surveillance after polypectomy only when colonoscopy is unfeasible. Weak recommendation, low quality evidence. There is insufficient evidence to recommend CCE in post-polypectomy surveillance. Very low quality evidence.8. ESGE/ESGAR recommend against CTC in patients with acute colonic inflammation and in those who have recently undergone colorectal surgery, pending a multidisciplinary evaluation. Strong recommendation, low quality evidence.9. ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp ≥6 mm detected at CTC or CCE. Follow-up CTC may be clinically considered for 6-9-mm CTC-detected lesions if patients do not undergo polypectomy because of patient choice, comorbidity, and/or low risk profile for advanced neoplasia. Strong recommendation, moderate quality evidence. Source and scope This is an update of the 2014-15 Guideline of the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR). It addresses the clinical indications for the use of imaging alternatives to standard colonoscopy. A targeted literature search was performed to evaluate the evidence supporting the use of computed tomographic colonography (CTC) or colon capsule endoscopy (CCE). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence.

MRI-enema for the assessment of pelvic intestinal anastomotic integrity.

AIM: Anastomotic leak causes significant morbidity for patients undergoing pelvic intestinal surgery. Fluoroscopic assessment of anastomotic integrity using water-soluble contrast enema (WSCE) is of questionable benefit over examination alone. We hypothesized that MRI-enema may be more accurate. The aim of this study was to compare MRI-enema with fluoroscopic WSCE. METHOD: Patients referred for WSCE with pelvic intestinal anastomosis and defunctioning ileostomy (including patients with suspected or known leaks) were invited to participate. WSCE and MRI-enema were undertaken within 48 h of each other. MRI sequences were performed before, during and immediately after the introduction of 400 ml of 1% gadolinium contrast solution per anus. MRI examinations were reported to protocol by two blinded gastrointestinal radiologists. A Likert-scale patient questionnaire was administered to compare patient experience. Follow-up was >12 months after ileostomy reversal. Anastomotic leak was determined by unblinded consensus of examination and radiological findings. RESULTS: Sixteen patients were recruited, with a median age of 39 years (range 22-69). Ten were men, 11 had ileoanal pouch formation and five had low anterior resection. Five patients had anastomotic leak identified by MRI and four by WSCE. The radial location of the anastomotic defect was identified in all five patients by MRI versus two on WSCE. MRI revealed additional information including contents of a widened presacral space. Patient experience was equivalent. Eleven patients eventually had ileostomy reversal without complications. CONCLUSION: MRI-enema is a feasible and tolerable alternative to WSCE and offers greater anatomical detail in the context of pelvic intestinal anastomotic leak. Larger prospective studies are required to define its potential role in the UK National Health Service.

Evolution of the management of retrorectal masses: A retrospective cohort study.

AIM: Retrorectal masses are abnormalities located anatomically in the retrorectal space. A significant proportion are asymptomatic with no malignant potential while others cause symptoms due to mechanical pressure or malignant infiltration. We reviewed and categorised the retrorectal masses encountered over a 30-year time period in a specialist colorectal hospital and describe our management algorithm for consideration by other multidisciplinary teams (MDT). METHODS: This was a retrospective analysis of consecutive patients referred between 1984-2019. A detailed review of clinical presentation, imaging features, postoperative histology and impact on morbidity and anorectal function is reported. RESULTS: A total of 143 patients with median age of 46 years and female preponderance (74%) were reviewed. The commonest presenting symptom was pain (46%) and all malignant cases had symptoms (n = 17). Over the last decade, more asymptomatic patients have presented with a retrorectal mass (33%, p = 0.04) and more patients are opting for surveillance rather than resection (33%, p = 0.013). Increasing age and lesion size were associated with malignancy (p < 0.05). Radiological features associated with malignancy included: solid/heterogeneous component, lobulated borders or locally invasive. Following surgery, complications included chronic pain (40%), poor wound healing (23%) and bowel dysfunction (10%). CONCLUSIONS: The management of retrorectal masses remains complex. There are features, both clinical and radiological, that can help determine the best management strategy. Management should be in a high-volume tertiary centre and preferably through a complex rectal cancer MDT. Long-term sequelae such as chronic pain must be highlighted to patients. We advocate the establishment of an international registry to further record and characterise these rare, potentially troublesome lesions.

