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Bowel Cancer Screening (UK)

Information Patients and the Public (8 links)


Information for Health Professionals / Researchers (6 links)

Latest Research Publications

Showing publications with corresponding authors from the UK (Source: PubMed).

Scarpinata R, Aly EH
Does robotic rectal cancer surgery offer improved early postoperative outcomes?
Dis Colon Rectum. 2013; 56(2):253-62 [PubMed]
BACKGROUND: Laparoscopic rectal surgery continues to be challenging, especially in low rectal cancers, because the technique has several limitations. Robotic rectal surgery could potentially address these limitations. However, it still remains unclear whether robotic surgery should be accepted as the new standard treatment in rectal cancer surgery.
OBJECTIVE: The aim of this study is to provide a comprehensive and critical analysis of the available literature to assess if robotic rectal surgery offers improved early postoperative outcomes in comparison with standard laparoscopic rectal surgery.
DATA SOURCES: A systematic review was conducted following the search of electronic databases (PubMed, Science Direct, Google Scholar) for the period 2007 to 2011 by using the key words "rectal surgery," "laparoscopic," "robotic."
STUDY SELECTION: All studies reporting outcomes on laparoscopic and robotic resection for extraperitoneal and intraperitoneal rectal cancer were included in the review process; all studies on colonic cancer and benign disease were excluded.
INTERVENTIONS: A comparison was conducted of robotic vs standard laparoscopic rectal cancer surgery.
MAIN OUTCOME MEASURES: The primary outcome measured was the assessment of whether robotic rectal cancer surgery provides improved short-term outcomes in comparison with standard laparoscopic rectal surgery.
RESULTS: Robotic rectal surgery was associated with increased cost and operating time, but lower conversion rates, even in obese individuals, distal rectal tumors, and patients who had preoperative chemoradiotherapy regardless of the experience of the surgeon. There is also marginally better outcome in anastomotic leak rates, circumferential resection margin positivity, and perseveration of autonomic function, but this did not reach statistical significance.
LIMITATIONS: This review has some limitations because it relies on the analysis of data collected from various nonrandomized controlled trials with variable quality and different methodology.
CONCLUSION: The current evidence suggests that robotic rectal surgery could potentially offer better short-term outcomes especially when applied in selected patients. Obesity, male sex, preoperative radiotherapy, and tumors in the lower two-thirds of the rectum may represent selection criteria for robotic surgery to justify its increased cost.
Laparoscopic Colorectal Surgery & Training Unit, Aberdeen Royal Infirmary, Aberdeen, Scotland


Ashraf SQ, Nicholls AM, Wilding JL, et al.
Direct and immune mediated antibody targeting of ERBB receptors in a colorectal cancer cell-line panel.
Proc Natl Acad Sci U S A. 2012; 109(51):21046-51 [PubMed] Article available free on PMC after 18/06/2013
A significant proportion of colorectal cancer (CRC) patients are resistant to anti-ERBB1 [avian erythroblastic leukemia viral (v-erb-b) oncogene homolog, receptor for EGF] monoclonal antibodies (Mabs). We evaluated both immune and nonimmune effects of cetuximab (anti-ERBB1 Mab), trastuzumab (anti-ERBB2 Mab), pertuzumab (anti-ERBB2 Mab), and lapatinib (dual ERBB1 and ERBB2 tyrosine kinase inhibitor) in a large well-characterized panel of 64 CRC cell lines to find response predictive tumor characteristics. There was a significant correlation between the direct effects of cetuximab and lapatinib. Both agents were associated (P = 0.0004) with "triple' wild-type status in KRAS, BRAF, and PIK3CA exon 20. Most cell lines were resistant to the direct effects of anti-ERBB2 Mabs, suggesting that the effects of lapatinib might mainly be through ERBB1. Microarray mRNA expression profiles of sensitive and resistant cell lines showed that although ERBB1 receptor or ligand levels did not associate with cetuximab sensitivity, high levels of ERBB2 (P = 0.036) and amphiregulin (P = 0.026) predicted sensitivity to lapatinib. However, higher ERBB1 expression predicted susceptibility to cetuximab-induced antibody-dependent cellular cytotoxicity and occurred independently of KRAS/BRAF/PIK3CA mutations (P = 0.69). Lapatinib may be an effective alternative therapy to cetuximab in triple wild-type tumors. Microarray analysis provides suggestive biomarkers for resistance. ERBB1 levels, independent of mutation status, predict immune killing. Therefore, anti-ERBB1 antibodies may be considered in CRC tumors with higher ERBB1 expression and favorable FcγR polymorphisms.
Cancer and Immunogenetics Laboratory, Department of Oncology, Weatherall Institute of Molecular Medicine, Oxford OX3 9DS


Renehan AG, Flood A, Adams KF, et al.
Body mass index at different adult ages, weight change, and colorectal cancer risk in the National Institutes of Health-AARP Cohort.
Am J Epidemiol. 2012; 176(12):1130-40 [PubMed]
The authors investigated the relations of body mass index at different ages and adult weight change to incident colorectal cancer risk in the prospective National Institutes of Health-AARP Diet and Health Study (1995-1996), using a subcohort with repeated recall weights (273,679 participants; mean baseline age = 62.8 years). During 2,509,662 person-years follow-up, 4076 incident colorectal cancers were ascertained. For men, an increased risk of colon cancer but not rectal cancer was associated with body mass index at baseline age (per 5-kg/m(2) increase, hazard ratio (HR) = 1.18, 95% confidence interval (CI): 1.11, 1.25), at age 50 years (HR = 1.18, 95% CI: 1.10, 1.26), and at age 35 years (HR = 1.16, 95% CI: 1.07, 1.25) but less so at age 18 years. Weight gained between the ages of 18 and 35 years and between 18 years of age and the baseline age was associated with an increased risk of colon cancer in men (per 0.5-kg/year increase, HR = 1.18, 95% CI: 1.11, 1.25 and HR = 1.29, 95% CI: 1.16, 1.56, respectively). For women, relations throughout were weaker than those observed for men. These findings suggest that weight gains during early to middle adulthood have important influences on colon cancer risk, especially in men.
Department of Surgery, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX


