A sensitive guaiac faecal occult blood test is less useful than an immunochemical test for colorectal cancer screening in a Chinese population

BACKGROUND: Colorectal cancer screening by guaiac faecal occult blood test has been shown to reduce the incidence and mortality of colorectal cancer in Western populations. The optimal faecal occult blood test, whether guaiac or immunochemical, for colorectal cancer screening in the Chinese population remains to be defined. AIM: To compare the performance characteristics of a sensitive guaiac-based faecal occult blood test (Hemoccult SENSA) and an immunochemical faecal occult blood test (FlexSure OBT) in a Chinese population referred for colonoscopy. METHODS: One hundred and thirty-five consecutive patients who were referred for colonoscopy and who met the study inclusion criteria took samples for the two faecal occult blood tests simultaneously from three successive stool specimens, with no dietary restrictions. All tests were developed and interpreted by a single experienced technician who was blind to the clinical diagnosis. The sensitivity, specificity and positive predictive value for the detection of colorectal adenomas and cancers were estimated for the two tests. RESULTS: The sensitivity, specificity and positive predictive value for the detection of significant colorectal neoplasia (adenomas > or = 1.0 cm and cancers) were 91%, 70% and 18% for Hemoccult SENSA and 82%, 94% and 47% for FlexSure OBT. The specificity and positive predictive value were significantly higher for FlexSure OBT than for Hemoccult SENSA (P < 0.001 and P = 0.016, respectively). Combining the positive results from both faecal occult blood tests did not improve the accuracy. CONCLUSION: The positive predictive value of the immunochemical faecal occult blood test for the detection of significant colorectal neoplasia was 29% better than that of the sensitive guaiac-based test. This may relate to the Chinese diet and requires further study. The poor specificity of the sensitive guaiac-based test, without dietary restriction, makes it less useful for colorectal cancer screening in a Chinese population.     

A quantitative immunochemical faecal occult blood test is more efficient for detecting significant colorectal neoplasia than a sensitive guaiac test

BACKGROUND: The sensitive guaiac faecal occult blood test, Haemoccult SENSA (HOS; Beckman Coulter, Fullerton, CA, USA), is our standard screening test for significant colorectal neoplasia. We evaluated an automatically-developed, quantified human haemoglobin immunochemical faecal test, OC-MICRO (Eiken Chemical Co., Tokyo, Japan), to improve test specificity and so reduce the colonoscopy burden. AIM: To compare guaiac faecal occult blood test and immunochemical faecal test diagnostic efficacy and costs for identifying significant neoplasia. METHODS: Colonoscopies were performed on patients who prepared three daily guaiac faecal occult blood tests with or without immunochemical faecal tests. RESULTS: Total colonoscopy was performed on 151 subjects who prepared both guaiac and immunochemical faecal tests (group 1) and the positive predictive values (PPV) were also compared to those of 162 subjects undergoing colonoscopy for positive guaiac faecal occult blood tests (group 2). In group 1, comparative sensitivity, specificity, and PPVs for significant neoplasia with guaiac faecal occult blood test were 75%, 34%, and 12% (PPV, 18% for group 2) and with immunochemical faecal test were 75%, 94% and 60% (P < 0.01 for specificity). The number of colonoscopy examinations needed to detect a significant neoplasm because of positive faecal occult blood tests was six to eight with HOS and two with OC-MICRO at 21-31% the cost of evaluating a positive guaiac faecal occult blood test. CONCLUSION: An immunochemical faecal test maintains the high sensitivity of guaiac faecal occult blood test, but significantly reduces the colonoscopy burden and screening costs.     

Can quantification of faecal occult blood predetermine the need for colonoscopy in patients at risk for non‐syndromic familial colorectal cancer?

