Leddin, Desmond; Enns, Robert; Hilsden, Robert; Fallone, Carlo A; Rabeneck, Linda; Sadowski, Daniel C; Singh, Harminder
BACKGROUND: Differences between American (United States [US]) and European guidelines for colonoscopy surveillance may create confusion for the practicing clinician. Under- or overutilization of surveillance colonoscopy can impact patient care. METHODS: The Canadian Association of Gastroenterology (CAG) convened a working group (CAG-WG) to review available guidelines and provide unified guidance to Canadian clinicians regarding appropriate follow-up for colorectal cancer (CRC) surveillance after index colonoscopy. A literature search was conducted for relevant data that postdated the published guidelines. RESULTS: The CAG-WG chose the 2012 US Multi-Society Task Force (MSTF) on Colorectal Cancer to serve as the basis for the Canadian position, primarily because the US approach was the simplest and comprehensively addressed the issue of serrated polyps. Aspects of other guidelines were incorporated where relevant. The CAG-WG recommendations differed from the US MSTF guidelines in three main areas: patients with negative index colonoscopy should be followed-up at 10 years using any of the appropriate screening tests, including colonos-copy, for average-risk individuals; among patients with >10 adenomas, a one-year interval for subsequent colonoscopy is recommended; and for long-term follow-up, patients with low-risk adenomas on both the index and first follow-up procedures can undergo second follow-up colonos-copy at an interval of five to 10 years. DISCUSSION: The CAG-WG adapted the US MSTF guidelines for colonoscopy surveillance to the Canadian health care environment with a few modifications. It is anticipated that the present article will provide unified guidance that will enhance physician acceptance and encourage appropriate utilization of recommended surveillance intervals. PMID:23616961
... After Colorectal Cancer Colorectal Cancer After Treatment Second Cancers After Colorectal Cancer Colorectal cancer survivors can be affected by a ... many of these cancers. Follow-up after colorectal cancer treatment After completing treatment for colorectal cancer, you ...
... rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...
Kuipers, Ernst J.; Grady, William M.; Lieberman, David; Seufferlein, Thomas; Sung, Joseph J.; Boelens, Petra G.; van de Velde, Cornelis J. H.; Watanabe, Toshiaki
Colorectal cancer had a low incidence several decades ago. However, it has become a predominant cancer and now accounts for approximately 10% of cancer-related mortality in western countries. The ‘rise’ of colorectal cancer in developed countries can be attributed to the increasingly ageing population, unfavourable modern dietary habits and an increase in risk factors such as smoking, low physical exercise and obesity. New treatments for primary and metastatic colorectal cancer have emerged, providing additional options for patients; these treatments include laparoscopic surgery for primary disease, more-aggressive resection of metastatic disease (such as liver and pulmonary metastases), radiotherapy for rectal cancer and neoadjuvant and palliative chemotherapies. However, these new treatment options have had limited impact on cure rates and long-term survival. For these reasons, and the recognition that colorectal cancer is long preceded by a polypoid precursor, screening programmes have gained momentum. This Primer provides an overview of the current state of art knowledge on the epidemiology and mechanisms of colorectal cancer, as well as on diagnosis and treatment. PMID:27189416
Kachuri, Linda; Villeneuve, Paul J; Parent, Marie-Élise; Johnson, Kenneth C; Harris, Shelley A
The International Agency for Research on Cancer (IARC) classified diesel exhaust as carcinogenic to humans (Group 1) and gasoline exhaust as a possible carcinogen (Group 2B) based studies of lung cancer, however the evidence for other sites is limited. We addressed this question by investigating exposure to diesel and gasoline emissions with respect to risk of colorectal cancer in men. We used data from a population-based case-control study with incident cases of colon (n = 931) and rectal (n = 840) cancer and 1360 controls from 7 Canadian provinces conducted in 1994-1997. Lifetime occupational history and information on other risk factors was collected. Occupational hygienists, blinded to case-control status, assigned exposures to each job for 3 dimensions: concentration, frequency, and reliability. Logistic regression was used to estimate odds ratios (OR) and their 95 % confidence intervals (CI), adjusted for age, province, use of proxy respondents, smoking, body-mass index, physical activity, intake of alcohol, processed meats, and occupational exposure to asbestos and aromatic amines. Among CRC cases, 638 (36 %) were exposed to diesel and 814 (46 %) were exposed to gasoline emissions. Relative to the unexposed, elevated risks were observed among subjects ever exposed to high concentration levels of diesel emissions for colorectal cancer (OR = 1.65, 95 % CI = 0.98-2.80) and rectal cancer (OR = 1.98, 95 % CI = 1.09-3.60), but not colon cancer. Prolonged (>10 years) exposure at high concentrations was also associated with high risks of rectal cancer (OR = 2.33 95 % CI = 0.94-5.78; p-trend = 0.02). No statistically significant associations were observed for gasoline emissions. Our findings suggest that sustained high-level exposure diesel emissions may increase the risk of rectal cancer.
Tsvetkova, E.; Sud, S.; Aucoin, N.; Biagi, J.; Burkes, R.; Samson, B.; Brule, S.; Cripps, C.; Colwell, B.; Falkson, C.; Dorreen, M.; Goel, R.; Halwani, F.; Maroun, J.; Michaud, N.; Tehfe, M.; Thirlwell, M.; Vickers, M.; Asmis, T.
The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, 23–25 October 2014. Expert radiation, medical, and surgical oncologists and pathologists involved in the management of patients with gastrointestinal malignancies participated in presentations and discussions resulting in consensus statements on such hot topics as management of neuroendocrine tumours, advanced and metastatic pancreatic cancer, and metastatic colorectal cancer. PMID:26300681
... Bar Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...
Shapero, Theodore F; Hoover, Jean; Paszat, Lawrence F; Burgis, Elaine; Hsieh, Eugene; Rothwell, Deanna M; Rabeneck, Linda
Despite highest-quality evidence that early detection of colorectal cancer (CRC) can lead to reduced mortality, no organized CRC screening programs exist in Canada. To report the safety, the feasibility, and the detection rate for the first Canadian community-based nurse-performed flexible sigmoidoscopy (FS) screening program for CRC, established in 1999. Cross-sectional analysis of data collected from a prospective study of FS done by nurses from March 1999 to November 2002. Estimate of differences between men and women in FS findings, with relative risks. Logistic regression used to calculate odds ratios for advanced neoplasia. Endoscopy suite of a community hospital. Asymptomatic men and women > or =50 years, with no previous history of CRC. FS done by a nurses, and colonoscopy for persons with abnormalities done by an experienced gastroenterologist. Mean depth of insertion of endoscope; duration of FS procedure; number and location of polyps found during FS; number, location, and type of polyps found during colonoscopy. A total of 1818 individuals (mean age, 62 years) underwent nurse-performed FS (mean duration, 7.3 minutes; mean depth of insertion of the endoscope, 53.5 cm), without complications. Results of the FS were abnormal for 240 (13.2%) of the 1818 participants; 231 (12.7%) underwent colonoscopy. Distal neoplasms (adenomas or cancer) were detected in 8.7% (158/1818). After adjustment for age and family history of CRC, the risk of advanced neoplasm in the distal colon for men was about twice that for women (odds ratio 1.95, 95% confidence interval 1.21-3.14). Cancer was detected in 5 of the 1818 participants screened (0.28%), and high-grade dysplasia was detected in an additional 5 (0.28%). One of the cancers and all the lesions with high-grade dysplasia were treated endoscopically. Our community-based nurse-performed FS screening program was feasible and safe. The referral rate for colonoscopy was 13%, and the cancer detection rate was 2.8 per 1000
Leddin, Desmond J; Enns, Robert; Hilsden, Robert; Plourde, Victor; Rabeneck, Linda; Sadowski, Daniel C; Signh, Harminder
The Canadian Association of Gastroenterology and the Canadian Digestive Health Foundation published guidelines on colon cancer screening in 2004. Subsequent to the publication of these guidelines, many advances have occurred, thereby necessitating a review of the existing guidelines in the context of new technologies and clinical knowledge. The assembled guideline panel recognized three recent American sets of guidelines and identified seven issues that required comment from a Canadian perspective. These issues included, among others, the role of program-based screening, flexible sigmoidoscopy, computed tomography colonography, barium enema and quality improvement. The panel also provided context for the selection of the fecal immunochemical test as the fecal occult blood test of choice, and the relative role of colonoscopy as a primary screening tool. Recommendations were also provided for an upper age limit for colon cancer screening, whether upper endoscopy should be performed following a negative colonoscopy for a positive fecal occult blood test and when colon cancer screening should resume following negative colonoscopy.
Chen, Eric X; Jonker, Derek J; Siu, Lillian L; McKeever, Karyn; Keller, Deborah; Wells, Julie; Hagerman, Linda; Seymour, Lesley
Background Olaparib is an orally available inhibitor of PARP-1. In pre-clinical studies, olaparib was shown to potentiate anti-tumor effects of irinotecan in colon cancer cell lines. This phase I study was conducted to evaluate the safety and tolerability of olaparib in combination with irinotecan. Patients and Methods Patients with advanced colorectal cancer whose disease progressed after at least one systemic therapy regimen were enrolled. Dose escalation and de-escalation were based on toxicity assessment. Pharmacokinetic samples were collected in Cycle 1 for olaparib, irinotecan and SN-38. Results Twenty-five patients were enrolled, 11 patients on a schedule of continuous olaparib and irinotecan every 3 weeks (Part A) and 14 patients on a schedule of intermittent olaparib and irinotecan every 2 weeks (Part B). Continuous olaparib administration was associated with higher than expected toxicities and was not considered to be tolerable. Intermittent olaparib administration was better tolerated, and the recommended phase 2 doses were olaparib 50 mg p.o twice daily days 1-5 and irinotecan 125 mg/m(2) i.v. every 2 weeks. Common toxicities included fatigue, anorexia, diarrhea, nausea, vomiting, neutropenia, thrombocytopenia and abdominal pain. Nine patients had stable disease as the best response, 2 from Part A (3 and 9 months respectively), and 7 from Part B (median duration: 7.4 months; range: 4 to 13 months). There was no pharmacokinetic interaction between olaparib and irinotecan. Conclusions Olaparib can be combined with irinotecan if administered intermittently. Both olaparib and irinotecan required significant dose reductions. The lack of anti-tumor efficacy observed in this trial makes this combination of little interest for further clinical development. Trial Registration ID NCT00535353.
Lao, Victoria Valinluck; Grady, William M.
Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer. PMID:22009203
Leddin, Desmond J; Enns, Robert; Hilsden, Robert; Plourde, Victor; Rabeneck, Linda; Sadowski, Daniel C; Singh, Harminder
The Canadian Association of Gastroenterology and the Canadian Digestive Health Foundation published guidelines on colon cancer screening in 2004. Subsequent to the publication of these guidelines, many advances have occurred, thereby necessitating a review of the existing guidelines in the context of new technologies and clinical knowledge. The assembled guideline panel recognized three recent American sets of guidelines and identified seven issues that required comment from a Canadian perspective. These issues included, among others, the role of program-based screening, flexible sigmoidoscopy, computed tomography colonography, barium enema and quality improvement. The panel also provided context for the selection of the fecal immunochemical test as the fecal occult blood test of choice, and the relative role of colonoscopy as a primary screening tool. Recommendations were also provided for an upper age limit for colon cancer screening, whether upper endoscopy should be performed following a negative colonoscopy for a positive fecal occult blood test and when colon cancer screening should resume following negative colonoscopy. PMID:21165377
Jochem, Carmen; Leitzmann, Michael
There is strong evidence that modifiable lifestyle factors such as obesity play a key role in colorectal carcinogenesis. Epidemiologic data have consistently reported a positive association between obesity and colorectal cancer. The relative risk associated with general obesity (as assessed by BMI) is higher in men than in women and for cancer of the colon than for cancer of the rectum. Abdominal obesity (as assessed by waist circumference (WC) or waist-to-hip ratio) is associated with an increased risk of colorectal cancer in both sexes, with stronger associations for cancer of the colon than for cancer of the rectum. Plausible biological mechanisms include insulin resistance, hyperinsulinemia, chronic inflammation, altered levels of growth factors, adipocytokines and steroid hormones. In addition to its effect on colorectal cancer incidence, obesity may play a role in colorectal cancer recurrence, treatment outcomes and survival. Understanding the effects of childhood and adolescent obesity and weight change over the life course in relation to future risk of colorectal cancer is incomplete but essential for targeted preventive recommendations. This chapter summarizes the current evidence on the relationship between obesity and colorectal cancer and colorectal adenoma, a common precursor lesion.
Charalampoudis, Petros; Kykalos, Stylianos; Stamopoulos, Paraskevas; Kouraklis, Gregory
Synchronous colorectal cancers (SCRCs) have been increasingly diagnosed due to emerging diagnostic modalities. The presence of three or more synchronous colorectal cancers has, however, only rarely been reported. A 76-year-old white man presented for management of two concurrent colorectal adenocarcinomas in the left colon evidenced on total colonoscopy. Preoperative abdominal ultrasonography and thoracoabdominal computed tomography were negative for metastatic disease. The patient underwent an elective left hemicolectomy. The pathology report ultimately showed the presence of three moderately differentiated, distinct colorectal cancers. The patient experienced an uneventful recovery. PMID:27695171
... linked to a decreased risk of colorectal cancer. Aspirin Studies have shown that taking aspirin lowers the ... cancer: Nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin It is not known if the use of ...
Herszényi, László; Juhász, Márk; Prónai, László; Tulassay, Zsolt
Although colorectal cancer is one of the most preventable forms of cancer, it remains the second leading cause of cancer death worldwide. Primary prevention involves the identification and elimination of factors, which cause or promote colorectal cancer. The goal of screening is to prevent colorectal cancer mortality through the detection and treatment of premalignant adenomas and curable-stage cancer. Most colorectal cancers are believed to arise from adenomatous polyps. Early identification and removal of adenomas can prevent the development of colorectal cancer. Chemoprevention is the use of specific chemical compounds to prevent, inhibit, or reverse carcinogenesis. Several chemoprevention options have been investigated and confirmed as effective. Aspirin and other nonsteroidal anti-inflammatory drugs are the most widely studied agents, their use has been consistently associated with reduction in the risk of mortality and the incidence of colorectal adenomas and cancers. The selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) have been demonstrated to decrease the number and the size of polyps in patients with familial adenomatous polyposis syndrome. Because the gastrointestinal toxicity of coxibs is lower, it might be safer than aspirin or other non-selective nonsteroidal anti-inflammatory drugs for long-term use. This review aims to summarize the recent theoretical and practical advances in the chemoprevention of colorectal cancer.
... Colorectal Cancer Risk Factors Download SAS and Gauss Code Page Options Print Page Quick Links Colon and Rectal Cancer Home Page Colon and Rectal Cancer: Prevention, Genetics, Causes Tests to Detect Colorectal Cancer and Polyps ...
Bouvier, Anne-Marie; Launoy, Guy
The incidence of colorectal cancer increased in France until the 2000s' then decreased. Time trends in incidence for this cancer varied according to its sublocation along the gut. Incidence increased for right and left colon cancers, whereas it remained stable for sigmoid cancers in males and decreased in females. Incidence decreased over time for rectal cancers. The proportion of colorectal cancer in the overall French cancer prevalence is 12%. In 2008, 121,000 patients had a colorectal cancer diagnosed in the 5 previous years. The cumulative risk of colorectal cancer increased from 3.9% for males born around 1900 to 4.9% for those born around 1930 and then slightly decreased, being 4.5% among those born around 1950. It remained at the same level for females and was 2.9% for those born around 1950. The prognosis of colorectal cancer improved over time. Net 5-year survival increased in males from 53% for cancers diagnosed between 1989 and 1991 to 58% for those diagnosed between 2001 and 2004. The highest improvement of 10 year survival rates concerned left colon and rectosigmoid junction (+19% in a decade). The progressive set up of national colorectal screening since the early 2000's and the introduction of recent immunological tests in 2015 should decrease the mortality for this cancer and, at term, should decrease its incidence too.
Na, Soo-Young; Myung, Seung-Jae
Obesity worldwide is constantly increasing. Obesity acts as an independent significant risk factor for malignant tumors of various organs including colorectal cancer. Visceral adipose tissue is physiologically more important than subcutaneous adipose tissue. The relative risk of colorectal cancer of obese patients is about 1.5 times higher than the normal-weight individuals, and obesity is also associated with premalignant colorectal adenoma. The colorectal cancer incidence of obese patients has gender-specific and site-specific characteristics that it is higher in men than women and in the colon than rectum. Obesity acts as a risk factor of colorectal carcinogenesis by several mechanisms. Isulin, insulin-like growth factor, leptin, adiponectin, microbiome, and cytokines of chronic inflammation etc. have been understood as its potential mechanisms. In addition, obesity in patients with colorectal cancer negatively affects the disease progression and response of chemotherapy. Although the evidence is not clear yet, there are some reports that weight loss as well as life-modification such as dietary change and physical activity can reduce the risk of colorectal cancer. It is very important knowledge in the point that obesity is a potentially modifiable risk factor that can alter the incidence and outcome of the colorectal cancer.
Chan, Pak Wo Webber; Ngu, Jing Hieng; Poh, Zhongxian; Soetikno, Roy
Colorectal cancer, which is the leading cancer in Singapore, can be prevented by increased use of screening and polypectomy. A range of screening strategies such as stool-based tests, flexible sigmoidoscopy, colonoscopy and computed tomography colonography are available, each with different strengths and limitations. Primary care physicians should discuss appropriate screening modalities with their patients, tailored to their individual needs. Physicians, patients and the government should work in partnership to improve uptake of colorectal cancer screening to reduce the morbidity and mortality from colorectal cancer. Copyright: © Singapore Medical Association.
Chan, Pak Wo Webber; Ngu, Jing Hieng; Poh, Zhongxian; Soetikno, Roy
Colorectal cancer, which is the leading cancer in Singapore, can be prevented by increased use of screening and polypectomy. A range of screening strategies such as stool-based tests, flexible sigmoidoscopy, colonoscopy and computed tomography colonography are available, each with different strengths and limitations. Primary care physicians should discuss appropriate screening modalities with their patients, tailored to their individual needs. Physicians, patients and the government should work in partnership to improve uptake of colorectal cancer screening to reduce the morbidity and mortality from colorectal cancer. PMID:28111691
Otani, Kensuke; Ishihara, Soichiro; Yamaguchi, Hironori; Murono, Koji; Yasuda, Koji; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Watanabe, Toshiaki
Colorectal cancer is an obesity-related malignancy. Adiponectin is an adipokine produced exclusively by adipose tissue, and its concentration in the serum is reduced in obesity. A low serum level of adiponectin is associated with an increased risk of various types of malignancies including colorectal cancer. These facts suggest that the epidemiological link between obesity and cancer may have a significant association with adiponectin. Although numerous studies of colorectal cancer have been reported, the results are conflicting about the anti-cancer effect of adiponectin, and how adiponectin affects carcinogenesis or cancer development remains controversial. Because adiponectin has multiple systemic effects and exists as a high serum concentration protein, the main role of adiponectin should be regulation of homeostasis, and it would not likely act as an anti-cancerous hormone. However, as epidemiological evidence shows, a low adiponectin level may be a basic risk factor for colorectal cancer. We speculate that when the colonic epithelium is stimulated or damaged by another carcinogen under the condition of a low adiponectin level, carcinogenesis is promoted and cancer development is facilitated. In this report, we summarize recent findings of the correlation between adiponectin and colorectal cancer and investigate the effect of adiponectin on colorectal cancer.
Marley, Andrew R; Nan, Hongmei
Colorectal cancer is currently the third deadliest cancer in the United States and will claim an estimated 49,190 U.S. lives in 2016. The purpose of this review is to summarize our current understanding of this disease, based on nationally published statistics and information presented in peer-reviewed journal articles. Specifically, this review will cover the following topics: descriptive epidemiology (including time and disease trends both in the United States and abroad), risk factors (environmental, genetic, and gene-environment interactions), screening, prevention and control, and treatment. Landmark discoveries in colorectal cancer risk factor research will also be presented. Based on the information reviewed for this report, we suggest that future U.S. public health efforts aim to increase colorectal cancer screening among African American communities, and that future worldwide colorectal cancer epidemiology studies should focus on researching nutrient-gene interactions towards the goal of improving personalized treatment and prevention strategies. PMID:27766137
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Aleksandrova, Krasimira; Nimptsch, Katharina; Pischon, Tobias
This review outlines the association of obesity with risk of colorectal cancer and the potential underlying mechanisms from an epidemiological perspective. Current research indicates that there is a moderate but consistently reported association between general obesity (as determined by BMI) and colorectal cancer incidence and mortality. The relative risk associated with obesity is higher for cancer of the colon than for cancer of the rectum and it is higher in men than in women. By contrast, abdominal adiposity (as determined by waist circumference or waist-to-hip ratio) is similarly strongly associated with colon cancer in men and women, suggesting that abdominal adiposity is a more important risk factor for colon cancer than general adiposity, at least in women. Putative mechanisms that may account for the link between adiposity and colorectal cancer risk include hyperinsulinemia, insulin resistance, inflammation, altered immune response, oxidative stress, as well as disturbances in insulin-like growth factors, adipokines, and sex steroids. Understanding the link between obesity and colorectal cancer may pave the way for targeted prevention of colorectal cancer morbidity and mortality.
... tested at age 45. Read More "Colorectal Cancer" Articles Colorectal Cancer: A Personal Journey / The Importance of Early Detection / Developments in Colorectal Cancer Screening Summer 2016 Issue: Volume 11 Number 2 Page ... Us | Viewers & Players Friends of the National Library of Medicine (FNLM)
... detection is early cure!” Read More "Colorectal Cancer" Articles Colorectal Cancer: A Personal Journey / The Importance of Early Detection / Developments in Colorectal Cancer Screening Summer 2016 Issue: Volume 11 Number 2 Page ... Us | Viewers & Players Friends of the National Library of Medicine (FNLM)
Ströhle, Alexander; Maike, Wolters; Hahn, Andreas
Diet plays an important role in the pathogenesis of colorectal cancer. Current prospective cohort studies and metaanalysis enable a reevaluation of how food or nutrients such as fiber and fat influence cancer risk. Based on the evidence criteria of the WHO/FAD, risk reduction by a high intake of fruit is assessed as possible, while a lowered risk by a high vegetable intake is probable. Especially raw vegetables and fruits seem to exert anticancer properties. The evidence of a risk reducing effect of whole grain relating to colorectal cancer is assessed as probable whereas the evidence of an increased risk by high consumption of refined white flour products and sweets is (still) insufficient despite some evidences. There is a probable risk reducing effect of milk and dairy products. e available data on eggs and red meat indicate a possible risk increasing influence. Stronger clues for a risk increasing effect have been shown for meat products leading to an evidence assessed as probable. Owing to varied interpretations of the data on fiber, the evidence of a risk reducing effect relating to colorectal cancer is assessed as possible or insufficient. The available data on alcohol consumption indicate a possible risk increasing effect. In contrast to former evaluations, diets rich in fat seem to increase colorectal cancer risk only indirectly as part of a hypercaloric diet by advancing the obesity risk. Thus, the evidence of obesity, especially visceral obesity, as a risk of colorectal cancer is judged as convincing today. Prospective cohort studies suggest that people who get higher than average amounts of folic acid from multivitamin supplements have lower risks of colorectal cancer. The evidence for a risk reducing effect of calcium, selenium, vitamin D and vitamin E on colorectal cancer is insufficient. As primary prevention, a diet rich in vegetables, fruits, whole grain products, and legumes added by low-fat dairy products, fish, and poultry can be recommended. In
Kim, E.E.; Deland, F.H.; Casper, S.; Corgan, R.L.; Primus, F.J.; Goldenberg, D.M.
This study examines the accuracy of colorectal cancer radioimmunodetection. Twenty-seven patients with a history of histologically-confirmed colonic or rectal carcinoma received a high-titer, purified goat anti-CEA IgG labelled with /sup 131/I at a total dose of at least 1.0 ..mu..Ci. Various body views were scanned at 24 and 48 hours after administration of the radioantibody. Three additional cases were evaluated; one had a villous adenoma in the rectum and received the /sup 131/I-labeled anti-CEA IgG, while two colonic carcinoma patients received normal goat IgG labelled with /sup 131/I. All of the 7 cases with primary colorectal cancer showed true-positive tumor localization, while 20 of 25 sites of metastatic colorectal cancer detected by immune scintigraphy were corroborated by other detection measures. The sensitivity of the radioimmunodetection of colorectal cancers (primary and metastatic) was found to be 90% (true-positive rate), the putative specificity (true-negative rate) was 94%, and the apparent overall accuracy of the technique was 93%. Neither the case of a villous adenoma receiving the anti-CEA IgG nor the two cases of colonic cancer receiving normal goat IgG showed tumor radiolocalization. Very high circulating CEA titers did not appear to hinder successful tumor radiolocalization. These findings suggest that in colorectal cancers the method of CEA radioimmunodetection may be of value in preoperatively determining the location and extent of disease, in assessing possible recurrence or spread postoperatively, and in localizing the source of CEA production in patients with rising or elevated CEA titers. An ancilliary benefit could be a more tumor-specific detection test for confirming the findings of other, more conventional diagnostic measures.
Colorectal cancer is one of malignancies showing the greatest benefit from preventive measures, especially screening or secondary prevention. Several screening strategies are available with demonstrated efficacy and efficiency. The most widely used are the faecal occult blood test in countries with population-based screening programmes, and colonoscopy in those conducting opportunistic screening. The present article reviews the most important presentations on colorectal cancer screening at the annual congress of the American Gastroenterological Association held in Washington in 2015, with special emphasis on the medium-term results of faecal occult blood testing strategies and determining factors and on strategies to reduce the development of interval cancer after colonoscopy. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.
Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos
Colorectal cancer is a serious health problem, a challenge for research, and a model for studying the molecular mechanisms involved in its development. According to its incidence, this pathology manifests itself in three forms: family, hereditary, and most commonly sporadic, apparently not associated with any hereditary or familial factor. For the types having inheritance patterns and a family predisposition, the tumours develop through defined stages ranging from adenomatous lesions to the manifestation of a malignant tumour. It has been established that environmental and hereditary factors contribute to the development of colorectal cancer, as indicated by the accumulation of mutations in oncogenes, genes which suppress and repair DNA, signaling the existence of various pathways through which the appearance of tumours may occur. In the case of the suppressive and mutating tracks, these are characterised by genetic disorders related to the phenotypical changes of the morphological progression sequence in the adenoma/carcinoma. Moreover, alternate pathways through mutation in BRAF and KRAS genes are associated with the progression of polyps to cancer. This review surveys the research done at the cellular and molecular level aimed at finding specific alternative therapeutic targets for fighting colorectal cancer. PMID:25932044
Bessa Caserras, Xavier
In the latest meeting of the American Gastroenterological Association, several clinical studies were presented that aimed to evaluate the various colorectal cancer screening strategies, although most assessed the various aspects of faecal immunochemical testing (FIT) and colonoscopy. Data were presented from consecutive FIT-based screening rounds, confirming the importance of adherence to consecutive screening rounds, achieving a similar or superior diagnostic yield to endoscopic studies. There was confirmation of the importance of not delaying endoscopic study after a positive result. Participants with a negative FIT (score of 0) had a low risk for colorectal cancer. Several studies seemed to confirm the importance of high-quality colonoscopy in colorectal cancer screening programmes. The implementation of high-quality colonoscopies has reduced mortality from proximal lesions and reduced interval cancers in various studies. Finally, participants with a normal colonoscopy result or with a small adenoma are at low risk for developing advanced neoplasms during follow-up. Copyright Â© 2016 Elsevier España, S.L.U. All rights reserved.
Pereyra, Lisandro; Gómez, Estanislao J; Mella, José M; Cimmino, Daniel G; Boerr, Luis A
Colorectal cancer is one of the leading causes of cancer death worldwide and also in Argentina. In the past few years colorectal cancer screening has become more popular and colonoscopy has been postulated as the gold standard. In this review we analyzed the evidence supporting this method in contrast with its complications and disadvantages.
Ng, Siew C; Wong, Sunny H
The incidence and mortality of colorectal cancer are rapidly rising in several countries in Asia. However, screening guidelines are lacking. Review of literature and local data published in peer review journals. The incidence, anatomical distribution and mortality of colorectal cancer among Asian populations are comparable to those in Western countries. Flat and depressed colonic lesions are not uncommon. Male gender, smoking, obesity, metabolic syndrome and family history are risk factors for colorectal cancer. Certain ethnic groups in Asia have increased susceptibility to colorectal cancer. Faecal occult blood test, flexible sigmoidoscopy and colonoscopy are recommended options for colorectal cancer screening in Asia. Regular screening should start at the age of 50 years. The optimal screening method in Asia remains unclear. Faecal immunochemical test has been suggested as the first choice of screening test in countries with limited resources. The role of nurse endoscopists in performing endoscopic procedures for colorectal cancer screening in Asia has not been defined. There is low public awareness and little support by health authorities for screening and prevention of this emerging disease. Screening for colorectal cancer should be a national health priority in most Asian countries. Studies on barriers to screening, education of the public and engagement of family physicians are important strategies in promoting colorectal cancer screening. With more health-care support, increased public acceptance and better access to the general population, colorectal cancer screening in Asia can be rewarding.
Colon Adenocarcinoma; Rectal Adenocarcinoma; Stage III Colorectal Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Colorectal Cancer; Stage IV Colorectal Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer
Bossé, D.; Ng, T.; Ahmad, C.; Alfakeeh, A.; Alruzug, I.; Biagi, J.; Brierley, J.; Chaudhury, P.; Cleary, S.; Colwell, B.; Cripps, C.; Dawson, L.A.; Dorreen, M.; Ferland, E.; Galiatsatos, P.; Girard, S.; Gray, S.; Halwani, F.; Kopek, N.; Mahmud, A.; Martel, G.; Robillard, L.; Samson, B.; Seal, M.; Siddiqui, J.; Sideris, L.; Snow, S.; Thirwell, M.; Vickers, M.; Goodwin, R.; Goel, R.; Hsu, T.; Tsvetkova, E.; Ward, B.; Asmis, T.
The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5–7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents PMID:28050151
LANGMAN, M; BOYLE, P
Department of Medicine, Queen Elizabeth Hospital, Birmingham B15 2TH, UK P BOYLE Colorectal cancer is the fourth commonest form of cancer in men with 678 000 estimated new cases per year worldwide, representing 8.9% of all new cancers. The disease is most frequent in Occidental countries and particularly so in North America, Australia, New Zealand, and parts of Europe. Prospects for colorectal cancer control are bright and a number of possible approaches could prove fruitful. Among these, pharmaceutical measures seem to be valid and logical approaches to the prevention of colorectal cancer and diminishing its impact. Such approaches could concentrate in primary prevention in at-risk subjects or be applied in altering the course of precursor or established disease. Treatments used must fulfil basic requirements of biological plausibility and safety in continued use in large numbers of subjects. Those available include vitamins and minerals, and other drugs with potential as antioxidants, immune modulators or promoters of cell differentiation or apoptosis. Of the various regimens suggested, vitamin A supplementation may even predispose to adverse outcomes, and antioxidant vitamins in general have no coherent body of evidence to support their use. N-acetylcysteine and ursodeoxycholic acid have promising characteristics but there are as yet no clinical data to support the use of the former in gut epithelial cancer, and formal dose ranging studies must be carried out before the latter is submitted to large scale trial. Folate shows promising characteristics but non-steroidal anti-inflammatory drugs and vitamin D seem the most promising agents. Both seem to reduce the incidence of disease, and to reduce growth rates and/or induce differentiation or apoptosis in gut epithelial cancer cells. Both are also well understood pharmacologically. They may be preferred to newer selective compounds in the same class until these newer compounds are confirmed as safe for widespread
Mandel, Jack S
Although there are several methods available for colon cancer screening, none is optimal. This article reviews methods for screening, including fecal occult blood tests, flexible sigmoidoscopy, colonoscopy, CT colonography, capsule endoscopy, and double contrast barium enema. A simple, inexpensive, noninvasive, and relatively sensitive screening test is needed to identify people at risk for developing advanced adenomas or colorectal cancer who would benefit from colonoscopy. It is hoped that new markers will be identified that perform better. Until then we fortunately have a variety of screening strategies that do work.
Lynch, Henry T; Shaw, Trudy G
Hereditary colorectal cancer (CRC) is highly heterogeneous, both genotypically and phenotypically. The most frequently occurring hereditary colorectal cancer syndrome is Lynch syndrome, accounting for approximately 3% of the total colorectal cancer burden. Polyposis syndromes, such as familial adenomatous polyposis, account for a lesser percentage. Familial colorectal cancer, defined by family history, occurs in an estimated 20% of all colorectal cancer cases. With a worldwide annual colorectal cancer incidence of over one million, and annual mortality of over 600,000, hereditary and familial forms of colorectal cancer are a major public health problem. Lynch syndrome is attributable to DNA mismatch repair germline mutations, with the MSH2, MLH1, MSH6, and PMS2 genes being implicated. The characteristics of Lynch syndrome-associated colorectal tumors, including early age of onset and predilection to the proximal colon, mandate surveillance by colonoscopy beginning by age 20 to 25 and repeated every other year through age 40 and annually thereafter. Besides colorectal cancer, Lynch syndrome also predisposes to a litany of extracolonic cancers, foremost of which is endometrial cancer, followed by cancer of the ovary, stomach, renal pelvis and ureter, small bowel, hepatobiliary tract, pancreas, glioblastoma multiforme in the Turcot's variant, and sebaceous skin tumors in the Muir-Torre variant and, more recently identified, cancers of the breast and prostate. The most common polyposis syndrome is familial adenomatous polyposis, caused by mutations in the APC gene. Affected individuals have multiple colonic adenomas and, without treatment invariably develop colorectal cancer. Colonic surveillance with polypectomy may be pursued until the appearance of multiple colonic adenomas, at which time prophylactic colectomy should be considered. Extra-intestinal manifestations include desmoid tumor, hepatoblastoma, thyroid carcinoma, and medulloblastoma. Other polyposis
Colorectal cancer is the paradigm of tumoral growth that is susceptible to preventive measures, especially screening. Various screening strategies with demonstrated efficacy and efficiency are currently available, notable examples being the fecal occult blood test and endoscopic tests. In addition, new modalities have appeared in the last few years that could become viable alternatives in the near future. The present article reviews the most important presentations on colorectal screening at the annual congress of the American Gastroenterological Association held in Orlando in May 2013, with special emphasis on the medium- and long-term results of strategies using the fecal occult blood test and flexible sigmoidoscopy, as well as initial experiences with the use of new biomarkers.
... Cancer Research? Colorectal Cancer About Colorectal Cancer What’s New in Colorectal Cancer Research? Research is always going ... ways to find colorectal cancer early by studying new types of screening tests and improving the ones ...
Cox, Thomas R; Erler, Janine T
Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has stimulated significant interest in lysyl oxidase as a strong candidate for developing and deploying inhibitors as functional efficacious cancer therapeutics. In this review, we discuss the rapidly expanding body of knowledge concerning lysyl oxidase in solid tumor progression, highlighting recent advancements in the field of colorectal cancer.
Goel, Ajay; Boland, C Richard
In the early years of the molecular biology revolution, cancer research was mainly focused on genetic changes (ie, those that altered DNA sequences). Although this has been extremely useful as our understanding of the pathogenesis and biology of cancer has grown and matured, there is another realm in tumor development that does not involve changing the sequence of cellular DNA. This field is called "epigenetics" and broadly encompasses changes in the methylation of cytosines in DNA, changes in histone and chromatin structure, and alterations in the expression of microRNAs, which control the stability of many messenger RNAs and serve as "master regulators" of gene expression. This review focuses on the epigenetics of colorectal cancer and illustrates the impact epigenetics has had on this field.
Up to 5% of all cases of colorectal cancer (CRC) are due to a known hereditary syndrome. These hereditary forms often require a high degree of suspicion for their diagnosis and specific and specialized management. Moreover, a diagnosis of hereditary CRC has important consequences, not only for patients-for whom highly effective preventive measures are available-, but also for their relatives, who may be carriers of the same condition. The most significant advances in the field of hereditary CRC have been produced in the diagnosis and characterization of these syndromes and in the discovery of new causative genes.
Bardou, Marc; Barkun, Alan N; Martel, Myriam
Excess body weight, as defined by the body mass index (BMI), has been associated with several diseases and includes subjects who are overweight (BMI ≥ 25-29.9 kg/m(2)) or obese (BMI ≥ 30 kg/m(2)). Overweight and obesity constitute the fifth leading risk for overall mortality, accounting for at least 2.8 million adult deaths each year. In addition around 11% of colorectal cancer (CRC) cases have been attributed to overweight and obesity in Europe. Epidemiological data suggest that obesity is associated with a 30-70% increased risk of colon cancer in men, whereas the association is less consistent in women. Similar trends exist for colorectal adenoma, although the risk appears lower. Visceral fat, or abdominal obesity, seems to be of greater concern than subcutaneous fat obesity, and any 1 kg/m(2) increase in BMI confers additional risk (HR 1.03). Obesity might be associated with worse cancer outcomes, such as recurrence of the primary cancer or mortality. Several factors, including reduced sensitivity to antiangiogenic-therapeutic regimens, might explain these differences. Except for wound infection, obesity has no significant impact on surgical procedures. The underlying mechanisms linking obesity to CRC are still a matter of debate, but metabolic syndrome, insulin resistance and modifications in levels of adipocytokines seem to be of great importance. Other biological factors such as the gut microbiota or bile acids are emerging. Many questions still remain unanswered: should preventive strategies specifically target obese patients? Is the risk of cancer great enough to propose prophylactic bariatric surgery in certain patients with obesity?
Chan, Andrew T.; Giovannucci, Edward L.
Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of the dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and the maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and non-steroidal anti-inflammatory drugs and post-menopausal hormones for women are associated with significant reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence. PMID:20420944
Lung, M S; Trainer, A H; Campbell, I; Lipton, L
Identifying individuals with a genetic predisposition to developing familial colorectal cancer (CRC) is crucial to the management of the affected individual and their family. In order to do so, the physician requires an understanding of the different gene mutations and clinical manifestations of familial CRC. This review summarises the genetics, clinical manifestations and management of the known familial CRC syndromes, specifically Lynch syndrome, familial adenomatous polyposis, MUTYH-associated neoplasia, juvenile polyposis syndrome and Peutz-Jeghers syndrome. An individual suspected of having a familial CRC with an underlying genetic predisposition should be referred to a familial cancer centre to enable pre-test counselling and appropriate follow up. © 2015 Royal Australasian College of Physicians.
Zhu, Bo; Li, Yongsheng
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. Understanding its pathophysiology is essential for developing efficient strategies to treat this disease. Lipidome, the sum of total lipids, related enzymes, receptors and signaling pathways, plays crucial roles in multiple cellular processes, such as metabolism, energy storage, proliferation and apoptosis. Dysregulation of lipid metabolism and function contributes to the development of CRC, and can be used towards the evaluation of prognosis. The strategies targeting lipidome have been applied in clinical trails and showed promising results. Here we discuss recent advances in abnormal lipid metabolism in CRC, the mechanisms by which the lipidome regulates tumorigenesis and tumor progression, and suggest potential therapeutic targets for clinical trials. PMID:26967051
Matsumata, T; Shikada, Y; Hasuda, S; Kishihara, F; Suehiro, T; Funahashi, S; Nagamatsu, Y; Iso, Y; Shima, I; Koga, C; Osamura, S; Ueda, M; Furuya, K; Sakino, I
Married couples share home environments and life style for years. In the case of colorectal cancer, an association with insulin resistance was reported. We determined the presence of the insulin-resistance syndrome (IRS, 1 or more of the following: body mass index of > 25 kg/m2, diabetes, or hyperlipidemia) in 84 colorectal cancer patients, of whom 61 patients (73%) had IRS. The incidence of the distal colorectal cancer, which has been declining in the United States, was significantly higher in the IRS group than in the non-IRS group (75.4 vs 52.2%, p = 0.0400). Some mechanisms may promote the progression of mucosal lesions to invasive cancers in the distal colorectum. There were no significant differences with respect to the age (64.6 +/- 9.4 vs 64.3 +/- 11.3 yr, p = 0.8298), height (159 +/- 9 vs 157 +/- 8 cm, p = 0.1375), and body mass index (22.2 +/- 3.6 vs 22.4 +/- 2.7 kg/m2, p = 0.6364) between the patients and their spouses. In 84 couples in whom colorectal cancer develops at least in one may then not illustrate the nursery rhyme: "Jack Sprat could eat no fat, His wife could eat no lean...". The spouses had been married for an average of 38 years, and in 30 spouses who had been followed in a colorectal cancer screening, 5 developed colorectal cancer. To diminish the incidence of colorectal cancer in Japan, we might advise screening colonoscopy to the spouses of colorectal cancer patients, or déjà vu all over again?
Up to 5% of all colorectal cancer cases are caused by a known hereditary syndrome. These hereditary types often need a higher degree of clinical suspicion to be diagnosed and require specific and specialized management. In addition, diagnosing hereditary colorectal cancer has significant consequences not only for the patient, for whom there are effective preventative measures, but also for their families, who could be carriers of the condition. The most significant advances in the field of colorectal cancer have come from the diagnosis and characterization of these syndromes.
Balogh, A; Kahán, Z; Maráz, A; Mikó, T; Nagy, F; Palkó, A; Thurzó, L; Tiszlavicz, L
A multidisciplinary program for the treatment of colorectal cancer is described. The main objective of the authors has been to define uniform up to date guidelines based on recent progress in the treatment of colorectal cancer. Preoperative diagnostic procedures are summarized which advance determination of clinical stage and prognosis. These information essentially determine care. Sequences of surgical methods, preoperative and postoperative radiotherapy and medical treatments are discussed according to tumor stages. Guidelines for surveillance following active treatment and recommendation for the screening of population at high risk for colorectal cancer are presented.
Boland, C. Richard; Goel, Ajay
Microsatellite instability (MSI) is a hypermutable phenotype caused by the loss of DNA mismatch repair activity. MSI is detected in about 15% of all colorectal cancers; 3% are of these are associated with Lynch syndrome and the other 12% are caused by sporadic, acquired hypermethylation of the promoter of the MLH1 gene, which occurs in tumors with the CpG island methylator phenotype. Colorectal tumors with MSI have distinctive features, including a tendency to arise in the proximal colon, lymphocytic infiltrate, and a poorly differentiated, mucinous or signet ring appearance. They have a slightly better prognosis than colorectal tumors without MSI and do not have the same response to chemotherapeutics. Discovery of MSI in colorectal tumors has increased awareness of the diversity of colorectal cancers and implications for specialized management of patients. PMID:20420947
Johnson, Robert L.; Fleet, James C.
Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the United States. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist. PMID:23076650
Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro; Ishigamori, Rikako
Colorectal cancer (CRC) is the third most common epithelial malignancy in the world. Since CRC develops slowly from removable precancerous lesions, detection of the lesion at an early stage by regular health examinations can reduce the incidence and mortality of this malignancy. Colonoscopy significantly improves the detection rate of CRC, but the examination is expensive and inconvenient. Therefore, we need novel biomarkers that are non-invasive to enable us to detect CRC quite early. A number of validation studies have been conducted to evaluate genetic, epigenetic or protein markers for identification in the stool and/or serum. Currently, the fecal occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics will lead to the discovery of novel non-invasive biomarkers. PMID:20957089
Colorectal cancer is one of the most frequent neoplasms in western countries; it is the third most common cancer in men after prostate and lung cancer and the second most common in women after breast cancer. Colorectal cancer is usually sporadic but in a small proportion is hereditary. The genetic cause is well established, allowing pre-symptomatic diagnosis in at-risk relatives. The present article reviews the most novel findings presented at the latest meeting of the American Gastroenterological Association on hereditary forms of colorectal cancer, especially Lynch syndrome and MUTYH-associated polyposis, as well as diverse organisational aspects that can favour the correct management of these patients and their relatives.
Kreisler, Esther; Biondo, Sebastiano; Martí-Ragué, Joan
Colorectal cancer continues to have a serious social impact. A large proportion of patients are diagnosed at an advanced stage of the disease. Approximately one-third of patients with colorectal cancer will undergo emergency surgery for a complicated tumor, with a high risk of mortality and poorer long-term prognosis. The most frequent complications are obstruction and perforation, while massive hemorrhage is rare. The curative potential of surgery, whether urgent or elective, depends on how radical the resection is, among other factors. In the literature on the management of urgent colorectal disease, there are few references to the oncological criteria for resection. Uncertainly about the optimal treatment has led to wide variability in the treatment of this entity. The present article aims to provide a critical appraisal of the controversies surrounding the role of surgery and its impact on complicated colorectal cancer.
Siegel, Rebecca L; Miller, Kimberly D; Fedewa, Stacey A; Ahnen, Dennis J; Meester, Reinier G S; Barzi, Afsaneh; Jemal, Ahmedin
Colorectal cancer (CRC) is one of the most common malignancies in the United States. Every 3 years, the American Cancer Society provides an update of CRC incidence, survival, and mortality rates and trends. Incidence data through 2013 were provided by the Surveillance, Epidemiology, and End Results program, the National Program of Cancer Registries, and the North American Association of Central Cancer Registries. Mortality data through 2014 were provided by the National Center for Health Statistics. CRC incidence rates are highest in Alaska Natives and blacks and lowest in Asian/Pacific Islanders, and they are 30% to 40% higher in men than in women. Recent temporal patterns are generally similar by race and sex, but differ by age. Between 2000 and 2013, incidence rates in adults aged ≥50 years declined by 32%, with the drop largest for distal tumors in people aged ≥65 years (incidence rate ratio [IRR], 0.50; 95% confidence interval [95% CI], 0.48-0.52) and smallest for rectal tumors in ages 50 to 64 years (male IRR, 0.91; 95% CI, 0.85-0.96; female IRR, 1.00; 95% CI, 0.93-1.08). Overall CRC incidence in individuals ages ≥50 years declined from 2009 to 2013 in every state except Arkansas, with the decrease exceeding 5% annually in 7 states; however, rectal tumor incidence in those ages 50 to 64 years was stable in most states. Among adults aged <50 years, CRC incidence rates increased by 22% from 2000 to 2013, driven solely by tumors in the distal colon (IRR, 1.24; 95% CI, 1.13-1.35) and rectum (IRR, 1.22; 95% CI, 1.13-1.31). Similar to incidence patterns, CRC death rates decreased by 34% among individuals aged ≥50 years during 2000 through 2014, but increased by 13% in those aged <50 years. Progress against CRC can be accelerated by increasing initiation of screening at age 50 years (average risk) or earlier (eg, family history of CRC/advanced adenomas) and eliminating disparities in high-quality treatment. In addition, research is needed to elucidate causes
Cancer Survivor; Healthy Subject; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer
Recurrent Colorectal Carcinoma; Solid Neoplasm; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7
Gillen, C D; Andrews, H A; Prior, P; Allan, R N
The colorectal cancer risk in Crohn's disease eliminating all known biases was assessed in a cohort of 281 patients with Crohn's disease who resided in the West Midlands at the time of diagnosis, and were first seen within five years of onset of symptoms between 1945-1975. All patients were 15 years of age or more at onset and were followed up from 12-35 years (total 5213 person years at risk (PYR)). The colorectal cancer risk in the series compared with the risk in the general population was computed by applying sex and age specific PYRs to the date of death or end of the study period 31 December 1991. There were six colonic and two rectal cancers. Six of the eight colorectal cancers were diagnosed 20 or more years after the onset of Crohn's disease. The relative risk (RR) of colorectal cancer for the series as a whole was 3.4 (p < 0.001), with a fivefold excess in the colon, but no significant excess in the rectum. Patients with extensive colitis showed an 18-fold increase in risk (RR = 18.2, p < 0.001), which decreased with increasing age at onset. This study shows that there is a statistical excess risk of developing colorectal cancer in patients who develop their Crohn's disease at a young age of onset (less than 30 years of age). PMID:8200559
Colorectal cancer (CRC) is the third most common cause of cancer death worldwide and a major health problem. In this review, the different approaches for CRC screening will be outlined with emphasis on evidence-based medicine. Evidence from randomized trials on the effectiveness of CRC screening is summarized. Several screening tools for CRC are available. They can be categorized according to their mode of action: early detection tools such as the faecal occult blood test (FOBT) and cancer prevention tools such as flexible sigmoidoscopy and colonoscopy. Meta-analyses of randomized trials show that FOBT screening reduces CRC mortality by 16% (risk ratio 0.84; 95% confidence interval (CI) 0.78-0.9) compared with 30% (risk ratio 0.7; 95% CI 0.6-0.81) for flexible sigmoidoscopy screening. FOBT screening is cheap and noninvasive, but results in large numbers of false-positive tests and needs to be repeated frequently. Flexible sigmoidoscopy is more invasive, but is effective for once-only screening. Although colonoscopy screening is used in some countries, no randomized trials have been conducted to estimate its benefit, and therefore, it should not be recommended at the present time. Faecal occult blood test and flexible sigmoidoscopy are the two CRC screening tools that can be recommended as they have been proven to reduce CRC mortality. Colonoscopy has the potential to be superior to FOBT and flexible sigmoidoscopy, but needs to be evaluated in randomized trials before any recommendation can be provided. © 2011 The Association for the Publication of the Journal of Internal Medicine.
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Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Colorectal Cancer; Colorectal Carcinoma; Colorectal Tumors; Neoplasms, Colorectal; HER-2 Gene Amplification; Metastatic Cancer; Metastatic Colon Cancer; Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum
El-Tawil, Ahmed Mahmoud
Published reports have revealed increased risk of colorectal cancers in people exposed to chlorinated drinking water or chemical derivatives of chlorination. Oestrogen plays a dual positive functions for diminishing the possibilities of such risk by reducing the entrance, and increasing the excretion, of these chemicals. In addition, there are supplementary measures that could be employed in order to reduce this risk further, such as boiling the drinking water, revising the standard concentrations of calcium, magnesium and iron in the public drinking water and prescribing oestrogen in susceptible individuals. Hypo-methylation of genomic DNA could be used as a biological marker for screening for the potential development of colorectal cancers.
El-Tawil, Ahmed Mahmoud
Published reports have revealed increased risk of colorectal cancers in people exposed to chlorinated drinking water or chemical derivatives of chlorination. Oestrogen plays a dual positive functions for diminishing the possibilities of such risk by reducing the entrance, and increasing the excretion, of these chemicals. In addition, there are supplementary measures that could be employed in order to reduce this risk further, such as boiling the drinking water, revising the standard concentrations of calcium, magnesium and iron in the public drinking water and prescribing oestrogen in susceptible individuals. Hypo-methylation of genomic DNA could be used as a biological marker for screening for the potential development of colorectal cancers. PMID:27096035
Song, Mingyang; Garrett, Wendy S; Chan, Andrew T
Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigations have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grains have been associated with a lower risk of colorectal cancer, and red meat and processed meat have been associated with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits, and vegetables. Nutrients and foods also may interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of overnutrition and obesity-risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence.
Song, Mingyang; Garrett, Wendy S.; Chan, Andrew T.
Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigation have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grain have been associated with a lower risk of colorectal cancer, and red meat and processed meat with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits and vegetables. Nutrients and foods may also interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of over-nutrition and obesity—risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence. PMID:25575572
... and processed meat you eat. If you drink alcohol, limit the amount to 1 drink per day for women, 2 per day for men. Don’t use tobacco in any form. Myth: African Americans are not at risk for colorectal cancer. Truth: African-American men and women are diagnosed ...
Pestalozzi, B C; Jäger, D; Knuth, A
Drug treatment of colorectal cancer has made impressive progress during the past 10 years. In addition to the traditional 5-fluorouracil, newer anticancer drugs are available including irinotecan and oxaliplatin. Monoclonal antibodies like bevacizumab and cetuximab have been integrated into modern treatment regimens. Based on randomized clinical trials we can formulate rational treatment strategies as outlined in this article.
Centelles, Josep J.
Colorectal cancer (CRC) is one of the main causes of death. Cancer is initiated by several DNA damages, affecting proto-oncogenes, tumour suppressor genes, and DNA repairing genes. The molecular origins of CRC are chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). A brief description of types of CRC cancer is presented, including sporadic CRC, hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndromes, familiar adenomatous polyposis (FAP), MYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), and juvenile polyposis syndrome (JPS). Some signalling systems for CRC are also described, including Wnt-β-catenin pathway, tyrosine kinase receptors pathway, TGF-β pathway, and Hedgehog pathway. Finally, this paper describes also some CRC treatments. PMID:23209942
Centelles, Josep J
Colorectal cancer (CRC) is one of the main causes of death. Cancer is initiated by several DNA damages, affecting proto-oncogenes, tumour suppressor genes, and DNA repairing genes. The molecular origins of CRC are chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). A brief description of types of CRC cancer is presented, including sporadic CRC, hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndromes, familiar adenomatous polyposis (FAP), MYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), and juvenile polyposis syndrome (JPS). Some signalling systems for CRC are also described, including Wnt-β-catenin pathway, tyrosine kinase receptors pathway, TGF-β pathway, and Hedgehog pathway. Finally, this paper describes also some CRC treatments.
Frías, Cristina; Morán, Alberto; de Juan, Carmen; Ortega, Paloma; Fernández-Marcelo, Tamara; Sánchez-Pernaute, Andrés; Torres, Antonio José; Díaz-Rubio, Eduardo; Benito, Manuel; Iniesta, Pilar
Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world. Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process. Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length. It is achieved mainly, by telomerase activation. Thus, the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized. Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours. Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis. Taking into account all the results achieved by different groups, quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma. PMID:21160767
Iron deficiency and anaemia are common in colorectal cancer. Replacement with oral or intravenous iron effectively treats this deficiency. However, mechanistic and population studies suggest that excess iron promotes colorectal carcinogenesis. Growing research into gut microbiota and dysbiosis suggests one explanation for this association. Iron is growth limiting for many pathogenic bacteria and may promote a shift in the ratio of pathogenic to protective bacteria. This may increase the toxic bacterial metabolites, promoting inflammation and carcinogenesis. This has important implications as we seek to correct anaemia in our patients.
Pestalozzi, B C; Jäger, D; Knuth, A
Drug treatment of colorectal cancer has made impressive progress during the past 10 years. In addition to fluorouracil new anticancer drugs like irinotecan and oxaliplatin have become available. The activity of fluorouracil was optimized by using schedules of prolonged infusion. Capecitabine is an oral pro-drug of fluorouracil. When colorectal metastases are limited to the liver they should be resected if possible. Sometimes they can be reduced in size by primary chemotherapy (downstaging) and resected later. Very new and exciting are reports with the monoclonal antibody bevacizumab in combination with chemotherapy. Bevacizumab blocks angiogenesis. So far it is available only in the USA.
Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H
The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. All Danish patients with newly diagnosed colorectal cancer who are either diagnosed or treated in a surgical department of a public Danish hospital. The database comprises an array of surgical, radiological, oncological, and pathological variables. The surgeons record data such as diagnostics performed, including type and results of radiological examinations, lifestyle factors, comorbidity and performance, treatment including the surgical procedure, urgency of surgery, and intra- and postoperative complications within 30 days after surgery. The pathologists record data such as tumor type, number of lymph nodes and metastatic lymph nodes, surgical margin status, and other pathological risk factors. The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal cancer patients. The stage distribution has been more or less constant until 2014 with a tendency toward a lower rate of stage IV and higher rate of stage I after introduction of the national screening program in 2014. The 30-day mortality rate after elective surgery has been reduced from >7% in 2001-2003 to <2% since 2013. The database is a national population-based clinical database with high patient and data completeness for the perioperative period. The resolution of data is high for description of the patient at the time of diagnosis, including comorbidities, and for characterizing diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish Colorectal Cancer Group provides high-quality data and has been documenting an
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Ahmad, Muayyad M; Dardas, Latefa; Dardas, Lubna; Ahmad, Huthaifa
The aim of this study was to describe the knowledge, attitudes, and practices toward colorectal cancer prevention and care in Jordan. A survey was designed to produce reliable estimates for the population's knowledge, attitudes, and practices in all 12 governorates of Jordan by using stratified random sampling. A representative sample of the adult population in Jordan completed a comprehensive tool which explored participants' knowledge about the risk factors associated with colorectal cancer, cancer prevention through lifestyle changes, and early cancer diagnosis and screening. According to the participants (n = 3196), colorectal cancer had the second highest percentage of screening recommendation (12.6%) after breast cancer (57.3%). Only 340 individuals (11%) reported ever screening for cancer. About 20% of the participants had heard of one of the screening tests for colorectal cancer. In fact, only 290 (9.1%) participants had performed the colorectal cancer screening tests. This study provides data that will help colorectal cancer prevention and treatment programs and may enhance the efficiency of colorectal cancer-controlling programs. The findings confirm the necessity of starting colorectal screening intervention that targets the most vulnerable individuals.