McCowan C, Munro AJ, Donnan PT, Steele RJ
Use of aspirin post-diagnosis in a cohort of patients with colorectal cancer and its association with all-cause and colorectal cancer specific mortality.
Eur J Cancer. 2013; 49(5):1049-57 [PubMed]
OBJECTIVE: Aspirin is associated with a reduced risk of developing colorectal cancer. This study examined whether patients with colorectal cancer prescribed aspirin had improved survival.
DESIGN: An observational population cohort study was undertaken using data linkage of cancer registry, dispensed prescriptions and death certificate records in Tayside, Scotland. All community prescribed aspirin pre- and post-diagnosis was extracted and periods of aspirin use post-diagnosis for each individual were analysed using Cox proportional hazard models. Main outcome measures were all-cause and colorectal mortality from death certificates.
RESULTS: Two thousand nine hundred ninety patients were identified with colorectal cancer between 1st January 1997 and 30th December 2006 and followed up until 28th February 2010. Median age at diagnosis was 73 (interquartile range [IQR] 65-80) with 52% male. One thousand nine hundred ninety-eight (67%) deaths were recorded with 1021 (34%) attributed to colorectal cancer. One thousand three hundred forty (45%) patients used aspirin at some stage of the study period. Aspirin use post-diagnosis was associated with lower risk of all cause mortality (hazard ratio [HR]=0.67, 95% confidence interval [CI]=0.57-0.79, p<0.001) and colorectal cancer specific mortality after allowing for age, Dukes' stage, gender, socio-economic status and aspirin use pre-diagnosis. Increasing age and stage at diagnosis were associated with increased risk, with more affluent patients at reduced risk.
CONCLUSIONS: Our study suggests that aspirin use post-diagnosis of colorectal cancer may reduce both all cause and colorectal cancer specific mortality. However further work is required to ensure this is a causal relationship and to identify whether it is best used in specific groups of patients.
Division of Population Health Sciences, Medical Research Institute, University of Dundee, Dundee


Tsiamoulos ZP, Saunders BP
A new accessory, endoscopic cuff, improves colonoscopic access for complex polyp resection and scar assessment in the sigmoid colon (with video).
Gastrointest Endosc. 2012; 76(6):1242-5 [PubMed]
BACKGROUND: Difficult and unstable endoscopic access to large sessile/flat colon polyps in the sigmoid colon may prevent successful and complete EMR.
OBJECTIVE: We report our experience with the use of an endoscopic cuff, a new endoscopic accessory, to improve endoscopic access during endoscopic therapy and scar assessment.
DESIGN: Single-center, retrospective, feasibility case series.
SETTING: Tertiary referral academic endoscopy unit.
PATIENTS: Nonconsecutive patients referred for endoscopic resection of large flat/sessile sigmoid colon polyps or surveillance of postpolypectomy scars in the sigmoid colon.
INTERVENTIONS: When conventional methods to achieve stable access and visualization were unsuccessful, the endoscopic cuff was used to retract sigmoid colon folds.
MAIN OUTCOME MEASUREMENTS: Safety, procedural success, and complications.
RESULTS: Five patients (mean age 62 years, 3 male/2 female) underwent endoscopic cuff-assisted EMR polypectomy, and 7 patients (mean age 62 years, 2 male/5 female) underwent post-EMR scar surveillance with an endoscopic cuff-assisted flexible sigmoidoscopy. All sessile/flat polyps (mean size 29 mm) or post-EMR scar sites (mean size 15 mm) were located at acute bends in the sigmoid colon. With the endoscopic cuff placed around the tip of the colonoscope, endoscopic access improved significantly by flattening/depressing colon folds close to the lesion/scar. The entire polyp/scar surface was revealed, facilitating a complete polyp excision and a meticulous scar assessment. No immediate or delayed adverse events were seen.
LIMITATIONS: Single-center, nonrandomized case series.
CONCLUSIONS: An endoscopic cuff appears to be a safe and easily used accessory to facilitate colonoscopic access for complex polypectomy and scar assessment in the sigmoid colon.
Wolfson Unit for Endoscopy, St. Mark's Hospital and Academic Institute, London


