Haemorrhoids

Clinical information monographHaemorrhoids are vascular-rich connective tissue cushions located within the anal canal. Internal haemorrhoids lie proximal to the dentate line in the anal canal, whereas external haemorrhoids are located distal to the dentate line. Haemorrhoidal disease presents as painless rectal bleeding or sudden onset of perianal pain with a tender palpable perianal mass. Diagnosis is confirmed with visualisation of the protruding tissue or anoscopic visualisation. Treatment includes increasing dietary fibre, rubber band ligation, infrared photocoagulation, sclerotherapy, or surgical haemorrhoidectomy. Complications include recurrence or worsening of symptoms, excessive bleeding, non-reducible prolapse, and, rarely, pelvic sepsis

Considerations for using potential surrogate endpoints in cancer screening trials.

The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Review aims to highlight the issues underlying the choice and use of surrogate endpoints for cancer screening trials, to propose criteria for when and how we might use such endpoints, and to suggest possible candidates. We present the current landscape and challenges, and discuss lessons and shortcomings from the therapeutic trial setting. It is hugely challenging to validate a surrogate endpoint, even with carefully designed clinical studies. Nevertheless, we consider whether there are candidates that might satisfy the requirements defined by research and regulatory bodies

Screen-detected colorectal cancers are associated with an improved outcome compared with stage-matched interval cancers

Background: Colorectal cancers (CRCs) detected through the NHS Bowel Cancer Screening Programme (BCSP) have been shown to have a more favourable outcome compared to non-screen-detected cancers. The aim was to identify whether this was solely due to the earlier stage shift of these cancers, or whether other factors were involved. Methods: A combination of a regional CRC registry (Northern Colorectal Cancer Audit Group) and the BCSP database were used to identify screen-detected and interval cancers (diagnosed after a negative faecal occult blood test, before the next screening round), diagnosed between April 2007 and March 2010, within the North East of England. For each Dukes' stage, patient demographics, tumour characteristics, and survival rates were compared between these two groups. Results: Overall, 322 screen-detected cancers were compared against 192 interval cancers. Screen-detected Dukes' C and D CRCs had a superior survival rate compared with interval cancers (P=0.014 and P=0.04, respectively). Cox proportional hazards regression showed that Dukes' stage, tumour location, and diagnostic group (HR 0.45, 95% CI 0.29-0.69, P<0.001 for screen-detected CRCs) were all found to have a significant impact on the survival of patients. Conclusions: The improved survival of screen-detected over interval cancers for stages C and D suggest that there may be a biological difference in the cancers in each group. Although lead-time bias may have a role, this may be related to a tumour's propensity to bleed and therefore may reflect detection through current screening tests

Is overexpression of HER-2 a predictor of prognosis in colorectal cancer?

<p>Abstract</p> <p>Background</p> <p>The development of novel chemotherapeutic agents in colorectal cancer has improved survival. Following initial response to chemotherapeutic strategies many patients develop refractory disease. This poses a significant challenge common to many cancer subtypes. Newer agents such as Bevacizumab have successfully targeted the tyrosine kinase receptor epidermal growth factor receptor in metastatic colorectal cancer. Human epidermal growth factor receptor-2 is another member of the tyrosine kinase receptor family which has been successfully targeted in breast cancer. This may play a role in colorectal cancer. We conducted a clinicopathological study to determine if overexpression of human epidermal growth factor receptor-2 is a predictor of outcome in a cohort of patients with colorectal cancer.</p> <p>Methods</p> <p>Clinicopathological data and paraffin-embedded specimens were collected on 132 consecutive patients who underwent colorectal resections over a 24-month period at Mayo General Hospital. Twenty-six contained non-malignant disease. Her-2/neu protein overexpression was detected using immunohistochemistry (IHC). The HER-2 4B5 Ventana monoclonal antibody was used. Fluorescent insitu hybridisation (FISH) was performed using INFORM HER-2/Neu Plus. Results were correlated with established clinical and pathological predictors of outcome including TNM stage. Statistical analysis was performed using SPSS version 11.5.</p> <p>Results</p> <p>114 were HER-2/Neu negative using IHC, 7 showed barely perceptible positivity (1+), 9 showed moderate staining (2+) and 2 were strongly positive (3+). There was no correlation with gender, age, grade, Dukes' stage, TNM stage, time to recurrence and 5-year survival (p > 0.05). FISH was applied to all 2+ and 3+ cases as well as some negative cases selected at random. Three were amplified (2 were 3+ and 1 was 2+). Similarly, HER-2 gene overexpression did not correlate with established prognostic indicators.</p> <p>Conclusion</p> <p>HER-2 protein is over expressed in 11% of colorectal cancer patients. The gene encoding HER-2 is amplified in 3% of cases. Overexpression of HER-2 is not a predictor of outcome. However, patients who over express HER-2 may respond to Herceptin therapy.</p

