Evaluation of fecal occult blood test with reverse passive hemagglutination for colorectal neoplasm screen

Lun Zhou, Hai Yu,  Shu Zheng

Subject heading  Colonic neoplasms Rectal neoplasms Colonic polyps Hemagglutination tests Occult blood

Zhou L, Yu H, Zheng S. Evaluation of fecal occult blood test with reverse passive hemagglutination for colorectal neoplasm screen. China Nati J New Gastroenterol, 1997;3(1):38-40

Abstract

AIM  To evaluate the one sampling and three sampling reverse passive hemagglutination fecal occult blood test (RPHA FOBT) for colorectal neoplasm screening.

METHODS  A group of 3034 individuals with histories of colorectal polyps and/or ulcers were screened for colorectal cancer, 3ª²day fecal samples were collected and 60cm fiberoptic colonoscopy was conducted for each subject. The fecal samples were tested for occult blood with RPHA method and the endoscopic and histopathologic diagnoses were used as standard reference for evaluation. The sensitivity, specificity, positive and negative predictive value of different samplings were compared.

RESULTS  About 521 cases of colorectal neoplasms were detected, including 12 cases of colorectal cancer and 509 cases of polyps. Results showed  that the mean sensitivity of one sampling RPHA FOBT for colorectal neoplasm was only 13.2%, the specificity was 90.3%, the positive and negative predictive values were 21.3% and 83.4% respectively; while for the three sampling taki ng one positivity as positive, the sensitivity increased to 22.0%, the specific ity decreased to 81.6%, and the positive and negative predictive values were 19.7% and 83.6% respectively.

CONCLUSION  A single RPHA FOBT seems to be less sensitive for screening colorectal neoplasm. But because it is convenient and economical, RPHA FOBT remains the most practical procedure for detection of early colorectal cancer and polyps if it is combined with other screening methods.



INTRODUCTION
Fecal occult blood test (FOBT) has been the important procedure for acreening colorectal cancer in population, since Greegor first reported it in 1967^£Û1-2£Ý. During the screening, both early colorectal cancer and precancerous lesions, such as adenomatous polyps, can be detected. So the screening for colorectal neoplasm with FOBT is not only a procedure of secondary prevention, but also a measure for primary prevention of colorectal cancer. The conventional chemical FOBT (e.g. hemoccult) requires dietary control to reduce the false positive rate and the three day sampling to reduce false negative rate. Although reverse passive hemagglutination (RPHA) method which developed in the 1980¡äs raised the sensitivity and specificity of screening, Saito et al suggested that a single sampling RPHA may be adequate for screening^£Û3£Ý. This has not been verified in large population screening. In the present study, we screened a highª²risk population for colorectal cancer with RPHA FOBT and 60cm fiberoptic colonoscopy, and evaluated various protocols of RPHA FOBT (one, two and three sampling) for screening colorectal neoplasm.

MATERIALS AND METHODS

Subjects
Individuals with history of rectal polyps and ulcers detected in mass screening 10 years ago were involved in Haining and Jiashan counties of Zhejiang Province. The total 3034 subjects included 1716 males and 1318 females, aged 32-72, with a mean age of 49-2 years.

Methods
All subjects received a 60cm fiberoptic colonoscopy, and those who had positive endoscopic findings received biopsy with histopathologic examination. The bowel preparation and endoscopic procedues were reported in an other paper^£Û4£Ý. No dietary control was required, before endoscopy, three day fecal samples were collected and submitted for lab test. The RPHA FOBT was performed for each sample according to Zhu  et al^£Û5£Ý. During analysis, subjects were divided into two groups: neoplasm (cancer, adenoma and polyps) and nonª²neoplasm, according to endoscopic and histopathologic diagnoses. For those who completed three RPHA FOBT, three test thresholds were used: 1) all tests positive as posi tive £Û3/3(+)£Ý; 2) two positive as positive £Û2/3(+)£Ý and 3) one positive as positive £Û1/3(+)£Ý. The sensitivity, specificity, positive predictive value and negative predictive value were used as efficacy indicators for evaluation. For comparison, ¦Ö-2 test was performed with Epi info software, the Mante Haeszel or Yate¡äs correction were used for significance analysis.

RESULTS
Out of 3034 subjects, 521 cases of colorectal neoplasms were diagnosed by endoscopic and histopathologic examination. There were 12 cases of cancer and 509 poly ps, in which adenoma accounted for 45.0% (229/509). Among 2553 subjects who completed at least one FOB test, there were 440 neoplasias (12 cancers and 428 poly ps); in 2431 subjects who had at least 2 FOB, there were 422 neoplasia (12 cancers and 410 polyps); in 2272 subjects who completed three FOB tests, 388 cases of  neoplasia were detected including 11 cancers and 377 polyps. The correlation between neoplasia and three FOBT results are presented in Tables 1, 2 and 3. The mean sensitivity, specificity, positive and negative predictive value for three tests were 13.2%, 90.3%, 21.3% and 83.4% respectively. In 2272 subjects who had three FOB tests, the sensitivity and specificity of FOB to neoplasia using different positive thresholds are shown in Tables 4, 5 and 6. It is demonstrated that with the elevation of positive threshold £Û1/3(+) to 3/3(+)£Ý, the sensitivity decreased from 22.0% to only 5.4%; while the specificity increased from 81.6% to 96.5%.
Table 1  Relationship between the 1st RPHA FOBT and colorectal neoplasm