BACKGROUND: Patients at risk for non-syndromic (Lynch or polyposis) familial colorectal neoplasia undergo colonoscopic surveillance at intervals determined by clinically ascertained protocols. The quantitative immunochemical faecal occult blood test for human haemoglobin is specific and sensitive for significant colorectal neoplasia (cancer or advanced adenomatous polyp). AIM: To determine immunochemical faecal occult blood test efficacy for identifying significant neoplasia in at-risk patients undergoing elective colonoscopy. METHODS: We retrospectively identified consecutive at-risk patients who provided three immunochemical faecal occult blood tests before colonoscopy. Quantitative haemoglobin analysis was performed by the OC-MICRO automated instrument using the 100 ng Hb/mL threshold to determine positivity. RESULTS: In 252 at-risk patients undergoing colonoscopy; five had cancer, 14 an advanced adenoma and 46 a non-advanced adenoma. The immunochemical faecal occult blood test was positive in 31 patients (12.3%). Sensitivity, specificity, positive and negative predictive values for cancer were: 100%, 90%, 16% and 100%, and for all significant neoplasia: 74%, 93%, 45% and 98%. With 88% fewer colonoscopies, all colorectal cancers and 74% of all significant neoplasia would have been identified by this one-time immunochemical faecal occult blood test screening. CONCLUSIONS: A sensitive, non-invasive, interval screening test might be useful to predetermine the need for colonoscopy in this at-risk population and minimize unnecessary examinations. This favourable retrospective evaluation will be extended to a prospective study.     

Comparative evaluation of a new bedside faecal occult blood test in a prospective multicentre study

BACKGROUND: Faecal occult blood testing is an established method of colorectal neoplasia screening. Guaiac-based tests are limited by poor patient compliance, low sensitivity, specificity and positive predictive value. Newer immunochemical-based tests, accurate but tedious, require a well-established laboratory set up. There is need for simpler immunochemical tests that can be performed at the out-patient clinic. AIM: To compare the performance characteristics of a new bedside immunological test strip device with a sensitive Guaiac-based and established immunochemical test for detection of faecal occult blood in patients undergoing colonoscopy. METHODS: A total of 389 consecutive patients from four centres who were referred for colonoscopy also provided the stool samples for detection of occult blood without dietary restrictions. Stool tests performed were (i) Guaiac-based, (ii) immunochemical enzyme-linked immunosorbent assay and (iii) bedside immunochemical strip test. RESULTS: At the optimal threshold level, the sensitivity and specificity of the beside immunochemical strip test for detection of significant colorectal neoplasia (adenomas >1.0 cm and carcinomas) were 60% and 95%, respectively. CONCLUSIONS: This bedside immunochemical strip test proved to be a simple, convenient, non-cumbersome and accurate tool with similar performance characteristics for detection of any bleeding lesion including colorectal neoplasia when compared with an established immunochemical faecal occult blood test.     

The investigation of colorectal disorders.

The investigation of colorectal disorders follows from a thorough clinical examination, examination of stools, and proctosigmoidoscopy. In many patients, barium enema examination will also be required, and the value of good air contrast examinations is stressed. Colonoscopy has revolutionised the diagnostic and therapeutic capabilities in colonic disease, but this examination is not readily available to all, its indications limited, and the risks and discomfort associated with it by no means small. In New Zealand, colorectal cancer is as common as anywhere else in the world, and the major hope of any improvement in this area is with preclinical diagnosis. This could be achieved by more widespread faecal occult blood testing especially in high risk groups (Table 2) and thorough investigation of those with positive results. Serological tests for colorectal cancer (carcino-embryonic antigen) have proved disappointing, and much less specific than originally hoped.     

非甾体抗炎药致中青年患者上消化道出血临床分析（附81例）

目的探讨非甾体抗炎药（NSAIDs）致中青年患者上消化道出血的临床特点。方法回顾分析81例非甾体抗炎药中青年患者的临床资料。结果本组81患者2周内均有服用NSAIDs病史,都经大便潜血及纤维胃镜确诊。伴有腹部疼痛症状18例占22．2％（18／81）;有嗜咖啡或酸辣饮食习惯53例（占65．4％）;有吸烟史48例（占59．3％）。结论中青年人群服用NSAIDs引起的上消化道出血起病隐匿、临床症状轻和体征不明显的特点,应引起临床医师和药师的警惕。     

Review article: faecal occult blood testing for colorectal cancer

Major health organizations recommend colorectal cancer screening using faecal occult blood tests, sigmoidoscopy or both for patients 50 years of age or older who are at average risk for colorectal cancer. However, no specific recommendations have been made regarding choice of test from among the tests currently or soon to be available. Therefore, to aid clinicians in rationally choosing a particular test for faecal occult blood, published data are reviewed regarding the performance characteristics, strengths and weaknesses of the various faecal occult blood tests. New studies suggest that immunochemical tests (e.g. HemeSelect) or a combination of sensitive guaiac tests and immunochemical tests (e.g. Hemoccult Sensa and HemeSelect) are the most sensitive, specific tests for detecting colorectal carcinoma and colorectal polyps ≥ 1 cm.     