Underhill, Meghan L; Germansky, Katharine A; Yurgelun, Matthew B
Innovations in genetic medicine have led to improvements in the early detection, prevention, and treatment of cancer for patients with inherited risks of gastrointestinal cancer, particularly hereditary colorectal cancer and hereditary pancreatic cancer. This review provides an update on recent data and key advances that have improved the identification, understanding, and management of patients with hereditary colorectal cancer and hereditary pancreatic cancer. This review details recent and emerging data that highlight the developing landscape of genetics in hereditary colorectal and pancreatic cancer risk. A summary is provided of the current state-of-the-art practices for identifying, evaluating, and managing patients with suspected hereditary colorectal cancer and pancreatic cancer risk. The impact of next-generation sequencing technologies in the clinical diagnosis of hereditary gastrointestinal cancer and also in discovery efforts of new genes linked to familial cancer risk are discussed. Emerging targeted therapies that may play a particularly important role in the treatment of patients with hereditary forms of colorectal cancer and pancreatic cancer are also reviewed. Current approaches for pancreatic cancer screening and the psychosocial impact of such procedures are also detailed. Given the availability of new diagnostic, risk-reducing, and therapeutic strategies that exist for patients with hereditary risk of colorectal or pancreatic cancer, it is imperative that clinicians be vigilant about evaluating patients for hereditary cancer syndromes. Continuing to advance genetics research in hereditary gastrointestinal cancers will allow for more progress to be made in personalized medicine and prevention. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.
Aykan, Nuri Faruk
Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton) is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association, observed link of some subtypes of red meat with CRC risk, potential carcinogenic compounds, their mechanisms and actual recommendations of international guidelines are presented.
Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton) is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association, observed link of some subtypes of red meat with CRC risk, potential carcinogenic compounds, their mechanisms and actual recommendations of international guidelines are presented. PMID:26779313
Rothenmund, H.; Singh, H.; Candas, B.; Chodirker, B.N.; Serfas, K.; Aronson, M.; Holter, S.; Volenik, A.; Green, J.; Dicks, E.; Woods, M.O.; Gilchrist, D.; Gryfe, R.; Cohen, Z.; Foulkes, W.D.
At a consensus meeting held in Montreal, October 28, 2011, a multidisciplinary group of Canadian experts in the fields of genetics, gastroenterology, surgery, oncology, pathology, and health care services participated in presentation and discussion sessions for the purpose of developing consensus statements pertaining to the development and maintenance of hereditary colorectal cancer registries in Canada. Five statements were approved by all participants. PMID:24155632
Soliman, A S; Bondy, M L; Levin, B; El-Badawy, S; Khaled, H; Hablas, A; Ismail, S; Adly, M; Mahgoub, K G; McPherson, R S; Beasley, R P
We have investigated the familial aggregation of colorectal cancer and hereditary nonpolyposis colorectal cancer (HNPCC) in Egypt because of the high incidence of colorectal cancer in Egyptian children and young adults and the prevalence of consanguinity there. In a pilot study, we conducted detailed interviews with 111 Egyptian colorectal cancer patients and 111 healthy Egyptian controls about their family histories of colorectal cancer, and other cancers, consanguinity, age at diagnosis, symptoms and recurrence. Eight patients (7.2%) had one or more first- or second-degree relatives under age 40 with colorectal cancer, suggestive of HNPCC by the Amsterdam criteria. One of these families had a typical history of HNPCC, with 4 relatives having colorectal cancer in 3 generations; 3 of these relatives were younger than age 45 at colon cancer diagnosis, and other relatives had extracolonic tumors. Another 14 patients (12.6%) had a first- or second-degree relative with a family history of other neoplasms such as endometrial, urinary and hepatobiliary cancers that could also be related to HNPCC. Four patients with early-onset colon cancer and a family history of other HNPCC-related cancers reported that their parents were first-degree cousins.
Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H
Aim of database The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. Study population All Danish patients with newly diagnosed colorectal cancer who are either diagnosed or treated in a surgical department of a public Danish hospital. Main variables The database comprises an array of surgical, radiological, oncological, and pathological variables. The surgeons record data such as diagnostics performed, including type and results of radiological examinations, lifestyle factors, comorbidity and performance, treatment including the surgical procedure, urgency of surgery, and intra- and postoperative complications within 30 days after surgery. The pathologists record data such as tumor type, number of lymph nodes and metastatic lymph nodes, surgical margin status, and other pathological risk factors. Descriptive data The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal cancer patients. The stage distribution has been more or less constant until 2014 with a tendency toward a lower rate of stage IV and higher rate of stage I after introduction of the national screening program in 2014. The 30-day mortality rate after elective surgery has been reduced from >7% in 2001–2003 to <2% since 2013. Conclusion The database is a national population-based clinical database with high patient and data completeness for the perioperative period. The resolution of data is high for description of the patient at the time of diagnosis, including comorbidities, and for characterizing diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish
Byun, Ju-Young; Yoon, Seok-Jun; Oh, In-Hwan; Kim, Young Ae; Seo, Hye-Young; Lee, Yo-Han
The incidence and survival rate of colorectal cancer in Korea are increasing because of improved screening, treatment technologies, and lifestyle changes. In this aging population, increases in economic cost result. This study was conducted to estimate the economic burden of colorectal cancer utilizing claims data from the Health Insurance Review and Assessment Service. Economic burdens of colorectal cancer were estimated using prevalence data and patients were defined as those who received ambulatory treatment from medical institutions or who had been hospitalized due to colorectal cancer under the International Classification of Disease 10th revision codes from C18-C21. The economic burdens of colorectal cancer were calculated as direct costs and indirect costs. The prevalence rate (per 100 000 people) of those who were treated for colorectal cancer during 2010 was 165.48. The economic burdens of colorectal cancer in 2010 were 3 trillion and 100 billion Korean won (KRW), respectively. Direct costs included 1 trillion and 960 billion KRW (62.85%), respectively and indirect costs were 1 trillion and 160 billion (37.15%), respectively. Colorectal cancer has a large economic burden. Efforts should be made to reduce the economic burden of the disease through primary and secondary prevention.
Rawl, Susan M.; Christy, Shannon M.; Monahan, Patrick O.; Ding, Yan; Krier, Connie; Champion, Victoria L.; Rex, Douglas
To compare the efficacy of two interventions to promote colorectal cancer screening participation and forward stage movement of colorectal cancer screening adoption among first-degree relatives of individuals diagnosed with adenomatous polyps. One hundred fifty-eight first-degree relatives of individuals diagnosed with adenomatous polyps were…
Nurses need up-to-date knowledge of colorectal cancer. This article provides an overview of the aetiology and risk factors for this disease, diagnostic and staging investigations, treatment options and future care. Managing colorectal cancer is complex. Patients can have a range of healthcare needs. Nurses play an increasingly important role in informing, supporting and coordinating care to improve patients' quality of life.
Rawl, Susan M.; Christy, Shannon M.; Monahan, Patrick O.; Ding, Yan; Krier, Connie; Champion, Victoria L.; Rex, Douglas
To compare the efficacy of two interventions to promote colorectal cancer screening participation and forward stage movement of colorectal cancer screening adoption among first-degree relatives of individuals diagnosed with adenomatous polyps. One hundred fifty-eight first-degree relatives of individuals diagnosed with adenomatous polyps were…
Weinrich, S P; Weinrich, M C; Boyd, M D; Johnson, E; Frank-Stromborg, M
Cancer screening is a national health priority, especially for colorectal cancer, the second leading cause of death due to cancer in the United States. The researchers measured colorectal cancer knowledge among 211 older Americans. A quasiexperimental pretest-posttest two-by-two factorial design was used to test the effect of knowledge on participation in fecal occult blood screening. The American Cancer Society's colorectal cancer educational slide-tape presentation served as the basis for all of the educational programs. Hemoccult II kits were distributed at no cost to the participants. Descriptive statistics, chi 2, and logistic regressions were used to analyze data. One-half of the participants had incomes below the poverty level. Almost one-half the subjects in the study sample stated that they had not received any information about colorectal cancer within the past year. Caucasians had more knowledge of colorectal cancer than African Americans [F(1, 78) = 7.92, p < 0.01] and persons with higher income had more knowledge than persons with less income [F(2, 76) = 3.01, p = 0.05]. Subjects showed significant increases in colorectal cancer knowledge 6 days after the colorectal cancer education program [t(79) = 2.59, p = 0.01] and this increased knowledge was a predictor of participation in free fecal occult blood screening [chi 2(1, n = 164) = 5.34, p = 0.02].
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Franceschi, S; Gallus, S; Talamini, R; Tavani, A; Negri, E; Vecchia, C La
Post-menopausal women who have never used hormone replacement therapy have a higher risk of colon, but not rectal, cancer than do premenopausal women of the same age, socio-cultural class and dietary habits. Such risk increase seems to last about 10 years and to be restricted to lean women, a group who have lower levels of oestradiol after ovarian function ceases after menopause. © 2000 Cancer Research Campaign PMID:10839302
Kerner, J; Liu, J; Wang, K; Fung, S; Landry, C; Lockwood, G; Zitzelsberger, L; Mai, V
Across Canada, introduction of the Pap test for cervical cancer screening, followed by mammography for breast cancer screening and, more recently, the fecal occult blood test for colorectal cancer screening, has contributed to a reduction in cancer mortality. However, another contribution of screening has been disparities in cancer mortality between certain populations. Here, we explore the disparities associated with breast and cervical cancer screening and preliminary data concerning disparities in colorectal cancer screening. Although some disparities in screening utilization have been successfully reduced over time (for example, mammography and Pap test screening in rural and remote populations), screening utilization data for other populations (for example, low-income groups) clearly indicate that disparities have existed and continue to exist across Canada. Organized screening programs in Canada have been able to successfully engage 80% of women for regular cervical cancer screening and 70% of women for regular mammography screening, but of the women who remain to be reached or engaged in regular screening, those with the least resources, those who are the most isolated, and those who are least culturally integrated into Canadian society as a whole are over-represented. Population differences are also observed for utilization of colorectal cancer screening services. The research literature on interventions to promote screening utilization provides some evidence about what can be done to increase participation in organized screening by vulnerable populations. Adaption and adoption of evidence-based screening promotion interventions can increase the utilization of available screening services by populations that have experienced the greatest burden of disease with the least access to screening services.
Lavasani, Sayeh; Chlebowski, Rowan T; Prentice, Ross L; Kato, Ikuko; Wactawski-Wende, Jean; Johnson, Karen C; Young, Alicia; Rodabough, Rebecca; Hubbell, F Allan; Mahinbakht, Ali; Simon, Michael S
The preponderance of observational studies describe an association between the use of estrogen alone and a lower incidence of colorectal cancer. In contrast, no difference in the incidence of colorectal cancer was seen in the Women's Health Initiative (WHI) randomized, placebo-controlled trial with estrogen alone after a mean intervention of 7.1 years and cumulative follow-up of 13.2 years. This study extends these findings by providing detailed analyses of the effects of estrogen alone on the histology, grade, and stage of colorectal cancer, relevant subgroups, and deaths from and after colorectal cancer. The WHI study was a randomized, double-blind, placebo-controlled trial involving 10,739 postmenopausal women with prior hysterectomy. Participants were assigned to conjugated equine estrogen at 0.625 mg/d (n = 5279) or a matching placebo (n = 5409). Rates of colorectal cancer diagnoses and deaths from and after colorectal cancer were assessed throughout the study. Colorectal cancer rates in the estrogen-alone and placebo groups were comparable: 0.14% and 0.12% per year, respectively (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.83-1.58; P = .43). Bowel screening examinations were comparable between the 2 groups throughout the study. The grade, stage, and location of colorectal cancer did not differ between the randomization groups. There were more colorectal cancer deaths in the estrogen-alone group (34 [0.05%] vs 24 [0.03%]; HR, 1.46, 95% CI, 0.86-2.46; P = .16), but the difference was not statistically significant. The colorectal cancer incidence was higher for participants with a history of colon polyp removal in the estrogen-alone group (0.23% vs 0.02%; HR, 13.47; nominal 95% CI, 1.76-103.0; P < .001). The use of estrogen alone in postmenopausal women with prior hysterectomy does not influence the incidence of colorectal cancer or deaths from or after colorectal cancer. A possibly higher risk of colorectal cancer in women with
Obuch, Joshua C; Ahnen, Dennis J
Cancer is fundamentally a genetic disease caused by mutational or epigenetic alterations in DNA. There has been a remarkable expansion of the molecular understanding of colonic carcinogenesis in the last 30 years and that understanding is changing many aspects of colorectal cancer care. It is becoming increasingly clear that there are genetic subsets of colorectal cancer that have different risk factors, prognosis, and response to treatment. This article provides a general update on colorectal cancer and highlights the ways that genetics is changing clinical care. Copyright © 2016 Elsevier Inc. All rights reserved.
Yao, Caroline; Nash, Guy F; Hickish, Tamas
Colorectal cancer is associated with diabetes mellitus and both of these common conditions are often managed together by a surgeon. The surgical focus is usually upon cancer treatment rather than diabetes management. The relationship between colorectal cancer and diabetes is a complex one and can raise problems in both diagnosis and the management of patients with both conditions. This literature review explores the relationship between diabetes, diabetic treatment and colorectal cancer and addresses the issues that arise in diagnosing and treating this patient group. By highlighting these difficulties, this review aims to improve understanding and to provide clearer insight into both surgical and non-surgical management. PMID:24334910
Salama, Paul; Platell, Cameron
Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.
Offerhaus, G. Johan A.
Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in men and women in the United States. Each year more than 140,000 new patients are diagnosed. About 30% of patients with CRC report a family history of CRC. However, only 5% of colorectal cancers arise in the setting of a well-established Mendelian inherited disorder such as Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, juvenile polyposis, hereditary mixed polyposis, or Peutz-Jeghers. In addition, serrated polyposis is a clinically defined syndrome with multiple serrated polyps in the colorectum and an increased CRC risk for which the genetics are unknown. The majority of familial colorectal cancers arise as so called non-syndromic familial colorectal cancer and likely have a more complex multigenetic cause. This review focuses on genetic and clinical aspects of Lynch syndrome, familial adenomatous polyposis and MUTYH-associated polyposis. PMID:26315524
Rawl, Susan M.; Christy, Shannon M.; Monahan, Patrick O.; Ding, Yan; Krier, Connie; Champion, Victoria L.; Rex, Douglas
To compare the efficacy of two interventions to promote colorectal cancer screening participation and forward stage movement of colorectal cancer screening adoption among first-degree relatives of individuals diagnosed with adenomatous polyps. One hundred fifty-eight first-degree relatives of individuals diagnosed with adenomatous polyps were randomly assigned to receive one of two interventions to promote colorectal cancer screening. Participants received either a tailored telephone counseling plus brochures intervention or a non-tailored print brochures intervention. Data were collected at baseline and 3 months post-baseline. Group differences and the effect of the interventions on adherence and stage movement for colorectal cancer screening were examined using t-tests, chi-square tests, and logistic regression. Individuals in the tailored telephone counseling plus brochures group were significantly more likely to complete colorectal cancer screening and to move forward on stage of change for fecal occult blood test, any colorectal cancer test stage and stage of the risk-appropriate test compared with individuals in the non-tailored brochure group at 3 months post-baseline. A tailored telephone counseling plus brochures intervention successfully promoted forward stage movement and colorectal cancer screening adherence among first-degree relatives of individuals diagnosed with adenomatous polyps. PMID:26025212
Bessa Caserras, Xavier
Colonoscopies play a vital role in population screening programs, either for initial examinations or as a test carried out after a positive result from a fecal occult blood test or sigmoidoscopy. Colonoscopies, and ancillary techniques such as polipectomies, must comply with basic quality criteria that must be reflected in the quality standards of screening programs. A quality colonoscopy is absolutely vital to avoid the occurrence of interval cancers. It is extremely important to detect any proximal lesions during a colonoscopy, especially those which are serrated, because they are difficult to identify and due to the increased risk of colorectal cancer. Regarding follow-up programs for resected colorectal polyps, current evidence of the relationship between the risk of neoplasia and certain variables (age, sex, smoker, BMI, diabetes, etc.) must allow for individualized risk and algorithms for screening and follow-up frequency to be developed for these patients. However, initial endoscopic exploration in a screening colonoscopy is essential to establishing the optimum interval and ensuring follow-up. Despite poor adherence to follow-up programs, mostly due to their overuse, follow-up colonoscopies 3 years after resection of all polypoid lesions detect clinically significant lesions as effectively as colonoscopies at one year.
Peters, H Charles; Liu, Xiuli; Iqbal, Atif; Cunningham, Lisa A; Tan, Sanda A
Despite improved screening modalities, 15-25% of newly diagnosed colorectal cancers are metastatic at the time of diagnosis. The vast majority of these cases present as hepatic metastasis; however, 22% present with concomitant extrahepatic disease. The thymus gland is an uncommon site of metastasis for any primary malignancy, particularly, colorectal cancer given its vascular and lymphatic drainage. This case report details our experience with a rare case of colorectal cancer metastasis to the thymus gland presenting as a symptomatic mediastinal mass.
Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía
Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca(2+) entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC. SOCE and store-operated currents (SOCs) are dramatically enhanced in CRC while Ca(2+) stores are partially empty in CRC cells. These features may contribute to CRC hallmarks including enhanced cell proliferation, migration, invasion and survival. At the molecular level, enhanced SOCE and depleted stores are mediated by overexpression of Orai1, Stromal interaction protein 1 (STIM1) and Transient receptor protein channel 1 (TRPC1) and downregulation of STIM2. In normal colonic cells, SOCE is mediated by Ca(2+)-release activated Ca(2+) channels made of STIM1, STIM2 and Orai1. In CRC cells, SOCE is mediated by different store-operated currents (SOCs) driven by STIM1, Orai1 and TRPC1. Loss of STIM2 contributes to depletion of Ca(2+) stores and enhanced resistance to cell death in CRC cells. Thus, SOCE is a novel key player in CRC and inhibition by salicylate and other NSAIDs may contribute to explain chemoprevention activity. Colorectal cancer (CRC) is the third most frequent form of cancer worldwide. Recent evidence suggests that intracellular Ca(2+) remodeling may contribute to cancer hallmarks. In addition, aspirin and other NSAIDs might prevent CRC acting on remodeled Ca(2+) entry pathways. In this review, we will briefly describe 1) the players involved in intracellular Ca(2+) homeostasis with a particular emphasis on the mechanisms involved in SOCE activation and inactivation, 2) the evidence that aspirin
Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Papa, Gennaro; Piepoli, Ada
Colorectal cancer is the most prevalent among digestive system cancers. Carcinogenesis relies on disrupted control of cellular processes, such as metabolism, proliferation, DNA damage recognition and repair, and apoptosis. Cell, tissue, organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery. Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis, and altered expression of clock genes has been found in cancer patients. Epidemiological studies have shown that circadian disruption, that is, alteration of bodily temporal organization, is a cancer risk factor, and an increased incidence of colorectal neoplastic disease is reported in shift workers. In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer. PMID:24764658
Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Papa, Gennaro; Piepoli, Ada
Colorectal cancer is the most prevalent among digestive system cancers. Carcinogenesis relies on disrupted control of cellular processes, such as metabolism, proliferation, DNA damage recognition and repair, and apoptosis. Cell, tissue, organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery. Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis, and altered expression of clock genes has been found in cancer patients. Epidemiological studies have shown that circadian disruption, that is, alteration of bodily temporal organization, is a cancer risk factor, and an increased incidence of colorectal neoplastic disease is reported in shift workers. In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.
... Cancer Home Questions to Ask Your Doctor About Colorectal Cancer Language: English Español (Spanish) Recommend on Facebook Tweet ... adults age 50 to 75 be screened for colorectal cancer. The decision to be screened after age 75 ...
Rothenberger, David A; Dalberg, Deanna L; Leininger, Anna
The aim of the Minnesota Colorectal Cancer Initiative is to implement risk-specific interventions to decrease colorectal cancer morbidity and mortality by 1) assisting clinicians to identify and educate individuals and families at high and increased risk for colorectal cancer; 2) providing professional and community education; 3) maintaining a database to evaluate the effectiveness of preventive intervention strategies; and 4) facilitating colorectal cancer research. Two physician groups and the University Cancer Center founded the Minnesota Colorectal Cancer Initiative as a not-for-profit organization. Health care organizations, pharmaceutical companies, a consulting firm, and other practice groups provide continuing financial and other support. A database registry, risk-assessment survey, and consent document were developed and then were approved by an institutional review board. A trial enrollment was conducted. Minnesota Colorectal Cancer Initiative services are available to the public. Participants are actively recruited through member organizations. Minnesota Colorectal Cancer Initiative assesses hereditary risk and will document family history in the medical record on request. A personally targeted reply letter reviews risk factors and recommends specific screening and surveillance strategies for participants and their family members, and when appropriate, provides information regarding genetic counseling and testing services. Minnesota Colorectal Cancer Initiative services are free to participants. Since 1999, Minnesota Colorectal Cancer Initiative has sent individually tailored reply letters providing risk-specific information about colorectal cancer to 717 participants and more than 3200 of their first-degree and second-degree relatives. More than 200 families, previously unidentified as having histories suggestive of hereditary colorectal cancer (attenuated familial polyposis and hereditary nonpolyposis colorectal cancer), have been identified; genetic
Colorectal Adenocarcinoma; RAS Wild Type; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7
Louvet, Christophe; de Gramont, Aimery
Pemetrexed (Alimta) shows single-agent activity in advanced colorectal cancer. In two phase II studies in which patients received pemetrexed at 600 mg/m2 or 500 mg/m2 as first-line treatment for metastatic disease, objective response rates were 15.4% and 17.2%. These trials were conducted prior to supplementation with folic acid and vitamin B12, which markedly decreased the frequency of hematologic toxicities of pemetrexed; routine supplementation is now included in all clinical trials of the agent. The marked improvement in toxicity and tolerance with vitamin supplementation suggests the need to reexamine optimal dosing in pemetrexed combination schedules. In a National Surgical Adjuvant Breast and Bowel Project phase II trial in 54 patients with previously untreated advanced colorectal cancer, pemetrexed at 500 mg/m2 plus oxaliplatin (Eloxatin) at 120 mg/m2 every 21 days with folic acid/vitamin B12 supplementation resulted in an objective response of 23%. Three additionalpatients (5.6%) had unconfirmed partial response (partial response at one visit), and 27 patients (50%) had stable disease. Median progression-free survival was 5.3 months and median duration of response was 5.7 months; median overall survival was approximately 11.05 months. Grade 3/4 neutropenia was observed in only 17% of patients and treatment was well tolerated. A phase I/II study is under way to identify and assess the optimal combination of pemetrexed/irinotecan in second-line treatment of advanced colorectal cancer. Planned studies include a phase I study examining the combination of pemetrexed and oxaliplatin given every 2 weeks as first-line treatment, and a phase I/II trial to identify the optimal pemetrexed/ oxaliplatin dose in a 21-day schedule and to compare pemetrexed/ oxaliplatin with FOLFOX4 in first-line treatment of metastatic disease. All of these trials include vitamin supplementation. A phase III trial comparing the every-3-week pemetrexed/oxaliplatin regimen with FOLFOX4 as
Baldwin, Graham S
This minireview explores the connections between circulating gastrins, iron status and colorectal cancer. The peptide hormone gastrin is a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. Gastrins bind two ferric ions with μM affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity. The ferric ion ligands have been identified as glutamates 7, 8 and 9 in the 18 amino acid peptide glycine-extended gastrin. An interaction between gastrin and transferrin was first demonstrated by covalent crosslinking techniques, and has been recently confirmed by surface plasmon resonance. We have therefore proposed that gastrins act as catalysts in the loading of transferrin with iron. Several recent lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease haemochromatosis, and that transferrin saturation positively correlates with circulating gastrin concentrations, suggest that gastrins may be involved in iron homeostasis. In addition the recognition that ferric ions may play an unexpected role in the biological activity of non-amidated gastrins may assist in the development of new therapies for colorectal carcinoma.
... genetic condition called Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer or HNPCC. About 3% (1 ... early if you get it. Lynch syndrome is hereditary, meaning that it is caused by an inherited ...
Kalady, Matthew F.; Heald, Brandie
Approximately 5 to 10% of colorectal cancers develop within a known hereditary syndrome. Specific underlying genetic mutations drive the clinical phenotype and it is imperative to determine the genetic etiology to provide meaningful surveillance and intervention. Recognizing potential patients and families with a hereditary predisposition is the first step in management. Syndromes can be categorized according to polyp burden as polyposis or nonpolyposis. Clinical assessment should start with a personal and family medical history, physical examination, and evaluation for the presence and type of colorectal polyps or cancers. Key information is gained from these simple steps and should guide the specific genetic analysis for diagnosis. Genetic counseling is a critical component to any hereditary colorectal cancer program and should be conducted before genetic testing to provide education about the implications of test results. This review focuses on the thought process that drives initial clinical evaluation and guides genetic testing for patients with suspected hereditary colorectal cancer syndromes. PMID:26664327
Kalady, Matthew F; Heald, Brandie
Approximately 5 to 10% of colorectal cancers develop within a known hereditary syndrome. Specific underlying genetic mutations drive the clinical phenotype and it is imperative to determine the genetic etiology to provide meaningful surveillance and intervention. Recognizing potential patients and families with a hereditary predisposition is the first step in management. Syndromes can be categorized according to polyp burden as polyposis or nonpolyposis. Clinical assessment should start with a personal and family medical history, physical examination, and evaluation for the presence and type of colorectal polyps or cancers. Key information is gained from these simple steps and should guide the specific genetic analysis for diagnosis. Genetic counseling is a critical component to any hereditary colorectal cancer program and should be conducted before genetic testing to provide education about the implications of test results. This review focuses on the thought process that drives initial clinical evaluation and guides genetic testing for patients with suspected hereditary colorectal cancer syndromes.
A summary of results from an international phase III trial that compared TAS-102 with placebo in patients with metastatic colorectal cancer whose disease progressed following prior treatments or who had health conditions that prevented the re-administrati
A summary of results from an international phase III trial that compared TAS-102 with placebo in patients with metastatic colorectal cancer whose disease progressed following prior treatments or who had health conditions that prevented the re-administrati
Guend, Hamza; Patel, Sunil
Patients with peritoneal metastasis from colorectal cancer represent a distinct subset with regional disease rather than systemic disease. They often have poorer survival outcomes with systemic chemotherapy. Optimal cytoreductive surgery and intraperitoneal chemotherapy (IPC) offers such patients a more directed therapy with improved survival. In this review, we discuss the diagnosis, evaluation and classification, as well as rational for treatment of peritoneal carcinomatosis (PC) secondary to colorectal cancer. PMID:26697203
Forte, Angelo; De Sanctis, Rita; Leonetti, Giovanni; Manfredelli, Simone; Urbano, Vincenzo; Bezzi, Marcello
Colorectal cancer is the second cause of morbidity and death in Italy. Genetic and environmental factors, i.e. inappropriate nutrition, are strongly involved in the aetiology of colon cancer. In the present review the authors analyze the possible mechanisms by which certain nutritive factors may interfere with the complex process of carcinogenesis. The authors identify studies by a literature search of Medline from January 1, 1970, through December 31, 2006. The mechanism of every protective compound is detailed, in particular the impact of antioxidant vitamins and minerals on tumor development. At present, the data suggest that vegetables are associated with lower risk and that their fbre content alone does not account for this association. Further, meat consumption is associated with an increased risk but this, too, is not explained solely by its fat content. Several microconstituents of the diet may be associated with reduced risk, including folate, methionine, calcium and vitamin D. Short chain fatty acids also contribute to colonic health. Nevertheless agricultural products contain several dangerous pesticides. Mutagenic compounds, particularly heterocyclic amines, produced when protein is cooked, plausibly explain the meat association. Healthy nutrition is a necessary but not sufficient condition for colon cancer prevention: accepted the feasibility of an accurate control on every patient's diet, fequently the difficulty encountered in nutritional chemoprevention is to establish individual metabolic profiles.
Sandouk, Fayez; Al Jerf, Feras; Al-Halabi, M. H. D. Bassel
Colorectal cancer (CRC) is the third most common cause of cancer death in the world. The incidence rate (ASR) and age distribution of this disease differ between most of African-Middle-Eastern (AMAGE) and North America and Europe for many reasons. However, in all areas, “CRC” is considered as one of the most preventable cancers, because it might develop from variant processes like polyps and IBD in addition to the genetic pathogenesis which became very well known in this disease. We tried in this paper to review all the possible reasons of the differences in incidence and age between the west and AMAGE. Also we reviewed all the mutations that lead to the hereditary and familiar clustering of this disease with the correlations with the surrounding food and environment of different areas. Then, we focused on the precancerous pathology of this disease with special focusing on early detection depending on new endoscopy technology and most important genetic studies. We lastly reviewed the evidence of some of the surveillance and put suggestions about future surveillance programs and how important those programs are on the psychological aspect of the patients and their families. PMID:23737765
Lopes, Joana Pedro; de Castro Cardoso Pereira, Paula Manuela; dos Reis Baltazar Vicente, Ana Filipa; Bernardo, Alexandra; de Mesquita, María Fernanda
The present study intended to evaluate the nutritional status of Portuguese colorectal patients and associated it with surgery type as well as quality of life outcomes. Malnutrition can affect up to 85% of cancer patients and specifically 30-60% in colorectal cancer and can significantly influence health outcomes. A sample of 50 colorectal cancer patients was evaluated in what refers to several anthropometric measures, food intake, clinical history, complications rate before and after surgery procedure. The sample was divided between convention and fast-track procedures. Most of the individuals were overweight or obese but had lost weight on the past six months. Despite mild, there were signs of malnutrition in this sample with high losses of fat free mass, weight and also fat mass during the hospitalization period. These results reinforce the importance of malnutrition assessment in colorectal patients as well as consider weight loss on the past months and body composition in order to complement nutritional status evaluation.
Expert-reviewed information summary about the genetics of colorectal cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for colorectal cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary colorectal cancer syndrome are also discussed.
Expert-reviewed information summary about the genetics of colorectal cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for colorectal cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary colorectal cancer syndrome are also discussed.
Iacopetta, Barry; Grieu, Fabienne; Amanuel, Benhur
Approximately 20 percent of right-sided colon cancers and 5 percent of left-sided colon and rectal cancers have a deficient DNA mismatch repair system. This results in the widespread accumulation of mutations to nucleotide repeats, some of which occur within the coding regions of cancer-related genes such as TGFβRII and BAX. A standardized definition for microsatellite instability (MSI) based on the presence of deletions to mononucleotide repeats is gaining widespread acceptance in both research and the clinic. Colorectal cancer (CRC) with MSI are characterized histologically by an abundance of tumor-infiltrating lymphocytes, poor differentiation and a signet ring or mucinous phenotype. In younger patients these tumors usually develop along the chromosomal instability pathway, in which case the mismatch repair genes are inactivated by germline mutation, somatic mutation and loss of heterozygosity. In older patients MSI CRC usually develops against a background of widespread hypermethylation that includes methylation-induced silencing of the mismatch repair gene MLH1. The overall biological and clinical phenotype of MSI CRC that arise in these two pathways is likely to be different and may account for some of the discordant results reported in the literature relating to the clinical properties of these tumors. The available evidence indicates that MSI is unlikely to be a clinically useful marker for the prognostic stratification of early-stage CRC. The predictive value of MSI for response to 5-fluorouracil-based chemotherapy remains controversial, while for other agents the predictive value is difficult to assess because they are used in combination regimens. The MSI phenotype is being actively investigated for novel therapeutic approaches based on the principle of synthetic lethality. Finally, the MSI status of CRC is an extremely useful marker for population-based screening programs that aim to identify individuals and families with the hereditary cancer
Lee, Bo-In; Hong, Sung Pil; Kim, Seong-Eun; Kim, Se Hyung; Hong, Sung Noh; Yang, Dong-Hoon; Shin, Sung Jae; Lee, Suck-Ho; Park, Dong Il; Kim, Young-Ho; Kim, Hyun Jung; Yang, Suk-Kyun; Kim, Hyo Jong; Jeon, Hae Jeong
Now colorectal cancer is the second most common cancer in males and the fourth most common cancer in females in Korea. Since most of colorectal cancers occur after the prolonged transformation of adenomas into carcinomas, early detection and removal of colorectal adenomas are one of the most effective methods to prevent colorectal cancer. Considering the increasing incidence of colorectal cancer and polyps in Korea, it is very important to establish Korean guideline for colorectal cancer screening and polyp detection. The guideline was developed by the Korean Multi-Society Take Force and we tried to establish the guideline by evidence-based methods. Parts of the statements were draw by systematic reviews and meta-analyses. Herein we discussed epidemiology of colorectal cancers and adenomas in Korea and optimal methods for screening of colorectal cancer and detection of adenomas including fecal occult blood tests, radiologic tests, and endoscopic examinations. PMID:22741131
Favoriti, Pasqualino; Carbone, Gabriele; Greco, Marco; Pirozzi, Felice; Pirozzi, Raffaele Emmanuele Maria; Corcione, Francesco
Colorectal cancer is a major public health problem, being the third most commonly diagnosed cancer and the fourth cause of cancer death worldwide. There is wide variation over time among the different geographic areas due to variable exposure to risk factors, introduction and uptake of screening as well as access to appropriate treatment services. Indeed, a large proportion of the disparities may be attributed to socioeconomic status. Although colorectal cancer continues to be a disease of the developed world, incidence rates have been rising in developing countries. Moreover, the global burden is expected to further increase due to the growth and aging of the population and because of the adoption of westernized behaviors and lifestyle. Colorectal cancer screening has been proven to greatly reduce mortality rates that have declined in many longstanding as well as newly economically developed countries. Statistics on colorectal cancer occurrence are essential to develop targeted strategies that could alleviate the burden of the disease. The aim of this paper is to provide a review of incidence, mortality and survival rates for colorectal cancer as well as their geographic variations and temporal trends.
The NCI CRCHD launches National Screen to Save Colorectal Cancer Outreach and Screening Initiative which aims to increase colorectal cancer screening rates among racially and ethnically diverse and rural communities.
Białek, Andrzej; Homa, Katarzyna; Marlicz, Krzysztof
Colorectal cancer is one of the most common neoplasms that often occurs in several members of family. In this communication we present the case of synchronous colorectal cancers with similar localization and similar clinical course in monozygotic twins.
Osmond, Allison; Li-Chang, Hector; Kirsch, Richard; Divaris, Dimitrios; Falck, Vincent; Liu, Dong Feng; Marginean, Celia; Newell, Ken; Parfitt, Jeremy; Rudrick, Brian; Sapp, Heidi; Smith, Sharyn; Walsh, Joanna; Wasty, Fasahat; Driman, David K
Following the introduction of colorectal cancer screening programmes throughout Canada, it became necessary to standardise the diagnosis of colorectal adenomas. Canadian guidelines for standardised reporting of adenomas were developed in 2011. The aims of the present study were (a) to assess interobserver variability in the classification of dysplasia and architecture in adenomas and (b) to determine if interobserver variability could be improved by the adoption of criteria specified in the national guidelines. An a priori power analysis was used to determine an adequate number of cases and participants. Twelve pathologists independently classified 40 whole-slide images of adenomas according to architecture and dysplasia grade. Following a wash-out period, participants were provided with the national guidelines and asked to reclassify the study set. At baseline, there was moderate interobserver agreement for architecture (K=0.4700; 95% CI 0.4427 to 0.4972) and dysplasia grade (K=0.5680; 95% CI 0.5299 to 0.6062). Following distribution of the guidelines, there was improved interobserver agreement in assessing architecture (K=0.5403; 95% CI 0.5133 to 0.5674)). For dysplasia grade, overall interobserver agreement remained moderate but decreased significantly (K=0.4833; 95% CI 0.4452 to 0.5215). Half of the cases contained high-grade dysplasia (HGD). Two pathologists diagnosed HGD in ≥75% of cases. The improvement in interobserver agreement in classifying adenoma architecture suggests that national guidelines can be useful in disseminating knowledge, however, the variability in the diagnosis of HGD, even following guideline review suggests the need for ongoing knowledge-transfer exercises.
Rama, A. R.; Aguilera, A.; Melguizo, C.; Caba, O.; Prados, J.
Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment. PMID:26648599
Gagnière, Johan; Raisch, Jennifer; Veziant, Julie; Barnich, Nicolas; Bonnet, Richard; Buc, Emmanuel; Bringer, Marie-Agnès; Pezet, Denis; Bonnet, Mathilde
The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies. PMID:26811603
Gagnière, Johan; Raisch, Jennifer; Veziant, Julie; Barnich, Nicolas; Bonnet, Richard; Buc, Emmanuel; Bringer, Marie-Agnès; Pezet, Denis; Bonnet, Mathilde
The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies.
Vogtmann, Emily; Corley, Douglas A; Almers, Lucy M; Cardwell, Chris R; Murray, Liam J; Abnet, Christian C
Use of oral bisphosphonates has been associated with a decreased risk of colorectal cancer (CRC), but the association may be related to residual confounding by healthy lifestyle or body mass index (BMI). Therefore, we conducted a prospective nested case-control study within the Kaiser Permanente, Northern California health system cohort. In total, 12,505 CRC cases were individually matched to 599,534 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression models with adjustment for important covariates extracted from the database. Participants who had ever used oral bisphosphonates were less likely than non-users to be diagnosed with CRC (OR 0.82; 95% CI: 0.74, 0.89). Colon and rectum site-specific associations were similar to the overall association. A stronger inverse association for ever use of bisphosphonates was observed for men (OR 0.63; 95% CI: 0.47, 0.85), however when stratified by previous lower endoscopy, the association was only observed in the participants who did not have a previous lower endoscopy (OR 0.73 (0.64, 0.83)). In conclusion, we found that oral bisphosphonate use was associated with a decreased odds of CRC, however this association may be due to residual confounding by BMI or another confounder.
The incidence of colorectal cancer (CRC) has been increasing during the past decades, and the lifetime risk for CRC in industrialised countries is about 5%. CRC is a good candidate for screening, because it is a disease with high prevalence, has recognised precursors, and early treatment is beneficial. This paper outlines the evidence for efficacy from randomised trials for the most commonly used CRC screening tests to reduce CRC incidence and mortality in the average-risk population. Four randomised trials have investigated the effect of guaiac-based fecal occult blood screening on CRC mortality, with a combined CRC mortality risk reduction of 15-17% in an intention-to-screen analysis, and 25% for those people who attended screening. Flexible sigmoidoscopy screening has been evaluated in three randomised trials. The observed reduction in CRC incidence varied between 23 and 80%, and between 27 and 67% for CRC mortality, respectively (intention-to-screen analyses) in the trials with long follow-up time. No randomised trials exist in other CRC screening tools, included colonoscopy screening. FOBT and flexible sigmoidoscopy are the two CRC screening methods which have been tested in randomised trials and shown to reduce CRC mortality. These tests can be recommended for CRC screening. Copyright © 2010 Elsevier Ltd. All rights reserved.
Vogtmann, Emily; Corley, Douglas A.; Almers, Lucy M.; Cardwell, Chris R.; Murray, Liam J.; Abnet, Christian C.
Use of oral bisphosphonates has been associated with a decreased risk of colorectal cancer (CRC), but the association may be related to residual confounding by healthy lifestyle or body mass index (BMI). Therefore, we conducted a prospective nested case-control study within the Kaiser Permanente, Northern California health system cohort. In total, 12,505 CRC cases were individually matched to 599,534 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression models with adjustment for important covariates extracted from the database. Participants who had ever used oral bisphosphonates were less likely than non-users to be diagnosed with CRC (OR 0.82; 95% CI: 0.74, 0.89). Colon and rectum site-specific associations were similar to the overall association. A stronger inverse association for ever use of bisphosphonates was observed for men (OR 0.63; 95% CI: 0.47, 0.85), however when stratified by previous lower endoscopy, the association was only observed in the participants who did not have a previous lower endoscopy (OR 0.73 (0.64, 0.83)). In conclusion, we found that oral bisphosphonate use was associated with a decreased odds of CRC, however this association may be due to residual confounding by BMI or another confounder. PMID:28281559
Peters, Ulrike; Bien, Stephanie; Zubair, Niha
Colorectal cancer (CRC) is a complex disease that develops as a consequence of both genetic and environmental risk factors. A small proportion (3–5%) of cases arises from hereditary syndromes predisposing to early onset CRC as a result of mutations in over a dozen well-defined genes. In contrast, CRC is predominantly a late-onset “sporadic” disease, developing in individuals with no obvious hereditary syndrome. In recent years genome-wide association studies have discovered over 40 genetic regions to be associated with weak effects on sporadic CRC and it has been estimated that increasingly large genome-wide scans will identify many additional novel genetic regions. Subsequent experimental validations have identified the causally related variant(s) in a limited number of these genetic regions. Further biological insight could be obtained through ethnically diverse study populations, larger genetic sequencing studies, and development of higher-throughput functional experiments. Along with inherited variation, integration of the tumour genome may shed light on the carcinogenic processes in CRC. In addition to summarizing the genetic architecture of CRC, this review discusses genetic factors that modify environmental predictors of CRC, as well as examples of how genetic insight has improved clinical surveillance, prevention, and treatment strategies. In summary, substantial progress has been made in uncovering the genetic architecture of CRC and continued research efforts are expected to identify additional genetic risk factors that further our biological understanding of this disease. PMID:26187503
Schlachta, Christopher M; Ashamalla, Shady; Smith, Andy
A consensus conference on the role of minimally invasive surgery (MIS) in the management of colon and rectal cancer was convened by the Colorectal Cancer Association of Canada in Toronto on April 18, 2012. This is a report of the consensus of an invited group of Canadian experts in MIS and surgery of the colon and rectum that addresses the role this technology should play in treatment and also considers advocacy and resources.
Yee, Judy; Kim, David H; Rosen, Max P; Lalani, Tasneem; Carucci, Laura R; Cash, Brooks D; Feig, Barry W; Fowler, Kathryn J; Katz, Douglas S; Smith, Martin P; Yaghmai, Vahid
Colorectal cancer is the third leading cause of cancer deaths in the United States. Most colorectal cancers can be prevented by detecting and removing the precursor adenomatous polyp. Individual risk factors for the development of colorectal cancer will influence the particular choice of screening tool. CT colonography (CTC) is the primary imaging test for colorectal cancer screening in average-risk individuals, whereas the double-contrast barium enema (DCBE) is now considered to be a test that may be appropriate, particularly in settings where CTC is unavailable. Single-contrast barium enema has a lower performance profile and is indicated for screening only when CTC and DCBE are not available. CTC is also the preferred test for colon evaluation following an incomplete colonoscopy. Imaging tests including CTC and DCBE are not indicated for colorectal cancer screening in high-risk patients with polyposis syndromes or inflammatory bowel disease. This paper presents the updated colorectal cancer imaging test ratings and is the result of evidence-based consensus by the ACR Appropriateness Criteria Expert Panel on Gastrointestinal Imaging. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Peters, H. Charles; Liu, Xiuli; Iqbal, Atif; Cunningham, Lisa A.
Despite improved screening modalities, 15–25% of newly diagnosed colorectal cancers are metastatic at the time of diagnosis. The vast majority of these cases present as hepatic metastasis; however, 22% present with concomitant extrahepatic disease. The thymus gland is an uncommon site of metastasis for any primary malignancy, particularly, colorectal cancer given its vascular and lymphatic drainage. This case report details our experience with a rare case of colorectal cancer metastasis to the thymus gland presenting as a symptomatic mediastinal mass. PMID:28116210
AWARD NUMBER: W81XWH-15-1-0273 TITLE: The Association between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer...ADDRESS. 1. REPORT DATE August 2016 2. REPORT TYPE Annual 3. DATES COVERED 1 Aug 2015 - 31 July 2016 4. TITLE AND SUBTITLE The Association Between...molecular markers associated with an increased risk of colorectal cancer in patients with sessile serrated colorectal polyps (SSPs). The project’s
Wang, Zhenjie; Uchida, Kazuhiro; Ohnaka, Keizo; Morita, Makiko; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji
A diet high in sugars may promote colorectal carcinogenesis, but it remains uncertain whether high intake of sugars or sucrose confers increased risk of colorectal cancer. The authors investigated the associations of sugars and sucrose intake with colorectal cancer risk in a community-based case-control study in Japan. The study subjects comprised 816 incident cases of colorectal cancer and 815 community controls. Consumption frequencies and portion sizes of 148 food and beverage items were ascertained by a computer-assisted interview. The authors used the consumption of 29 food items to estimate sugars and sucrose intake. The odds ratios of colorectal cancer risk according to intake categories were obtained using a logistic regression model with adjustment for potential confounding variables. Overall, intakes of sugars and sucrose were not related to colorectal cancer risk either in men or women. The association between sugars intake and colorectal cancer risk differed by smoking status and alcohol use in men, but not in women. In men, sugars intake tended to be associated with colorectal cancer risk inversely among never-smokers and positively among male ever-smokers (interaction p=0.01). Sugars intake was associated with an increased risk among men with no alcohol consumption, but was unrelated to the risk among male alcohol drinkers (interaction p=0.02). Body mass index did not modify the association with sugars intake in either men or women. Sugars intake was associated with increased risk of colorectal cancer among smokers and non-alcohol drinkers in men selectively.
Grady, William M.; Pritchard, Colin C.
The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577
Melosky, B.; Ho, C.
Each February, the Canadian Lung Cancer Conference brings together lung cancer researchers, clinicians, and care professionals who are united in their commitment to improve the care of patients with lung cancer. This year’s meeting, held 11–12 February, featured a resident education session, a welcome dinner, networking sessions, lectures, breakout sessions, debates, and a satellite symposium. Key themes from this year’s meeting included innovations across the care spectrum and results of recent clinical trials with targeted agents, immuno-oncology agents, and novel drug combinations.
Obstein, Keith L; Valdastri, Pietro
Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Diagnosing colorectal has been increasingly successful due to advances in technology. Flexible endoscopy is considered to be an effective method for early diagnosis and treatment of gastrointestinal cancer, making it a popular choice for screening programs. However, millions of people who may benefit from endoscopic colorectal cancer screening fail to have the procedure performed. Main reasons include psychological barriers due to the indignity of the procedure, fear of procedure related pain, bowel preparation discomfort, and potential need for sedation. Therefore, an urgent need for new technologies addressing these issues clearly exists. In this review, we discuss a set of advanced endoscopic technologies for colorectal cancer screening that are either already available or close to clinical trial. In particular, we focus on visual-inspection-only advanced flexible colonoscopes, interventional colonoscopes with alternative propulsion mechanisms, wireless capsule colonoscopy, and technologies for intraprocedural bowel cleansing. Many of these devices have the potential to reduce exam related patient discomfort, obviate the need for sedation, increase diagnostic yield, reduce learning curves, improve access to screening, and possibly avert the need for a bowel preparation.
Obstein, Keith L; Valdastri, Pietro
Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Diagnosing colorectal has been increasingly successful due to advances in technology. Flexible endoscopy is considered to be an effective method for early diagnosis and treatment of gastrointestinal cancer, making it a popular choice for screening programs. However, millions of people who may benefit from endoscopic colorectal cancer screening fail to have the procedure performed. Main reasons include psychological barriers due to the indignity of the procedure, fear of procedure related pain, bowel preparation discomfort, and potential need for sedation. Therefore, an urgent need for new technologies addressing these issues clearly exists. In this review, we discuss a set of advanced endoscopic technologies for colorectal cancer screening that are either already available or close to clinical trial. In particular, we focus on visual-inspection-only advanced flexible colonoscopes, interventional colonoscopes with alternative propulsion mechanisms, wireless capsule colonoscopy, and technologies for intraprocedural bowel cleansing. Many of these devices have the potential to reduce exam related patient discomfort, obviate the need for sedation, increase diagnostic yield, reduce learning curves, improve access to screening, and possibly avert the need for a bowel preparation. PMID:23382621
Colorectal cancer is the most frequent malignancy in both sexes in Spain. Between 20% and 25% of affected individuals have a family history of the disease, and 5% to 6% have a germ mutation, i.e. the disease develops in the context of a hereditary syndrome. The importance of identifying patients with hereditary syndromes predisposing them to colorectal cancer lies in the possibility of applying preventive measures, screening, and more appropriate management of both patients and their families. The present article outlines the most important studies presented at the congress of the American Gastroenterological Association. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.
... of fiber . Talk with your doctor about taking aspirin every day. Taking aspirin every day can lower your risk of colorectal ... 50 to 59, ask your doctor if daily aspirin is right for you . Previous section Get Tested ...
Christy, Shannon M.; Perkins, Susan M.; Tong, Yan; Krier, Connie; Champion, Victoria L.; Skinner, Celette Sugg; Springston, Jeffrey K.; Imperiale, Thomas F.; Rawl, Susan M.
Background Provider recommendation is a predictor of colorectal cancer (CRC) screening. Purpose To compare the effects of two clinic-based interventions on patient–provider discussions about CRC screening. Design Two-group RCT with data collected at baseline and 1 week post-intervention. Participants/setting African-American patients that were non-adherent to CRC screening recommendations (n=693) with a primary care visit between 2008 and 2010 in one of 11 urban primary care clinics. Intervention Participants received either a computer-delivered tailored CRC screening intervention or a nontailored informational brochure about CRC screening immediately prior to their primary care visit. Main outcome measures Between-group differences in odds of having had a CRC screening discussion about a colon test, with and without adjusting for demographic, clinic, health literacy, health belief, and social support variables, were examined as predictors of a CRC screening discussion using logistic regression. Intervention effects on CRC screening test order by PCPs were examined using logistic regression. Analyses were conducted in 2011 and 2012. Results Compared to the brochure group, a greater proportions of those in the computer-delivered tailored intervention group reported having had a discussion with their provider about CRC screening (63% vs 48%, OR=1.81, p<0.001). Predictors of a discussion about CRC screening included computer group participation, younger age, reason for visit, being unmarried, colonoscopy self-efficacy, and family member/friend recommendation (all p-values <0.05). Conclusions The computer-delivered tailored intervention was more effective than a nontailored brochure at stimulating patient–provider discussions about CRC screening. Those who received the computer-delivered intervention also were more likely to have a CRC screening test (fecal occult blood test or colonoscopy) ordered by their PCP. Trial registration This study is registered at www
Preisich, P; Siba, S; Szakátsy, E
Haemoccult screening for colorectal tumours was carried out in Hungary in small cities and villages around Budapest. Haemoccult slides were supplied to 17,662 individuals over 40 years of age, and 15,431 (87%) were returned. Of these, 346 (2.2%) were positive and 18 colorectal carcinomas were detected. Additionally, 24 patients with one or more polyps greater than 1 cm diameter were found. Of the screened cases of cancer 39% were in Dukes' stage A and B, a rate twice as good as when screening was not done. The cost per tumour detected amounted to about three times more than one monthly income, indicating that the costs of screening for colorectal cancer are relatively much higher in Hungary than in Western countries. All expenses were met from state funds. PMID:3625689
Simpson, W. John; McKinney, Steven E.
We report the results of a multicentre retrospective chart review of 2214 patients with thyroid cancer registered at 13 radiotherapy centres between 1958 and 1978. The data analysed included sex, age at the time of diagnosis, pathological diagnosis, extent of disease before treatment, types of treatment and their complications, and the rates of recurrence and survival up to 24 years after diagnosis. Although papillary cancers were most common, anaplastic and miscellaneous tumours were more frequent than expected, which reflects the type of patients referred by endocrinologists and surgeons to radiotherapy centres. There were marked differences in patterns of referral to the centres. Some patients with papillary and follicular thyroid cancers died of these cancers up to 20 years after diagnosis. The clinical manifestations, treatment and outcome of the rarer types of thyroid malignant tumours were of particular interest. The influence of age at the time of diagnosis on survival rates for patients with papillary or follicular thyroid cancer was highly significant, indicating much more aggressive behaviour of these cancers in older patients, particularly those beyond the age of 60 years. A more detailed analysis of tumour subtypes should provide new information on their natural history and lead to better management. PMID:3978516
Kang, Wonmo; Lee, Sujin; Jeon, Eunyi; Yun, Ye-Rang; Kim, Kook-Hyun; Jang, Jun-Hyeog
Colorectal cancer is a common cancer and the fourth leading cause of death in Korea. The incidence and mortality of colorectal cancer varies according to risk factors, such as age, family history, genetic history, food habits, and physical activities. Some studies have focused on the association between vitamin D and colorectal cancer. Today, there is growing evidence that high vitamin D intake and a plasma level of 25(OH)D(3) reduce the incidence of colorectal cancer by modifying cancer angiogenesis, cell apoptosis, differentiation, and proliferation. Taken together, these results suggest that vitamin D supplementation alone, or in combination with anti-cancer agents, might reduce the incidence of colorectal cancer. In this review, we discuss the function and mechanism of vitamin D including the effect of vitamin D on colorectal cancer.
Lynch, H T; Watson, P; Lanspa, S J; Marcus, J; Smyrk, T; Fitzgibbons, R J; Kriegler, M; Lynch, J F
Approximately 5 to 6 percent of the total colorectal cancer burden is accounted for by hereditary nonpolyposis colorectal cancer (HNPCC). Because clinical premonitory signs such as those seen in familial polyposis coli (FPC) are lacking, the clinician must recognize clinical findings and family history typical of HNPCC. The authors have described colorectal cancer expression from a survey of ten HNPCC kindreds. Kindred members with colorectal cancer differed significantly (P less than .05) from patients with sporadic colorectal cancer: 1) mean age of initial colon cancer diagnosis was 44.6 years; 2) 72.3 percent of first colon cancers were located in the right colon, and only 25 percent were in the sigmoid colon and rectum; 3) 18.1 percent had synchronous colon cancers; and 4) 24.2 percent developed metachronous colon cancer, with a risk for metachronous lesions in ten years of 40 percent. Affecteds and their first-degree relatives should undergo early intensive education and surveillance. In families with an early age of onset, colonoscopy should begin at age 25, and biannually thereafter, with fecal occult blood testing of the stool semiannually. Third-party carriers must become more responsive to the costly surveillance measures required for these otherwise healthy patients.
Povlow, Michael R
Colorectal cancer is a rare occurrence during pregnancy and can present with symptoms that are common during pregnancy such as constipation.This can make the diagnosis of colorectal cancer during pregnancy difficult. Management of colorectal cancer during pregnancy is similar to the treatment of non-pregnant patients, but with fetal safety in mind. This case report describes a 33-year-old female gravida two para one (G2P1) at 29 weeks gestation who presented with a complete bowel obstruction. Colonoscopy, magnetic resonance imaging (MRI) and later resection showed an obstructing malignancy which was then resected through an exploratory laparotomy with left hemicolectomy. Postoperatively, there was a concern for sepsis, so labor was induced and the baby was delivered vaginally. The patient then continued with chemotherapy with hematology-oncology. High clinical suspicion is needed to diagnose colorectal cancer during pregnancy. Once diagnosed, surgery can be considered if resectable, taking into account gestational age. Fetal safety is a major consideration during treatment. PMID:28553568
Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH) examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35%) pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) and 15 cases (1.73%) were suspected of HNPCC. In 69 cases (8%) with a cancer family aggregation (CFA) were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC) followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.
Ha, Joo Young; Oh, Edward Hynseung; Jung, Moon Ki; Park, Song Ee; Kim, Ji Tak; Hwang, In Gyu
Choroidal and skin metastasis of colon cancer is rare. In women, the frequency of cutaneous metastasis from colon cancer as the primary lesion in is 9% and skin metastasis occurs in 0.81% of all colorectal cancers. We report a patient with colonic adenocarcinoma who presented with visual disorder in her right eye and scalp pain as her initial symptoms. Contrast-enhance orbital magnetic resonance imaging with fat suppression revealed an infrabulbar mass, and skin biopsy of the posterior parietal scalp confirmed adenocarcinoma. These symptoms were diagnosed as being caused by choroidal and skin metastases of colonic adenocarcinoma. We started palliative chemotherapy with oral capecitabine (1000 mg/m2, twice a day, on days 1-14) every 3 wk, which was effective at shrinking the brain masses and improving the visual disorder. This is the first report that capecitabine is effective at reducing a choroidal and cutaneous metastatic lesion from right-sided colorectal cancer. PMID:27920486
Ha, Joo Young; Oh, Edward Hynseung; Jung, Moon Ki; Park, Song Ee; Kim, Ji Tak; Hwang, In Gyu
Choroidal and skin metastasis of colon cancer is rare. In women, the frequency of cutaneous metastasis from colon cancer as the primary lesion in is 9% and skin metastasis occurs in 0.81% of all colorectal cancers. We report a patient with colonic adenocarcinoma who presented with visual disorder in her right eye and scalp pain as her initial symptoms. Contrast-enhance orbital magnetic resonance imaging with fat suppression revealed an infrabulbar mass, and skin biopsy of the posterior parietal scalp confirmed adenocarcinoma. These symptoms were diagnosed as being caused by choroidal and skin metastases of colonic adenocarcinoma. We started palliative chemotherapy with oral capecitabine (1000 mg/m(2), twice a day, on days 1-14) every 3 wk, which was effective at shrinking the brain masses and improving the visual disorder. This is the first report that capecitabine is effective at reducing a choroidal and cutaneous metastatic lesion from right-sided colorectal cancer.