Imaging alternatives to colonoscopy: CT colonography and colon capsule. European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline - Update 2020.

1: ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia.Strong recommendation, high quality evidence.ESGE/ESGAR do not recommend barium enema in this setting.Strong recommendation, high quality evidence. 2: ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. The timing depends on an interdisciplinary decision including endoscopic and radiological factors.Strong recommendation, low quality evidence.ESGE/ESGAR suggests that, in centers with expertise in and availability of colon capsule endoscopy (CCE), CCE preferably the same or the next day may be considered if colonoscopy is incomplete.Weak recommendation, low quality evidence. 3: When colonoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with alarm symptoms.Strong recommendation, high quality evidence.Because of lack of direct evidence, ESGE/ESGAR do not recommend CCE in this situation.Very low quality evidence.ESGE/ESGAR recommend CTC as an acceptable alternative to colonoscopy for patients with non-alarm symptoms.Strong recommendation, high quality evidence.In centers with availability, ESGE/ESGAR suggests that CCE may be considered in patients with non-alarm symptoms.Weak recommendation, low quality evidence. 4: Where there is no organized fecal immunochemical test (FIT)-based population colorectal screening program, ESGE/ESGAR recommend CTC as an option for colorectal cancer screening, providing the screenee is adequately informed about test characteristics, benefits, and risks, and depending on local service- and patient-related factors.Strong recommendation, high quality evidence.ESGE/ESGAR do not suggest CCE as a first-line screening test for colorectal cancer.Weak recommendation, low quality evidence. 5: ESGE/ESGAR recommend CTC in the case of a positive fecal occult blood test (FOBT) or FIT with incomplete or unfeasible colonoscopy, within organized population screening programs.Strong recommendation, moderate quality evidence.ESGE/ESGAR also suggest the use of CCE in this setting based on availability.Weak recommendation, moderate quality evidence. 6: ESGE/ESGAR suggest CTC with intravenous contrast medium injection for surveillance after curative-intent resection of colorectal cancer only in patients in whom colonoscopy is contraindicated or unfeasibleWeak recommendation, low quality evidence.There is insufficient evidence to recommend CCE in this setting.Very low quality evidence. 7: ESGE/ESGAR suggest CTC in patients with high risk polyps undergoing surveillance after polypectomy only when colonoscopy is unfeasible.Weak recommendation, low quality evidence.There is insufficient evidence to recommend CCE in post-polypectomy surveillance.Very low quality evidence. 8: ESGE/ESGAR recommend against CTC in patients with acute colonic inflammation and in those who have recently undergone colorectal surgery, pending a multidisciplinary evaluation.Strong recommendation, low quality evidence. 9: ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp ≥ 6 mm detected at CTC or CCE.Follow-up CTC may be clinically considered for 6 - 9-mm CTC-detected lesions if patients do not undergo polypectomy because of patient choice, comorbidity, and/or low risk profile for advanced neoplasia.Strong recommendation, moderate quality evidence.

Computed tomographic colonography: how many and how fast should radiologists report?

