Six hundred twenty-one asymptomatic persons with negative fecal occult blood tests (ages 50-75 yr), including 496 with no known risk factors for colorectal cancer and 125 with a single first-degree relative with a history of colonic neoplasia developed after age 40, underwent screening colonoscopy. Three Dukes A cancers were detected in average-risk persons. The overall prevalence of adenomatous polyps was 27%. Multiple logistic regression analysis revealed that increasing age and male gender were both strong predictors of colonic neoplasia (p < 0.001). A positive family history of a single first-degree relative with colorectal cancer was not associated with an increased prevalence of colonic neoplasia (p = 0.29), although an effect may be present if the relative was < 60 yr at diagnosis. Overall 16% of males and 7% of women > or = 60 yr had at least one adenoma that was large (> or = 1 cm in size), villous or tubulovillous, or had grade 3 dysplasia. We conclude that the prevalence of colonic neoplasia in asymptomatic persons with negative fecal occult blood tests is substantial, particularly in elderly males. A family history of a single first-degree relative diagnosed at age > or = 60 yr with colorectal cancer is not associated with an increased prevalence of colonic adenomas.
BACKGROUND/AIMS: This study was carried out to assess the validity of three testing methods of immunochemical occult blood according to the number of collection times as a means for colorectal cancer screening. METHODOLOGY: Four thousand six hundred and eleven asymptomatic individuals, who received both an immunochemical occult blood test with a three-day method and colonoscopy during a medical checkup, served as subjects for this study. For evaluation of the desirable number of sampling times, we used the results of the first day for the 1-day method, the results of the first and second days for the 2-day method, and the results of three-consecutive days for the 3-day method. Sensitivities and specificities of these three testing methods were evaluated. RESULTS: Sensitivities and specificities for colorectal cancer were calculated to be 56% and 97% for the 1-day method, 83% and 96% for the 2-day method, and 89% and 94% for the 3-day method, respectively, showing a significant difference in sensitivity between the 1-day and the 2-day methods, as well as the 3-day method (p < 0.01), and in specificity between the 1-day as well as the 2-day and 3-day methods (p < 0.05). CONCLUSIONS: These findings indicate that the immunochemical fecal occult blood test is useful for the diagnosis of colorectal cancer, and that 2-day testing is recommended as a means of screening for colorectal cancer.
OBJECTIVE: Fecal immunochemical testing (FIT) is increasingly used for colorectal cancer (CRC) screening. We aimed to estimate its diagnostic accuracy in invitational population screening measured against colonoscopy. METHODS: Participants (50-75 years) in an invitational primary colonoscopy screening program were asked to complete one sample FIT before colonoscopy. We estimated FIT sensitivity, specificity, and predictive values in detecting CRC and advanced neoplasia (carcinomas and advanced adenomas) for cutoff levels of 50 (FIT50), 75 (FIT75), and 100 (FIT100) ng hemoglobin (Hb)/ml, corresponding with, respectively, 10, 15 and 20 μg Hb/g feces. RESULTS: A total of 1,256 participants underwent a FIT and screening colonoscopy. Advanced neoplasia was detected by colonoscopy in 119 (9%), 8 (0.6%) of them had CRC. At FIT50, 121 (10%) had a positive test result; 45 (37%) had advanced neoplasia and 7 (6%) had CRC. A total of 74 of 1,135 FIT50 negatives (7%) had advanced neoplasia including 1 (0.1%) CRC. FIT50 had a sensitivity of 38% (95% confidence interval (CI): 29-47) for advanced neoplasia and 88% (95% CI: 37-99) for CRC at a specificity of 93% (95% CI: 92-95) and 91% (95% CI: 89-92), respectively. The positive and negative predictive values for FIT50 were 6% (95% CI: 3-12) and almost 100% (95% CI: 99-100) for CRC, and 37% (95% CI: 29-46) and 93% (95% CI: 92-95) for advanced neoplasia. The sensitivity and specificity of FIT75 for advanced neoplasia were 33% (95% CI: 25-42) and 96% (95% CI: 94-97). At FIT100, 71 screenees (6%) had a positive test result. The sensitivity and specificity of FIT100 were for advanced neoplasia 31% (95% CI: 23-40) and 97% (95% CI: 96-98), and for CRC 75% (95% CI: 36-96) and 95% (95% CI: 93-96). The area under curve for detecting advanced neoplasia was 0.70 (95% CI: 0.64-0.76). FIT had a similar sensitivity for proximal and distal advanced neoplasia at cutoffs of 50 (38% vs. 37%; P=0.99), 75 (33% vs. 31%; P=0.85) and 100 (33% vs. 29%; P=0.68) ng Hb/ml. DISCUSSION: Nine out of ten screening participants with CRC and four out of ten with advanced neoplasia will be detected using one single FIT at low cutoff. Sensitivity in detecting proximal and distal advanced neoplasia is comparable.