Adair RA, Scott KJ, Fraser S, et al.
Cytotoxic and immune-mediated killing of human colorectal cancer by reovirus-loaded blood and liver mononuclear cells.
Int J Cancer. 2013; 132(10):2327-38 [PubMed]
Reovirus is a promising oncolytic virus, acting by both direct and immune-mediated mechanisms, although its potential may be limited by inactivation after systemic delivery. Our study addressed whether systemically delivered reovirus might be shielded from neutralising antibodies by cell carriage and whether virus-loaded blood or hepatic innate immune effector cells become activated to kill colorectal cancer cells metastatic to the liver in human systems. We found that reovirus was directly cytotoxic against tumour cells but not against fresh hepatocytes. Although direct tumour cell killing by neat virus was significantly reduced in the presence of neutralising serum, reovirus was protected when loaded onto peripheral blood mononuclear cells, which may carry virus after intravenous administration in patients. As well as handing off virus for direct oncolytic killing, natural killer (NK) cells within reovirus-treated blood mononuclear cells were stimulated to kill tumour targets, but not normal hepatocytes, in a Type I interferon-dependent manner. Similarly, NK cells within liver mononuclear cells became selectively cytotoxic towards tumour cells when activated by reovirus. Hence, intravenous reovirus may evade neutralisation by serum via binding to circulating mononuclear cells, and this blood cell carriage has the potential to investigate both direct and innate immune-mediated therapy against human colorectal or other cancers metastatic to the liver.
Leeds Institute of Molecular Medicine, University of Leeds, Leeds


Bates DO, Catalano PJ, Symonds KE, et al.
Association between VEGF splice isoforms and progression-free survival in metastatic colorectal cancer patients treated with bevacizumab.
Clin Cancer Res. 2012; 18(22):6384-91 [PubMed] Article available free on PMC after 18/06/2013
PURPOSE: Bevacizumab improves survival for patients with metastatic colorectal cancer with chemotherapy, but no proven predictive markers exist. The VEGF-A splice form, VEGF(165)b, anti-angiogenic in animal models, binds bevacizumab. We tested the hypothesis that prolonged progression-free survival (PFS) would occur only in patients with low relative VEGF(165)b levels treated with bevacizumab.
EXPERIMENTAL DESIGN: Blinded tumor samples from the phase III trial of FOLFOX4 ± bevacizumab were assessed for VEGF(165)b and VEGF(total) by immunohistochemistry and scored relative to normal tissue. A predictive index (PI) was derived from the ratio of VEGF(165)b:VEGF(total) for 44 samples from patients treated with FOLFOX + bevacizumab (arm A) and 53 samples from patients treated with FOLFOX4 (arm B), and PFS, and overall survival (OS) analyzed on the basis of PI relative to median ratio.
RESULTS: Unadjusted analysis of PFS showed significantly better outcome for individuals with VEGF(165)b:VEGF(total) ratio scores below median treated with FOLFOX4 + bevacizumab compared with FOLFOX4 alone (median, 8.0 vs. 5.2 months; P < 0.02), but no effect of bevacizumab on PFS in patients with VEGF(165)b:VEGF(total) ratio >median (5.9 vs. 6.3 months). These findings held after adjustment for other clinical and demographic features. OS was increased in arm A (median, 13.6 months) compared with arm B (10.6 months) in the low VEGF(165)b group, but this did not reach statistical significance. There was no difference in the high VEGF(165)b:VEGF(total) group between FOLFOX + bevacizumab (10.8 months) and FOLFOX alone (11.3 months).
CONCLUSION: Low VEGF(165)b:VEGF(total) ratio may be a predictive marker for bevacizumab in metastatic colorectal cancer, and individuals with high relative levels may not benefit.
Microvascular Research Laboratories, Department of Physiology and Pharmacology, University of Bristol, Bristol
Research funded by:


Goh V, Shastry M, Engledow A, et al.
Integrated (18)F-FDG PET/CT and perfusion CT of primary colorectal cancer: effect of inter- and intraobserver agreement on metabolic-vascular parameters.
AJR Am J Roentgenol. 2012; 199(5):1003-9 [PubMed]
OBJECTIVE: The purpose of this article is to assess the effect of observers on combined metabolic-vascular parameters in colorectal cancer.
SUBJECTS AND METHODS: Twenty-five prospective patients (12 men and 13 women; mean age, 66.9 years) with proven primary colorectal adenocarcinoma underwent integrated (18)F-FDG PET/perfusion CT to assess tumor metabolism (mean and maximum standardized uptake value [SUV(mean) and SUV(max), respectively]) and vascularization (blood flow [BF], blood volume [BV], permeability surface-area product, and standardized perfusion value). Intra- and interobserver agreement for PET, perfusion CT, and combined metabolic-flow parameters were determined by Bland-Altman statistics and intraclass correlation coefficients (ICCs).
RESULTS: The mean tumor size was 3.8 ± 1.6 cm; there were five stage IA/B, six stage IIA/B, eight stage IIIA/B, and six stage IV tumors. Intra- and interobserver agreement for individual parameters was fair to good, with mean differences between observers of -0.74 for SUV(max), -0.16 for SUV(mean), 9.72 for BF, 0.15 for BV, -0.76 for permeability surface-area product, and 0.09 for standardized perfusion value. ICCs were 0.44-0.99 and 0.38-0.89 for intra- and interobserver agreement, respectively. Interobserver agreement was variable for combined metabolic-flow parameters but better for metabolic-flow difference than for metabolic-flow ratio: ICCs were 0.69-0.88 for the metabolic-flow difference and 0.44-0.94 for the metabolic-flow ratio.
CONCLUSION: Combined parameters to assess the metabolic-flow relationship are influenced by observer variation. Intra- and interobserver agreement are better for the metabolic-flow differences than for the ratios, suggesting that metabolic-flow differences may be a more robust parameter for clinical practice.
Division of Imaging Sciences and Biomedical Engineering, King's College London, Imaging 2, Level 1, Lambeth Wing, St. Thomas' Hospital, Lambeth Palace Rd, Middlesex, London SE1 7EH


