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Occult hepatitis B virus infection and its clinical implications.

Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Serum HBV level is usually less than 104 copies/mL in these patients. Diagnosis of occult HBV infection requires sensitive HBV-DNA PCR assay. Several possibilities have been hypothesized as the mechanisms of occult HBV infection. These include: (i) mutations of HBV-DNA sequence; (ii) integration of HBV-DNA into host's chromosomes; (iii) infection of peripheral blood mononuclear cells by HBV; (iv) formation of HBV-containing immune complex; (v) altered host immune response; and (vi) interference of HBV by other viruses. The precise prevalence of occult HBV infection remains to be defined. The clinical implications of occult HBV infection involve different clinical aspects. First of all, occult HBV infection harbours potential risk of HBV transmission through blood transfusion, haemodialysis, and organ transplantation. Second, it may serve as the cause of cryptogenic liver disease, contribute to acute exacerbation of chronic hepatitis B, or even fulminant hepatitis. Third, it is associated with development of hepatocellular carcinoma. Fourth, it may affect disease progression and treatment response of chronic hepatitis C. Most of the previous studies utilized retrospective observation without control groups, and lacked direct association of occult HBV infection with specific pathological changes and disease progression. Highly sensitive, quantitative, and functional molecular analyses of HBV, combined with a well-designed prospective clinical assessment will provide the best approach for the future study of occult HBV infection.

Animals↗

Occult infection of old nonfunctioning arteriovenous grafts: a novel cause of erythropoietin resistance and chronic inflammation in hemodialysis patients.

BACKGROUND: Occult infection of old nonfunctioning arteriovenous grafts (AVGs) is frequent among hemodialysis patients. It is a recognized cause of bacteremia and other infectious complications. Additionally, old nonfunctioning AVGs may be harbingers of other noninfectious complications. The aim of this study was to investigate whether occult infection of old nonfunctioning AVGs is a cause of a chronic inflammatory state in hemodialysis patients. METHODS: This study was performed in two phases: In the first phase (study 1), 22 patients with clinically proven occult infection of old nonfunctioning AVG were identified, and data on hemoglobin, weekly erythropoietin dose, and albumin levels were collected retrospectively. Comparisons were made between values obtained pre- and post-AVG resection. In the second phase (study 2), we examined whether the presence of a chronic inflammatory state is associated with occult AVG infection in old nonfunctioning AVGs. Twenty hemodialysis patients were identified with chronic inflammatory state based on erythropoietin dose (units/wk)/hematocrit ratio>470, serum albumin <3.3 g/dL, and CRP>25 mg/L. Among these patients, we found eight with old nonfunctioning AVGs. We then performed indium-labeled white blood cell (WBC) scans on the eight patients to screen for occult infection of old nonfunctioning AVGs. The AVGs with positive indium scan were resected and cultured. Data on hematocrit, erythropoietin dosing, serum albumin, ferritin, and CRP were obtained at 2 months following AVG resection and compared to pre-resection values. RESULTS: In study 1, the 22 patients with occult infection of old nonfunctioning AVG exhibited profound anemia and hypoalbuminemia. Their mean hemoglobin was 9.2 +/- 1.2 g/dL which improved to 11.6 +/- 0.8 g/dL (P < 0.05) 3 months after AVG resection. Their mean serum albumin was 3.3 +/- 0.5 g/dL which improved to 3.8 +/- 0.2 g/dL (P < 0.05) 3 months after AVG resection. Their mean erythropoietin dosages (units/patient/wk) fell from 14,240 +/- 350 to 6,675 +/- 455 (P < 0.05). In study 2, among the 8 patients with chronic inflammatory state and old nonfunctioning AVG, 6 (75%) had positive indium scans and underwent surgical resection that proved bacterial infection. Upon follow-up, the 2-month data showed a remarkable improvement in the following parameters: weekly erythropoietin dose/hematocrit ratio from 622 +/- 137 to 254 +/- 28 (P < 0.05), plasma ferritin values from 690 +/- 126 ng/mL to 247 +/- 42 ng/mL (P < 0.01), and plasma CRP from 56.7 +/- 9.0 to 14.5 +/- 3.8 mg/L (P < 0.01). Serum albumin values also improved from 3.07 +/- 0.08 g/dL to 3.34 +/- 0.14 g/dL (P = 0.13). Percent plasma iron saturation did not appreciably differ from baseline (20.5% +/- 4.4% to 19.8 +/- 1.9%, P = 0.89). CONCLUSIONS: Occult infection of old nonfunctioning AVG is a common cause of erythropoietin resistance and chronic inflammatory state among hemodialysis patients. Resection of old nonfunctioning AVGs with occult infection is associated with resolution of markers of chronic inflammatory state.

Algorithms↗

Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection.