Recommendations on population screening for colorectal cancer in New Zealand. Members of the National Health Committee Working Party on Population Screening for Colorectal Cancer

The National Advisory Committee on Health and Disability invited a working party to make recommendations on population screening for colorectal cancer in New Zealand. Recent results from randomised controlled trials of screening with guaiac faecal occult blood tests have provided evidence that population screening could reduce mortality from colorectal cancer. However, given the modest potential level of benefit, the considerable commitment of health sector resources, and the small but real potential for harm, the working party does not recommend population screening for colorectal cancer with faecal occult blood tests in New Zealand. The working party does nto recommend pilot colorectal cancer screening programmes in New Zealand because pilot programmes cannot address the issues of concern: the modest potential benefit and the small, but real, potential for harm. The working party does not recommend faecal occult blood testing as a screening test for colorectal cancer in average-risk individuals outside a population screening programme. Those requesting screening by faecal occult blood test should be given information about the potential risks and benefits. Follow-up bowel investigations in the public health system cannot be guaranteed without an increased allocation of resources. As there is yet no evidence from randomised controlled trials that screening with flexible sigmoidoscopy, colonoscopy or double-contrast barium enema produces a reduction in colorectal cancer mortality, the working party does not recommend population screening with these modalities. Wider consultation and further consideration should be undertaken to develop appropriate advice on surveillance recommendations for groups identified to be at increased risk of colorectal cancer. These decisions should be reviewed as evidence of benefit from new types of faecal occult blood test and other screening modalities becomes available. The working party recognises that colorectal cancer is an important cause of morbidity and mortality and recommends that New Zealand participate in international research in this area.     

厦门市海沧地区大肠癌筛查结果分析

目的 探讨粪便隐血试验及结肠镜检查作为大肠癌筛查主要方式的临床价值.方法 2008年12月至2010年10月,结合问卷调查和粪便隐血试验,对海沧周边农村地区4个行政村40～74岁常住居民进行初筛,高危人群接受全结肠镜检查,对检查结果进行分析.结果 总调查人数6 380例,高危人群共1 035例,1次以上粪便隐血试验阳性者580例,阳性率为9.09%.全结肠镜检查共839例,其中检出结肠癌14例,201例发现了息肉,包括腺瘤64例、非腺瘤性息肉137例,并发高级别上皮内瘤变8例.结论 结合粪隐血、问卷调查及结肠镜检查适合社区、广大农村地区患者大肠癌的筛查,有利于大肠癌及癌前病变的早期诊断及早期治疗.     

Review article: Population screening for colorectal cancer

Colorectal cancer is a common cancer and common cause of death. The mortality rate from colorectal cancer can be reduced by identification and removal of cancer precursors, adenomas, or by detection of cancer at an earlier stage. Pilot screening programmes have demonstrated decreased colorectal cancer mortality; as a result many countries are developing colorectal cancer screening programmes. The most common modalities being evaluated are faecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Implementation of screening tests has been hampered by cost, invasiveness, availability of resources and patient acceptance. New technologies such at computed tomographic colonography and stool screening for molecular markers of neoplasia are in development as potential minimally invasive tools. This review considers who should be screened, which test to use and how often to screen.     