Outcome after extended follow-up in a prospective study of operable breast cancer: key factors and a prognostic index

In 1990, 215 patients with operable breast cancer were entered into a prospective study of the prognostic significance of five biochemical markers and 15 other factors (pathological/chronological/patient). After a median follow-up of 6.6 years, there were 77 recurrences and 77 deaths (59 breast cancer-related). By univariate analysis, patient outcome related significantly to 13 factors. By multivariate analysis, the most important of nine independent factors were: number of nodes involved, steroid receptors (for oestrogen or progestogen), age, clinical or pathological tumour size and grade. Receptors and grade exerted their influence only in the first 3 years. Progestogen receptors (immunohistochemical) and oestrogen receptors (biochemical) were of similar prognostic significance. The two receptors were correlated (r=+0.50, P=0.001) and displaced each other from the analytical model but some evidence for the additivity of their prognostic values was seen when their levels were discordant

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

Guaiac faecal occult blood test performance at initial and repeat screens in the English Bowel Cancer Screening Programme

BACKGROUND: In many countries, screening for colorectal cancer (CRC) relies on repeat testing using the guaiac faecal occult blood test (gFOBT). This study aimed to compare gFOBT performance measures between initial and repeat screens. METHODS: Data on screening uptake and outcomes from the English Bowel Cancer Screening Programme (BCSP) for the years 2008 and 2011 were used. An existing CRC natural history model was used to estimate gFOBT sensitivity and specificity, and the cost-effectiveness of different screening strategies. RESULTS: The gFOBT sensitivity for CRC was estimated to decrease from 27.35% at the initial screen to 20.22% at the repeat screen. Decreases were also observed for the positive predictive value (8.4–7.2%) and detection rate for CRC (0.19–0.14%). Assuming equal performance measures for both the initial and repeat screens led to an overestimate of the cost effectiveness of gFOBT screening compared with the other screening modalities. CONCLUSIONS: Performance measures for gFOBT screening were generally lower in the repeat screen compared with the initial screen. Screening for CRC using gFOBT is likely to be cost-effective; however, the use of different screening modalities may result in additional benefits. Future economic evaluations of gFOBT should not assume equal sensitivities between screening rounds

An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact

Behavioural and demographic predictors of adherence to three consecutive faecal occult blood test screening opportunities: a population study

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Social cognitive variables are often examined for their association with initial participation in colorectal cancer screening. Few studies have examined the association of these variables with adherence to multiple screening offers i.e., rescreening. This study aimed to describe patterns of participatory behaviour after three rounds of screening using faecal immunochemical tests (FIT) and to determine social cognitive, demographic and background variables predictive of variations in adherence. Methods Participants were 1,540 men and women aged 50 to 75 living in South Australia who completed a behavioural survey measuring demographic (for example, age, gender) and social cognitive variables relevant to FIT screening (for example, perceived barriers, benefits, self-efficacy). The survey was followed by three, free FIT screening offers mailed on an annual basis from 2008 to 2010. Patterns of participation after three screening rounds were described as one of five screening behaviours; 1) consistent re-participation (adherent with all screening rounds), 2) consistent refusal (adherent with no screening rounds), 3) drop out (adherent with earlier but not later rounds), 4) intermittent re-participation (adherent with alternate rounds) and 5) delayed entry (adherent with later but not initial round(s)). Univariate (Chi Square and Analysis of Variance) and multivariate (Generalised Estimating Equations) analyses were conducted to determine variables predictive of each category of non-adherence (those that did not participate in every screening offer, groups 2, 3, 4 and 5) relative to consistent re-participation. Results Significant social cognitive predictors of non-adherence were; less self-efficacy (drop out and consistent refusal), greater perceived barriers (drop out) and lower levels of response efficacy (consistent refusal). Demographic predictors of non-adherence included; male gender (delayed entry), younger age (intermittent, delayed and consistent refusal), less frequent GP visits (intermittent re-participation) and lack of adequate health insurance (drop out). Less satisfaction with screening at baseline predicted drop out, consistent refusal and delayed entry. Conclusions Different combinations of demographic and behavioural variables predicted different patterns of rescreening adherence. Rescreening interventions may benefit from a targeted approach that considers the different needs of the population subgroups. Satisfaction with past FOBT screening measured prior to the study screening offers was an important predictor of adherence