Baldwin, Laura-Mae; Cai, Yong; Larson, Eric H.; Dobie, Sharon A.; Wright, George E.; Goodman, David C.; Matthews, Barbara; Hart, L. Gary
Context: Cancer care requires specialty surgical and medical resources that are less likely to be found in rural areas. Purpose: To examine the travel patterns and distances of rural and urban colorectal cancer (CRC) patients to 3 types of specialty cancer care services--surgery, medical oncology consultation, and radiation oncology consultation.…
Baldwin, Laura-Mae; Cai, Yong; Larson, Eric H.; Dobie, Sharon A.; Wright, George E.; Goodman, David C.; Matthews, Barbara; Hart, L. Gary
Context: Cancer care requires specialty surgical and medical resources that are less likely to be found in rural areas. Purpose: To examine the travel patterns and distances of rural and urban colorectal cancer (CRC) patients to 3 types of specialty cancer care services--surgery, medical oncology consultation, and radiation oncology consultation.…
The Canadian Cancer Society has changed its attitude to public education about cancer from concentration on danger signals to emphasis on safeguards. There is much public ignorance about the nature of cancer. One in four Canadians, for instance, believes that cancer cannot be cured. With our present medical organization it would be impossible for each person to have yearly check-ups for cancer but each area should work out the best way of providing this service to the public by using medical and paramedical personnel to the best advantage. Increasing emphasis is being placed on the value of sigmoidoscopic examinations. Overall incidence of cancer in Canada is increasing. Only with the continued support and active participation of the family physician can the Society's education program be successful. Imagesp37-a PMID:20468455
Sameer, Aga Syed; Nissar, Saniya
Colorectal cancer (CRC) is a third most common epithelial carcinoma. CRC is known to develop from the early precancerous lesion to full blown malignancy via definite phases due to cumulative mutations and aberrant methylation of number of genes. The use of serum biomarkers that is non-invasive to discriminate cancer patients from healthy persons will prove to be an important tool to improve the early diagnosis of CRC. This will serve as the boon to the clinical management of the disease.
Zhang, Ya-Li; Zhang, Zhen-Su; Wu, Ba-Ping; Zhou, Dian-Yuan
AIM: To review the present studies on early diagnosis of colorectal cancer. METHODS: The detective rate for early cancer is 1.7%-26.1% based on various statistical data, with much higher detective rate in endoscopy. Since early cancer means invasion involved in the mucosa or submucosa, the diagnosis can only be made when the invasive depth is identified. Pathological tissue materials from both surgical operation or endoscopic resection are suitable for early cancer evaluation. RESULTS: Incidence of polyp malignancy is 1.4%-20.4%. The various constitutive proportion of polyps may explain the different rates. Malignant incidence is higher in adenomatous polyps, that for villous polyps can reach 21.3%-58.3%. Type II early stage of colorectal carcinoma is rarely reported in China. It is shownd that majority of them were not malignant, most of type IIa being adenoma or hyperplasia, and IIb being inflammatory and IIc might be the isolated ulcers. The occurrence of malignancy of type II is far lower than that of polypoid lesion. In China, the qualitative diagnosis and classification of neoplasm generally adopted the WHO standard, including surgical excision or biopsies. There is impersonal evaluation between colorectal pre-malignancy and cancer. The former emphasizes the dysplasia of nuclei and gland, while the latter is marked with cancer invasion. Diagnosis of early stage colorectal cancer in endoscopy is made with too much caution which made the detective rate much lower. Mass screening for asymptomatic subjects and follow-up for high risk population are mainly used to find the early stage colorectal cancer in China. Fecal occult blood test is also widely made as primary screening test, galactose oxygenase test of rectal mucus (T antigen), fecal occult albumin test are also used. The detective rate of colorectal cancer is 24-36.5 per 105 mass population. CONCLUSION: Although carcinoma associated antigen in blood or stool, microsatellite DNA instability for high risk
Richardson, Ann K; Potter, John D
Prostate cancer and colorectal cancer are the most commonly registered cancers in New Zealanders and among the five most commonly registered cancers worldwide, but the balance of benefits and harms, and therefore appropriate screening policies, for these cancers differ. We aimed to compare the potential benefits and harms of screening for prostate cancer and colorectal cancer to aid prioritisation in New Zealand. Relevant reports from randomised controlled trials and systematic reviews of prostate cancer and colorectal cancer screening were reviewed to obtain estimates of the potential benefits and harms of screening for prostate cancer and colorectal cancer. The balance of potential benefits and harms of screening is better for colorectal cancer screening than for prostate cancer screening. For colorectal cancer, the balance of benefits and harms is better for flexible sigmoidoscopy screening than for faecal occult blood screening. In New Zealand, colorectal cancer screening should be a priority. Challenges include colonoscopy capacity, and decisions about the most appropriate screening modality.
Morita, Makiko; Yin, Guang; Yoshimitsu, Shin-ichiro; Ohnaka, Keizo; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji
One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B6 intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin B2, vitamin B6, and vitamin B12 with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin B12 intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin B6. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.
Lee, Kyung-Jae; Inoue, Manami; Otani, Tetsuya; Iwasaki, Motoki; Sasazuki, Shizuka; Tsugane, Shoichiro
To investigate prospectively the association between colorectal cancer screening and subsequent risk of colorectal cancer death in a large-scale population-based cohort study (the JPHC study) with a 13-year follow-up period in Japan. We analyzed data from a population-based cohort of 42,150 (20,326 men and 21,824 women) subjects. Subjects who had undergone fecal occult blood test (FOBT) screening during the preceding 12 months were defined as the screened group. A total of 132 colorectal cancer deaths and 597 cases of newly diagnosed colorectal cancer were identified during the follow-up period. We observed a nearly 70% decrease in colorectal cancer mortality in screened versus unscreened subjects (RR=0.28, 95% CI=0.13-0.61). Screening participation was associated with a 30% reduced risk of death from all causes other than colorectal cancer (RR=0.70, 95% CI=0.61-0.79). However, the extent of mortality reduction was greater for colorectal cancer than other causes. A significant decrease in the incidence of advanced colorectal cancer was seen in screened subjects (RR=0.41, 95% CI=0.27-0.63), although the overall incidence rate did not differ significantly between the screened and unscreened groups. Although self-selection bias could not be fully controlled, these findings suggest that colorectal cancer screening may be associated with a reduction in mortality from colorectal cancer in the Japanese population.
Colorectal cancer (CRC) is still one of the deadliest cancer-related diseases. About 10% of CRC patients are characterized by a mutation in the B-Raf proto-oncogene serine/threonine kinase (BRAF) gene resulting in a valine-to-glutamate change at the residue 600 (V600E). This mutation is also present in more than 60% of melanoma patients. BRAF inhibitors were developed and found to improve patient survival; however, most patients at the end of the track ultimately develop resistance to these inhibitors. Melanoma patients benefit from the combination of BRAF inhibitors with mitogen/extracellular signal-regulated kinase (MEK) inhibitors, among others. Unfortunately, colorectal patients do not respond much efficiently, which suggests different resistance mechanisms between the two cancer types. This review aims at shedding light on recent discoveries that improve our understanding of the BRAF mutation biology in CRC. PMID:26396549
Panduro Cerda, A; Lima González, G; Villalobos, J J
Genetic and environmental aspects play an important role in the development of colorectal cancer. However, the common molecular alteration in both hereditary and sporadic colon cancer is localized in the APC gene. the APC gene maps in the long arm of chromosome 5 and was discovered in patients with familial adenomatous polyposis (FAP). The search for the APC gene led to the identification of restriction fragment length polymorphisms (RFLPs) in FAP patients. Using these RFLPs in relatives of FAP patients it is possible to make the presymptomatic and prenatal diagnosis. The FAP syndrome is an interesting model of carcinogenesis in vivo. Thus the different stages involved in the FAP syndrome which include hyperproliferative epithelium, adenoma, adenocarcinoma and metastases, have allowed the analysis of molecular alterations in oncogenes and tumor suppressor genes. The APC gene alteration if not inherited, occurs as the earliest molecular alteration in the development of colorectal cancer whereas structural alterations of the genes myc, ras, p53, MCC and DCC are considered to be late events. All these investigations have lead to 1) a better understanding of the ethiology of cancer and 2) early diagnosis of colorectal cancer in both the hereditary and sporadic forms of the disease.
Chong, Dawn Q; Mehta, Raaj S; Song, Mingyang; Kedrin, Dmitriy; Meyerhardt, Jeffrey A; Ng, Kimmie; Wu, Kana; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Chan, Andrew T
Circulating adiponectin is inversely related to the risk of colorectal cancer. However, its influence on colorectal cancer survival is unclear. We conducted a prospective study to evaluate the association between prediagnostic plasma levels of adiponectin and mortality in patients with colorectal cancer. We identified 621 incident colorectal cancer cases who provided blood specimens prior to diagnosis within the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI). After a median follow-up of 9 years, there were 269 (43%) total deaths, of which 181 (67%) were due to colorectal cancer. Compared with participants in the lowest quartile of adiponectin, those in the highest quartile had multivariate HRs of 1.89 (95% CI, 1.21-2.97; P(trend) = 0.01) for colorectal cancer-specific mortality and 1.66 (95% CI, 1.15-2.39; P(trend) = 0.009) for overall mortality. The apparent increased risk in colorectal cancer-specific mortality was more pronounced in patients with metastatic disease (HR, 3.02: 95% CI, 1.50-6.08). Among patients with colorectal cancer, prediagnostic plasma adiponectin is associated with an increased risk of colorectal cancer-specific and overall mortality and is more apparent in patients with metastatic disease. Adiponectin may be a marker for cancers which develop through specific pathways that may be associated with worsened prognosis. Further studies are needed to validate these findings.
Tape, Christopher J
Tissues contain multiple different cell types and can be considered to be heterocellular systems. Signaling between different cells allows tissues to achieve phenotypes that no cell type can achieve in isolation. Such emergent tissue-level phenotypes can be said to 'supervene upon' heterocellular signaling. It is proposed here that cancer is also an emergent phenotype that supervenes upon heterocellular signaling. Using colorectal cancer (CRC) as an example, I review how heterotypic cells differentially communicate to support emergent malignancy. Studying tumors as integrated heterocellular systems - rather than as solitary expansions of mutated cells - may reveal novel ways to treat cancer.
Brosens, Lodewijk A A; Offerhaus, G Johan A; Giardiello, Francis M
Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in men and women in the United States. About 30% of patients with CRC report a family history of CRC. However, only 5% of CRCs arise in the setting of a well-established mendelian inherited disorder. In addition, serrated polyposis is a clinically defined syndrome with multiple serrated polyps in the colorectum and an increased CRC risk for which the genetics are unknown. This article focuses on genetic and clinical aspects of Lynch syndrome, familial adenomatous polyposis, and MUTYH-associated polyposis. Copyright © 2015 Elsevier Inc. All rights reserved.
Millan, Monica; Merino, Sandra; Caro, Aleidis; Feliu, Francesc; Escuder, Jordi; Francesch, Tani
Colorectal cancer has a high incidence, and approximately 60% of colorectal cancer patients are older than 70, with this incidence likely increasing in the near future. Elderly patients (> 70-75 years of age) are a very heterogeneous group, ranging from the very fit to the very frail. Traditionally, these patients have often been under-treated and recruited less frequently to clinical trials than younger patients, and thus are under-represented in publications about cancer treatment. Recent studies suggest that fit elderly patients can be treated in the same way as their younger counterparts, but the treatment of frail patients with comorbidities is still a matter of controversy. Many factors should be taken into account, including fitness for treatment, the wishes of the patient and family, and quality of life. This review will focus on the existing evidence for surgical, oncologic, and palliative treatment in patients over 70 years old with colorectal cancer. Careful patient assessment is necessary in order to individualize treatment approach, and this should rely on a multidisciplinary process. More well-designed controlled trials are needed in this patient population. PMID:26483875
Body image is understood to be a person's perception of his or her own physical appearance although, as this article highlights, it embraces a greater range of bodily attributes than is often appreciated. It can be significantly affected by a diagnosis of colorectal cancer and subsequent treatment, which may modify the way the body looks, feels and functions. One of the major aesthetic and functional consequences of colorectal cancer surgery is the possibility of stoma formation, which is of particular concern to many. However, the range of other bodily effects following surgery should not be overlooked, not least because of they may result in distress. While concerns about changes in body image generally decrease over time, people recovering from cancer treatment often feel their relationship with their body has been permanently altered. Specialist support is often required when adjusting to any changes in bodily appearance and function. Care outcomes can be improved by having a sound understanding of the body image concerns likely to arise following treatment, as well as the skills to identify and support patients at risk of altered body image. This article provides guidance to nurses caring for individuals who may be experiencing distress over how their body is now perceived by themselves and others following colorectal cancer surgery.
Campos, Fábio Guilherme; Figueiredo, Marleny Novaes; Martinez, Carlos Augusto Real
Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as “hamartomatous polyposis syndromes”, “Peutz-Jeghers syndrome”, “juvenile polyposis syndrome”, “juvenile polyp”, and “PTEN hamartoma tumour syndrome” (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented. PMID:25848489
Campos, Fábio Guilherme; Figueiredo, Marleny Novaes; Martinez, Carlos Augusto Real
Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as "hamartomatous polyposis syndromes", "Peutz-Jeghers syndrome", "juvenile polyposis syndrome", "juvenile polyp", and "PTEN hamartoma tumour syndrome" (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented.
Thomas, Joe; Ohtsuka, Masahisa; Pichler, Martin; Ling, Hui
Colorectal cancer is one of the most common cancer diagnoses and causes of mortality worldwide. MicroRNAs are a class of small, non-coding regulatory RNAs that have shown strong associations with colorectal cancer. Through the repression of target messenger RNAs, microRNAs modulate many cellular pathways, such as those involved in cell proliferation, apoptosis, and differentiation. The utilization of microRNAs has shown significant promise in the diagnosis and prognosis of colorectal cancer, owing to their unique expression profile associations with cancer types and malignancies. Moreover, microRNA therapeutics with mimics or antagonists show great promise in preclinical studies, which encourages further development of their clinical use for colorectal cancer patients. The unique ability of microRNAs to affect multiple downstream pathways represents a novel approach for cancer therapy. Although still early in its development, we believe that microRNAs can be used in the near future as biomarkers and therapeutic targets for colorectal cancer.
Wang, Zhen-Jie; Ohnaka, Keizo; Morita, Makiko; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji
AIM: To investigate the associations between dietary intake of polyphenols and colorectal cancer. METHODS: The study subjects were derived from the Fukuoka colorectal cancer study, a community-based case-control study. The study subjects were 816 cases of colorectal cancer and 815 community-based controls. The consumption of 148 food items was assessed by a computer-assisted interview. We used the consumption of 97 food items to estimate dietary intakes of total, tea and coffee polyphenols. The Phenol-Explorer database was used for 92 food items. Of the 5 foods which were not listed in the Phenol-Explorer Database, polyphenol contents of 3 foods (sweet potatoes, satoimo and daikon) were based on a Japanese study and 2 foods (soybeans and fried potatoes) were estimated by ORAC-based polyphenol contents in the United States Department of Agriculture Database. Odds ratios (OR) and 95%CI of colorectal cancer risk according to quintile categories of intake were obtained by using logistic regression models with adjustment for age, sex, residential area, parental history of colorectal cancer, smoking, alcohol consumption, body mass index 10 years before, type of job, leisure-time physical activity and dietary intakes of calcium and n-3 polyunsaturated fatty acids. RESULTS: There was no measurable difference in total or tea polyphenol intake between cases and controls, but intake of coffee polyphenols was lower in cases than in controls. The multivariate-adjusted OR of colorectal cancer according to quintile categories of coffee polyphenols (from the first to top quintile) were 1.00 (referent), 0.81 (95%CI: 0.60-1.10), 0.65 (95%CI: 0.47-0.89), 0.65 (95%CI: 0.46-0.89) and 0.82 (95%CI: 0.60-1.10), respectively (Ptrend = 0.07). Similar, but less pronounced, decreases in the OR were also noted for the third and fourth quintiles of total polyphenol intake. Tea polyphenols and non-coffee polyphenols showed no association with colorectal cancer risk. The site-specific analysis
Pericleous, Marinos; Mandair, Dalvinder
Background Colorectal cancer is the third commonest cancer and the third leading cause of cancer death among men and women. It has been proposed that dietary factors are responsible for 70-90% of colorectal cancer and diet optimization may prevent most cases. Aim To evaluate the role of dietary components and supplements in colorectal cancer. Methods Bibliographical searches were performed in Pubmed for the terms “diet and colorectal cancer”, “diet and colon cancer”, “diet and rectal cancer”, “nutrition and colorectal cancer”, “probiotics and colorectal cancer”, “prebiotics and colorectal cancer”, “alcohol and cancer” and “colorectal cancer epidemiology”. Results Consumption of processed or red meat, especially when cooked at high temperatures may be associated with increased risk of colorectal cancer. The evidence for dietary fibre is unclear but foods that contain high amounts of fibre are usually rich in polyphenols which have been shown to alter molecular processes that can encourage colorectal carcinogenesis. Meta-analyses provide evidence on the benefits of circulating, diet-derived and supplemented, vitamin D and Calcium. We also found that diets rich in Folate may prevent colorectal carcinoma. The evidence on dietary micronutrients such as Zinc and Selenium in association with colorectal cancer is not conclusive. It has been suggested that there may be a direct association between alcohol intake and colorectal cancer. In vitro and in vivo studies have highlighted a possible protective role of prebiotics and probiotics. Conclusions The lack of randomized trials and the presence of confounding factors including smoking, physical activity, obesity and diabetes may often yield inconclusive results. Carefully designed randomized trials are recommended. PMID:24294513
Migliore, Lucia; Migheli, Francesca; Spisni, Roberto; Coppedè, Fabio
Most of the colorectal cancer (CRC) cases are sporadic, only 25% of the patients have a family history of the disease, and major genes causing syndromes predisposing to CRC only account for 5-6% of the total cases. The following subtypes can be recognized: MIN (microsatellite instability), CIN (chromosomal instability), and CIMP (CpG island methylator phenotype). CIN occurs in 80–85% of CRC. Chromosomal instability proceeds through two major mechanisms, missegregation that results in aneuploidy through the gain or loss of whole chromosomes, and unbalanced structural rearrangements that lead to the loss and/or gain of chromosomal regions. The loss of heterozygosity that occur in the first phases of the CRC cancerogenesis (in particular for the genes on 18q) as well as the alteration of methylation pattern of multiple key genes can drive the development of colorectal cancer by facilitating the acquisition of multiple tumor-associated mutations and the instability phenotype. PMID:21490705
Houlston, Richard S.
Many colorectal cancers (CRCs) develop in genetically susceptible individuals most of whom are not carriers of germ line mismatch repair or APC gene mutations and much of the heritable risk of CRC appears to be attributable to the co-inheritance of multiple low-risk variants. The accumulated experience to date in identifying this class of susceptibility allele has highlighted the need to conduct statistically and methodologically rigorous studies and the need for the multi-centre collaboration. This has been the motivation for establishing the COGENT (COlorectal cancer GENeTics) consortium which now includes over 20 research groups in Europe, Australia, the Americas, China and Japan actively working on CRC genetics. Here, we review the rationale for identifying low-penetrance variants for CRC and the current and future challenges for COGENT. PMID:22294761
Van Dam, Jacques
Premalignant diseases of the gastrointestinal tract, such as Barrett's esophagus, long-standing ulcerative colitis, and adenomatous polyps, have a significantly increased risk for development of adenocarcinoma, most often through an intermediate stage of dysplasia. Adenocarcinoma of the colon is the second most common cancer in the United States. Because patients with colorectal cancer often present with advanced disease, the outcomes are associated with significant morbidity and mortality. Effective methods of early detection are essential. As non-polypoid dysplasia is not visible using conventional endoscopy, surveillance of patients with Barrett's esophagus and ulcerative colitis is performed via a system in which multiple random biopsies are obtained at prescribed intervals. Sampling error and missed diagnoses occur frequently and render current screening methods inadequate. Also, the examination of a tissue biopsy is time consuming and costly, and significant intra- and inter-observer variation may occur. The newer methods discussed herein demonstrate the potential to solve these problems by early detection of disease with high sensitivity and specificity. Conventional endoscopy is based on the observation of white light reflected off the tissue surface. Subtle changes in color and shadow reveal structural changes. New developments in optical imaging go beyond white light, exploiting other properties of light. Several promising methods will be discussed at this meeting and shall be briefly discussed below. However, few such imaging modalities have arrived at our clinical practice. Some much more practical methods to improve colorectal cancer screening are currently being evaluated for their clinical impact. These methods seek to overcome limitations other than those of detecting dysplasia not visible under white light endoscopy. The current standard practice of colorectal cancer screening utilizes colonoscopy, an uncomfortable, sometimes difficult medical
Guillén-Ponce, C; Serrano, R; Sánchez-Heras, A B; Teulé, A; Chirivella, I; Martín, T; Martínez, E; Morales, R; Robles, L
Genetic mutations have been identified as the cause of inherited cancer risk in some colon cancer; these mutations are estimated to account for only 5-6 % of colorectal cancer (CRC) cases overall. Up to 25-30 % of patients have a family history of CRC that suggests a hereditary component, common exposures among family members, or a combination of both. Cancers in people with a hereditary predisposition typically occur at an earlier age than in sporadic cases. A predisposition to CRC may include a predisposition to other cancers, such as endometrial cancer. We describe genetics, current diagnosis and management of CRC hereditary syndromes pointing to a multidisciplinary approach to achieve the best results in patients and family outcomes.
McCafferty, Michael H
The purpose of this review is to provide the practicing surgeon with an outline of several significant developments in colorectal cancer treatment that have affected the care of patients. This review is not intended to report on every important publication of the past few years nor is it intended to be encyclopedic. The author simply hopes to provide a useful reference for surgeons in their daily practice.
Locker, Gershon Y; Lynch, Henry T
The observed increased incidence of colorectal cancer in Ashkenazi Jews compared to other populations is unexplained but likely has a genetic component. The I1307K APC polymorphism/mutation is carried by 6-8% of Ashkenazim and increases the risk of colorectal cancer 1.5-2 fold. There are few differences between the phenotype of colorectal cancer in I1307K carriers and sporadic cases. It is estimated that the mutation accounts for 6% of cases of colorectal cancer in Jews of Eastern European heritage. It should not be the subject of mass screening in Ashkenazi Jews, although it may be important in cases of familial colorectal cancer. Even rarer is the 1906G-->C MSH2 mutation carried by less than 1% of Ashkenazim, but as with other HNPCC mutations likely associated with a high risk of malignancy. Mutations at 15q13-14 are associated with the colorectal adenoma and carcinoma syndrome (CRAC) described in Ashkenazi families. The prevalence of the mutation is not known, nor its significance as a cause of colorectal cancer. Despite the paucity of genetic explanations for the high risk of colorectal cancer in Ashkenazim, that risk warrants aggressive colorectal cancer screening and particular attention to family history of malignancy in all Jews of Ashkenazi descent.
Torino, Francesco; Bonmassar, Enzo; Bonmassar, Laura; De Vecchis, Liana; Barnabei, Agnese; Zuppi, Cecilia; Capoluongo, Ettore; Aquino, Angelo
The availability of sensitive methods has allowed the detailed study of circulating tumor cells only recently. Evolving evidence support the prognostic and predictive role of these cells in patients affected by several solid tumors, including colorectal cancer. Ongoing studies are aimed at confirming that the molecular characterization of circulating tumor cells in peripheral blood and in bone marrow of patients is a powerful tool to improve the patient risk-stratification, to monitor activity of the drugs, to develop more appropriate targeted therapies and tailored treatments. In parallel, results from these correlative studies promise to gain a better biological understanding of the metastatic process. The clinical utility of the detection of circulating tumor cells in patients affected by colorectal cancer is still hampered by a number of specific hurdles. Improvement in sensitivity and specificity of the available methods of detection, standardization of these methods and functional characterization of circulating tumor cells in well designed and statistically well powered studies are the key steps to reach these ambitious objectives in colorectal cancer patients as well. Copyright © 2013 Elsevier Ltd. All rights reserved.
Landi, Stefano; Gemignani, Federica; Bottari, Fabio; Gioia-Patricola, Lydie; Guino, Elisabet; Cambray, María; Biondo, Sebastiano; Capella, Gabriel; Boldrini, Laura; Canzian, Federico; Moreno, Victor
Background Chronic inflammation is a risk factor for colorectal cancer and polymorphisms in the inflammatory genes could modulate the levels of inflammation. We have investigated ten single nucleotide polymorphisms (SNPs) in the following inflammation-related genes: TLR4 (Asp299Gly), CD14 (-260 T>C), MCP1 (-2518 A>G), IL12A (+7506 A>T, +8707 A>G, +9177 T>A, +9508 G>A), NOS2A (+524T>C), TNF (-857C>T), and PTGS1 (V444I) in 377 colorectal (CRC) cancer cases and 326 controls from Barcelona (Spain). Results There was no statistically significant association between the SNPs investigated and colorectal cancer risk. Conclusion The lack of association may show that the inflammatory genes selected for this study are not involved in the carcinogenic process of colorectum. Alternatively, the negative results may derive from no particular biological effect of the analysed polymorphisms in relation to CRC. Otherwise, the eventual biological effect is so little to go undetected, unless analysing a much larger sample size. PMID:17062130
Kostakis, Ioannis D; Agrogiannis, George; Vaiopoulos, Aristeidis G; Mylona, Eleni; Patsouris, Efstratios; Kouraklis, Gregory; Koutsilieris, Michael
Kisspeptins, the products of the KISS1 gene, are involved in cancer invasion, migration, metastasis and angiogenesis, while they induce apoptosis in various cancers. Herein, we studied KISS1 expression in colorectal cancer. We analyzed KISS1 expression using immunohistochemistry and image analysis in normal and malignant tissue samples from 60 patients with colorectal adenocarcinoma. The results correlated with various clinicopathological parameters. The expression of KISS1 was much higher in normal than in malignant colonic mucosa. However, among malignant tissues, KISS1 expression was higher in larger tumors (>4 cm) than in smaller ones (≤4 cm) and in stages III and IV than in stages I and II. In addition, it was higher in patients with lymph node metastases. Moreover, KISS1 levels in the normal mucosa and their difference from those in the malignant mucosa were higher in the right part of the large intestine than in the left one. KISS1 expression is reduced during the malignant transformation of the colonic mucosa and there is a difference in the expression pattern between the right and the left part of the large intestine. However, larger and advanced colorectal tumors express higher KISS1 levels than smaller and localized ones.
Budhathoki, Sanjeev; Joshi, Amit Man; Ohnaka, Keizo; Yin, Guang; Toyomura, Kengo; Kono, Suminori; Mibu, Ryuichi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji
It has been suggested that soy food and isoflavone intake may be protective against the risk of colorectal cancer. However, epidemiologic evidence remains sparse and inconsistent. We addressed this issue in the Fukuoka Colorectal Cancer Study. The study subjects were the 816 incident cases of histologically confirmed colorectal cancer and 815 community controls. Intakes of soy foods and isoflavones were assessed by in-person interview using a computer-assisted dietary method. Logistic regression analysis was applied to estimate odds ratio (OR) and 95% confidence interval (CI) of colorectal cancer with adjustment for dietary intakes of calcium and n-3 polyunsaturated fatty acids as well as for body mass index, physical activity, alcohol use, and other lifestyle factors. Energy-adjusted intakes of soy foods (dry weight) and isoflavones were inversely associated with colorectal cancer risk in men and postmenopausal women, but not in premenopausal women. The multivariate-adjusted OR for the highest versus lowest quintile was 0.65 (95% CI 0.41-1.03, p for trend = 0.03) for soy foods and 0.68 (95% CI 0.42-1.10, p for trend = 0.051) for isoflavones in men. The corresponding values for postmenopausal women were 0.60 (95% CI 0.29-1.25, p for trend = 0.053) and 0.68 (95% CI 0.33-1.40, p for trend = 0.049). The site-specific analysis showed inverse associations of soy foods (p for trend = 0.007) and isoflavones (p for trend = 0.02) with rectal cancer in men. The findings add to epidemiologic evidence for protective effects of soy foods and isoflavones in colorectal carcinogenesis.
Mazzolini, Guillermo; Murillo, Oihana; Atorrasagasti, Catalina; Dubrot, Juan; Tirapu, Iñigo; Rizzo, Miguel; Arina, Ainhoa; Alfaro, Carlos; Azpilicueta, Arantza; Berasain, Carmen; Perez-Gracia, José L; Gonzalez, Alvaro; Melero, Ignacio
Immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. Importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (IDO) by IFNγ in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma. PMID:17990348
Guo, Chunguang; Liu, Qian; Dai, Min
Colorectal cancer (CRC) is the fourth most common cause of cancer death in China and the incidence has been increasing during the decades. It is reported to take decades for adenoma to transform to carcinoma, which is known as the main CRC pre-cancer lesion. It is important to carry out mass screening in the average risk populations to find the pre-cancer lesion and early cancer, which was the key approach to improve CRC survival. Fecal occult blood test and flexible sigmoidoscopy are the two CRC screening methods, which have been shown to reduce CRC mortality. It still needs to be confirmed in random clinical trials that the value of colonoscopy in CRC screening. In China, the most CRC screening experience was drawn from the works in Zhejiang province in 1970s. Consequently, the Chinese CRC treatment and guideline was founded to provide standard for the CRC screening project.
Sameer, Aga Syed; Nissar, Saniya
Colorectal cancer (CRC) is a third most common epithelial carcinoma. CRC is known to develop from the early precancerous lesion to full blown malignancy via definite phases due to cumulative mutations and aberrant methylation of number of genes. The use of serum biomarkers that is non-invasive to discriminate cancer patients from healthy persons will prove to be an important tool to improve the early diagnosis of CRC. This will serve as the boon to the clinical management of the disease. PMID:27844020
Nayani, Rahul; Ashktorab, Hassan; Brim, Hassan; Laiyemo, Adeyinka O.
African Americans suffer the highest burden from colorectal cancer (CRC) in the USA. Studies have suggested that healthcare access and poorer utilization of preventive services may be playing more of a role in this disparity. However, African Americans also tend to develop CRC at younger ages and are more likely to have proximal cancers. This raises the possibility of higher genetic predisposition to CRC among African Americans and this has not been well studied. In this article, we reviewed possible genetic basis underpinning biological differences in CRC burden in the USA. PMID:26997937
Norton, Samuel E; Ward-Hartstonge, Kirsten A; Taylor, Edward S; Kemp, Roslyn A
The immune response to colorectal cancer has proven to be a reliable measure of patient outcome in several studies. However, the complexity of the immune response in this disease is not well understood, particularly the interactions between tumour-associated cells and cells of the innate and adaptive immune system. This review will discuss the relationship between cancer associated fibroblasts and macrophages, as well as between macrophages and T cells, and demonstrate how each population may support or prevent tumour growth in a different immune environment.
Brim, Hassan; Ashktorab, Hassan
Genome-wide studies are increasingly becoming a must, especially for complex diseases such as cancer where multiple genes and diverse molecular mechanisms are known to be involved in genes’ function alteration. In this review, we report our latest genomic and epigenomic findings in African-American colorectal cancer patients. This population suffers a higher burden of the disease and most investigators in this field are looking for the underlying genetic and epigenetic targets that might be responsible for this disparity. We here report genome-wide copy number variations, single nucleotide mutations and DNA methylation findings that might be specific to this population. PMID:27917406
DESCRIPTION (provided by applicant): Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain;numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. |
Brenner, H; Hoffmeister, M
Colorectal cancer (CRC) is the second most common cancer among both men and women in Germany. Owing to its relatively slow growth, perspectives for effective early detection are much better than for other forms of cancer. To summarize the evidence on effectiveness and cost-effectiveness of CRC screening, and to provide an overview on the current state and perspectives for effective CRC screening. Summary and critical review of evidence from randomized trials and observational epidemiological studies. A reduction in CRC mortality by offering annual fecal occult blood tests or once-only flexible sigmoidoscopy has been demonstrated in randomized trials. Novel fecal immunochemical tests for hemoglobin in stool have been shown to be more sensitive than traditional fecal occult blood tests and could substantially improve noninvasive CRC screening. Epidemiological studies suggest that the majority of CRC cases and deaths could be prevented by colonoscopy and removal of colorectal adenomas. However, adherence to screening offered outside organized screening programs is low. The National Cancer Plan recommends an organized CRC screening program in Germany. The law on the early detection of cancer from April 2013 has paved the way for its implementation. The great potential for CRC prevention by early detection has so far only been realized to a very limited extent in Germany. Introduction of an organized screening program and the offer of enhanced noninvasive screening tests could strongly enhance the utilization and effectiveness of CRC screening in Germany. The political frame has been set, and timely quality-assured implementation is required.
Patel, Sandip P; Osada, Takuya; Lyerly, H Kim; Morse, Michael A
Achieving long-term control of colorectal cancers with therapeutic vaccines that generate potent anti-tumor T cell and antibody responses has been a goal for more than two decades. To date, clinical trials of these vaccines have demonstrated induction of immune responses, but clinical benefit has been limited. Improved vector delivery systems with enhanced immunostimulatory properties, decreased immunogenicity against vector and improved antigen presentation are some of the key features of modern tumor vaccines. Furthermore, an improved understanding of the various immunosuppressive factors in the tumor microenvironment and regional lymph nodes, coupled with a burgeoning ability to impair inhibitory immune synapses, highlights a growing opportunity to induce beneficial antigen-specific responses against tumor. The combination of improved antigenic delivery systems, coupled with therapeutic immune activation, represents state-of-the-art colorectal vaccine design concepts with the goal of augmenting immune responses against tumor and improving clinical outcomes.
Coughlin, Steven S; Blumenthal, Daniel S; Seay, Shirley Jordan; Smith, Selina A
In the USA, race and socioeconomic status are well-known factors associated with colorectal cancer incidence and mortality rates. These are higher among blacks than whites and other racial/ethnic groups. In this article, we review opportunities to address disparities in colorectal cancer incidence, mortality, and survivorship among African Americans. First, we summarize the primary prevention of colorectal cancer and recent advances in the early detection of the disease and disparities in screening. Then, we consider black-white disparities in colorectal cancer treatment and survival including factors that may contribute to such disparities and the important roles played by cultural competency, patient trust in one's physician, and health literacy in addressing colorectal cancer disparities, including the need for studies involving the use of colorectal cancer patient navigators who are culturally competent. To reduce these disparities, intervention efforts should focus on providing high-quality screening and treatment for colorectal cancer and on educating African Americans about the value of diet, weight control, screening, and treatment. Organized approaches for delivering colorectal cancer screening should be accompanied by programs and policies that provide access to diagnostic follow-up and treatment for underserved populations.
Blumenthal, Daniel S.; Seay, Shirley Jordan; Smith, Selina A.
Background In the USA, race and socioeconomic status are well-known factors associated with colorectal cancer incidence and mortality rates. These are higher among blacks than whites and other racial/ethnic groups. Methods In this article, we review opportunities to address disparities in colorectal cancer incidence, mortality, and survivorship among African Americans. Results First, we summarize the primary prevention of colorectal cancer and recent advances in the early detection of the disease and disparities in screening. Then, we consider black-white disparities in colorectal cancer treatment and survival including factors that may contribute to such disparities and the important roles played by cultural competency, patient trust in one’s physician, and health literacy in addressing colorectal cancer disparities, including the need for studies involving the use of colorectal cancer patient navigators who are culturally competent. Conclusion To reduce these disparities, intervention efforts should focus on providing high-quality screening and treatment for colorectal cancer and on educating African Americans about the value of diet, weight control, screening, and treatment. Organized approaches for delivering colorectal cancer screening should be accompanied by programs and policies that provide access to diagnostic follow-up and treatment for underserved populations. PMID:27294749
Fei, Weiqiang; Liu, Shuiping; Hu, Xiaotong
The human FAD-dependent oxidoreductase domain containing 1 (FOXRED1) protein is reported as an assembly factor which promotes the correct assembly and stability of mitochondrial Complex I (CI). Alterations of mitochondrial CI might cause tumorigenesis and metastasis, but it’s molecular mechanisms remain unclear. In this study, we selected 145 cases of colorectal cancer for immunohistochemistry to explore the role of FOXRED1 played in the tumor progression of colorectal cancer. The relationship between FOXRED1 expression and clinicopathological features of colorectal cancers was evaluated. FOXRED1 mainly localized in the cytoplasm in the colorectal cancer tissues, and had significant association with histopathological grading, depth of invasion, lymph node metastasis, distant metastasis and TNM stage (P<0.05 for each). However, age, gender and tumor location was not found to be associated with FOXRED1 expression. Colorectal cancer patients with higher expression of FOXRED1 had the higher 3 year survival rate (P=0.003). Moreover, FOXRED1 had potentiality to be an independent prognostic factor for survival in colorectal cancer (P=0.04). Low FOXRED1 expression correlated with poor prognosis of colorectal cancer and targeting this molecular will be a potential treatment strategy for colorectal cancer. PMID:27904784
Mulcahy, Hugh E; Hyland, John; O'Donoghue, Diarmuid P
The roots of colorectal cancer date back to antiquity. In this short history of colorectal cancer we trace its clinical and research origins from ancient times through the dark ages, middle ages, to the scientific and medical advances of the seventeenth to twentieth centuries and into the twenty-first century.
Enstrom, J. E.
Secular, socioeconomic and urban-rural gradients and geographical differences in beef and fat consumption within the United States of America are compared with corresponding data on colorectal cancer incidence and mortality rates. These results, together with the results of most previous epidemiological studies, appear to contradict the hypothesis that beef and fat consumption are involved in the aetiology of colorectal cancer. PMID:1212410
Study finds that flexible sigmoidoscopy is effective in reducing the rates of new cases and deaths due to colorectal cancer. Researchers found that overall colorectal cancer mortality was reduced by 26 percent and incidence was reduced by 21 percent as a
Zheng, Yu-Fang; Yang, Jun; Zhao, Xin-Jie; Feng, Bo; Kong, Hong-Wei; Chen, Ying-Jie; Lv, Shen; Zheng, Min-Hua; Xu, Guo-Wang
AIM: Fourteen urinary nucleosides, primary degradation products of tRNA, were evaluated to know the potential as biological markers for patients with colorectal cancer. METHODS: The concentrations of 14 kinds of urinary nucleosides from 52 patients with colorectal cancer, 10 patients with intestinal villous adenoma and 60 healthy adults were determined by column switching high performance liquid chromatography method. RESULTS: The mean levels of 12 kinds of urinary nucleosides (except uridine and guanosine) in the patients with colorectal cancer were significantly higher than those in patients with intestinal villous adenoma or the healthy adults. Using the levels of 14 kinds of urinary nucleosides as the data vectors for principal component analysis, 71% (37/52) patients with colorectal cancer were correctly classified from healthy adults, in which the identification rate was much higher than that of CEA method (29%). Only 10% (1/10) of patients with intestinal villous adenoma were indistinguishable from patients with colorectal cancer. The levels of m1G, Pseu and m1A were positively related with tumor size and Duke’s stages of colorectal cancer. When monitoring the changes in urinary nucleoside concentrations of patients with colorectal cancer associated with surgery, it was found that the overall correlations with clinical assessment were 84% (27/32) and 91% (10/11) in response group and progressive group, respectively. CONCLUSION: These findings indicate that urinary nucleosides determined by column switching high performance liquid chromatography method may be useful as biological markers for colorectal cancer. PMID:15991285
Vinson, Kaitlyn E; George, Dennis C; Fender, Alexander W; Bertrand, Fred E; Sigounas, George
Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. It is also the third most common cancer diagnosis among men, and the second most common cancer diagnosis among women. Globally, CRC can account for nearly 694,000 annual deaths. It is widely appreciated that CRC is the result of dysregulated cellular pathways that promote an inappropriate stem-cell-like phenotype, apoptotic resistance, unchecked proliferation and metastatic spread. While no single pathway is responsible for all of these attributes, an array of recent studies suggests a pivotal role for abnormal Notch-1 signaling in CRC, in part due to interconnectivity of Notch with other pathways. This review will summarize recent evidence for a role of Notch signaling in CRC, will consider interconnectivity between Notch and other pathways involved in CRC and will discuss the possible utility of targeting Notch as a CRC therapeutic.
Spiegelman, D; Wegman, D H
Several population data bases were used to generate hypotheses about associations between colorectal cancer and workplace exposures. The Third National Cancer Survey interview sample was used to select 343 male and 208 female cases and 626 male and 1,235 female cancer controls. Potential work exposures were assigned with the use of data from the National Institute for Occupational Safety and Health National Occupational Hazard Survey. Dietary factors were modeled from the National Health and Nutrition Examination Survey data. Work-related stress was considered with the use of a model based on the U.S. Department of Labor's Quality of Employment Survey. Other risk factors included age, race, ponderosity, and menopausal status. Logistic analysis yielded hypotheses for colon cancer risk in males with potentially high exposure to solvents, abrasives, and fuel oil and in those in jobs with high demand and low control (high "stress"). Hypotheses emerged for females with potentially high exposure to dyes, solvents, and grinding wheel dust.
Auman, J Todd; McLeod, Howard L
Clinically and histopathologically similar colorectal cancers exhibit considerable variability in their responses to chemotherapeutics. The advent of genomic technologies has enabled the unbiased determination of changes in DNA and RNA, alterations that may be responsible for, or predictive of the variability in response to chemotherapy. This review highlights several advances made in applying genomic tools toward colorectal cancer therapeutics. Progress has been made using gene expression profiling to identify which colorectal cancer patients would benefit most from adjuvant chemotherapy. In addition, advances have been made in colorectal cancer pharmacogenomics by identifying gene expression patterns associated with sensitivity to specific chemotherapeutic agents. Lastly, the use of genome-wide mutation screening of individual tumor samples to identify the profiles of mutated genes is explored. Future research toward integrating genomic information with clinical and histopathological data is expected to lead to improved therapeutic management of colorectal cancer.
Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang
Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal. The elucidation of the molecular mechanisms behind self-renewal may lead to the development of novel targeted interventions for the treatment of colorectal cancer. PMID:27909729
Bretagne, Jean-François; Manfredi, Sylvain; Heresbach, Denis
Hemoccult II is the only method of screening for colorectal cancer whose effectiveness in reducing specific mortality has been proved by randomized controlled trials. The first experience of French districts based on this strategy reproduced on a population scale the results of the experimental studies. Expanding screening in France to the general public is a public health priority. Large-scale media campaigns, which currently do not exist, could then be launched, and prevention opportunities seized. Immunological tests identifying the presence of blood in the stool have better sensitivity than the guaiac smear tests, especially for the diagnosis of adenomas and to a lesser extent, for that of cancers as a whole. These tests may constitute an alternative to guaiac tests, but are more expensive. Total colonoscopy, proposed every 10 years from the age of 50 years or once in a lifetime around the age of 60 years, is not a realistic method because of its cost and its risks. Sigmoidoscopies are under evaluation in several countries in randomized controlled trials but do not seem appropriate to either the epidemiologic trends of colorectal cancer or to the practice of endoscopy in France. Virtual colonoscopy is an attractive alternative to searching for blood in stool. The evaluation now underway should not interfere with the broad expansion of methods of proven efficacy. Virtual colonoscopy may face competition from numerous emerging techniques of endoscopic exploration of the colon, including the video-capsule. To obtain widespread participation in colorectal cancer screening, policy-makers must take the opinions of healthcare professionals and of the public into account. The medicoeconomic data will be a decisive factor in the choice between these new strategies.
Choi, Yun-Hee; Cotterchio, Michelle; McKeown-Eyssen, Gail; Neerav, Monga; Bapat, Bharati; Boyd, Kevin; Gallinger, Steven; McLaughlin, John; Aronson, Melyssa; Briollais, Laurent
Background Several DNA mismatch repair (MMR) genes, responsible for the majority of Lynch Syndrome cancers, have been identified, predominantly MLH1 and MSH2, but the risk associated with these mutations is still not well established. The aim of this study is to provide population-based estimates of the risks of colorectal cancer (CRC) by gender and mutation type from the Ontario population. Methods We analyzed 32 families segregating MMR mutations selected from the Ontario Familial Colorectal Cancer Registry and including 199 first-degree and 421 second-degree relatives. The cumulative risks were estimated using a modified segregation-based approach, which allows correction for the ascertainment of the Lynch Syndrome families and permits account to be taken for missing genotype information. Results The risks of developing CRC by age 70 were 60% and 47% among men and women carriers of any MMR mutation, respectively. Among MLH1 mutation carriers, males had significantly higher risks than females at all ages (67% vs. 35% by age 70, p-value = 0.02), while the risks were similar in MSH2 carriers (about 54%). The relative risk associated with MLH1 was almost constant with age (hazard ratio (HR) varied between 5.5-5.1 over age 30–70), while the HR for MSH2 decreased with age (from 13.1 at age 30 to 5.4 at age 70). Conclusion This study provides a unique population-based study of CRC risks among MSH2/MLH1 mutation carriers in a Canadian population and can help to better define and understand the patterns of risks among members of Lynch Syndrome families. PMID:19698169
Helewa, Ramzi M; Turner, Donna; Wirtzfeld, Debrah; Park, Jason; Hochman, David; Czaykowski, Piotr; Singh, Harminder; Shu, Emma; Xue, Lin; McKay, Andrew
The Canadian province of Manitoba covers a large geographical area but only has one major urban center, Winnipeg. We sought to determine if regional differences existed in the quality of colorectal cancer care in a publicly funded health care system. This was a population-based historical cohort analysis of the treatment and outcomes of Manitobans diagnosed with colorectal cancer between 2004 and 2006. Administrative databases were utilized to assess quality of care using published quality indicators. A total of 2,086 patients were diagnosed with stage I to IV colorectal cancer and 42.2% lived outside of Winnipeg. Patients from North Manitoba had a lower odds of undergoing major surgery after controlling for other confounders (odds ratio (OR): 0.48, 95% confidence interval (CI): 0.26 to 0.90). No geographic differences existed in the quality measures of 30-day operative mortality, consultations with oncologists, surveillance colonoscopy, and 5-year survival. However, there was a trend towards lower survival in North Manitoba. We found minimal differences by geography. However, overall compliance with quality measures is low and there are concerning trends in North Manitoba. This study is one of the few to evaluate population-based benchmarks for colorectal cancer therapy in Canada.
Sozucan, Y; Kalender, M E; Sari, I; Suner, A; Oztuzcu, S; Arman, K; Yumrutas, O; Bozgeyik, I; Cengiz, B; Igci, Y Z; Balakan, O; Camci, C
Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. Different factors are responsible for the development of CRC. Transient Receptor Potential (TRP) which is an important component of calcium channel is associated with several pathological conditions like cancer, neurodegenerative and cardiovascular diseases. Thirty members of the family of TRP ion channel in mammals have been determined till now. The aim of this study is to investigate TRPM, TRPV and TRPC gene expression levels in tumor tissues of CRC patients and to analyze the relationship of expression in tumor tissue of CRC with other known prognostic factors. In this study, 93 CRC patients were included. The level of TRP gene expression in paraffin blocks of normal and cancerous colorectal tissue samples were studied at the level of mRNA with Real-time PCR. The mRNA expression level of TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 genes in 37 female and 56 male patients diagnosed with CRC was revealed lower in tumor tissue as compared to normal tissue (p < 0.05). No statistically significant differences of mRNA expression levels of other TRP genes were found. TRP gene family like TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 may be thought as potential genes contributing to tumorigenesis as their expression decreases in CRC as compared to normal tissues.
Boyle, T; Fritschi, L; Platell, C; Heyworth, J
Background: Aside from tumour stage and treatment, little is known about potential factors that may influence survival in colorectal cancer patients. The aim of this study was to investigate the associations between physical activity, obesity and smoking and disease-specific and overall mortality after a colorectal cancer diagnosis. Methods: A cohort of 879 colorectal cancer patients, diagnosed in Western Australia between 2005 and 2007, were followed up to 30 June 2012. Cox's regression models were used to estimate the hazard ratios (HR) for colorectal cancer-specific and overall mortality associated with self-reported pre-diagnosis physical activity, body mass index (BMI) and smoking. Results: Significantly lower overall and colorectal cancer-specific mortality was seen in females who reported any level of recent physical activity than in females reporting no activity. The colorectal cancer-specific mortality HR for increasing levels of physical activity in females were 0.34 (95% CI=0.15, 0.75), 0.37 (95% CI=0.17, 0.81) and 0.41 (95% CI=0.18, 0.90). Overweight and obese women had almost twice the risk of dying from any cause or colorectal cancer compared with women of normal weight. Females who were current smokers had worse overall and colorectal cancer-specific mortality than never smokers (overall HR=2.64, 95% CI=1.18, 5.93; colorectal cancer-specific HR=2.70, 95% CI=1.16, 6.29). No significant associations were found in males. Conclusion: Physical activity, BMI and smoking may influence survival after a diagnosis of colorectal cancer, with more pronounced results found for females than for males. PMID:23787918
Established in 1995, the Hereditary Gastrointestinal Cancer Registry aimed at cancer prevention due to hereditary colorectal cancer syndromes in Hong Kong through early detection, timely treatment, education and ongoing research. This article details the history, structure and work of the Registry. A summary is also provided on the results of various research work conducted by the Registry which facilitates the clinical management of hereditary colorectal cancer syndromes in Hong Kong Chinese families. PMID:20223041
The SCAN colorectal cancer systemic therapy workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for colorectal cancer in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated-those developed by the National Comprehensive Cancer Network for colon (2014) and rectal (2014) cancer, the European Society of Medical Oncology for advanced (2012) and early (2013) cancer and the National Institute of Clinical Excellence (2011). Recommendations on systemic therapy in colorectal cancer were produced. These adapted guidelines form the SCAN Guidelines 2015 for systemic therapy of colorectal cancer.
Fidler, Miranda M; Bray, Freddie; Vaccarella, Salvatore; Soerjomataram, Isabelle
Colorectal cancer incidence has paralleled increases in human development across most countries. Yet, marked decreases in incidence are now observed in countries that have attained very high human development. Thus, in this study, we explored the relationship between human development and colorectal cancer incidence, and in particular assessed whether national transitions to very high human development are linked to temporal patterns in colorectal cancer incidence. For these analyses, we utilized the Human Development Index (HDI) and annual incidence data from regional and national cancer registries. Truncated (30-74 years) age-standardized incidence rates were calculated. Yearly incidence rate ratios and HDI ratios, before and after transitioning to very high human development, were also estimated. Among the 29 countries investigated, colorectal cancer incidence was observed to decrease after reaching the very high human development threshold for 12 countries; decreases were also observed in a further five countries, but the age-standardized incidence rates remained higher than that observed at the threshold. Such declines or stabilizations are likely due to colorectal cancer screening in some populations, as well as varying levels of exposure to protective factors. In summary, it appears that there is a threshold at which human development predicts a stabilization or decline in colorectal cancer incidence, though this pattern was not observed for all countries assessed. Future cancer planning must consider the increasing colorectal cancer burden expected in countries transitioning towards higher levels of human development, as well as possible declines in incidence among countries reaching the highest development level. © 2017 UICC.
Harbaum, Lars; Pollheimer, Marion J; Kornprat, Peter; Lindtner, Richard A; Bokemeyer, Carsten; Langner, Cord
In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; P<0.001) and with the intensity of the overall inflammatory cell reaction (R=0.318; P<0.001). Both increasing peri- and intratumoral eosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58-0.98; P=0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52-0.93; P=0.01)-independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients
Ge, Yaorong; Vining, David J.; Ahn, David K.; Stelts, David R.
Early detection and removal of colorectal polyps have been proven to reduce mortality from colorectal carcinoma (CRC), the second leading cause of cancer deaths in the United States. Unfortunately, traditional techniques for CRC examination (i.e., barium enema, sigmoidoscopy, and colonoscopy) are unsuitable for mass screening because of either low accuracy or poor public acceptance, costs, and risks. Virtual colonoscopy (VC) is a minimally invasive alternative that is based on tomographic scanning of the colon. After a patient's bowel is optimally cleansed and distended with gas, a fast tomographic scan, typically helical computed tomography (CT), of the abdomen is performed during a single breath-hold acquisition. Two-dimensional (2D) slices and three-dimensional (3D) rendered views of the colon lumen generated from the tomographic data are then examined for colorectal polyps. Recent clinical studies conducted at several institutions including ours have shown great potential for this technology to be an effective CRC screening tool. In this paper, we describe new methods to improve bowel preparation, colon lumen visualization, colon segmentation, and polyp detection. Our initial results show that VC with the new bowel preparation and imaging protocol is capable of achieving accuracy comparable to conventional colonoscopy and our new algorithms for image analysis contribute to increased accuracy and efficiency in VC examinations.
Muzaffar, Mahvish; Irlam, John; Mohamed, Iman
Recent research has provided compelling evidence that a subset of hyperplastic polyps may be associated with a risk of colorectal cancer. Colorectal cancer with extracolonic manifestation is usually seen in a hereditary syndrome setting, but some association with meningioma has been reported. The association of colorectal cancer with hyperplastic polyposis and meningioma is extremely rare. This report in a 57-year-old female with no family history of colon cancer or polyps, could be the first case of hyperplastic polyposis syndrome, colorectal cancer and meningioma. Hyperplastic polyposis syndrome was diagnosed as per WHO criteria at the time of colon cancer diagnosis. Within 4 months of colon cancer diagnosis she developed seizures. Imaging of the brain revealed meningioma of the left cerebellopontine angle. The patient underwent surgery followed by chemotherapy.
Fletcher, Robert H; Colditz, Graham A; Pawlson, L Greg; Richman, Howard; Rosenthal, David; Salber, Patricia R
Colorectal cancer screening is advocated by expert groups based on strong evidence of effectiveness, yet only approximately 1 in 3 Americans are screened. For a screening program to be effective, it is necessary for providers to offer and patients to accept screening, insurers to pay for screening, and provider groups to have monitoring and reminder systems and the expertise and facilities to perform the tests well. Whether and when such screening programs become successful depends on the priorities of healthcare decision makers as much as on the efforts of individual physicians and patients. There are strong arguments for decision makers giving colorectal cancer screening programs high priority: it saves as many lives as other services now in common use; it is a good use of scarce resources, costing less than $20,000 per year of life saved; and members of insurance programs increasingly expect screening benefits and programs, and failure to offer them might lead to member dissatisfaction and malpractice claims. Screening is costly, however, taking into account the cost of screening, follow-up tests, and treatments, and the costs occur many years before the benefits. Programs that are promoted to members but not fully implemented could create disappointment and backlash. Also, this screening can cause medical complications. Nevertheless, successful programs have been developed, proving that they are feasible in today's cost-conscious environment. We believe that colorectal cancer screening programs are integral to any organization purporting to provide high-quality care. Organizations without such programs should give them high priority for implementation.
Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7
Patai, Árpád V; Molnár, Béla; Tulassay, Zsolt; Sipos, Ferenc
Serrated polyps have been an area of intense focus for gastroenterologists over the past several years. Contrary to what was thought before, a growing body of literature indicates that these polyps can be precursors of colorectal cancer (CRC). Most of these lesions, particularly those in the proximal colon, have so far been under-recognized and missed during colonoscopy, qualifying these lesions to be the main cause of interval cancers. It is estimated that 10%-20% of CRCs evolve through this alternative, serrated pathway, with a distinct genetic and epigenetic profile. Aberrant DNA methylation plays a central role in the development of this CRC subtype. This characteristic molecular background is reflected in a unique pathological and clinical manifestation different from cancers arising via the traditional pathway. In this review we would like to highlight morphological, molecular and clinical features of this emerging pathway that are essential for gastroenterologists and may influence their everyday practice. PMID:23431044
Johnston, S J; Ridge, S A; Cassidy, J; McLeod, H L
Dihydropyrimidine dehydrogenase (DPD) is responsible for degradation of the pyrimidines uracil and thymine and the inactivation of the chemotherapeutic agent 5-fluorouracil. DPD activity is highly variable in cancer populations, and this variation may influence the antitumor efficacy of 5-fluorouracil. However, little is known about the regulation of DPD mRNA expression in any tissues. Using a reverse transcription competitive PCR assay, we quantified DPD mRNA levels in 10 matched colorectal tumors and adjacent normal mucosae and 7 colorectal liver metastases and adjacent normal livers. Lower levels of DPD mRNA expression were observed in colorectal tumor compared with adjacent normal colon mucosa (median, 0.01 versus 0.37 amole/microg total RNA, P = 0.02). DPD mRNA expression was also lower in metastases than adjacent normal liver tissue (median, 0.11 versus 1.17 amole/microg total RNA, P = 0.001). DPD mRNA expression was higher in normal liver than normal colonic mucosa (median, 1.17 versus 0.37 amole/microg total RNA, P = 0.02). A significant relationship was observed between DPD mRNA and catalytic activity (r(s) = 0.66, P<0.001). The tumor:normal ratio for DPD mRNA, protein, and activity was relatively stable in liver (0.25, 0.55, and 0.51, respectively) but varied considerably in colon (0.085, 0.9, and 1.25, respectively), consistent with enhanced translation of DPD transcript in primary colorectal tumor. This suggests that DPD can be regulated at the levels of both transcription and translation.