As tests evolve and costs of cancer care rise: reappraising stool-based screening for colorectal neoplasia

Background Colorectal cancer screening and treatment are rapidly evolving. Aims To reappraise stool‐based colorectal cancer screening in light of changing test performance characteristics, lower test cost and increasing colorectal cancer care costs. Methods Using a Markov model, we compared faecal DNA testing every 3 years, annual faecal occult blood testing or immunochemical testing, and colonoscopy every 10 years. Results In the base case, faecal occult blood testing and faecal immunochemical testing gained life‐years/person and cost less than no screening. Faecal DNA testing version 1.1 at $300 (the current PreGen Plus test) gained 5323 life‐years/100 000 persons at $16 900/life‐year gained and faecal DNA testing version 2 (enhanced test) gained 5795 life‐years/100 000 persons at $15 700/life‐year gained vs. no screening. In the base case and most sensitivity analyses, faecal occult blood testing and faecal immunochemical testing were preferred to faecal DNA testing. Faecal DNA testing version 2 cost $100 000/life‐year gained vs. faecal immunochemical testing when per‐cycle adherence with faecal immunochemical testing was 22%. Faecal immunochemical testing with excellent adherence was superior to colonoscopy every 10 years. Conclusions As novel biological therapies increase colorectal cancer treatment costs, faecal occult blood testing and faecal immunochemical testing could become cost‐saving. The cost‐effectiveness of faecal DNA testing compared with no screening has improved, but faecal occult blood testing and faecal immunochemical testing are preferred to faecal DNA testing when patient adherence is high. Faecal immunochemical testing may be comparable to colonoscopy every 10 years in persons adhering to yearly testing.     

Complementary studies of the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib

BACKGROUND: Cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs are intended to preserve cyclo-oxygenase-1-mediated gastroprotection and platelet function, whilst inhibiting cyclo-oxygenase-2-mediated inflammation. AIM: To assess the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib vs. non-selective non-steroidal anti-inflammatory drugs. METHODS: Two randomized, double-blind, placebo- and active-controlled studies were performed: (i) daily faecal red blood cell loss was measured in 62 subjects receiving etoricoxib (120 mg once daily), ibuprofen (800 mg t.d.s.) or placebo for 28 days; (ii) the incidence of endoscopically detectable gastric/duodenal ulcers was determined in 742 osteoarthritis or rheumatoid arthritis patients receiving etoricoxib (120 mg once daily), naproxen (500 mg b.d.) or placebo over 12 weeks. RESULTS: In the first study, the between-treatment ratio of faecal blood loss for etoricoxib vs. placebo (1.06) was not significantly different from unity; however, the ratios for ibuprofen vs. placebo (3.26) and etoricoxib (3.08) were significantly greater than unity (P < 0.001). In the second study, the incidence of ulcers of > or = 3 mm with naproxen (25.3%) was significantly higher than that with etoricoxib (7.4%) or placebo (1.4%; P < 0.001); the results were similar for ulcers of > or = 5 mm. CONCLUSIONS: The reduced toxicity of etoricoxib (less faecal blood loss and fewer endoscopically detectable lesions) suggests that use of this drug will may be associated with a reduced incidence of gastrointestinal perforations, ulcers and bleeds.     

Review article: the potential of combinational regimen with non-steroidal anti-inflammatory drugs in the chemoprevention of colorectal cancer

Non-steroidal anti-inflammatory drugs are chemopreventive agents in colorectal cancer. Non-steroidal anti-inflammatory drugs do not, however, offer complete protection against adenoma and carcinoma development. There is increasing interest in combining non-steroidal anti-inflammatory drugs with agents that target specific cell signalling pathways in malignant and premalignant cells. This review aims to describe the current knowledge regarding the efficacy of peroxisome proliferator-activated receptor-gamma ligands, cholesterol synthesis inhibitors (statins), epidermal growth factor signalling inhibitors and tumour necrosis factor-related apoptosis-inducing ligand against colorectal neoplasms and the rationale for combining these drugs with non-steroidal anti-inflammatory drugs to improve efficacy in the chemoprevention of colorectal cancer, a PUBMED computer search of the English language literature was conducted to identify relevant papers published before July 2004. Peroxisome proliferator-activated receptor-gamma ligands and statins, both in clinical use, reduce the growth rate of human colon cancer cells in vitro and in rodents models. In vitro, preclinical in vivo and clinical studies have shown efficacy of epidermal growth factor signalling inhibition in colorectal cancer. In vitro, tumour necrosis factor-related apoptosis-inducing ligand induces apoptosis in human colon cancer cells, but not in normal cells. These drugs have all been shown to interact with non-steroidal anti-inflammatory drugs in colorectal cancer cells and/or in rodent models. Combinational regimen are a promising strategy for the chemoprevention of colorectal cancer and should be further explored.     