OBJECTIVES: To determine if polyp detection at computed tomographic colonography (CTC) is associated with (a) the number of CTC examinations interpreted per day and (b) the length of time spent scrutinising the scan. METHODS: Retrospective observational study from two hospitals. We extracted Radiology Information System data for CTC examinations from Jan 2012 to Dec 2015. For each examination, we determined how many prior CTCs had been interpreted by the reporting radiologist on that day and how long radiologists spent on interpretation. For each radiologist, we calculated their referral rate (proportion deemed positive for 6 mm+ polyp/cancer), positive predictive value (PPV) and endoscopic/surgically proven polyp detection rate (PDR). We also calculated the mean time each radiologist spent interpreting normal studies ("negative interpretation time"). We used multilevel logistic regression to investigate the relationship between the number of scans reported each day, negative interpretation time and referral rate, PPV and PDR. RESULTS: Five thousand one hundred ninety-one scans were interpreted by seven radiologists; 892 (17.2%) were reported as positive, and 534 (10.3%) had polyps confirmed. Both referral rate and PDR reduced as more CTCs were reported on a given day (p < 0.001), the odds reducing by 7% for each successive CTC interpreted. Radiologists reporting more slowly than their colleagues detected more polyps (p = 0.028), with each 16% increase in interpretation time associated with a 1% increase in PDR. PPV was unaffected. CONCLUSIONS: Reporting multiple CTCs on a given day and rapid CTC interpretation are associated with decreased polyp detection. Radiologists should be protected from requirements to report too many CTCs or too quickly. KEY POINTS: • CT colonography services should protect radiologists from a need to report too fast (> 20 min per case) or for too long (> 4 cases consecutively without a break). • Professional bodies should consider introducing a target minimum interpretation time for CT colonography examinations as a quality marker.

CT colonography for surveillance of patients with colorectal cancer: Systematic review and meta-analysis of diagnostic efficacy.

PURPOSE: To review primary research evidence investigating performance of CT colonography for colorectal cancer surveillance. The financial impact of using CT colonography for surveillance was also estimated. METHODS: We identified primary studies of CT colonography for surveillance of colorectal cancer patients. A summary ROC curve was constructed. Inter-study heterogeneity was explored using the I2 value. Financial impact was estimated for a theoretical cohort of patients, based on Cancer Research UK statistics. RESULTS: Seven studies provided data on 880 patients. Five of seven studies (765 patients) were included for qualitative analysis. Sensitivity of CT colonography for detection of anastomotic recurrence was 95 % (95 % CI 62 - 100), specificity 100 % (95 % CI 75 - 100) and sensitivity for metachronous cancers was 100 %. No statistical heterogeneity was detected (I2 = 0 %). We estimated that CT colonography as a 'single test' alternative to colonoscopy and standard CT for surveillance would potentially save €20,785,232 (£14,803,404) for an annual cohort of UK patients. CONCLUSION: CT colonography compares favourably to colonoscopy for detection of anastomotic recurrence and metachronous colorectal cancer, and appears financially beneficial. These findings should be considered alongside limitations of small patient numbers and high clinical heterogeneity between studies. KEY POINTS: • CT colonography compares favourably to colonoscopy/standard CT for colorectal cancer surveillance. • CT colonography offers single-test luminal, serosal and extra-colonic assessment. • CT colonography is a potentially cost-saving alternative to standard surveillance protocols.

Appearances of screen-detected versus symptomatic colorectal cancers at CT colonography.