Hubbard, Joleen M
Treatment for colorectal cancer should not be based on age alone. Pooled analyses from clinical trials show that fit older adults are able to tolerate treatment well with similar efficacy as younger adults. When an older adult is considered for treatment, the clinical encounter must evaluate for deficits in physical and cognitive function, and assess comorbidities, medications, and the degree of social support, all which have may affect tolerance of treatment. Based on the degree of fitness of the patient, multiple alternatives to aggressive treatment regimens and strategies exist to minimize toxicity and preserve quality of life during treatment.
Palmieri, Valentina; Lucchetti, Donatella; Maiorana, Alessandro; Papi, Massimiliano; Maulucci, Giuseppe; Ciasca, Gabriele; Svelto, Maria; De Spirito, Marco; Sgambato, Alessandro
The nanomechanical properties of SW480 colon cancer cells were investigated using Atomic Force Microscopy. SW480 cells are composed of two sub-populations with different shape and invasiveness. These two cells populations showed similar adhesion properties while appeared significantly different in term of cells stiffness. Since cell stiffness is related to invasiveness and growth, we suggest elasticity as a useful parameter to distinguish invasive cells inside the colorectal tumor bulk and the high-resolution mechanical mapping as a promising diagnostic tool for the identification of malignant cells.
Yang, Meng; Hu, Frank B.; Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.; Fuchs, Charles S.; Wu, Kana; Bao, Ying
Background/Objectives Increasing nut consumption has been associated with reduced risk of obesity and type II diabetes, which are risk factors for colorectal cancer. However, the association between nut consumption and colorectal cancer risk is unclear. We aimed to examine the association of long-term nut consumption with risk of colorectal cancer. Subjects/Methods We prospectively followed 75,680 women who were free of cancer at baseline in the Nurses’ Health Study, and examined the association between nut consumption and colorectal cancer risk. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Results During 2,103,037 person-years of follow-up, we identified 1,503 colorectal cancer cases. After adjustment for other known or suspected risk factors, women who consumed nuts 2 or more times per week (i.e., ≥56 grams per week) had a 13% lower risk of colorectal cancer compared to those who rarely consumed nuts, but the association was not statistically significant (RR: 0.87; 95% CI: 0.72, 1.05; P trend: 0.06). No association was observed for peanut butter. Conclusions In this large prospective cohort of women, frequent nut consumption was not significantly associated with colorectal cancer risk after adjusting for other risk factors. PMID:25944181
Takahashi, Kazuto; Hosokawa, Masashi; Kasajima, Hiroyuki; Hatanaka, Kazuteru; Kudo, Kazuhiro; Shimoyama, Norihiko; Miyashita, Kazuo
Colorectal cancer is one of the most malignant neoplasms worldwide. Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. In the present study, the anticancer effects of fucoxanthin and its metabolite, fucoxanthinol, on 6 colorectal cancer cell lines and 20 tissue samples from surgically resected clinical colorectal cancer specimens were examined using a collagen-gel droplet embedded culture drug sensitivity test (CD-DST). The in vitro sensitivity to fucoxanthin, fucoxanthinol and the anticancer drugs is expressed as T/C (%), where T is the absorbance of cells which stained by neutral red treated with carotenoids and C is the absorbance of non-staining cells. Fucoxanthin and fucoxanthinol decreased the T/C (%) of Caco-2, WiDr, HCT116, and DLD-1 cell lines at doses of 20 µM. Fucoxanthinol also decreased the T/C (%) of SW620 cells, while the T/C (%) of Colo205 cells was not reduced by treatment with either carotenoid. Specifically, the T/C (%) of Caco-2 and WiDr cells, which were incubated in carotenoid-free medium for 6 days following treatment with 20 µM fucoxanthinol for 24 h, was markedly decreased to 1.4±0.2 and 12.0±0.3%, respectively. Furthermore, fucoxanthin and fucoxanthinol decreased the T/C (%) in colorectal cancer tissue samples. Notably, 20 µM fucoxanthinol treatment resulted in a higher proportion of colorectal cancer samples with a T/C (%) of <50% (13/20, 65%) compared with samples treated with 20 µM fucoxanthin (2/20, 10%). The median T/C (%) value of 35.1% for the 20 cancers specimens treated with 20 µM fucoxanthinol was lower than the median T/C (%) values of 86.3% and 75.8% for those treated with fluorouracil and paclitaxel, respectively. These results suggested that fucoxanthin and fucoxanthinol may be of use as chemotherapeutic agents in colorectal cancer.
Levi, F; Pasche, C; La Vecchia, C; Lucchini, F; Franceschi, S
Most studies of diet and colorectal cancer have considered nutrients and micronutrients, but the role of foods or food groups remains open to debate. To elucidate the issue, we examined data from a case–control study conducted between 1992 and 1997 in the Swiss canton of Vaud. Cases were 223 patients (142 men, 81 women) with incident, histologically confirmed colon (n = 119) or rectal (n = 104) cancer (median age 63 years), linked with the Cancer Registry of the Swiss Canton of Vaud, and controls were 491 subjects (211 men, 280 women, median age 58 years) admitted to the same university hospital for a wide spectrum of acute non-neoplastic conditions unrelated to long-term modifications of diet. Odds ratios (OR) were obtained after allowance for age, sex, education, smoking, alcohol, body mass index, physical activity and total energy intake. Significant associations were observed for refined grain (OR = 1.32 for an increase of one serving per day), and red meat (OR = 1.54), pork and processed meat (OR = 1.27), alcohol (OR = 1.28), and significant protections for whole grain (OR = 0.85), raw (OR = 0.85) and cooked vegetables (OR = 0.69), citrus (OR = 0.86) and other fruits (OR = 0.85), and for coffee (OR = 0.73). Garlic was also protective (OR = 0.32 for the highest tertile of intake). These findings in a central European population support the hypothesis that a diet rich in refined grains and red meat increases the risk of colorectal cancer; they, therefore, support the recommendation to substitute whole grains for refined grain, to limit meat intake, and to increase fruit and vegetable consumption. © 1999 Cancer Research Campaign PMID:10098773
Ho, Gloria Y F; Wang, Tao; Gunter, Marc J; Strickler, Howard D; Cushman, Mary; Kaplan, Robert C; Wassertheil-Smoller, Sylvia; Xue, Xiaonan; Rajpathak, Swapnil N; Chlebowski, Rowan T; Vitolins, Mara Z; Scherer, Philipp E; Rohan, Thomas E
Mechanistic associations between obesity and colorectal cancer remain unclear. In this study, we investigated whether adipokines are risk factors for colorectal cancer and whether they may mediate its association with obesity. In a case-cohort study nested within the Women's Health Initiative cohort of postmenopausal women, baseline plasma samples from 457 colorectal cancer cases and 841 subcohort subjects were assayed for seven adipokines-adiponectin, leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, hepatocyte growth factor, interleukin-6 (IL-6), and TNF-α. Serum insulin and estradiol values measured previously were also available for data analysis. After adjusting for age, race, smoking, colonoscopy history, and estrogen level, a low level of anti-inflammatory adiponectin and high levels of proinflammatory leptin, PAI-1, and IL-6 were associated with increased colorectal cancer risk, though only leptin remained significant after further adjustment for insulin [HRs comparing extreme quartiles (HR(Q4-Q1)), 1.84; 95% CI, 1.17-2.90]. Mediation analyses showed that leptin and insulin partially explained the association between waist circumference and colorectal cancer and attenuated it by 25% and 37%, respectively, with insulin being a significant mediator (P = 0.041). Our findings support the conclusion that adipokines involved in inflammation are associated with colorectal cancer risk, but that their effects may be mediated mostly by insulin, with leptin exerting an independent effect. Hyperinsulinemia and hyperleptinemia may therefore partially explain the adiposity association with colorectal cancer in postmenopausal women.
Yu, TaChung; Guo, Fangfang; Yu, Yanan; Sun, Tiantian; Ma, Dan; Han, Jixuan; Qian, Yun; Kryczek, Ilona; Sun, Danfeng; Nagarsheth, Nisha; Chen, Yingxuan; Chen, Haoyan; Hong, Jie; Zou, Weiping; Fang, Jing-Yuan
Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, microRNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.
Ho, Gloria Y.F.; Wang, Tao; Gunter, Marc J.; Strickler, Howard D.; Cushman, Mary; Kaplan, Robert C.; Wassertheil-Smoller, Sylvia; Xue, Xiaonan; Rajpathak, Swapnil N.; Chlebowski, Rowan T.; Vitolins, Mara Z.; Scherer, Philipp E.; Rohan, Thomas E.
Mechanistic associations between obesity and colorectal cancer remain unclear. In this study, we investigated whether adipokines are risk factors for colorectal cancer and whether they may mediate its association with obesity. In a case–cohort study nested within the Women’s Health Initiative cohort of postmenopausal women, baseline plasma samples from 457 colorectal cancer cases and 841 subcohort subjects were assayed for seven adipokines—adiponectin, leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, hepatocyte growth factor, interleukin-6 (IL-6), and TNF-α. Serum insulin and estradiol values measured previously were also available for data analysis. After adjusting for age, race, smoking, colonoscopy history, and estrogen level, a low level of antiinflammatory adiponectin and high levels of proinflammatory leptin, PAI-1, and IL-6 were associated with increased colorectal cancer risk, though only leptin remained significant after further adjustment for insulin [HRs comparing extreme quartiles (HRQ4–Q1), 1.84; 95% CI, 1.17–2.90]. Mediation analyses showed that leptin and insulin partially explained the association between waist circumference and colorectal cancer and attenuated it by 25% and 37%, respectively, with insulin being a significant mediator (P = 0.041). Our findings support the conclusion that adipokines involved in inflammation are associated with colorectal cancer risk, but that their effects may be mediated mostly by insulin, with leptin exerting an independent effect. Hyperinsulinemia and hyperleptinemia may therefore partially explain the adiposity association with colorectal cancer in postmenopausal women. PMID:22511581
Feng, Zhe; Chen, Ji-Wei; Feng, Jian-Hua; Shen, Fei; Cai, Wen-Song; Cao, Jie; Xu, Bo
There are conflicting reports on the correlation between serum levels of ferritin with colorectal cancer. The purpose of the present study is to clarify the association between serum ferritin with colorectal cancer using a meta-analysis approach. We searched articles indexed in Pubmed published as of July 2015 that met our predefined criteria. Six eligible articles involving 927 subjects were identified. Overall, pooled analysis indicated that subjects with colorectal cancer had lower serum level of ferritin than the healthy controls (SMD=-1.569, 95% CI=[-2.718, -0.420], P= 0.007). Further subgroup analysis found lower serum level of ferritin among patients with colorectal cancer in eastern country (SMD=-1.956, 95% CI=[-3.750, -0.162], P=0.033), but not in western country (SMD=-1.285, 95% CI=[-2.778, 0.207], P=0.091). In conclusion, this meta-analysis supports a significant association between serum ferritin with colorectal cancer. However, the subgroup analysis found that there was significant effect modification of ferritin level by ethnic. Thus this finding needs further confirmation by trans-regional multicenter, long-term observation in a cohort design to obtain better understanding of causal relationships between serum ferrintin levels and colorectal cancer, through measuring ferritin at baseline to investigate whether the highest ferritin category versus lowest is associated with colorectal cancer risk.
The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.
The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.
Woo, Hae Dong; Kim, Jeongseon
Stomach and colorectal cancers are common cancers and leading causes of cancer deaths. Because the alimentary tract can interact directly with dietary components, stomach and colorectal cancer may be closely related to dietary intake. We systematically searched published literature written in English via PubMed by searching for terms related to stomach and colorectal cancer risk and dietary flavonoids up to June 30, 2012. Twenty-three studies out of 209 identified articles were finally selected for the analysis. Log point effect estimates and the corresponding standard errors were calculated using covariate-adjusted point effect estimates and 95%CIs from the selected studies. Total dietary flavonoid intake was not associated with a reduced risk of colorectal or stomach cancer [odds ratio (OR) (95%CI) = 1.00 (0.90-1.11) and 1.07 (0.70-1.61), respectively]. Among flavonoid subclasses, the intake of flavonols, flavan-3-ols, anthocyanidins, and proanthocyanidins showed a significant inverse association with colorectal cancer risk [OR (95%CI) = 0.71 (0.63-0.81), 0.88 (0.79-0.97), 0.68 (0.56-0.82), and 0.72 (0.61-0.85), respectively]. A significant association was found only between flavonols and stomach cancer risk based on a limited number of selected studies [OR (95%CI) = 0.68 (0.46-0.99)]. In the summary estimates from case-control studies, all flavonoid subclasses except flavones and flavanones were inversely associated with colorectal cancer risk, whereas neither total flavonoids nor any subclasses of flavonoids were associated with colorectal cancer risk in the summary estimates based on the cohort studies. The significant association between flavonoid subclasses and cancer risk might be closely related to bias derived from the case-control design. There was no clear evidence that dietary flavonoids are associated with reduced risk of stomach and colorectal cancer. PMID:23467443
Woo, Hae Dong; Kim, Jeongseon
Stomach and colorectal cancers are common cancers and leading causes of cancer deaths. Because the alimentary tract can interact directly with dietary components, stomach and colorectal cancer may be closely related to dietary intake. We systematically searched published literature written in English via PubMed by searching for terms related to stomach and colorectal cancer risk and dietary flavonoids up to June 30, 2012. Twenty-three studies out of 209 identified articles were finally selected for the analysis. Log point effect estimates and the corresponding standard errors were calculated using covariate-adjusted point effect estimates and 95%CIs from the selected studies. Total dietary flavonoid intake was not associated with a reduced risk of colorectal or stomach cancer [odds ratio (OR) (95%CI) = 1.00 (0.90-1.11) and 1.07 (0.70-1.61), respectively]. Among flavonoid subclasses, the intake of flavonols, flavan-3-ols, anthocyanidins, and proanthocyanidins showed a significant inverse association with colorectal cancer risk [OR (95%CI) = 0.71 (0.63-0.81), 0.88 (0.79-0.97), 0.68 (0.56-0.82), and 0.72 (0.61-0.85), respectively]. A significant association was found only between flavonols and stomach cancer risk based on a limited number of selected studies [OR (95%CI) = 0.68 (0.46-0.99)]. In the summary estimates from case-control studies, all flavonoid subclasses except flavones and flavanones were inversely associated with colorectal cancer risk, whereas neither total flavonoids nor any subclasses of flavonoids were associated with colorectal cancer risk in the summary estimates based on the cohort studies. The significant association between flavonoid subclasses and cancer risk might be closely related to bias derived from the case-control design. There was no clear evidence that dietary flavonoids are associated with reduced risk of stomach and colorectal cancer.
Bujanda, Luis; Sarasqueta, Cristina; Hijona, Elisabeth; Hijona, Lander; Cosme, Angel; Gil, Ines; Elorza, Jose Luis; Asensio, Jose I; Larburu, Santiago; Enríquez-Navascués, José M; Jover, Rodrigo; Balaguer, Francesc; Llor, Xavier; Bessa, Xavier; Andreu, Montserrat; Paya, Artemio; Castells, Antoni; Association, Gastrointestinal Oncology Group of the Spanish Gastroenterological
AIM: To evaluate changes in colorectal cancer (CRC) survival over the last 20 years. METHODS: We compared two groups of consecutive CRC patients that were prospectively recruited: Group I included 1990 patients diagnosed between 1980 and 1994. Group II included 871 patients diagnosed in 2001. RESULTS: The average follow up time was 21 mo (1-229) for Group I and 50 mo (1-73.4) for Group II. Overall median survival was significantly longer in Group II than in Group I (73 mo vs 25 mo, P < 0.001) and the difference was significant for all tumor stages. Post surgical mortality was 8% for Group Iand 2% for Group II (P < 0.001). Only 17% of GroupI patients received chemotherapy compared with 50% of Group II patients (P < 0.001). CONCLUSION: Survival in colorectal cancer patients has doubled over the past 20 years. This increase seems to be partly due to the generalization in the administration of chemotherapy and to the decrease of post surgical mortality. PMID:20143465
Van Blarigan, Erin L.; Meyerhardt, Jeffrey A.
This review summarizes the evidence regarding physical activity and diet after colorectal cancer diagnosis in relation to quality of life, disease recurrence, and survival. There have been extensive reports on adiposity, inactivity, and certain diets, particularly those high in red and processed meats, and increased risk of colorectal cancer. Only in the past decade have data emerged on how such lifestyle factors are associated with outcomes in colorectal cancer survivors. Prospective observational studies have consistently reported that physical activity after colorectal cancer diagnosis reduces mortality. A meta-analysis estimated that each 15 metabolic equivalent task-hour per week increase in physical activity after colorectal cancer diagnosis was associated with a 38% lower risk of mortality. No randomized controlled trials have been completed to confirm that physical activity lowers risk of mortality among colorectal cancer survivors; however, trials have shown that physical activity, including structured exercise, is safe for colorectal cancer survivors (localized to metastatic stage, during and after treatment) and improves cardiorespiratory fitness and physical function. In addition, prospective observational studies have suggested that a Western dietary pattern, high carbohydrate intake, and consuming sugar-sweetened beverages after diagnosis may increase risk of colorectal cancer recurrence and mortality, but these data are limited to single analyses from one of two US cohorts. Additional data from prospective studies and randomized controlled trials are needed. Nonetheless, on the basis of the available evidence, it is reasonable to counsel colorectal cancer survivors to engage in regular physical activity and limit consumption of refined carbohydrates, red and processed meats, and sugar-sweetened beverages. PMID:25918293
Van Blarigan, Erin L; Meyerhardt, Jeffrey A
This review summarizes the evidence regarding physical activity and diet after colorectal cancer diagnosis in relation to quality of life, disease recurrence, and survival. There have been extensive reports on adiposity, inactivity, and certain diets, particularly those high in red and processed meats, and increased risk of colorectal cancer. Only in the past decade have data emerged on how such lifestyle factors are associated with outcomes in colorectal cancer survivors. Prospective observational studies have consistently reported that physical activity after colorectal cancer diagnosis reduces mortality. A meta-analysis estimated that each 15 metabolic equivalent task-hour per week increase in physical activity after colorectal cancer diagnosis was associated with a 38% lower risk of mortality. No randomized controlled trials have been completed to confirm that physical activity lowers risk of mortality among colorectal cancer survivors; however, trials have shown that physical activity, including structured exercise, is safe for colorectal cancer survivors (localized to metastatic stage, during and after treatment) and improves cardiorespiratory fitness and physical function. In addition, prospective observational studies have suggested that a Western dietary pattern, high carbohydrate intake, and consuming sugar-sweetened beverages after diagnosis may increase risk of colorectal cancer recurrence and mortality, but these data are limited to single analyses from one of two US cohorts. Additional data from prospective studies and randomized controlled trials are needed. Nonetheless, on the basis of the available evidence, it is reasonable to counsel colorectal cancer survivors to engage in regular physical activity and limit consumption of refined carbohydrates, red and processed meats, and sugar-sweetened beverages. © 2015 by American Society of Clinical Oncology.
Rafiemanesh, Hosein; Pakzad, Reza; Abedi, Mehdi; Kor, Yones; Moludi, Jalal; Towhidi, Farhad; Reza Makhsosi, Behnam; Salehiniya, Hamid
Colorectal cancer is one of the most prevalent cancers in different countries, including Iran. No comprehensive study has been done in the country for colorectal cancer, but information on the incidence and trends is essential to planning. This study aimed to evaluate the occurrence and morphology of colorectal cancer and its trend in Iran. This study was conducted using data from the national cancer registry system in Iran from 2003-2008. We used joinpoint regression analysis for assessing incidence time trends and morphology change percentage. Of all cases of colorectal cancer, 61.83 % were colon cancer, 27.54 % rectal cancer, 7.46 % rectosigmoid cancer, and 3.10 anal cancer. The most common histological types with the frequencies of 80.85 % was related to adenocarcinoma, NOS. The Annual percentage changes (APC) in ASIR for colorectal cancer significantly increased in both men and women. APC in ASIR was 13.7 (CI: 10.5-17.1) in women and 16.4 (CI: 12.4-20.5) in men. APC of adenocarcinoma in villous adenoma showed significant declining trend (p<0.05), while APC of adenocarcinoma, NOS had a constant trend. The incidence of the cancer in recent years has increased in Iran because of changes in lifestyle and diet. Therefore, further studies are necessary to detect the cause of this cancer and perform preventive measures. PMID:28337105
Sun, Jun; Kato, Ikuko
Although genes contribute to colorectal cancer, the gut microbiota are an important player. Accumulating evidence suggests that chronic infection and the ensuing inflammation contributes to tumor initiation and tumor progression. A variety of bacterial species and tumor-promoting virulence mechanisms have been investigated. Significant advances have been made in understanding the composition and functional capabilities of the gut microbiota and its roles in cancer. In the current review, we discuss the novel roles of microbiota in the progression of colon cancer. Although microbiota technically include organisms other than bacteria e.g., viruses and fungi, this review will primarily focus on bacteria. We summarize epidemiological studies of human microbiome and colon cancer. We discuss the progress in the scientific understanding of the interplay between the gut microbiota, barrier function, and host responses in experimental models. Further, we discuss the potential application in prevention, diagnosis, and therapy of colon cancer by targeting microbiota. We discuss the challenges lie ahead and the future direction in studying gut microbiome in colon cancer to close the gap between the basic sciences and clinical application. PMID:28078319
Aronson, Melyssa; Holter, Spring; Semotiuk, Kara; Winter, Laura; Pollett, Aaron; Gallinger, Steven; Cohen, Zane; Gryfe, Robert
The treatment of colorectal cancer in young patients involves both management of the incident cancer and consideration of the possibility of Lynch syndrome and the development of metachronous colorectal cancers. This study aims to assess the prognostic role of DNA mismatch repair deficiency and extended colorectal resection for metachronous colorectal neoplasia risk in young patients with colorectal cancer. This is a retrospective review of 285 patients identified in our GI cancer registry with colorectal cancer diagnosed at 35 years or younger in the absence of polyposis. Using univariate and multivariate analysis, we assessed the prognostic role of mismatch repair deficiency and standard clinicopathologic characteristics, including the extent of resection, on the rate of developing metachronous colorectal neoplasia requiring resection. Mismatch repair deficiency was identified in biospecimens from 44% of patients and was significantly associated with an increased risk for metachronous colorectal neoplasia requiring resection (10-year cumulative risk, 13.5% ± 4.2%) compared with 56% of patients with mismatch repair-intact colorectal cancer (10-year cumulative risk, 5.8% ± 3.3%; p = 0.011). In multivariate analysis, mismatch repair deficiency was associated with a HR of 3.65 (95% CI, 1.44-9.21; p = 0.006) for metachronous colorectal neoplasia, whereas extended resection with ileorectal or ileosigmoid anastomosis significantly decreased the risk of metachronous colorectal neoplasia (HR, 0.21; 95% CI, 0.05-0.90; p = 0.036). This study had a retrospective design, and, therefore, recommendations for colorectal cancer surgery and screening were not fully standardized. Quality of life after colorectal cancer surgery was not assessed. Young patients with colorectal cancer with molecular hallmarks of Lynch syndrome were at significantly higher risk for the development of subsequent colorectal neoplasia. This risk was significantly reduced in those who underwent extended
Ambalam, Padma; Raman, Maya; Purama, Ravi Kiran; Doble, Mukesh
Colorectal cancer (CRC), the third major cause of mortality among various cancer types in United States, has been increasing in developing countries due to varying diet and dietary habits and occupational hazards. Recent evidences showed that composition of gut microbiota could be associated with the development of CRC and other gut dysbiosis. Modulation of gut microbiota by probiotics and prebiotics, either alone or in combination could positively influence the cross-talk between immune system and microbiota, would be beneficial in preventing inflammation and CRC. In this review, role of probiotics and prebiotics in the prevention of CRC has been discussed. Various epidemiological and experimental studies, specifically gut microbiome research has effectively improved the understanding about the role of probiotics and microbial treatment as anticarcinogenic agents. A few human studies support the beneficial effect of probiotics and prebiotics; hence, comprehensive understanding is urgent to realize the clinical applications of probiotics and prebiotics in CRC prevention.
Dulal, Santosh; Deveaux, April; Jovov, Biljana; Han, Xuesong
The human gut is home to a complex and diverse microbiota that contributes to the overall homeostasis of the host. Increasingly, the intestinal microbiota is recognized as an important player in human illness such as colorectal cancer (CRC), inflammatory bowel diseases, and obesity. CRC in itself is one of the major causes of cancer mortality in the Western world. The mechanisms by which bacteria contribute to CRC are complex and not fully understood, but increasing evidence suggests a link between the intestinal microbiota and CRC as well as diet and inflammation, which are believed to play a role in carcinogenesis. It is thought that the gut microbiota interact with dietary factors to promote chronic inflammation and CRC through direct influence on host cell physiology, cellular homeostasis, energy regulation, and/or metabolism of xenobiotics. This review provides an overview on the role of commensal gut microbiota in the development of human CRC and explores its association with diet and inflammation. PMID:25540232
Keku, Temitope O; Dulal, Santosh; Deveaux, April; Jovov, Biljana; Han, Xuesong
The human gut is home to a complex and diverse microbiota that contributes to the overall homeostasis of the host. Increasingly, the intestinal microbiota is recognized as an important player in human illness such as colorectal cancer (CRC), inflammatory bowel diseases, and obesity. CRC in itself is one of the major causes of cancer mortality in the Western world. The mechanisms by which bacteria contribute to CRC are complex and not fully understood, but increasing evidence suggests a link between the intestinal microbiota and CRC as well as diet and inflammation, which are believed to play a role in carcinogenesis. It is thought that the gut microbiota interact with dietary factors to promote chronic inflammation and CRC through direct influence on host cell physiology, cellular homeostasis, energy regulation, and/or metabolism of xenobiotics. This review provides an overview on the role of commensal gut microbiota in the development of human CRC and explores its association with diet and inflammation.
Li, Yu-Hua; Niu, Yin-Bo; Sun, Yang; Zhang, Feng; Liu, Chang-Xu; Fan, Lei; Mei, Qi-Bing
Although the incidence of colorectal cancer (CRC) has been declining in recent decades, it remains a major public health issue as a leading cause of cancer mortality and morbidity worldwide. Prevention is one milestone for this disease. Extensive study has demonstrated that a diet containing fruits, vegetables, and spices has the potential to prevent CRC. The specific constituents in the dietary foods which are responsible for preventing CRC and the possible mechanisms have also been investigated extensively. Various phytochemicals have been identified in fruits, vegetables, and spices which exhibit chemopreventive potential. In this review article, chemopreventive effects of phytochemicals including curcumin, polysaccharides (apple polysaccharides and mushroom glucans), saponins (Paris saponins, ginsenosides and soy saponins), resveratrol, and quercetin on CRC and the mechanisms are discussed. This review proposes the need for more clinical evidence for the effects of phytochemicals against CRC in large trials. The conclusion of the review is that these phytochemicals might be therapeutic candidates in the campaign against CRC.
Spreadborough, P; Doran, C
Colorectal cancer (CRC) is the fourth most common cancer in the UK and the incidence has increased over recent decades. Although only 1.5% of cases are diagnosed in those aged under 40 years, it remains an important condition to be aware of in the military population. Patients who are genetically predisposed can have a lifetime risk of 80-100% of developing CRC and are likely to develop symptoms during their service. 20% of patients will present with metastatic disease. While surgical and oncological treatments have improved outcomes, early diagnosis of CRC is essential to reducing mortality. This paper provides an overview of the aetiology, investigations and treatment options for CRC. Explanation of primary surgical options and the principles of adjuvant therapies are included to aid informed discussions with patients.
Tariq, Kanwal; Ghias, Kulsoom
Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men globally. CRC arises from one or a combination of chromosomal instability, CpG island methylator phenotype, and microsatellite instability. Genetic instability is usually caused by aneuploidy and loss of heterozygosity. Mutations in the tumor suppressor or cell cycle genes may also lead to cellular transformation. Similarly, epigenetic and/or genetic alterations resulting in impaired cellular pathways, such as DNA repair mechanism, may lead to microsatellite instability and mutator phenotype. Non-coding RNAs, more importantly microRNAs and long non-coding RNAs have also been implicated at various CRC stages. Understanding the specific mechanisms of tumorigenesis and the underlying genetic and epigenetic traits is critical in comprehending the disease phenotype. This paper reviews these mechanisms along with the roles of various non-coding RNAs in CRCs.
Manzano, A.; Pérez-Segura, P.
Colorectal cancer (CRC) is presently one of the most common causes of cancer-related death in our setting and affects a great number of people each year. Screening strategies are commonly used but they do not seem enough to avoid CRC development or prevent completely its mortality. Because of this fact other prevention strategies have gained interest in recent years. Chemoprevention seems to be an attractive option in this setting and several drugs have been studied in this field. This review is focused on salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs) and cycloxygenase-2 inhibitors (COXIBs), whose mechanism of action could be directly related to colon cancer chemoprevention. PMID:22649288
Pritchard, Colin C.; Grady, William M.
The promise of personalized medicine is now a clinical reality, with colorectal cancer genetics at the forefront of this next major advance in clinical medicine. This is no more evident than in the recent advances in testing of colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we examine genetic mechanisms of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:20921207
Green, Chadwick John; de Dauwe, Palina; Boyle, Terry; Tabatabaei, Seyed Mehdi; Fritschi, Lin; Heyworth, Jane Shirley
Data regarding the effects of tea, coffee, and milk on the risk of colorectal cancer are inconsistent. We investigated associations of tea, coffee, and milk consumption with colorectal cancer risk and attempted to determine if these exposures were differentially associated with the risks of proximal colon, distal colon, and rectal cancers. Data from 854 incident cases and 948 controls were analyzed in a case-control study of colorectal cancer in Western Australia during 2005-07. Multivariable logistic regression was used to analyze the associations of black tea (with and without milk), green tea, herbal tea, hot coffee, iced coffee, and milk with colorectal cancer. Consumption of 1 or more cups of herbal tea per week was associated with a significantly decreased risk of distal colon cancer (adjusted odds ratio, 0.37; 95% CI, 0.16-0.82; PTrend = 0.044), and consumption of 1 or more cups of iced coffee per week was associated with increased risk of rectal cancer (adjusted odds ratio, 1.52; 95% CI, 0.91-2.54; PTrend = 0.004). Neither herbal tea nor iced coffee was associated with the risk of proximal colon cancer. Hot coffee was associated with a possible increased risk of distal colon cancer. Black tea (with or without milk), green tea, decaffeinated coffee, and milk were not significantly associated with colorectal cancer risk. Consumption of herbal tea was associated with reduced risk of distal colon cancer, and consumption of iced coffee was associated with increased rectal cancer risk.
Abraha, Aman M; Ketema, Ezra B
Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment.
Martínez, María Elena
The past two decades have provided a vast amount of literature related to the primary prevention of colorectal cancer. Large international variation in colorectal cancer incidence and mortality rates and the prominent increases in the incidence of colorectal cancer in groups that migrated from low- to high-incidence areas provided important evidence that lifestyle factors influence the development of this malignancy. Moreover, there is convincing evidence from epidemiological and experimental studies that dietary intake is an important etiological factor in colorectal neoplasia. Although the precise mechanisms have not been clarified, several lifestyle factors are likely to have a major impact on colorectal cancer development. Physical inactivity and to a lesser extent, excess body weight, are consistent risk factors for colon cancer. Exposure to tobacco products early in life is associated with a higher risk of developing colorectal neoplasia. Diet and nutritional factors are also clearly important. Diets high in red and processed meat increase risk. Excess alcohol consumption, probably in combination with a diet low in some micronutrients such as folate and methionine, appear to increase risk. There is also recent evidence supporting a protective effect of calcium and vitamin D in the etiology of colorectal neoplasia. The relationship between intake of dietary fiber and risk of colon cancer has been studied for three decades but the results are still inconclusive. However, some micronutrients or phytochemicals in fiber-rich foods may be important; folic acid is one such micronutrient that has been shown to protect against the development of colorectal neoplasia and is currently being studied in intervention trials of adenoma recurrence. The overwhelming evidence indicates that primary prevention of colon cancer is feasible. Continued focus on primary prevention of colorectal cancer, in combination with efforts aimed at screening and surveillance, will be vital in
Tárraga López, Pedro J; Albero, Juan Solera; Rodríguez-Montes, José Antonio
INTRODUCTION Cancer is a worldwide problem as it will affect one in three men and one in four women during their lifetime. Colorectal cancer (CRC) is the third most frequent cancer in men, after lung and prostate cancer, and is the second most frequent cancer in women after breast cancer. It is also the third cause of death in men and women separately, and is the second most frequent cause of death by cancer if both genders are considered together. CRC represents approximately 10% of deaths by cancer. Modifiable risk factors of CRC include smoking, physical inactivity, being overweight and obesity, eating processed meat, and drinking alcohol excessively. CRC screening programs are possible only in economically developed countries. However, attention should be paid in the future to geographical areas with ageing populations and a western lifestyle.19,20 Sigmoidoscopy screening done with people aged 55–64 years has been demonstrated to reduce the incidence of CRC by 33% and mortality by CRC by 43%. OBJECTIVE To assess the effect on the incidence and mortality of CRC diet and lifestyle and to determine the effect of secondary prevention through early diagnosis of CRC. METHODOLOGY: A comprehensive search of Medline and Pubmed articles related to primary and secondary prevention of CRC and subsequently, a meta-analysis of the same blocks are performed. RESULTS 225 articles related to primary or secondary prevention of CRC were retrieved. Of these 145 were considered valid on meta-analysis: 12 on epidemiology, 56 on diet and lifestyle, and over 77 different screenings for early detection of CRC. Cancer is a worldwide problem as it will affect one in three men and one in four women during their lifetime. There is no doubt whatsoever which environmental factors, probably diet, may account for these cancer rates. Excessive alcohol consumption and cholesterol-rich diet are associated with a high risk of colon cancer. A diet poor in folic acid and vitamin B6 is also
Rawl, S M; Menon, U; Champion, V L; Foster, J L; Skinner, C S
The purpose of this paper is to describe the perceived benefits and barriers to colorectal cancer screening reported by first-degree relatives of colorectal cancer patients. In this study, the authors used focus groups to identify perceived benefits and barriers to colorectal cancer screening among parents and children of colorectal cancer patients. Four focus groups were conducted with relatives of colorectal cancer patients seen at two university medical centers in the Midwest. The groups ranged in size from five to eight members each and were stratified by gender. Four benefits of colorectal cancer screening were identified by participants: finding colorectal cancer early, decreasing the chances of dying from colorectal cancer, freedom from worry about colorectal cancer, and reassurance that one was cancer-free. Four main barriers were identified that applied to all four types of colorectal cancer screening or to colorectal cancer screening in general. These included inadequate public awareness of colorectal cancer, inconsistent recommendations from healthcare providers, concerns about the efficacy of screening tests, and embarrassment. Barriers unique to each screening test also were identified. Understanding individual beliefs about the benefits and barriers to colorectal cancer screening will allow clinicians and researchers to develop effective interventions to increase screening. Results from the focus groups have been used to develop an instrument to measure benefits and barriers to colorectal cancer screening, which now needs to be tested with more culturally and socioeconomically diverse groups.
Marin, Jose J G; Sanchez de Medina, Fermin; Castaño, Beatriz; Bujanda, Luis; Romero, Marta R; Martinez-Augustin, Olga; Moral-Avila, Rosario Del; Briz, Oscar
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.
Okugawa, Yoshinaga; Grady, William M.; Goel, Ajay
Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. One of the fundamental processes driving the initiation and progression of CRC is the accumulation of a variety of genetic and epigenetic changes in colon epithelial cells. Over the past decade, major advances have been made in our understanding of cancer epigenetics, particularly regarding aberrant DNA methylation, microRNA (miRNA) and noncoding RNA deregulation, and alterations in histone modification states. Assessment of the colon cancer “epigenome” has revealed that virtually all CRCs have aberrantly methylated genes and altered miRNA expression. The average CRC methylome has hundreds to thousands of abnormally methylated genes and dozens of altered miRNAs. As with gene mutations in the cancer genome, a subset of these epigenetic alterations, called driver events, is presumed to have a functional role in CRC. In addition, the advances in our understanding of epigenetic alterations in CRC have led to these alterations being developed as clinical biomarkers for diagnostic, prognostic and therapeutic applications. Progress in this field suggests that these epigenetic alterations will be commonly used in the near future to direct the prevention and treatment of CRC. PMID:26216839
Tuncer, Sinem; Banerjee, Sreeparna
Enzymatic metabolism of the 20C polyunsaturated fatty acid (PUFA) arachidonic acid (AA) occurs via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, and leads to the production of various bioactive lipids termed eicosanoids. These eicosanoids have a variety of functions, including stimulation of homeostatic responses in the cardiovascular system, induction and resolution of inflammation, and modulation of immune responses against diseases associated with chronic inflammation, such as cancer. Because chronic inflammation is essential for the development of colorectal cancer (CRC), it is not surprising that many eicosanoids are implicated in CRC. Oftentimes, these autacoids work in an antagonistic and highly temporal manner in inflammation; therefore, inhibition of the pro-inflammatory COX-2 or 5-LOX enzymes may subsequently inhibit the formation of their essential products, or shunt substrates from one pathway to another, leading to undesirable side-effects. A better understanding of these different enzymes and their products is essential not only for understanding the importance of eicosanoids, but also for designing more effective drugs that solely target the inflammatory molecules found in both chronic inflammation and cancer. In this review, we have evaluated the cancer promoting and anti-cancer roles of different eicosanoids in CRC, and highlighted the most recent literature which describes how those molecules affect not only tumor tissue, but also the tumor microenvironment. Additionally, we have attempted to delineate the roles that eicosanoids with opposing functions play in neoplastic transformation in CRC through their effects on proliferation, apoptosis, motility, metastasis, and angiogenesis. PMID:26557000
Kim, Jung Han
Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the elderly. However, elderly patients with CRC tend to be under-presented in clinical trials and undertreated in clinical practice. Advanced age alone should not be the only criteria to preclude effective therapy in elderly patients with CRC. The best guide about optimal cancer treatment can be provided by comprehensive geriatric assessment. Elderly patients with stage III colon cancer can enjoy the same benefit from adjuvant chemotherapy with 5-fluorouracil/leucovorin or capecitabine as younger patients, without a substantial increase in toxicity. With conflicting results of retrospective studies and a lack of data available from randomized studies, combined modality treatment should be used with great caution in elderly patients with locally advanced rectal cancer. Combination chemotherapy can be considered for older patients with metastatic CRC. For elderly patients who are frail or vulnerable, however, monotherapy or a stop-and-go strategy may be desirable. The use of targeted therapies in older patients with metastatic CRC appears to be promising in view of their better efficacy and toxicity. Treatment should be individualized based on the nature of the disease, the physiologic or functional status, and the patient's preference.
Gao, Zhiguang; Guo, Bomin; Gao, Renyuan; Zhu, Qingchao; Qin, Huanlong
The dysbiosis of the human intestinal microbiota is linked to sporadic colorectal carcinoma (CRC). The present study was designed to investigate the gut microbiota distribution features in CRC patients. We performed pyrosequencing based analysis of the 16S rRNA gene V3 region to investigate microbiota of the cancerous tissue and adjacent non-cancerous normal tissue in proximal and distal CRC samples. The results revealed that the microbial structures of the CRC patients and healthy individuals differed significantly. Firmicutes and Fusobacteria were over-represented whereas Proteobacteria was under-represented in CRC patients. In addition, Lactococcus and Fusobacterium exhibited a relatively higher abundance while Pseudomonas and Escherichia-Shigella was reduced in cancerous tissues compared to adjacent non-cancerous tissues. Meanwhile, the overall microbial structures of proximal and distal colon cancerous tissues were similar; but certain potential pro-oncogenic pathogens were different. These results suggested that the mucosa-associated microbiota is dynamically associated with CRC, which may provide evidences for microbiota-associated diagnostic, prognostic, preventive, and therapeutic strategies for CRC.
Simon, Michael S.; Chlebowski, Rowan T.; Wactawski-Wende, Jean; Johnson, Karen C.; Muskovitz, Andrew; Kato, Ikuko; Young, Alicia; Hubbell, F. Allan; Prentice, Ross L.
Purpose During the intervention phase in the Women's Health Initiative (WHI) clinical trial, use of estrogen plus progestin reduced the colorectal cancer diagnosis rate, but the cancers were found at a substantially higher stage. To assess the clinical relevance of the findings, analyses of the influence of combined hormone therapy on colorectal cancer incidence and colorectal cancer mortality were conducted after extended follow-up. Patients and Methods The WHI study was a randomized, double-blind, placebo-controlled clinical trial involving 16,608 postmenopausal women with an intact uterus who were randomly assigned to daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or matching placebo (n = 8,102). Colorectal cancer diagnosis rates and colorectal cancer mortality were assessed. Results After a mean of 5.6 years (standard deviation [SD], 1.03 years) of intervention and 11.6 years (SD, 3.1 years) of total follow-up, fewer colorectal cancers were diagnosed in the combined hormone therapy group compared with the placebo group (diagnoses/year, 0.12% v 0.16%; hazard ratio [HR], 0.72; 95% CI, 0.56 to 0.94; P = .014). Bowel screening examinations were comparable between groups throughout. Cancers in the combined hormone therapy group more commonly had positive lymph nodes (50.5% v 28.6%; P < .001) and were at higher stage (regional or distant, 68.8% v 51.4%; P = .003). Although not statistically significant, there was a higher number of colorectal cancer deaths in the combined hormone therapy group (37 v 27 deaths; 0.04% v 0.03%; HR, 1.29; 95% CI, 0.78 to 2.11; P = .320). Conclusion The findings, suggestive of diagnostic delay, do not support a clinically meaningful benefit for combined hormone therapy on colorectal cancer. PMID:23008295
Curtis, N. J.; Noble, E.; Cortina-Borja, M.; Salib, E.
Introduction. The developmental origins of health and disease hypothesis and season of birth have been linked to a wide variety of later life conditions including cancer. Whether any relationship between month and season of birth and colorectal cancer exists is unknown. Methods. A case-control study was performed with month of birth extracted from a dedicated colorectal cancer database. Age and gender matched patients were used as a control group. Generalised linear models were fitted with Poisson and negative binomial responses and logarithmic links. A forward stepwise approach was followed adding seasonal components with 6- and 12-month periods. Results. 1019 colorectal cancer patients and 1277 randomly selected age and gender matched controls were included. For both men and women there is an excess of colorectal cancer in those born in autumn and a corresponding reduction of risk among those born in spring (p = 0.026). For the identified September peak, the excess risk for colorectal cancer was 14.8% (95% CI 5.6–32.3%) larger than the spring trough. Conclusion. There is a seasonal effect in the monthly birth rates of people who are operated for colorectal cancer with a disproportionate excess of cancer in those born in September. Further large studies are required to validate these findings. PMID:28133478
Francis, N K; Curtis, N J; Noble, E; Cortina-Borja, M; Salib, E
Introduction. The developmental origins of health and disease hypothesis and season of birth have been linked to a wide variety of later life conditions including cancer. Whether any relationship between month and season of birth and colorectal cancer exists is unknown. Methods. A case-control study was performed with month of birth extracted from a dedicated colorectal cancer database. Age and gender matched patients were used as a control group. Generalised linear models were fitted with Poisson and negative binomial responses and logarithmic links. A forward stepwise approach was followed adding seasonal components with 6- and 12-month periods. Results. 1019 colorectal cancer patients and 1277 randomly selected age and gender matched controls were included. For both men and women there is an excess of colorectal cancer in those born in autumn and a corresponding reduction of risk among those born in spring (p = 0.026). For the identified September peak, the excess risk for colorectal cancer was 14.8% (95% CI 5.6-32.3%) larger than the spring trough. Conclusion. There is a seasonal effect in the monthly birth rates of people who are operated for colorectal cancer with a disproportionate excess of cancer in those born in September. Further large studies are required to validate these findings.
Kitahara, Cari M.; Berndt, Sonja I.; de González, Amy Berrington; Coleman, Helen G.; Schoen, Robert E.; Hayes, Richard B.; Huang, Wen-Yi
Purpose Obesity has consistently been linked to an increased risk of colorectal cancer, particularly among men. Whether body mass index (BMI) differentially influences the risk across the stages of colorectal cancer development remains unclear. We evaluated the associations of BMI with colorectal adenoma incidence, adenoma recurrence, and cancer in the context of a large screening trial, in which cases and controls had an equal chance for disease detection. Methods We prospectively evaluated the association between baseline BMI and the risk of incident distal adenoma (1,213 cases), recurrent adenoma (752 cases), and incident colorectal cancer (966 cases) among men and women, ages 55 to 74 years, randomly assigned to receive flexible sigmoidoscopy screening as part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We calculated odds ratios (ORs) and 95% CIs for adenoma incidence and recurrence, and hazard ratios (HRs) and 95% CIs for colorectal cancer incidence, using multivariable-adjusted models. Results Compared with normal-weight men (18.5 to 24.9 kg/m2), obese men (≥ 30 kg/m2) had significantly higher risk of incident adenoma (OR, 1.32; 95% CI, 1.06 to 1.65) and colorectal cancer (HR, 1.48; 95% CI, 1.16 to 1.89) and a borderline increased risk of recurrent adenoma (OR, 1.50; 95% CI, 0.98 to 2.30). No associations were observed for either adenoma or cancer in women. Conclusion Data from this large prospective study suggest that obesity is important throughout the natural history of colorectal cancer, at least in men, and colorectal cancer prevention efforts should encourage the achievement and maintenance of a healthy body weight in addition to regular screenings. PMID:23715565
Kitahara, Cari M; Berndt, Sonja I; de González, Amy Berrington; Coleman, Helen G; Schoen, Robert E; Hayes, Richard B; Huang, Wen-Yi
Obesity has consistently been linked to an increased risk of colorectal cancer, particularly among men. Whether body mass index (BMI) differentially influences the risk across the stages of colorectal cancer development remains unclear. We evaluated the associations of BMI with colorectal adenoma incidence, adenoma recurrence, and cancer in the context of a large screening trial, in which cases and controls had an equal chance for disease detection. We prospectively evaluated the association between baseline BMI and the risk of incident distal adenoma (1,213 cases), recurrent adenoma (752 cases), and incident colorectal cancer (966 cases) among men and women, ages 55 to 74 years, randomly assigned to receive flexible sigmoidoscopy screening as part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We calculated odds ratios (ORs) and 95% CIs for adenoma incidence and recurrence, and hazard ratios (HRs) and 95% CIs for colorectal cancer incidence, using multivariable-adjusted models. Compared with normal-weight men (18.5 to 24.9 kg/m(2)), obese men (≥ 30 kg/m(2)) had significantly higher risk of incident adenoma (OR, 1.32; 95% CI, 1.06 to 1.65) and colorectal cancer (HR, 1.48; 95% CI, 1.16 to 1.89) and a borderline increased risk of recurrent adenoma (OR, 1.50; 95% CI, 0.98 to 2.30). No associations were observed for either adenoma or cancer in women. Data from this large prospective study suggest that obesity is important throughout the natural history of colorectal cancer, at least in men, and colorectal cancer prevention efforts should encourage the achievement and maintenance of a healthy body weight in addition to regular screenings.
Biswas, S; Holyoake, D; Maughan, T S
Over the last 5 years there has been a surge in interest in the molecular classification of colorectal cancer. The effect of molecular subtyping on current treatment decisions is limited to avoidance of adjuvant 5-fluorouracil chemotherapy in stage II microsatellite unstable-high disease and avoidance of epidermal growth factor receptor-targeted antibodies in extended RAS mutant tumours. The emergence of specific novel combination therapy for the BRAF-mutant cohort and of the microsatellite unstable-high cohort as a responsive group to immune checkpoint inhibition shows the growing importance of a clinically relevant molecular taxonomy. Clinical trials such as the Medical Research Council FOCUS4 trial using biomarkers to select patients for specific therapies are currently open and testing such approaches. The integration of mutation, gene expression and pathological analyses is refining our understanding of the biological subtypes within colorectal cancer. Sharing of data sets of parallel sequencing and gene expression of thousands of cancers among independent groups has allowed the description of disease subsets and the need for a validated consensus classification has become apparent. This biological understanding of the disease is a key step forward in developing a stratified approach to patient management. The discovery of stratifiers that predict a response to existing and emerging therapies will enable better use of these treatments. Improved scientific understanding of the biological characteristics of poorly responsive subgroups will facilitate the design of novel biologically rational combinations. Novel treatment regimens, including the combination of new drugs with radiation, and the discovery and validation of their associated predictive biomarkers will gradually lead to improved outcomes from therapy. Copyright © 2015. Published by Elsevier Ltd.
Wang, Jun; Luo, Mao-Hong; Zhang, Zuo-Xing; Zhang, Pei-Da; Jiang, Xi-Li; Ma, Dong-Wang; Suo, Rong-Zeng; Zhao, Li-Zhong; Qi, Qing-Hui
AIM: To analyze the frequency of hereditary non-polyposis colorectal cancer (HNPCC) in Chinese colorectal cancer (CRC) patients, and to discuss the value of microsatellite instability (MSI) and/or immunohistochemistry (IHC) for MSH2/MLH1 protein analysis as pre-screening tests in China. METHODS: The Amsterdam criteriaIandII(clinical diagnosis) and/or germline hMLH1/hMSH2 mutations (genetic diagnosis) were used to classify HNPCC families. Genetic tests, including microsatellite instability, immunohistochemistry for MSH2/MLH1 proteins and hMSH2/hMLH1 genes, were performed in each proband. RESULTS: From July 2000 to June 2004, 1988 patients with colorectal cancer were analysed and 114 CRC patients (5.7%) from 48 families were categorized as having HNPCC, including 76 from 26 families diagnosed clinically and 38 from the other 22 families diagnosed genetically. The sensitivity and specificity of high MSI and IHC for predicting mutations were 100% and 54%, and 79% and 77%, respectively. CONCLUSION: The frequency of HNPCC is approximately 10% among all Chinese CRC cases. The MSI and IHC detections for hMSH2/hMLH1 proteins are reliable pre-screening tests for hMLH1/hMSH2 germline mutations in families suspected of having HNPCC. PMID:17461458
Kovac, Suzana; Anderson, Gregory J; Baldwin, Graham S
The peptide hormone gastrin has been identified as a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. The importance of gastric acid in the absorption of dietary iron first became evident 50 years ago when iron deficiency anemia was recognized as a long-term consequence of partial gastrectomy. This review summarizes the connections between circulating gastrins, iron status and colorectal cancer. Gastrins bind two ferric ions with micromolar affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity in vitro and in vivo. The demonstration of an interaction between gastrin and transferrin by biochemical techniques led to the proposal that gastrins catalyze the loading of transferrin with iron. Several lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease hemochromatosis and that transferrin saturation positively correlates with circulating gastrin concentration, suggest the potential involvement of gastrins in iron homeostasis. Conversely, recognition that ferric ions play an unexpected role in the biological activity of gastrins may assist in the development of useful therapies for colorectal carcinoma and other disorders of mucosal proliferation in the gastrointestinal tract. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
Nag, S. )
Radical surgical excision of locoregional recurrence of colorectal carcinoma usually produces the best survival and should be attempted whenever possible. However, recurrences are often unresectable; hence palliative local therapy may be indicated. There are several options for the radiation therapy of local, unresectable, recurrent, or metastatic colorectal cancer. Whole pelvis irradiation of 4,000-5,000 cGy followed by a coned-down boost of 1,000-1,500 cGy generally provides good symptomatic palliation in 80-90% of patients, but long-term control or cure is rarely achieved. External beam irradiation of 2,000-3,000 cGy to the whole liver with or without concurrent chemotherapy may be used for palliation of metastatic disease to the liver. A combination of intraoperative radiation therapy applied directly to the tumor bed and external beam irradiation may improve local control and survival rates. Multiple options are available for the intraoperative use of brachytherapy which can deliver high radiation doses to the residual tumor, or tumor bed, sparing normal tissue.
Kovac, Suzana; Anderson, Gregory J.; Baldwin, Graham S.
The peptide hormone gastrin has been identified as a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. The importance of gastric acid in the absorption of dietary iron first became evident 50 years ago when iron-deficiency anemia was recognised as a long-term consequence of partial gastrectomy. This review summarises the connections between circulating gastrins, iron status and colorectal cancer. Gastrins bind two ferric ions with micromolar affinity and, in the case of non-amidated forms of the hormone, iron-binding is essential for biological activity in vitro and in vivo. The demonstration of an interaction between gastrin and transferrin by biochemical techniques led to the proposal that gastrins catalyse the loading of transferrin with iron. Several lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron-overload disease hemochromatosis and that transferrin saturation positively correlates with circulating gastrin concentration, suggest the potential involvement of gastrins in iron homeostasis. Conversely, recognition that ferric ions play an unexpected role in the biological activity of gastrins may assist in the development of useful therapies for colorectal carcinoma and other disorders of mucosal proliferation in the gastrointestinal tract. PMID:21320535
Bailey, James R; Aggarwal, Ashish; Imperiale, Thomas F
Colorectal cancer screening dates to the discovery of precancerous adenomatous tissue. Screening modalities and guidelines directed at prevention and early detection have evolved and resulted in a significant decrease in the prevalence and mortality of colorectal cancer via direct visualization or using specific markers. Despite continued efforts and an overall reduction in deaths attributed to colorectal cancer over the last 25 years, colorectal cancer remains one of the most common causes of malignancy-associated deaths. In attempt to further reduce the prevalence of colorectal cancer and associated deaths, continued improvement in screening quality and adherence remains key. Noninvasive screening modalities are actively being explored. Identification of specific genetic alterations in the adenoma-cancer sequence allow for the study and development of noninvasive screening modalities beyond guaiac-based fecal occult blood testing which target specific alterations or a panel of alterations. The stool DNA test is the first noninvasive screening tool that targets both human hemoglobin and specific genetic alterations. In this review we discuss stool DNA and other commercially available noninvasive colorectal cancer screening modalities in addition to other targets which previously have been or are currently under study.
There are five types of tests that are used to screen for colorectal cancer: fecal occult blood test, sigmoidoscopy, colonoscopy, virtual colonoscopy, and DNA stool test. Learn more about these and other tests in this expert-reviewed summary.
Passot, Guillaume; Mohkam, Kayvan; Cotte, Eddy; Glehen, Olivier
Free cancer cells can be detected in peritoneal fluid at the time of colorectal surgery. Peritoneal lavage in colorectal surgery for cancer is not used in routine, and the prognostic significance of intraperitoneal free cancer cells (IPCC) remains unclear. Data concerning the technique of peritoneal lavage to detect IPCC and its timing regarding colorectal resection are scarce. However, positive IPCC might be the first step of peritoneal spread in colorectal cancers, which could lead to early specific treatments. Because of the important heterogeneity of IPCC determination in reported studies, no treatment have been proposed to patients with positive IPCC. Herein, we provide an overview of IPCC detection and its impact on recurrence and survival, and we suggest further multi-institutional studies to evaluate new treatment strategies. PMID:24616569
Passot, Guillaume; Mohkam, Kayvan; Cotte, Eddy; Glehen, Olivier
Free cancer cells can be detected in peritoneal fluid at the time of colorectal surgery. Peritoneal lavage in colorectal surgery for cancer is not used in routine, and the prognostic significance of intraperitoneal free cancer cells (IPCC) remains unclear. Data concerning the technique of peritoneal lavage to detect IPCC and its timing regarding colorectal resection are scarce. However, positive IPCC might be the first step of peritoneal spread in colorectal cancers, which could lead to early specific treatments. Because of the important heterogeneity of IPCC determination in reported studies, no treatment have been proposed to patients with positive IPCC. Herein, we provide an overview of IPCC detection and its impact on recurrence and survival, and we suggest further multi-institutional studies to evaluate new treatment strategies.
An herbal extract used for centuries to prevent heart disease has now been shown to be effective against colorectal cancer when tested in laboratory cell cultures. From left to right: Weidong Li, principal investigator, China Academy of Chinese Medic
Formica, Vincenzo; Cereda, Vittore; Nardecchia, Antonella; Tesauro, Manfredi; Roselli, Mario
The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors. Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship. Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified, still no approved therapies based on host immunity intensification have so far been introduced in clinical practice. Moreover, a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach. The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease. PMID:25253941
Bours, V; Jerusalem, G; Fillet, G
Colorectal adenocarcinoma is a major cause of cancer-related morbidity and mortality in Belgium and in other western countries. Prevention implies a modification of alimentation and maybe a chronic uptake of acetylsalicylic acid. Treatment of colorectal cancers is based on surgery and the prognosis is determined by the locoregional or metastatic tumor spread. Complete resection of any Astler Coller stage C colorectal malignant tumor has to be followed by a 5-fluorouracil-based adjuvant chemotherapy. In these protocols, 5-fluorouracil is administered together with folinic acid or levamisole. The administration of an adjuvant chemotherapy could also be considered for stage BII diseases. As rectal cancers are characterized by high local relapse rates, their treatment should associate radiotherapy, given either post-surgery or preferentially pre-surgery, with resection and chemotherapy. Appropriate treatment of colorectal cancers thus requires a concerted multidisciplinary approach.