BACKGROUND: Fecal occult-blood testing and sigmoidoscopy have been recommended for screening for colorectal cancer, but the sensitivity of such combined testing for detecting neoplasia is uncertain. At 13 Veterans Affairs medical centers, we performed colonoscopy to determine the prevalence of neoplasia and the sensitivity of one-time screening with a fecal occult-blood test plus sigmoidoscopy. METHODS: Asymptomatic subjects (age range, 50 to 75 years) provided stool specimens on cards from three consecutive days for fecal occult-blood testing, which were rehydrated for interpretation. They then underwent colonoscopy. Sigmoidoscopy was defined in this study as examination of the rectum and sigmoid colon during colonoscopy, and sensitivity was estimated by determining how many patients with advanced neoplasia had an adenoma in the rectum or sigmoid colon. Advanced colonic neoplasia was defined as an adenoma 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer. Classification of subjects according to the findings was based on the most advanced lesion. RESULTS: A total of 2885 subjects returned the three specimen cards for fecal occult-blood testing and underwent a complete colonoscopic examination. A total of 23.9 percent of subjects with advanced neoplasia had a positive test for fecal occult blood. As compared with subjects who had a negative test for fecal occult blood, the relative risk of advanced neoplasia in subjects who had a positive test was 3.47 (95 percent confidence interval, 2.76 to 4.35). Sigmoidoscopy identified 70.3 percent of all subjects with advanced neoplasia. Combined one-time screening with a fecal occult-blood test and sigmoidoscopy identified 75.8 percent of subjects with advanced neoplasia. CONCLUSIONS: One-time screening with both a fecal occult-blood test with rehydration and sigmoidoscopy fails to detect advanced colonic neoplasia in 24 percent of subjects with the condition.
The secondary prevention of colorectal cancer is based on the early detection of noninvasive cancer and removal of adenomatous polyps. The two commonly used screening tests are flexible sigmoidoscopy and guaiac fecal occult blood testing. Both were performed simultaneously and independently on 1176 asymptomatic volunteers followed by colonoscopic examination if either occult blood or a neoplasm was detected. Neoplasia (adenomatous polyps or cancer) were found in 48 screenees. Only ten had positive stool occult blood while 45 were detected by sigmoidoscopy. Analysis of sensitivity for neoplasia was 93.8% for sigmoidoscopy but only 20.8% for the occult blood tests, while the positive predictive values for neoplasia were 100% and 23.8% respectively. The fecal occult blood test detected only 18% of screenees with adenomas and 60% with invasive cancer. Flexible sigmoidoscopy detected 95% and 80% respectively. Analysis (kappa statistic) demonstrated little agreement between the two tests (P greater than 0.05), indicating that they are diagnosing different neoplasia. Evaluation of expected gain in diagnosing neoplasia, by combining both tests, gave 18% for the fecal blood test and 94% for the endoscopic test. These results confirm the complementary value of performing both tests, but especially the high sensitivity and predictive value positive of flexible sigmoidoscopy for adenomas, including those with severe dysplasia, and the converse for the fecal occult blood test. This latter test must be recommended and used within a screening program with caution and full understanding of its limitations.
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.
BACKGROUND: Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality. METHODS: We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions. RESULTS: The clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7). CONCLUSIONS: In an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. (Funded by Guardant Health; ECLIPSE ClinicalTrials.gov number, NCT04136002.).
