Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening

Colorectal cancer (CRC) is the second most common cause of cancer deaths in Canadian men and women - accounting for almost 12% of all cancer deaths. In Ontario, it is estimated that 8100 persons were diagnosed with CRC in 2011, and 3250 died from the disease. CRC incidence and mortality rates in Ontario are among the highest in the world. Screening offers the best opportunity to reduce this burden of disease. The present report describes the findings and recommendations of Cancer Care Ontario's Fecal Immunochemical Tests (FIT) Guidelines Expert Panel, which was convened in September 2010 by the Program in Evidence-Based Care. The purpose of the present guideline is to evaluate the existing evidence concerning FIT to inform the decision on how to replace the current guaiac fecal occult blood test with FIT in the Ontario ColonCancerCheck Program. Eleven articles were included in the present guideline, comprising two systematic reviews, five articles reporting on three randomized controlled trials, and reports of four other studies. Additionally, one laboratory study was obtained that reported on several parameters of FIT tests that helped to inform the present recommendation. The performance of FIT is superior to the standard guaiac fecal occult blood test in terms of screening participation rates and the detection of CRC and advanced adenoma. Given greater specimen instability with the use of FIT, a pilot study should be undertaken to determine how to implement the FIT in Ontario.     

Fecal occult blood test in colorectal cancer screening

Colorectal cancer (CRC) is one of the leading causes of cancer‐related mortality worldwide. Cancer screening is known to decrease mortality from CRC. One important test for CRC screening is the fecal occult blood test (FOBT), which includes guaiac FOBT and fecal immunological tests. In this review we discussed the development and application of the FOBT in CRC screening.     

Mass screening for colorectal cancer

A voluntary community colorectal cancer screening project to detect occult blood in the stool of asymptomatic individuals was undertaken; 49,353 Hemoccult^® II kits were distributed. A total of 23,674 completed kits were returned to a central repository and processed (compliance rate, 48 percent); 851 participants had positive results (3.6 percent). Of the 640 who underwent further medical evaluation, 299 participants (46.7 percent) who had adequate follow-up had no evidence of disease. Diverse disease entities were detected in 341 participants, which was 1.4 percent of those enrolled. Forty-one patients (0.17 percent) showed significant findings that included 29 cancers (0.12 percent) and 12 (0.05 percent) noninvasive malignant polyps. Of the cancers, there were 27 colorectal, one nonHodgkin's lymphoma, and one carcinoma of the vocal cord. In addition, 107 patients (0.45 percent) had benign polyps and 193 patients (0.82 percent) had various diseases of the gastrointestinal tract and other medical conditions. The cost of the program was modest and the results conformed to those found in previous screening surveys. The heightened public awareness of testing for colorectal disease and the detection of early lesions justifies the guaiac test screening program for mass survey.     

现阶段我国大肠癌筛查策略的思考

出现明确症状的大肠癌患者，大多已进人中、晚期，治疗效果很不理想。为提高患者生存率，改善生存质量，近年来许多国家开展了自然人群大肠癌筛查。事实证明，这种筛查不仅大大提高了大肠癌的早诊率，提高了患者的长期存活率，而且降低了人群的大肠癌发病率。迄今，很多国家已将大肠癌筛查列入国家公众健康方案，有的国家已将其纳入医疗保险。然而，这种人群筛查在不同国家的可行性却受到质疑。其主要原因是，在这些国家缺乏开展这种筛查的必要条件：人群的高水平健康意识；足够数量的医务人员和国家的财政支持。许多国家和地区限于经济条件和人们的健康意识，很难开展大面积的自然人群筛查。在这些国家和地区，如何开展旨在提高大肠癌早诊水平，改善治疗效果的工作呢？     