Luo, Yanxin; Tsuchiya, Karen D.; Park, Dong Il; Fausel, Rebecca; Kanngurn, Samornmas; Welcsh, Piri; Dzieciatkowski, Slavomir; Wang, Jianping; Grady, William M.
Cancer arises as the consequence of mutations and epigenetic alterations that activate oncogenes and inactivate tumor suppressor genes. Through a genome-wide screen for methylated genes in colon neoplasms, we identified aberrantly methylated RET in colorectal cancer. RET, a transmembrane receptor tyrosine kinase and a receptor for the GDNF-family ligands, was one of the first oncogenes to be identified and has been shown to be an oncogene in thyroid cancer and pheochromocytoma. However, unexpectedly, we found RET is methylated in 27% of colon adenomas and in 63% of colorectal cancers, and now provide evidence that RET has tumor suppressor activity in colon cancer. The aberrant methylation of RET correlates with decreased RET expression, whereas the restoration of RET in colorectal cancer cell lines results in apoptosis. Furthermore, in support of a tumor suppressor function of RET, mutant RET has also been found in primary colorectal cancer. We now show that these mutations inactivate RET, which is consistent with RET being a tumor suppressor gene in the colon. These findings suggest that the aberrant methylation of RET and the mutational inactivation of RET promote colorectal cancer formation and that RET can serve as a tumor suppressor gene in the colon. Moreover, the increased frequency of methylated RET in colon cancers compared to adenomas suggests RET inactivation is involved in the progression of colon adenomas to cancer. PMID:22751117
Sun, Q; Ding, Y; Zhang, J
To study the methodology and significance of flow cytometry in detecting lymph node micrometastasis of colorectal cancer. One hundred sixty-two cellular suspensions were prepared with lymph nodes which were resected radically on 25 patients with colorectal cancer and in which no cancer cells were found by HE staining. Different concentrations of cultured Lovo colorectal cancer cells were added into the celular suspension prepared from lymph node tissue of persons without colorectal cancer in order to prepare a control model. Dual staining with CK/FTTC and PI was made to the sedimetns from those 2 kinds of suspension. Flow cytometry was used to detect cancer cells. An ideal correlation was obtained between the detection value and the theoretical value of cancer cells in the specimen suspensions and control models (r = 0.097 6) with a sensitivity rate of 10/10(5). Cancer cells were detected from 7 out of the 25 patients and 30 of the 162 cellular suspensions. The detection rate was correlated with the size and infiltrating depth of the cancer. Flow cytometry is a reliable, rapid, and quantitative method for detecting lymph node micrometastasis in colorectal cancer.
De Groote, Kerlijne; Prenen, Hans
In patients with metastatic colorectal cancer, the liver is the most common site of metastatic disease. In patients with liver-dominant disease, consideration needs to be given to locoregional treatments such as hepatic arterial infusion chemotherapy, transarterial chemoembolisation and selective internal radiation therapy because hepatic metastases are a major cause of liver failure especially in chemorefractory disease. In this review we provide insights on the published literature for locoregional treatment of liver metastases in metastatic colorectal cancer. PMID:26380058
Haiman, Christopher A; Le Marchand, Loïc; Yamamato, Jennifer; Stram, Daniel O; Sheng, Xin; Kolonel, Laurence N; Wu, Anna H; Reich, David; Henderson, Brian E
Variants on chromosome 8q24 contribute risk for prostate cancer; here, we tested whether they also modulate risk for colorectal cancer. We studied 1,807 affected individuals and 5,511 controls and found that one variant, rs6983267, is also significantly associated with colorectal cancer (odds ratio = 1.22; P = 4.4 × 10−6) and that the apportionment of risk among the variants differs significantly between the two cancers. Comprehensive testing in the region uncovered variants capturing significant additional risk. Our results show that variants at 8q24 have different effects on cancer development that depend on the tissue type. PMID:17618282
Hammond, William A.; Swaika, Abhisek; Mody, Kabir
Colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. This is in spite of widespread, effective measures of preventive screening, and also major advances in treatment options. Despite advances in cytotoxic and targeted therapy, resistance to chemotherapy remains one of the greatest challenges in long-term management of incurable metastatic disease and eventually contributes to death as tumors accumulate means of evading treatment. We performed a comprehensive literature search on the data available through PubMed, Medline, Scopus, and the ASCO Annual Symposium abstracts through June 2015 for the purpose of this review. We discuss the current state of knowledge of clinically relevant mechanisms of resistance to cytotoxic and targeted therapies now in use for the treatment of CRC. PMID:26753006
Kelly, Kimberly M.; Dickinson, Stephanie L.; DeGraffinreid, Cecilia R.; Tatum, Cathy M.; Paskett, Electra D.
Objectives To understand predictors of colorectal cancer (CRC) screening in African Americans, European Americans, and Native Americans as these groups differ in CRC incidence and mortality. Methods Participants were surveyed for knowledge, beliefs, and behaviors related to CRC. Results Predictive regression modeling found, after adjusting for race, CRC risk, and CRC worry, the odds of screening within guidelines were increased for men, those receiving doctor’s recommendation, those with polyp/tumor history, those under 70, those with more knowledge about CRC, and those with fewer barriers to screening. CRC screening rates did not differ by race. Conclusions These results reiterate the importance of knowledge, barriers, and physician recommendation for CRC screening in all racial groups. PMID:17555381
Aziz, Mohammad Azhar; Yousef, Zeyad; Saleh, Ayman M; Mohammad, Sameer; Al Knawy, Bandar
Efforts in colorectal cancer (CRC) research aim to improve early detection and treatment for metastatic stages which could translate into better prognosis of this disease. One of the major challenges that hinder these efforts is the heterogeneous nature of CRC and involvement of diverse molecular pathways. New large-scale 'omics' technologies are making it possible to generate, analyze and interpret biological data from molecular determinants of CRC. The developments of sophisticated computational analyses would allow information from different omics platforms to be integrated, thus providing new insights into the biology of CRC. Together, these technological advances and an improved mechanistic understanding might allow CRC to be clinically managed at the level of the individual patient. This review provides an account of the current challenges in CRC management and an insight into how new technologies could allow the development of personalized medicine for CRC. Copyright © 2017 Elsevier B.V. All rights reserved.
Robertson, Douglas J; Imperiale, Thomas F
Colorectal cancer (CRC) screening has been shown to reduce CRC incidence and mortality and is widely recommended. However, despite the demonstrated benefits of screening and ongoing efforts to improve screening rates, a large percentage of the population remains unscreened. Noninvasive stool based tests offer great opportunity to enhance screening uptake. The evidence supporting the use of both fecal immunochemical testing (FIT) and stool DNA (sDNA) has been growing rapidly and both tests are now commercially available for use. Other stool biomarkers (eg, RNA and protein based) are also actively under study both for use independently and as adjuncts to the currently available tests. This mini review provides current, state of the art knowledge about noninvasive stool based screening. It includes a more detailed examination of those tests currently in use (ie, FIT and sDNA) but also provides an overview of stool testing options under development (ie, protein and RNA).
Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M.; Morris, Jeffrey S.; Simon, Iris M.; Gerster, Sarah; Fessler, Evelyn; de Sousa e Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C.; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W.; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H.; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine
Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression–based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC – with clear biological interpretability – and the basis for future clinical stratification and subtype–based targeted interventions. PMID:26457759
Maddison, André R.; Asada, Yukiko; Urquhart, Robin; Johnston, Grace; Burge, Frederick; Porter, Geoff
Cancer continues to be one of the heaviest burdens of disease in Canada, and assessing potential inequities in access to cancer care may serve as a barometer of the health of Canadian health systems. This study tackled three limitations of the current literature by clearly differentiating between inequality and inequity, by assessing inequity in receipt of care and wait times for care, and by taking advantage of inequity indices to enhance comparability of inequities between studies and populations. We measured income-, age-, sex- and distance-related inequities among colorectal cancer (CRC) patients in Nova Scotia by accounting for clinical guidelines and patient need. Results reveal statistically significant inequity in access to chemotherapy and radiotherapy for CRC by age, sex and distance, but not income. This study demonstrates the importance of carefully examining inequity in access to cancer care and highlights one method to report and compare inequities with conceptual clarity. PMID:23968617
Lechner, P; Lind, P; Snyder, M; Haushofer, H
Anti-CEA-scintigraphy turned out to be very reliable in detecting primary and recurrent colorectal cancer, its overall accuracy being more than 90%. The intraoperative application of this technology should provide similar results when focussing at extrahepatic tumor deposits, for example in lymph nodes, thus allowing accurate staging of the underlying disease. To test this hypothesis we launched the following feasibility study the results of which are compared to those reported in the recent literature. We investigated 20 patients, six with rectum and 14 with colon cancer. 24 hours before surgery they were intravenously given 1 ml of a fab'-fragment-antibody to CEA, labeled with 25 mCi of 99mTc (CEA-Scan). During surgery the radioactivity in lymph glands regional to the tumors was measured and compared to the much lower activity in healthy nodes. For this we used a scintillation probe (C-Trak, Care Wise, Inc., Morgan Hill, CA). All lymph nodes of interest were then excised and submitted to frozen section pathology. In 7 out of 20 cases scintimetry led to an up-staging of the disease. In addition we found metastatic spread to lymph nodes that were basically not regional to the primary tumor (retroperitoneum, renal hilum etc.). Scintimetry can precisely identify even very small tumor deposits. So it leads to accurate staging while surgery is still ongoing. In a further step the concept of sentinel node diagnosis, which is right now being clinically evaluated, may some day be applied in colorectal surgical oncology.
Kim, Sung-Hyun; Choi, So-Jung; Park, Joon Suk; Lee, Jinseon; Cho, Yong Beom; Kang, Min-Woong; Lee, Woo Yong; Choi, Yong Soo; Kim, Hong Kwan; Han, Joungho; Chun, Ho-Kyung; Kim, Jhingook
In metastatic colorectal cancers, tumor cells are disseminated prior to surgical resection of the primary tumor but remain dormant until proper colonization mechanisms are activated. To identify the colonization mechanisms of the metastatic tumors, we conducted a pairwise comparison between primary colorectal cancers and metastatic tumors (n=12 pairs), including six hepatic pairs and six pulmonary pairs. The mRNA levels of 224 genes previously reported to be associated with metastasis, cytokines and angiogenesis were quantitatively determined by PCR arrays. Among them, 27 genes were duplicated or triplicated to show consistent expression. Unsupervised hierarchical clustering of the Ct values of metastasis-related genes revealed that liver metastases were indistinguishable from primary colorectal cancers (n=5/6), whereas lung metastases were highly diversified from one another and from the primary tumors (n=6/6). Cytokines and receptor gene expression array data also confirmed the divergence of pulmonary metastases from primary colorectal cancers (n=6/6). Heat map analyses of ΔCt values of the metastasis-related genes identified a 17-gene tropism signature that was sufficient not only to distinguish liver and the lung metastases, but also reconstituted the clustering of primary tumors with the hepatic metastases (n=17/18). In this pilot experiment, pulmonary metastases were significantly diverged from hepatic metastases that were indistinguishable from primary colorectal cancers. Further genomic and clinical studies are in progress to evaluate the potential of the tropism signature as a therapeutic target to inhibit the colonization of metastatic colorectal cancers.
Shahidi, Neal; Cheung, Winson Y
Colorectal cancer screening has become a standard of care in industrialized nations for those 50 to 75 years of age, along with selected high-risk populations. While colorectal cancer screening has been shown to reduce both the incidence and mortality of colorectal cancer, it is a complex multi-disciplinary process with a number of important steps that require optimization before tangible improvements in outcomes are possible. For both opportunistic and programmatic colorectal cancer screening, poor participant uptake remains an ongoing concern. Furthermore, current screening modalities (such as the guaiac based fecal occult blood test, fecal immunochemical test and colonoscopy) may be used or performed suboptimally, which can lead to missed neoplastic lesions and unnecessary endoscopic evaluations. The latter poses the risk of adverse events, such as perforation and post-polypectomy bleeding, as well as financial impacts to the healthcare system. Moreover, ongoing disparities in colorectal cancer screening persist among marginalized populations, including specific ethnic minorities (African Americans, Hispanics, Asians, Indigenous groups), immigrants, and those who are economically disenfranchised. Given this context, we aimed to review the current literature on these important areas pertaining to colorectal cancer screening, particularly focusing on the guaiac based fecal occult blood test, the fecal immunochemical test and colonoscopy. PMID:28042387
Fu, Sheng; Kwek, Leong-Chuan; Chia, Teck-Chee; Lim, Chu-Sing; Tang, Choong-Leong; Ang, Wuan-Suan; Zhou, Miao-Chang; Loke, Po-Ling
As we know Quantum mechanics is a mathematical theory that can describe the behavior of objects that are at microscopic level. Time-resolved autofluorescence spectrometer monitors events that occur during the lifetime of the excited state. This time ranges from a few picoseconds to hundreds of nanoseconds. That is an extremely important advance as it allows environmental parameters to be monitored in a spatially defined manner in the specimen under study. This technique is based on the application of Quantum Mechanics. This principle is applied in our project as we are trying to use different fluorescence spectra to detect biological molecules commonly found in cancerous colorectal tissue and thereby differentiate the cancerous and non-cancerous colorectal polyps more accurately and specifically. In this paper, we use Fluorescence Lifetime Spectrometer (Edinburgh Instruments FL920) to measure decay time of autofluorescence of colorectal cancerous and normal tissue sample. All specimens are from Department of Colorectal Surgery, Singapore General Hospital. The tissues are placed in the time-resolved autofluorescence instrument, which records and calculates the decay time of the autofluorescence in the tissue sample at the excitation and emission wavelengths pre-determined from a conventional spectrometer. By studying the decay time,τ, etc. for cancerous and normal tissue, we aim to present time-resolved autofluorescence as a feasible technique for earlier detection of malignant colorectal tissues. By using this concept, we try to contribute an algorithm even an application tool for real time early diagnosis of colorectal cancer for clinical services.
Groessl, Erik J.; Allison, Matthew A.; Larson, Joseph C.; Ho, Samuel B.; Snetslaar, Linda G.; Lane, Dorothy S.; Tharp, Katie M.; Stefanick, Marcia L.
Background. Higher coffee consumption has been associated with decreased incidence of colorectal cancer. Our objective was to examine the relationship of coffee intake to colorectal cancer incidence in a large observational cohort of postmenopausal US women. Methods. Data were collected for the Women's Health Initiative Observational Study providing a follow-up period of 12.9 years. The mean age of our sample (N = 83,778 women) was 63.5 years. Daily coffee intake was grouped into 3 categories: None, moderate (>0–<4 cups), and high (4+ cups). Proportional hazards modeling was used to evaluate the relationship between coffee intake and colorectal cancer. Results. There were 1,282 (1.53%) new cases of colorectal cancer during follow-up. Compared to nondrinkers, moderate and high coffee drinkers had an increased incidence of colorectal cancer in multivariate analysis (HR 1.15, 1.02–1.29; HR 1.14, 0.93–1.38). Moderate drip brew coffee intake (HR 1.20, 1.05–1.36) and high nondrip brew coffee intake (HR 1.43, 1.01–2.02) were associated with increased odds. Conclusion. Our results suggesting increased incidence of colorectal cancer associated with higher coffee consumption contradict recent meta-analyses but agree with a number of other studies showing that coffee increases risk or has no effect. Brew method results are novel and warrant further research. PMID:27239197
Henry, Kevin A; Niu, Xiaoling; Boscoe, Francis P
Background Examining geographic variation in cancer patient survival can help identify important prognostic factors that are linked by geography and generate hypotheses about the underlying causes of survival disparities. In this study, we apply a recently developed spatial scan statistic method, designed for time-to-event data, to determine whether colorectal cancer (CRC) patient survival varies by place of residence after adjusting survival times for several prognostic factors. Methods Using data from a population-based, statewide cancer registry, we examined a cohort of 25,040 men and women from New Jersey who were newly diagnosed with local or regional stage colorectal cancer from 1996 through 2003 and followed to the end of 2006. Survival times were adjusted for significant prognostic factors (sex, age, stage at diagnosis, race/ethnicity and census tract socioeconomic deprivation) and evaluated using a spatial scan statistic to identify places where CRC survival was significantly longer or shorter than the statewide experience. Results Age, sex and stage adjusted survival times revealed several areas in the northern part of the state where CRC survival was significantly different than expected. The shortest and longest survival areas had an adjusted 5-year survival rate of 73.1% (95% CI 71.5, 74.9) and 88.3% (95% CI 85.4, 91.3) respectively, compared with the state average of 80.0% (95% CI 79.4, 80.5). Analysis of survival times adjusted for age, sex and stage as well as race/ethnicity and area socioeconomic deprivation attenuated the risk of death from CRC in several areas, but survival disparities persisted. Conclusion The results suggest that in areas where additional adjustments for race/ethnicity and area socioeconomic deprivation changed the geographic survival patterns and reduced the risk of death from CRC, the adjustment factors may be contributing causes of the disparities. Further studies should focus on specific and modifiable individual and
Sanford, Stacy D; Zhao, Fengmin; Salsman, John M; Chang, Victor T; Wagner, Lynne I; Fisch, Michael J
Cancer incidence has increased among young adults (YAs) and survival rates have not improved compared with other age groups. Patient-reported outcomes may enhance our understanding of this vulnerable population. In a multisite prospective study, patients completed a cancer symptom inventory at the time of enrollment (T1) and 4 weeks to 5 weeks later (T2). YAs (those aged ≤ 39 years) with breast or colorectal cancer were compared with older adults (those aged ≥ 40 years) with breast or colorectal cancer with regard to symptom severity, symptom interference, changes over time, and medical care. Participants included 1544 patients with breast cancer (96 of whom were YAs) and 718 patients with colorectal cancer (37 of whom were YAs). Compared with older adults, YAs with breast cancer were more likely to report moderate/severe drowsiness, hair loss, and symptom interference with relationships at T1. YAs with colorectal cancer were more likely to report moderate/severe pain, fatigue, nausea, distress, drowsiness, shortness of breath, and rash plus interference in general activity, mood, work, relationships, and life enjoyment compared with older adults. Compared with older adults, shortness of breath, appetite, and sore mouth were more likely to improve in YAs with breast cancer; vomiting was less likely to improve in YAs with colorectal cancer. Referrals for supportive care were few, especially among patients with colorectal cancer. YAs with breast cancer were somewhat more likely to be referred to nutrition and psychiatry services than older patients. YAs reported symptom severity, symptom interference, and variations over time that were distinct from older patients. Distinctions were found to differ by diagnostic group. These findings enhance the understanding of symptom burden in YAs and inform the development of targeted interventions and future research. © 2014 American Cancer Society.
Pho, K; Geller, A; Schroy, P C
Sufficient evidence has accumulated to suggest that the first-degree relatives of patients diagnosed with colorectal adenomas before the age of 60 are at increased risk of colorectal cancer. The principal objective of this study was to assess the extent to which channels of communication exist between physicians, patients and their at-risk first-degree relatives regarding both familial risk and screening recommendations. A telephone survey was conducted among 79 patients (age < or = 60 years) with newly diagnosed colorectal adenomas. Information regarding patient demographics, awareness of familial risk, physician recommendations, and extent of communication with family members about their risk status and need for screening was ascertained. Forty-four (56%) of the 79 eligible subjects completed the survey. Only 18 (41%) responders were aware that their first-degree relatives were at increased risk of colorectal cancer, and the majority claimed to have gained their awareness through sources other than their physicians. Only five (28%) of the 18 knowledgeable patients notified their at-risk relatives of their status, and only two (11%) communicated the need for screening. This survey demonstrates poor communication about familial colorectal cancer risk associated with colorectal adenomas, and highlights the need for novel strategies to both promote awareness and facilitate screening of at-risk relatives.
Vitaglione, Paola; Fogliano, Vincenzo; Pellegrini, Nicoletta
For several years the physiological effects of coffee have been focused on its caffeine content, disregarding the hundreds of bioactive coffee components, such as polyphenols, melanoidins, carbohydrates, diterpenes, etc. These compounds may exert their protection against colorectal cancer (CRC), the third most common cancer worldwide. However, the amount and type of compounds ingested with the beverage may be highly different depending on the variety of coffee used, the roasting degree, the type of brewing method as well as the serving size. In this frame, this paper reviews the mechanisms by which coffee may influence the risk of CRC development focusing on espresso and filtered coffee, as well as on the components that totally or partially reach the colon i.e. polyphenols and dietary fiber, including melanoidins. In particular the effects of coffee on some colon conditions whose deregulation may lead to cancer, namely microbiota composition and lumen reducing environment, were considered. Taken together the discussed studies indicated that, due to their in vivo metabolism and composition, both coffee chlorogenic acids and dietary fiber, including melanoidins, may reduce CRC risk, increasing colon motility and antioxidant status. Further studies should finally assess whether the coffee benefits for colon are driven through a prebiotic effect.
Mager, Lukas F.; Wasmer, Marie-Hélène; Rau, Tilman T.; Krebs, Philippe
The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies. PMID:27148488
Garborg, K; Holme, Ø; Løberg, M; Kalager, M; Adami, H O; Bretthauer, M
Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. A well-defined precursor lesion (adenoma) and a long preclinical course make CRC a candidate for screening. This paper reviews the current evidence for the most important tests that are widely used or under development for population-based screening. In this narrative review, we scrutinized all papers we have been aware of, and carried out searches in PubMed and Cochrane library for relevant literature. Two screening methods have been shown to reduce CRC mortality in randomised trials: repetitive faecal occult blood testing (FOBT) reduces CRC mortality by 16%; once-only flexible sigmoidoscopy (FS) by 28%. FS screening also reduces CRC incidence (by 18%), FOBT does not. Colonoscopy screening has a potentially larger effect on CRC incidence and mortality, but randomised trials are lacking. New screening methods are on the horizon but need to be tested in large clinical trials before implementation in population screening. FS screening reduces CRC incidence and CRC mortality by removal of adenomas; FOBT reduces CRC mortality by early detection of cancer. Several other tests are available, but none has been evaluated in randomised trials. Screening strategies differ considerably across countries.
In the US, colorectal cancer is the fourth most common cancer and the second most deadly. Screening is recommended, not only to reduce mortality, but to prevent cancer by detecting precancerous polyps. Many screening methods are available now, and newer methods based on molecular markers show promise for the future.
Jacobs, Rutger J; Kodach, Liudmila L; Hardwick, James C H
Colorectal cancer is a leading cause of death by cancer in the western world. Despite major progress, even new chemotherapeutic regimens have had relatively little impact on long term survival in the approximately 50% of patients with advanced disease at presentation meaning that prevention is the only realistic way to reduce the burden of this disease. Many countries have implemented population-based screening methods to prevent colorectal cancer by the physical removal of its precursor lesion the adenoma, or to detect cancer at an earlier stage when it is amenable to surgical cure. However these programs have only been shown to reduce colorectal cancer deaths by 30% in those screened and therefore new or complimentary approaches are needed. One such approach is chemoprevention. A number of compounds have shown potential in reducing the incidence of colorectal cancer. Most widely known are NSAIDs but recently inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, also known as statins, commonly prescribed medications that lower serum cholesterol, have been shown to reduce colorectal cancer incidence. A critical issue in chemoprevention is the weighing of benefits against risks. In chemoprevention this balance is likely to be unfavourable when used in a wide unselected population even for the safest of compounds. Therapy should therefore be tailored to the individual patient. The balance will be more favourable in high risk groups such as individuals especially susceptible to neoplasia because of environmental risk factors, patients with inflammatory bowel disease, those with a hereditary predisposition and patients with a previous history of colorectal cancer or polyps. Furthermore colorectal cancer is not one disease but a heterogeneous group of diseases with different underlying molecular mechanisms. It is likely that both prevention and therapy will need to be tailored to the molecular subtype of the cancer in question. This may explain
Schoen, Robert E; Pinsky, Paul F; Weissfeld, Joel L; Yokochi, Lance A; Church, Timothy; Laiyemo, Adeyinka O; Bresalier, Robert; Andriole, Gerald L; Buys, Saundra S; Crawford, E David; Fouad, Mona N; Isaacs, Claudine; Johnson, Christine C; Reding, Douglas J; O'Brien, Barbara; Carrick, Danielle M; Wright, Patrick; Riley, Thomas L; Purdue, Mark P; Izmirlian, Grant; Kramer, Barnett S; Miller, Anthony B; Gohagan, John K; Prorok, Philip C; Berg, Christine D
The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality. From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. Cases of colorectal cancer and deaths from the disease were ascertained. Of the 77,445 participants randomly assigned to screening (intervention group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012 cases), as compared with 15.2 cases per 10,000 person-years in the usual-care group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95% confidence interval [CI], 0.72 to 0.85; P<0.001). Significant reductions were observed in the incidence of both distal colorectal cancer (479 cases in the intervention group vs. 669 cases in the usual-care group; relative risk, 0.71; 95% CI, 0.64 to 0.80; P<0.001) and proximal colorectal cancer (512 cases vs. 595 cases; relative risk, 0.86; 95% CI, 0.76 to 0.97; P=0.01). There were 2.9 deaths from colorectal cancer per 10,000 person-years in the intervention group (252 deaths), as compared with 3.9 per 10,000 person-years in the usual-care group (341 deaths), which represents a 26% reduction (relative risk, 0.74; 95% CI, 0.63 to 0.87; P<0.001). Mortality from distal colorectal cancer was reduced by 50% (87 deaths in the intervention group vs. 175 in the usual-care group; relative risk, 0.50; 95% CI, 0.38 to 0.64; P<0.001); mortality from proximal colorectal cancer was unaffected (143 and 147 deaths, respectively; relative risk, 0.97; 95% CI, 0.77 to 1.22; P=0.81). Screening with flexible sigmoidoscopy was associated with a significant decrease in
Schoen, Robert E.; Pinsky, Paul F.; Weissfeld, Joel L.; Yokochi, Lance A.; Church, Timothy; Laiyemo, Adeyinka O.; Bresalier, Robert; Andriole, Gerald L.; Buys, Saundra S.; Crawford, E. David; Fouad, Mona N.; Isaacs, Claudine; Johnson, Christine C.; Reding, Douglas J.; O'Brien, Barbara; Carrick, Danielle M.; Wright, Patrick; Riley, Thomas L.; Purdue, Mark P.; Izmirlian, Grant; Kramer, Barnett S.; Miller, Anthony B.; Gohagan, John K.; Prorok, Philip C.; Berg, Christine D.
Background The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality. Methods From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. Cases of colorectal cancer and deaths from the disease were ascertained. Results Of the 77,445 participants randomly assigned to screening (intervention group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012 cases), as compared with 15.2 cases per 10,000 person-years in the usual-care group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95% confidence interval [CI], 0.72 to 0.85; P<0.001). Significant reductions were observed in the incidence of both distal colorectal cancer (479 cases in the intervention group vs. 669 cases in the usual-care group; relative risk, 0.71; 95% CI, 0.64 to 0.80; P<0.001) and proximal colorectal cancer (512 cases vs. 595 cases; relative risk, 0.86; 95% CI, 0.76 to 0.97; P = 0.01). There were 2.9 deaths from colorectal cancer per 10,000 person-years in the intervention group (252 deaths), as compared with 3.9 per 10,000 person-years in the usual-care group (341 deaths), which represents a 26% reduction (relative risk, 0.74; 95% CI, 0.63 to 0.87; P<0.001). Mortality from distal colorectal cancer was reduced by 50% (87 deaths in the intervention group vs. 175 in the usual-care group; relative risk, 0.50; 95% CI, 0.38 to 0.64; P<0.001); mortality from proximal colorectal cancer was unaffected (143 and 147 deaths, respectively; relative risk, 0.97; 95% CI, 0.77 to 1.22; P = 0.81). Conclusions Screening with flexible sigmoidoscopy was
Thomas, Joe; Ohtsuka, Masahisa; Pichler, Martin; Ling, Hui
Colorectal cancer is one of the most common cancer diagnoses and causes of mortality worldwide. MicroRNAs are a class of small, non-coding regulatory RNAs that have shown strong associations with colorectal cancer. Through the repression of target messenger RNAs, microRNAs modulate many cellular pathways, such as those involved in cell proliferation, apoptosis, and differentiation. The utilization of microRNAs has shown significant promise in the diagnosis and prognosis of colorectal cancer, owing to their unique expression profile associations with cancer types and malignancies. Moreover, microRNA therapeutics with mimics or antagonists show great promise in preclinical studies, which encourages further development of their clinical use for colorectal cancer patients. The unique ability of microRNAs to affect multiple downstream pathways represents a novel approach for cancer therapy. Although still early in its development, we believe that microRNAs can be used in the near future as biomarkers and therapeutic targets for colorectal cancer. PMID:26602923
Toriola, Adetunji T; Kurl, Sudhir; Laukanen, Jari A; Mazengo, Charles; Kauhanen, Jussi
We investigated the association between alcohol consumption and colorectal cancer because previous studies have yielded conflicting results. As part of the Findrink study, data from the Kuopio Ischaemic Heart Disease (KIHD) Risk Factor Study were analysed. The KIHD study is a cohort of 2,682 men from Eastern Finland with no history of cancer at baseline. The men were grouped into five groups according to their weekly alcohol intake in grams. Association between alcohol and colorectal cancer was examined using Cox proportional hazard models. There were 59 cases of colorectal cancer during an average follow up of 16.7 years. Men within the highest quintile of alcohol consumption had a median weekly alcohol intake of 198.8 g. Age and examination year adjusted risk ratio of colorectal cancer among men within the highest quintile of alcohol consumption was 4.4 (95% CI: 1.6-11.9, P-value = 0.004). After adjusting for potential confounders, such as vegetable consumption, fibre intake, smoking, family history of cancer, socio-economic status, leisure time physical activity, men with the highest amount of alcohol consumption still had a 3.5-fold (95% CI: 1.2-9.9, P-value = 0.021) increased risk of colorectal cancer. Exclusion of men diagnosed with colorectal cancer during the first 2 years of follow up from the analyses did not alter the risk increase. In conclusion, this study gives further evidence of a positive association between alcohol consumption and the risk of colorectal cancer.
Binefa, Gemma; Rodríguez-Moranta, Francisco; Teule, Àlex; Medina-Hayas, Manuel
Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy
Sobhani, Iradj; Tap, Julien; Roudot-Thoraval, Françoise; Roperch, Jean P.; Letulle, Sophie; Langella, Philippe; Corthier, Gérard; Van Nhieu, Jeanne Tran; Furet, Jean P.
The composition of the human intestinal microbiota is linked to health status. The aim was to analyze the microbiota of normal and colon cancer patients in order to establish cancer-related dysbiosis. Patients and Methods Stool bacterial DNA was extracted prior to colonoscopy from 179 patients: 60 with colorectal cancer, and 119 with normal colonoscopy. Bacterial genes obtained by pyrosequencing of 12 stool samples (6 Normal and 6 Cancer) were subjected to a validated Principal Component Analysis (PCA) test. The dominant and subdominant bacterial population (C. leptum, C. coccoides, Bacteroides/Prevotella, Lactobacillus/Leuconostoc/Pediococcus groups, Bifidobacterium genus, and E. coli, and Faecalibacterium prausnitzii species) were quantified in all individuals using qPCR and specific IL17 producer cells in the intestinal mucosa were characterized using immunohistochemistry. Findings Pyrosequencing (Minimal sequence 200 nucleotide reads) revealed 80% of all sequences could be assigned to a total of 819 taxa based on default parameter of Classifier software. The phylogenetic core in Cancer individuals was different from that in Normal individuals according to the PCA analysis, with trends towards differences in the dominant and subdominant families of bacteria. Consequently, All-bacteria [log10 (bacteria/g of stool)] in Normal, and Cancer individuals were similar [11.88±0.35, and 11.80±0.56, respectively, (P = 0.16)], according to qPCR values whereas among all dominant and subdominant species only those of Bacteroides/Prevotella were higher (All bacteria-specific bacterium; P = 0.009) in Cancer (-1.04±0.55) than in Normal (-1.40±0.83) individuals. IL17 immunoreactive cells were significantly expressed more in the normal mucosa of cancer patients than in those with normal colonoscopy. Conclusion This is the first large series to demonstrate a composition change in the microbiota of colon cancer patients with possible impact on mucosal immune response
Werner, Simone; Krause, Friedemann; Rolny, Vinzent; Strobl, Matthias; Morgenstern, David; Datz, Christian; Chen, Hongda; Brenner, Hermann
In initial studies that included colorectal cancer patients undergoing diagnostic colonoscopy, we had identified a serum marker combination able to detect colorectal cancer with similar diagnostic performance as fecal immunochemical test (FIT). In this study, we aimed to validate the results in participants of a large colorectal cancer screening study conducted in the average-risk, asymptomatic screening population. We tested serum samples from 1,200 controls, 420 advanced adenoma patients, 4 carcinoma in situ patients, and 36 colorectal cancer patients with a 5-marker blood test [carcinoembryonic antigen (CEA)+anti-p53+osteopontin+seprase+ferritin]. The diagnostic performance of individual markers and marker combinations was assessed and compared with stool test results. AUCs for the detection of colorectal cancer and advanced adenomas with the 5-marker blood test were 0.78 [95% confidence interval (CI), 0.68-0.87] and 0.56 (95% CI, 0.53-0.59), respectively, which now is comparable with guaiac-based fecal occult blood test (gFOBT) but inferior to FIT. With cutoffs yielding specificities of 80%, 90%, and 95%, the sensitivities for the detection of colorectal cancer were 64%, 50%, and 42%, and early-stage cancers were detected as well as late-stage cancers. For osteopontin, seprase, and ferritin, the diagnostic performance in the screening setting was reduced compared with previous studies in diagnostic settings while CEA and anti-p53 showed similar diagnostic performance in both settings. Performance of the 5-marker blood test under screening conditions is inferior to FIT even though it is still comparable with the performance of gFOBT. CEA and anti-p53 could contribute to the development of a multiple marker blood-based test for early detection of colorectal cancer. ©2015 American Association for Cancer Research.
Zhang, Xuehong; Ma, Jing; Wu, Kana; Chan, Andrew T; Fuchs, Charles S; Giovannucci, Edward L
Although blood donations may reduce body iron stores, to date, prospective data on frequent blood donation and colorectal cancer risk are limited. We tested whether frequent blood donation is associated with a lower risk of colorectal cancer in the Health Professionals Follow-up Study. We prospectively followed 35,121 men who provide the information on lifetime number of blood donations in 1992 through 2008. Serum ferritin levels were measured in a random sample of 305 men. Cox proportional hazard regression models were used to calculate the multivariable relative risks (RRs, 95%CIs) after adjusting for age and other established colorectal cancer risk factors. We documented 684 incident colorectal cancer cases and 224 deaths from colorectal cancer. The mean serum ferritin levels varied from 178 µg/L for men who did not donate blood to 98 µg/L for men who had at least 30 donations. Age-adjusted results for both incidence and mortality were essentially the same as the multivariable-adjusted results. Comparing with non-donors, the multivariable RRs (95%CIs) for colorectal cancer incidence were 0.92 (0.77, 1.11) for 1-5 donation, 0.85 (0.64, 1.11) for 6-9 donations, 0.96 (0.73, 1.26) for 10-19 donations, 0.91 (0.63, 1.32) for 20-29 donations, and 0.97 (0.68, 1.38) for at least 30 donations (P(trend) = 0.92). The multivariable RRs for colorectal cancer mortality were 0.99 (0.72, 1.36) for 1-5 donation, 0.93 (0.57, 1.51) for 6-9 donations, 0.85 (0.50, 1.42) for 10-19 donations, and 1.14 (0.72, 1.83) for at least 20 donations (P(trend) = 0.82). The results did not vary by cancer sub-sites, intake levels of total iron, heme iron, or family history of colorectal cancer. Frequent blood donations were not associated with colorectal cancer incidence and mortality in men. Our results do not support an important role of body iron stores in colorectal carcinogenesis.
Orlich, Michael J; Singh, Pramil N; Sabaté, Joan; Fan, Jing; Sveen, Lars; Bennett, Hannelore; Knutsen, Synnove F; Beeson, W Lawrence; Jaceldo-Siegl, Karen; Butler, Terry L; Herring, R Patti; Fraser, Gary E
Colorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable. The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established. To evaluate the association between vegetarian dietary patterns and incident colorectal cancers. The Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96,354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007. Follow-up varied by state and was indicated by the cancer registry linkage dates. Of these participants, an analytic sample of 77,659 remained after exclusions. Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. The analysis was conducted between June 1, 2014, and October 20, 2014. Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern. The relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages. During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64-0.95) for all colorectal cancers, 0.81 (95% CI, 0.65-1.00) for colon cancer, and 0.71 (95% CI, 0.47-1.06) for rectal cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59-1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65-1.02); in pescovegetarians, 0.57 (95% CI, 0.40-0.82); and in semivegetarians, 0.92 (95% CI, 0.62-1.37) compared with nonvegetarians. Effect estimates were similar for men and women and for black and nonblack individuals. Vegetarian diets are
Orlich, Michael J.; Singh, Pramil N.; Sabaté, Joan; Fan, Jing; Sveen, Lars; Bennett, Hannelore; Knutsen, Synnove F.; Beeson, W. Lawrence; Jaceldo-Siegl, Karen; Butler, Terry L.; Herring, R. Patti; Fraser, Gary E.
IMPORTANCE Colorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable. The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established. OBJECTIVE To evaluate the association between vegetarian dietary patterns and incident colorectal cancers. DESIGN, SETTING, AND PARTICIPANTS The Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96 354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007. Follow-up varied by state and was indicated by the cancer registry linkage dates. Of these participants, an analytic sample of 77 659 remained after exclusions. Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. The analysis was conducted between June 1, 2014, and October 20, 2014. EXPOSURES Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern. MAIN OUTCOMES AND MEASURES The relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages. RESULTS During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64–0.95) for all colorectal cancers, 0.81 (95%CI, 0.65–1.00) for colon cancer, and 0.71 (95% CI, 0.47–1.06) for rectal cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59–1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65–1.02); in pescovegetarians, 0.57 (95% CI, 0.40–0.82); and in semivegetarians, 0.92 (95% CI, 0.62–1.37) compared with
Genova, Ts.; Borisova, E.; Penkov, N.; Vladimirov, B.; Terziev, I.; Zhelyazkova, Al.; Avramov, L.
The wide spread of colorectal cancer and high mortality rate among the patients, brings it to a level of high public health concern. Implementation of standard endoscopic surveillance proves to be effective for reduction of colorectal cancer patients' mortality, since its early diagnosis allows eradication of the disease prior to invasive cancer development, but its application in common clinical practice is still limited. Therefore the development of complimentary diagnostic techniques of the standard white-light endoscopy is on high demand. The non-invasive and highly informative nature of the fluorescence spectroscopy allow to use it as the most realistic prospect of an add-on "red flag" technique for early endoscopy detection of colorectal cancer. Synchronous fluorescence spectroscopy (SFS) is a steady-state approach that is used for evaluation of specific fluorescence characteristics of cancerous colorectal tissues in our studies. The feasibility of polarization fluorescence technique to enhance the contrast between normal and cancerous tissues was investigated as well. Additional linear polarizing optics was used on the way of the excitation and emission fluorescence light beams. The polarizing effects were investigated in parallel and perpendicular linear polarization modes respectively. The excitation applied was in the region of 280 - 440 nm, with 10 nm scanning step, and the fluorescence emission was detected in the region of 300 - 800 nm. Our previous experience with SFS technique showed its great potential for accurate, highly sensitive and specific discrimination between cancerous and normal colorectal tissue. Since one of the major sources of endogenous fluorescence with diagnostic meaning is the structural protein - collagen, which is characterized with high anisotropy, we've expected and observed an enhancement of the spectral differences between cancerous and normal colorectal tissue, which could be beneficial for the colorectal tumour' diagnostics
Derogar, Maryam; Hull, Mark A; Kant, Prashant; Östlund, Magdalena; Lu, Yunxia; Lagergren, Jesper
The purpose was to determine whether obesity surgery is associated with a long-term increased risk of colorectal cancer. Long-term cancer risk after obesity surgery is not well characterized. Preliminary epidemiological observations and human tissue biomarker studies recently suggested an increased risk of colorectal cancer after obesity surgery. A nationwide retrospective register-based cohort study in Sweden was conducted in 1980-2009. The long-term risk of colorectal cancer in patients who underwent obesity surgery, and in an obese no surgery cohort, was compared with that of the age-, sex- and calendar year-matched general background population between 1980 and 2009. Obese individuals were stratified into an obesity surgery cohort and an obese no surgery cohort. The standardized incidence ratio (SIR), with 95% confidence interval (CI), was calculated. Of 77,111 obese patients, 15,095 constituted the obesity surgery cohort and 62,016 constituted the obese no surgery cohort. In the obesity surgery cohort, we observed 70 patients with colorectal cancer, rendering an overall SIR of 1.60 (95% CI 1.25-2.02). The SIR for colorectal cancer increased with length of time after surgery, with a SIR of 2.00 (95% CI 1.48-2.64) after 10 years or more. In contrast, the overall SIR in the obese no surgery cohort (containing 373 colorectal cancers) was 1.26 (95% CI 1.14-1.40) and remained stable with increasing follow-up time. Obesity surgery seems to be associated with an increased risk of colorectal cancer over time. These findings would prompt evaluation of colonoscopy surveillance for the increasingly large population who undergo obesity surgery.
Li, Xiaofeng; Kong, Lixia; Liao, Suhuan; Lu, Jing; Ma, Lin; Long, Xiaohua
Background/Aim: This study aims to explore the expression and significance of feces cyclooxygensae-2 (COX-2) mRNA in colorectal cancer and colorectal adenomas. Materials and Methods: The expression of feces COX-2 mRNA in colorectal cancer (n = 28), colorectal adenomas (n = 54), and normal control group (n = 11) were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The positive rate of fecal occult blood test (FOBT) were detected in colorectal cancer (n = 30), colorectal adenomas (n = 56), and normal control group (n = 11); the sensitivity of the two methods was also compared. Results: The positive rate of feces COX-2 mRNA in colorectal cancer was 82.1% (25/28), which was significantly higher than colorectal adenomas 59.3% (32/54), and normal tissues 18.2% (2/11), the difference being significant between the three groups (χ2= 13.842, P = 0.001). The positive rate of FOBT in colorectal cancer was 73.3% (10/30), which was significantly higher than colorectal adenomas 10.7% (6/56) and normal tissues 9.1% (1/11), the difference being significant between these three groups (χ2= 7.525, P = 0.023). There was no significant association between feces COX-2 expression and various clinical pathological features of colorectal cancer and colorectal adenomas (P > 0.05). The sensitivity of the RT-PCR method is higher than FOBT, however, the specificity of FOBT is slightly higher than RT-PCR. Conclusions: High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer. Feces COX-2 mRNA has a high sensitivity for detect colorectal cancer; combination with FOBT will be the best alternative. Feces COX-2 can be potentially used in the early diagnosis and screening of colorectal cancer. PMID:28139497
Babaei, Masoud; Balavarca, Yesilda; Jansen, Lina; Gondos, Adam; Lemmens, Valery; Sjövall, Annika; B⊘rge Johannesen, Tom; Moreau, Michel; Gabriel, Liberale; Gonçalves, Ana Filipa; Bento, Maria José; van de Velde, Tony; Kempfer, Lana Raffaela; Becker, Nikolaus; Ulrich, Alexis; Ulrich, Cornelia M.; Schrotz-King, Petra; Brenner, Hermann
Abstract Minimally invasive surgery (MIS) of colorectal cancer (CRC) was first introduced over 20 years ago and recently has gained increasing acceptance and usage beyond clinical trials. However, data on dissemination of the method across countries and on long-term outcomes are still sparse. In the context of a European collaborative study, a total of 112,023 CRC cases from 3 population-based (N = 109,695) and 4 institute-based clinical cancer registries (N = 2328) were studied and compared on the utilization of MIS versus open surgery. Cox regression models were applied to study associations between surgery type and survival of patients from the population-based registries. The study considered adjustment for potential confounders. The percentage of CRC patients undergoing MIS differed substantially between centers and generally increased over time. MIS was significantly less often used in stage II to IV colon cancer compared with stage I in most centers. MIS tended to be less often used in older (70+) than in younger colon cancer patients. MIS tended to be more often used in women than in men with rectal cancer. MIS was associated with significantly reduced mortality among colon cancer patients in the Netherlands (hazard ratio [HR] 0.66, 95% confidence interval [CI] (0.63–0.69), Sweden (HR 0.68, 95% CI 0.60–0.76), and Norway (HR 0.73, 95% CI 0.67–0.79). Likewise, MIS was associated with reduced mortality of rectal cancer patients in the Netherlands (HR 0.74, 95% CI 0.68–0.80) and Sweden (HR 0.77, 95% CI 0.66–0.90). Utilization of MIS in CRC resection is increasing, but large variation between European countries and clinical centers prevails. Our results support association of MIS with substantially enhanced survival among colon cancer patients. Further studies controlling for selection bias and residual confounding are needed to establish role of MIS in survival of patients. PMID:27258522
Köküer, Münevver; Naguib, Raouf N G; Jancovic, Peter; Younghusband, H Banfield; Green, Roger C
Colorectal cancer (CRC) is one of the most common fatal cancers in developed countries and represents a significant public-health issue. About 3%-5% of patients with CRC have hereditary nonpolyposis colorectal cancer (HNPCC). Cancer morbidity and mortality can be reduced if early and intensive screening is pursued. However, despite advances in screening, population-wide genetic screening for HNPCC is not currently considered feasible due to its complexity and expense. If the risk of a family having HNPCC can be identified/assessed, then only the high-risk fraction of the population would undergo intensive screening. This identification is currently performed by a genetic counselor/physician who makes the decision based on some pre-defined criteria. Here, we report on a system to identify the risk of a family having HNPCC based on its history. We compare artificial neural networks and statistical approaches for assessing the risk of a family having HNPCC and discuss the experimental results obtained by these two approaches.
Sarkar, Debalina; Shields, Brian; Davies, Melanie L; Müller, Jürgen; Wakeman, Jane A
Cancer stem cells (CSCs) are initiating cells in colorectal cancer (CRC). Colorectal tumours undergo epithelial to mesenchymal transition (EMT)-like processes at the invasive front, enabling invasion and metastasis, and recent studies have linked this process to the acquisition of stem cell-like properties. It is of fundamental importance to understand the molecular events leading to the establishment of cancer initiating cells and how these mechanisms relate to cellular transitions during tumourigenesis. We use an in vitro system to recapitulate changes in CRC cells at the invasive front (mesenchymal-like cells) and central mass (epithelial-like cells) of tumours. We show that the mesoderm inducer BRACHYURY is expressed in a subpopulation of CRC cells that resemble invasive front mesenchymal-like cells, where it acts to impose characteristics of CSCs in a fully reversible manner, suggesting reversible formation and modulation of such cells. BRACHYURY, itself regulated by the oncogene β-catenin, influences NANOG and other 'stemness' markers including a panel of markers defining CRC-CSC whose presence has been linked to poor patient prognosis. Similar regulation of NANOG through BRACHYURY was observed in other cells lines, suggesting this might be a pathway common to cancer cells undergoing mesenchymal transition. We suggest that BRACHYURY may regulate NANOG in mesenchymal-like CRC cells to impose a 'plastic-state', allowing competence of cells to respond to signals prompting invasion or metastasis.
Naing, Cho; Lai, Pei Kuan; Mak, Joon Wah
This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population. Gender specific population-attributable fractions (PAFs) for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions). Exposure prevalence were sourced from a large-scale national representative survey. Risk estimates of the relationship between the exposure of interest and colorectal cancer were obtained from published meta-analyses. The overall PAF was then estimated, using the 2013 national cancer incidence data from the Malaysian Cancer Registry. Overall, the mean incidence rate for colorectal cancer in Malaysia from 2008 to 2013 was 21.3 per 100,000 population, with the mean age of 61.6 years (±12.7) and the majority were men (56.6%). Amongst 369 colorectal cancer cases in 2013, 40 cases (20 men, 20 women), 10 cases (9 men, 1 woman) or 20 cases (16 men,4 women) would be prevented, if they had done physical exercises, could reduce their body weight to normal level or avoided alcohol consumption, assuming that these factors are causally related to colorectal cancer. It was estimated that 66 (17.8%;66/369) colorectal cancer cases (42 men, 24 women) who had all these three risk factors for the last 10 years would have been prevented, if they could control these three risk factors through effective preventive measures. Findings suggest that approximately 18% of colorectal cancer cases in Malaysia would be prevented through appropriate preventive measures such as doing regular physical exercises, reducing their body weight to normal level and avoiding alcohol consumption, if these factors are causally related to colorectal cancer. Scaling-up nationwide public health campaigns tailored to increase physical activity, controlling body weight within normal
Klusek, Justyna; Głuszek, Stanisław; Klusek, Jolanta
Increasingly often, molecular studies of colorectal cancer focus on low penetrance genes. Among the factors potentially modifying the risk of contracting colorectal cancer is the glutathione S-transferase (GST) gene family, encoding enzymes of the glutathione transferase type. Proteins of the GST family (glutathione S-transferases) are enzymes detoxifying a wide range of hazardous substances, such as reactive oxygen species (ROS) or xenobionts. Thus, their role, among other things, is the protection of DNA against oxidative damage, which may lead to mutations, and in consequence, favour carcinogenesis. GST gene polymorphisms may affect the functioning of the encoded enzymes, exerting an effect on the level of DNA damage, and therefore may have an indirect influence on the risk of the development of cancer. At present, there are many studies available concerning GST gene polymorphisms as factors modulating the risk of developing cancer, including colorectal cancer.
Wang, Dingzhi; DuBois, Raymond N.
Chronic inflammation is a risk factor for several gastrointestinal malignancies, including esophageal, gastric, hepatic, pancreatic and colorectal cancer. It has long been known that long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the relative risk of developing colorectal cancer. NSAIDs exert their anti-inflammatory and anti-tumor effects primarily by inhibiting activity of cyclooxygenase (COX) enzymes. Cyclooxygenase enzymes catalyze the conversion of arachidonic acid into prostanoids, including prostaglandins (PGs) and thromboxanes (TXs). Emerging evidence demonstrates that prostaglandins play an important role in inflammation and cancer. In this review, we highlight recent breakthroughs in our understanding of the roles of the different prostaglandins in colorectal cancer (CRC) and inflammatory bowel disease (IBD). These findings may provide a rationale for the development of new anti-inflammatory therapeutic approaches to cancer prevention and/or treatment. PMID:18406516
Rigter, Lisanne S; Spaander, Manon C W; Moons, Leon M; Bisseling, Tanya M; Aleman, Berthe M P; de Boer, Jan Paul; Lugtenburg, Pieternella J; Janus, Cecile P M; Petersen, Eefke J; Roesink, Judith M; Raemaekers, John M M; van der Maazen, Richard W M; Cats, Annemieke; Bleiker, Eveline M A; Snaebjornsson, Petur; Carvalho, Beatriz; Lansdorp-Vogelaar, Iris; Jóźwiak, Katarzyna; Te Riele, Hein; Meijer, Gerrit A; van Leeuwen, Flora E; van Leerdam, Monique E
Second primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine have an increased risk to develop colorectal cancer. Colonoscopy surveillance plays an important role in colorectal cancer prevention by removal of the precursor lesions (adenomas) and early detection of cancer, resulting in improved survival rates. Therefore, Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine could benefit from colonoscopy, or other surveillance modalities, which are expected to reduce colorectal cancer incidence and mortality. Current knowledge on clinicopathological and molecular characteristics of therapy-related colorectal cancer is limited. The pathogenesis of such colorectal cancers might be different from the pathogenesis in the general population and therefore these patients might require a different clinical approach. We designed a study with the primary aim to assess the diagnostic yield of a first surveillance colonoscopy among Hodgkin lymphoma survivors at increased risk of colorectal cancer and to compare these results with different screening modalities in the general population. Secondary aims include assessment of the test characteristics of stool tests and evaluation of burden, acceptance and satisfaction of CRC surveillance through two questionnaires. This prospective multicenter cohort study will include Hodgkin lymphoma survivors who survived ≥8 years after treatment with infradiaphragmatic radiotherapy and/or procarbazine (planned inclusion of 259 participants). Study procedures will consist of a surveillance colonoscopy with removal of precursor lesions (adenomas) and 6-8 normal colonic tissue biopsies, a fecal immunochemical test and a stool DNA test. All neoplastic lesions encountered will be classified using relevant histomorphological, immunohistochemical and
Kimura, Yasumi; Kono, Suminori; Toyomura, Kengo; Nagano, Jun; Mizoue, Tetsuya; Moore, Malcolm A; Mibu, Ryuichi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Yasunami, Yohichi; Maekawa, Takafumi; Takenaka, Kenji; Ichimiya, Hitoshi; Imaizumi, Nobutoshi
High intake of red meat has been associated with increased risk of colorectal cancer in Western countries. There has been much interest in the role of n-3 polyunsaturated fatty acids (PUFA) in colorectal cancer prevention, but epidemiological findings are limited and inconsistent. The objective of our study was to examine associations of meat, fish and fat intake with risk of colorectal cancer, paying particular attention to the subsite within the colorectum. Data were from the Fukuoka Colorectal Cancer Study, a population-based case-control study, covering 782 cases and 793 controls. Diet was assessed by interview, using newly developed personal-computer software for registering semiquantitative food frequencies. The intake of beef/pork, processed meat, total fat, saturated fat or n-6 PUFA showed no clear association with the overall or subsite-specific risk of colorectal cancer. There was an almost significant inverse association between n-3 PUFA and the risk of colorectal cancer; the covariate-adjusted odds ratio for the highest (median 3.94 g/day) versus lowest (median 1.99 g/day) quintile of energy-adjusted intake was 0.74 (95% confidence interval 0.52-1.06, trend P=0.050). The consumption of fish and fish products was similarly inversely related to the risk although the association was not statistically significant. These associations were more evident for distal colon cancer; adjusted odds ratio for the highest versus lowest quintile of n-3 PUFA intake was 0.56 (95% confidence interval 0.34-0.92, trend P=0.02). Our findings do not support the hypothesis that consumption of red meat increases colorectal cancer risk but do suggest that high intake of fish may decrease the risk, particularly of distal colon cancer.
Song, Li-Peng; Wang, Hao-Yu
Colorectal Cancer (CRC) is becoming a major threat to people’s life in China. Screening methods adopted by many other countries as effective counter-cancer methods have not been explicitly explored for people there. Thus, we present a Markov model with detailed precancerous adenoma states and then evaluate various screening strategies in this paper. Different from current researches, our model considers the population’s heterogeneous risk of developing adenomas and observation-based screening strategies. Furthermore, we also give a new cost-effectiveness metric. After calibrating, the model is simulated using the Monte Carlo method. Numerical results show that there are threshold values of compliance rates below which strategy with every ten-year colonoscopy becomes the most cost-effective method; otherwise, an observation-based screening strategy is the most cost-effective. We also find that strategy with single colonoscopy for adenoma-free individuals and every three-year colonoscopy for those with adenoma is recommended when the observation-based strategy is not considered. Our findings give an explicit and complete instruction in CRC screening protocol in average-risk Chinese. PMID:27536786
Esteban-Jurado, Clara; Garre, Pilar; Vila, Maria; Lozano, Juan José; Pristoupilova, Anna; Beltrán, Sergi; Abulí, Anna; Muñoz, Jenifer; Balaguer, Francesc; Ocaña, Teresa; Castells, Antoni; Piqué, Josep M; Carracedo, Angel; Ruiz-Ponte, Clara; Bessa, Xavier; Andreu, Montserrat; Bujanda, Luis; Caldés, Trinidad; Castellví-Bel, Sergi
Colorectal cancer (CRC) is one of the most frequent neoplasms and an important cause of mortality in the developed world. This cancer is caused by both genetic and environmental factors although 35% of the variation in CRC susceptibility involves inherited genetic differences. Mendelian syndromes account for about 5% of the total burden of CRC, with Lynch syndrome and familial adenomatous polyposis the most common forms. Excluding hereditary forms, there is an important fraction of CRC cases that present familial aggregation for the disease with an unknown germline genetic cause. CRC can be also considered as a complex disease taking into account the common disease-commom variant hypothesis with a polygenic model of inheritance where the genetic components of common complex diseases correspond mostly to variants of low/moderate effect. So far, 30 common, low-penetrance susceptibility variants have been identified for CRC. Recently, new sequencing technologies including exome- and whole-genome sequencing have permitted to add a new approach to facilitate the identification of new genes responsible for human disease predisposition. By using whole-genome sequencing, germline mutations in the POLE and POLD1 genes have been found to be responsible for a new form of CRC genetic predisposition called polymerase proofreading-associated polyposis. PMID:24587672
Galindo, Rodolfo J; Romao, Isabela; Valsamis, Ageliki; Weinerman, Stuart; Harris, Yael Tobi
Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25-dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean ± SD: 56.7 ± 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean ± SD: 15.6 ± 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control.