<h3>Objectives.</h3> —To define the validity of fecal blood as a marker for colorectal neoplasia in the screening setting and to compare yields by Hemoccult and HemoQuant fecal occult blood screening tests. <h3>Design.</h3> —A multicenter masked comparison of fecal blood test results against structural colorectal evaluations and longitudinal follow-up, serving as criterion standards, in nonreferred subjects at risk for colorectal neoplasia. <h3>Setting.</h3> —Communities, primary care centers, referral centers. <h3>Participants.</h3> —Two groups: (1) 1217 patients aged at least 18 years undergoing routine structural surveillance evaluations following curative resection of a colorectal tumor and (2) 12312 relatives of colorectal cancer patients aged at least 50 years. <h3>Interventions.</h3> —Blinded Hemoccult II and HemoQuant testing on three mailedin stool samples per subject. <h3>Main Outcome Measure.</h3> —Sensitivity of fecal blood tests for colorectal neoplasia. <h3>Results.</h3> —In the postresection group, surveillance evaluations revealed 46 malignant colorectal neoplasms and 402 polyps. At matched specificity, sensitivity of either test for cancer was 26% (95% confidence interval, 13% to 39%). Hemoccult was positive in 21% of intraluminal recurrences, 33% of all new primary tumors, and 29% of Dukes A or B cancers; HemoQuant was elevated in 24%, 28%, and 29%, respectively. Sensitivity for polyps 1.0 cm or larger was 13% by Hemoccult and 11% by HemoQuant. In the group of relatives, estimated sensitivity for cancer at 1 to 3 years of follow-up was 25% to 33% by Hemoccult, not significantly different from the 29% to 43% by HemoQuant. <h3>Conclusions.</h3> —Based on our observations in the screening setting, fecal blood appears to be a poor marker for colorectal neoplasia. Most cancers and the vast majority of polyps will be missed. Hemoccult and HemoQuant are similarly insensitive. (<i>JAMA</i>. 1993;269:1262-1267)
OBJECTIVES: To compare the performance of a new blood test for colorectal cancer (CRC) to an established fecal immunochemical test (FIT) in a study population with the full range of neoplastic and non-neoplastic pathologies encountered in the colon and rectum. METHODS: Volunteers were asked to complete a FIT prior to colonoscopy. Blood was collected after bowel preparation but prior to colonoscopy, and plasma was assayed for the presence of methylated BCAT1 and IKZF1 DNA using a multiplex real-time PCR assay. Sensitivity and specificity estimates for the blood test were calculated from true- and false-positive rates for neoplasia and compared with FIT at a range of fecal hemoglobin (Hb) concentration positivity thresholds. RESULTS: In total, 1,381 volunteers (median age 64 years; 49% male) completed both tests prior to colonoscopy. Estimated sensitivity of the BCAT1/IKZF1 blood test for CRC was 62% (41/66; 95% confidence interval 49-74%) with a specificity of 92% (1207/1315; 90-93%). FIT returned the same specificity at a cutoff of 60 μg Hb/g, at which its corresponding sensitivity for cancer was 64% (42/66; 51-75%). In the range of commonly used FIT cutoffs, respective cancer sensitivity and specificity estimates with FIT were: 59% (46-71%) and 93% (92-95%) at 80 μg Hb/g, and 79% (67-88%) and 81% (78-83%) at 10 μg Hb/g. Although estimated sensitivities were not significantly different between the two tests for any stage of cancer, FIT showed a significantly higher sensitivity for advanced adenoma at the lower cutoffs. Specificity of FIT, but not of the BCAT1/IKZF1 blood test, deteriorated substantially in people with overt blood in the feces. When combining FIT (cutoff 10 μg Hb/g) with the BCAT1/IKZF1 blood test, sensitivity for cancer was 89% (79-96%) at 74% (72-77%) specificity. CONCLUSIONS: A test based on detection of methylated BCAT1/IKZF1 DNA in blood has comparable sensitivity but better specificity for CRC than FIT at the commonly used positivity threshold of 10 μg Hb/g. Further evaluation of the new test relative to FIT in the population screening context is now required to fully understand the potential advantages and disadvantages of these biomarkers in screening.