Sensitivity: 13.6% (60/440),specificity: 88.2% (1863/2113),positive predictive value: 16.1% (60/310),negative predictive value: 83.1% (1863/2243).
Table 2  Relationship between the 2nd RPHA FOBT and colorectal neoplasm

Sensitivity: 11.8% (50/422),specificity: 90.7% (1823/2009),positive predictive value: 21.2% (50/236),negative predictive value: 83.1% (1823/2195).
Table 3  Relationship between the 3rd RPHA FOBT and colorectal neoplasm

Sensitivity: 14.2% (55/388),specificity: 92.0% (1733/1884),positive predictive value: 26.7% (55/206),negative predictive value: 83.9% (1773/2066).
Table 4  Relationship between three sampling 1/3(+) and colorectal neoplasm

Sensitivity: 22.0% (85/387),specificity: 81.6% (1539/1885),positive predictive value: 19.7% (85/431),negative predictive value: 83.6% (1539/1841).
Table 5  Relationship between three sampling 2/3(+) and colorectal neoplasm

Sensitivity: 11.9% (46/341),specificity: 92.7% (1747/1885),positive predictive value: 25.0% (46/184),negative predictive value: 83.7% (1747/2088).
Table 6  Relationship between threeª²sampling 3/3(+) and colorectal neoplasm

Sensitivity: 5.4% (21/387),specificity: 96.5% (1819/1885),positive predictive value: 24.1% (21/87),negative predictive value: 83.2% (1819/2185)

DISCUSSION
Occult bleeding of lower digestive tract is the most common symptom of early cancer or polyps of large bowel. Meanwhile, in physiological conditions, there can be a samll amount of bleeding in the apparently normal digestive tract; it is, however, seldom more than 2mL over 24 hours. The conventional chemical FOB test has a low sensitivity, and can only detect more than 10mL/24h of bleeding in lower digestive tract^£Û6£Ý. Therefore, a threeª²day sampling has been recommended clinically to elevate the sensitivity of test. But it is difficult to implement in large population screening because of greatly increased work load of sample collection, lab test, data process as well as the cost for reagents. In 1984, Saito first reported the application of RPHA FOBT in screening colorectal cancer, and suggested that one sampling RPHA might replace three day hemoccult test^£Û3£Ý, because the former had a higher sensitivity. In China, Zhou and Zhu also successfully developed the RPHA FOB test kits, and it can detect intestinal bleeding as little as 0.48mL/24h^£Û7£Ý.
    In order to objectively evaluate the efficacy of RPHA in screening colorectal neoplasia, the present study compared the results of one sampling with those of three sampling RPHA FOBT, using 60cm fiberoptic colonoscopy as standard reference. Our study revealed that the mean sensitivity of one sampling RPHA FOBT was only 13.2% which means as many as 86.8% of colorectal neoplasia might be missed if FOBT is used as the only measure for screening. However, when three sampling method is used and taking 1/3(+) as positive criteria, 22.0% of the colorectal neoplasia can be detected. The authors have previously reported that the sensitivity of three sampling RPHA FOBT for colorectal cancer was 63.6% and for villous or tubulovillous adenoma was 40%, which has an increasing tendency to malignant transformation^£Û8£Ý.ª¥
      The low sensitivity of one sampling RPHA FOBT may result from the variation of bleeding status of early colorectal neoplasia, particularly polyps. Ahlquist et al measured FOB with hemoccult test consecutively for 2 weeks in a group of patients with colorectal cancer. They found that only one quarter of the patients presented consistent positivity, for the remainders the FOB fluctuated day by day^£Û9£Ý. So threeª²day sampling should have more chances to find occult intestinal bleeding; on the other hand, it will definitely increase the cost and work load of screening, particularly in large population. Coping with the dilemma, we have designed a new screening protocol comprising one sampling RPHA FOBT plus computerized risk assessment as primary screening procedure. With the complement of two methods, the sensitivity of primary screening will be raised. In a high incidence area, we screened 62667 individuals aged 30 and above by u sing this protocol, among them, 4299 subjects required endoscopic examination; i n 3162 people who completed endoscopy, 397 cases of colorectal neoplasia were de tected including 41 cancers and 356 polyps. In all cases of neoplasia, 172 patie nts (43.3%) had positive FOBT, and the remaining 56.7% cases were screened endoscopically only according to risk assessment^£Û10£Ý. In conclusion, RPHA FOBT is a convenient, ecomonical and noninvasive method for screening colorectal neoplasia, although it is less sensitive. If it is used in combination with other screening measures, RPHA FOBT can still be an effective method for detecting early colorectal cancer and polyps. Whether to choose one sampling or three sampling methods depends on the size of the screened population and the availability  of resources.

Cancer Institute, Zhejiang Medical University, Hangzhou 310009, China
Dr. ZHOU Lun, Associate Professor, engaged in prevention and treatment research on cancer, having 25 papers published.ª¤
*Supported by the National ¡°Eighth Fiveª²Year Plan¡± Key Research Project (No. 85-914-01-09).ª¤
Correspondence to  Dr. ZHOU Lunª¤
Tel:+86¡¤571¡¤7027427.
Received  28th July, 1996.