粪便隐血试验在大肠癌筛检中的作用

目的 :分析粪便隐血在大肠癌发生、发展中的规律 ,进而发挥粪便隐血检测在大肠癌诊断中的作用。方法 :收集以北京地区为主的 2 7所医院 2 0 0 2年 4月 1日～ 2 0 0 3年 4月 1日内镜 (病理 )诊断的大肠癌患者 5 97例 ,粪便免疫隐血条形试纸检测粪便隐血 ,分析粪便隐血与癌胚抗原 (CEA)、肉眼血便、肿瘤部位、病理分型及分期的相关性。结果 :44 8例有隐血结果 ,其中阳性 3 64例 ,阳性率为 81 2 5 % ;隐血试验对大肠癌检出的阳性率为 79 75 % ,CEA检出率为 45 45 % ;3 0 8例肉眼血便中粪便隐血试验阳性率为88 96% ,14 0例无肉眼血便的患者粪便隐血试验阳性率为 64 2 9% ;左半结肠癌粪隐血阳性率为 81 3 9% ,右半结肠癌为 81 60 % ;中、高分化腺癌隐血阳性率为 81 3 5 % ,类癌阳性率为 3 3 3 3 % ;Duck’sA、Duck’sB粪隐血阳性滤为 78 48% ,Duck’sC、Duck’sD期粪隐血阳性率为 81 86%。结论 :粪便隐血试验仍是大肠肿瘤筛检的重要手段 ,且阳性率优于CEA ;隐血试验操作时要参考有无肉眼血便 ;隐血试验的阳性与否与发病部位及分期无关 ,但与大肠癌的病理分型有关。     

Double-blind clinical evaluation of a new anti-inflammatory drug,protacine, versus indomethacin

Summary

A double-blind clinical trial was carried out in 69 rheumatic in-patients to compare the eficacy and tolerance of a new, non-steroidal anti-inflammatory agent, protacine, with that of indomethacin. Patients received either 150?mg protacine or 50?mg indomethacin 3-times daily for 21 days, The time course of symptoms was recorded by semiquantitativr scoring, as were side-effects. Uropepsinogen excretion, occult blood in faeces and stundard physiological parameters were also monitored. Protacine globally decreased symptom scores by 58.5 % and indomethacin by 24.3 %(p < 0.001). The computed time to reduce symptom scores by 50% was 17.2 days with protacine as compared to 39.2 clays with indomethacin (p<0.001). Physiological parameters did not change, except white blood cells which decreased after protacine (each subject however, remaining well within the physiological range) and erythrocyte sedimentation rate, which decreased in both groups. Uropepsinogen ewretion increased 6.v 70 % after protacine, and threefold after indomethacin (p < 0.001). Occult blood search was positive in 1 patient receiving protacine, while 2 who were already positive before receiving protacine became negative during the treatment. Four patients taking indomethacin were journal to be positive, 1 showing melaena. The one who was already positive before treatment showed increasing severity of occult bleeding during indomethacin administration. Frequency and severity of side-effects were significantly less with protacine (p =0.004). In conclusion, protacine showed analgesic and anti-inflammatory actions significantly more potent and rapid than those of indomethacin, with significantly fewer and less severe side-effects.     

Double-blind clinical evaluation of a new anti-inflammatory drug, protacine, versus indomethacin.