PURPOSE: Endoscopic examination has proven effective in both detecting and preventing colorectal cancer; however, only about a quarter of eligible patients undergo screening. Even if the compliance rate increased, limited endoscopic capacity and cost would be prohibitive. There is a need for an accurate method to target colonoscopy to those most at risk of harboring colonic neoplasia. Exploiting field carcinogenesis seems to be a promising avenue. Our group recently reported that an early increase in blood supply (EIBS) is a reliable marker of field carcinogenesis in experimental models. We now investigate whether in situ detection of EIBS in the rectum can predict neoplasia elsewhere in the colon. EXPERIMENTAL DESIGN: We developed a novel polarization-gated spectroscopy fiber-optic probe that allows depth-selective interrogation of microvascular blood content. Using the probe, we examined the blood content in vivo from the rectal mucosa of 216 patients undergoing screening colonoscopy. RESULTS: Microvascular blood content was increased by approximately 50% in the endoscopically normal rectal mucosa of patients harboring advanced adenomas when compared with neoplasia-free patients irrespective of lesion location. Demographic factors and nonneoplastic lesions did not confound this observation. Logistic regression using mucosal oxyhemoglobin concentration and patient age resulted in a sensitivity of 83%, a specificity of 82%, and an area under the receiver operating characteristic curve of 0.88 for the detection of advanced adenomas. CONCLUSIONS: Increased microvascular blood supply in the normal rectal mucosa is associated with the presence of clinically significant neoplasia elsewhere in the colon, supporting the development of rectal EIBS as a colon cancer risk-stratification tool.
BACKGROUND: Guaiac-based fecal occult blood tests (FOBTs) for colorectal cancer screening are not specific for human hemoglobin and have low sensitivity. Automated-development, immunochemical FOBT is quality-controlled, is specific for human hemoglobin, and does not require diet restriction. OBJECTIVES: To measure the sensitivity and specificity of quantitative immunochemical fecal hemoglobin measurements for detection of cancer and advanced adenoma in patients undergoing colonoscopy, to determine fecal hemoglobin thresholds that give the highest posttest probability for neoplasia, and to determine the number of immunochemical FOBTs needed. DESIGN: Prospective, cross-sectional study. SETTING: Ambulatory endoscopy services of the main health medical organization in Tel Aviv, Israel. PARTICIPANTS: 1000 consecutive ambulatory patients--some asymptomatic but at increased risk for colorectal neoplasia and some symptomatic--who were undergoing elective colonoscopy and volunteered to prepare immunochemical FOBTs. INTERVENTION: The hemoglobin content of 3 bowel movements was measured, and the highest value was compared with colonoscopy findings. MEASUREMENTS: Sensitivity, specificity, predictive values, likelihood ratios, and 95% CIs of fecal hemoglobin measurements for clinically significant neoplasia, their relationship to the amount of fecal hemoglobin measured, and the number of immunochemical FOBTs performed. RESULTS: Colonoscopy identified clinically significant neoplasia in 91 patients (cancer in 17 patients and advanced adenomas in 74 patients). Using 3 immunochemical FOBTs and a hemoglobin threshold of 75 ng/mL of buffer, sensitivity and specificity were 94.1% (95% CI, 82.9% to 100.0%) and 87.5% (CI, 85.4% to 89.6%), respectively, for cancer and 67% (CI, 57.4% to 76.7%) and 91.4% (CI, 89.6% to 93.2%), respectively, for any clinically significant neoplasia. LIMITATIONS: The fecal sampling method is standardized, but the sample size depends on fecal consistency. Some patients were tested while discontinuing aspirin and anticoagulant therapies. Study patients were at increased risk, and results might not apply to average-risk populations. CONCLUSIONS: Quantitative immunochemical FOBT has good sensitivity and specificity for detection of clinically significant neoplasia. Test performance in screening average-risk populations is not known.