Haan, Josien C; Labots, Mariette; Rausch, Christian; Koopman, Miriam; Tol, Jolien; Mekenkamp, Leonie J M; van de Wiel, Mark A; Israeli, Danielle; van Essen, Hendrik F; van Grieken, Nicole C T; Voorham, Quirinus J M; Bosch, Linda J W; Qu, Xueping; Kabbarah, Omar; Verheul, Henk M W; Nagtegaal, Iris D; Punt, Cornelis J A; Ylstra, Bauke; Meijer, Gerrit A
Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumour biology. Here we describe the genomic landscape of tumour samples of a homogeneous well-annotated series of patients with metastatic CRC (mCRC) of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal subregions are associated with progression-free survival (PFS; uncorrected single-test P-values <0.005). These subregions are filtered for effect on messenger RNA expression, using an independent data set from The Cancer Genome Atlas which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of mCRC reveals a number of DNA copy number aberrations associated with response to drug therapy.
Haan, Josien C.; Labots, Mariette; Rausch, Christian; Koopman, Miriam; Tol, Jolien; Mekenkamp, Leonie J. M.; van de Wiel, Mark A.; Israeli, Danielle; van Essen, Hendrik F.; van Grieken, Nicole C. T.; Voorham, Quirinus J. M.; Bosch, Linda J. W.; Qu, Xueping; Kabbarah, Omar; Verheul, Henk M. W.; Nagtegaal, Iris D.; Punt, Cornelis J. A.; Ylstra, Bauke; Meijer, Gerrit A.
Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumour biology. Here we describe the genomic landscape of tumour samples of a homogeneous well-annotated series of patients with metastatic CRC (mCRC) of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal subregions are associated with progression-free survival (PFS; uncorrected single-test P-values <0.005). These subregions are filtered for effect on messenger RNA expression, using an independent data set from The Cancer Genome Atlas which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1–q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of mCRC reveals a number of DNA copy number aberrations associated with response to drug therapy. PMID:25394515
Sinha, Rupal; Doval, Dinesh Chandra; Hussain, Showket; Kumar, Kapil; Singh, Shivendra; Basir, Seemi Farhat; Bharadwaj, Mausumi
The study evaluated the patient, lifestyle and tumor profile in patients undergoing upfront surgery for sporadic colorectal cancer (CRC) in Indian population. One hundred consecutive patients were included. Details related to their demographic profile, habits, signs and symptoms, tumor profile, further treatment and follow up were recorded. The majority of the patients had colonic cancer (68%), advanced tumor stage 3 and 4 (46%), moderately differentiated tumors (70%) with absence of lymphatic invasion (60%) and metastasis (90%). Correlations between tumor location and abdominal pain (p-value 0.002), bleeding per rectum (p-value <0.001), difficulty in micturition (p-value 0.012) and constipation (p-value 0.007) were found to be statistically significant. Abdominal pain was more frequently reported in patients with metastasis (p-value 0.031). Loss of weight statistically correlated with absence of lymphatic invasion (p-value 0.047). Associations between tumor stage and alcohol intake (p-value 0.050) and non vegetarian diet (p-value 0.006); lymphatic invasion and intake of spicy food (p-value 0.040) and non vegetarian diet (p-value 0.001) and metastasis and alcohol intake (p-value 0.041) were also observed. Age and tumor grade were also correlated (p-value 0.020). Minimizing the adverse lifestyle factors can help in reducing the overall incidence of CRC in the Indian population.
Colorectal cancer (CRC) cells express renin and chymase through which they can activate angiotensin. Renin expression is induced by hyperglycemic conditions. As angiotensinogen is produced in the liver, CRC cells that can activate angiotensin have an enhanced ability to metastasize to this organ. In human CRC cases, patients with diabetes have higher activities of rennin and angiotensin-II in primary tumors, and on average, have a more progressed disease stage, especially with respect to liver metastasis. These patients exhibit a stronger association with Hemoglobin A1c levels and metastasis compared to patients without diabetes. In a combined diabetes/CRC liver metastasis mouse model, concurrent treatment with anti-angiotensin and hypoglycemic agents shows a synergic effect in terms of reduced liver metastasis and improved survival. The effect of anti-angiotensin treatment and blood sugar control as a baseline management for colon cancer patients with diabetes needs to be examined in clinical trials to establish whether it can prevent liver metastasis. PMID:23293754
Alagaratnam, Sharmini; Zhao, Sen; Nome, Torfinn; Løvf, Marthe; Bakken, Anne C.; Hektoen, Merete; Sveen, Anita; Lothe, Ragnhild A.; Skotheim, Rolf I.
With an annual estimated incidence of 1.4 million, and a five-year survival rate of 60%, colorectal cancer (CRC) is a major clinical burden. To identify novel RNA variants in CRC, we analyzed exon-level microarray expression data from a cohort of 202 CRCs. We nominated 25 genes with increased expression of their 3′ parts in at least one cancer sample each. To efficiently investigate underlying transcript structures, we developed an approach using rapid amplification of cDNA ends followed by high throughput sequencing (RACE-seq). RACE products from the targeted genes in 23 CRC samples were pooled together and sequenced. We identified VWA2-TCF7L2, DHX35-BPIFA2 and CASZ1-MASP2 as private fusion events, and novel transcript structures for 17 of the 23 other candidate genes. The high-throughput approach facilitated identification of CRC specific RNA variants. These include a recurrent read-through fusion transcript between KLK8 and KLK7, and a splice variant of S100A2. Both of these were overrepresented in CRC tissue and cell lines from external RNA-seq datasets. PMID:26474385
Rheem, Dae S; Baylink, David J; Olafsson, Snorri; Jackson, Christian S; Walter, Michael H
The fact that colorectal cancer (CRC) is the second leading cause of cancer mortality in the United States emphasizes the need for more effective preventive and therapeutic modalities. There is growing evidence that vitamin D may reduce the incidence of CRC. Results of epidemiologic, in vitro, in vivo animal and clinical studies suggest that a low serum vitamin D level may be a serious risk factor for CRC and a high serum vitamin D level may reduce the risk of CRC. On a molecular level, vitamin D suppresses CRC development and growth by affecting cell proliferation, differentiation, apoptosis, and angiogenesis. Vitamin D insufficiency and CRC are common in the elderly population. Vitamin D insufficiency is simple to screen for and treatable with vitamin D supplementation. Serum 25-hydroxyvitamin D (calcidiol) is the best measure of vitamin D status and should be checked routinely for individuals with risk factors for CRC. Maintaining serum concentrations of calcidiol above 32 ng/ml (80 nmol/l) in individuals whose serum calcidiol level is low may help prevent CRC as well as osteoporosis, fractures, infections, and cardiovascular disease. Daily calcidiol intake of 1000 International Units can increase serum vitamin D to sufficient levels in most elderly persons and, based on available data, may substantially lower the incidence of CRC with minimal risks.
Huang, Tao; Lin, Chengyuan; Zhong, Linda L. D.; Zhao, Ling; Zhang, Ge; Lu, Aiping; Wu, Jiang; Bian, Zhaoxiang
As a leading cause of cancer deaths worldwide, colorectal cancer (CRC) results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in CRC, particularly aberrant histone methylation mediated by histone methyltransferases (HMTs) and demethylases (HDMs), have drawn increasing interest in recent years. In this paper, we aim to review the roles of histone methylation and associated enzymes in the pathogenesis of CRC, and the development of small-molecule modulators to regulate histone methylation for treating CRC. Multiple levels of evidence suggest that aberrant histone methylations play important roles in CRC. More than 20 histone-methylation enzymes are found to be clinically relevant to CRC, including 17 oncoproteins and 8 tumor suppressors. Inhibitors of EZH2 and DOT1L have demonstrated promising therapeutic effects in preclinical CRC treatment. Potent and selective chemical probes of histone-methylation enzymes are required for validation of their functional roles in carcinogenesis and clinical translations as CRC therapies. With EZH2 inhibitor EPZ-6438 entering into phase I/II trials for advanced solid tumors, histone methylation is emerging as a promising target for CRC. PMID:28286564
Fedewa, Stacey A; Sauer, Ann Goding; Siegel, Rebecca L; Smith, Robert A; Torre, Lindsey A; Jemal, Ahmedin
Asian Americans (AA) are less likely to be screened for colorectal cancer compared with non-Hispanic Whites (NHW), with a widening disparity for some AA subgroups in the early 2000s. Whether these patterns have continued in more recent years is unknown. We examined temporal trends in colorectal cancer screening among AA overall compared with NHWs and by AA subgroup (Chinese, Japanese, Korean, Filipino, South Asian, Vietnamese) using data from the 2003, 2005, 2007, and 2009 California Health Interview Surveys. Unadjusted (PR) and adjusted (aPR) prevalence ratios for colorectal cancer screening, accounting for sociodemographic, health care, and acculturation factors, were calculated for respondents ages 50 to 75 years (NHW n = 60,125; AA n = 6,630). Between 2003 and 2009, colorectal cancer screening prevalence increased from 43.3% to 64.6% in AA (P ≤ 0.001) and from 58.1% to 71.4% in NHW (P ≤ 0.001). Unadjusted colorectal cancer screening was significantly lower among AA compared with NHW in 2003 [PR = 0.74; 95% confidence interval (CI), 0.68-0.82], 2005 (PR = 0.78; 95% CI, 0.72-0.84), 2007 (PR = 0.91; 95% CI, 0.85-0.96), and 2009 (PR = 0.90; 95% CI, 0.84-0.97), though disparities narrowed over time. After adjustment, there were no significant differences in colorectal cancer screening between the two groups, except in 2003. In subgroup analyses, between 2003 and 2009, colorectal cancer screening significantly increased by 22% in Japanese, 56% in Chinese, 47% in Filipino, and 94% in Koreans. In our study of California residents, colorectal cancer screening disparities between AA and NHW narrowed, but were not eliminated and screening prevalence among AA remains below nationwide goals, including the Healthy People 2020 goal of increasing colorectal cancer screening prevalence to 70.5%. Cancer Epidemiol Biomarkers Prev; 25(6); 995-1000. ©2016 AACR. ©2016 American Association for Cancer Research.
Cao, Yin; Meyerhardt, Jeffrey A.; Chan, Andrew T.; Wu, Kana; Fuchs, Charles S.; Giovannucci, Edward L.
Purpose To assess the association between pre- and postdiagnostic time spent sitting watching TV as well as other sedentary behaviors (other sitting at home and at work/driving) and mortality from colorectal cancer or other causes, and overall mortality. Methods We followed stage I-III colorectal cancer patients from the Health Professionals Follow-up Study (1986–2010). Cox models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results 926 and 714 patients were included in the analysis of pre- and postdiagnostic TV watching respectively, and 471 and 325 died during follow-up. Prolonged prediagnostic TV viewing was associated with increased risk of colorectal cancer-specific mortality independent of leisure-time physical activity. The HRs (95% CIs) for 0–6, 7–13,14–20 and ≥21 h/wk were 1.00 (referent), 0.84 (0.56–1.25), 1.15 (0.75–1.78), 2.13 (1.31–3.45) (Ptrend=0.01). The association was observed primarily among overweight and obese individuals. Prediagnostic TV watching was also associated with overall mortality within 5 years of diagnosis, largely due to the association with colorectal cancer mortality. Other prediagnostic sitting at home or at work/driving was not associated with mortality. Postdiagnostic TV viewing was associated with non-significant increased risk of colorectal cancer-specific mortality (HR for ≥21 vs 0–6 h/wk=1.45; 95% CI 0.73–2.87) adjusting for TV viewing before diagnosis. Conclusion Prolonged prediagnostic TV watching is associated with higher colorectal cancer-specific mortality independent of leisure-time physical activity among colorectal cancer patients. PMID:26293240
Yang, Baiyu; Gapstur, Susan M; Newton, Christina C; Jacobs, Eric J; Campbell, Peter T
Alcohol consumption is associated with a higher risk of colorectal cancer, but to the authors' knowledge its influence on survival after a diagnosis of colorectal cancer is unclear. The authors investigated associations between prediagnosis and postdiagnosis alcohol intake with mortality among survivors of colorectal cancer. The authors identified 2458 men and women who were diagnosed with invasive, nonmetastatic colorectal cancer between 1992 (enrollment into the Cancer Prevention Study II Nutrition Cohort) and 2011. Alcohol consumption was self-reported at baseline and updated in 1997, 1999, 2003, and 2007. Postdiagnosis alcohol data were available for 1599 participants. Of the 2458 participants diagnosed with colorectal cancer, 1156 died during follow-up through 2012. Prediagnosis and postdiagnosis alcohol consumption were not found to be associated with all-cause mortality, except for an association between prediagnosis consumption of <2 drinks per day and a slightly lower risk of all-cause mortality (relative risk [RR], 0.86; 95% confidence interval [95% CI], 0.74-1.00) compared with never drinking. Alcohol use was generally not associated with colorectal cancer-specific mortality, although there was some suggestion of increased colorectal cancer-specific mortality with postdiagnosis drinking (RR, 1.27 [95% CI, 0.87-1.86] for current drinking of <2 drinks/day and RR, 1.44 [95% CI, 0.80-2.60] for current drinking of ≥2 drinks/day). The results of the current study do not support an association between alcohol consumption and all-cause mortality among individuals with nonmetastatic colorectal cancer. The association between postdiagnosis drinking and colorectal cancer-specific mortality should be examined in larger studies of individuals diagnosed with nonmetastatic colorectal cancer. Cancer 2017;123:2006-2013. © 2017 American Cancer Society. © 2017 American Cancer Society.
Hemminki, K; Li, X
Although estimates are available of the proportion of hereditary nonpolyposis colorectal cancer (HNPCC) among all colorectal cancer (CRC), its proportion among familial CRC is unclear. We estimated these proportions epidemiologically from the nationwide Swedish Family-Cancer Database on 9.6 million individuals. Colorectal adenocarcinomas were retrieved from the Cancer Registry covering years 1958–1996. Standardized incidence ratios (SIRs) were calculated for offspring (aged less than 62 years) when their parent had colorectal adenocarcinoma. In 9.82% of all families, an offspring and a parent were affected, giving a population attributable proportion of 4.91% and a familial SIR of 2.00. When offspring and parents shared the anatomic site, the SIR was 2.32 for proximal and 2.00 for distal CRC. When offspring were diagnosed before age 40 years and parents before age 50 years, the SIR was 25.72 for familial proximal CRC. In older age groups familial risks did not differ between proximal and distal CRC. Familial risks were increased also for endometrial, small intestinal and gastric cancers, manifestations in HNPCC. Depending on which assumptions were made, HNPCC was calculated to account for 20 to 50% of familial CRC, corresponding to 1 or 2.5% of all CRC among 0–61-year-old individuals. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11286479
Zhang, Shuyu; Wu, Yong; Wu, Yongyou; Zhao, Kui; Xing, Chungen; Cao, Jianping; Zhu, Hong; Li, Ming; Ye, Zhenyu; Peng, Wei
Autophagy is a double-edged sword in tumor development. Recent studies have found that miRNAs have an inhibitory effect on the regulation of autophagy. It has been reported that miR-31 plays an important role in the development of colorectal cancer. However, what role miR-31 plays in colorectal cancer-associated fibroblasts (CAFs) has not been determined. In this study, we confirmed that the expression of miR-31 in CAFs was higher than in normal colorectal fibroblasts (NFs). We also found that treatment of CAFs with miR-31 mimic inhibited the expression of the autophagy-related genes Beclin-1, ATG, DRAM and LC3. In addition, we found up-regulation of miR-31 significantly affected colorectal cancer cell behaviors, including proliferation, invasion and apoptosis. Also, up-regulation of miR-31 in CAF could increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. In summary, miR-31 can inhibit autophagy in colorectal CAFs, affect colorectal cancer development, and increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. We hypothesize that miR-31 may become a new target of treatments for colorectal cancer. PMID:27793031
Ion, D; Stoian, RV; Serban, MB
The case presented raised our scientific curiosity and it is worthy of being brought in front of the medical audience because of several reasons presented below. Presently, there are 3 hereditary syndromes that have a demonstrated etiological relationship with the colorectal cancer: Familiar Adenomatous Polyposis (FAP syndrome), HNPCC syndrome (Hereditary Nonpoliposis Colorectal Cancer) and MAP syndrome. Discovered only in 2002, the MAP syndrome (MYH associated polyposis) is the first hereditary syndrome that has autosomal recessive transmission. The APC gene can be mutated in several ways during the colonic oncogenesis: congenital in the FAP syndrome, somatic in sporadic colorectal cancers and secondary to the MYH gene inactivation in MAP syndrome. MAP phenotype is similar to the FAP phenotype because of the somatic mutations to the APC gene. Colonic polyposis is lower than FAP syndrome and appeared later, in the 40's and 50's. Colorectal cancers are frequent and discovered in the same moment as the colonic polyposis. Patients are diagnosed mostly in cancer stages. Colonoscopy shows polyps disseminated around the entire colic frame. Treatment in these cases is total rectocolectomy with ileoanal anastomosis. When working in a general emergency surgery clinic, physicians are often faced with colorectal cancers in different evolutive stages, and mostly they are faced with their complications. PMID:21505584
Cappellani, Alessandro; Zanghì, Antonio; Di Vita, Maria; Cavallaro, Andrea; Piccolo, Gaetano; Veroux, Pierfrancesco; Lo Menzo, Emanuele; Cavallaro, Vincenzo; de Paoli, Paolo; Veroux, Massimiliano; Berretta, Massimiliano
Multiple factors have been described among the causes of non-hereditary colorectal cancer. In Western countries, the most common risk factors include upper-middle socioeconomic status and dietary regimens rich in proteins and animal fats. High consumption of red meats, smoked foods, cold cuts, or canned foods is believed to contribute to carcinogenesis as they directly affect epithlial turnover and cause metabolism of biliary acids. Dietary fibers have protective effects in that they capture the fats and biliary acids, thereby inhibiting their activity. Tobacco smoking acts both locally and systemically on the colorectal mucosa through the production of carcinogenic agents. Finally, the action of alcohol, in association with nicotine addiction, also increases the risk of developing colorectal tumors. Knowledge of dietary and environmental factors is of paramount importance in implementing preventive strategies for colorectal cancer.
Metastatic Malignant Neoplasm in the Brain; Metastatic Solid Neoplasm; Recurrent Colorectal Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Solid Neoplasm; Stage IV Colorectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Pancreatic Cancer; Unresectable Solid Neoplasm
Jarrar, Awad M; Church, James M; Fay, Susan; Kalady, Matthew F
Hereditary nonpolyposis colorectal cancer is a hereditary syndrome defined by personal and family history of colorectal and other cancers. Some patients with this condition have multiple serrated polyps, which are the hallmark of hyperplastic polyposis syndrome, a rare colorectal cancer syndrome characterized by multiple hyperplastic/serrated polyps and an increased risk of colorectal cancer. We hypothesized that this may represent a unique group of patients, and this study investigates a possible association between the two syndromes. A hereditary colorectal cancer registry was reviewed for patients who fit hereditary nonpolyposis colorectal cancer or familial colorectal cancer and hyperplastic polyposis syndrome criteria. Twelve patients from seven families were identified. Four families had more than one person meeting the criteria. All patients were white, and four were women. Ten of 12 patients fit Amsterdam criteria, and two were designated with familial colorectal cancer. The median cumulative number of hyperplastic polyps resected per patient was 6, half of which were located in the right colon. Seven of the 12 patients developed colorectal cancer. Ten patients had personal or family history of other cancers: prostate, breast, testicular, salivary gland, lung, and Hodgkin's disease. Patients meeting criteria for hereditary nonpolyposis colorectal cancer may also carry a diagnosis of hyperplastic polyposis syndrome. Possible explanations include: 1) two hereditary syndromes are present in the same patient, 2) serrated polyps are part of the phenotype of hereditary nonpolyposis colorectal cancer, or 3) hereditary nonpolyposis colorectal cancer is potentially misdiagnosed in some families who do, in fact, have hyperplastic polyposis.
Homan, Sherri G.; Yun, Shumei; Stewart, Bob R.; Armer, Jane M.
Breast cancer survivors are at risk of developing a second primary cancer. Colorectal cancer (CRC) is one of the leading second primary cancers, and it is often preventable. We developed a multi-component educational tool to inform and encourage women breast cancer survivors to engage in CRC screening. To assess the strengths and weakness of the tool and to improve the relevancy to the target audience, we convened four focus groups of women breast cancer survivors in Missouri. We also assessed the potential impact of the tool on the knowledge, attitudes, and beliefs regarding CRC and collected information on the barriers to CRC screening through pre- and post-focus groups’ questionnaires. A total of 43 women breast cancer survivors participated and provided very valuable suggestions on design and content to update the tool. Through the process and comparing pre- and post-focus group assessments, a significantly higher proportion of breast cancer survivors strongly agreed or agreed that CRC is preventable (78.6% vs. 96.9%, p = 0.02) and became aware that they were at a slightly increased risk for CRC (18.6% vs. 51.7%, p = 0.003). The most cited barrier was the complexity of preparation for colonoscopy. PMID:26258794
Stanners, Greig; Lang, Jaroslaw; Brewster, David H; Carey, Francis A; Fraser, Callum G
Background Little is known about interval cancers (ICs) in colorectal cancer (CRC) screening. Objective The purpose of this study was to identify IC characteristics and compare these with screen-detected cancers (SCs) and cancers in non-participants (NPCs) over the same time period. Design This was an observational study done in the first round of the Scottish Bowel Screening Programme. All individuals (772,790), aged 50–74 years, invited to participate between 1 January 2007 and 31 May 2009 were studied by linking their screening records with confirmed CRC records in the Scottish Cancer Registry (SCR). Characteristics of SC, IC and NPC were determined. Results There were 555 SCs, 502 ICs and 922 NPCs. SCs were at an earlier stage than ICs and NPCs (33.9% Dukes’ A as against 18.7% in IC and 11.3% in NPC), screening preferentially detected cancers in males (64.7% as against 52.8% in IC and 59.7% in NPC): this was independent of a different cancer site distribution in males and females. SC in the colon were less advanced than IC, but not in the rectum. Conclusion ICs account for 47.5% of the CRCs in the screened population, indicating approximately 50% screening test sensitivity: guaiac faecal occult blood testing (gFOBT) sensitivity is less for women than for men and gFOBT screening may not be effective for rectal cancer. PMID:27536369
Homan, Sherri G; Yun, Shumei; Stewart, Bob R; Armer, Jane M
Breast cancer survivors are at risk of developing a second primary cancer. Colorectal cancer (CRC) is one of the leading second primary cancers, and it is often preventable. We developed a multi-component educational tool to inform and encourage women breast cancer survivors to engage in CRC screening. To assess the strengths and weakness of the tool and to improve the relevancy to the target audience, we convened four focus groups of women breast cancer survivors in Missouri. We also assessed the potential impact of the tool on the knowledge, attitudes, and beliefs regarding CRC and collected information on the barriers to CRC screening through pre- and post-focus groups' questionnaires. A total of 43 women breast cancer survivors participated and provided very valuable suggestions on design and content to update the tool. Through the process and comparing pre- and post-focus group assessments, a significantly higher proportion of breast cancer survivors strongly agreed or agreed that CRC is preventable (78.6% vs. 96.9%, p = 0.02) and became aware that they were at a slightly increased risk for CRC (18.6% vs. 51.7%, p = 0.003). The most cited barrier was the complexity of preparation for colonoscopy.
Ulrich, Cornelia M
The B vitamin folate is essential for one-carbon transfer reactions, including those related to the methylation of DNA or other substrates and nucleotide synthesis. Epidemiologic and experimental studies implicate low-folate intakes in elevated risk of colorectal neoplasia and suggest that biologic mechanisms underlying this relation include disturbances in DNA methylation patterns or adverse effects on DNA synthesis and repair. With the completion of the Human Genome Project, a vast amount of data on inherited genetic variability has become available. This genetic information can be used in studies of molecular epidemiology to provide information on multiple aspects of folate metabolism. First, studies linking polymorphisms in folate metabolism to an altered risk of cancer provide evidence for a causal link between this pathway and colorectal carcinogenesis. Second, studies on genetic characteristics can help clarify whether certain individuals may benefit from higher or lower intakes of folate or nutrients relevant to folate metabolism. Third, studies on genetic polymorphisms can generate hypotheses regarding possible biologic mechanisms that connect this pathway to carcinogenesis. Last, genetic variability in folate metabolism may predict survival after a cancer diagnosis, possibly via pharmacogenetic effects. To solve the puzzle of the folate-cancer relation, a transdisciplinary approach is needed that integrates knowledge from epidemiology, clinical studies, experimental nutrition, and mathematical modeling. This review illustrates knowledge that can be gained from molecular epidemiology in the context of nutrigenetics, and the questions that this approach can answer or raise.
Ragusa, Marco; Barbagallo, Cristina; Statello, Luisa; Condorelli, Angelo Giuseppe; Battaglia, Rosalia; Tamburello, Lucia; Barbagallo, Davide; Di Pietro, Cinzia; Purrello, Michele
For two decades Vogelstein’s model has been the paradigm for describing the sequence of molecular changes within protein-coding genes that would lead to overt colorectal cancer (CRC). This model is now too simplistic in the light of recent studies, which have shown that our genome is pervasively transcribed in RNAs other than mRNAs, denominated non-coding RNAs (ncRNAs). The discovery that mutations in genes encoding these RNAs [i.e., microRNAs (miRNAs), long non-coding RNAs, and circular RNAs] are causally involved in cancer phenotypes has profoundly modified our vision of tumour molecular genetics and pathobiology. By exploiting a wide range of different mechanisms, ncRNAs control fundamental cellular processes, such as proliferation, differentiation, migration, angiogenesis and apoptosis: these data have also confirmed their role as oncogenes or tumor suppressors in cancer development and progression. The existence of a sophisticated RNA-based regulatory system, which dictates the correct functioning of protein-coding networks, has relevant biological and biomedical consequences. Different miRNAs involved in neoplastic and degenerative diseases exhibit potential predictive and prognostic properties. Furthermore, the key roles of ncRNAs make them very attractive targets for innovative therapeutic approaches. Several recent reports have shown that ncRNAs can be secreted by cells into the extracellular environment (i.e., blood and other body fluids): this suggests the existence of extracellular signalling mechanisms, which may be exploited by cells in physiology and pathology. In this review, we will summarize the most relevant issues on the involvement of cellular and extracellular ncRNAs in disease. We will then specifically describe their involvement in CRC pathobiology and their translational applications to CRC diagnosis, prognosis and therapy. PMID:26556998
Green, Chadwick John; de Dauwe, Palina; Boyle, Terry; Tabatabaei, Seyed Mehdi; Fritschi, Lin; Heyworth, Jane Shirley
Background Data regarding the effects of tea, coffee, and milk on the risk of colorectal cancer are inconsistent. We investigated associations of tea, coffee, and milk consumption with colorectal cancer risk and attempted to determine if these exposures were differentially associated with the risks of proximal colon, distal colon, and rectal cancers. Methods Data from 854 incident cases and 948 controls were analyzed in a case-control study of colorectal cancer in Western Australia during 2005–07. Multivariable logistic regression was used to analyze the associations of black tea (with and without milk), green tea, herbal tea, hot coffee, iced coffee, and milk with colorectal cancer. Results Consumption of 1 or more cups of herbal tea per week was associated with a significantly decreased risk of distal colon cancer (adjusted odds ratio, 0.37; 95% CI, 0.16–0.82; PTrend = 0.044), and consumption of 1 or more cups of iced coffee per week was associated with increased risk of rectal cancer (adjusted odds ratio, 1.52; 95% CI, 0.91–2.54; PTrend = 0.004). Neither herbal tea nor iced coffee was associated with the risk of proximal colon cancer. Hot coffee was associated with a possible increased risk of distal colon cancer. Black tea (with or without milk), green tea, decaffeinated coffee, and milk were not significantly associated with colorectal cancer risk. Conclusions Consumption of herbal tea was associated with reduced risk of distal colon cancer, and consumption of iced coffee was associated with increased rectal cancer risk. PMID:24531002
Colorectal cancer is the third commonest malignancy worldwide and the second commonest cause of cancer-related deaths.1,2 Around 15-25% of patients with colorectal cancer have metastases at presentation, and a further 20-25% develop them subsequently.3 Management for metastatic disease is mainly palliative and traditionally 5-year survival has been rare.3-5 In colorectal cancer, metastases mostly occur in the liver and in 30-50% of patients with liver involvement, this is the only site of spread. For those with liver-only metastases, resection of these lesions provides a chance of longer-term survival or even cure (e.g. 5-year survival 25-71%).4,6-13 Here we focus on recent advances in chemotherapy for patients with initially unresectable liver metastases, aimed at rendering such lesions operable, with potential improvements in survival.4,13,14.
Mihalache, A; Rogoveanu, I
Colorectal cancer stands at the top of oncologic pathology in the world, and in the same measure in Romania because is the third most frequent cancer diagnosed in men and women. Colorectal cancer develops as a result of mutations in genes that control proliferation and cell death. It was established that in the development of a tumor there is originally a prevascular phase followed by a phase of tumor angiogenesis. In the future it is necessary to develop new clinical protocols that angiogenesis inhibitors are associated with chemo or radiotherapy, conventional or other methods such as immunotherapy and gene therapy.
MIHALACHE, A.; ROGOVEANU, I.
Colorectal cancer stands at the top of oncologic pathology in the world, and in the same measure in Romania because is the third most frequent cancer diagnosed in men and women. Colorectal cancer develops as a result of mutations in genes that control proliferation and cell death. It was established that in the development of a tumor there is originally a prevascular phase followed by a phase of tumor angiogenesis. In the future it is necessary to develop new clinical protocols that angiogenesis inhibitors are associated with chemo or radiotherapy, conventional or other methods such as immunotherapy and gene therapy. PMID:24791198
Schmit, Stephanie L; Rennert, Hedy S; Rennert, Gad; Gruber, Stephen B
Coffee contains several bioactive compounds relevant to colon physiology. Although coffee intake is a proposed protective factor for colorectal cancer, current evidence remains inconclusive. We investigated the association between coffee consumption and risk of colorectal cancer in 5,145 cases and 4,097 controls from the Molecular Epidemiology of Colorectal Cancer (MECC) study, a population-based case-control study in northern Israel. We also examined this association by type of coffee, by cancer site (colon and rectum), and by ethnic subgroup (Ashkenazi Jews, Sephardi Jews, and Arabs). Coffee data were collected by interview using a validated, semi-quantitative food frequency questionnaire. Coffee consumption was associated with 26% lower odds of developing colorectal cancer [OR (drinkers vs. non-drinkers), 0.74; 95% confidence interval (CI), 0.64-0.86; P < 0.001]. The inverse association was also observed for decaffeinated coffee consumption alone (OR, 0.82; 95% CI, 0.68-0.99; P = 0.04) and for boiled coffee (OR, 0.82; 95% CI, 0.71-0.94; P = 0.004). Increasing consumption of coffee was associated with lower odds of developing colorectal cancer. Compared with <1 serving/day, intake of 1 to <2 servings/day (OR, 0.78; 95% CI, 0.68-0.90; P < 0.001), 2 to 2.5 servings/day (OR, 0.59; 95% CI, 0.51-0.68; P < 0.001), and >2.5 servings/day (OR, 0.46; 95% CI, 0.39-0.54; P < 0.001) were associated with significantly lower odds of colorectal cancer (Ptrend < 0.001), and the dose-response trend was statistically significant for both colon and rectal cancers. Coffee consumption may be inversely associated with risk of colorectal cancer in a dose-response manner. Global coffee consumption patterns suggest potential health benefits of the beverage for reducing the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 634-9. ©2016 AACR. ©2016 American Association for Cancer Research.
... 42 Public Health 2 2012-10-01 2012-10-01 false Colorectal cancer screening tests: Conditions for...) BENEFITS Medical and Other Health Services § 410.37 Colorectal cancer screening tests: Conditions for and...) Colorectal cancer screening tests means any of the following procedures furnished to an individual for the...
... 42 Public Health 2 2011-10-01 2011-10-01 false Colorectal cancer screening tests: Conditions for...) BENEFITS Medical and Other Health Services § 410.37 Colorectal cancer screening tests: Conditions for and...) Colorectal cancer screening tests means any of the following procedures furnished to an individual for the...
... 42 Public Health 2 2013-10-01 2013-10-01 false Colorectal cancer screening tests: Conditions for...) BENEFITS Medical and Other Health Services § 410.37 Colorectal cancer screening tests: Conditions for and...) Colorectal cancer screening tests means any of the following procedures furnished to an individual for the...
... 42 Public Health 2 2014-10-01 2014-10-01 false Colorectal cancer screening tests: Conditions for...) BENEFITS Medical and Other Health Services § 410.37 Colorectal cancer screening tests: Conditions for and...) Colorectal cancer screening tests means any of the following procedures furnished to an individual for the...
... 42 Public Health 2 2010-10-01 2010-10-01 false Colorectal cancer screening tests: Conditions for...) BENEFITS Medical and Other Health Services § 410.37 Colorectal cancer screening tests: Conditions for and...) Colorectal cancer screening tests means any of the following procedures furnished to an individual for the...
Mitchell, R J; Brewster, D; Campbell, H; Porteous, M E M; Wyllie, A H; Bird, C C; Dunlop, M G
Background and aims: Family history is used extensively to estimate the risk of colorectal cancer but there is considerable potential for recall bias and inaccuracy. Hence we systematically assessed the accuracy of family history reported at interview compared with actual cancer experience in relatives. Methods: Using face to face interviews, we recorded family history from 199 colorectal cancer cases and 133 community controls, totalling 5637 first and second degree relatives (FDRs/SDRs). We linked computerised cancer registry data to interview information to determine the accuracy of family history reporting. Results: Cases substantially underreported colorectal cancer arising both in FDRs (sensitivity 0.566 (95% confidence interval (CI) 0.433, 0.690); specificity 0.990 (95% CI 0.983, 0.994)) and SDRs (sensitivity 0.271 (95% CI 0.166, 0.410); specificity 0.996 (95% CI 0.992, 0.998)). There was no observable difference in accuracy of reporting family history between case and control interviewees. Control subjects similarly underreported colorectal cancer in FDRs (sensitivity 0.529 (95% CI 0.310, 0.738); specificity 0.995 (95% CI 0.989, 0.998)) and SDRs (sensitivity 0.333 (95% CI 0.192, 0.512); specificity 0.995 (95% CI 0.991, 0.995)). To determine practical implications of inaccurate family history, we applied family history criteria before and after record linkage. Only two of five families reported at interview to meet surveillance criteria did so after validation, whereas only two of six families that actually merited surveillance were identified by interview. Conclusions: This study has quantified the inaccuracy of interview in identifying people at risk of colorectal cancer due to a family history. Colorectal cancer was substantially underreported and so family history information should be interpreted with caution. These findings have considerable relevance to identifying patients who merit surveillance colonoscopy and to epidemiological studies. PMID
Lemon, Stephenie C; Zapka, Jane G; Estabrook, Barbara; Erban, Stephen; Luckmann, Roger
The aim of this study was to assess knowledge, beliefs, and practices of primary care clinicians regarding colorectal cancer screening. We surveyed 77 primary care providers in six clinics in central Massachusetts to evaluate several factors related to colorectal cancer screening. Most agreed with guidelines for fecal occult blood test (97%) and sigmoidoscopy (87%), which were reported commonly as usual practice. Although the majority (86%) recommended colonoscopy as a colorectal cancer screening test, it was infrequently reported as usual practice. Also, 36% considered barium enema a colorectal cancer screening option, and it was rarely reported as usual practice. Despite lack of evidence supporting effectiveness, digital rectal examinations and in-office fecal occult blood test were commonly reported as usual practice. However, these were usually reported in combination with a guideline-endorsed testing option. Although only 10% reported that fecal occult blood test/home was frequently refused, 60% reported sigmoidoscopy was. Frequently cited patient barriers to sigmoidoscopy compliance included fear the procedure would hurt and that patients assume symptoms occur if there is a problem. Perceptions of health systems barriers to sigmoidoscopy were less strong. Most providers recommended guideline-endorsed colorectal cancer screening. However, patient refusal for sigmoidoscopy was common. Results indicate that multiple levels of intervention, including patient and provider education and systems strategies, may help increase prevalence.
Azizi, Hosein; Asadollahi, Khairollah; Davtalab Esmaeili, Elham; Mirzapoor, Mohammad
Background: Role of diet on colorectal cancer (CRC) has been considered in terms of single foods and nutrients, but less frequently in terms of dietary patterns in Iran. The objective of this study was to determine the association between Iranian dietary patterns and CRC. Methods: This case–control study was conducted in four hospitals in Tabriz City of Iran including 414 participants aged 35–75 years:207 cases with CRC confirmed by pathology and colonoscopy findings were selected and 207 controls free of neoplastic conditions and diet-related chronic diseases (from the same hospital at the same period for the cases). Dietary data were assessed using a 123-item semi-quantitative food frequency questionnaire. Two dietary patterns were found by using of Principal Component Analysis (PCA) method;“Healthy pattern”and “Iranian pattern”. Multivariate logistic regression analysis was used to estimate adjusted odds ratios (OR) for relationship between dietary patterns and colorectal cancer. Results: After adjusting for confounding factors, the Iranian dietary pattern was significantly associated with an increased odds of colorectal cancer (OR= 1.46; 95% Confidenec Interval (CI)=1.05–2.19) while a reduced odds of colorectal cancer was observed with the Healthy dietary pattern (OR=0.18; 95% CI= 0.091-0.47). Conclusion: Iranian dietary pattern (IDP) seems to increase the odds of colorectal cancer and protective effect of Healthy dietary pattern. PMID:26000248
Li, W; Ye, X; Yang, X; Li, Y; Huang, G; Wang, J; Han, X; Ni, X; Wei, Z; Zheng, A; Meng, M
Patients suffering local recurrence of colorectal cancer which cannot be surgically removed are troubled with severe pain and poor quality of life. The aim of this study is to evaluate the efficacy and safety of computed tomography (CT)-guided microwave ablation (MWA) as palliative treatment for recurrent unresectable colorectal cancer. Thirty-one patients were suffering locally recurrent colorectal cancer underwent MWA with CT guidance. The MWA power was set at 60-80 W, 6-8 min. Effectiveness was evaluated by visual analog scale (VAS) with a follow-up of 6-month. Complications were also recorded. Technical success was achieved in all patients. Mean VAS preprocedure was 7.10. Mean VAS postprocedure were as follows: 1 week, 2.65 (P < 0.001); 1 month, 0.81 (P < 0.001); 3 months 0.45 (P < 0.001); and 6 months 0.19 (P < 0.001). No serious complications were observed including intestinal fistulas, bladder fistulas, or peripheral vascular or nerve injury. CT-guided MWA as treatment of recurrent colorectal cancer can quickly and effectively relieve pain. It is a minimally invasive, safe, and efficient palliative treatment of recurrent colorectal cancer.
The consensus of epidemiologic evidence indicates that an abundant intake of foodstuffs rich in folate conveys protection against the development of colorectal cancer, and perhaps some other common cancers as well. Pre-clinical models substantiate that the relationship is a genuinely causal one. Pre...
The treatment of colorectal cancer is undergoing serious transformation. Surgical techniques have evolved, the role of adjuvant radio- and chemotherapy has been confirmed as an essential part of the current treatment of these cancer and new drugs, established in advanced disease are now being introduced in combination schemes of promise in both palliative and adjuvant chemotherapy.
Early detection of cancer through screening is an important step in decreasing both morbidity and mortality. Likewise, specific modifiable lifestyle behaviors are associated with reduced risk of colorectal cancer. Lifestyle practices have also been shown to maximize health after the primary treatmen...
... The three main testsâ€“colonoscopy, FOBT/FIT, and flexible sigmoidoscopy are all effective at finding cancer early. ... Tested for Colorectal Cancer? [PSA - 0:60 seconds] Screen for Life: Meryl Streep/Control [0:60 seconds] ...
Ponz de Leon, M; Benatti, P; Borghi, F; Pedroni, M; Scarselli, A; Di Gregorio, C; Losi, L; Viel, A; Genuardi, M; Abbati, G; Rossi, G; Menigatti, M; Lamberti, I; Ponti, G; Roncucci, L
Background and aims: Although diet and lifestyle are associated with the development of colorectal malignancies, the only clearly identified aetiological factors in colorectal cancer are inheritance (hereditary non-polyposis colorectal cancer (HNPCC) and familial polyposis), inflammatory bowel diseases, papillomavirus, and acquired immunodeficiency syndrome (AIDS). Our aim was to determine what proportion of colorectal neoplasms could be attributed to these specific factors. Patients and methods: Data from a colorectal cancer registry were analysed over a 15 year period, during which nearly 2500 cases were recorded. In patients with suspected HNPCC, microsatellite instability and immunohistochemical expression of proteins encoded by the main DNA mismatch repair genes were assessed. In families with unstable neoplasms, constitutional mutations of the mismatch repair genes hMSH2, hMLH1, and hMSH6 were evaluated by single strand conformation polymorphism analysis and sequencing. Results: Inflammatory bowel diseases, familial polyposis, and AIDS were rare causes of colorectal cancer (three, three, and one case, respectively). Anal squamous carcinoma developed in 27 patients (1.0%) and could be attributed to papillomavirus infection. In 58 patients (from 34 families) a clinical diagnosis of HNPCC was established (2.4%). In total, cases with a known aetiology were 92 (3.7% of all patients). Microsatellite instability was detected in 15 cancers from HNPCC families, and germline mutations in six families (12 patients, 0.5% of the total). Families with unstable tumours, with or without mutations, were clinically similar, suggesting the involvement of the mismatch repair system even when mutations were not detected. Conclusions: The study suggests that the aetiology of colorectal malignancies remains elusive in the large majority of cases. Among specific causes, HNPCC represents the most frequent. However, with a population based approach, constitutional mutations of the
Zapka, Jane G; Puleo, Elaine; Vickers-Lahti, Maureen; Luckmann, Roger
Developing effective programs to promote colorectal cancer (CRC) screening requires understanding of the effect of healthcare system factors on access to screening and adherence to guidelines. This study assessed the role of insurance status, type of plan, the frequency of preventive health visits, and provider recommendation on utilization of CRC screening tests using a cross-sectional, random-digit-dial survey of 1002 Massachusetts residents aged > or =50. A broad definition of CRC screening status included colonoscopy or barium enema (screening or diagnostic) within 10 years, flexible sigmoidoscopy (FSIG) within 5 years, and fecal occult blood testing (FOBT) in the past year as options; 51.7% of subjects aged 50 to 64 and 61.5% of older subjects were current. The uninsured had the lowest current testing rate. Among insured participants, type of insurance had little impact on CRC testing; older subjects enrolled in HMOs had marginally higher rates, although not statistically significant. Increased frequency of preventive health visits and ever receiving a physician's recommendation for FSIG or ever receiving FOBT cards were associated with higher rates of CRC screening among both age groups. Even when broad criteria are used to define current CRC screening status, a substantial proportion of the age-eligible population remains underscreened. Obtaining regular preventive care and receiving a physician's recommendation for screening appear to be potent facilitators of screening that should be considered in designing promotional efforts.
Belov, Larissa; Zhou, Jerry; Christopherson, Richard I.
The classification of colorectal cancers (CRC) is currently based largely on histologically determined tumour characteristics, such as differentiation status and tumour stage, i.e., depth of tumour invasion, involvement of regional lymph nodes and the occurrence of metastatic spread to other organs. These are the conventional prognostic factors for patient survival and often determine the requirement for adjuvant therapy after surgical resection of the primary tumour. However, patients with the same CRC stage can have very different disease-related outcomes. For some, surgical removal of early-stage tumours leads to full recovery, while for others, disease recurrence and metastasis may occur regardless of adjuvant therapy. It is therefore important to understand the molecular processes that lead to disease progression and metastasis and to find more reliable prognostic markers and novel targets for therapy. This review focuses on cell surface proteins that correlate with tumour progression, metastasis and patient outcome, and discusses some of the challenges in finding prognostic protein markers in CRC. PMID:21339979
Owen, R W; Spiegelhalder, B; Bartsch, H
Reproducible high-performance liquid chromatography methods have been developed and validated which allow an accurate quantification of phytic acid in faeces and food and reactive oxygen species in an in vitro model system and in faecal specimens. When applied to the evaluation of reactive oxygen species generation by faeces, this method has shown that 1:100 dilutions of matrix obtained from stool samples of adenoma patients are capable of generating significant quantities of reactive oxygen species as evinced by the production of diphenols from salicylic acid. Moreover, it has been shown that the major product of HO. attack on salicylic acid is 2,5-dihydroxy benzoic acid and not 2, 3-dihydroxy benzoic acid as previously reported. In the presence of the antioxidant ascorbic acid the inhibitory capacity of phytic acid on the generation of reactive oxygen species is completely subverted. Therefore, the kinetics of reactive oxygen species production by faeces is currently under further investigation by high-performance liquid chromatography and chemiluminescence in various patient groups and may give an insight into the role of reactive oxygen species in the aetiology of colorectal cancer.
Vega, Pablo; Valentín, Fátima; Cubiella, Joaquín
Colorectal cancer (CRC) is a major health problem in the Western world. The diagnostic process is a challenge in all health systems for many reasons: There are often no specific symptoms; lower abdominal symptoms are very common and mostly related to non-neoplastic diseases, not CRC; diagnosis of CRC is mainly based on colonoscopy, an invasive procedure; and the resource for diagnosis is usually scarce. Furthermore, the available predictive models for CRC are based on the evaluation of symptoms, and their diagnostic accuracy is limited. Moreover, diagnosis is a complex process involving a sequence of events related to the patient, the initial consulting physician and the health system. Understanding this process is the first step in identifying avoidable factors and reducing the effects of diagnostic delay on the prognosis of CRC. In this article, we describe the predictive value of symptoms for CRC detection. We summarize the available evidence concerning the diagnostic process, as well as the factors implicated in its delay and the methods proposed to reduce it. We describe the different prioritization criteria and predictive models for CRC detection, specifically addressing the two-week wait referral guideline from the National Institute of Clinical Excellence in terms of efficacy, efficiency and diagnostic accuracy. Finally, we collected information on the usefulness of biomarkers, specifically the faecal immunochemical test, as non-invasive diagnostic tests for CRC detection in symptomatic patients. PMID:26690833
Heresbach, Denis; Manfrédi, Sylvain; Branger, Bernard; Bretagne, Jean-François
Colorectal cancer (CRC) screening in France is based on a faecal occult blood test every two years in average risk subjects 50-74 years of age while other endoscopic or non-endoscopic screening methods are used in Europe and in the USA. Beside the reduced incidence of and mortality from CRC found in available studies, cost-effectiveness data need to be taken into account. Because of the delay between randomized controlled trials and clinical results, transitional probabilistic models of screening programs are useful for public health policy makers. The aim of the present review was to promote the implementation of cost-effectiveness studies, to provide a guide to analyze cost-effectiveness studies on CRC screening and, to propose a French cost effectiveness study comparing CRC screening strategies. Most of these trials were performed by US or UK authors and demonstrate that the incremental cost-effectiveness ratio varies between 5 000 and 15 000 US dollars/one year life gained, with wide variations: these results were highly dependent on the unit costs of the different devices as well as the predictive values of the screening tests. Although CRC screening programs have been implemented in several administrative districts of France since 2002, and the results of these randomized controlled trials using fecal occult blood have been updated, cost-effectiveness criteria need to be integrated; especially since the results of screening campaigns based on other tools such as flexible sigmoidoscopy should be available in 2007.
Sarfati, Diana; Shaw, Caroline; McLeod, Melissa; Blakely, Tony; Bissett, Ian
There are many different potential screening strategies for colorectal cancer (CRC) that vary both in the likely magnitude of their benefits on CRC mortality and their impact on health services. Many approaches to CRC screening are cost-effective, but there is substantial uncertainty about the optimal approach. Decision models using Markov or microsimulation modelling that compare the cost-effectiveness of different screening strategies are useful in this regard. We have reviewed recent decision models that compare the cost-effectiveness of one-off flexible sigmoidoscopy screening with immunochemical faecal occult blood (FIT) based screening. Models consistently show that any population-based screening is cost-effective compared with no screening, and that FIT-based screening is more effective than one-off sigmoidoscopy screening. The combination of one-off sigmoidoscopy with FIT is more effective in saving lives than either modality alone, but has the greatest impact on health service resources. The recent decision to proceed with biennial FIT-based screening is consistent with current evidence.
Williams, Renee; White, Pascale; Nieto, Jose; Vieira, Dorice; Francois, Fritz; Hamilton, Frank
This review is an update to the American College of Gastroenterology (ACG) Committee on Minority Affairs and Cultural Diversity's paper on colorectal cancer (CRC) in African Americans published in 2005. Over the past 10 years, the incidence and mortality rates of CRC in the United States has steadily declined. However, reductions have been strikingly much slower among African Americans who continue to have the highest rate of mortality and lowest survival when compared with all other racial groups. The reasons for the health disparities are multifactorial and encompass physician and patient barriers. Patient factors that contribute to disparities include poor knowledge of benefits of CRC screening, limited access to health care, insurance status along with fear and anxiety. Physician factors include lack of knowledge of screening guidelines along with disparate recommendations for screening. Earlier screening has been recommended as an effective strategy to decrease observed disparities; currently the ACG and American Society of Gastrointestinal Endoscopists recommend CRC screening in African Americans to begin at age 45. Despite the decline in CRC deaths in all racial and ethnic groups, there still exists a significant burden of CRC in African Americans, thus other strategies including educational outreach for health care providers and patients and the utilization of patient navigation systems emphasizing the importance of screening are necessary. These strategies have been piloted in both local communities and Statewide resulting in notable significant decreases in observed disparities. PMID:27467183
Zamora-Ros, Raul; Guinó, Elisabeth; Henar Alonso, M.; Vidal, Carmen; Barenys, Mercè; Soriano, Antonio; Moreno, Victor
Flavonoids and lignans are polyphenol classes with anticarcinogenic activities against colorectal cancer (CRC). However, very limited epidemiological evidence exists on their effects on CRC prognosis. This study aimed to evaluate the association between flavonoid and lignan intakes with the risk of CRC recurrence and overall survival in CRC patients. The study followed incident histologically confirmed CRC cases in Barcelona (Spain). Validated dietary questionnaires and lifestyle information were collected at recruitment. An ad hoc food composition database on flavonoids and lignans was compiled by using data from the US Department of Agriculture and Phenol-Explorer databases. Adjusted hazards ratios (HR) and 95% confidence intervals (CIs) were estimated using multivariable Cox models. After 8.6 years of mean follow-up, 133 of 409 (32.5%) participants died and 77 of 319 (24.1%) had a CRC recurrence. Total flavonoids were associated neither with CRC recurrence (HR comparing extreme tertiles 1.13, 95% CI 0.64–2.02; P-trend 0.67) nor with overall survival (HRT3vsT1 1.06, 95% CI 0.69–1.65; P-trend 0.78) in the multivariable models. No associations were also observed with either total lignans or any flavonoid subclass intake. In conclusion, the results of the current study do not support a role of flavonoid and lignan intake in the CRC prognosis. PMID:26369380
Kim, Karen; Chapman, Christopher; Vallina, Helen
The purpose of this study was to examine the factors determining fecal occult blood test (FOBT) uptake in Chinese American immigrants. This study used a prospective, cross-sectional design with convenience sampling. An educational session on colorectal cancer screening (CRS) was provided to the participants during a health fair, and each participant was offered a no-cost FOBT kit. Data was collected over two consecutive years during three different health fairs. A questionnaire was used to collect demographic data. A total of 113 participants were recruited and 72% of them returned the FOBT kit. There was a significant association between having a primary-care physician (PCP) and having CRS in the past, even after controlling for age, gender and the length of time in the US (P = .009). Participants who visited a doctor for health maintenance were less likely to participate in the FOBT, compared to participants who never visited a doctor or who only visited a doctor when they were sick (P = .001). The length of time in the US had a significant effect on having a PCP (P = .002). However, having a PCP or having CRS in the past was not associated with participating in the screening and so was feeling at risk for CRC. In fact, 49% of Chinese women and 45% of Chinese men felt no risk of CRC. Future research and interventions that address knowledge deficits and focus on recent immigrants and their access to health care may have the potential to increase CRS among Chinese American immigrants.
Leung, Wai K; Chen, Wei-Qing; Gu, Li; Long, Dan; Law, W L
The incidence of colorectal cancer (CRC) is rising rapidly in Chinese. We studied the anatomic distributions and characteristics of CRC in Hong Kong (HK) and Chongqing (CQ) with different CRC epidemiology. It was a retrospective study conducted in three large regional hospitals of the two cities. We identified all patients newly diagnosed with CRC between 2003 and 2012. The distribution and characteristics of CRC of the two cities were compared. Of CRC, 3664 new cases were diagnosed within the study period. CRC was more common in men (>56%) in both cities. The mean age at diagnosis was significantly younger in CQ, the lower prevalence area, than in HK (62.1 vs 70.4 years; P < 0.001). Rectal cancer was the predominant (61.3%) cancer in CQ, but only 18% of cancers in HK were rectal cancer (P = 0.0001). Right-sided colonic cancer, however, was more common in HK than CQ (27.2% vs 17.4%; P < 0.001). Women had more right-sided colonic cancer than men in both cities (P < 0.002), and there was an age-related increase in right-sided colonic cancer in HK but not in CQ. Multivariate analysis showed that older age, female, and living in HK were independent risk factors associated with right-sided colonic cancer. There are significant differences in the distribution of CRC between HK and CQ. The discrepancy may be partly accounted by older population and an increase in proximal colonic cancer, particularly in women, in HK. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
Stigliano, Vittoria; Sanchez-Mete, Lupe; Martayan, Aline; Anti, Marcello
Colorectal cancer is the third most common cancer diagnosed worldwide. Although epidemiology data show a marked variability around the world, its overall incidence rate shows a slow but steady decrease, mainly in developed countries. Conversely, early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%. Colorectal cancer has a substantial proportion of familial cases. In particular, early age at onset is especially suggestive of hereditary predisposition. The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group. Two distinct subtypes of early-onset colorectal cancers can be identified: a "sporadic" subtype, usually without family history, and an inherited subtype arising in the context of well defined hereditary syndromes. The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype, which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases, whereas in the "sporadic" subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants, so far largely unidentified, displaying variable penetrance. These variants are thought to act cumulatively to increase the risk of colorectal cancer, and presumably to also anticipate its onset. Efforts are ongoing in the attempt to unravel the intricate genetic basis of this "sporadic" early-onset disease. A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies.
Galindo, Rodolfo J.; Romao, Isabela; Valsamis, Ageliki; Weinerman, Stuart; Harris, Yael Tobi
Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25-dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean ± SD: 56.7 ± 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean ± SD: 15.6 ± 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control. PMID:26998187
Seeff, Laura C; Rohan, Elizabeth A
This report briefly summarizes 13 articles in this dedicated supplement to Cancer documenting the full implementation and evaluation of CDC's Colorectal Cancer Screening Demonstration Program (CRCSDP). The supplement includes 3 articles that describe clinical and quality outcomes; 2 articles that describe programmatic and clinical costs; 3 that were based on a multiple case study, using qualitative methods to describe the overall implementation experience of this initiative; and 4 articles written by and about individual program sites. The comprehensive, multi-methods evaluation conducted alongside the program produced many important lessons regarding the design, start-up, and implementation of colorectal cancer screening in this high-need population, and paved the way for the CDC to establish a larger, population-based colorectal cancer control initiative, broadly aligned with expectations of the Patient Protection and Affordable Care Act through its population-based emphasis on using a health systems approach to increase colorectal cancer screening. Cancer 2013;119(15 suppl):2817-9. © 2013 American Cancer Society.
Toyota, Minoru; Ahuja, Nita; Ohe-Toyota, Mutsumi; Herman, James G.; Baylin, Stephen B.; Issa, Jean-Pierre J.
Aberrant methylation of promoter region CpG islands is associated with transcriptional inactivation of tumor-suppressor genes in neoplasia. To understand global patterns of CpG island methylation in colorectal cancer, we have used a recently developed technique called methylated CpG island amplification to examine 30 newly cloned differentially methylated DNA sequences. Of these 30 clones, 19 (63%) were progressively methylated in an age-dependent manner in normal colon, 7 (23%) were methylated in a cancer-specific manner, and 4 (13%) were methylated only in cell lines. Thus, a majority of CpG islands methylated in colon cancer are also methylated in a subset of normal colonic cells during the process of aging. In contrast, methylation of the cancer-specific clones was found exclusively in a subset of colorectal cancers, which appear to display a CpG island methylator phenotype (CIMP). CIMP+ tumors also have a high incidence of p16 and THBS1 methylation, and they include the majority of sporadic colorectal cancers with microsatellite instability related to hMLH1 methylation. We thus define a pathway in colorectal cancer that appears to be responsible for the majority of sporadic tumors with mismatch repair deficiency. PMID:10411935
Jayasekara, Harindra; Reece, Jeanette C; Buchanan, Daniel D; Rosty, Christophe; Dashti, S Ghazaleh; Ait Ouakrim, Driss; Winship, Ingrid M; Macrae, Finlay A; Boussioutas, Alex; Giles, Graham G; Ahnen, Dennis J; Lowery, Jan; Casey, Graham; Haile, Robert W; Gallinger, Steven; Le Marchand, Loic; Newcomb, Polly A; Lindor, Noralane M; Hopper, John L; Parry, Susan; Jenkins, Mark A; Win, Aung Ko
Individuals diagnosed with colorectal cancer (CRC) are at risk of developing a metachronous CRC. We examined the associations between personal, tumour-related and lifestyle risk factors, and risk of metachronous CRC. A total of 7,863 participants with incident colon or rectal cancer who were recruited in the USA, Canada and Australia to the Colon Cancer Family Registry during 1997-2012, except those identified as high-risk, for example, Lynch syndrome, were followed up approximately every 5 years. We estimated the risk of metachronous CRC, defined as the first new primary CRC following an interval of at least one year after the initial CRC diagnosis. Observation time started at the age at diagnosis of the initial CRC and ended at the age at diagnosis of the metachronous CRC, last contact or death whichever occurred earliest, or were censored at the age at diagnosis of any metachronous colorectal adenoma. Cox regression was used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow-up of 6.6 years, 142 (1.81%) metachronous CRCs were diagnosed (mean age at diagnosis 59.8; incidence 2.7/1,000 person-years). An increased risk of metachronous CRC was associated with the presence of a synchronous CRC (HR = 2.73; 95% CI: 1.30-5.72) and the location of cancer in the proximal colon at initial diagnosis (compared with distal colon or rectum, HR = 4.16; 95% CI: 2.80-6.18). The presence of a synchronous CRC and the location of the initial CRC might be useful for deciding the intensity of surveillance colonoscopy for individuals diagnosed with CRC.
