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ObjectiveLow adenoma detection rates (ADR) are linked to increased postcolonoscopy colorectal cancer rates and reduced cancer survival. Devices to enhance mucosal visualisation such as Endocuff Vision (EV) may improve ADR. This multicentre randomised controlled trial compared ADR between EV-assisted colonoscopy (EAC) and standard colonoscopy (SC).DesignPatients referred because of symptoms, surveillance or following a positive faecal occult blood test (FOBt) as part of the Bowel Cancer Screening Programme were recruited from seven hospitals. ADR, mean adenomas per procedure, size and location of adenomas, sessile serrated polyps, EV removal rate, caecal intubation rate, procedural time, patient experience, effect of EV on workload and adverse events were measured.Results1772 patients (57% male, mean age 62 years) were recruited over 16 months with 45% recruited through screening. EAC increased ADR globally from 36.2% to 40.9% (P=0.02). The increase was driven by a 10.8% increase in FOBt-positive screening patients (50.9% SC vs 61.7% EAC, PConclusionEV significantly improved ADR in bowel cancer screening patients and should be used to improve colonoscopic detection.Trial registration numberNCT02552017, Results; ISRCTN11821044, Results.

Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that accumulate in circulation of cancer patients and at tumor sites where they suppress anti-tumor immunity. We previously reported that in a colon cancer prevention trial of a MUC1 vaccine tested in individuals at increased risk for colon cancer, those who did not mount immune response to the vaccine had higher pre-vaccination levels of circulating MDSC compared to those who did. We also reported that individuals with pancreatic premalignancy, Intraductal Papillary Mucinous Neoplasm (IPMN), had increased circulating levels of MDSC that inversely correlated with spontaneous antibody responses against the pancreatic tumor associated antigen MUC1, abnormally expressed on IPMN. Accumulation of MDSC in cancer and their immunosuppressive role had been well established but their presence in premalignancy was unexpected. In this study we compared MDSC in premalignancy with those in cancer with the hypothesis that there might be differences in the composition of various MDSC subpopulations and their immunosuppressive functions due to different lengths of exposure to disease and/or different tissue microenvironments. In cohorts of patients with premalignant polyps, colon cancer, premalignant IPMN, and pancreatic cancer, we confirmed higher levels of MDSC in premalignancy compared to healthy controls, higher levels of MDSC in cancer compared to premalignancy, but no difference in their subpopulation composition or immunosuppressive capacity. We show that levels of MDSC in premalignancy correlate negatively in vivo with spontaneous MUC1-specific antibody responses and in vitro with polyclonal T cell proliferation and IFN-γ secretion.

Background and aimColorectal cancer (CRC) has an increased impact on the Lebanese population’s morbidity and mortality. This study evaluated the situation of adenoma detection in an outpatient clinic in Lebanon.Patients and methods918 patients underwent colonoscopy over a period of 24 months by a qualified physician. Biopsy results were divided into normal versus abnormal colonic tissue, which was further subdivided into number of polyps and cancer.ResultsOut of 918 individuals included, 82 cases of Crohn’s colitis (8.93%) and 22 cases of ulcerative colitis (2.39%) were identified. A total of 42 cases of CRC (4.58%) and 188 cases of adenomatous polyps (20.48%) were identified. The data show that age >50 years and male gender significantly correlate with increased incidence of precancerous and cancerous polyps. Further exploring the results by age groups and gender, detection of adenomatous polyps in women aged 40–49 (8.33%) was significantly different from their female counterparts aged ≥50 years old (25.26%) (pConclusionWithin the limitations of this study, the incidence of CRC and adenomatous polyps falls in the high range compared with international studies. Furthermore, symptomatic male patients aged 40–49 appear to exhibit detection rates of adenomas similar to their counterparts aged ≥50 years old. Subjects younger than 50 years underwent diagnostic rather than screening colonoscopy, which introduces some selection bias. Nevertheless, these findings can serve as a basis for further studies.