BACKGROUND AND AIMS: Occult hepatitis B virus (HBV) infection is characterized by persistence of HBV DNA into the tissue of hepatitis B surface antigen-negative individuals. The clinical relevance of this peculiar infection is still under debate. In particular, the impact of occult HBV infection in cases of hepatocellular carcinoma (HCC) is uncertain. We investigated the prevalence and molecular status of occult HBV in patients with HCC. METHODS: We tested tumor tissues from 107 patients with HCC and the corresponding nontumor liver tissue from 72 of these patients for HBV DNA. We also examined liver specimens from 192 patients with chronic hepatitis. All cases were hepatitis B surface antigen negative. Covalently closed circular HBV genomes, HBV transcripts, and viral integrated forms were investigated in cases of HCC found positive for occult HBV. RESULTS: Viral DNA was detected in 68 of 107 cases of HCC (63.5%) and in 63 of 192 cases of chronic hepatitis (32.8%) (P < 0.0001; odds ratio, 3.6; 95% confidence interval, 2.2-5.9). The significant association of occult HBV with HCC was irrespective of age, sex, and contemporary hepatitis C virus infection. Both integrated viral DNA and covalently closed circular HBV genomes were detected in patients with occult HBV. Moreover, the presence of free HBV genomes was associated with persistence of viral transcription and replication. CONCLUSIONS: Our findings provide clear evidence that occult HBV is a risk factor for development of HCC and show that the potential mechanisms whereby overt HBV might induce tumor formation are mostly maintained in cases of occult infection.

Aged↗

Transpupillary thermotherapy of occult CNV with no or minimally classic CNV in age-related macular degeneration.

Transpupillary thermotherapy (TTT) has been suggested as a putative treatment for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). This prospective study comprised 66 consecutive patients referred for exudative AMD with predominantly occult subfoveal CNV. Based on fluorescein angiography, there were 38 cases with occult CNV only, and 28 eyes with minimally classic CNV as well. Visual acuity was determined using the logarithmic ETDRS chart. For TTT a diode laser (810nm) with a power of 800 mW or 500-600 mW for a 3.0 mm spot was used (duration 60 sec.). Follow-up included clinical examination with biomicroscopy and fluorescein angiography at 2-3 months and 6 months in all cases. In the entire case material (n = 66), the mean visual acuity was preoperatively 20/125 (47.4 letters) and postoperatively 20/160 (41.8 letters) yielding a decay of 5.6 letters ("one line"). Visual acuity improved in 8 cases (12.1%), deteriorated in 17 (25.8%), and remained stable in 74.2%. In purely occult CNV visual acuity remained stable in 81.6% as compared to 64.3% in occult & minimally classic CNV; the former subgroup lost on the average 3.6 letters, the latter 8.3 letters (close to "two lines") over 6 months. The proportion of eyes losing at least 15 letters was 13.2% in purely occult CNV versus 35.7% in the occult & minimally classic subgroup. In 39 of 66 cases (59.1%) fluorescein leakage regressed to staining only concomitant with absorption of subretinal fluid. Complications associated with deterioration of visual acuity (17 cases) included postoperative hemorrhage, increase of exudation on angiography, and progressive fibrosis. The results indicate that TTT stabilizes visual acuity concomitant with regression of exudation and resorption of subretinal fluid in the majority of cases with predominantly occult CNV Cases with occult CNV only seem to do better than those with minimally classic CNV as well. The safety and complication rate appear to be acceptable. A randomized controlled trial is in progress.

Aged↗

Biological significance of occult micrometastases in histologically negative axillary lymph nodes in breast cancer patients using the recent American Joint Committee on Cancer breast cancer staging system.

The biological significance of occult metastases in axillary lymph nodes of breast cancer patients is controversial. The purpose of the study was to determine the prognostic significance of occult micrometastases using the current American Joint Committee on Cancer (AJCC) staging system in a cohort of women with node-negative breast cancer, of whom 5% received adjuvant systemic therapy and who all had long-term follow-up. We studied a cohort of 214 consecutive histologically node-negative breast cancer patients with a median follow-up of 8 years. Blocks of the axillary lymph nodes were assessed for occult micrometastases by examination of an additional hematoxylin-eosin-stained slide and by immunohistochemical staining using an antibody to low molecular weight keratin. Occult metastases were classified according to the sixth edition of the AJCC cancer staging manual. We examined the prognostic effects of occult micrometastases and other clinicopathologic features on recurrence outside the breast with disease-free interval (DFI) and survival from breast cancer with disease-specific survival (DSS). Cytokeratin-positive tumor cells were identified in the lymph nodes in 29 of 214 cases (14%). Two cases had isolated tumor cells and no cluster larger than 0.2 mm [pN0(i+)], whereas 27 of 214 (13%) had micrometastases (larger than 0.2 mm and <or=2.0 mm] (pN1mi). None of the cases had macrometastases. With median 8 years follow-up, occult micrometastases were not significantly associated with any of the clinicopathologic features. In addition, occult micrometastases were not significantly associated with DFI or DSS and thus were not included in the multivariate analysis. On multivariate analysis, lymphovascular invasion was significantly associated with DFI (p < 0.001) and DSS (p = 0.02), whereas percentage S-phase was significantly associated with DSS (p = 0.02). This study, in which 95% of patients did not receive adjuvant systemic therapy, suggests that breast cancer patients with occult micrometastases in axillary lymph nodes have a similar prognosis to those with no micrometastases. This information is important with regard to the practice of sentinel node biopsy and subsequent axillary node dissection and to the decision to administer adjuvant therapy based on detection of micrometastases in lymph nodes.