OBJECTIVES: The aim of this study was to compare the morphology, radiological stage, conspicuity, and computer-assisted detection (CAD) characteristics of colorectal cancers (CRC) detected by computed tomographic colonography (CTC) in screening and symptomatic populations. METHODS: Two radiologists independently analyzed CTC images from 133 patients diagnosed with CRC in (a) two randomized trials of symptomatic patients (35 patients with 36 tumours) and (b) a screening program using fecal occult blood testing (FOBt; 98 patients with 100 tumours), measuring tumour length, volume, morphology, radiological stage, and subjective conspicuity. A commercial CAD package was applied to both datasets. We compared CTC characteristics between screening and symptomatic populations with multivariable regression. RESULTS: Screen-detected CRC were significantly smaller (mean 3.0 vs 4.3 cm, p < 0.001), of lower volume (median 9.1 vs 23.2 cm3, p < 0.001) and more frequently polypoid (34/100, 34 % vs. 5/36, 13.9 %, p = 0.02) than symptomatic CRC. They were of earlier stage than symptomatic tumours (OR = 0.17, 95 %CI 0.07-0.41, p < 0.001), and were judged as significantly less conspicuous (mean conspicuity 54.1/100 vs. 72.8/100, p < 0.001). CAD detection was significantly lower for screen-detected (77.4 %; 95 %CI 67.9-84.7 %) than symptomatic CRC (96.9 %; 95 %CI 83.8-99.4 %, p = 0.02). CONCLUSIONS: Screen-detected CRC are significantly smaller, more frequently polypoid, subjectively less conspicuous, and less likely to be identified by CAD than those in symptomatic patients. KEY POINTS: • Screen-detected colorectal cancers (CRC) are significantly smaller than symptomatic CRC. • Screening cases are significantly less conspicuous to radiologists than symptomatic tumours. • Screen-detected CRC have different morphology compared to symptomatic tumours (more polypoid, fewer annular). • A commercial computer-aided detection (CAD) system was significantly less likely to note screen-detected CRC.

Use of CT colonography in the English Bowel Cancer Screening Programme.

OBJECTIVE: To examine use of CT colonography (CTC) in the English Bowel Cancer Screening Programme (BCSP) and investigate detection rates. DESIGN: Retrospective analysis of routinely coded BCSP data. Guaiac faecal occult blood test (gFOBt)-positive screenees undergoing CTC from June 2006 to July 2012 as their first-line colonic investigation were included. Abnormalities found at CTC, subsequent polyp, adenoma and cancer detection and positive predictive value (PPV) were calculated. Detection rates were compared with those observed in gFOBt-positive screenees investigated by colonoscopy. Multilevel logistic regression was used to examine factors associated with variable detection. RESULTS: 2731 screenees underwent CTC. Colorectal cancer (CRC) or polyps were suspected in 1027 individuals (37.6%; 95% CI 33.8% to 41.4%); 911 of these underwent confirmatory testing. 124 screenees had CRC (4.5%) and 533 had polyps (19.5%), 468 adenomatous (17.1%). Overall detection was 24.1% (95% CI 21.5% to 26.6%) for CRC or polyps and 21.7% (95% CI 19.2% to 24.1%) for CRC or adenoma. Advanced neoplasia was detected in 504 screenees (18.5%; 95% CI 16.1% to 20.8%). PPV for CRC or polyp was 72.1% (95% CI 66.6% to 77.6%). By comparison, 9.0% of 72 817 screenees undergoing colonoscopy had cancer and 50.6% had polyps; advanced neoplasia was detected in 32.7%. CTC detection rates and PPV were higher at centres with experienced radiologists (>1000 examinations) and at high-volume centres (>175 cases/radiologist/annum). Centres using three-dimensional interpretation detected more neoplasia. CONCLUSIONS: In the BCSP, detection rates after positive gFOBt are lower for CTC than colonoscopy, although populations undergoing the two tests are different. Centres with more experienced radiologists have higher detection and accuracy. Rigorous quality assurance of BCSP radiology is needed.

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.

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.

In vitro study of radiosensitivity in colorectal cancer cell lines associated with Lynch syndrome.