Zhao L, Lim SY, Gordon-Weeks AN, et al.
Recruitment of a myeloid cell subset (CD11b/Gr1 mid) via CCL2/CCR2 promotes the development of colorectal cancer liver metastasis.
Hepatology. 2013; 57(2):829-39 [PubMed]
UNLABELLED: Liver metastasis from colorectal cancer is a leading cause of cancer mortality. Myeloid cells play pivotal roles in the metastatic process, but their prometastatic functions in liver metastasis remain incompletely understood. To investigate their role, we simulated liver metastasis in C57BL/6 mice through intrasplenic inoculation of MC38 colon carcinoma cells. Among the heterogeneous myeloid infiltrate, we identified a distinct population of CD11b/Gr1(mid) cells different from other myeloid populations previously associated with liver metastasis. These cells increased in number dramatically during establishment of liver metastases and were recruited from bone marrow by tumor-derived CCL2. Liver metastasis of Lewis lung carcinoma cells followed this pattern but this mechanism is not universal as liver colonization by B16F1 melanoma cells did not recruit similar subsets. Inhibition of CCL2 signaling and absence of its cognate receptor CCR2 reduced CD11b/Gr1(mid) recruitment and decreased tumor burden. Depletion of the CD11b/Gr1(mid) subset in a transgenic CD11b-diphtheria toxin receptor mouse model markedly reduced tumor cell proliferation. There was no evidence for involvement of an adaptive immune response in the prometastatic effects of CD11b/Gr1(mid) cells. Additionally, an analogous myeloid subset was found in liver metastases of some colorectal cancer patients.
CONCLUSION: Collectively, our findings highlight the importance of myeloid cells--in this case a selective CD11b/Gr1(mid) subset--in sustaining development of colorectal cancer liver metastasis and identify a potential target for antimetastatic therapy.
Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, OX3 7LJ
Research funded by:


Williams JP, Phillips BE, Smith K, et al.
Effect of tumor burden and subsequent surgical resection on skeletal muscle mass and protein turnover in colorectal cancer patients.
Am J Clin Nutr. 2012; 96(5):1064-70 [PubMed]
BACKGROUND: Cachexia is a consequence of tumor burden caused by ill-defined catabolic alterations in muscle protein turnover.
OBJECTIVE: We aimed to explore the effect of tumor burden and resection on muscle protein turnover in patients with nonmetastatic colorectal cancer (CRC), which is a surgically curable tumor that induces cachexia.
DESIGN: We recruited the following 2 groups: patients with CRC [n = 13; mean ± SEM age: 66 ± 3 y; BMI (in kg/m(2)): 27.6 ± 1.1] and matched healthy controls (n = 8; age: 71 ± 2 y; BMI: 26.2 ± 1). Control subjects underwent a single study, whereas CRC patients were studied twice before and ~6 wk after surgical resection to assess muscle protein synthesis (MPS), muscle protein breakdown (MPB), and muscle mass by using dual-energy X-ray absorptiometry.
RESULTS: Leg muscle mass was lower in CRC patients than in control subjects (6290 ± 456 compared with 7839 ± 617 g; P < 0.05) and had an additional decline after surgery (5840 ± 456 g; P < 0.001). Although postabsorptive MPS was unaffected, catabolic changes with tumor burden included the complete blunting of postprandial MPS (0.038 ± 0.004%/h in the CRC group compared with 0.065 ± 0.006%/h in the control group; P < 0.01) and a trend toward increased MPB under postabsorptive conditions (P = 0.09). Although surgical resection exacerbated muscle atrophy (-7.2%), catabolic changes in protein metabolism had normalized 6 wk after surgery. The recovery in postprandial MPS after surgery was inversely related to the degree of muscle atrophy (r = 0.65, P < 0.01).
CONCLUSIONS: CRC patients display reduced postprandial MPS and a trend toward increased MPB, and tumor resection reverses these derangements. With no effective treatment of cancer cachexia, future therapies directed at preserving muscle mass should concentrate on alleviating proteolysis and enhancing anabolic responses to nutrition before surgery while augmenting muscle anabolism after resection.
School of Graduate Entry Medicine and Health, University of Nottingham, Derby
Research funded by:


Valori R, Rey JF, Atkin WS, et al.
European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Quality assurance in endoscopy in colorectal cancer screening and diagnosis.
Endoscopy. 2012; 44 Suppl 3:SE88-105 [PubMed]
Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on quality assurance in endoscopy includes 50 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of endoscopy and other elements in the screening process, including multidisciplinary diagnosis and management of the disease.
Gloucestershire Royal Hospital, Gloucester


Halloran SP, Launoy G, Zappa M,
European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Faecal occult blood testing.
Endoscopy. 2012; 44 Suppl 3:SE65-87 [PubMed]
Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on faecal occult blood testing includes 21 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of screening programmes and services.
Bowel Cancer Screening Southern Programme Hub, Royal Surrey County Hospital NHS Foundation Trust and University of Surrey, Guildford


Moss S, Ancelle-Park R, Brenner H,
European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Evaluation and interpretation of screening outcomes.
Endoscopy. 2012; 44 Suppl 3:SE49-64 [PubMed]
Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on evaluation and interpretation of screening outcomes includes 20 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of the screening process, including multi-disciplinary diagnosis and management of the disease.
Centre for Cancer Prevention, Wolfson Institute, Queen Mary University of London


Austoker J, Giordano L, Hewitson P, et al.
European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Communication.
Endoscopy. 2012; 44 Suppl 3:SE164-85 [PubMed]
Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on communication includes 35 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of screening programmes and services.
University of Oxford, Oxford


