Role of colonoscopy in colorectal cancer

Colorectal cancer (CRC) represents the third most common malignancy throughout the world. Little or no improvement in survival has been effectively achieved in the last 50 years. Extensive epidemiological and genetic data are able to identify more precisely definite risk-groups so screening and early diagnosis can be more frequently accomplished. CRC is best detected by colonoscopy, which allows sampling for histologic diagnosis. Colonoscopy is the gold standard for detection of small and premalignant lesions, although it is not cost-effective for screening average-risk population. Colonoscopic polypectomy and mucosal resection constitute curative treatment for selective cases of invasive CRC. Similarly, alternative trans-colonoscopic treatment can be offered for adequate palliation, thus avoiding surgery.

Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective

This review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85 % of all incident CC and 50 % of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country.

Development of a novel aptamer-based multi-sensor device for the detection of osteopontin

Doctoral Dissertation for PhD degree in Chemical and Biological Engineering

Choline-PET in prostate cancer management: The point of view of the radiation oncologist.

Among PET radiotracers, FDG seems to be quite accepted as an accurate oncology diagnostic tool, frequently helpful also in the evaluation of treatment response and in radiation therapy treatment planning for several cancer sites. To the contrary, the reliability of Choline as a tracer for prostate cancer (PC) still remains an object of debate for clinicians, including radiation oncologists. This review focuses on the available data about the potential impact of Choline-PET in the daily clinical practice of radiation oncologists managing PC patients. In summary, routine Choline-PET is not indicated for initial local T staging, but it seems better than conventional imaging for nodal staging and for all patients with suspected metastases. In these settings, Choline-PET showed the potential to change patient management. A critical limit remains spatial resolution, limiting the accuracy and reliability for small lesions. After a PSA rise, the problem of the trigger PSA value remains crucial. Indeed, the overall detection rate of Choline-PET is significantly increased when the trigger PSA, or the doubling time, increases, but higher PSA levels are often a sign of metastatic spread, a contraindication for potentially curable local treatments such as radiation therapy. Even if several published data seem to be promising, the current role of PET in treatment planning in PC patients to be irradiated still remains under investigation. Based on available literature data, all these issues are addressed and discussed in this review.

COLOX: a new blood-based test for colorectal cancer screening

INTRODUCTION/OBJECTIVES: Detection rates for adenoma and early colorectal cancer (CRC) are insufficient due to low compliance towards invasive screening procedures, like colonoscopy.Available non-invasive screening tests have unfortunately low sensitivity and specificity performances.Therefore, there is a large unmet need calling for a cost-effective, reliable and non-invasive test to screen for early neoplastic and pre-neoplastic lesions AIMS & Methods: The objective is to develop a screening test able to detect early CRCs and adenomas.This test is based on a nucleic acids multi-gene assay performed on peripheral blood mononuclear cells (PBMCs).A colonoscopy-controlled feasibility study was conducted on 179 subjects.The first 92 subjects was used as training set to generate a statistical significant signature.Colonoscopy revealed 21 subjects with CRC,30 with adenoma bigger than 1 cm and 41 with no neoplastic or inflammatory lesions.The second group of 48 subjects (controls, CRC and polyps) was used as a test set and will be kept blinded for the entire data analysis.To determine the organ and disease specificity 38 subjects were used:24 with inflammatory bowel disease (IBD),14 with other cancers than CRC (OC).Blood samples were taken from each patient the day of the colonoscopy and PBMCs were purified. Total RNA was extracted following standard procedures.Multiplex RT-qPCR was applied on 92 different candidate biomarkers.Different univariate and multivariate statistical methods were applied on these candidates and among them 60 biomarkers with significant p-values (<0.01) were selected.These biomarkers are involved in several different biological functions as cellular movement,cell signaling and interaction,tissue and cellular development,cancer and cell growth and proliferation.Two distinct biomarker signatures are used to separate patients without lesion from those with cancer or with adenoma, named COLOX CRC and COLOX POL respectively.COLOX performances were validated using random resampling method, bootstrap. RESULTS: COLOX CRC and POL tests successfully separate patients without lesions from those with CRC (Se 67%,Sp 93%,AUC 0.87) and from those with adenoma bigger than 1cm (Se 63%,Sp 83%,AUC 0.77),respectively. 6/24 patients in the IBD group and 1/14 patients in the OC group have a positive COLOX CRC CONCLUSION: The two COLOX tests demonstrated a high sensitivity and specificity to detect the presence of CRCs and adenomas bigger than 1 cm.A prospective, multicenter, pivotal study is underway in order to confirm these promising results in a larger cohort.

