The following reprint is provided withthe compliments of Cenogenics Corporation,620 Route 520, Morganvile, NJ 07751

(908) 536-6457.

A Clinician's Guide: Tips onFecal Occult Blood Testing

Questions from our PrimaryCare advisors:

. "How effective is routinescreening for fecal occultblood?"

. "Which methods for fecaloccult blood testing aremost accurate?"

. "What steps can be taken to

avoid false negative/positveresults ?"

Robert E. Rakel, MDProfessor and HeadDepartment of Family PracticeUniversity of Iowa

CASE REPORT

A 52-year-old white female wasseen for her annual pelvic examand Pap smear. She had stoppedmenstruating one year previously,had a history of rectal fissures,and recently noted occasionalblood streaking of the stool whichshe attributed to her earlier prob-

lems with rectal fissures. A bariumenema fifteen years previouslywas interpreted as a "spastic co-Ion." There was no history of me-lena and no family history of can-cer.

The physical examination wasunremarkable. The uterus wasslightly enlarged but normal incontour, the cervix was parous,and there was good vaginal sup-port. Rectovaginal examinationwas also normaL. A guaiac test onstool from the rectal exam wastrace positive; the Pap smear wasClass I. The rectal exam revealedno evidence of fissure or hemor-rhoids.· Assessment: Healthy menopau-sal female with a positive fecal

occult blood test.· Plan: Since the stool exami-nation was without dietary prep-aration and there was some ques-tion of blood being transferred onthe glove from the vaginal exam,

three Hemoccult slides (six tests)were given to the patient for ob-taining samples from three suc-cessive bowel movements.

Two of the six tests were tracepositive and the patient wasscheduled for a flexible fiberopticsigmoidoscopy, at which time asingle polyp 1 cm in diameter wasobserved at 10 cm. The exam wasotherwise normaL. The patientwas referred for colonoscopy; thepolyp was removed by snare tech-nique and the base cauterized. Asecond polyp 1.5 cm in diameterwas found in the transverse colonand also removed. The pathologyreport revealed both to be hyper-

plastic polyps. The patient has re-mained asymptomatic on follow-up and repeat fecal occult bloodtests have been negative. -RER

The routine screeningof patients at average risk forcolorectal cancer should beginat age 40 while that of highrisk patients should begin atage 20. As with carcinoma ofthe cervix, there is an induc-tion time of 5 to 10 years be-

fore colorectal cancer be-comes clinically apparent andit is during this time that de-tection provides the greatest

benefit. Since it is believed

that almost all colorectal can-cers develop from adenomas,the objective is to identify andremove the adenomas, espe-cially those larger than 1 cm indiameter.

While there may be grossbleeding with advanced can-cer, the bleeding from earlycancers and adenomas is in-termittent, and often so slight

DECEMBER 1983 . YOUR PATIENT & CANCER

that it cannot be identified vi-sually. However, most bleed-ing colorectal lesions inasymptomatic patients can bedetected by the fecal occultblood test. In fact, this simpIetest wil detect 90% of all colo-rectal lesions that bleed, al-though a single such test is nota very effective method ofscreening because of the inter-mittent quality of the bleeding.

To obtain reliable results,therefore, it is necessary to testsix specimens, two from eachof three consecutive bowelmovements. A positive resultin anyone of the six speci-mens warrants the same de-gree of investigation as if twoor more were positive.

Which Test to UseA variety of methods for fe-

cal occult blood testing arecurrently available using re-agents that interact with the

peroxidase activity of hemo-globin. Thp.se include guaiac,benzidine, ortho-tolidine, andortho-dianisidine, and they dif-fer chiefly in sensitivity. Ben-

zidine is the most sensitive

and as a result has ä high inci-dence of false positives. Thenormal individual loses 2.0 to2.5 ml of blood into the gas-

trointestinal tract daily. Theideal test, then, is one thatturns positive when there isblood loss greater than 5 to 10

ml per day. There are a num-ber of commercial prepara-tions that are currently avail-able (see box on page 38), butour major experience has beenwith Hematest,Q! a hospital testwhich has an ortho-tolidinebase, and HemoccultQ!, whichuses guaiac-impregnated fiter

/'Figure 1: The Hemoccult Test Kit-Each Hemoc-cult card, like most of the other fecal occult bloodtests, has a flap on the front under which there aretwo rectangular cutouts backed by guaiac-impreg-

nated filter paper. Using a wooden applicator, thepatient applies stool specimens to each of the cut-outs.

paper. In our practice, theHemoccult test is the mostpopular and in our experience

has the lowest percentage offalse positive results (1 to 2%),

whereas Hematest, because ofits high sensitivity, has beenreported to have a 27 to 76%false positive rate.3 The Hem-occult begins to turn positive

in the presence of about 2 to 4ml of additional hemoglobinper 100 grams of stool, abouttwice the normal daily fecalblood loss in an adult.