Atkin WS, Valori R, Kuipers EJ, et al.
European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Colonoscopic surveillance following adenoma removal.
Endoscopy. 2012; 44 Suppl 3:SE151-63 [PubMed]
Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on colonoscopic surveillance following adenoma removal includes 24 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of surveillance and other elements in the screening process, including multi-disciplinary diagnosis and management of the disease.
Department of Surgery and Cancer, Imperial College London, London


Steele RJ, Pox C, Kuipers EJ, et al.
European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Management of lesions detected in colorectal cancer screening.
Endoscopy. 2012; 44 Suppl 3:SE140-50 [PubMed]
Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on management of lesions detected in colorectal cancer screening includes 32 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of the screening process, including multi-disciplinary diagnosis and management of the disease.
Ninewells Hospital and Medical School, Dundee


Quirke P, Risio M, Lambert R, et al.
European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Quality assurance in pathology in colorectal cancer screening and diagnosis.
Endoscopy. 2012; 44 Suppl 3:SE116-30 [PubMed]
Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on quality assurance in pathology in colorectal cancer screening and diagnosis includes 23 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of the screening process, including multi-disciplinary diagnosis and management of the disease.
Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, University of Leeds, Leeds
Research funded by:


Steele RJ, Rey JF, Lambert R,
European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Professional requirements and training.
Endoscopy. 2012; 44 Suppl 3:SE106-15 [PubMed]
Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on professional requirements and training includes 23 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of surveillance and other elements in the screening process, including multi-disciplinary diagnosis and management of the disease.
Ninewells Hospital and Medical School, Dundee


Glynne-Jones R, Sebag-Montefiore D, Adams R, et al.
Prognostic factors for recurrence and survival in anal cancer: generating hypotheses from the mature outcomes of the first United Kingdom Coordinating Committee on Cancer Research Anal Cancer Trial (ACT I).
Cancer. 2013; 119(4):748-55 [PubMed]
BACKGROUND: Only 2 prospective studies have previously reported prognostic factors for anal cancer, European Organization for Research and Treatment of Cancer trial 22861 (EORTC 22861) and Radiation Therapy Oncology Group trial 98-11 (RTOG 98-11). Both of those trials reported that clinically positive lymph nodes and male sex predicted poorer overall survival (OS). The EORTC 22861 trial indicated that the same factors were prognostic for locoregional control. In the current report, the authors investigated potential prognostic factors from the first United Kingdom Coordinating Committee on Cancer Research Anal Cancer Trial (ACT I), in which patients were randomized to receive either radiotherapy alone or chemoradiation (CRT) with concurrent 5-fluorouracil/mitomycin C.
METHODS: In the ACT I trial, associations between several baseline characteristics and 3 endpoints were investigated: locoregional failure (LRF), anal cancer death (ACD), and OS. The analyses were restricted to 292 patients who received CRT, which subsequently became standard treatment. A score was derived using multivariable Cox regression to identify the set of factors that, together, had the best prognostic performance. This score was then validated with a large, independent prospective trial (the ACT II trial).
RESULTS: Palpable, clinically positive lymph nodes were associated with LRF (P = .012), a greater risk of ACD (P = .031), and decreased OS (P = .006) in multivariable analyses. Men had worse outcomes than women for LRF (P = .036), ACD (P = .039), and OS (P = .008). On average, a lower hemoglobin level had an adverse effect on ACD (P = .008), and a higher white blood cell count had an adverse effect on OS (P = .001). However, external validation of the score was poor for LRF (area under the curve [AUC] = 54%) but was better for ACD (AUC = 67%) and OS (AUC = 63%).
CONCLUSIONS: The results from this analysis of the ACT I trial supported evidence for palpable lymph nodes and male sex as prognostic factors for LRF and OS, and lower hemoglobin levels and a higher white blood cell count were identified as prognostic factors for ACD and OS, respectively.
Mount Vernon Center for Cancer Treatment, Northwood


Carvajal-Carmona LG, Zauber AG, Jones AM, et al.
Much of the genetic risk of colorectal cancer is likely to be mediated through susceptibility to adenomas.
Gastroenterology. 2013; 144(1):53-5 [PubMed] Article available free on PMC after 01/01/2014
Several single-nucleotide polymorphisms (SNPs) have been associated with colorectal cancer (CRC) susceptibility. Most CRCs arise from adenomas, and SNPs therefore might affect predisposition to CRC by increasing adenoma risk. We found that 8 of 18 known CRC-associated SNPs (rs10936599, rs6983267, rs10795668, rs3802842, rs4444235, rs1957636, rs4939827, and rs961253) were over-represented in CRC-free patients with adenomas, compared with controls. Ten other CRC-associated SNPs (rs6691170, rs6687758, rs16892766, rs7136702, rs11169552, rs4779584, rs9929218, rs10411210, rs4813802, and rs4925386) were not associated significantly with adenoma risk. Genetic susceptibility to CRC in the general population is likely to be mediated in part by predisposition to adenomas.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford
Research funded by:


Melchini A, Needs PW, Mithen RF, Traka MH
Enhanced in vitro biological activity of synthetic 2-(2-pyridyl) ethyl isothiocyanate compared to natural 4-(methylsulfinyl) butyl isothiocyanate.
J Med Chem. 2012; 55(22):9682-92 [PubMed]
Dietary isothiocyanates (ITC) derived from cruciferous vegetables have been shown to have numerous biological effects consistent with chemoprotective activity. In this study we synthesized a novel ITC, 2-(2-pyridyl) ethyl ITC (PY-ITC), and assessed its chemopreventive ability in comparison to sulforaphane (SF), the ITC derived from broccoli. PY-ITC suppressed cancerous cell growth and proliferation at lower concentrations than SF and was more potent at inducing p21 protein. Through the use of whole genome arrays we demonstrate that prostate cells exposed to PY-ITC or SF have similar biological response, albeit PY-ITC alters a greater number of genes, and to a greater extent. In the presence of a phosphatidylinositol-3-kinase (PI3K) inhibitor PY-ITC had a more pronounced effect on gene expression, emphasizing the important role of PI3K/AKT signaling in mediating the chemopreventive effects of ITCs. These results highlight the importance of the ITC side chain in bioactivity.
Food & Health Programme, Institute of Food Research , Norwich Research Park, NR4 7UA United Kingdom.
Research funded by:


Patel UB, Blomqvist LK, Taylor F, et al.
MRI after treatment of locally advanced rectal cancer: how to report tumor response--the MERCURY experience.
AJR Am J Roentgenol. 2012; 199(4):W486-95 [PubMed]
OBJECTIVE: The Magnetic Resonance Imaging and Rectal Cancer European Equivalence (MERCURY) Study validated the use of MRI for posttreatment staging and its correlation with survival outcomes. As a consequence, reassessment of MRI scans after preoperative therapy has implications for surgical planning, the timing of surgery, sphincter preservation, deferral of surgery for good responders, and development of further preoperative treatments for radiologically identified poor responders.
CONCLUSION: In this article we report a validated systematic approach to the interpretation of MR images of patients with rectal cancer after chemoradiation.
Department of Radiology, Royal Marsden Hospital, Downs Rd, Sutton SM2 5PT


Bhandari S, Taylor NJ, Sinha A, et al.
Can combined 18F-FDG-PET and dynamic contrast-enhanced MRI predict behavior of desmoid tumors in patients with familial adenomatous polyposis?
Dis Colon Rectum. 2012; 55(10):1032-7 [PubMed]
BACKGROUND: Desmoid tumors associated with familial adenomatous polyposis show variable behavior; about 10% grow relentlessly, resulting in severe morbidity or mortality. Investigations that could identify the minority of desmoid tumors that behave aggressively would allow these tumors to be treated early and spare the majority of patients who have more benign disease from unnecessary intervention.
OBJECTIVE: The aim of this study was to investigate whether imaging the tumor metabolic-vascular phenotype by modern methods predicts growth.
DESIGN: This is a prospective case series study.
SETTINGS: The study was conducted at a tertiary center specializing in familial adenomatous polyposis and desmoid disease.
PATIENTS: Nine patients with familial adenomatous polyposis (4 male, mean age 39 years) with desmoid tumor underwent 18F-FDG-PET and dynamic contrast-enhanced MRI. Standard MRI was repeated a year later to assess tumor growth.
MAIN OUTCOME MEASURES: The primary outcome measured was the correlation between 18F-FDG-PET and dynamic contrast-enhanced MRI parameters and subsequent desmoid growth.
RESULTS: Failed intravenous access precluded dynamic contrast-enhanced MRI in 1 female patient. Thirteen desmoid tumors (4 intra-abdominal, 2 extra-abdominal, 7 abdominal wall; mean area, 68 cm) were analyzed in the remaining 8 patients. Two patients died before follow-up MRI. Five tumors decreased in size, 3 increased in size, and 3 remained stable after a year. Significant correlation (Spearman rank correlation, significance at 5%) existed between maximum standardized uptake value and k(ep) (r = -0.56, p = 0.04), but not with other vascular parameters (K(trans) (r = -0.47, p = 0.09); v(e) (r = -0.11, p = 0.72); integrated area under the gadolinium-time curve at 60 seconds (r = -0.47, p = 0.10)). There was no significant difference in the maximum standardized uptake value or dynamic contrast-enhanced MRI parameters (K(trans), v(e), k(ep), integrated area under the gadolinium-time curve at 60 seconds) between the tumors that grew or decreased in size or between the tumor sites. However, vascular metabolic ratio (maximum standardized uptake value/K(trans)) was significantly different for tumor site (p = 0.001) and size (p = 0.001, 1-way ANOVA).
LIMITATIONS: This investigation is limited because of its exploratory nature and small patient numbers.
CONCLUSIONS: Although not predictive for tumor behavior, some correlations existed between dynamic contrast-enhanced MRI and 18F-FDG-PET parameters. Vascular metabolic ratio may provide further information on tumor behavior; however, this needs to be evaluated with further larger studies.
1The Polyposis Registry, St Mark's Hospital, Harrow, London


Kochhar R, Plumb AA, Carrington BM, Saunders M
Imaging of anal carcinoma.
AJR Am J Roentgenol. 2012; 199(3):W335-44 [PubMed]
OBJECTIVE: The purpose of this article is to review the role of imaging in the management of patients with anal cancer. The relevant anatomy, imaging techniques, and interpretation of images of patients before and after therapy will be discussed.
CONCLUSION: Anal carcinomas are uncommon but increasing in frequency. Radiologists must recognize typical patterns of disease at initial evaluation, posttherapy appearances, and when to suspect residual or recurrent disease to guide clinicians and achieve optimal patient outcome.
Department of Radiology, The Christie NHS Foundation Trust, Manchester


