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A study of laboratory based faecal occult blood testing in Melbourne, Australia. The Faecal Occult Blood Testing Study Group.

Faecal occult blood tests (FOBT) are widely used in clinical practice and are under increasing scrutiny as a tool for colorectal cancer screening. However, there is little information regarding the quality of testing performed in pathology laboratories. Therefore, we asked 13 pathology laboratories in Melbourne, Australia, to test coded contrived faecal samples prepared from a composite stool specimen which had been spiked to various concentrations of haemoglobin. The samples were provided to the laboratories in two forms: (i) on/in the sample collection device appropriate for the faecal occult blood test they normally used; and (ii) as a moist faecal sample. Some variation in threshold analytical sensitivity between laboratories for the same FOBT was observed for Hemoccult SENSA, ColoRectal, Hematest, MonoHaem and Hemolex suggesting that, at least for those tests, technician training could be improved. Two tests, Hematest and an in-house FOBT did not perform as well as the other FOBT. When samples were sent in moist form, Hemoccult SENSA (P = 0.0002), ColoRectal (P = 0.02) and MonoHaem (P = 0.04) had significantly lower overall positivity rates; for Hemolex the decrease was not significant (P = 0.3). The lower positivity rate with moist samples is important, given that 11 of the 13 laboratories in the study stated that they receive at least some samples in moist form. Thus, technician training and laboratory procedure need to be reviewed to maximize the benefits of faecal occult blood testing in clinical practice, especially with its expanding role in colorectal cancer screening.

Australia

Human occult loiasis: field evaluation of a nested polymerase chain reaction assay for the detection of occult infection.

A nested polymerase chain reaction (nested PCR) assay, targeted on the repeat 3 region (15r3) of the gene coding for a Loa loa 15 kD polyprotein, was developed to detect L. loa infection. The assay has a sensitivity of 95% and is 100% specific with regard to sympatric filarial parasites: Mansonella perstans, Onchocerca volvulus and Wuchereria bancrofti. In this field study in a mixed filarial (L. loa and M. perstans) endemic region of Gabon, 157 L. loa amicrofilaraemic blood samples (AMF; diagnosed by leucoconcentration followed by standard microscopic examination) from the residents from four villages were screened by the 15r3-nested PCR assay. The assay detected 106 occult infected subjects among the 157 AMF individuals (68%), including 59 of 87 adults (68%) and 47 of 70 children (67%). In each village the prevalence of occult infection was, respectively, 38%, 52%, 79% and 80% for Moyabi, Djoutou, N'djokaye and Okoumbi. The annual transmission potential (ATP) of loiasis has been estimated to be 250 infective larvae (L 3) per man per year for Moyabi and Djoutou, 1800 for N'djokaye and 433000 L3/man/year for Okoumbi. This implies a correlation between occult infection of loiasis and the intensity of transmission. By contrast, the prevalence of L. loa microfilariae was 21% for Okoumbi, 22%, for N'djokaye and 19% for Djoutou and Moyabi. These results show that the prevalence of loiasis in this region of Gabon is higher than previously described by standard microscopic examination and that the application of this assay will be significant in the development of control strategies for loiasis.

Adolescent

Fecal occult blood tests in occult gastrointestinal bleeding.

Occult gastrointestinal bleeding is diagnosed by using one of the commercially available fecal occult blood tests (FOBTs). Guaiac-based slide tests are most frequently used, although the more specific immunochemical methods are promising. The guaiac tests are inexpensive, nonspecific, qualitative measures of stool blood, and their use requires dietary and drug restrictions. Clinicians need to be aware of the causes of false-positive and false-negative test results. Although specific for the presence of human blood, immunochemical tests are more expensive and tend to react also to physiological quantities of blood in fecal specimens. Whichever test is chosen, it must be processed and read correctly. Annual FOBT screening for colorectal cancer, combined with periodic flexible sigmoidoscopy, is a cost-effective method of detecting early, curable colorectal cancer.

Adenocarcinoma

Circadian breast skin temperature rhythms: overt and occult benign and occult primary malignant breast disease.

Circadian variations of breast surface temperature have been measured in patients with overt or occult benign breast disease, or in those with occult breast cancer. Subjects were studied in a hospital ward environment well-controlled with respect to ambient temperature. Using manual techniques temperatures were recorded half-hourly for 96 hr from replicate sensors placed on quadrants of the left and right breasts inclusive of tumour areas and similar sites on the contralateral breast. Application of time series analysis failed to consistently demonstrate differences in values for the rhythm parameters for the tumour area and contralateral site. It was apparent, however, that the tumour area was generally associated with a reduced initial variance of the series in addition to a reduced percentage variance explained by a time series model with two rhythmic components when compared to the control site. These data suggest that efforts to identify early breast disease from signals of breast temperature should, at least, be directed to studies of temperature variance.