The Hemoccult card for test-ing each stool has a flap on thefront under which there aretwo rectangular cutoutsbacked by guaiac-impregnated

fiter paper. The patient shouldapply specimens from differ-ent portions of the same stoolto each cutout (Figure 1), usingonly thin smears of the stoolspecimen. On the reverse sideof each slide is another flap;when you (or the lab) receivethe specimens from the pa-tient, open the flap and applytwo drops of the developer (astabilized solution of hydrogenperoxide and denatured ethylalcohol) to the fiter paper cov-ering each stool specimen

(Figure 2). This creates aguaiac/peroxidase reactionthat turns the fiter paper bluewithin 30 to 60 seconds if oc-cult blood is present in the

Figure 2: Obtaining the Results-After applyingdifferent portions of the same stool to each cutout,the patient closes the flap and returns the test cardsto you. You then open the flap on the reverse side ofeach slide and apply two drops of developer to thefiter paper covering each stool specimen, as shownhere. The fiter paper wil turn blue within 30 to 60

seconds if occult blood is present.

Figure 3: A Performance-Test Window-The newerHemoccult test packets contain a control window,as do most of the other products. After you developeach stool specimen, apply a single drop of devel-oper between the two white dots within the red rec-

tangle. If the slide is operating correctly, the "posi-tive" dot wil turn blue and the "negative" dot wilremain white.

stool specimen. Any trace ofblue on or at the edge of any ofthe six specimens is a positiveindication of occult blood. Re-

member that proper testingconsists of three cards, one foreach of three consecutive test-ing days or bowel movements(a total of six tests).

Because specimens r 'dY losetheir reactivity and proluce afalse negative result if they be-come dehydrated, they shouldnot be exposed to excessiveheat nor should more thanfour days elapse before the testis performed. If the tests aremailed to your office, theyshould be received and pro-cessed no later than four days

after the third set of speci-

mens has been collected.The newer Hemoccult tests

(and most of the other prod-ucts) also contain a perform-ance-test window that servesas a control. Beneath the flapon the developing side of theslide, there is a red rectanglewith two white dots. After youdevelop each stool specimen,apply a single drop of devel-

oper between the two dots andread the results within 30 sec-

onds (Figure 3). If the slide isoperating correctly, the "posi-tive" dot wil turn blue and the"negative" dot wil remainwhite. If this reaction does notoccur, discard the slide and re-

test the developing solution ona fresh slide; if there is a probelem, it is almost always withthe slide rather than with thedeveloping solution.

Avoiding FalseNegative/Positive Results

There are several points thatshould be noted to avoid falsenegative/positive results in afecal occult blood test:

1. Fecal occult blood testslides remain stable for fouryears, although some bluing ofthe paper can occur from airpollutants. The developer doesnot have to be stored in any

special way and is unlikely todeteriorate.

2. Before obtaining stoolsamples for the fecal occultblood test, patients shouldavoid ingesting high doses ofVitamin C (ascorbic acid) be-cause it interacts with theguaiac to produce a false neg-ative reaction.

3. Women should not betested during or immediatelyfollowing a menstrual period.

4. Foods containing blood orhigh amounts of peroxidaseeaten prior to the test may pro-duce a false positive result. Toincrease the accuracy of thetest, therefore, patients shouldrefrain from eating such foodsas red meat (because of itshemoglobin content), and veg-

etables such as turnips andhorseradish (because of theirhigh peroxidase content) for 48hours prior to obtaining the

specimen. The patient shouldalso avoid ingesting gastric ir-ritants such as aspirin-contain-ing compounds, antibiotics,and anti-inflammatory drugsthat may cause bleeding fromnormal mucosa. Some physi-cians do, however, recom-mend that patients eat fruit,raw vegetables, cereaL, or otherfoods containing roughage inan effort to stimulate lesions tobleed.