粪便转铁蛋白和免疫粪隐血试验在结直肠癌筛查中效能的比较

目的评估粪便转铁蛋白(TF)和免疫粪隐血试验(IFOBT)在筛查结直肠癌中的效能。方法筛查对象为1 943例无症状受试者。收集1次粪便标本,同时用于TF和IFOBT检测。两者任一结果为阳性,即通知受试者行结肠镜检查。分别计算TF、IF-OBT和两者联合检测的性能指标。结果共有1 737例受试者接受TF和IFOBT检查,其中251例(14.5%)至少1项结果为阳性。共有193例接受结肠镜检查,共发现3例结直肠癌和43例进展期腺瘤。与单独使用IFOBT相比,TF和IFOBT联合检测(并联)明显提高了结直肠癌和进展期腺瘤的检出率(2.6%vs 1.6%,P=0.034)。结论 TF和IFOBT联合检测能提高筛查时结直肠癌和进展期腺瘤的检出率。     

Switching from guaiac to immunochemical faecal occult blood test increases participation and diagnostic yield of colorectal cancer screening

BackgroundCompared with the guaiac-faecal occult blood test (gFOBT), faecal immunological tests (FIT) are considered to be more effective for colorectal cancer (CRC) screening. However, only scarce research has examined the outcomes of switching to FIT within a mature gFOBT-based CRC screening programme.MethodsWe reported a 15-year experience of biennial FOBT screening in a well-defined population of approximately one million inhabitants, including six gFOBT-based screening rounds and one round with FIT at the 30 μg Hb/g cut-off. The main outcome measures were screening participation, FOBT positivity and advanced neoplasia detection in each round.ResultsIn this study, 647 676 screenings were performed in 228 716 different individuals, leading to 17 819 positives and 16 580 follow-up colonoscopies. Compared with the last gFOBT round, switching to FIT led to an increased participation of nearly 20% points, and a fivefold increased detection of CRC and advanced adenoma among invitees (3-fold among attendees). The numbers needed to screen and scope to detect one advanced neoplasia declined from 221 to 66 and from 4.7 to 2.6, respectively.ConclusionsThe present population-based study demonstrated a dramatical increase in the diagnostic yield of advanced neoplasia by switching to FIT within a mature gFOBT-based CRC screening programme.     

Barriers to colorectal cancer screening： A case-control study

AIM： To investigate barriers to colorectal cancer （CRC） screening in a community population. METHODS： We conducted a community-based case-control study in an urban Chinese population by questionnaire. Cases were selected from those completing both a fecal occult blood test （FOBT） case and colonoscopy in a CRC screening program in 2004. Control groups were matched by gender, age group and community. Control 1 included those having a positive FOBT but refusing a colonoscopy. Control 2 included those who refused both an FOBT and colonoscopy. RESULTS： The impact of occupation on willingness to attend a colorectal screening program differed by gender. P for heterogeneity was 0.009 for case vs control group 1, 0.01 for case versus control group 2, and 0.80 for control group 1 vs 2. Poor awareness of CRC and its screening program, characteristics of screening tests, and lack of time affected thescreening rate. Financial support, fear of pain and bowel preparation were barriers to a colonoscopy as a screening test. Eighty-two percent of control group 1 and 87.1% of control group 2 were willing attend if the colonoscopy was free, but only 56.3% and 53.1%, respectively, if it was self-paid. Multivariate odds ratios for case vs control group 1 were 0.10 among those unwilling to attend a free colonoscopy and 0.50 among those unwilling to attend a self-paid colonoscopy. CONCLUSION： Raising the public awareness of CRC and its screening, integrating CRC screening into the health care system, and using a painless colonoscopy would increase its screening rate.     

Comparison of immunochemical and guaiac-based fecal occult blood test in screening and surveillance for advanced colorectal neoplasms: A meta-analysis