Colonoscopy is the preferred colorectal cancer screening method in a population-based program.

BACKGROUND AND STUDY AIMS: Various screening methods for colorectal cancer (CRC) are promoted by professional societies; however, few data are available about the factors that determine patient participation in screening, which is crucial to the success of population-based programs. This study aimed (i) to identify factors that determine acceptance of screening and preference of screening method, and (ii) to evaluate procedure success, detection of colorectal neoplasia, and patient satisfaction with screening colonoscopy. PATIENTS AND METHODS: Following a public awareness campaign, the population aged 50 - 80 years was offered CRC screening in the form of annual fecal occult blood tests, flexible sigmoidoscopy, a combination of both, or colonoscopy. RESULTS: 2731 asymptomatic persons (12.0 % of the target population) registered with and were eligible to take part in the screening program. Access to information and a positive attitude to screening were major determinants of participation. Colonoscopy was the method preferred by 74.8 % of participants. Advanced colorectal neoplasia was present in 8.5 %; its prevalence was higher in males and increased with age. Significant complications occurred in 0.5 % of those undergoing colonoscopy and were associated with polypectomy or sedation. Most patients were satisfied with colonoscopy and over 90 % would choose it again for CRC screening. CONCLUSIONS: In this population-based study, only a small proportion of the target population underwent CRC screening despite an extensive information campaign. Colonoscopy was the preferred method and was safe. The determinants of participation in screening and preference of screening method, together with the distribution of colorectal neoplasia in different demographic categories, provide a rationale for improving screening procedures.

Dépistage du cancer de la prostate: actualité. [Prostate cancer screening: an update]

Prostate cancer screening using PSA is controversial because of a low specificity and detection of non clinically relevant cancer. Two important studies have been published recently. One of two studies suggests a 20% lowering in specific prostate cancer mortality due to PSA screening. This benefit is relevant but implies at a high risk of overtreatment and treatment-related complications. Currently PSA screening is only proposed as an individual screening for informed patients.

Molecular pathology of colorectal cancer.

Colorectal cancer (CRC) is one of the most intensively studied cancer types, partly because of its high prevalence but also because of the existence of its precursor lesions, tubular or villous adenomas, and more recently (sessile) serrated adenomas, which can be detected endoscopically and removed. The morphological steps in the adenoma-carcinoma sequence have been elucidated at a molecular level, which has been facilitated by identification of the genes responsible for familial intestinal cancer. However, apart from early detection of familial forms of CRC and its use in genetic counseling, until recently such detailed molecular knowledge has had little impact on clinical management of the disease. This has dramatically changed in the last decade. With drugs specifically targeting the epidermal growth factor receptor (EGFR) having been shown effective in CRC, mechanisms responsible for resistance have been explored. The finding that KRAS mutated cancers do not respond to anti-EGFR treatment has had a profound impact on clinical management and on molecular diagnostics of CRC. Additional genetic tests for mutations in NRAS, BRAF and PIK3CA contribute to determining who to treat, and others will follow. New therapies effective in patients with advanced CRC are under investigation. Remaining burning questions for optimal management are which patients will relapse after resection of the primary tumor and which patients will respond to the standard 5FU-oxaliplatin adjuvant treatment regimen. Predictive tests to address these issues are eagerly awaited. New classifications of CRC, based on molecular parameters, are emerging, and we will be confronted with new subtypes of CRC, for which the definition is based on combinations of gene expression patterns, chromosomal alterations, gene mutations and epigenetic characteristics. This will be instrumental in designing new approaches for therapy but will also be translated into molecular diagnostics. Both will contribute to improved clinical management of CRC.

