Colorectal cancer screening and surveillance

Screening and surveillance substantially reduce both the incidence and mortality of colorectal cancer. Screening of normal-risk individuals may be accomplished by several methods, including fecal occult blood testing, fiberoptic sigmoidoscopy, double contrast barium enema, and colonoscopy. New technologies for screening are being developed, such as fecal immunochemical testing for blood,fecal DNA testing, and virtual colonoscopy. Patients at increased risk for colorectal cancer, such as those with a positive family history, previous adenomatous polyps or cancer, and inflammatory bowel disease, should be offered more intensive evaluation and surveillance.     

Cancer screening guidelines and prevention factors for high-risk patients with a family history of colorectal cancer

Family history of colorectal cancer or of adenomas may confer significant risk of colorectal cancer. Ideally, diagnosis of an inherited syndrome such as familial adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC) enables a molecular biology-driven approach to screening and management. When no hereditary syndrome can be established, clinicians must rely on empiric risk estimates and offer screening accordingly. Detailed rationale and guidelines for use of syndrome characteristics including genetic testing, counseling, and selection of surveillance tools are discussed.     

Family history of colorectal adenomatous polyps as a risk factor for colorectal cancer

The aim of this study was to evaluate the risk of common colorectal cancer among first-degree relatives of patients with colorectal adenomatous polyps. In a population screening programme, 59406 subjects underwent an immunochemical faecal occult blood test. In a medical check-up-based cross-sectional study, 6139 subjects had a colonoscopic examination. They were divided into two groups, according to the results of a questionnaire on family history of colorectal adenomatous polyps, and the detection rates for colorectal cancer were compared in the groups positive or negative for a family history of colorectal adenomatous polyps. In the screening programme-based cross-sectional study, the detection rate for colorectal cancer was 0.57% (95% confidence interval (CI): 0.38-0.76) and 0.15% (95% CI: 0.12-0.18) in subjects with and without a family history of colorectal adenomatous polyps, respectively, showing a significant difference in the detection rate for colorectal cancer between the two groups (P<0.05). In the medical check-up-based cross-sectional study, the detection rate for colorectal cancer was 2.31% (95% CI: 1.15-3.47) and 0.53% (95% CI: 0. 34-0.72) in subjects with and without a family history of colorectal adenomatous polyps, respectively, indicating a significant difference between the two groups (P<0.05). These findings indicate that first-degree relatives of patients with colorectal adenomatous polyps have an elevated risk for common colorectal cancer, and that people with a family history of colorectal adenomatous polyps should be considered as a priority group for colorectal cancer screening.     

Current approaches in familial colorectal cancer: a clinical perspective

Individuals with a family history of colorectal cancer or colorectal adenomas have an increased risk for colorectal cancer. When no hereditary syndrome is evident, screening is based on empiric risk estimates. The risk is greatest for individuals with specific inherited cancer-predisposing disorders. When conditions such as familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer are diagnosed, specific neoplasm risk estimates can usually be performed based on advances in molecular genetics. These estimates lead to more straightforward and cost-effective approaches to surveillance and management. The National Comprehensive Cancer Center Network (NCCN) and other groups have provided detailed guidelines for evaluating patients based on recognition of clinical syndrome characteristics, followed by appropriate genetic counseling, genetic testing, and optimal surveillance. The NCCN guidelines are used as a frame of reference for this discussion of selected recent advances in human cancer genetics as they apply to clinical practice.     

Hereditary nonpolyposis colorectal cancer: preventive management

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of hereditary colorectal cancer. Inherited mutations in the mismatch repair genes associated with this syndrome have an approximate 80% lifetime risk of colorectal cancer. Since there are no premonitory signs of susceptibility to HNPCC, family history is the initial method for identifying those at increased risk. At risk individuals should undergo genetic counseling and testing. Although an algorithmic indication for genetic testing in at risk HNPCC patients is yet to be determined, many advocate initial screening for microsatellite instability (MSI) of the cancer specimen in individuals suspected of carrying HNPCC mutations. Those who test positive for MSI can then undergo further testing for mutations in the associated germline mismatch repair genes. Techniques for detecting these mutations currently include in vitro synthesized-protein assay, single-strand conformational polymorphism, and DNA sequencing. Given the aggressive nature of HNPCC adenomas, individuals who test positive for HNPCC mutations are recommended to undergo yearly colonoscopic surveillance starting at the age of 25. A reasonable alternative to lifetime colonoscopic surveillance for the prevention of colorectal cancer in these individuals is prophylactic colectomy. The prevention of colorectal cancer through pharmacological means is under investigation as another option in the management of HNPCC patients. Specifically, chemoprevention trials are currently ongoing to evaluate the efficacy of COX-2 inhibitors in the prevention of colorectal cancer in HNPCC and familial adenomatous polyposis patients.     