5. Bleeding from the uppergastrointestinal tract can re-sult in a negative fecal occult

blood test if stool transit timeis prolonged. As blood trav-erses the gut, it is brokendown and upon reaching thecolon wil have decreased pe-roxidase activity that may notbe sufficient to trigger a posi-

tive test. An increased transittime (slow movement of stoolthrough the bowel) wil thusdecrease the peroxidase activ-ity of hemoglobin and maygive a false negative reaction,depending upon the level ofbleeding in the gut.

It is hoped that new testswil be available within thenext few years that are spe-cific for human hemoglobin,and thus avoid the problem of

false positive tests from in-gested materials.

Additional DiagnosticModalitiesOther diagnostic techniques

that should be used in the pa-tient at risk of colorectal can-

cer include:

· Digital rectal examination· Proctosigmoidoscopy· Barium enema· Colonoscopy

A sigmoidoscopy is recom-mended in all individuals overthe age of 40. However, itshould be done around age 20if there is a family history offamilal polyposis or colorectal

cancer. The frequency with

which sigmoidoscopy shouldbe performed is controversiaL.Some recommend the proce-dure be done annually for twoyears and, if both are negative,then every three to five years;others recommend a sigmoi-doscopy at age 40, and if it isnegative, they feel that sigmoi-doscopy is unnecessary andthat early detection can best beaccomplished by annual fecaloccult blood tests and digitalexaminations.

Approximately one in eightpatients who have a positivefecal occult blood test wilhave a cancer somewhere inthe bowel, most of which are

at an early stage. The majorityof colorectal lesions are usu-

ally found in the mid-descend-ing and sigmoid colon andare detectable by the 65 cmflexible sigmoidoscope. Unfor-tunately, the controversycontinues as to the appropri-ate workup in patients with apositive fecal occult blood testbut a negative digital rectal ex-amination and negative sig-moidoscopy. Most investiga-tors recommend either a dou-ble-contrast barium enema orcolonoscopy, but some recom-mend both of these proce-dures. The double-contrastbarium enema involves the in-stilation of a small quantity of

Manufacturers and Costs of Office Fecal Occult Blood Tests

Approximate CostIProduct Company to MD Per Test . Chemical How to Order

(Specimens from Base *3 stools)

" ColoScreen Helena Laboratories $ .89 Guaiac Call toll free800-231-5663800-392-3126 (Texas)

" Fe-Cult Gamma Diologicals $ .83 Guaiac Call toll free800-231-5655

" Hema-Chek Ames Division, $ .98 Guaiac I Physician andMiles Laboratories hospital

supply distributors

" Hemoccult SmithKline $1.23 Guaiac Call toll freetDiagnostics 800-538-1581

" Occult-Alert BetaMED $2.70 Tetramethyl- Call toll free(vials) Pharmaceuticals benzidine 800-BetaMED

" Stool Blood Test Cenogenics Corp. $ .66 Guaiac Call collect for direct

order or distributorinformation(908) 536-6457

" Detecatest Fleet Approximately Guaiac(otc, direct Pharmaceuticals $5.00 (price toto patient) consumer)

'See text for information on sensitivity and false positive rates.'In California, Alaska and Hawaii, call collect 408-732-6000

barium that is much higher indensity than that used in a sin-gle column enema. A columnof air is then introduced topush the barium through thecolon and the patient is ro-tated so the mucosa is com-pletely coated. Although thisprocedure can detect lesionsas small as 1 cm in diameter,

many studies have shown thatfrom 14 to 30% of cancers arestil missed. One particularly

interesting study was con-ducted by Macrae et aI, inwhich patients received eachof the following; Rigid sig-moidoscopy, flexible sigmoid-oscopy, colonoscopy, and dou-

ble-contrast barium enema.Macrae found that 38 lesionswere missed by barium enema,but only five were missed bycolonoscopy. If colonoscopy isreadily available, you may pre-fer it to barium enema for

screening patients with posi-tive fecal occult blood tests. .

References1. Colorectal cancer: essentials for pri-

mary care physicians. Clinical round-tables. Vali, No. 1-6, April 1982-February1983. Sponsored by the Offce of Continu-ing Medical Education of Memorial Sloan-Kettering Cancer Center.

2. Williams CB, Macrae FA, Bartram CL:A Prospective study of diagnostic meth-ods in adenoma follow-up. Endoscopy14:74-78, 1982.

3. Henry jB: Clinical Diagnosis andManagement by Laboratory Methods.Philadelphia. WB Saunders Company, Six-teenth Edition, 1979.

For additional information or to place anorder, please call collect or write:CENOGENICS CORPORATION

620 Route 520Morganvile, NJ 07751

(908) 536-6457 Telex 136479