Jones C, Badger SA, McKie LD, et al.
PET-CT accurately predicts the pre-operative characteristics of colorectal hepatic metastases.
Eur J Surg Oncol. 2012; 38(12):1184-8 [PubMed]
BACKGROUND: Since 2002, Positron Emission Tomography (PET-CT) has been considered to be an essential pre-operative investigation in the management of colorectal liver metastases (CRLM) in our institution. This study aimed to compare characteristics of hepatic metastases on PET-CT with post-operative histological findings and pathology of the primary tumour.
METHODS: All patients with CRLM, who underwent surgical intervention from 2002 to 2008, were reviewed. PET-CT and pathology reports of hepatic resections and original colorectal resections were retrieved. Patient demographics, colorectal staging, number of metastases and their maximum diameter from both PET-CT and pathology reports were recorded. Values were expressed as mean (±SD).
RESULTS: 141 patients were identified. The maximum diameter on PET-CT (4.2 ± 2.6) was similar to pathology (4.8 ± 3.6; p = 0.39), with significant correlation (r = 0.72, p < 0.0001). The number of lesions on PET-CT (1.6 ± 1.0) was similar to pathology (1.7 ± 1.3; p = 0.43) with significant correlation (r = 0.80, p < 0.0001). Mean SUV max was 9.22 (±4.39), with no correlation to lesion diameter (r = 0.25, p = 0.045), but significantly increased with decreasing differentiation (p = 0.01).
CONCLUSIONS: PET-CT scanning accurately detected the number of lesions and their maximum diameter, with radiological evidence of poorer differentiation. Further studies of non-surgical patients are required to assess its overall accuracy.
Department of Hepatobiliary Surgery, Mater Hospital, Crumlin Road, Belfast BT14 6AB


Richards CH, Roxburgh CS, MacMillan MT, et al.
The relationships between body composition and the systemic inflammatory response in patients with primary operable colorectal cancer.
PLoS One. 2012; 7(8):e41883 [PubMed] Article available free on PMC after 01/01/2014
BACKGROUND: Weight loss is recognised as a marker of poor prognosis in patients with cancer but the aetiology of cancer cachexia remains unclear. The aim of the present study was to examine the relationships between CT measured parameters of body composition and the systemic inflammatory response in patients with primary operable colorectal cancer.
PATIENT AND METHODS: 174 patients with primary operable colorectal cancer who underwent resection with curative intent (2003-2010). Image analysis of CT scans was used to measure total fat index (cm(2)/m(2)), subcutaneous fat index (cm(2)/m(2)), visceral fat index (cm(2)/m(2)) and skeletal muscle index (cm(2)/m(2)). Systemic inflammatory response was measured by serum white cell count (WCC), neutrophil:lymphocyte ratio (NLR) and the Glasgow Prognostic Score (mGPS).
RESULTS: There were no relationships between any parameter of body composition and serum WCC or NLR. There was a significant relationship between low skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p = 0.001). This was confirmed by linear relationships between skeletal muscle index and both C-reactive protein (r = -0.21, p = 0.005) and albumin (r = 0.31, p<0.001). There was no association between skeletal muscle index and tumour stage.
CONCLUSIONS: The present study highlights a direct relationship between low levels of skeletal muscle and the presence of a systemic inflammatory response in patients with primary operable colorectal cancer.
University Department of Surgery, Glasgow Royal Infirmary, Glasgow


Di Fabio F, Whistance R, Rahman S, et al.
Exploring the role of laparoscopic surgery in two-stage hepatectomy for bilobar colorectal liver metastases.
J Laparoendosc Adv Surg Tech A. 2012; 22(7):647-50 [PubMed]
BACKGROUND: The role of laparoscopy in two-stage hepatectomy for bilobar colorectal liver metastases (CRLMs) has not yet been extensively investigated.
PATIENTS AND METHODS: We reviewed a prospectively collected database of 302 consecutive patients undergoing laparoscopic liver resection at our institution between 2003 and 2011.
RESULTS: Eight patients undergoing laparoscopic first/second-stage hepatectomy for bilobar CRLMs (male/female 6:2; median age, 64 years) were analyzed. The first stage consisted of laparoscopic clearance of the left lobe in all patients with no postoperative morbidity and mortality. Seven patients underwent portal vein embolization or ligation. The median interval between first- and second-stage hepatic resections was 89 days (range, 36-123 days). Second-stage hepatectomy with right lobar clearance (open, n=5; laparoscopic, n=2; laparoscopic to open, n=1) was associated with no mortality and an operative morbidity rate of 50%. Adhesions were judged to be minimal or absent during the second-stage procedure. Complications included intra-abdominal collection (n=2), bleeding requiring re-operation (n=1), and bile leak (n=1). R0 resection was obtained in 7 of 8 cases after first-stage resection and in 8 of 8 cases after second-stage resection. Three patients (38%) died from disease recurrence. Of the remaining 5 patients, 4 are disease-free at a median follow-up of 24 months (range, 9-27 months).
CONCLUSIONS: The well-recognized advantages of laparoscopy may play a favorable role in the management of patients with bilobar CRLMs candidate for a two-stage resection. The first-stage laparoscopic clearance of the left lobe could progressively become the "gold standard." Laparoscopic second-stage hepatectomy should be limited to selected cases.
Department of Colorectal Surgery, University Hospital Southampton NHS Foundation Trust, Southampton