OBJECTIVE: To systematically evaluate whether immunochemical fecal occult blood tests (iFOBT) could improve clinical performance and test accuracy in screening and surveillance for advanced colorectal neoplasms. METHODS: Eligible articles were identified by searches of electronic databases. All randomized trials and diagnostic cohort trials directly comparing iFOBT with guaiac-based FOBT (gFOBT) were included. A statistical analysis was performed using RevMan 4.2.8. A sensitivity, specificity and summary receiver operating characteristic curve was performed using Meta Disc. RESULTS: We identified five randomized trials and 11 diagnostic cohort trials. In the randomized trials, the detection rates of advanced colorectal neoplasms with iFOBT or gFOBT were 2.23 percent and 1.24 percent, respectively. The pooled odds ratio (OR) was 1.50 (95% CI 0.94–2.39). In cohort trials, the advanced neoplasm detection rates of iFOBT or gFOBT were 1.44 percent and 0.50 percent (OR 1.99, 95% CI 1.24–3.19) in the average-risk screened population, and were 8.8 percent and 7.1 percent (OR 1.27, 95% CI 1.01–1.60) in diagnosed patients scheduled for colonoscopy. The sensitivity of iFOBT (0.67, 95% CI 0.61–0.73) was superior to that of gFOBT (0.54, 95% CI 0.48–0.60), as well as the specificities (0.85, 95% CI 0.83–0.87 vs 0.80, 95% CI 0.78–0.82) and positive predictive values (0.41 vs 0.29) in cohort trials of diagnosed patients. CONCLUSION: Our review suggests that iFOBT could perform better in increasing the detection rate of advanced colorectal neoplasm than gFOBT and possesses higher sensitivity and specificity in the surveillance of advanced colorectal neoplasm for patients.     

"序贯粪隐血大肠肿瘤筛检方案"应用价值的再探讨

目的 通过自然人群大肠肿瘤普查了解近年北京市大肠癌发病情况，进一步探讨“序贯粪便隐血大肠癌筛检方案”的有效性和可行性。方法 选定15家医院医疗责任区内48100自然人群为本次普查靶人群。对其中30岁以上的社区或企业职工26827人进行普查登记，并连续进行3d序贯粪隐血检查。隐血阳性者接受结肠镜检查。符合高危条件者，全部接受隐血和肠镜检查。结果 预计普查人为26827人，实际普查人数为19852人，普查率为74％。男女比例为1．05：1。中位年龄50岁。序贯粪隐血阳性率为5．6％，检出大肠癌12例，其中DukesA期4例，B期7例，C期1例。Dukes A B共11例，占全部检出癌的91．66％。40岁以下人群未检出大肠癌，50岁以上人群中，检出大肠癌的比例随年龄升高而逐渐增加。高危人群中检出2例大肠癌，占该人群的0．28％，一般危险人群中检出10例大肠癌，占该人群的0．05％。结论 普查靶人群的大肠癌患病率为36．57／10^5，提示北京市城区有较高的患病率。采用“序贯粪隐血筛检方案”检出了91．66％的早期和较早期癌。提示该方案的有效性和可行性。高危人群和50岁以上的一般危险人群为大肠癌的重点普查对象。     

Colorectal cancer screening

INTRODUCTION Colorectal cancer is a major public health burden. It is the fourth most common form of cancer worldwide and the most frequent in North America, Australia, New Zealand, Argentina, and parts of Europe[1]. When colorectal can- cer is detected a…     

粪便DNA与粪隐血试验机会性筛查大肠肿瘤的比较研究

[目的]探讨粪便DNA检测在大肠肿瘤机会性筛查中的价值。[方法]进入筛查的人群中连续收集46例大肠癌(CRC)、60例大肠腺瘤(CRA)及30例正常粪便标本,采用PCR-SSCP银染法检测粪便DNA突变情况,并与免疫法粪便隐血试验(IFOBT)比较。[结果]CRC组、CRA组和正常组IFOBT的阳性率分别为45.7%(21/46)、18.3%(11/60)和13.33%(4/30);CRC组、CRA组和正常组APC的突变率分别为58.7%(27/46)、20.0%(12/60)和3.33%(1/30),p53的突变率分别为65.2%(30/46)、25.0%(15/60)和0%(0/30),K-ras的突变率分别为60.9%(28/46)、23.3%(14/60)和0%(0/30),粪便DNA 3个基因联合检测的突变率分别为76.1%(35/46)、35.0%(21/60)和3.33%(1/30)。CRC组、CRA组中APC、p53、K-ras基因单独检测的敏感性与IFOBT比较,差异均无统计学意义(P0.05);CRC组、CRA组粪便DNA 3个基因联合检测的敏感性均高于IFOBT,差异有统计学意义(P0.05);CRC组、CRA组粪便DNA 3个基因单独和联合检测大肠肿瘤的特异性均高于IFOBT,但均差异无统计学意义(P0.05)。[结论]粪便DNA联合检测大肠肿瘤的敏感性高于IFOBT,提示粪便DNA检测可能是更适于机会性筛查大肠肿瘤的无创性筛查方法。     