Emerging technologies in screening for colorectal cancer: CT colonography,immunochemical fecal occult blood tests,and stool screening using molecular markers

The American Cancer Society's (ACS) Colorectal Cancer Advisory Group held a workshop on new technologies for the early detection of colorectal cancer and adenomatous polyps as part of a regular review of ACS guidelines for colorectal cancer screening. The Advisory Group formally reviewed CT colonography, immunochemical fecal occult blood tests (FOBT), and stool screening using molecular markers, and also addressed other technologies including capsule video endoscopy. With the exception of immunochemical stool testing, the ACS has determined that at this time there is insufficient evidence to recommend these technologies for routine colorectal cancer screening. Based on recommendations of the Advisory Group, only a minor modification has been made to the ACS's Recommendations for Screening and Surveillance of the Early Detection of Adenomatous Polyps and Colorectal Cancer.     

FAP, gastric cancer, and genetic counseling featuring children and young adults: a family study and review

Familial adenomatous polyposis is a highly complex and multifaceted colorectal cancer prone disorder which is often significantly confounded by extracolonic cancers inclusive of gastric cancer, a significant problem in the Orient. Gastric cancer in familial adenomatous polyposis is heavily influenced by fundic gland polyps which are often so voluminous as to defy effective endoscopic surveillance. This study involves more than two decades of investigation of an attenuated familial adenomatous polyposis family where gastric cancer posed an early diagnostic problem because it was obscured by multiple fundic gland polyps. Fundic gland polyps are common in familial adenomatous polyposis and attenuated familial adenomatous polyposis and, if voluminous, may interfere with effective endoscopic gastric cancer surveillance. This family is believed to be the first of its type reported with focus upon education and genetic counseling in the setting of a family information service. Cancer control in familial adenomatous polyposis may be partially resolved through use of familial colorectal cancer registries, with greater attention to family history and its interpretation, genetic counseling, and clinical translation for diagnosis and management.     

Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society

Adenomatous polyps are the most common neoplastic findings uncovered in people who undergo colorectal screening or have a diagnostic workup for symptoms. It was common practice in the 1970s for these patients to have annual follow-up surveillance examinations to detect additional new adenomas as well as missed synchronous adenomas. As a result of the National Polyp Study report in 1993, which demonstrated clearly in a randomized design that the first postpolypectomy examination could be deferred for 3 years, guidelines published by a gastrointestinal consortium in 1997 recommended that the first follow-up surveillance be 3 years after polypectomy for most patients. In 2003, these guidelines were updated, colonoscopy was recommended as the only follow-up examination, and stratification at baseline into lower and higher risk for subsequent adenomas was suggested. The 1997 and 2003 guidelines dealt with both screening and surveillance. However, it has become increasingly clear that postpolypectomy surveillance is now a large part of endoscopic practice, draining resources from screening and diagnosis. In addition, surveys have demonstrated that a large proportion of endoscopists are conducting surveillance examinations at shorter intervals than recommended in the guidelines. In the present paper, a careful analytic approach was designed addressing all evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced adenomas, so that patients can be more definitely stratified at their baseline colonoscopy into those at lower or increased risk for a subsequent advanced neoplasia. People at increased risk have either three or more adenomas, or high-grade dysplasia, or villous features, or an adenoma > or =1 cm in size. It is recommended that they have a 3-year follow-up colonoscopy. People at lower risk who have one or two small (< 1 cm) tubular adenomas with no high-grade dysplasia can have a follow-up in 5 to 10 years, whereas people with hyperplastic polyps only should have a 10-year follow-up as average-risk people. Recent papers have reported a significant number of missed cancers by colonoscopy. However, high-quality baseline colonoscopy with excellent patient preparation and adequate withdrawal time should minimize this and reduce clinicians' concerns. These guidelines were developed jointly by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society to provide a broader consensus and thereby increase utilization of the recommendations by endoscopists. Adoption of these guidelines nationally can have a dramatic impact on shifting available resources from intensive surveillance to screening. It has been shown that the first screening colonoscopy and polypectomy produces the greatest effects on reducing the incidence of colorectal cancer in patients with adenomatous polyps.     

Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology

In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer. CRC largely can be prevented by the detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized. In 2006 to 2007, the American Cancer Society, the US Multi Society Task Force on Colorectal Cancer, and the American College of Radiology came together to develop consensus guidelines for the detection of adenomatous polyps and CRC in asymptomatic average-risk adults. In this update of each organization's guidelines, screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy. When possible, clinicians should make patients aware of the full range of screening options, but at a minimum they should be prepared to offer patients a choice between a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps and a screening test that primarily is effective at early cancer detection. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening.     

How to manage a patient with multiple adenomatous polyps

Adenomatous polyps are found on screening colonoscopy in 22.5% to 58.2% of the adult population and therefore represent a common problem. Patients with multiple adenomatous polyps are of unique interest because a proportion of these patients have an inheritable form of colorectal cancer. This article discusses the history and clinical features, genetic testing, surveillance, and treatments for the condition.     

Current approaches in hereditary nonpolyposis colorectal cancer

This article emphasizes the central role of tumor-based testing for microsatellite instability followed by performance of genetic counselor-driven germline mutation testing in hereditary nonpolyposis colorectal cancer (HNPCC). Suitably aggressive colorectal neoplasm surveillance is shown to be critical. Limitations of the evidentiary base for extracolonic screening are conceded, with some cautious suggestions for possible strategies notwithstanding the lack of data. Advances in chemoprevention have been made in both familial adenomatous polyposis (clinical trial data favoring eicosapentaenoic acid) and HNPCC (controversial aspirin data). For various reasons, however, no agent or combination of agents has yet come into routine use in either condition, with further trials underway or being designed for both conditions.     

外周血黏附分子CD24在结直肠癌筛查中的作用

目的:探讨外周血CD24在结直肠癌及大肠息肉筛查中的作用。方法:应用流式细胞仪分别检测新发结直肠癌患者、大肠息肉患者及健康对照者外周血白细胞中的CD24表达情况。进一步根据病理类型将大肠息肉患者分为炎症性息肉、增生性息肉、腺瘤性息肉及腺瘤性息肉伴不典型增生四组,比较组间差异。结果:结直肠癌患者（15.56±5.28）、大肠息肉患者（12.05±3.43）外周血白细胞中CD24的荧光强度显著高于健康对照（9.42±1.48）（P＜0.01）。炎症性息肉（10.75±1.80）、增生性息肉（12.14±3.11）、腺瘤性息肉患者（10.77±2.67）外周血白细胞中CD24的荧光强度无统计学差异,腺瘤性息肉伴不典型增生组患者（17.08±5.12）外周血白细胞中CD24的荧光强度显著高于前三组（P＜0.01）。结论:非侵入性的外周血CD24表达水平的检测对于结直肠癌的筛查可能有一定的意义。     

Genomic era diagnosis and management of hereditary and sporadic colon cancer

The morbidity and mortality attributable to heritable and sporadic carcinomas of the colon are substantial and affect children and adults alike. Despite current colonoscopy screening recommendations colorectal adenocarcinoma (CRC) still accounts for almost 140000 cancer cases yearly. Familial adenomatous polyposis (FAP) is a colon cancer predisposition due to alterations in the adenomatous polyposis coli gene, which is mutated in most CRC. Since the beginning of the genomic era next-generation sequencing analyses of CRC continue to improve our understanding of the genetics of tumorigenesis and promise to expand our ability to identify and treat this disease. Advances in genome sequence analysis have facilitated the molecular diagnosis of individuals with FAP, which enables initiation of appropriate monitoring and timely intervention. Genome sequencing also has potential clinical impact for individuals with sporadic forms of CRC, providing means for molecular diagnosis of CRC tumor type, data guiding selection of tumor targeted therapies, and pharmacogenomic profiles specifying patient specific drug tolerances. There is even a potential role for genomic sequencing in surveillance for recurrence, and early detection, of CRC. We review strategies for diagnostic assessment and management of FAP and sporadic CRC in the current genomic era, with emphasis on the current, and potential for future, impact of genome sequencing on the clinical care of these conditions.     