Kim, Yun Jung; Kim, Eun Soo; Lee, Jeong Eun; Park, Woo Young; Kwon, Jee Suk; Park, Kyung Sik; Cho, Kwang Bum; Jang, Byoung Kuk; Chung, Woo Jin; Hwang, Jae Seok; Park, Joon Cheol
The relationship between colorectal neoplasia and cervical cancer has not been evaluated. This study aimed to assess the prevalence of colorectal adenoma in patients with cervical cancer and compare it with that of control subjects. Between January 2005 and December 2009, the medical records of patients diagnosed with cervical cancer were retrospectively reviewed. Patients undergoing sigmoidoscopy or colonoscopy for the preoperative evaluation of the colon were enrolled in this study. Age-matched female healthy subjects who underwent colonoscopy for screening purposes were included as control subjects. We compared demographic and clinicopathological characteristics between the groups. Overall, 285 patients with cervical cancer and 284 healthy subjects were included (age, 56.93±11.92 vs. 56.10±9.31 years). The mean body weight, body mass index (BMI), the incidence of diabetes mellitus and impaired fasting glucose were not statistically different between the 2 groups. The prevalence of colorectal adenoma was not different between the patient and control groups, regardless of examination extent. Multivariate analysis showed that age and BMI were significant independent risk factors for colorectal adenomatous polyps (age, p<0.001; BMI, p=0.002). There might not be any significant association between cervical cancer and colorectal adenomatous polyps.
Yu, Deng-Feng; Jiang, Su-Juan; Pan, Zhi-Peng; Cheng, Wei-Dong; Zhang, Wen-Jun; Yao, Xiao-Kun; Li, Yu-Cheng; Lun, Yong-Zhi
The objective of the present study was to examine the expression of Silent information regulator 1 (Sirt1) in colorectal cancer and peritumoral normal mucosa tissue, and therefore analyze the role and molecular mechanism of Sirt1 in the pathogenesis of colorectal cancer. Colorectal cancer tissue specimens were employed as the experimental group, and adjacent normal mucosa tissues >5 cm from tumor lesions were used as the control group. The expression of Sirt1 was detected by the immunohistochemical streptavidin peroxidase detection method in paraffin-embedded sections, whilst Sirt1 protein expression was examined by western blot analysis in the fresh tissues. Sirt1 protein was primarily expressed in the nuclei of the tumor cells, and positive staining was brownish-yellow in color. The relative expression quantities of Sirt1 in the peritumoral normal rectal mucosa and rectal carcinoma were 1.15 and 2.62, and the differences between the two groups were statistically significant (P<0.05). The expression level of Sirt1 in colorectal carcinoma was significantly associated with the depth of tumor invasion, differentiation and tumor size (P<0.05). Sirt1 expression was also found to be associated with tumor tissue type, lymph node metastasis, Duke's stage and patient age. These characteristics combined may therefore be used as markers for the early diagnosis of colorectal cancer pathogenesis.
Myung, Dae Seong; Joo, Young Eun
The human intestinal microbiota is a community of 10(13)-10(14) microorganisms that harbor in the intestine and normally participate in a symbiotic relationship with human. Technical and conceptual advances have enabled rapid progress in characterizing the taxonomic composition, metabolic capacity and immunomodulatory activity of the human intestinal microbiota. Their collective genome, defined as microbiome, is estimated to contain ≥150 times as many genes as 2.85 billion base pair human genome. The intestinal microbiota and its microbiome form a diverse and complex ecological community that profoundly impact intestinal homeostasis and disease states. It is becoming increasingly evident that the large and complex bacterial population of the large intestine plays an important role in colorectal carcinogenesis. Numerous studies show that gut immunity and inflammation have impact on the development of colorectal cancer. Additionally, bacteria have been linked to colorectal cancer by the production of toxic and genotoxic bacterial metabolite. In this review, we discuss the multifactorial role of intestinal microbiota in colorectal cancer and role for probiotics in the prevention of colorectal cancer.
Cooper, Crystale Purvis; Gelb, Cynthia A; Lobb, Kathleen
The Centers for Disease Control and Prevention's Screen for Life: National Colorectal Cancer Action Campaign works with the Entertainment Industry Foundation's National Colorectal Cancer Research Alliance to develop public service announcements (PSAs) featuring celebrities. Selection of Screen for Life celebrity spokespersons is based on a variety of factors, including their general appeal and personal connection to colorectal cancer. Screen for Life PSAs featuring celebrities have been disseminated exclusively through donated media placements and have been formatted for television, radio, print, and out-of-home displays such as dioramas in airports, other transit stations, and shopping malls. A 2012 national survey with women aged 50-75 years (n=772) investigated reported exposure to Screen for Life PSAs featuring actor Terrence Howard. In total, 8.3% of women recalled exposure to the PSAs. Celebrity spokespersons can attract the attention of both target audiences and media gatekeepers who decide which PSAs will receive donated placements.
Kircher, Sheetal Mehta; Nimeiri, Halla S; Benson, Al B
Colorectal cancer is commonly diagnosed throughout the world, and treatment options have greatly expanded over the last 2 decades. Targeting angiogenesis has been a major focus of study in a variety of malignancy types. Targeting angiogenesis has been achieved by several mechanisms in colorectal cancer, including use of antiangiogenic small molecule tyrosine kinase inhibitors (TKIs). There have been many attempts and failures to prove efficacy of TKIs in the treatment of colorectal cancer including sorafenib, sunitinib, vatalanib, and tivozanib. Regorafenib was the first TKI to demonstrate efficacy and is an orally active inhibitor of angiogenic (including the vascular endothelial growth factor receptors 1, 2, and 3), stromal, and oncogenic receptor tyrosine kinases. There are ongoing investigations of both regorafenib and ninetanib; however, there remains a critical need to better understand novel combinations with TKIs that could prove more efficacious than available options.
Schoen, Robert E; Razzak, Anthony; Yu, Kelly J; Berndt, Sonja I; Firl, Kevin; Riley, Thomas L; Pinsky, Paul F
Little is known about the change in risk conferred by family history of colorectal cancer (CRC) as a person ages. We evaluated the effect of family history on CRC incidence and mortality after 55 years of age, when the risk of early onset cancer had passed. We collected data from participants in the randomized, controlled Prostate, Lung, Colorectal and Ovarian cancer screening trial of flexible sigmoidoscopy versus usual care (55-74 years old, no history of CRC), performed at 10 US centers from 1993 to 2001. A detailed family history of colorectal cancer was obtained at enrollment, and subjects were followed for CRC incidence and mortality for up to 13 years. Among 144,768 participants, 14,961 subjects (10.3%) reported a family of CRC. Of 2090 incident cases, 273 cases (13.1%) had a family history of CRC; among 538 deaths from CRC, 71 (13.2%) had a family history of CRC. Overall, family history of CRC was associated with an increased risk of CRC incidence (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.50; P<.0001) and increased mortality (HR, 1.31; 95% CI, 1.02-1.69; P = .03). Subjects with 1 first degree relative (FDR) with CRC (n = 238; HR, 1.23; 95% CI, 1.07-1.42) or ≥2 FDRs with CRC (n = 35; HR, 2.04; 95% CI, 1.44-2.86) were at increased risk for incident CRC. However, among individuals with 1 FDR with CRC, there were no differences in risk based on age at diagnosis in the FDR (for FDR <60 years of age: HR, 1.27; 95% CI, 0.97-1.63; for FDR 60-70 years of age: HR, 1.33; 95% CI, 1.06-1.62; for FDR >70 years of age: HR, 1.14; 95% CI, 0.93-1.45; P trend = .59). After 55 years of age, subjects with 1 FDR with CRC had only a modest increase in risk for CRC incidence and death; age of onset in the FDR was not significantly associated with risk. Individuals with ≥2 FDRs with CRC had continued increased risk in older age. Guidelines and clinical practice for subjects with a family history of CRC should be modified to align CRC testing to risk
Duncan, R; Carpenter, B; Main, L C; Telfer, C; Murray, G I
The annexins are family of calcium-regulated phospholipid-binding proteins with diverse roles in cell biology. Individual annexins have been implicated in tumour development and progression, and in this investigation a range of annexins have been studied in colorectal cancer. Annexins A1, A2, A4 and A11 were identified by comparative proteomic analysis to be overexpressed in colorectal cancer. Annexins A1, A2, A4 and A11 were further studied by immunohistochemistry with a colorectal cancer tissue microarray containing primary and metastatic colorectal cancer and also normal colon. There was significant increase in expression in annexins A1 (P=0.01), A2 (P<0.001), A4 (P<0.001) and A11 (P<0.001) in primary tumours compared with normal colon. There was increasing expression of annexins A2 (P=0.001), A4 (P=0.03) and A11 (P=0.006) with increasing tumour stage. An annexin expression profile was identified by k-means cluster analysis, and the annexin profile was associated with tumour stage (P=0.01) and also patient survival. Patients in annexin cluster group 1 (low annexin expression) had a better survival (log rank=5.33, P=0.02) than patients in cluster group 2 (high annexins A4 and A11 expression). In conclusion, this study has shown that individual annexins are present in colorectal cancer, specific annexins are overexpressed in colorectal cancer and the annexin expression profile is associated with survival.
van Eeghen, Elmer E.; Bakker, Sandra D.; van Bochove, Aart
Background Patients with colorectal cancer are often excluded from clinical trials based on age or a poor performance score. However, 70% of colorectal cancer is diagnosed in patients over 65. Evaluation on the influence of age and comorbidity on survival and cause of death in a non-selected population. Methods Included were 621 consecutive patients with colorectal cancer. An extensive chart review was performed for 392 patients with colon cancer and 143 patients with rectal cancer. Analyses were performed separately for both groups. Results Median survival of colon cancer patients was 5.13 years, 131 patients (34.3%) died from tumour progression. Age and comorbidity were significant predictors for overall survival (P<0.001). Age was also a significant predictor of cause of death (P=0.001). In rectal cancer patients median survival was 4.67 years, 51 (35.7%) of patients died from tumour progression. Neither age nor comorbidity was significant predictors of survival. Age was a significant predictor of cause of death (P<0.001). Conclusions In colon cancer patient age and comorbidity predict survival. This represents possible bias or a reduced survival benefit of treatment, and is an indication that colon cancer is not the prognosis defining illness in the majority of patients. In rectal cancer patients neither age or comorbidity significantly impacted survival. PMID:26697191
Sanchez-Castañón, María; Er, Tze-Kiong; Bujanda, Luis; Herreros-Villanueva, Marta
After decades of progress based on chemotherapy and targeted agents, patients with metastatic colorectal cancer still have low long-term survival, with more than 500,000 deaths occurring worldwide every year. Recent results showing clinical evidence of efficacy using immunotherapy in other types of tumors, such as melanoma and lung cancer, have also made this a viable therapy for evaluation in colorectal cancer in clinical trials. The development of cancer immunotherapies is progressing quickly, with a variety of technological approaches. This review summarizes the current status of clinical trials testing immunotherapy in colorectal cancer and discusses what has been learned based on previous results. Immunotherapy strategies, such as various models of vaccines, effector-cell therapy and checkpoint inhibitor antibodies, provide protection against progression for a limited subset of patients diagnosed with colorectal cancer. A better understanding of particular immune cell types and pathways in each patient is still needed. These findings will enable the development of novel biomarkers to select the appropriate subset of patients to be treated with a particular immunotherapy, and the tendencies determined from recent results can guide clinical practice for oncologists in this new therapeutic area and in the design of the next round of clinical trials.
Viloria, Cristina G; Obaya, Alvaro J; Moncada-Pazos, Angela; Llamazares, María; Astudillo, Aurora; Capellá, Gabriel; Cal, Santiago; López-Otín, Carlos
Matrix metalloproteinases have been traditionally linked to cancer dissemination through their ability to degrade most extracellular matrix components, thus facilitating invasion and metastasis of tumor cells. However, recent functional studies have revealed that some metalloproteases, including several members of the ADAMTS family, also exhibit tumor suppressor properties. In particular, ADAMTS1, ADAMTS9, and ADAMTS18 have been found to be epigenetically silenced in malignant tumors of different sources, suggesting that they may function as tumor suppressor genes. Herein, we show that ADAMTS15 is genetically inactivated in colon cancer. We have performed a mutational analysis of the ADAMTS15 gene in human colorectal carcinomas, with the finding of four mutations in 50 primary tumors and 6 colorectal cancer cell lines. Moreover, functional in vitro and in vivo studies using HCT-116 and SW-620 colorectal cancer cells and severe combined immunodeficient mice have revealed that ADAMTS15 restrains tumor growth and invasion. Furthermore, the presence of ADAMTS15 in human colorectal cancer samples showed a negative correlation with the histopathologic differentiation grade of the corresponding tumors. Collectively, these results provide evidence that extracellular proteases, including ADAMTS15, may be targets of inactivating mutations in human cancer and further validate the concept that secreted metalloproteases may show tumor suppressor properties.
Schoenfeld, Philip S; Cohen, Jonathan
The growing importance of colonoscopy in the prevention of colorectal cancer has stimulated an effort to identify and track quality indicators for this procedure. Several factors have been identified so far which are readily measurable and in many cases have been associated with improved patient outcomes. There is also ample evidence of variations in performance of this procedure. As a result, gathering data about quality indicators may play a vital role in the process of continuous quality improvement. Quality indicators for colonoscopy in colorectal cancer prevention are described along with the evidence that supports their use in benchmarking, quality reporting, and continuous quality improvement.
Yoshimatsu, Kazuhiko; Ishibashi, Keiichiro; Hashimoto, Masahiko; Umehara, Arihiro; Yokomizo, Hajime; Yoshida, Kiyohito; Fujimoto, Takashi; Iwasaki, Kiyo; Ogawa, Kenji
We herein report the result of a prospective study to investigate the efficacy of cimetidine administration in conjunction with chemotherapy for stage IV colorectal cancer. Sixty-two patients treated with Leucovorin/5-fluorouracil therapy were enrolled from 1996 to 2000. Both groups were well matched for pre-treatment characteristics. There was no difference in survival in cur B patients. However, the cimetidine group had significantly prolonged survival in the patients with cur C or non-resectable carcinoma. This study suggests that cimetidine treatment may improve the survival of patients with non-curative surgery for stage IV colorectal cancer.
Moreno-Elola, A; Moreno-Gonzalez, E; Alonso-Casado, O; Meneu-Diaz, J C; García-García, I; Abradelo-Usera, M
We report a very uncommon case of bilateral adrenal metastasis treated at our institution. The patient was 65 years old, with a history of low anterior resection for colorectal cancer in 2001. One year later, he was diagnosed with bilateral adrenal metastasis, based on the results of abdominal computed tomography-scan. A bilateral adrenalectomy extended to distal pancreatectomy and splenectomy was performed. Postoperative course was uneventful. He is alive and free of disease 12 months after adrenalectomy. We conclude adrenal metastasis from colorectal cancer should be managed surgically, even if they are bilateral.
Mishra, Nitin; Hall, Jason
Diagnosis of hereditary colorectal cancer syndromes requires clinical suspicion and knowledge of such syndromes. Lynch syndrome is the most common cause of hereditary colorectal cancer. Other less common causes include familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome, and others. There have been a growing number of clinical and molecular tools used to screen and test at risk individuals. Screening tools include diagnostic clinical criteria, family history, genetic prediction models, and tumor testing. Patients who are high risk based on screening should be referred for genetic testing. PMID:23730221
de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.
The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.
El-Shami, Khaled; Oeffinger, Kevin C; Erb, Nicole L; Willis, Anne; Bretsch, Jennifer K; Pratt-Chapman, Mandi L; Cannady, Rachel S; Wong, Sandra L; Rose, Johnie; Barbour, April L; Stein, Kevin D; Sharpe, Katherine B; Brooks, Durado D; Cowens-Alvarado, Rebecca L
Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer death in both men and women and second leading cause of cancer death when men and women are combined in the United States (US). Almost two-thirds of CRC survivors are living 5 years after diagnosis. Considering the recent decline in both incidence and mortality, the prevalence of CRC survivors is likely to increase dramatically over the coming decades with the increase in rates of CRC screening, further advances in early detection and treatment and the aging and growth of the US population. Survivors are at risk for a CRC recurrence, a new primary CRC, other cancers, as well as both short-term and long-term adverse effects of the CRC and the modalities used to treat it. CRC survivors may also have psychological, reproductive, genetic, social, and employment concerns after treatment. Communication and coordination of care between the treating oncologist and the primary care clinician is critical to effectively and efficiently manage the long-term care of CRC survivors. The guidelines in this article are intended to assist primary care clinicians in delivering risk-based health care for CRC survivors who have completed active therapy.
Väyrynen, Juha; Böhm, Jan
Immune system contributes to the pathogenesis of cancer. Immunoediting describes a process in which the immune system can recognize transformed cancer cells and establish an anti-tumor response, potentially leading to the selection of less immunogenic tumor cells. Additionally, inflammation may contribute to cancer progression by activating angiogenesis and oncogenic signaling pathways. In colorectal cancer, dense inflammatory infiltrate in tumor samples is generally associated with improved prognosis but this association is dependent on the type of immune cells and their location. In future, increased knowledge on cancer immunology is expected to benefit the diagnostics, prognostication, follow-up and treatment of cancer.
An herbal extract used for centuries to prevent heart disease has now been shown to be effective against colorectal cancer when tested in laboratory cell cultures. Scientists from NCI at Frederick found that the natural extract cryptotanshinone (CPT) stops the uncontrolled cell growth characteristic of cancer by interfering with a protein that has been implicated in several cancers, including those of the colon and rectum. The results appear in the journal Molecular and Cellular Biochemistry.
An herbal extract used for centuries to prevent heart disease has now been shown to be effective against colorectal cancer when tested in laboratory cell cultures. Scientists from NCI at Frederick found that the natural extract cryptotanshinone (CPT) stops the uncontrolled cell growth characteristic of cancer by interfering with a protein that has been implicated in several cancers, including those of the colon and rectum. The results appear in the journal Molecular and Cellular Biochemistry.
Bae, Susie; Asadi, Muslim; Jones, Ian; McLaughlin, Stephen; Bui, Andrew; Steele, Malcolm; Tie, Jeanne; Gibbs, Peter
Oncology literature is increasingly recognizing prevalence of second primary cancers including several longitudinal studies showing an increased risk of colorectal cancer following a prostate cancer diagnosis. A retrospective study was conducted to examine the relationship between prior prostate cancer diagnoses and subsequent colorectal cancer diagnoses. A multi-centre prospective colorectal cancer registry was queried for patients with a prior history of prostate, breast or lung cancer. Characteristics of these patients were compared to patients with colorectal cancer and no prior cancer history. Of 4660 cases of colorectal cancer diagnosed between 1998 and 2011, 2665 (57.2%) were male, median age was 68 years. For patients with a history of prostate cancer (n = 111), breast cancer (n = 61) and lung cancer (n = 23), the great majority of subsequent colorectal cancer diagnoses occurred in the initial 2 to 4 years after the first cancer diagnosis. This was accompanied by an increased rate of asymptomatic colorectal cancer at presentation, due to both screen detected and incidental cancer diagnoses. There was no clear relationship between any prostate cancer treatment and subsequent colorectal cancer risk, location or timing. In the modern era, there is an increased rate of colorectal cancer diagnosis in years shortly following another common cancer history. This is consistently seen across different primary tumour streams including prostate, breast and lung cancers and in part contributed by screen detected and incidental colorectal cancer diagnoses. Future studies should consider this potential confounding factor when asserting an increased rate of colorectal cancer as a second primary cancer. © 2013 The Authors. ANZ Journal of Surgery © 2013 Royal Australasian College of Surgeons.
Yusof, Afzaninawati Suria; Isa, Zaleha Md; Shah, Shamsul Azhar
Changes in dietary practices are known to be associated with changes in the health and disease pattern of a population. This study aimed to qualitatively explore the perception of colorectal cancer patients regarding causes of colorectal cancer and the influence of diet. Twelve respondents from three major ethnicities in Malaysia were selected from the quantitative study on dietary pattern and colorectal cancer carried out earlier in this study. In-depth interviews (IDI), conducted from April until June 2012, were mainly in the Malay language with additional use of English and continued until the saturation point was reached. All interviews were autorecorded so that verbatim transcriptions could be created. Causes of colorectal cancer were categorized into internal and external factors. The majority of respondents agreed that there is an association between Western foods and colorectal cancer. Malaysian traditional diet was not related to colorectal cancer as less preservative agents were used. Malaysian diet preparation consisting of taste of cooking (spicy, salty and sour foods) plus type of cooking (fry, grilled and smoked) were considered causes of colorectal cancer. All respondents changed their dietary pattern to healthy food after being diagnosed with colorectal cancer. Advice from doctors regarding suitable food for colorectal cancer was useful in this regard. Eating outside, use of food flavoring ingredients and preservative agents were considered to be the main factors causing colorectal cancer. All respondents admitted that they changed to a healthy diet after being diagnosed with colorectal cancer.
Shangkuan, Wei-Chuan; Lin, Hung-Che; Chang, Yu-Tien; Jian, Chen-En; Fan, Hueng-Chuen; Chen, Kang-Hua; Liu, Ya-Fang; Hsu, Huan-Ming; Chou, Hsiu-Ling; Yao, Chung-Tay
Background Colorectal cancer (CRC) is one of the leading cancers worldwide. Several studies have performed microarray data analyses for cancer classification and prognostic analyses. Microarray assays also enable the identification of gene signatures for molecular characterization and treatment prediction. Objective Microarray gene expression data from the online Gene Expression Omnibus (GEO) database were used to to distinguish colorectal cancer from normal colon tissue samples. Methods We collected microarray data from the GEO database to establish colorectal cancer microarray gene expression datasets for a combined analysis. Using the Prediction Analysis for Microarrays (PAM) method and the GSEA MSigDB resource, we analyzed the 14,698 genes that were identified through an examination of their expression values between normal and tumor tissues. Results Ten genes (ABCG2, AQP8, SPIB, CA7, CLDN8, SCNN1B, SLC30A10, CD177, PADI2, and TGFBI) were found to be good indicators of the candidate genes that correlate with CRC. From these selected genes, an average of six significant genes were obtained using the PAM method, with an accuracy rate of 95%. The results demonstrate the potential of utilizing a model with the PAM method for data mining. After a detailed review of the published reports, the results confirmed that the screened candidate genes are good indicators for cancer risk analysis using the PAM method. Conclusions Six genes were selected with 95% accuracy to effectively classify normal and colorectal cancer tissues. We hope that these results will provide the basis for new research projects in clinical practice that aim to rapidly assess colorectal cancer risk using microarray gene expression analysis. PMID:28229027
Jeong, Hyun Yong
Background/Aims. To evaluate the incidence of gastric adenoma and gastric cancer in colorectal cancer patients, as well as the clinicopathological features that affect their incidence. Methods. Among patients who underwent surgery after being diagnosed with colorectal cancer between January 2004 and December 2013 at Chungnam National University Hospital, 142 patients who underwent follow-up upper gastrointestinal endoscopy were assigned to the patient group. The control group included 426 subjects randomly selected. The patient group was subdivided into two: one that developed gastric adenoma or cancer and one that did not. Clinicopathological characteristics were compared between these groups. Results. In total, 35 (24.6%) colorectal cancer patients developed a gastric adenoma or gastric cancer, which was higher than the number in the control group (20 [4.7%] patients; p < 0.001). Age, alcohol history, and differentiation of colorectal cancer were associated with higher risks of gastric adenoma or gastric cancer, with odds ratios of 1.062, 6.506, and 5.901, respectively. Conclusions. In colorectal cancer patients, screening with upper gastrointestinal endoscopy is important, even if no lesions are noted in the upper gastrointestinal tract at colorectal cancer diagnosis. Endoscopic screening is particularly important with increasing age, history of alcohol consumption, and poor cancer differentiation. PMID:28105047
Campos, Fábio Guilherme C M DE; Figueiredo, Marleny Novaes; Monteiro, Mariane; Nahas, Sérgio Carlos; Cecconello, Ivan
Sporadic colorectal cancer (CRC) is traditionally diagnosed after de sixth decade of life, although a small percentage of cases are diagnosed in patients under 40 years of age, and incidence is increasing. There exists a great volume of controversy regarding clinical outcome of young patients diagnosed with colorectal cancer (CRC) when compared to elder counterparts. Our aims were to evaluate the rate of CRC in young patients, to review the pertaining literature and to discuss outcomes and clinical prognosis. A retrospective review involving patients with CRC was undertaken, focusing on age at diagnosis. The information extracted from this literature review showed a trend towards a decreased incidence in older people with an opposite effect among adolescents and young adults. Moreover, biological aggressiveness in young adults diagnosed with CRC has not been fully recognized, although it is usually diagnosed later and in association with adverse histological features. Besides that, these features don't affect outcome. These apparent increase in CRC incidence among young patients during the last decades raises the need for a greater suspicious when evaluating common symptoms in this group. Thus, educational programs should widespread information for both population and physicians to improve prevention and early diagnosis results. RESUMO O câncer colorretal (CCR) esporádico é tradicionalmente diagnosticado após a sexta década de vida, embora uma pequena porcentagem de casos seja diagnosticada em doentes abaixo dos 40 anos de idade, e a incidência está aumentando. Existe uma grande controvérsia a respeito da evolução clínica de doentes jovens portadores de CCR em comparação aos mais idosos. Os objetivos deste estudo foram avaliar a prevalência de CCR em doentes jovens, rever a literatura pertinente e discutir suas características mais importantes nesta faixa etária. Para tanto realizou-se revisão da literatura envolvendo doentes com CCR com foco na
Chau, Rowena; Jenkins, Mark A; Buchanan, Daniel D; Ait Ouakrim, Driss; Giles, Graham G; Casey, Graham; Gallinger, Steven; Haile, Robert W; Le Marchand, Loic; Newcomb, Polly A; Lindor, Noralane M; Hopper, John L; Win, Aung Ko
This study was aimed to characterize the distribution of colorectal cancer risk using family history of cancers by data mining. Family histories for 10,066 colorectal cancer cases recruited to population cancer registries of the Colon Cancer Family Registry were analyzed using a data mining framework. A novel index was developed to quantify familial cancer aggregation. Artificial neural network was used to identify distinct categories of familial risk. Standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs) of colorectal cancer were calculated for each category. We identified five major, and 66 minor categories of familial risk for developing colorectal cancer. The distribution the major risk categories were: (1) 7% of families (SIR = 7.11; 95% CI 6.65-7.59) had a strong family history of colorectal cancer; (2) 13% of families (SIR = 2.94; 95% CI 2.78-3.10) had a moderate family history of colorectal cancer; (3) 11% of families (SIR = 1.23; 95% CI 1.12-1.36) had a strong family history of breast cancer and a weak family history of colorectal cancer; (4) 9 % of families (SIR = 1.06; 95 % CI 0.96-1.18) had strong family history of prostate cancer and weak family history of colorectal cancer; and (5) 60% of families (SIR = 0.61; 95% CI 0.57-0.65) had a weak family history of all cancers. There is a wide variation of colorectal cancer risk that can be categorized by family history of cancer, with a strong gradient of colorectal cancer risk between the highest and lowest risk categories. The risk of colorectal cancer for people with the highest risk category of family history (7% of the population) was 12-times that for people in the lowest risk category (60%) of the population. Data mining was proven an effective approach for gaining insight into the underlying cancer aggregation patterns and for categorizing familial risk of colorectal cancer.
Goldman, Roberta E.; Diaz, Joseph A.; Kim, Ivone
Colorectal cancer is the second most common cancer among Latinos, but a lower percentage of Latinos are screened than Whites and Blacks. Along with recognized economic barriers, differences in knowledge and perceptions might impede colorectal screening among Latinos. We conducted 147 individual, qualitative interviews with Dominicans and Puerto Ricans in the northeastern United States to explore their explanatory models for colorectal cancer and screening barriers. Many participants had not previously heard of colorectal cancer. The most commonly mentioned cause of colorectal cancer was anal sex. Also considered risks were “bad food,” digestion leading to constipation, and strained bowel movements. Screening barriers included stigma, misperceptions, embarrassment, and machismo. Progress toward increasing colorectal cancer screening requires normalization of this screening among Latinos. Higher patient familiarity, along with improved physician counseling and referral, might contribute to reducing stigma and other barriers, and to enhancing knowledge and Latino community support of colorectal cancer screening. PMID:19776255
Goldman, Roberta E; Diaz, Joseph A; Kim, Ivone
Colorectal cancer is the second most common cancer among Latinos, but a lower percentage of Latinos are screened than Whites and Blacks. Along with recognized economic barriers, differences in knowledge and perceptions might impede colorectal screening among Latinos. We conducted 147 individual, qualitative interviews with Dominicans and Puerto Ricans in the northeastern United States to explore their explanatory models for colorectal cancer and screening barriers. Many participants had not previously heard of colorectal cancer. The most commonly mentioned cause of colorectal cancer was anal sex. Also considered risks were "bad food," digestion leading to constipation, and strained bowel movements. Screening barriers included stigma, misperceptions, embarrassment, and machismo. Progress toward increasing colorectal cancer screening requires normalization of this screening among Latinos. Higher patient familiarity, along with improved physician counseling and referral, might contribute to reducing stigma and other barriers, and to enhancing knowledge and Latino community support of colorectal cancer screening.
Jenkins, Mark A; Makalic, Enes; Dowty, James G; Schmidt, Daniel F; Dite, Gillian S; MacInnis, Robert J; Ait Ouakrim, Driss; Clendenning, Mark; Flander, Louisa B; Stanesby, Oliver K; Hopper, John L; Win, Aung K; Buchanan, Daniel D
Aim: To determine whether single nucleotide polymorphisms (SNPs) can be used to identify people who should be screened for colorectal cancer. Methods: We simulated one million people with and without colorectal cancer based on published SNP allele frequencies and strengths of colorectal cancer association. We estimated 5-year risks of colorectal cancer by number of risk alleles. Results: We identified 45 SNPs with an average 1.14-fold increase colorectal cancer risk per allele (range: 1.05–1.53). The colorectal cancer risk for people in the highest quintile of risk alleles was 1.81-times that for the average person. Conclusion: We have quantified the extent to which known susceptibility SNPs can stratify the population into clinically useful colorectal cancer risk categories. PMID:26846999
Hardingham, J; Butler, W; Roder, D; Dobrovic, A; Dymock, R; Sage, R; Roberts-Thomson, I
Background—Somatic mutations in K-ras and TP53 may be associated with both acetylator status and prognosis in colorectal cancer. Aims—To determine whether cancers with somatic mutations are more frequent in fast acetylators and whether mutations or acetylator status influence prognosis after colorectal surgery. Patients—One hundred consecutive subjects undergoing elective surgery for colorectal cancer. Methods—Acetylator status was determined by polymerase chain reaction (PCR) genotyping for polymorphism in the N-acetyltransferase 2 (NAT2) gene. Mutations in K-ras (codon 12) and TP53 were determined by PCR analysis using restriction enzyme digestion and single strand conformation polymorphism respectively. Survival from colorectal cancer for up to five years after diagnosis was analysed using the Kaplan-Meier product limit estimator. Cox proportional hazards regression was used to compare survival rates after adjusting for tumour stage. Results—Mutations in K-ras and TP53 were independent of acetylator status. By log rank test, survival was significantly reduced in subjects with TP53 mutations (p=0.003) but was not significantly related to acetylator status or the presence of K-ras mutations. After adjustment for tumour stage, subjects with both TP53 and K-ras mutations had a 4.2-fold case fatality (95% confidence interval 1.5 to 11.6) when compared with that of a TP53 negative reference group. Conclusion—The presence of both TP53 and K-ras mutations in colorectal tumours is an adverse prognostic marker which is independent of tumour stage. Keywords: colorectal cancer; TP53 and K-ras mutations; acetylator status; prognosis PMID:9659162
Dickinson, Brandon T.; Kisiel, John; Ahlquist, David A.; Grady, William M.
Colorectal cancer (CRC), although a significant cause of morbidity and mortality worldwide, has seen a declining incidence and mortality in countries with programmatic screening. Fecal occult blood testing (FOBT) and endoscopic approaches are the predominant screening methods currently. The discovery of the adenoma→carcinoma sequence and a greater understanding of the genetic and epigenetic changes that drive the formation of CRC have contributed to innovative research to identify molecular markers for highly accurate, non-invasive screening tests for CRC. DNA, proteins, messenger RNA, and micro-RNA have all been evaluated. The observation of tumor cell exfoliation into the mucocellular layer of the colonic epithelium and proven stability of DNA in a harsh stool environment make stool DNA a particularly promising marker. The development of a clinically useful stool DNA test has required numerous technical advances, including optimization in DNA stabilization, the development of assays with high analytical sensitivity, and the identification of specific and broadly informative molecular markers. A multi-target stool DNA (MT-sDNA) test, which combines both mutant and methylated DNA markers and a fecal immunochemical test (FIT), recently performed favorably in a large cross-sectional validation study and has been approved by the US Food and Drug Administration (FDA) for the screening of asymptomatic, average risk individuals. The ultimate way in which molecular marker screening assays will be used in clinical practice will require additional studies to determine optimal screening intervals, factors affecting compliance, management of false positive results, and the use of these assays in high-risk populations, as well as other considerations. PMID:25994221
Dickinson, Brandon T; Kisiel, John; Ahlquist, David A; Grady, William M
Colorectal cancer (CRC), although a significant cause of morbidity and mortality worldwide, has seen a declining incidence and mortality in countries with programmatic screening. Faecal occult blood testing and endoscopic approaches are the predominant screening methods currently. The discovery of the adenoma-carcinoma sequence and a greater understanding of the genetic and epigenetic changes that drive the formation of CRC have contributed to innovative research to identify molecular markers for highly accurate, non-invasive screening tests for CRC. DNA, proteins, messenger RNA and micro-RNA have all been evaluated. The observation of tumour cell exfoliation into the mucocellular layer of the colonic epithelium and proven stability of DNA in a harsh stool environment make stool DNA a particularly promising marker. The development of a clinically useful stool DNA test has required numerous technical advances, including optimisation in DNA stabilisation, the development of assays with high analytical sensitivity, and the identification of specific and broadly informative molecular markers. A multitarget stool DNA test, which combines mutant and methylated DNA markers and a faecal immunochemical test, recently performed favourably in a large cross-sectional validation study and has been approved by the US Food and Drug Administration for the screening of asymptomatic, average-risk individuals. The ultimate way in which molecular marker screening assays will be used in clinical practice will require additional studies to determine optimal screening intervals, factors affecting compliance, management of false-positive results, and the use of these assays in high-risk populations, as well as other considerations.
Klarich, DawnKylee S; Brasser, Susan M; Hong, Mee Young
Heavy alcohol drinking is a risk factor for colorectal cancer (CRC); previous studies have shown a linear dose-dependent association between alcohol intake and CRC. However, some studies suggest that moderate alcohol consumption may have a protective effect, similar to that seen in cardiovascular disease. Other factors may interact with alcohol and contribute additional risk for CRC. We aimed to determine the association between moderate alcohol consumption, limited to 30 g of alcohol per day, by beverage type on CRC risk and to assess the effects of other factors that interact with alcohol to influence CRC risk. The PubMed database was used to find articles published between 2008 and 2014 related to alcohol and CRC. Twenty-one relevant articles were evaluated and summarized, including 11 articles reporting on CRC risk associated with moderate intake and 10 articles focusing on genetic interactions associated with alcohol and CRC risk. The association between alcohol and increased risk for CRC was found when intakes exceeded 30 g/d alcohol. Nonsignificant results were consistently reported for intakes <30 g/d. Additional risks for CRC were found to be related to obesity and folate status for regular alcohol consumers. Some significant results suggest that the development of CRC is dependent on the interaction of gene and environment. The association between the amount of alcohol consumed and the incidence of CRC was not significant at moderate intake levels. Moderate alcohol consumption was associated with a reduced CRC risk in study populations with greater adherence to a Mediterranean diet, where wine contributed substantially to the alcoholic beverage consumed. Other factors such as obesity, folate deficiency, and genetic susceptibility may contribute additional CRC risk for those consuming alcohol. To minimize CRC risk, appropriate recommendations should encourage intakes below 30 g of alcohol each day. Copyright © 2015 by the Research Society on
Hasan, Fariha; Mahmood Shah, Sayed Mustafa; Munaf, Misbah; Khan, Muhammad R; Marsia, Shayan; Haaris, Syed Muhammad; Shaikh, Muhammad Hammad; Abdur Rahim, Ismail; Anwar, Muhammad Salar; Qureshi, Kassam S; Iqbal, Maham; Qazi, Sara; Kasi, Burhanuddin A; Tahir, Mahnoor; Ur Rehman, Syed Inam; Fatima, Kaneez
Background The prevalence of colorectal cancer (CRC) is growing in Pakistan; however, there are no national screening programs or guidelines in place to curb its development. This study was conducted with the aim of ascertaining public awareness and attitudes regarding CRC and current screening practices. Furthermore, the study assessed perceived barriers which could impact future screening processes. Methods A cross-sectional, questionnaire-based study was conducted among urban dwellers of Karachi, Pakistan. We excluded any individuals belonging to the medical profession, those diagnosed previously with CRC or having any significant co-morbidity. The validated and pre-tested questionnaire was administered among the study participants to record demographic information, awareness of CRC risk factors, symptoms and screening tests. Attitudes towards screening and perceived barriers to screening were also assessed. Data were analyzed using Statistical Package for Social Sciences (SPSS version 20.0) (IBM Corp., Armonk, NY). A knowledge score, out of a total of 14 points was calculated to reflect a participant's overall knowledge regarding CRC risk factors and signs/symptoms. Results The prevalence of CRC screening in eligible individuals (50 years or older) was 2.6% in our study population. Positive attitudes towards CRC management and screening were observed, with 75.1% (n = 296) acknowledging the preventive role of screening tests. Despite this only 14.9% (n = 58) of study participants expressed a future desire to undergo screening. Major barriers to screening were reported to be "a lack of knowledge regarding the screening procedure", a "lack of screening facilities" and that the "screening procedure is too expensive". A majority (n = 285, 72.3%) of the participants expressed a greater willingness to undergo screening if their doctor recommended it. Conclusion A national CRC screening and awareness program should be launched to promote awareness and facilitate
Huang, Q C; Ye, D; Jiang, X Y; Li, Q L; Yao, K Y; Wang, J B; Jin, M J; Chen, K
Objective: To evaluate the cost-effectiveness of colorectal cancer screening program in different age groups from the view of health economics. Methods: The screening compliance rates, detection rates in different age groups were calculated by using the data from colorectal cancer screening program in Jiashan county, Zhejiang province. The differences in indicator among age groups were analyzed with χ(2) test or trend χ(2) test. The ratios of cost to the number of case were calculated according to cost statistics. Results: The detection rates of immunochemical fecal occult blood test (iFOBT) positivity, advanced adenoma and colorectal cancer and early stage cancer increased with age, while the early diagnosis rates were negatively associated with age. After exclusion the younger counterpart, the cost-effectiveness of individuals aged >50 years could be reduced by 15%-30%. Conclusion: From health economic perspective, it is beneficial to start colorectal cancer screening at age of 50 years to improve the efficiency of the screening.
E, Shuang; Yamamoto, Kazushi; Sakamoto, Yu; Mizowaki, Yui; Iwagaki, Yui; Kimura, Toshiyuki; Nakagawa, Kiyotaka; Miyazawa, Teruo; Tsuduki, Tsuyoshi
The effect of 1-deoxynojirimycin, a caloric restriction mimetic, was examined in ICR mice with azoxymethane dextran sodium sulfate-induced colorectal cancer. Azoxymethane is a carcinogen (10 mg/kg body weight), and 2% dextran sodium sulfate (w/v) used as a colitis-inducing agent. Mice were separated into 5 groups: a group without colorectal cancer fed a normal diet (CO- group), and groups with colorectal cancer fed a normal diet (CO+ group), a calorie-restricted diet (caloric restriction group), and diets including 0.02% and 0.1% 1-deoxynojirimycin (l-1-deoxynojirimycin and H-1-deoxynojirimycin groups). The tumor incidence and number were reduced significantly in the caloric restriction group compared to the CO+ group, and were also suppressed in a dose-dependent manner by 1-deoxynojirimycin. mRNA for anti-apoptotic Bcl-2 was decreased and that for pro-apoptotic Bax was increased in the carcinoma tissue of CR, l-1-deoxynojirimycin and H-1-deoxynojirimycin groups. These results suggest that caloric restriction and 1-deoxynojirimycin inhibit growth of colorectal cancer by inducing apoptosis in an induced cancer model in mice.
E, Shuang; Yamamoto, Kazushi; Sakamoto, Yu; Mizowaki, Yui; Iwagaki, Yui; Kimura, Toshiyuki; Nakagawa, Kiyotaka; Miyazawa, Teruo; Tsuduki, Tsuyoshi
The effect of 1-deoxynojirimycin, a caloric restriction mimetic, was examined in ICR mice with azoxymethane dextran sodium sulfate-induced colorectal cancer. Azoxymethane is a carcinogen (10 mg/kg body weight), and 2% dextran sodium sulfate (w/v) used as a colitis-inducing agent. Mice were separated into 5 groups: a group without colorectal cancer fed a normal diet (CO– group), and groups with colorectal cancer fed a normal diet (CO+ group), a calorie-restricted diet (caloric restriction group), and diets including 0.02% and 0.1% 1-deoxynojirimycin (l-1-deoxynojirimycin and H-1-deoxynojirimycin groups). The tumor incidence and number were reduced significantly in the caloric restriction group compared to the CO+ group, and were also suppressed in a dose-dependent manner by 1-deoxynojirimycin. mRNA for anti-apoptotic Bcl-2 was decreased and that for pro-apoptotic Bax was increased in the carcinoma tissue of CR, l-1-deoxynojirimycin and H-1-deoxynojirimycin groups. These results suggest that caloric restriction and 1-deoxynojirimycin inhibit growth of colorectal cancer by inducing apoptosis in an induced cancer model in mice. PMID:28751809
Durso, Danielle Fernandes; Bacalini, Maria Giulia; do Valle, Ítalo Faria; Pirazzini, Chiara; Bonafé, Massimiliano; Castellani, Gastone; Faria, Ana Maria Caetano; Franceschi, Claudio; Garagnani, Paolo; Nardini, Christine
Colorectal cancer is among the leading causes of cancer death worldwide. Despite numerous molecular characterizations of the phenomenon, the exact dynamics of its onset and progression remain elusive. Colorectal cancer onset has been characterized by changes in DNA methylation profiles, that, owing to the stability of their patterns, are promising candidates to shed light on the molecular events laying at the base of this phenomenon.To exploit this stability and reinforce it, we conducted a meta-analysis on publicly available DNA methylation datasets generated on: normal colorectal, adenoma (ADE) and adenocarcinoma (CRC) samples using the Illumina 450k array, in the systems medicine frame, searching for tumor gene episignatures, to produce a carefully selected list of potential drivers, markers and targets of the disease. The analysis proceeds from a differential meta-analysis of the methylation profiles using an analytical pipeline recently developed by our group , through network reconstruction, topological and functional analyses, to finally highlight relevant epigenomic features. Our results show that genes already highlighted for their genetic or transcriptional alteration in colorectal cancer are also differentially methylated, reinforcing -regardless of the level of cellular control- their role in the complex of alterations involved in tumorigenesis.These findings were finally validated in an independent cohort from The Cancer Genome Atlas (TCGA).
Huang, Rui; Wang, Guiyu; Song, Yanni; Wang, Feng; Zhu, Bing; Tang, Qingchao; Liu, Zheng; Chen, Yinggang; Zhang, Qian; Muhammad, Shan; Wang, Xishan
Although somatic alterations in CAG repeats in the androgen receptor (AR) gene have been suggested to predispose to colorectal cancer, less is known about AR in colorectal cancer carcinogenesis. Because of lack of relevant analysis on CAG repeat length and AR expression in colorectal cancer, we aimed to investigate the prognostic value of polymorphic CAG and protein expression of the AR gene in patients with colorectal cancer. A case-control study was carried out on 550 patients with colorectal cancer and 540 healthy controls to investigate whether polymorphic CAG within the AR gene is linked to increased risk for colorectal cancer. Polymorphic CAG and AR expression were analyzed to clarify their relationship with clinicopathologic and prognostic factors in patients with colorectal cancer. The study showed that the AR gene in patients with colorectal cancer had a longer CAG repeat sequence than those in the control group, as well as increased risk for colorectal cancer among females (P = 0.013), males (P = 0.002), and total colorectal cancer population (P < 0.001), respectively. AR expression exhibited a significant difference in long CAG repeat sequence among males (P < 0.001), females (P < 0.001), and total colorectal cancer study population (P < 0.001). Both long CAG repeat sequence and negative AR expression were associated with a short 5-year overall survival (OS) rate in colorectal cancer. Long CAG repeat sequences and the absence of AR expression were closely related to the development of colorectal cancer. Both long CAG and decreased AR expression were correlated with the poor 5-year OS in patients with colorectal cancer.
Balakrishnan, Archana; Vyas, Arpita; Deshpande, Kaivalya; Vyas, Dinesh
Colorectal cancer accounts for a significant proportion of cancer deaths worldwide. The need to develop more chemotherapeutic agents to combat this disease is critical. Cyclin dependent kinases (CDKs), along with its binding partner cyclins, serve to control the growth of cells through the cell cycle. A new class of drugs, termed CDK inhibitors, has been studied in preclinical and now clinical trials. These inhibitors are believed to act as an anti-cancer drug by blocking CDKs to block the uncontrolled cellular proliferation that is hallmark of cancers like colorectal cancer. CDK article provides overview of the emerging drug class of CDK inhibitors and provides a list of ones that are currently in clinical trials.
With the exponential growth of research efforts on non-coding microRNAs (miRNAs) in the past decade, miRNAs have been demonstrated to be important in many major human diseases, including diabetes, heart disease, and cancer. Due to the broad regulatory function of miRNAs, alterations of their expression can have profound consequences on multiple critical genes and pathways. One of the major issues related to the success of treating advanced colorectal cancer is chemoresistance. In this review, we will present some of the recent advancements in miRNA research related to chemoresistance mechanisms to 5-FU based chemotherapy in colorectal cancer and cancer stem cells. We believe that this miRNA-mediated resistance mechanism will offer novel strategies to develop future anti-cancer therapies.
McClelland, David; Murray, Graeme I
Colorectal cancer is a common malignancy and a leading cause of cancer related death. Cancer staging following resection is key to determining any adjuvant therapy in those patients with high risk disease. In colorectal cancer, tumour stage and lymph node stage are the main pathological factors which have been considered to influence outcome. Increasing emphasis is now being placed on other factors, especially the presence of extramural venous invasion (EMVI). It is important to understand the relationship of EMVI with other pathological factors and to confirm that in an individual centre that EMVI is being detected at an appropriate rate and is of prognostic significance. This comprehensive study assesses the reporting and prognostic significance of EMVI in a single centre, using prospectively collected data from histopathology reports of a cohort of 2405 patients who underwent surgery for colorectal cancer over a nine year period. Overall, EMVI was reported in 27.9% of colorectal cancer excision specimens. In tumours (n = 1928) that had not received neoadjuvant therapy, the presence of EMVI varied significantly depending on tumour site (χ2 = 12.03, p<0.005), tumour stage (χ2 = 268.188, p<0.001), lymph node stage (χ2 = 294.368, p<0.001) and Dukes’ stage (χ2 = 253.753, p<0.001). Multivariate analysis confirmed EMVI as a significant independent prognostic indicator (p<0.001). In conclusion, the presence of EMVI as an independent prognostic indicator is shown and is related to other pathological and prognostic factors. This study emphasises the requirement for the accurate identification of EMVI in colorectal cancer excision specimens and also understanding the relationship of EMVI with other prognostic factors. PMID:26671331
Qin, Chunzhi; Ren, Li; Ji, Meiling; Lv, Shixu; Wei, Ye; Zhu, Dexiang; Lin, Qi; Xu, Pingping; Chang, Wenju; Xu, Jianmin
Background CDKL1 is a member of the cell division cycle 2 (CDC2)-related serine threonine protein kinase family and is overexpressed in malignant tumors such as melanoma, breast cancer, and gastric cancer. Objective This study aimed to evaluate whether CDKL1 can serve as a potential molecular target for colorectal cancer therapy. Materials and methods Expression of CDKL1 in colorectal cancer tissues and cell lines was measured by immunohistochemistry and Western blot, respectively. To investigate the role of CDKL1 in colorectal cancer, CDKL1-small hairpin RNA-expressing lentivirus was constructed and infected into HCT116 and Caco2 cells. The effects of RNA interference (RNAi)-mediated CDKL1 downregulation on cell proliferation and invasion were assessed by CCK-8, colony formation, transwell, and tumorigenicity assays in nude mice. The effects of CDKL1 downregulation on cell cycle and apoptosis were analyzed by flow cytometry. Furthermore, microarray method and data analysis elucidated the molecular mechanisms underlying the phenomenon. Results CDKL1 protein was overexpressed in colorectal cancer tissues compared with paired normal tissues. Knockdown of CDKL1 in HCT116 and Caco2 significantly inhibited cell growth, colony formation ability, tumor invasion, and G1–S phase transition of the cell cycle. The knockdown of CDKL1 stimulated the upregulation of p15 and retinoblastoma protein. Conclusion CDKL1 plays a vital role in tumor proliferation and invasion in colorectal cancer in vitro and in vivo and, thus, may be considered as a valuable target for therapeutic intervention. PMID:28352193
Masood, Umair; Sharma, Anuj; Lowe, Dhruv; Khan, Rashad; Manocha, Divey
Streptococcus anginosus is part of the normal flora of the human gastrointestinal tract. Their ability to cause abscesses is very unique and sets them apart from the rest of the streptococci groups. While an association of group D streptococcus bacteremia and endocarditis with colorectal carcinoma is well established, S. anginosus infections are rarely implicated with colonic malignancy. We present a case of a 62-year-old male who presented to the hospital with fatigue and generalized abdominal pain. Computed tomography of the abdomen revealed multiple liver abscesses and rectal thickening. Blood cultures were found to grow S. anginosus bacteria. Colonoscopy revealed a rectal mass which was later confirmed to be rectal adenocarcinoma. This case presents an association between S. anginosus bacteremia and presence of colorectal cancer which has been highlighted in only a few case reports in literature. This should prompt clinicians to screen for colorectal cancer in patients with S. anginosus bacteremia. PMID:28100999
Alvarez-Chaver, Paula; Rodríguez-Piñeiro, Ana M; Rodríguez-Berrocal, Francisco J; Martínez-Zorzano, Vicenta S; Páez de la Cadena, María
Nowadays, colorectal cancer is one of the major causes of cancer death in Western countries. Due to the lack of biomarkers with clinical utility for this pathology, and considering that membrane and hydrophobic proteins have not been studied in depth, we performed a prefractionation of colorectal tissues prior to two-dimensional gel electrophoresis in order to identify hydrophobic proteins differentially expressed in colorectal cancer patients. Fractions enriched in hydrophobic proteins were obtained from healthy mucosa and tumor tissue by a specific extraction method based on temperature-dependent phase partitioning with Triton X-114. Proteins were separated by two-dimensional gel electrophoresis and gels were silver-stained, scanned and compared using the PDQuest software. Those spots presenting significantly different abundance were submitted to mass spectrometry for protein identification. Alterations in the expression of cytoskeletal proteins, including a decrease of vimentin and the absence of desmin, were found. We also detected alterations in antioxidant and transport proteins, chaperones, and in two isoforms of the calcium-binding protein S100A6. On the other hand, vimentin was chosen to corroborate the electrophoretic results by specific immunodetection. Most of the altered proteins have been related to cellular membranes, many of them to lipid rafts microdomains in the plasma membrane, and they have also been implicated in the control of cell proliferation, apoptosis, or metastasis. In conclusion, all the proteins found altered in colorectal tumor samples could be considered as candidates for future studies focused on their utility as markers for colorectal diagnosis and prognosis, or as targets for colorectal cancer therapy.
Ruiz, Eloy; Celis, Juan; Berrospi, Francisco; Payet, Eduardo
OBJECTIVE: In the absence of extra hepatic disease, the hepatic resection is the treatment of choice for liver metastases from colorectal carcinoma, but a no treatment attitude or the use of chemotherapy still persists in some health centers. This study was done to evaluate the peri operative morbi-mortality and survival after resection of hepatic metastases from colorectal cancer in our institution.METHODS: Clinical, pathologic and outcome data of patients undergoing liver resection for metastatic colorectal cancer at the Instituto de Enfermedades Neoplasicas de Lima Peru between January 1986 and July 2000 was examined.RESULTS: Of 300 liver resections, 24 were performed in patients with liver metastases of colorectal cancer; 17 patients were men and 7 women, who ranged in age from 21 to 79 years ( a mean of 52.66 years), the site of primary disease was the rectum in 7 and colon in 17, 20 patients were Dukes C and 4 Dukes B.Synchronous secondary disease were found in 9 patients and metachronous lesions were found in 15 patients Forty nine metastases were resected (Mean size 4.5 cm, range 1.5 cm 24 cm)Seven patients underwent right hepatectomy, one right hepatectomy plus non anatomic wedge resection, two right trisegmentectomy, 4 left lobectomy and ten a non anatomical resection.The overall post operative morbidity was 8% and the 30 day post operative mortality rate was 0% Estimated three and five year survival rates using Kaplan-Meier method was 50 % and 20% respectively.CONCLUSION: Hepatic resection for a secondary malignant liver growth from colorectal cancer is relatively safe with low morbidity and mortality rates, an remains the only potentially curative treatment. We continue to recommend an aggressive surgical approach to hepatic metastases of colorectal origin in the abscense of extra hepatic disease.