Skin Cancer Prevention Strategy and Action Plan (PDF 455KB)

Northern Ireland may not enjoy the sunniest climate in the world, or even in the UK, however, in spite of this we have witnessed a significant rise in the incidence of melanoma skin cancer cases in recent years - from 80 cases in 1984 to 282 in 2009 (the latest year for which published figures are available). In relation to non-melanoma skin cancers, there are approximately 2,850 new cases here each year, making it the most common type of cancer diagnosed in Northern Ireland. åÊ The rise in the number of skin cancer cases is alarming. We know that the increase in this particular type of cancer is global and not just confined to our part of the world. We also know there are many factors involved: the significant rise in people travelling on foreign sun holidays; more leisure time being spent out of doors; and damage caused to the ozone layer to name but a few. åÊ Substantial progress in the area of skin cancer awareness raising and prevention has been made through the previous “Melanoma Strategy” which was developed in 1997. However, the unfortunate reality is that we will continue to see rising rates of skin cancer for some time to come as a result of many years of overexposure to the sun before skin cancer prevention programmes were developed. Until we can reverse this trend through effective campaigning and awareness raising, early detection will be key to bringing down mortality rates. While the 1997 strategy was right for its time, there have been many developments since then, necessitating a new strategy to reflect today’s position. åÊ For example, recent studies about the importance of vitamin D have highlighted the need for balance in sun safety messages. This new strategy is not about stopping people from enjoying the sun and its many benefits. Rather, it is about encouraging people to take proportionate measures to prevent overexposure. åÊ åÊ

Axillary Lymph Node Dissection for Sentinel Lymph Node Micrometastases May Be Safely Omitted in Early-Stage Breast Cancer Patients: Long-Term Outcomes of a Prospective Study.

OBJECTIVES: To evaluate the long-term disease-free and overall survival of patients with sentinel lymph node (SLN) micrometastases, in whom a completion axillary lymph node dissection (ALND) was systematically omitted. BACKGROUND: The use of step sectioning and immunohistochemistry for SLN analysis results in a more accurate histopathologic examination and a higher detection rate of micrometastases. However, the clinical relevance and therapeutic implications of SLN micrometastases remain a matter of debate. METHODS: In this prospective study, 236 SLN biopsies were performed in 234 consecutive early-stage breast cancer patients (T1, T2 </= 3 cm, cN0 M0) between 1998 and 2002. The SLN were examined by step sectioning and stained with hematoxylin and eosin and immunohistochemistry. None of the patients with negative SLN or SLN micrometastases (International Union Against Cancer classification, >.2 mm to </=2 mm) underwent a completion ALND or radiation to the axilla. Long-term overall and disease-free survivals were compared between patients with negative SLN and those with SLN micrometastases by log rank tests. RESULTS: The SLN was negative in 55% of patients (123 of 224). SLN micrometastases were detected in 27 patients (27 of 224, 12%). After a median follow-up of 77 months (range, 24-106 months), neither locoregional recurrences nor distant metastases occurred in any of the 27 patients with SLN micrometastases. There were no statistically significant differences for overall (P = .656), locoregional (P = .174), and axillary and distant disease-free survival (P = .15) between patients with negative SLN and SLN micrometastases. CONCLUSIONS: This analysis of unselected patients provides evidence that a completion level I and II ALND may be safely omitted in early-stage breast cancer patients with SLN micrometastases.