Introduction: Lynch syndrome patients have an inherited predisposition to cancer due to a deficiency in DNA mismatch repair (MMR) genes which could lead to a higher risk of developing cancer if exposed to ionizing radiation. This pilot study aims to reveal the association between MMR deficiency and radiosensitivity at both a CT relevant low dose (20 mGy) and a therapeutic higher dose (2 Gy). Methods: Human colorectal cancer cell lines with (dMMR) or without MMR deficiency (pMMR) were analyzed before and after exposure to radiation using cellular and cytogenetic analyses i.e., clonogenic assay to determine cell reproductive death; sister chromatid exchange (SCE) assay to detect the exchange of DNA between sister chromatids; γH2AX assay to analyze DNA damage repair; and apoptosis analysis to compare cell death response. The advantages and limitations of these assays were assessed in vitro, and their applicability and feasibility investigated for their potential to be used for further studies using clinical samples. Results: Results from the clonogenic assay indicated that the pMMR cell line (HT29) was significantly more radio-resistant than the dMMR cell lines (HCT116, SW48, and LoVo) after 2 Gy X-irradiation. Both cell type and radiation dose had a significant effect on the yield of SCEs/chromosome. When the yield of SCEs/chromosome for the irradiated samples (2 Gy) was normalized against the controls, no significant difference was observed between the cell lines. For the γH2AX assay, 0, 20 mGy and 2 Gy were examined at post-exposure time points of 30 min (min), 4 and 24 h (h). Statistical analysis revealed that HT29 was only significantly more radio-resistant than the MLH1-deficient cells lines, but not the MSH2-deficient cell line. Apoptosis analysis (4 Gy) revealed that HT29 was significantly more radio-resistant than HCT116 albeit with very few apoptotic cells observed. Discussion: Overall, this study showed radio-resistance of the MMR proficient cell line in some assays, but not in the others. All methods used within this study have been validated; however, due to the limitations associated with cancer cell lines, the next step will be to use these assays in clinical samples in an effort to understand the biological and mechanistic effects of radiation in Lynch patients as well as the health implications.

Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients.

The aim of this review is to investigate the literature pertaining to the potential risks of low-dose ionizing radiation to Lynch syndrome patients by use of computed tomography (CT), either diagnostic CT colonography (CTC), standard staging CT or CT surveillance. Furthermore, this review explores the potential risks of using radiotherapy for treatment of rectal cancer in these patients. No data or longitudinal observational studies of the impact of radiation exposure on humans with Lynch syndrome were identified. Limited experimental studies utilizing cell lines and primary cells exposed to both low and high radiation doses have been carried out to help determine radio-sensitivity associated with DNA mismatch repair gene deficiency, the defining feature of Lynch syndrome. On balance, these studies suggest that mismatch repair deficient cells may be relatively radio-resistant (particularly for low dose rate exposures) with higher mutation rates, albeit no firm conclusions can be drawn. Mouse model studies, though, showed an increased risk of developing colorectal tumors in mismatch repair deficient mice exposed to radiation doses around 2 Gy. With appropriate ethical approval, further studies investigating radiation risks associated with CT imaging and radiotherapy relevant doses using cells/tissues derived from confirmed Lynch patients or genetically modified animal models are urgently required for future clinical guidance.

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, I = 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, I = 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).

Training in Computed Tomographic Colonography Interpretation: Recommendations for Best Practice.

The value of computed tomographic colonography (CTC) as a sensitive diagnostic investigation for colorectal cancer is well established. However, there is lack of consensus in the best way to achieve expertise in interpreting these studies. In this review we discuss the value of CTC training, accreditation and performance monitoring; the qualities of good CTC interpretation training, and specific training cases with associated learning points.

Effectiveness of Training in CT Colonography Interpretation: Review of Current Literature.

International guidance recommends that readers be specifically trained before embarking on independent interpretation of CT colonography (CTC) examinations. Systematic comparison of both international training requirements and the effectiveness of CTC training is lacking in the published literature. Therefore, we identified available international training standards for CTC and performed a review of studies published in the last 20 years to assess the impact of CTC interpretation training on reader diagnostic accuracy. A wide variation in training requirements was observed. Studies of the effectiveness of CTC reader training were heterogenous in methodology, with large variation in sample size and the type of training administered. Although training in CTC interpretation improves reader sensitivity overall, it has varying impact on specificity. Consensus agreement on the best way to train and assess readers in CTC interpretation may lead to lasting improvements in reader performance.