Portillo, Isabel; Arana-Arri, Eunate; Idigoras, Isabel; Bilbao, Isabel; Martínez-Indart, Lorea; Bujanda, Luis; Gutierrez-Ibarluzea, Iñaki
AIM To assess proportions, related conditions and survival of interval cancer (IC). METHODS The programme has a linkage with different clinical databases and cancer registers to allow suitable evaluation. This evaluation involves the detection of ICs after a negative faecal inmunochemical test (FIT), interval cancer FIT (IC-FIT) prior to a subsequent invitation, and the detection of ICs after a positive FIT and confirmatory diagnosis without colorectal cancer (CRC) detected and before the following recommended colonoscopy, IC-colonoscopy. We conducted a retrospective observational study analyzing from January 2009 to December 2015 1193602 invited people onto the Programme (participation rate of 68.6%). RESULTS Two thousand five hundred and eighteen cancers were diagnosed through the programme, 18 cases of IC-colonoscopy were found before the recommended follow-up (43542 colonoscopies performed) and 186 IC-FIT were identified before the following invitation of the 769200 negative FITs. There was no statistically significant relation between the predictor variables of ICs with sex, age and deprivation index, but there was relation between location and stage. Additionally, it was observed that there was less risk when the location was distal rather than proximal (OR = 0.28, 95%CI: 0.20-0.40, P < 0.0001), with no statistical significance when the location was in the rectum as opposed to proximal. When comparing the screen-detected cancers (SCs) with ICs, significant differences in survival were found (P < 0.001); being the 5-years survival for SCs 91.6% and IC-FIT 77.8%. CONCLUSION These findings in a Population Based CRC Screening Programme indicate the need of population-based studies that continue analyzing related factors to improve their detection and reducing harm. PMID:28487610
Colorectal cancer is one of the commonly encountered cancers across the Western World. In United Kingdom, this constitutes third most common ranked cancer and second most common ranked cause of cancer related deaths. Its acute presentation as a malignant colonic obstruction imposes challenges in its management. Colonic stent has been used for many years to alleviate acute obstruction in such cases allowing optimisation of patient’s physiological status and adequate staging of cancer. In this review, current literature evidence regarding use of colonic stent in acute malignant colonic obstruction is critically appraised and recommendations on the use of colonic stent are advocated. PMID:26962401
Corley, Douglas A; Jensen, Christopher D; Marks, Amy R; Zhao, Wei K; Lee, Jeffrey K; Doubeni, Chyke A; Zauber, Ann G; de Boer, Jolanda; Fireman, Bruce H; Schottinger, Joanne E; Quinn, Virginia P; Ghai, Nirupa R; Levin, Theodore R; Quesenberry, Charles P
The proportion of screening colonoscopic examinations performed by a physician that detect one or more adenomas (the adenoma detection rate) is a recommended quality measure. However, little is known about the association between this rate and patients' risks of a subsequent colorectal cancer (interval cancer) and death. Using data from an integrated health care delivery organization, we evaluated the associations between the adenoma detection rate and the risks of colorectal cancer diagnosed 6 months to 10 years after colonoscopy and of cancer-related death. With the use of Cox regression, our estimates of attributable risk were adjusted for the demographic characteristics of the patients, indications for colonoscopy, and coexisting conditions. We evaluated 314,872 colonoscopies performed by 136 gastroenterologists; the adenoma detection rates ranged from 7.4 to 52.5%. During the follow-up period, we identified 712 interval colorectal adenocarcinomas, including 255 advanced-stage cancers, and 147 deaths from interval colorectal cancer. The unadjusted risks of interval cancer according to quintiles of adenoma detection rates, from lowest to highest, were 9.8, 8.6, 8.0, 7.0, and 4.8 cases per 10,000 person-years of follow-up, respectively. Among patients of physicians with adenoma detection rates in the highest quintile, as compared with patients of physicians with detection rates in the lowest quintile, the adjusted hazard ratio for any interval cancer was 0.52 (95% confidence interval [CI], 0.39 to 0.69), for advanced-stage interval cancer, 0.43 (95% CI, 0.29 to 0.64), and for fatal interval cancer, 0.38 (95% CI, 0.22 to 0.65). Each 1.0% increase in the adenoma detection rate was associated with a 3.0% decrease in the risk of cancer (hazard ratio, 0.97; 95% CI, 0.96 to 0.98). The adenoma detection rate was inversely associated with the risks of interval colorectal cancer, advanced-stage interval cancer, and fatal interval cancer. (Funded by the Kaiser Permanente
Auman, James Todd; McLeod, Howard L
Histologically similar colorectal cancers (CRCs) exhibit a wide range of outcomes, suggesting that knowledge of the molecular differences might provide insight into this heterogeneity. Cancer cell lines have been used in preclinical studies to identify gene expression alterations that influence response to chemotherapeutic agents. However, it is not clear to what extent available CRC cell lines reflect the molecular heterogeneity observed in clinical colorectal tumors. We compared genome-wide gene expression data from 22 CRC cell lines and 276 clinical colorectal tumors to determine whether the cell lines were able to represent the variability in expression profiles seen in the clinical tissues. Following mean centered data normalization, hierarchical clustering was performed on the samples using literature-derived biologic and pharmacogenomic gene sets. In general, the majority of cell lines tended to cluster together in a single group, as a subcluster within the clinical tissues, although a few cell lines showed distinct expression profiles from the majority of cell lines. The gene expression data comparison suggests that CRC cell lines do not adequately reflect the molecular heterogeneity of clinical colorectal tumors.
de Vogel, Stefan; van Engeland, Manon; Lüchtenborg, Margreet; de Bruïne, Adriaan P; Roemen, Guido M J M; Lentjes, Marjolein H F M; Goldbohm, R Alexandra; van den Brandt, Piet A; de Goeij, Anton F P M; Weijenberg, Matty P
Folate deficiency has been associated with colorectal cancer risk and may be involved in colorectal carcinogenesis through increased chromosome instability, gene mutations, and aberrant DNA methylation. Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between dietary folate intake and colorectal cancer risk with (APC(+)) and without (APC(-)) truncating APC mutations, accounting for hMLH1 expression and K-ras mutations. In total, 528 cases and 4200 subcohort members were available for data analyses of the study cohort (n = 120,852) from a follow-up period between 2.3 and 7.3 y after baseline. Adjusted gender-specific incidence rate ratios (RR) over tertiles of folate intake were calculated in case-cohort analyses for colon and rectal cancer. Although relatively high folate intake was not associated with overall colorectal cancer risk, it reduced the risk of APC(-)colon tumors in men (RR 0.58, 95% CI 0.32-1.05, P(trend) = 0.06 for the highest vs. lowest tertile of folate intake). In contrast, it was positively associated with APC(+) colon tumors in men (highest vs. lowest tertile: RR 2.77, 95% CI 1.29-5.95, P(trend) = 0.008) and was even stronger when the lack of hMLH1 expression and K-ras mutations were excluded (RR 3.99, 95% CI 1.43-11.14, P(trend) = 0.007). Such positive associations were not observed among women; nor was folate intake associated with rectal cancer when APC mutation status was taken into account. Relatively high folate consumption reduced the risk of APC(-) colon tumors, but folate intake was positively associated with APC(+) colon tumors among men. These opposite results may indicate that folate enhances colorectal carcinogenesis through a distinct APC mutated pathway.
Kehlet, S. N.; Sanz-Pamplona, R.; Brix, S.; Leeming, D. J.; Karsdal, M. A.; Moreno, V.
During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of protein fragments of collagen type I, III and IV as novel biomarkers for colorectal cancer. Specific fragments of degraded type I, III and IV collagen (C1M, C3M, C4M) and type III collagen formation (Pro-C3) were assessed in serum from colorectal cancer patients, subjects with adenomas and matched healthy controls using well-characterized and validated ELISAs. Serum levels of the biomarkers were significantly elevated in colorectal cancer patients compared to subjects with adenomas (C1M, Pro-C3, C3M) and controls (C1M, Pro-C3). When patients were stratified according to their tumour stage, all four biomarkers were able to differentiate stage IV metastatic patients from all other stages. Combination of all markers with age and gender in a logistic regression model discriminated between metastatic and non-metastatic patients with an AUROC of 0.80. The data suggest that the levels of these collagen remodeling biomarkers may be a measure of tumour activity and invasiveness and may provide new clinical tools for monitoring of patients with advanced stage colorectal cancer. PMID:27465284
Balacescu, Loredana; Gherman, Claudia; Chira, Romeo I.; Craiu, Anca; Mircea, Petru A.
Introduction. Colorectal cancer (CRC) is an important cause of morbidity and mortality worldwide. Angiogenesis was reported as one important mechanism activated in colorectal carcinogenesis. Tumor microenvironment associated angiogenesis involves a large spectrum of signaling molecules and deciphering their role in colorectal carcinogenesis still represents a major challenge. The aim of our study is to point out the diagnosis and prediction role of PDGF family and their receptors in colorectal carcinogenesis. Material and Methods. A systematic search in Medline and PubMed for studies reporting the role of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) in tumor biology related to CRC was made. Results. PDGFs are important growth factors for normal tissue growth and division, with an important role in blood vessel formation. PDGFs/PDGFRs signaling pathway has been demonstrated to be involved in angiogenesis mainly by targeting pericytes and vascular smooth muscle cells. High levels of PDGF-BB were reported in CRC patients compared to those with adenomas, while elevated levels of PDGFR α/β in the stroma of CRC patients were correlated with invasion and metastasis. Moreover, PDGF-AB and PDGF-C were correlated with early diagnosis, cancer grading, and metastatic disease. Conclusions. Both PDGFs and PDGFRs families play an important role in colorectal carcinogenesis and could be considered to be investigated as useful biomarkers both for diagnosis and treatment of CRC. PMID:28163397
Papanikolaou, Ioannis G
Surgical practice has been changed since the introduction of robotic techniques and robotic colorectal surgery is an emerging field. Innovative robotic technologies have helped surgeons overcome many technical difficulties of conventional laparoscopic surgery. Herein, we review the clinical studies regarding the application of surgical robots in resections for colorectal cancer. A systematic review of the literature was conducted for articles published up to September 9, 2012, using the MEDLINE database. The keywords that were used in various combinations were: "surgical robotics," "robotic surgery," "computer-assisted surgery," "colectomy," "sigmoid resection," "sigmoidectomy," and "rectal resection." Fifty-nine articles reporting on robot-assisted resections of colon and/or rectum were identified and 41 studies were finally included in the analysis. A total of 1635 colorectal procedures were performed: 254 right colectomies, 185 left colectomies/sigmoid resections, 969 anterior resections, 182 abdominoperineal or intersphincteric resections, 34 colectomies (without being specified as right or left), and 11 total/subtotal colectomies. In general, blood loss, conversion rates, and complications were low but the operative time was longer than the open procedures, whereas the duration of hospitalization was shorter. The number of harvested lymph nodes was also quite satisfactory. Robotic colorectal operations provide favorable results, with acceptable operative times and low conversion rates and morbidity. Surgical robots may provide additional benefits treating challenging pathologies, such as rectal cancer. Further clinical studies and long-term follow-up are required to better evaluate the outcomes of robotic colorectal surgery.
Goel, Vivek; Gray, Ross; Chart, Pam; Fitch, Marg; Saibil, Fred; Zdanowicz, Yola
Abstract Objective To assess attitudes and acceptability of Ontario consumers and doctors towards colorectal screening with faecal occult blood testing (FOBT) and colonoscopy. Design, setting and participants Focus groups with gender‐specific samples of the population, high‐risk gastroenterology patients and family doctors. Method Semi‐structured interview guides used by facilitator to lead groups through knowledge of risk factors and prevention of colorectal cancer, the screening modalities, requirements for implementing screening programmes, barriers to screening and preferences towards screening. Main findings There were low levels of knowledge about colorectal cancer and its prevention in the general population. FOBT was an acceptable screening modality, but considerable education about its use and benefits would be necessary to implement a screening programme. Colonoscopy was not perceived to be a good choice for a primary screen in the general population. The high‐risk group supported use of FOBT in the general population and emphasized the need for education. The doctors were more reluctant about screening, requesting clear guidelines. They also identified the time and resources that would be required if a screening programme were initiated. Conclusion While colorectal screening is acceptable in this sample, information and decision aids are required to enable consumers and providers to make effective decisions. Implementation of colorectal screening programmes requires substantial educational efforts for both consumers and doctors. PMID:14982499
Raices, Micaela; Boccalatte, Luis; Rossi, Gustavo; Wright, Fernando
The most frequent sites of distant metastasis of colorectal cancer (CRC) are primarily liver and lung, followed by brain and bone metastases. Infrequently, metastases are found in the adrenal glands. They usually have a metachronous and homolateral character. We present a case of contralateral synchronic adrenal metastasis of CRC and its surgical resolution.
Raices, Micaela; Boccalatte, Luis; Wright, Fernando
Abstract The most frequent sites of distant metastasis of colorectal cancer (CRC) are primarily liver and lung, followed by brain and bone metastases. Infrequently, metastases are found in the adrenal glands. They usually have a metachronous and homolateral character. We present a case of contralateral synchronic adrenal metastasis of CRC and its surgical resolution. PMID:28616158
Goldstein, Daniel A.; Ahmad, Bilal B.; Chen, Qiushi; Ayer, Turgay; Howard, David H.; Lipscomb, Joseph; El-Rayes, Bassel F.; Flowers, Christopher R.
Purpose Regorafenib is a standard-care option for treatment-refractory metastatic colorectal cancer that increases median overall survival by 6 weeks compared with placebo. Given this small incremental clinical benefit, we evaluated the cost-effectiveness of regorafenib in the third-line setting for patients with metastatic colorectal cancer from the US payer perspective. Methods We developed a Markov model to compare the cost and effectiveness of regorafenib with those of placebo in the third-line treatment of metastatic colorectal cancer. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were based on Medicare reimbursement rates in 2014. Model robustness was addressed in univariable and probabilistic sensitivity analyses. Results Regorafenib provided an additional 0.04 QALYs (0.13 life-years) at a cost of $40,000, resulting in an incremental cost-effectiveness ratio of $900,000 per QALY. The incremental cost-effectiveness ratio for regorafenib was > $550,000 per QALY in all of our univariable and probabilistic sensitivity analyses. Conclusion Regorafenib provides minimal incremental benefit at high incremental cost per QALY in the third-line management of metastatic colorectal cancer. The cost-effectiveness of regorafenib could be improved by the use of value-based pricing. PMID:26304904
Zheng, Yi; Luo, Yun; Lv, Yinxiang; Huang, Chen; Sheng, Qinsong; Zhao, Peng; Ye, Julian; Jiang, Weiqin; Liu, Lulu; Song, Xiaojun; Tong, Zhou; Chen, Wenbin; Lin, Jianjiang; Tang, Yi-Wei; Jin, Dazhi; Fang, Weijia
The entire process of Clostridium difficile colonization to infection develops in large intestine. However, the real colonization pattern of C. difficile in preoperative colorectal cancer patients has not been studied. In this study, 33 C. difficile strains (16.1%) were isolated from stool samples of 205 preoperative colorectal cancer patients. C. difficile colonization rates in lymph node metastasis patients (22.3%) were significantly higher than lymph node negative patients (10.8%) (OR=2.314, 95%CI=1.023-5.235, P =0.025). Meanwhile, patients positive for stool occult blood had lower C. difficile colonization rates than negative patients (11.5% vs. 24.0%, OR=0.300, 95%CI=0.131-0.685, P =0.019). A total of 16 sequence types were revealed by multilocus sequence typing. Minimum spanning tree and time-space cluster analysis indicated that all C. difficile isolates were epidemiologically unrelated. Antibiotic susceptibility testing showed all isolates were susceptible to vancomycin and metronidazole. The results suggested that the prevalence of C. difficile colonization is high in preoperative colorectal cancer patients, and the colonization is not acquired in the hospital. Since lymph node metastasis colorectal cancer patients inevitably require adjuvant chemotherapy and C. difficile infection may halt the ongoing treatment, the call for sustained monitoring of C. difficile in those patients is apparently urgent.
Mar, Javier; Errasti, Jose; Soto-Gordoa, Myriam; Mar-Barrutia, Gilen; Martinez-Llorente, José Miguel; Domínguez, Severina; García-Albás, Juan José; Arrospide, Arantzazu
The aim of this study was to measure the cost of treatment of colorectal cancer in the Basque public health system according to the clinical stage. We retrospectively collected demographic data, clinical data and resource use of a sample of 529 patients. For stagesi toiii the initial and follow-up costs were measured. The calculation of cost for stageiv combined generalized linear models to relate the cost to the duration of follow-up based on parametric survival analysis. Unit costs were obtained from the analytical accounting system of the Basque Health Service. The sample included 110 patients with stagei, 171 with stageii, 158 with stageiii and 90 with stageiv colorectal cancer. The initial total cost per patient was 8,644€ for stagei, 12,675€ for stageii and 13,034€ for stageiii. The main component was hospitalization cost. Calculated by extrapolation for stageiv mean survival was 1.27years. Its average annual cost was 22,403€, and 24,509€ to death. The total annual cost for colorectal cancer extrapolated to the whole Spanish health system was 623.9million€. The economic burden of colorectal cancer is important and should be taken into account in decision-making. The combination of generalized linear models and survival analysis allows estimation of the cost of metastatic stage. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
Sulżyc-Bielicka, Violetta; Kołodziejczyk, Lidia; Jaczewska, Sylwia; Bielicki, Dariusz; Kładny, Józef; Safranow, Krzysztof
Parasitic protozoans of the Cryptosporidium genus are intracellular intestinal parasites of mammals, causing cryptosporidiosis. Clinically, cryptosporidiosis manifests as chronic diarrhoea. Individuals with immune disorders, including those with neoplasms, are at risk of symptomatic invasion. Was the evaluation of Cryptosporidium sp. prevalence in patients with diagnosed colorectal cancer. The studied group encompassed 87 patients with diagnosed colorectal cancer, undergoing surgery at the Department of General and Oncological Surgery, Pomeranian Medical University, in the years 2009-2010. Immunoenzymatic tests for Cryptosporidium sp. on faeces samples were performed with the use of commercial test kit, ProSpecT(®)Cryptosporidium Microplate Assay (Remel Inc). The presence of Cryptosporidium sp. was found in 12.6% of studied patients with colorectal cancer. The performed statistical analysis did not reveal any correlation between Cryptosporidium sp. infection and gender, age, neoplasm advancement stage as per Astler-Coller scale, neoplasm differentiation grade, or neoplastic tumour localisation in relation to the splenic flexure. There was found high prevalence of Cryptosporidium sp. in patients with colorectal cancer. It was comparable to the prevalence reported for patients with immune deficiency.
Ciombor, Kristen K.; Goldberg, Richard M.
Angiogenesis is a complex biologic process critical to growth and proliferation of colorectal cancer. The safety and efficacy of various anti-angiogenic agents have been investigated in many treatment settings. Bevacizumab, an anti-vascular endothelial growth factor agent, has efficacy in both the first-line setting and beyond progression in metastatic colorectal cancer. The decoy vascular endothelial growth factor receptor aflibercept has been approved in combination with 5-fluorouracil, leucovorin and irinotecan-based chemotherapy in metastatic colorectal cancer patients whose disease has progressed on a prior oxaliplatin-based chemotherapy regimen. The multikinase inhibitor regorafenib is modestly effective in the refractory colorectal cancer setting but confers significant toxicity. Ramucirumab, an anti-vascular endothelial growth factor receptor 2 molecule, has efficacy in combination with 5-fluorouracil, leucovorin and irinotecan after disease progression on a first-line bevacizumab-, oxaliplatin- and fluoropyrimidine-containing regimen. Questions regarding optimal treatment setting, predictive biomarkers of response, and cost effectiveness of these anti-angiogenic agents and others are as yet unanswered. PMID:27551256
Goldstein, Daniel A; Ahmad, Bilal B; Chen, Qiushi; Ayer, Turgay; Howard, David H; Lipscomb, Joseph; El-Rayes, Bassel F; Flowers, Christopher R
Regorafenib is a standard-care option for treatment-refractory metastatic colorectal cancer that increases median overall survival by 6 weeks compared with placebo. Given this small incremental clinical benefit, we evaluated the cost-effectiveness of regorafenib in the third-line setting for patients with metastatic colorectal cancer from the US payer perspective. We developed a Markov model to compare the cost and effectiveness of regorafenib with those of placebo in the third-line treatment of metastatic colorectal cancer. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were based on Medicare reimbursement rates in 2014. Model robustness was addressed in univariable and probabilistic sensitivity analyses. Regorafenib provided an additional 0.04 QALYs (0.13 life-years) at a cost of $40,000, resulting in an incremental cost-effectiveness ratio of $900,000 per QALY. The incremental cost-effectiveness ratio for regorafenib was > $550,000 per QALY in all of our univariable and probabilistic sensitivity analyses. Regorafenib provides minimal incremental benefit at high incremental cost per QALY in the third-line management of metastatic colorectal cancer. The cost-effectiveness of regorafenib could be improved by the use of value-based pricing. © 2015 by American Society of Clinical Oncology.
Wang, Siqi; Zhang, Shiwu; Zhao, Zhenying; Zhang, Chunze; Yang, Xiaoyun; Wang, Yijia
Colorectal cancer has a relatively low sensitivity to paclitaxel. The purpose of this study was to investigate the role of connexin 43 (Cx43), which is a structural component of gap junctional communication (GJC), in paclitaxel cytotoxicity in colorectal cancer cells. Three colorectal cancer cell lines (HCT106, HCT116 and LoVo) were transfected with Cx43 and used to examine paclitaxel cytotoxicity. A western blot assay was used to confirm Cx43 expression in transfected cell lines as well as the expression of several proteins that are associated with paclitaxel cytotoxicity. A parachute dye-coupling assay was used to measure GJC function. An MTT assay was used to analyze the viability of paclitaxel-treated cells. Cx43 expression level and GJC function were significantly upregulated by the transfection (P<0.05). The viability of transfected cells was significantly inhibited compared with that of untransfected cells when treated with paclitaxel (20 or 80 nM) at high culture density but not at low culture density (P<0.05). Cx43 transfection significantly increased the mitotic arrest, tubulin polymerization and apoptosis effects of paclitaxel (P<0.05). It was also found that paclitaxel had an inhibitory effect on GJC function after 12 h of treatment in LoVo cells (P<0.05). These results indicate that Cx43 may serve as a target of paclitaxel chemotherapy for colorectal cancer. PMID:28810580
Lv, Yinxiang; Huang, Chen; Sheng, Qinsong; Zhao, Peng; Ye, Julian; Jiang, Weiqin; Liu, Lulu; Song, Xiaojun; Tong, Zhou; Chen, Wenbin; Lin, Jianjiang; Tang, Yi-Wei; Jin, Dazhi; Fang, Weijia
The entire process of Clostridium difficile colonization to infection develops in large intestine. However, the real colonization pattern of C. difficile in preoperative colorectal cancer patients has not been studied. In this study, 33 C. difficile strains (16.1%) were isolated from stool samples of 205 preoperative colorectal cancer patients. C. difficile colonization rates in lymph node metastasis patients (22.3%) were significantly higher than lymph node negative patients (10.8%) (OR=2.314, 95%CI=1.023-5.235, P =0.025). Meanwhile, patients positive for stool occult blood had lower C. difficile colonization rates than negative patients (11.5% vs. 24.0%, OR=0.300, 95%CI=0.131-0.685, P =0.019). A total of 16 sequence types were revealed by multilocus sequence typing. Minimum spanning tree and time-space cluster analysis indicated that all C. difficile isolates were epidemiologically unrelated. Antibiotic susceptibility testing showed all isolates were susceptible to vancomycin and metronidazole. The results suggested that the prevalence of C. difficile colonization is high in preoperative colorectal cancer patients, and the colonization is not acquired in the hospital. Since lymph node metastasis colorectal cancer patients inevitably require adjuvant chemotherapy and C. difficile infection may halt the ongoing treatment, the call for sustained monitoring of C. difficile in those patients is apparently urgent. PMID:28060753
Liu, Li; Zhao, Liang; Zhang, Yanfei; Zhang, Qinling; Ding, Yanqing
Tiam1 (T lymphoma invasion and metastasis 1), a guanine nucleotide exchange factor that activates Rac, was recently identified as a novel colorectal cancer metastasis-related gene. To better understand the mechanism underlying Tiam1-mediated metastasis, we applied two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis to identify differentially expressed proteins between Tiam1 transfected and mock transfected colorectal cancer HT29 cells. Eleven differentially expressed proteins were identified and further validated by Western blot and/or real-time PCR. The results revealed that Tiam1 transfection in colorectal cancer cells could upregulate the expression of Fascin-1, heat shock protein 27 (HSP27), high-mobility group box 1 (HMGB1), glutathione S-transferase omega 1 (GSTO1) and downregulate the expression of annexin IV. These differentially expressed proteins may be directly or indirectly regulated by Tiam1 and be helpful in studying mechanisms that lead to the function of Tiam1. These results give some clues to elucidate the mechanism of Tiam1-mediated metastasis for colorectal cancer.
Arribas-Martin, Antonio; Díaz-Pizarro-Graf, José Ignacio; Muñoz-Hinojosa, Jorge Demetrio; Valdés-Castañeda, Alberto; Cruz-Ramírez, Omar; Bertrand, Martin Marie
Laparoscopic surgery for colorectal cancer is currently accepted and widespread worldwide. However, according tol the surgical experience on this approach, surgical and short-term oncologic results may vary. Studies comparing laparoscopic vs. open surgery in our population are scarce. To determine the superiority of the laparoscopic vs. open technique for colorectal cancer surgery. This retrospective and comparative study collected data from patients operated on for colorectal cancer between 1999 and 2011 at the Angeles Lomas Hospital, Mexico. A total of 82 patients were included in this study; 47 were operated through an open approach and 35 laparoscopically. Mean operative time was significantly lower in the open approach group (p= 0.008). There were no significant difference between both techniques for intraoperative bleeding (p= 0.3980), number of lymph nodes (p= 0.27), time to initiate oral feeding (p= 0.31), hospital stay (p= 0.12), and postoperative pain (p= 0.19). Procedure-related complications rate and type were not significantly different in both groups (p= 0.44). Patients operated laparoscopically required significantly less analgesic drugs (p= 0.04) and less need for epidural postoperative analgesia (p= 0.01). Laparoscopic approach is as safe as the traditional open approach for colorectal cancer. Early oncological and surgical results confirm its suitability according to this indication.
Thomson, Maria D.; Siminoff, Laura A.; Longo, Daniel R.
Background: This study explored the characteristics of colorectal cancer (CRC) patients who accessed Internet-based health information as part of their symptom appraisal process prior to consulting a health care provider. Method: Newly diagnosed CRC patients who experienced symptoms prior to diagnosis were interviewed. Brief COPE was used to…
Skeie, Guri; Braaten, Tonje; Olsen, Anja; Kyrø, Cecilie; Tjønneland, Anne; Nilsson, Lena Maria; Landberg, Rikard; Lund, Eiliv
To our knowledge, no studies of associations between intake of whole grain (WHG) and survival of colorectal cancer have been published, despite evidence that dietary fiber, and to some extent WHG, are associated with lower risk of colorectal cancer. Scandinavia is an area where the WHG consumption traditionally is high. We performed a case-only (N = 1119) study in the Scandinavian HELGA cohort of pre-diagnosis WHG intake (total WHG, WHG wheat, WHG rye, and WHG oats) and survival of colorectal cancer. Cox regression analyses were used to study the associations, both in categorical and continuous models, stratified by location (proximal, distal, rectum) and country. No evidence of an association was found, neither for total WHG intake (hazard ratio = 1.32, 95% confidence interval: 0.88-1.97 lowest vs. highest tertile, adjusted for age at diagnosis, metastasis status, smoking, folate, margarine, and energy), nor for specific grains. Prediagnosis consumption of WHG does not seem to improve survival of colorectal cancer in subjects diagnosed within this prospective population-based Scandinavian cohort.
Gonzalez, J. R.; Fernandez, E.; Moreno, V.; Ribes, J.; Peris, M.; Navarro, M.; Cambray, M.; Borras, J. M.
Background: While several studies have analysed sex and socioeconomic differences in cancer incidence and mortality, sex differences in oncological health care have been seldom considered. Objective: To investigate sex based inequalities in hospital readmission among patients diagnosed with colorectal cancer. Design: Prospective cohort study. Setting: Hospital Universitary in L'Hospitalet (Barcelona, Spain). Participants: Four hundred and three patients diagnosed with colorectal between January 1996 and December 1998 were actively followed up until 2002. Main outcome measurements and methods: Hospital readmission times related to colorectal cancer after surgical procedure. Cox proportional model with random effect (frailty) was used to estimate hazard rate ratios and 95% confidence intervals of readmission time for covariates analysed. Results: Crude hazard rate ratio of hospital readmission in men was 1.61 (95% CI 1.21 to 2.15). When other significant determinants of readmission were controlled for (including Dukes's stage, mortality, and Charlson's index) a significant risk of readmission was still present for men (hazard rate ratio: 1.52, 95% CI 1.17 to 1.96). Conclusions: In the case of colorectal cancer, women are less likely than men to be readmitted to the hospital, even after controlling for tumour characteristics, mortality, and comorbidity. New studies should investigate the role of other non-clinical variable such as differences in help seeking behaviours or structural or personal sex bias in the attention given to patients. PMID:15911648
Background Germline mutations in APC and AXIN2 are both associated with colon neoplasia as well as anomalous dental development. We tested the hypothesis that congenitally missing teeth may occur more commonly in individuals diagnosed with colorectal cancer than in individuals without this diagnosis. Methods Via a survey conducted on 1636 individuals with colorectal cancer (CRC) and 2788 individuals with no colorectal cancer from the Colon Cancer Family Registry, self-reported information on congenitally missing teeth was collected. The frequency of missing teeth between cases and controls was compared using Pearson’s chi-squared test or Fisher’s exact test. Results 4.8% of cases and 5.7% of controls reported having at least one missing tooth (p = 0.20). When we stratified by recruitment site, gender, and mutation status where available, frequency of missing teeth was not statistically significantly different between cases and controls. Conclusions This study did not provide support for there being a general predisposition to missing teeth among a large cohort of CRC patients. The study neither addresses nor excludes the possibility, however, that individuals presenting with notable hypodontia/oligodontia might still have an increased risk for colorectal neoplasia. PMID:24607150
Thomson, Maria D.; Siminoff, Laura A.; Longo, Daniel R.
Background: This study explored the characteristics of colorectal cancer (CRC) patients who accessed Internet-based health information as part of their symptom appraisal process prior to consulting a health care provider. Method: Newly diagnosed CRC patients who experienced symptoms prior to diagnosis were interviewed. Brief COPE was used to…
Wernli, Karen J; Wang, Yinghui; Zheng, Yingye; Potter, John D; Newcomb, Polly A
The influence of hormonal changes caused by pregnancy has been well studied in relation to colorectal cancer risk, but the association remains undefined. The purpose of this investigation was to examine in a case-control study the relationship between differences in gravidity and parity and colorectal cancer risk and if the association varied by microsatellite instability (MSI), a feature more common in women. The study population included incident colorectal cancer patients (n = 1014), aged 50-74 years, diagnosed in 1998-2002 in Washington state and controls (n = 1064) randomly selected from population lists. All study subjects completed telephone interviews to ascertain prior pregnancies, live births, and other covariates. Case tissue samples were obtained for MSI analyses. Multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, family history of colorectal cancer, body mass index (BMI), education, endoscopy screening, oral contraceptive use, hormone therapy use, smoking, and alcohol consumption. There was an approximate 30%-50% reduction in risk of colon cancer associated with gravidity, which was attenuated in the analysis with parity. Increasing gravidity and parity were associated with a suggestion of a decreasing trend in risk for rectal cancer (p for trend = 0.07). Compared with women who had equal numbers of pregnancies and live births, women who were nulligravid and nulliparous had a 40%-60% increased risk of colon cancer. There was a suggestion of a reduced risk of both colon and rectal cancer associated with one more pregnancy than live birth. There was a suggestion of an increased risk of MSI-high tumors with nulligravidity and nulliparity. These results confirm the importance of pregnancy events in the etiology of colon and rectal cancer.
Wang, Yinghui; Zheng, Yingye; Potter, John D.; Newcomb, Polly A.
Abstract Objectives The influence of hormonal changes caused by pregnancy has been well studied in relation to colorectal cancer risk, but the association remains undefined. The purpose of this investigation was to examine in a case-control study the relationship between differences in gravidity and parity and colorectal cancer risk and if the association varied by microsatellite instability (MSI), a feature more common in women. Methods The study population included incident colorectal cancer patients (n = 1014), aged 50–74 years, diagnosed in 1998–2002 in Washington state and controls (n = 1064) randomly selected from population lists. All study subjects completed telephone interviews to ascertain prior pregnancies, live births, and other covariates. Case tissue samples were obtained for MSI analyses. Multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, family history of colorectal cancer, body mass index (BMI), education, endoscopy screening, oral contraceptive use, hormone therapy use, smoking, and alcohol consumption. Results There was an approximate 30%–50% reduction in risk of colon cancer associated with gravidity, which was attenuated in the analysis with parity. Increasing gravidity and parity were associated with a suggestion of a decreasing trend in risk for rectal cancer (p for trend = 0.07). Compared with women who had equal numbers of pregnancies and live births, women who were nulligravid and nulliparous had a 40%–60% increased risk of colon cancer. There was a suggestion of a reduced risk of both colon and rectal cancer associated with one more pregnancy than live birth. There was a suggestion of an increased risk of MSI-high tumors with nulligravidity and nulliparity. Conclusions These results confirm the importance of pregnancy events in the etiology of colon and rectal cancer. PMID:19575687
Bai, Jinghui; Xu, Jian; Zhao, Jian; Zhang, Rui
A hybrid drug delivery system (DDS) composed of hyaluronan and calcium carbonate (CC) was developed. By taking advantage of the tumor-targeting ability of hyaluronan and the drug-loading property of CC, the well-formed hyaluronan–CC nanoparticles were able to serve as a DDS targeting colorectal cancer with a decent drug loading content, which is beneficial in the chemotherapy of colorectal cancer. In this study, hyaluronan–CC nanoparticles smaller than 100 nm were successfully developed to load the wide-range anti-cancer drug adriamycin (Adr) to construct hyaluronan–CC/Adr nanoparticles. On the other hand, we also found that hyaluronan–CC/Adr nanoparticles can possibly increase the uptake ratio of Adr into HT29 colorectal cancer cells when compared with hyaluronan-free nanoparticles (CC/Adr) via the CD44 receptor-mediated endocytosis via competitive uptake and in vivo imaging assays. Note that both in vitro (CCK-8 assay on HT29 cells) and in vivo (anti-cancer assay on HT-29 tumor-bearing nude mice model) experiments revealed that hyaluronan–CC/Adr nanoparticles exhibited stronger anti-cancer activity than free Adr or CC/Adr nanoparticles with minimized toxic side effects and preferable cancer-suppression potential.
Cernat, Laura; Blaj, Cristina; Jackstadt, Rene; Brandl, Lydia; Engel, Jutta; Hermeking, Heiko; Jung, Andreas; Kirchner, Thomas; Horst, David
Colonic crypts are stereotypical structures with distinct stem cell, proliferating, and differentiating compartments. Colorectal cancers derive from colonic crypt epithelia but, in contrast, form morphologically disarrayed glands. In this study, we investigated to which extent colorectal cancers phenocopy colonic crypt architecture and thus preserve structural organization of the normal intestinal epithelium. A subset of colon cancers showed crypt-like compartments with high WNT activity and nuclear β-Catenin at the leading tumor edge, adjacent proliferation, and enhanced Cytokeratin 20 expression in most differentiated tumor epithelia of the tumor center. This architecture strongly depended on growth conditions, and was fully reproducible in mouse xenografts of cultured and primary colon cancer cells. Full crypt-like organization was associated with low tumor grade and was an independent prognostic marker of better survival in a collection of 221 colorectal cancers. Our findings suggest that full activation of preserved intestinal morphogenetic programs in colon cancer requires in vivo growth environments. Furthermore, crypt-like architecture was linked with less aggressive tumor biology, and may be useful to improve current colon cancer grading schemes. PMID:25111606
Zhang, Peili; Zuo, Zhigui; Shang, Wenjing; Wu, Aihua; Bi, Ruichun; Wu, Jianbo; Li, Shaotang; Sun, Xuecheng; Jiang, Lei
Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p < 0.0001) and hsa_circRNA_104700 ( p = 0.0003) were significantly lower in colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p < 0.0001) and 0.616 ( p < 0.0001), respectively. In conclusion, these results suggest that hsa_circRNA_103809 and hsa_circRNA_104700 may be potentially involved in the development of colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.
Lee, Byoung Chul; Yu, Chang Sik; Kim, Jihun; Lee, Jong Lyul; Kim, Chan Wook; Yoon, Yong Sik; Park, In Ja; Lim, Seok-Byung; Kim, Jin Cheon
Abstract This study was conducted to investigate the clinicopathological features of synchronous cancers and treatment options according to their locations. Records of 8368 patients with colorectal cancer treated at our center between July 2003 and December 2010 were analyzed retrospectively. All synchronous colorectal cancer patients who underwent surgical treatment were included. Synchronous cancers were identified in 217 patients (2.6%). Seventy-nine patients underwent either total colectomy, subtotal colectomy, or total proctocolectomy; 116 underwent 1 regional resection, including local excision; and 22 underwent 2 regional resections. The mean age was 62 years, slightly higher than that for the single-cancer patients. Synchronous cancers were more common in male patients, more frequently located in the left colon, had more microsatellite instability-high status, and showed more advanced stage than single cancer. Extensive resection was mainly performed for synchronous cancers located in both the right and left colon. Two regional resections were performed for cancers in the right colon and rectum. There were no differences in complication rates or the occurrence of metachronous cancer between the 2-region resection and extensive resection groups. Eight years postoperatively, the mean number of daily bowel movements for these 2 groups were 1.9 and 4.3, respectively. We found that synchronous cancer was different from single cancer in terms of age, gender, location, and pathologic features. Synchronous colorectal cancer requires different treatment strategy according to the distribution of lesions. Comparison between the 2 regional resections and extensive resection approaches suggests that 2 regional resections are preferable. PMID:28248880
Chen, Junxiong; Wang, Chenliang; Lan, Wenjian; Huang, Chunying; Lin, Mengmeng; Wang, Zhongyang; Liang, Wanling; Iwamoto, Aikichi; Yang, Xiangling; Liu, Huanliang
The discovery of new bioactive compounds from marine natural sources is very important in pharmacological research. Here we developed a Wnt responsive luciferase reporter assay to screen small molecule inhibitors of cancer associated constitutive Wnt signaling pathway. We identified that gliotoxin (GTX) and some of its analogues, the secondary metabolites from marine fungus Neosartorya pseufofischeri, acted as inhibitors of the Wnt signaling pathway. In addition, we found that GTX downregulated the β-catenin levels in colorectal cancer cells with inactivating mutations of adenomatous polyposis coli (APC) or activating mutations of β-catenin. Furthermore, we demonstrated that GTX induced growth inhibition and apoptosis in multiple colorectal cancer cell lines with mutations of the Wnt signaling pathway. Together, we illustrated a practical approach to identify small-molecule inhibitors of the Wnt signaling pathway and our study indicated that GTX has therapeutic potential for the prevention or treatment of Wnt dependent cancers and other Wnt related diseases. PMID:26445050
Li, Chen; Wang, Jingyu; Kong, Jianlu; Tang, Jinlong; Wu, Yihua; Xu, Enping; Zhang, Honghe; Lai, Maode
Metastasis is the major cause of cancer deaths, and the epithelial-mesenchymal transition (EMT) has been considered to be a fundamental event in cancer metastasis. However, the role of growth differentiation factor 15 (GDF15) in colorectal cancer (CRC) metastasis and EMT remains poorly understood. Here, we showed that GDF15 promoted CRC cell metastasis both in vitro and in vivo. In addition, the EMT process was enhanced by GDF15 through binding to TGF-β receptor to activate Smad2 and Smad3 pathways. Clinical data showed GDF15 level in tumor tissues, and the serum was significantly increased, in which high GDF15 level correlated with a reduced overall survival in CRC. Thus, GDF15 may promote colorectal cancer metastasis through activating EMT. Promisingly, GDF15 could be considered as a novel prognostic marker for CRC in the clinic.
Hanusch, J; Friedl, H P; Schemper, M; Schiessel, R
Based on data obtained from the official Austrian cancer registry, we evaluated the incidence of, and death rate from cancer of the colon and rectum. The increase in the incidence of colorectal cancer in Austria is comparable to that of other western industrial countries. There is an estimated rise in the annual figures of newly registered patients from 3174 in 1971 to 3981 cases in 1981. Regional distribution within Austria is not homogeneous: the highest risk of disease was observed in Vienna (60 new cases per year per 100000 inhabitants), the lowest in Tyrol with 40 new cases per 100000. The marked east-west slope in the incidence of colorectal cancer in Austria is a good basis for the investigation of pathogenetic factors.
Zhang, Yanmei; Fang, Mengdie; Song, Yongfei; Ren, Juan; Fang, Jianfei; Wang, Xiaoju
Identifying oncogenes that promote cancer cell proliferation or survival is critical for treatment of colorectal cancer. The Brother of Regulator of Imprinted Sites (BORIS) is frequently expressed in most types of cancer, but rarely in normal tissues. Aberrantly expressed BORIS relates to colorectal cancer, but its function in colorectal cancer cells remains unclear. In addition, previous studies indicated the significance of cytoplasm-localized BORIS in cancer cells. However, none of them investigated its function. Herein, we investigated the functions of BORIS in cancer cell proliferation and apoptosis and the role of cytoplasm-localized BORIS in colorectal cancer. BORIS expression correlated with colorectal cancer proliferation. BORIS overexpression promoted colorectal cancer cell growth, whereas BORIS knockdown suppressed cell proliferation. Sensitivity of colorectal cancer cells to 5-fluorouracil (5-FU) was inversely correlated with BORIS expression. These data suggest that BORIS functions as an oncogene in colorectal cancer. BORIS silencing induced reactive oxygen species (ROS) production and apoptosis, whereas BORIS supplementation inhibited apoptosis induced by BORIS short interfering RNA (siRNA), hydrogen peroxide (H2O2) or 5-FU. Introduction of BORIS-ZFdel showed that cytoplasmic localization of BORIS inhibited apoptosis but not ROS production. Our study highlights the anti-apoptotic function of BORIS in colorectal cancer. PMID:28098226
Wolf, Michael S.; Baker, David W.
Background Despite the documented benefits of colorectal cancer screening, patient participation rates remain low. Physician recommendation has been identified as a significant predictor of screening completion. Objective The aim of this study is to investigate how primary care physicians perceive colorectal cancer screening communication tasks, as well as to explore the form and content of actual screening discussions. Design The research design includes a mailed physician survey and a separate observational study in a sample of videotaped medical encounters. Participants and Data Sources The participants were 270 primary care physicians who completed a mailed questionnaire (57.9% response rate) and 18 physician–patient encounters that included discussions of colorectal cancer screening. Measurement The questionnaire focused on perceived importance and accomplishment of communication tasks relevant to colorectal cancer screening. Two of the authors reviewed transcripts of videotaped physician encounters to determine whether the same communication tasks assessed in the survey were accomplished. Interrater reliability was high across all of the mutually exclusive coding categories (Kappa > .90). Results Physicians rated colonoscopy as the most important screening option to discuss; self-reports indicate that colonoscopy (84.8%) is more frequently mentioned than fecal occult blood test (FOBT; 49.4%), flexible sigmoidoscopy (34.1%), or computed tomography (CT) imaging (18.1%). Explaining benefits and risks, describing test procedure and frequency, eliciting patient preferences, and making a plan for screening were all viewed as very important. Self-reported accomplishment of these communication tasks was considerably higher than that observed in our separate videotape sample. Conclusion Most physicians recognize and espouse the importance of recommending colorectal cancer screening to eligible patients. However, findings from both the physician survey and
Background Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60-mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results After an exhaustive process of pre-processing to ensure data quality--lost values imputation, probes quality, data smoothing and intraclass variability filtering--the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955). PMID:22280244
Karasneh, Reema A; Murray, Liam J; Hughes, Carmel M; Cardwell, Chris R
Digoxin has been shown to affect a number of pathways that are of relevance to cancer, and its use has been associated with increased risks of breast and uterus cancer and, more recently, a 40% increase in colorectal cancer risk. These findings raise questions about the safety of digoxin use in colorectal cancer patients, and, therefore, we investigated whether digoxin use after colorectal cancer diagnosis increased the risk of colorectal cancer-specific mortality. A cohort of 10,357 colorectal cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries and linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify 2,724 colorectal cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted HRs and 95% confidence intervals (CI) were calculated for the association between postdiagnostic exposure to digoxin and colorectal cancer-specific mortality. Overall, 682 (6%) colorectal cancer patients used digoxin after diagnosis. Digoxin use was associated with a small increase in colorectal cancer-specific mortality before adjustment (HR, 1.25; 95% CI, 1.07-1.46), but after adjustment for confounders, the association was attenuated (adjusted HR, 1.10; 95% CI, 0.91-1.34) and there was no evidence of a dose response. In this large population-based colorectal cancer cohort, there was little evidence of an increase in colorectal cancer-specific mortality with digoxin use after diagnosis. These results provide some reassurance that digoxin use is safe in colorectal cancer patients. ©2015 American Association for Cancer Research.
Porter, Geoffrey; Urquhart, Robin; Bu, Jingyu; Kendell, Cynthia; Macintyre, Maureen; Dewar, Ron; Kephart, George; Asada, Yukiko; Grunfeld, Eva
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Canada and accounts for 11.9% of all cancer-related mortality. Fortunately, previous studies have provided evidence of improved outcomes from access to timely and appropriate health services along the disease trajectory in CRC. As a result, the CIHR/CCNS Team in Access to Colorectal Cancer Services in Nova Scotia (Team ACCESS) was created to build colorectal cancer (CRC) research capacity in Nova Scotia (NS) and to study access to and quality of CRC services along the entire continuum of cancer care. The objectives of this paper are to: 1) provide a detailed description of the methodologies employed across the various studies being conducted by Team ACCESS; 2) demonstrate how administrative health data can be used to evaluate access and quality in CRC services; and 3) provide an example of an interdisciplinary team approach to addressing health service delivery issues. All patients diagnosed with CRC in NS between 2001 and 2005 were identified through the Nova Scotia Cancer Registry (NSCR) and staged using the Collaborative Stage Data Collection System. Using administrative databases that were linked at the patient level, Team ACCESS created a retrospective longitudinal cohort with comprehensive demographic, clinical, and healthcare utilization data. These data were used to examine access to and quality of CRC services in NS, as well as factors affecting access to and quality of care, at various transition points along the continuum of care. Team ACCESS has also implemented integrated knowledge translation strategies targeting policy- and decision- makers. The development of Team ACCESS represents a unique approach to CRC research. We anticipate that the skills, tools, and knowledge generated from our work will also advance the study of other cancer disease sites in NS. Given the increasing prevalence of cancer, and with national and provincial funding agencies promoting collaborative research
Murcia, Oscar; Juárez, Miriam; Hernández-Illán, Eva; Egoavil, Cecilia; Giner-Calabuig, Mar; Rodríguez-Soler, María; Jover, Rodrigo
Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer (CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of CpG islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy. PMID:27053844
Chisanga, David; Keerthikumar, Shivakumar; Pathan, Mohashin; Ariyaratne, Dinuka; Kalra, Hina; Boukouris, Stephanie; Mathew, Nidhi Abraham; Al Saffar, Haidar; Gangoda, Lahiru; Ang, Ching-Seng; Sieber, Oliver M; Mariadason, John M; Dasgupta, Ramanuj; Chilamkurti, Naveen; Mathivanan, Suresh
In order to advance our understanding of colorectal cancer (CRC) development and progression, biomedical researchers have generated large amounts of OMICS data from CRC patient samples and representative cell lines. However, these data are deposited in various repositories or in supplementary tables. A database which integrates data from heterogeneous resources and enables analysis of the multidimensional data sets, specifically pertaining to CRC is currently lacking. Here, we have developed Colorectal Cancer Atlas (http://www.colonatlas.org), an integrated web-based resource that catalogues the genomic and proteomic annotations identified in CRC tissues and cell lines. The data catalogued to-date include sequence variations as well as quantitative and non-quantitative protein expression data. The database enables the analysis of these data in the context of signaling pathways, protein-protein interactions, Gene Ontology terms, protein domains and post-translational modifications. Currently, Colorectal Cancer Atlas contains data for >13 711 CRC tissues, >165 CRC cell lines, 62 251 protein identifications, >8.3 million MS/MS spectra, >18 410 genes with sequence variations (404 278 entries) and 351 pathways with sequence variants. Overall, Colorectal Cancer Atlas has been designed to serve as a central resource to facilitate research in CRC. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
Benson, Victoria S; Atkin, Wendy S; Green, Jane; Nadel, Marion R; Patnick, Julietta; Smith, Robert A; Villain, Patricia
The International Colorectal Cancer Screening Network was established in 2003 to promote best practice in the delivery of organized colorectal cancer screening programs. To facilitate evaluation of such programs, we defined a set of universally applicable colorectal cancer screening measures and indicators. To test the feasibility of data collection, we requested data on these variables and basic program characteristics from 26 organized full programs and 9 pilot programs in 24 countries. The size of the target population for each program varied considerably from a few thousand to 36 million. The majority of programs used fecal occult blood tests for primary screening, with more using guaiac than immunochemical tests. There was wide variation in the ability of screening programs to report the requested measures and in the values reported. In general, pilot programs were more likely to provide screening measure values than were full programs. As expected, detection rates for polyps and neoplasia were substantially higher in programs screening with endoscopy than in those using fecal occult blood tests. It is hoped that the screening measures and indicators, once revised in the light of this survey, will be adopted and used by existing programs and those in the early planning stages, allowing international comparison with the goal of improved colorectal cancer screening quality. Copyright © 2011 UICC.
Chatel, Guillaume; Ganeff, Corine; Boussif, Naima; Delacroix, Laurence; Briquet, Alexandra; Nolens, Gregory; Winkler, Rosita
The Hedgehog (Hh) signaling pathway plays an important role in human development. Abnormal activation of this pathway has been observed in several types of human cancers, such as the upper gastro-intestinal tract cancers. However, activation of the Hh pathway in colorectal cancers is controversial. We analyzed the expression of the main key members of the Hh pathway in 7 colon cancer cell lines in order to discover whether the pathway is constitutively active in these cells. We estimated the expression of SHH, IHH, PTCH, SMO, GLI1, GLI2, GLI3, SUFU and HHIP genes by RT-PCR. Moreover, Hh ligand, Gli3 and Sufu protein levels were quantified by western blotting. None of the cell lines expressed the complete set of Hh pathway members. The ligands were absent from Colo320 and HCT116 cells, Smo from Colo205, HT29 and WiDr. GLI1 gene was not expressed in SW480 cells nor were GLI2/GLI3 in Colo205 or Caco-2 cells. Furthermore the repressive form of Gli3, characteristic of an inactive pathway, was detected in SW480 and Colo320 cells. Finally treatment of colon cancer cells with cyclopamine, a specific inhibitor of the Hh pathway, did not downregulate PTCH and GLI1 genes expression in the colorectal cells, whereas it did so in PANC1 control cells. Taken together, these results indicate that the aberrant activation of the Hh signaling pathway is not common in colorectal cancer cell lines.
Allsopp, Philip; Rowland, Ian
Colorectal cancer (CRC) is the fourth most frequent cause of cancer related mortality in the world. Approximately 944,000 new cases were diagnosed globally in 2000 and this accounts for 9.2% of all new cancer cases (IARC, 2000). In Western societies namely Europe, North America and Australasia, it is the second most prevalent cancer after lung/breast (Boyle and Langman, 2000). About 363,000 new cases were reported in Europe in 2000 and it affects 6% of men and women by age 75, in almost equal proportion.
Lee, Yu Mi; Huh, Kyu Chan
Interval colorectal cancer (I-CRC) is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the “mean sojourn time.” It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps) share many genomic and colonic site characteristics with I-CRCs. The clinical and biological features of I-CRC should be elucidated to prevent the development of interval colon cancer. PMID:28320200
Pritchard, A. J.; Chatterjee, T.; Wilkinson, M.; Powe, D. G.; Gray, T.; Hewitt, R. E.
Many previous qualitative studies have shown that tumours are less vascular in the centre, and that host tissues become more vascular in close proximity to tumours. However, quantitative findings presented here for human colorectal cancer reveal some significant differences. Sections from 20 colorectal carcinomas (ten moderately and ten poorly differentiated) were immunostained with the QB/end/10 monoclonal to demonstrate blood vessels. These were measured by interactive morphometry and vascular volume density, surface density (Sv) and length density were recorded. In poorly differentiated carcinomas, the tumour centre was significantly less vascular than the periphery for all three parameters (P = 0.008 for Sv). However, no significant difference was seen for moderately differentiated tumours, which constitute the majority of colorectal cancers. Surrounding host tissues did not show a general increase in vascular density close to tumours. Furthermore, when total viable tissue was considered, the vascular density of carcinomas was not markedly different from normal mucosa. In the centre of moderately differentiated carcinomas for example, the mean value for Sv was only 1.4 times higher than the mean value for normal mucosa. These findings suggest that colorectal cancers may elicit a relatively weak angiogenic response, consistent with their exceptionally slow growth rate. Images Figure 1 Figure 2 Figure 3 PMID:7537517
Soumaoro, Labile Togba; Iida, Satoru; Uetake, Hiroyuki; Ishiguro, Megumi; Takagi, Yoko; Higuchi, Tetsuro; Yasuno, Masamichi; Enomoto, Masayuki; Sugihara, Kenichi
AIM: To evaluate the 5-lipoxygenases (Loxs) expression level in human colorectal cancer specimens in order to determine its clinicopathologic significance in human tumorigenesis. METHODS: The relative quantity of 5-Lox mRNA in paired 91 colorectal tumor and adjacent normal mucosa samples was determined by real time quantitative PCR. Additionally, the expression of 5-Lox and cyclooxygenase (Cox)-2 proteins was also examined using immunohistochemical staining methods. RESULTS: There was a marked increase in 5-Lox mRNA levels in the tumor compared with paired normal mucosa samples (P < 0.0001). Sixty six (72.5%) tumors showed high 5-Lox mRNA levels. The positivity rate of 5-Lox and Cox-2 protein expression was 68.7% and 79.1% respectively. There was a significant association between tumoral 5-Lox mRNA level and tumor size (Rho = 0.392, P = 0.0002), depth or vessel invasion. CONCLUSION: These results suggest that 5-Lox is up-regulated in colorectal cancer and that inhibition of its expression might be valuable in the prevention and treatment of colorectal cancer. PMID:17072961
Crocetti, Emanuele; Buzzoni, Carlotta; Zappa, Marco
We analyzed colorectal cancer incidence data from the Tuscany Cancer Registry, central Italy, for the period 1985-2005. We carried out a trend analysis through a Joinpoint regression analysis, and summarized trends as annual percent change (APC) of the standardized (European standard) rates. Colorectal incidence rates increased until 1996 (APC=+1.4, 95% CI: 0.8-1.9), then decreased significantly (APC=-1.1, 95% CI: -0.8 to -0.4). The change was detected as statistically significant in the age group of 54+ years. Among younger individuals, we observed an increasing incidence until 2003. In the same geographical area, a colorectal screening programme has been active from 1982; it was initially based on guaiac faecal occult blood testing (GFOBT) and on immunological testing (IFOBT) since the mid 1990s. The decline in colorectal cancer incidence since 1996, in the whole population and especially among individuals older than 54 years, may suggest the effect of FOBT screening in terms of precancerous polyps removal.
Song, Le-Le; Li, Yue-Min
Colorectal cancer (CRC) has become the third most common cancer in the world. Screening has been shown to be an effective way to identify early CRC and precancerous lesions, and to reduce its morbidity and mortality. Several types of noninvasive tests have been developed for CRC screening, including the fecal occult blood test (FOBT), the fecal immunochemical test (FIT), the fecal-based DNA test and the blood-based DNA test (the SEPT9 assay). FIT has replaced FOBT and become the major screening test due to high sensitivity, specificity and low costs. The fecal DNA test exhibited higher sensitivity than FIT but its current cost is high for a screening assay. The SEPT9 assay showed good compliance while its performance in screening needs further improvements. These tests exhibited distinct sensitivity and specificity in screening for CRC and adenoma. This article will focus on the performance of the current noninvasive in vitro diagnostic tests that have been used for CRC screening. The merits and drawbacks for these screening methods will also be compared regarding the techniques, usage and costs. We hope this review can provide suggestions for both the public and clinicians in choosing the appropriate method for CRC screening. PMID:27895817
Kikuchi, Norimasa; Nishiyama, Takeshi; Sawada, Takayuki; Wang, Chaochen; Lin, Yingsong; Watanabe, Yoshiyuki; Tamakoshi, Akiko; Kikuchi, Shogo
Colorectal cancer is the third most common cancer worldwide, and many risk factors for colorectal cancer have been established. However, it remains uncertain whether psychological stress contributes to the onset of colorectal cancer. Therefore, we conducted a large-scale prospective cohort study to confirm the association between perceived stress and colorectal cancer incidence. We identified 680 cases of colon cancer and 330 cases of rectal cancer during a maximum of 21-year follow-up of 61,563 Japanese men and women. Cox regression analysis adjusted for potential confounders revealed a significant association of perceived stress with rectal cancer incidence but not with colon cancer incidence. This finding is partly consistent with that from only one previous study that addressed an association between perceived stress and the risk of colorectal cancer. However, studies on this topic are sparse and warrant further exploration. PMID:28091607
Parr, C; Jiang, W G
Lymphatic spread of colorectal cancer cells to regional lymph nodes is one of the early events in metastatic cancer, and is often associated with distant metastatic spread and a poor prognosis. This study examined lymphangiogenic factors, and in particular a panel of newly discovered lymphangiogenic markers, in colorectal cancer tissues from a cohort of patients. Paired samples (background normal mucosa and cancer) of colon tissue were obtained from patients with colorectal cancer. The expression and levels of the VEGF-C and VEGF-D cytokines, the VEGF receptors VEGFR-2 and VEGFR-3, and newly described lymphatic endothelial markers, LYVE-1, Prox-1, podoplanin and 5'-nucleotidase were assessed. RNA was extracted from the frozen colon tissues. The level of expression for each factor/marker was determined using RT-PCR and quantified using a real-time quantitative PCR (RT-QPCR) technique, with respective cloned cDNA plasmids as internal standards. VEGF-D was expressed to a significantly higher degree in the colon tumour tissues. There was no significant difference between the expression levels for both VEGF-C and its receptor, VEGFR-2, in background and cancer tissues. However, levels of the VEGFR-3 receptor were found to be significantly higher in colon cancer than the normal background tissues. LYVE-1 levels were below detection in most cases. There was a significant increase in the degree of Prox-1 and 5'-nucleotidase expression in colon cancer tissue. Podoplanin expression was also increased in the