Is there an increased incidence of adenomatous polyps in breast cancer patients?

Using flexible proctosigmoidoscopy, the incidence of adenomatous polyps was studied in 161 patients previously operated on for breast cancer and also in 147 hospitalized controls not presenting with colorectal symptoms. The acceptance and tolerance of the examination were good in both populations. The mean age and length of the colons explored were not statistically different for the two groups. The incidence of adenomas was high in the breast cancer group (14.2%) in comparison to the control group (4.7%) (P less than 0.01). This strong incidence especially concerned very small polyps with a diameter smaller than 3 mm. There were also two polyps with superficial carcinomas in the breast cancer group. Breast cancer does indeed seem to represent a condition with a high risk of colorectal adenomas. Our results prompt us to propose the adoption of systematic screening measures and a surveillance schedule as soon as the breast cancer is found.     

Colonoscopy surveillance in asymptomatic subjects with increased risk for colorectal cancer: clinical evaluation and cost analysis of an Italian experience.

The aim of this study was three-fold: (a) to present a surveillance plan for colorectal cancer prevention with colonoscopy, focused on first-degree relatives of colorectal cancer patients in the province of Ferrara (Italy); (b) to analyse the cost of colonoscopy at the University Hospital of Ferrara; and (c) to analyse the cost of the surveillance plan in our province. In January 2000, in the province of Ferrara, following a campaign of public sensitization, a plan of surveillance with colonoscopy was started, addressing the population at an increased risk for colorectal cancer (i.e. over 45-year-old first-degree relatives of patients with either colorectal cancer or adenomatous polyps revealed before 60 years of age). In addition, we estimated the cost of colonoscopy both at the University Hospital of Ferrara and of the surveillance plan. Between January 2000 and October 2003, 585 individuals at increased risk were interviewed. Five hundred and forty-four (94%) accepted to undergo a colonoscopy. By October 2003, 439 (81%) colonoscopies had been performed. Colonoscopy was normal in 330 individuals (75%). In 109 individuals (25%), 144 lesions were found: 35 patients (32%) had hyperplastic polyps, 66 (61%) had adenomas, and eight (7%) adenocarcinomas (six Dukes A, one Dukes B, and one Dukes C stage). Out of a total of 101 adenomas, 68 were tubular adenomas (67%), 24 tubulo-villous adenomas (24%), and nine adenomas with high-grade dysplasia (9%). The cost of colonoscopy at our hospital and the costs of the surveillance plan amounted to euro 130.84 (euro 169.57 with single biopsy) and euro 43,103.66 (euro 42 310.34/year), respectively. These data show (a) the efficacy of colonoscopy in the early diagnosis of colorectal cancer and premalignant lesions in first-degree relatives of colorectal cancer patients; (b) the low cost of colonoscopy at the centre performing the surveillance; and (c) the feasibility of screening and surveillance programmes for colorectal cancer prevention.     

The genetics, epidemiology, and early detection of gastrointestinal cancers.

Current recommendations for screening large populations for colorectal neoplasia have been promulgated by a number of researchers and authorities who generally agree that ongoing screening is justifiable in high-risk groups but not yet in average-risk groups. Nonetheless, it is thought to be justifiable to provide screening for average-risk individuals upon request. Choice of tools for screening remains under discussion. Colonoscopy is generally agreed to be justifiable in those patients with the highest risk, ie, members of families with a clear inherited tendency to develop colorectal cancer or those with a personal history of colorectal neoplasia. There is currently no agreement concerning the recommended tools for those with a weaker family history (one or two affected relatives), but regular fecal occult blood testing with occasional limited endoscopic examination of the bowel is usually favored. The new immunochemical-based occult blood tests show great promise for improved sensitivity and specificity. The evidence of the association between Helicobacter pylori gastritis and gastric cancer has been strengthened by three studies that show that patients with gastric cancer are more likely to have had infection in the years (up to 20) prior to diagnosis. The relative risk for cancer when infected with H. pylori is 3.6 to 6, but many H. pylori-positive individuals do not develop gastric cancer and additional factors must be operative. Probably the most exciting development for gastroenterology in 1991 is the identification of the gene on chromosome 5, designated APC, which is responsible for familial adenomatous polyposis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Colorectal cancer screening in elderly patients: When should be more useful?