Voluntary Organisations Represented on the Northern Ireland Cancer Forum (PDF 141 KB)

Mission statement: åÊ To save lives of those at risk of developing cancer and enhance the quality of life of those living with cancer in Northern Ireland. åÊ Services include: - Women’s early detection service åÊ – mammography, cervical screening and breast awareness (including a mobile clinic) åÊ - Awareness campaigns on breast, cervical, prostate and testicular cancer åÊ - Counselling and complementary therapy for cancer patients and their families åÊ - Health promotion in schools, workplaces and communities åÊ - Funding for cancer research and the Regional Cancer Genetics Servic åÊ

The Growing Importance of CNVs: New Insights for Detection and Clinical Interpretation.

Differences between genomes can be due to single nucleotide variants, translocations, inversions, and copy number variants (CNVs, gain or loss of DNA). The latter can range from sub-microscopic events to complete chromosomal aneuploidies. Small CNVs are often benign but those larger than 500 kb are strongly associated with morbid consequences such as developmental disorders and cancer. Detecting CNVs within and between populations is essential to better understand the plasticity of our genome and to elucidate its possible contribution to disease. Hence there is a need for better-tailored and more robust tools for the detection and genome-wide analyses of CNVs. While a link between a given CNV and a disease may have often been established, the relative CNV contribution to disease progression and impact on drug response is not necessarily understood. In this review we discuss the progress, challenges, and limitations that occur at different stages of CNV analysis from the detection (using DNA microarrays and next-generation sequencing) and identification of recurrent CNVs to the association with phenotypes. We emphasize the importance of germline CNVs and propose strategies to aid clinicians to better interpret structural variations and assess their clinical implications.

TLR3 as a biomarker for the therapeutic efficacy of double-stranded RNA in breast cancer.

The discovery of a targeted therapeutic compound along with its companion predictive biomarker is a major goal of clinical development for a personalized anticancer therapy to date. Here we present evidence of the predictive value of TLR3 expression by tumor cells for the efficacy of Poly (A:U) dsRNA in 194 breast cancer patients enrolled in a randomized clinical trial. Adjuvant treatment with double-stranded RNA (dsRNA) was associated with a significant decrease in the risk of metastatic relapse in TLR3 positive but not in TLR3-negative breast cancers. Moreover, we show the functional relevance of TLR3 expression by human tumor cells for the antitumor effects mediated by dsRNA in several preclinical mouse models carried out in immunocompromised animals. These 2 independent lines of evidence relied upon the generation of a novel tool, an anti-TLR3 antibody (40F9.6) validated for routine detection of TLR3 expression on paraffin-embedded tissues. Altogether, these data suggest that dsRNA mediates its therapeutic effect through TLR3 expressed on tumor cells, and could therefore represent an effective targeted treatment in patients with TLR3-positive cancers.

Potential value of biliary CEA assay in early detection of colorectal adenocarcinoma liver metastases.

Elevation of the biliary CEA level in patients with liver metastases from colorectal carcinoma has been reported. The aim of this study is to determine the potential value of biliary CEA assay in the early detection of liver metastases. Biliary and serum CEA levels were determined in patients operated on for a colorectal cancer and in control groups. Among 13 patients with liver metastases from colorectal carcinomas, biliary CEA levels were markedly elevated (> 40 ng/ml) in nine, moderately elevated (5-40 ng/ml) in two and normal (arbitrarily defined as < 5 ng/ml) in two. Of 28 patients with primary colorectal carcinoma without detectable hepatic secondaries, three had marked CEA elevation in the bile, 10 had moderate CEA elevation and 15 had normal levels. Among nine patients with non-malignant hepatobiliary pathology, there was one marked biliary CEA elevation, one moderate elevation and seven normal levels. None of the 13 individuals with no identified hepatobiliary pathology had elevated biliary CEA levels. The follow-up of patients with a primary colorectal tumour, no evidence of hepatic secondaries and a biliary CEA elevation is of particular interest. If subsequent appearance of liver metastases is found in such cases, intra-operative biliary CEA assay could be considered a valuable diagnostic test. Further studies will then have to prove the possible benefit of a specific treatment for this group of patients.