Adult

Analysis of clinically occult and mammographically occult breast tumors.

Findings by xeromammography and clinical examination were compared in 16,000 self-selected women aged 45-64 who participated in a voluntary breast cancer screening program. A total of 138 malignancies were detected: 108 (78%) by mammography and 78 (57%) by clinical examination. Mammography was more effective for large breasts, fatty breasts, and in older women. Conversely, clinical examination was more effective for small breasts, dense breasts, and retroareolar lesions. Clinical detection decreased strikingly for lesions with negative lymph nodes, in situ and microinvasive lesions, deeply situated lesions, and lesions where microcalcifications were the sole mammographic finding.

Age Factors

Occult choroidal neovascularization. Influence on visual outcome in patients with age-related macular degeneration. Macular Photocoagulation Study Group.

OBJECTIVE: To determine whether the presence of occult choroidal neovascularization (CNV) influenced the anatomic and visual acuity outcomes in a randomized clinical trial of krypton red laser photocoagulation to treat juxtafoveal neovascular lesions in age-related macular degeneration. DESIGN, SETTING, AND PATIENTS: The fluorescein angiograms obtained at the baseline examination at tertiary retinal referral centers between April 1, 1981, and December 31, 1987, as part of the Macular Photocoagulation Study (MPS) Age-Related Macular Degeneration Study-Krypton Laser were evaluated retrospectively at the MPS Fundus Photograph Reading Center by two senior readers independently (with open adjudication of any differences) from 1992 to 1994. Criteria for classifying classic and occult CNV by the MPS Group were established in 1989, 2 years after the last patient had been assigned randomly to treatment or observation in the krypton laser study. MAIN OUTCOME MEASURES: Treatment coverage of classic and occult CNV, persistent CNV, recurrent CNV, and visual acuity from scheduled follow-up examinations for up to 5 years were analyzed for the absence or presence of occult CNV at baseline. RESULTS: The number of eyes with classic CNV but not occult CNV, classic and occult CNV, and occult CNV but no classic CNV were almost identical for the eyes assigned randomly to treatment or observation. Classic CNV almost always was covered completely with intense laser treatment; nevertheless, recurrent CNV developed in more than half of these eyes within 1 year after initial laser treatment. In contrast, in more than half of the eyes with occult CNV, more than 50% of the occult CNV was not covered with heavy laser treatment. Laser treatment was clearly beneficial for eyes with classic CNV but no occult CNV and almost equivalent to no treatment for eyes with classic and occult CNV. The few eyes with occult CNV but no classic CNV precluded conclusions about the value of treatment in this subgroup. CONCLUSIONS: These results strengthen previous reports that laser treatment is beneficial for eyes with juxtafoveal choroidal neovascular lesions when classic CNV is present, even though CNV often recurs. Treatment of classic CNV alone in eyes with classic and occult CNV was not beneficial in this study. Distinguishing classic CNV from occult CNV can aid in the selection of patients who will benefit most from laser treatment.

Adult

Occult bacteremia with group B streptococci in an outpatient setting.

OBJECTIVES: We undertook this study to determine the relative frequency of occult bacteremia with group B streptococci (GBS) and to define the clinical features of infants with occult bacteremia attributable to GBS at the time of initial clinical contact. DESIGN: The logs of the microbiology laboratory were reviewed for blood and cerebrospinal fluid isolates of GBS from 1982 to 1996. Records of patients identified with GBS were abstracted. Patients were classified as having occult bacteremia if GBS were isolated from their blood and they seemed nontoxic and had no apparent clinical or laboratory evidence of focal infection. All other patients were diagnosed with sepsis, meningitis, or nonmeningeal foci. RESULTS: We reviewed the medical records of 147 children with GBS and identified 108 outpatients, including 47 (44%) with occult bacteremia, 42 (39%) with meningitis, 11 (10%) with nonmeningeal foci, and 8 (7%) with sepsis. Compared with patients with sepsis or focal infections, those with occult bacteremia were older (61.1 vs 39.1 days) and had slightly, although not significantly, higher white blood cell (WBC) counts (13 280 +/- 6854 vs 10 688 +/- 8574), but similar degrees of fever. Among the 47 patients with occult bacteremia, none died, as compared with 2 of 61 with serious infections, and fewer had neurologic sequelae (0/47 vs 11/61). Patients with occult bacteremia >90 days of age generally had temperatures >39 degreesC (9/11, mean 39.3 degreesC) and WBC counts >15 000/mm3 (7/10, mean 19 070/mm3), both of which differed significantly compared with those who were <90 days of age. Thirty of the 47 patients with occult bacteremia received intravenous antibiotics and recovered. One of 8 patients discharged without antibiotics and none of 8 with antibiotics developed a focal complication; 1 discharged patient was lost to follow-up. CONCLUSIONS: Almost one-half of the children with GBS disease beyond the immediate neonatal period had occult bacteremia. Among 8 untreated patients with bacteremia, 1 developed a focal complication. Although the small proportion of children with GBS occult bacteremia who were >90 days of age usually had the risk factors of temperature >39 degrees C and WBC >15 000/mm3, as seen with occult bacteremia attributable to other organisms, the majority of the patients who were younger did not have a characteristic clinical syndrome. Prevention of sequelae in these young infants will require a low threshold for diagnosis and treatment.