BACKGROUND: Faecal occult blood tests (FOBTs) are used for colorectal cancer (CRC) screening. We aimed to assess the sensitivity of an immunochemical FOBT for detecting advanced colorectal neoplasia in the left vs the right colon and to explore reasons for potential differences in site-specific test performance. METHODS: We prospectively measured faecal occult blood levels by a quantitative immunochemical FOBT (RIDASCREEN) in 2310 average-risk subjects undergoing screening colonoscopy. We compared diagnostic performance for subjects with left- vs right-sided advanced neoplasia, as well as patient characteristics and adenoma characteristics that have been suggested to impact faecal haemoglobin levels. RESULTS: Sensitivities for subjects with left- vs right-sided advanced neoplasia were 33% (95% confidence interval (CI), 26-41%) and 20% (CI, 11-31%) (P=0.04) at a specificity of 95% (overall sensitivity: 29%) and the areas under the receiver-operating characteristics curve were 0.71 (CI, 0.69-0.72) and 0.60 (CI, 0.58-0.63), respectively. Pedunculated shape was strikingly more common in participants with left- vs right-sided advanced neoplasia (47% vs 14%). In logistic regression analyses adjusted for site, pedunculated shape was statistically significantly associated with test sensitivity (P=0.04). CONCLUSIONS: The immunochemical FOBT in our study was more sensitive for detecting subjects with left- vs right-sided advanced colorectal neoplasia. Our findings may stimulate further diagnostic research in the field as well as modelling analyses to estimate the potential effect of site-specific test performance on the effectiveness of annual or biennial FOBT-based screening programmes, in particular with respect to protection from right-sided CRC.
BACKGROUND: Cervical intraepithelial neoplasia (CIN) is the most common pre-malignant lesion. Surgical treatments for CIN are commonly associated with blood loss. OBJECTIVES: To assess the effectiveness and safety of interventions for preventing blood loss during the treatment of CIN. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE and CENTRAL up to November 2012. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of vasopressin, tranexamic acid, haemostatic sutures, Amino-Cerv or Monsel's solution in women undergoing surgery for CIN. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data and assessed risk of bias. Risk ratios comparing adverse events in women who received one of the interventions were pooled in a random-effects meta-analyses or included in single trial analyses. MAIN RESULTS: Twelve RCTs (N = 1602, of whom 1512 were assessed) were included.Vasopressin significantly reduced perioperative bleeding (mean difference (MD) = -100.80, 95% confidence interval (CI) -129.48 to -72.12) and was associated with a decreased risk of bleeding that required haemostatic sutures or further vasopressin, compared to placebo (risk ratio (RR) = 0.39, 95% CI 0.27 to 0.56).Tranexamic acid significantly reduced risk of secondary haemorrhage (RR = 0.23, 95% CI 0.11 to 0.50), but not primary haemorrhage (RR = 1.24, 95% CI 0.04 to 38.23) after knife and laser cone biopsy, compared with placebo. There was also a statistically significant reduction in postoperative blood loss compared with placebo (MD = -55.60, 95% CI -94.91 to -16.29).Packing with Monsel's solution resulted in less perioperative blood loss (MD = -22.00, 95% CI -23.09 to -20.91) and decreased the risk of dysmenorrhoea (RR = 0.37, 95% CI 0.16 to 0.84), unsatisfactory colposcopy (RR = 0.43, 95% CI 0.30 to 0.63) and cervical stenosis (RR = 0.35, 95% CI 0.25 to 0.49) compared to routine suturing, but was not statistically different to sutures for risk of primary and secondary haemorrhages.Amino-Cerv antibiotic gel failed to make a difference on secondary haemorrhage but was associated with significantly less vaginal discharge at 2 weeks compared with routine care (RR = 0.27, 95% CI 0.09 to 0.86).There was no significant difference in blood loss between women who received ball electrode diathermy and those who received Monsel's paste (MD = 4.82, 95% CI -3.45 to 13.09). AUTHORS' CONCLUSIONS: Bleeding associated with surgery of the cervix appears to be reduced by vasopressin, used in combination with local anaesthetic. Tranexamic acid appears to be beneficial after knife and laser cone biopsy. There are insufficient data to assess the effects on primary haemorrhage. There is some evidence that haemostatic suturing has an adverse effect on blood loss, cervical stenosis and satisfactory colposcopy.