Acheson AG, Brookes MJ, Spahn DR
Effects of allogeneic red blood cell transfusions on clinical outcomes in patients undergoing colorectal cancer surgery: a systematic review and meta-analysis.
Ann Surg. 2012; 256(2):235-44 [PubMed]
OBJECTIVE: To determine the effect of allogeneic blood transfusion (ABT) on clinical outcomes in patients with colorectal cancer undergoing surgery.
BACKGROUND: Perioperative ABTs may be associated with adverse clinical outcomes.
METHODS: Systematic review of the literature with odds ratio (OR) and incidence rate ratio (IRR) meta-analyses of predefined clinical outcomes based on a MEDLINE search.
RESULTS: In total, 20,795 colorectal cancer (CRC) patients observed for more than 59.2 ± 26.1 months (108,838 patient years) were included, of which 58.8% were transfused. ABT was associated with increased all-cause mortality OR = 1.72 (95% confidence interval [CI] 1.55-1.91, P < 0.001); I(2) = 23.3% (0-51.1) and IRR = 1.31 (1.23-1.39, P < 0.001), I(2) = 0.0% (0-37.0). ABT was also associated with increased ORs (95% CI, P) for cancer-related mortality of 1.71 (1.43-2.05, P <0.001), combined recurrence-metastasis-death 1.66 (1.41-1.97, P < 0.001), postoperative infection 3.27 (2.05-5.20, P < 0.001), and surgical reintervention 4.08 (2.18-7.62, <0.001). IRR (95% CI, P) was 1.45 (1.26-1.66, <0.001) for cancer-related mortality and 1.32 (1.19-1.46, <0.001) for recurrence-metastasis-death. Mean length of hospital stay was significantly longer in transfused compared with nontransfused patients (17.8 ± 4.8 vs 13.9 ± 4.7 days, P = 0.005).
CONCLUSIONS: In patients with colorectal cancer (CRC) undergoing surgery, ABTs are associated with adverse clinical outcomes, including increased mortality. Measures aimed at limiting the use of ABTs should be investigated further.
Division of Gastrointestinal Surgery, Nottingham Digestive Disease Centre NIHR, Biomedical Research Unit, Queen's Medical Centre, Nottingham


Murphy N, Norat T, Ferrari P, et al.
Dietary fibre intake and risks of cancers of the colon and rectum in the European prospective investigation into cancer and nutrition (EPIC).
PLoS One. 2012; 7(6):e39361 [PubMed] Article available free on PMC after 01/01/2014
BACKGROUND: Earlier analyses within the EPIC study showed that dietary fibre intake was inversely associated with colorectal cancer risk, but results from some large cohort studies do not support this finding. We explored whether the association remained after longer follow-up with a near threefold increase in colorectal cancer cases, and if the association varied by gender and tumour location.
METHODOLOGY/PRINCIPAL FINDINGS: After a mean follow-up of 11.0 years, 4,517 incident cases of colorectal cancer were documented. Total, cereal, fruit, and vegetable fibre intakes were estimated from dietary questionnaires at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models stratified by age, sex, and centre, and adjusted for total energy intake, body mass index, physical activity, smoking, education, menopausal status, hormone replacement therapy, oral contraceptive use, and intakes of alcohol, folate, red and processed meats, and calcium. After multivariable adjustments, total dietary fibre was inversely associated with colorectal cancer (HR per 10 g/day increase in fibre 0.87, 95% CI: 0.79-0.96). Similar linear associations were observed for colon and rectal cancers. The association between total dietary fibre and risk of colorectal cancer risk did not differ by age, sex, or anthropometric, lifestyle, and dietary variables. Fibre from cereals and fibre from fruit and vegetables were similarly associated with colon cancer; but for rectal cancer, the inverse association was only evident for fibre from cereals.
CONCLUSIONS/SIGNIFICANCE: Our results strengthen the evidence for the role of high dietary fibre intake in colorectal cancer prevention.
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London
Research funded by:


Mallucci L, Shi DY, Davies D, et al.
Killing of Kras-mutant colon cancer cells via Rac-independent actin remodeling by the βGBP cytokine, a physiological PI3K inhibitor therapeutically effective in vivo.
Mol Cancer Ther. 2012; 11(9):1884-93 [PubMed] Article available free on PMC after 01/01/2014
Activating mutations in Kras are the most frequent mutations in human cancer. They define a subset of patients who do not respond to current therapies and for whom prognosis is poor. Oncogenic Kras has been shown to deregulate numerous signaling pathways of which the most intensively studied are the Ras/extracellular signal-regulated kinase cascade and the phosphoinositide 3-kinase (PI3K)/Akt cascade. However, to date, there are no effective targeted therapies in the clinic against Kras-mutant cancers. Here, we report that the β-galactoside-binding protein (βGBP) cytokine, a physiologic inhibitor of class I PI3Ks, is a potent activator of apoptosis in Kras-mutant colorectal cancer cells, even when coharboring mutant-activated PIK3CA. Our study unveils an elective route to intrinsic and extrinsic apoptosis, which involves the cytoskeleton. Early events are inhibition of PI3K activity and Rac-independent actin rearrangement assignable to phosphoinositide changes at the plasma membrane. Cyclin E deregulation, arrest of DNA synthesis, and checkpoint kinase 2 activation underscore events critical to the activation of an intrinsic apoptotic program. Clustering of CD95/Fas death receptors underscore events critical to the activation of extrinsic apoptosis. In nude mice, we present the first evidence that xenograft tumor development is strongly inhibited by Hu-r-βGBP. Taken together, our results open a new therapeutic opportunity to a subset of patients refractive to current treatments. This first demonstration of therapeutic efficacy against Kras-mutant colon cancer suggests that Hu-r-βGBP may also be therapeutically effective against other cancers harboring activating Ras mutations as well as PIK3CA mutations.
School of Biomedical and Health Sciences, King's College London, London
Research funded by:


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