A double-blind clinical trial was carried out in 69 rheumatic in-patients to compare the efficacy and tolerance of a new, non-steroidal anti-inflammatory agent, protacine, with that of indomethacin. Patients received either 150 mg protacine or 50 mg indomethacin 3-times daily for 21 days. The time course of symptoms was recorded by semiquantitative scoring, as were side-effects. Uropepsinogen excretion, occult blood in faeces and standard physiological parameters were also monitored. Protacine globally decreased symptom scores by 58.5% and indomethacin by 24.3% (p less than 0.001). The computed time to reduce symptom scores by 50% was 17.2 days with protacine as compared to 39.2 days with indomethacin (p less than 0.001). Physiological parameters did not change, except white blood cells which decreased after protacine (each subject however, remaining well within the physiological range) and erythrocyte sedimentation rate, which decreased in both groups. Uropepsinogen excretion increased by 70% after protacine, and threefold after indomethacin (p less than 0.001). Occult blood search was positive in 1 patient receiving protacine, while 2 who were already positive before receiving protacine became negative during the treatment. Four patients taking indomethacin were found to be positive, 1 showing melaena. The one who was already positive before treatment showed increasing severity of occult bleeding during indomethacin administration. Frequency and severity of side-effects were significantly less with protacine (p = 0.004). In conclusion, protacine showed analgesic and anti-inflammatory actions significantly more potent and rapid than those of indomethacin, with significantly fewer and less severe side-effects.     

Physicians' approaches to the use of gastroprotective strategies in low-risk non-steroidal anti-inflammatory drug users

BACKGROUND: Many doctors unnecessarily prescribe gastroprotective strategies to non-steroidal anti-inflammatory drugs users at low risk of non-steroidal anti-inflammatory drug-related gastrointestinal complications. AIM: To identify factors that predict the overuse of gastroprotective strategies in low-risk non-steroidal anti-inflammatory drug users. METHODS: We distributed a questionnaire to family doctors and general internists consisting of a clinical vignette describing a low-risk hypothetical patient with osteoarthritis who was a candidate for non-steroidal anti-inflammatory drug therapy. Respondents were asked whether they would prescribe this patient a gastroprotective strategy and to estimate the annual risk of that patient developing a gastrointestinal complication with non-steroidal anti-inflammatory drug use. Respondents inappropriately recommending a gastroprotective strategy were compared with respondents who opted not to use gastroprotection. RESULTS: We received 340 responses (response rate of 28.3%), of which 278 supplied analysable data. Thirty-five percent of respondents inappropriately recommended a gastroprotective strategy for the low-risk subject. Inappropriate prescribers were significantly more likely to overestimate the risk of gastrointestinal complications with traditional non-steroidal anti-inflammatory drugs and this was strongly predictive of gastroprotective strategy recommendation in logistic regression. CONCLUSIONS: Many doctors inappropriately recommend gastroprotective strategies in low-risk non-steroidal anti-inflammatory drug users. Improving doctors' awareness of non-steroidal anti-inflammatory drug-associated gastrointestinal risks may lead to a decrease in inappropriate utilization of gastroprotective strategies in low-risk patients.     

Cyclooxygenase as a target for colorectal cancer chemoprevention

Colorectal cancer (CRC) is one of the most common neoplasia in Western countries and the second leading cause of cancer-related death. The vast majority of cases belong to sporadic forms, whereas a small but relevant proportion of them corresponds to inherited disorders, i.e. familial adenomatous polyposis and Lynch syndrome. These individuals with germline mutations in cancer-promoting genes, along with those who had already developed a colorectal neoplasm, either adenoma or carcinoma, stand to benefit from chemopreventive interventions. A large body of evidence indicates that the use of aspirin and other non-steroidal anti-inflammatory drugs (NSAID) can reduce the risk of CRC. Experimental studies have demonstrated that these drugs decrease the incidence of carcinogen-induced colon tumors in rodents, and several epidemiological investigations and therapeutic trials have also shown a 40-50% reduction in the risk of colorectal adenoma and cancer in individuals taking NSAIDs. Moreover, patients with familial adenomatous polyposis taking sulindac or celecoxib experience a reduction in adenoma size and number. The chemopreventive effects of NSAID are largely related to inhibition of cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenase that catalyzes the conversion of arachidonic acid to prostaglandins. COX-2 overexpression is a frequent, but not universal event in colorectal neoplasms. Indeed, approximately 50% of adenomas and 80% of CRC express high levels of COX-2 mRNA and protein in neoplastic tissue. In this article, we will review the role of cyclooxygenase as a target for CRC chemoprevention, with special attention to the use of selective and non-selective COX-2 inhibitors in both individuals genetically predisposed and those who have already developed a colorectal neoplasm.