Current guidelines endorse colon cancer screening every 5-10 years in persons over 50 years of age. However, there is no consensus regarding what age is appropriate to stop screening. Prior history of neoplasia seems to be a strong risk factor for colorectal neoplasia development in elderly people and should be considered when deciding the need for continuing screening/surveillance, however, clinical judgment of comorbidities is still required to individualize screening practice. Screening colonoscopy in very elderly persons (aged 80 years), i.e. should be performed only after careful consideration of potential benefits, risks and patient preferences. The aims of this paper are to: (1) determine the best type of colorectal cancer screening (faecal occult blood testing, flexible sigmoidoscopy, double-contrast barium enema and colonoscopy) and its association with age and health status among elderly veterans and (2) describe the outcomes of colorectal cancer screening among older veterans who have widely differing life expectancies (based on age and health status).     

Endoscopic follow-up in resected colorectal cancer patients

Patients resected for colorectal cancer are at risk for anastomotic recurrence, for adenomatous polyps and for metachronous cancer. The present retrospective study was conducted to evaluate the incidence of neoplasms of the colon, both metachronous or recurrent, in 322 patients. They were observed and resected for colorectal cancer between 1970 and 1988, with complete staging, and all agreed to be included in a follow-up program (median followup: 105 months). All the patients were submitted to colonoscopy once yearly for the first 5 years and then every 2 years. Anastomotic recurrence was observed in 22 of the 253 patients who underwent resection for rectal or sigmoid adenocarcinoma (8.7%). Sixteen of these patients were submitted to a second curative resection with a median survival of 35 months; the median survival was 6 months in the 6 patients who could not undergo this operation (p=0.0018). Metachronous adenomas of the residual colon were found in 24 patients and metachronous cancers in 5 at Stage A, according to Dukes' classification. In conclusion, a regular colonoscopic surveillance in patients resected for colorectal cancer is justified for early detection and potential resection of anastomotic recurrences, new primary cancer and adenomatous polyps. In patients resected for rectal or sigmoid carcinoma, a sigmoidoscopy should be performed every 6 months for the first 2 years for the early detection of anastomotic recurrences. In all cases, a colonoscopy should be performed every 5 years after surgery to detect metachronous lesions. Before surgery, a "clean colon" should always be established to detect possible synchronous lesions.     

Genetic Evaluation of Polyposis

There is substantial ongoing work in elucidating the genetics of colorectal cancer (CRC). In this article, the state of the art and clinical application of CRC genetics for syndromic, familial, and sporadic carcinoma are discussed in detail. Clinical manifestations, genetics, diagnosis, and surveillance are discussed for major colorectal cancer syndromes. When a genetic polyposis syndrome is suspected, diagnosis should be confirmed. Careful consideration of screening for associated extracolonic conditions will lead to better patient outcomes. Genetic counseling and screening of family members is often indicated.     

What is the Best Colonoscopy Surveillance for Lynch Syndrome Patients?

Lynch syndrome is the most common form of hereditary colorectal cancer. Screening programs have reduced colon cancer mortality. Despite intensive surveillance, the cumulative risk of developing colorectal cancer is substantial. Identification of modifiable factors has the potential to improve outcome of surveillance. Our article will review current guidelines for Lynch syndrome and how to perform colonoscopy. High-quality surveillance colonoscopy should be performed in an experimented center every 1–2 years, starting at the age of 20–25 years. Colonoscopy should include meticulous inspection and precise removal of all polyps, with special attention to the right colon especially of flat lesions. News endoscopic techniques, such as chromoendoscopy, were developed and recommended to improve the detection of adenomas, particularly of flat adenomas, and minimize the risk of developing interval cancer. Finally, educational intervention in a surveillance program is essential for optimizing screening including adherence.