Ambulatory Care

Screening for colorectal cancer with fecal occult blood testing and sigmoidoscopy.

BACKGROUND: The high incidence of and mortality from colorectal cancer (160,000 new cases and 60,000 deaths in the United States each year) are compelling public health concerns. Following the evolution of effective surgery for this disease since the 1960s, the focus has been on improving methods of detection and integrating them into effective screening programs. PURPOSE: This was the first study to evaluate the effectiveness, in a setting of comprehensive medical examinations, of using the fecal occult blood test in conjunction with sigmoidoscopy, rather than sigmoidoscopy alone, to screen for colorectal cancer. Our end points were extent of compliance with fecal occult blood test and sigmoidoscopy, numbers of cancers detected, and mortality rate. METHODS: From 1975 through 1979, a total of 21,756 patients (aged 40 and older) who presented at the Preventive Medicine Institute-Strang Clinic for routine medical examinations were enrolled by calendar period into study and control groups. Study patients were offered annually both rigid sigmoidoscopy examinations and fecal occult blood tests requiring two stool specimens per day for 3 days, while control patients were offered only annual sigmoidoscopy. The majority of fecal occult blood test cards were not rehydrated before assay. Patients with positive tests were referred for double-contrast barium enema and colonoscopy. Two distinct trials were carried out. Trial I was primarily a demonstration of feasibility of using the fecal occult blood test as a supplemental screening method. Of the 9277 participants, 7168 (77%) were assigned to the study group and offered the fecal occult blood test. In trial II, approximately half of the 12,479 patients were assigned to each group. Patients in both trials had follow-up through 1984. RESULTS: Compliance with the fecal occult blood test was initially high in both trials, but diminished such that only 56% of study patients in trial I and 20% of those in trial II returned for second tests. On the initial (prevalence) screen, a substantial number of early-stage cancers were detected by the fecal occult blood test, primarily in trial II. In trial II, survival probability was significantly greater (P < .001) in the study group than in the controls (70% versus 48%), and colorectal cancer mortality was lower (0.36 versus 0.63) with borderline significance (P = .053, one-sided). CONCLUSIONS AND IMPLICATIONS: The screening of average-risk individuals (aged 50 and older) for colorectal cancer through use of the fecal occult blood test in conjunction with sigmoidoscopy can increase the likelihood of early detection of this disease. This practice, coupled with prompt diagnostic work-up following positive tests, will result in treatment of earlier stage cancers and increased survival after treatment.

Aged

A case-control study to evaluate efficacy of screening for faecal occult blood.

OBJECTIVES: Faecal occult blood testing is routinely used for early detection of colorectal cancer, but evidence of its efficacy in preventing death from colorectal cancer is limited. A case-control study was carried out to evaluate whether screening for faecal occult blood is associated with a reduced risk of fatal colorectal cancer. SETTING: A health maintenance organisation in western Washington State, which has offered its members faecal occult blood testing every two years since 1983. METHODS: Cases (n = 248) were members of the health maintenance organisation who died from colorectal cancer between 1986 and 1991. For each case, two control subjects, who did not die from colorectal cancer and who were similar to each case in age, gender, and year of enrollment at the health maintenance organisation, were randomly selected from the membership list of the year in which the case was diagnosed (n = 496). Information about episodes of faecal occult blood testing (including the location and reason for the test, and the evaluation of positive tests) and potential confounders was obtained from medical records. RESULTS: Cases were less likely than controls to have ever been screened (odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.5 to 1.0), consistent with a beneficial impact of screening. There was little difference, however, for screening that had taken place within a three year period before diagnosis (OR = 0.9, 95% CI 0.6 to 1.2), the maximum interval during which most tumours ought to have been detectable by faecal occult blood testing. A reduction in risk was seen for home testing but not for office testing, and in individuals aged less than 75 but not in those aged 75 or older. Although most of the 21 controls with a positive faecal occult blood test underwent some additional testing, only five (24%) were evaluated with colonoscopy or air contrast barium enema. CONCLUSIONS: While there can be uncertainty as to whether specific faecal occult blood tests were performed as screening or diagnostic tests, those performed at home and in younger persons may be relatively less likely to be diagnostic tests that were misclassified as screening. Thus the modest reduced risk associated with faecal occult blood testing in these settings/persons may reflect genuine benefit. However, the presence of a reduced risk associated with a screening faecal occult blood test received in the past, well before a tumour or polyp might bleed enough to allow detection, is compatible with uncontrolled confounding. Interpretation is further complicated by the fact that a number of individuals in the study group who had positive test results underwent limited or no diagnostic testing. Thus our results should be interpreted with considerable caution.