Clinicopathologic studies of immunologic fecal occult blood test for colorectal cancer

In our hospital, 83 patients with colorectal cancer underwent the immunologic fecal occult blood test (IFOBT). The positive rate for IFOBT in all patients was 87%. Colon cancers more proximal than the transverse colon were 100% positive. Carcinomas of the ulcerative type showed a significantly higher positive rate than those of the non-ulcerative type (94% vs 73%). Carcinomas penetrating the muscularis or beyond showed a significantly higher positive rate, of 96% (52/54 cases) compared to carcinomas confined to the mucosa or submucosa, which gave positive rates of 64% and 60%, respectively. In the investigation of the 7 patients with colorectal cancer who showed negative results on the IFOBT, IFOBT had been performed only once in of these patients. Accordingly, it was considered necessary to perform IFOBT more than once. The cancers in 5 of these 7 patients were found to be carcinomas confined to the mucosa. This result suggests the advisability of annual IFOBTs. It is also considered necessary to manage patients who show undefinable but possibly positive (±) results with caution.     

Fecal occult blood and flexible sigmoidoscopy screening for colorectal cancer: modeling the impact on colonoscopy requirements and cancer detection rates

AiM: The aim of this study was to estimate the colonoscopy requirements and the likely impact of fecal occult blood and flexible sigmoidoscopy screening on the detection of colorectal cancer by using previously published data. METHODS: Fecal occult blood and flexible sigmoidoscopy screening programs were applied to the 2.04 million subjects aged 50-65 years, at a participation rate of 40%. The following strategies were evaluated: Fecal occult blood testing with colonoscopy follow up of all positive tests; flexible sigmoidoscopy with colonoscopy follow up of all adenomatous polyps; and flexible sigmoidoscopy with colonoscopy follow up of all adenomatous polyps > 10 mm in size. RESULTS: The fecal occult blood program detected 5.6% of all colorectal cancer cases at a rate of 2,914 colonoscopies/percentage of detection of colorectal cancer. The flexible sigmoidoscopy program detected 14% of all colorectal cancer cases at a rate of 8,160 colonoscopies/percentage of detection of colorectal cancer. The flexible sigmoidoscopy program with follow up of adenomatous polyps > 10 mm in size detected 13% of all colorectal cancer cases at a rate of 1,230 colonoscopies/percentage of detection of colorectal cancer. CONCLUSIONS: Flexible sigmoidoscopy screening followed by colonoscopic follow up of adenomatous polyps > 10 mm in size is the most efficient screening strategy in terms of colonoscopies generated and cases of colorectal cancer detected.     

Colorectal cancer screening:20 years of development and recent progress

Colorectal cancer(CRC)is the second most common cancer in Europe and its incidence is steadily increasing.This trend could be reversed through timely secondary prevention(screening).In the last twenty years,CRC screening programs across Europe have experienced considerable improvements(fecal occult blood testing;transition from opportunistic to population based program settings).The Czech Republic is a typical example of a country with a long history of nationwide CRC screening programs in the face of very high CRC incidence and mortality rates.Each year,approximately 8000 people are diagnosed with CRC and some 4000 die from this malignancy.Twenty years ago,the first pilot studies on CRC screening led to the introduction of the opportunistic Czech National Colorectal Cancer Screening Program in 2000.Originally,this program was based on the guaiac fecal occult blood test(FOBT)offered by general practitioners,followed by colonoscopy in cases of FOBT positivity.The program has continuously evolved,namely with the implementation of immunochemical FOBTs and screening colonoscopy,as well as the involvement of gynecologists.Since the establishment of the Czech CRC Screening Registry in 2006,2405850 FOBTs have been performed and 104565 preventive colonoscopies recorded within the screening program.The overall program expanded to cover 25.0%of the target population by 2011.However,stagnation in the annual number of performed FOBTs lately has led to switching to the option of a population-based program with personal invitation,which is currently being prepared.     