To the Editor We read with interest the recent data reported by IJspeert et al ,1 Biswas et al 2 and Moreira et al 3 whom evaluated the prevalence of serrated polyposis syndrome (SPS), a disease characterised by the development of multiple serrated polyps throughout the colon with an increased risk to develop colorectal cancer (CRC),4 inside CRC screening programmes. A guaiac faecal occult blood test cohort from the UK showed a frequency of SPS ranging from 0.03% to 0.66%.1 ,2 Other cohorts based on primary colonoscopy showed a prevalence of SPS between 0.1% and 0.4%.1 The only published data on SPS frequency within faecal immunochemical test (FIT) programmes are from Spain and ranged from 0.34% to 0.8%.1 ,3 Since FIT has widely become the method of choice for …

BackgroundColonoscopy is a commonly used modality for screening and surveillance of colorectal cancer (CRC). Therefore, it is essential to have adequate bowel preparation (prep) for the procedure which depends on type of bowel regimens, diet before colonoscopy and timing of the procedure.AimsThe purpose of this study is to analyse the effect of multiple factors on adenoma detection rate (ADR) and prep quality of colonoscopy. This is the also the first study determining outcomes based on various combinations of diet, timing of the procedure and bowel prep regimens.MethodsThis is a retrospective single-centre observational study. Data about diet before procedure, bowel prepprep regimen and timing of the procedure was collected for patients coming for screening colonoscopy.ResultsPatients with split prep had higher good prep rates (73.8% vs 56.2%) and higher ADRs (34.2 % vs 29.9%) as compared with non-split prep. The good prep quality (65.8% vs 62.1%) and ADRs (31.9% vs 31.5%) were comparable in patients who received clear liquid diet as compared with low residue diet. The good results of bowel prep were obtained with split prep with either clear liquids or low residue diet irrespective of the timing of procedure. The poor prep was noticed in patients who underwent procedure in afternoon, with a low restrictive diet and non-split bowel regimen.ConclusionsThe current study adds to our knowledge about the combined effect of multiple variables affecting the bowel prep quality and ADR. It is imperative to opt for the best combination required for colonoscopy, as this will influence the effectiveness of colonoscopies regarding timely cancer detection and prevention.

Background Most colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context. Objective To investigate if HAMLET can be used for colon cancer treatment and prevention. Apc Min/+ mice, which carry mutations relevant to hereditary and sporadic human colorectal tumours, were used as a model for human disease. Method HAMLET was given perorally in therapeutic and prophylactic regimens. Tumour burden and animal survival of HAMLET-treated and sham-fed mice were compared. Tissue analysis focused on Wnt/β-catenin signalling, proliferation markers and gene expression, using microarrays, immunoblotting, immunohistochemistry and ELISA. Confocal microscopy, reporter assay, immunoprecipitation, immunoblotting, ion flux assays and holographic imaging were used to determine effects on colon cancer cells. Results Peroral HAMLET administration reduced tumour progression and mortality in Apc Min/+ mice. HAMLET accumulated specifically in tumour tissue, reduced β-catenin and related tumour markers. Gene expression analysis detected inhibition of Wnt signalling and a shift to a more differentiated phenotype. In colon cancer cells with APC mutations, HAMLET altered β-catenin integrity and localisation through an ion channel-dependent pathway, defining a new mechanism for controlling β-catenin signalling. Remarkably, supplying HAMLET to the drinking water from the time of weaning also significantly prevented tumour development. Conclusions These data identify HAMLET as a new, peroral agent for colon cancer prevention and treatment, especially needed in people carrying APC mutations, where colon cancer remains a leading cause of death.