Age Factors

Digital indocyanine-green videoangiography of occult choroidal neovascularization.

BACKGROUND: Occult choroidal neovascularization (CNV) secondary to age-related macular degeneration occurs in the majority of patients with exudative maculopathy. Since occult CNV cannot be imaged clearly by fluorescein angiography, this condition is untreatable. The authors performed digital indocyanine-green videoangiography (ICG-V) on 657 consecutive eyes with occult CNV by fluorescein angiography to determine if this technique could be useful in enhancing the imaging of the neovascularization, and thus increasing treatment eligibility. MATERIALS AND METHODS: Six hundred fifty-seven consecutive eyes with occult CNV were studied. The fluorescein and ICG angiograms were compared, and the percentage of patients potentially eligible for laser therapy based on ICG findings was calculated. RESULTS: Of 413 eyes with occult CNV without pigment epithelial detachments, focal areas of neovascularization were noted in 89 (22%). Overall, 142 (34.3%) eyes had lesions that were potentially treatable by laser photocoagulation based on additional information provided by ICG-V. Of the 235 eyes with occult CNV and vascularized pigment epithelial detachments, 98 (42%) were eligible for laser therapy based on ICG-V findings. The authors calculate that ICG-V enhances the treatment eligibility by approximately one third. CONCLUSIONS: In diagnosing occult CNV, ICG-V is an important adjunctive technique to fluorescein angiography. This technique is especially useful in delineating occult neovascularization, neovascularization with overlying subretinal hemorrhage or serosanguineous fluid, and neovascularization associated with pigment epithelial detachments. The authors currently suggest that ICG-V be performed in eyes in which well-delineated neovascularization cannot be identified by fluorescein angiography. Based on their preliminary study, it can be expected that one in three patients with occult CNV potentially will be eligible for laser photocoagulation based on ICG-V. Further studies are necessary to confirm these findings.

Aged

Occult intracranial injury in infants.

STUDY OBJECTIVES: The objectives of this study were as follows: (1) to determine whether clinical symptoms and signs of brain injury are sensitive indicators of intracranial injury (ICI) in infants admitted with head trauma, (2) to describe the clinical characteristics of infants who have ICI in the absence of symptoms and signs of brain injury, and (3) to determine the clinical significance of those ICIs diagnosed in asymptomatic infants. METHODS: We conducted a retrospective analysis of all infants younger than 2 years of age admitted to a tertiary care pediatric hospital with acute ICI during a 6(1/2)-year period. Infants were considered symptomatic if they had loss of consciousness, history of behavior change, seizures, vomiting, bulging fontanel, retinal hemorrhages, abnormal neurologic examination, depressed mental status, or irritability. All others were considered to have occult ICI. RESULTS: Of 101 infants studied, 19 (19%; 95% confidence interval [CI] 12%, 28%) had occult ICI. Fourteen of 52 (27%) infants younger than 6 months of age had occult ICI, compared with 5 of 34 (15%) infants 6 months to 1 year, and none of 15 (0%) infants older than 1 year. Eighteen (95%) infants with occult ICI had scalp contusion or hematoma, and 18 (95%) had skull fracture. Nine (47%) infants with occult ICI received therapy for the ICI. No infants with occult ICI (0%) (95% CI 0, 14%) required surgery or medical management for increased intracranial pressure. Only 1 subject (5%) with occult ICI had any late symptoms or complications: a brief, self-limited convulsion. CONCLUSION: We found that 19 of 101 ICIs in infants admitted with head trauma were clinically occult. All 19 occult ICIs occurred in infants younger than 12 months of age, and 18 of 19 had skull fractures. None experienced serious neurologic deterioration or required surgical intervention. Physicians cannot depend on the absence of clinical signs of brain injury to exclude ICI in infants younger than 1 year of age.

Acute Disease