Ethical issues in colorectal cancer screening

In many countries, colorectal cancer screening is currently an established population screening program due to the evidence on its reduction of colorectal cancer mortality. There is general consensus that colorectal cancer screening meets the screening criteria as proposed by Wilson and Jungner. However, as for all population screening programs, colorectal cancer screening also has disadvantages and thereby entails ethical issues. There are the general issues concerning the introduction of screening programs (e.g. medicalization, overdiagnosis and overtreatment, information provision to screenees), evaluation of cancer screening programs (e.g. lead time and length bias), chosen screening method (e.g. false-positive and false-negative test results, reduction of all-cause mortality, choice between different screening methods). The different colorectal cancer screening methods and the ethical issues concerning colorectal cancer screening will be discussed in this review.     

免疫法粪便潜血试验在结直肠癌筛查中的价值

目的 探讨免疫法粪便潜血试验(IFOBT)在大系列健康体检人群中筛查结直肠癌及其癌前病变的临床价值.方法 对2006年7月至2007年6月间在上海交通大学医学院附属仁济医院行健康体检的5919例采用IFOBT筛查结直肠癌及其癌前病变,对阳性病例进行结直肠镜检查或x线钡剂灌肠检查,结合临床及病理资料进行分析.结果 5919例体检人群中IFOBT阳性者314例,阳性率为5.30%,其中241例(76.75%)接受了结直肠镜检查,23例(7.32%)接受了X线钡剂灌肠检查,总随访率达84.08%,失访50例.剔除失访病例后,共发现结直肠癌16例,检出率为2.73‰(16/5869),其中Dukes A期8例(50.00%),Dukes B期7例(43.75%),Dukes C期1例(6.25%),IFOBT阳性者中的结直肠癌检出率为6.06%(16/264).共发现结直肠腺瘤样息肉94例,检出率为16.01‰(94/5869),包括管状腺瘤55例(58.51%),绒毛状-管状腺瘤23例(24.47%),绒毛状腺瘤16例(17.02%),其中单发者55例(58.51%),多发者39例(41.49%);另见活动期溃疡性结肠炎6例.IFOBT阳性者中共检出116例结直肠癌或癌前病变,检出率为43.94%(116/264).结论 IFOBT适合于大系列人群结直肠癌及其癌前病变的筛查,能发现较早期结直肠癌和癌前病变,使疾病在可治愈阶段得到根治,从而有望减少结直肠癌的发病率和死亡率.     

Age-related cancer detection rate and costs for one cancer detected in one screening by immunochemical fecal occult blood test

PURPOSE: This study was performed to assess, from the aspects of screening efficiency and cost-effectiveness, the optimal lower limit of age in immunochemical occult blood screening for colorectal cancer. METHODS: Seven thousand four hundred asymptomatic individuals were the subjects of this study. They gave samples for an immunochemical fecal occult blood test (OC-Hemodia®), and colonoscopy was performed during a medical checkup. They were divided into three groups according to their ages: younger (40–49), middle (50–59), and older (60+) groups. The detection rate for colorectal cancer and the average costs to detect one patient with colorectal cancer were evaluated among the three groups. RESULTS: The detection rate for colorectal cancer and the average costs to detect one cancer patient were calculated as 0.3 percent and $6024 for the younger group, 1.6 percent and $1425 for the middle group, and 1.7 percent and $1410 for the older group, respectively. The cancer detection rate was significantly different between the younger and middle groups (P<0.05) and between the younger and older groups (P<0.05). CONCLUSIONS: This analysis suggests that the subjects aged less than 50 have some disadvantage when carrying out the immunochemical fecal occult blood test, OC-Hemodia® for colorectal cancer screening, from the aspects of screening efficiency and cost-effectiveness.Supported in part by Grants-in-Aid for Scientific Research (No. 09670384) from the Ministry of Education, Science and Culture of Japan and Cancer Research (No. 8-2) from the Ministry of Health and Welfare of Japan.