BACKGROUND: Stool DNA testing is a new approach to colorectal cancer detection. Few data are available from the screening setting. OBJECTIVE: To compare stool DNA and fecal blood testing for detection of screen-relevant neoplasia (curable-stage cancer, high-grade dysplasia, or adenomas >1 cm). DESIGN: Blinded, multicenter, cross-sectional study. SETTING: Communities surrounding 22 participating academic and regional health care systems in the United States. PARTICIPANTS: 4482 average-risk adults. MEASUREMENTS: Fecal blood and DNA markers. Participants collected 3 stools, smeared fecal blood test cards and used same-day shipment to a central facility. Fecal blood cards (Hemoccult and HemoccultSensa, Beckman Coulter, Fullerton, California) were tested on 3 stools and DNA assays on 1 stool per patient. Stool DNA test 1 (SDT-1) was a precommercial 23-marker assay, and a novel test (SDT-2) targeted 3 broadly informative markers. The criterion standard was colonoscopy. RESULTS: Sensitivity for screen-relevant neoplasms was 20% by SDT-1, 11% by Hemoccult (P = 0.020), 21% by HemoccultSensa (P = 0.80); sensitivity for cancer plus high-grade dysplasia did not differ among tests. Specificity was 96% by SDT-1, compared with 98% by Hemoccult (P < 0.001) and 97% by HemoccultSensa (P = 0.20). Stool DNA test 2 detected 46% of screen-relevant neoplasms, compared with 16% by Hemoccult (P < 0.001) and 24% by HemoccultSensa (P < 0.001). Stool DNA test 2 detected 46% of adenomas 1 cm or larger, compared with 10% by Hemoccult (P < 0.001) and 17% by HemoccultSensa (P < 0.001). Among colonoscopically normal patients, the positivity rate was 16% with SDT-2, compared with 4% with Hemoccult (P = 0.010) and 5% with HemoccultSensa (P = 0.030). LIMITATIONS: Stool DNA test 2 was not performed on all subsets of patients without screen-relevant neoplasms. Stools were collected without preservative, which reduced detection of some DNA markers. CONCLUSION: Stool DNA test 1 provides no improvement over HemoccultSensa for detection of screen-relevant neoplasms. Stool DNA test 2 detects significantly more neoplasms than does Hemoccult or HemoccultSensa, but with more positive results in colonoscopically normal patients. Higher sensitivity of SDT-2 was particularly apparent for adenomas.
BACKGROUND: Published data suggest that screening might reduce the mortality rate from colorectal neoplasia. Faecal occult blood (FOB) testing suffers from poor sensitivity and significant numbers of interval cancers, both of which should be improved by the addition of flexible sigmoidoscopy (FOS). METHODS: This prospective, randomized study aimed to assess the compliance and neoplasia yield of FOB testing and FOS compared with that of FOB testing alone. From general practitioner registers, 6371 asymptomatic patients (3124 men, 3247 women; age range 50-74 years) were invited for screening by means of FOB testing (3128 patients) performed at home, or a combination of FOB testing and FOS (3243 patients). RESULTS: Compliance with FOB testing alone was 50 per cent. In the FOB testing/FOS group, 48 per cent returned the FOB test but only 20 per cent went on to FOS. Despite the poor compliance, the neoplasia yield was four times greater in the FOB testing/FOS group. CONCLUSION: FOS increase the neoplasia yield but strategies to improve compliance must be identified for this to become a population screening test.
Our controlled trial of screening for colorectal cancer has now been in progress for almost five years. Screening is accomplished by rigid sigmoidoscopy in control and study groups and, in addition, by fecal occult blood testing in the study group. Patients screened are men and women age 40 and older, mostly at average risk. Fecal occult blood testing is with Hemoccult slides with patients on a meat-free, high-bulk diet without hydration, and with a four-day storage interval between slide preparation and testing. Patients with positive slides undergo diagnostic investigation that includes both colonoscopy and double-contrast barium enema and, in some, an upper gastrointestinal series. Preliminary results to date include: patient baseline statistics and subgroup comparability, rate of positive slides of 1-4%, predictive value for neoplasia of 44-50%, false-positives of 0.5-2.1%, favorable Dukes' staging of cancers in the study group, and high patient compliance. Considerably more follow-up is need in our study and control population, and issues such as mortality and cost need to be addressed. Additional time will be necessary to provide firm conclusions.