Introduction The Bowel Cancer Screening Programme in England began operating in 2006 with the aim of full roll out across England by December 2009. Subjects aged 60–69 are being invited to complete three guaiac faecal occult blood tests (6 windows) every 2 years. The programme aims to reduce mortality from colorectal cancer by 16% in those invited for screening. Methods All subjects eligible for screening in the National Health Service in England are included on one database, which is populated from National Health Service registration data covering about 98% of the population of England. This analysis is only of subjects invited to participate in the first (prevalent) round of screening. Results By October 2008 almost 2.1 million had been invited to participate, with tests being returned by 49.6% of men and 54.4% of women invited. Uptake ranged between 55–60% across the four provincial hubs which administer the programme but was lower in the London hub (40%). Of the 1.08 million returning tests 2.5% of men and 1.5% of women had an abnormal test. 17 518 (10 608 M, 6910 F) underwent investigation, with 98% having a colonoscopy as their first investigation. Cancer (n=1772) and higher risk adenomas (n=6543) were found in 11.6% and 43% of men and 7.8% and 29% of women investigated, respectively. 71% of cancers were ‘early’ (10% polyp cancer, 32% Dukes A, 30% Dukes B) and 77% were left-sided (29% rectal, 45% sigmoid) with only 14% being right-sided compared with expected figures of 67% and 24% for left and right side from UK cancer registration. Conclusion In this first round of screening in England uptake and fecal occult blood test positivity was in line with that from the pilot and the original European trials. Although there was the expected improvement in cancer stage at diagnosis, the proportion with left-sided cancers was higher than expected.

OBJECTIVE: Wnt signalling is critical for normal intestinal development and homeostasis. Wnt dysregulation occurs in almost all human and murine intestinal tumours and an optimal but not excessive level of Wnt activation is considered favourable for tumourigenesis. The authors assessed effects of pan-intestinal Wnt activation on tissue homeostasis, taking into account underlying physiological Wnt activity and stem-cell number in each region of the bowel. DESIGN: The authors generated mice that expressed temporally controlled, stabilised β-catenin along the crypt-villus axis throughout the intestines. Physiological Wnt target gene activity was assessed in different regions of normal mouse and human tissue. Human intestinal tumour mutation spectra were analysed. RESULTS: In the mouse, β-catenin stabilisation resulted in a graduated neoplastic response, ranging from dysplastic transformation of the entire epithelium in the proximal small bowel to slightly enlarged crypts of non-dysplastic morphology in the colorectum. In contrast, stem and proliferating cell numbers were increased in all intestinal regions. In the normal mouse and human intestines, stem-cell and Wnt gradients were non-identical, but higher in the small bowel than large bowel in both species. There was also variation in the expression of some Wnt modulators. Human tumour analysis confirmed that different APC mutation spectra are selected in different regions of the bowel. CONCLUSIONS: There are variable gradients in stem-cell number, physiological Wnt activity and response to pathologically increased Wnt signalling along the crypt-villus axis and throughout the length of the intestinal tract. The authors propose that this variation influences regional mutation spectra, tumour susceptibility and lesion distribution in mice and humans.

Objectives Capsule colonoscopy is an additional screening modality for colorectal cancer. Second-generation capsule colonoscopy (CC2) may have improved efficacy in the detection of colon adenomas as compared with prior devices. The purpose of this study was to evaluate the performance of CC2 in the detection of polyps in symptomatic and screening patients in the USA. Design Prospective, multicentre study. Setting and participants Two academic medical centres and two private practice facilities, evaluating patients with indications for colonoscopy. Methods Patients underwent capsule colonoscopy procedure using magnesium citrate as a boost, followed by colonoscopy on the same day. The main outcome measurement was accuracy of CC2 for the detection of colorectal polyps ≥6 and ≥10 mm as compared with conventional colonoscopy. Results 51 patients were enrolled, 50 of whom had CC2 and colonoscopy examinations and were included in the accuracy analysis. 30% and 14% of patients had polyps ≥6 and ≥10 mm, respectively. For lesions ≥10 mm identified on conventional colonoscopy, CC2 sensitivity was 100% (95% CI 56.1% to 100%) with a specificity of 93.0% (79.9% to 98.2%). For polyps ≥6 mm, the CC2 sensitivity was 93.3% (66.0% to 99.7%) and the specificity was 80.0% (62.5% to 90.9%). There was a 61% adequate cleansing rate with 64% of CC2 procedures being complete. Conclusions In the initial US experience with CC2 there was adequate sensitivity for detecting patients with polyps ≥6 mm in size. Magnesium citrate was inadequate as a boost agent. Trial registration number NCT01087528.