BACKGROUND: Fecal immunochemical tests (FIT) are an advanced fecal occult blood test (FOBT) technology that reduces barriers to population screening by simplifying the logistics of stool-sampling. The current study was conducted to undertake a paired comparison of a sensitive guaiac FOBT (GFOBT; Hemoccult II Sensa, Beckman Coulter, Fullerton, CA) with a brush-sampling FIT (InSure; Enterix, North Ryde, NSW, Australia), to determine whether this FIT improves detection of significant neoplasia. METHODS: Individuals sampled consecutive stools, at home, with both FIT and GFOBT sampling devices while following dietary restrictions appropriate for GFOBT. Study populations included a screening cohort (n = 2351) and a symptomatic diagnostic group (n = 161). Paired comparison of positivity rates was undertaken in those found to have cancer and/or significant adenoma (high-grade dysplasia, villous change, > or =10 mm, serrated histology or > or =3 polyps), benign pathology, or no pathology. RESULTS: Combined results for both cohorts showed that the FIT returned a true-positive result significantly more often in cancer (n = 24; 87.5% vs. 54.2%) and in significant adenomas (n = 61; 42.6% vs. 23.0%). Of all UICC Stage I cancers, the FIT was positive in 12 of 13 compared with 4 of 13 with the GFOBT (P = .002). In analyses of just the screening cohort, the FIT remained significantly better at detecting cancers and significant adenomas; the false-positive rate for any neoplasia was marginally higher with the FIT than the GFOBT (3.4% vs. 2.5%; 95% CI of difference, 0-1.8%), whereas positive predictive values were 41.9% and 40.4%, respectively. CONCLUSIONS: This brush-sampling FIT is more sensitive for cancers and significant adenomas than a sensitive GFOBT. As such, it should deliver greater reductions in colorectal cancer mortality and incidence than the GFOBT.
Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1 were determined in EDTA-plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high-risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had 'clean' colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood-based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC.
PURPOSE: This study was designed to investigate the validity of a single immunochemical fecal occult blood test (FOBT) for detection of colorectal neoplasia. MATERIALS AND METHODS: A total of 3,794 average-risk screenees and 304 colorectal cancer patients admitted to the National Cancer Center, Korea, between May 2001 and November 2002, were studied prospectively. All screenees and admitted patients underwent FOBT and total colonoscopic examinations. Stools were self-collected, and examined using an immunochemical fecal occult blood test (OC-hemodia, Eiken Chemical Co. Tokyo, Japan) and an OC-sensor analyzer(R) (Eiken Chemical Co. Tokyo, Japan). RESULTS: Of the 3,794 asymptomatic screenees, the colonoscopy identified colorectal adenomas and cancers in 613 (16.2%) and 12 (0.3%) subjects, respectively. The sensitivities of a single immunochemical FOBT for detecting colorectal cancers and adenomas in screenees were 25.0 and 2.4%, respectively. The false positive rate of FOBT for colorectal cancer in screenees was 1.19%. For the total 316 colorectal cancer cases (including 12 cases from screenees), the FOBT sensitivities according to the T-stage were 38.5, 75.0%, 78.9 and 79.2% for T1, 2, 3 and 4 cancers, respectively. The sensitivities according to the Dukes stages A, B and C were 63.4, 79.3 and 78.6%, respectively. CONCLUSION: The sensitivities of a single immunochemical FOBT for detecting colorectal cancers and adenomas in screenees were 25.0 and 2.4%, respectively. The sensitivities of FOBT were about 80% for Dukes B or C colorectal cancers and 63.4% for Dukes A.
BACKGROUND: The aim of this study was to evaluate the incidence of lower gastrointestinal symptoms in faecal occult blood (FOB) test-positive participants in a colorectal screening programme, and to compare the colonoscopic findings in symptomatic and asymptomatic individuals. METHODS: Five hundred and sixty-three consecutive individuals with a positive FOB test in the Scottish arm of the national colorectal cancer screening pilot were studied. All were aged between 50 and 69 years and underwent colonoscopy. Before the procedure the participants were given a standard questionnaire to elicit gastrointestinal symptoms; these were correlated with the colonoscopic findings. RESULTS: Of the 563 participants, 439 (78.0 per cent) had one or more lower gastrointestinal symptoms and 124 (22.0 per cent) were symptom free. Taking adenoma and carcinoma together, 322 (57.2 per cent) of the subjects were found to have colorectal neoplasia, and 128 (22.7 per cent) had a completely normal colon. Rectal bleeding was the most common symptom, followed by change in bowel habit, abdominal pain, tenesmus, unexplained weight loss, rectal pain and unexplained anaemia. No significant associations were found between any of these symptoms and the findings at colonoscopy. CONCLUSION: In a FOB test-positive screened population, lower gastrointestinal symptoms are common, but are not predictive of colorectal neoplasia.