Axilla↗

Comparative study between occult hepatitis C virus infection and chronic hepatitis C.

We have recently described the presence of occult hepatitis C virus (HCV) infection (HCV-RNA in liver in the absence of anti-HCV and serum HCV-RNA) in patients with persistently abnormal liver function tests of unknown aetiology. The aim of this study was to compare the characteristics of patients with occult HCV infection vs those of patients with chronic hepatitis C. We compared clinical features of 68 patients with occult HCV infection and 69 untreated chronic HCV patients (anti-HCV and serum HCV-RNA positive), matched for age, gender, duration of abnormal liver function tests and body mass index. Aspartate aminotransferase and alanine aminotransferase were higher (P < 0.001) in chronic HCV, but cholesterol and triglycerides were significantly higher in patients with occult HCV infection (P < 0.001 and P = 0.002). Chronic HCV patients had higher gamma-globulin (P = 0.005), alpha-foetoprotein (P < 0.001) and iron (P < 0.001) levels. Percentage of patients with necroinflammatory activity and fibrosis was higher (P < 0.001) in chronic HCV than in occult HCV infection. Mean percentage of infected hepatocytes was higher (P = 0.001) in chronic HCV (10.1%) than in occult HCV infection (5.3%). This occult HCV infection is a milder disease than chronic HCV, and this could be related to the significantly lower number of infected hepatocytes observed in occult HCV.

Adult↗

Natural history of patients with recurrent chronic hepatitis C virus and occult hepatitis B co-infection after liver transplantation.

It is uncertain whether occult hepatitis B virus co-infection will hasten progressive liver disease in chronic hepatitis C patients after liver transplantation. This study evaluated fibrosis progression and severe fibrosis in 118 consecutive hepatitis B surface antigen-negative patients with virological and histological evidence of recurrent chronic hepatitis C infection co-infected with occult hepatitis B virus after liver transplantation. HBV DNA was detected from serum at the time of recurrent chronic hepatitis C infection by polymerase chain reaction. Each subject underwent a repeat liver biopsy 5 years post-liver transplantation. Occult hepatitis B virus co-infection was present in 41 of the 118 (34.7%) patients. At 5 years post-liver transplantation, 13 of the 41 occult hepatitis B virus co-infected patients compared with 16 of the 77 patients without occult hepatitis B virus co-infection developed fibrosis progression (31.7% vs. 20.8%, respectively, p = 0.39). Eight of 41 the occult hepatitis B virus co-infected patients compared with 13 of the 77 patients without occult hepatitis B virus co-infection had severe fibrosis (19.5% vs. 16.9%, respectively, p = 0.97). In conclusion, occult hepatitis B virus co-infection in patients with recurrent chronic hepatitis C infection was not associated with accelerated fibrosis progression or severe fibrosis after liver transplantation.

Adult↗

Serotype prevalence of occult pneumococcal bacteremia.

OBJECTIVE: The licensure and use of a pneumococcal conjugate vaccine that is immunogenic in children who are younger than 2 years may affect the epidemiology of occult bacteremia. This study was conducted to determine the serotype prevalence of Streptococcus pneumoniae isolates from children with occult bacteremia and to document the proportion that would be covered by the recently licensed heptavalent pneumococcal conjugate vaccine. METHODS: A cohort of 5901 children who were 2 to 24 months of age and had a temperature of >/=39.0 degrees C evaluated with a blood culture at an urban tertiary care children's hospital emergency department was studied to determine the prevalence of S pneumoniae serotypes. Patients were excluded if their immune system was suppressed, they had a diagnosis of a focal infection, they were evaluated by lumbar puncture, they were admitted to the hospital, or they died during initial evaluation. Blood cultures were inoculated into pediatric blood culture bottles and processed using an automated carbon dioxide monitoring system. All pneumococcal isolates were serotyped on the basis of capsular swelling with type-specific antisera (Quellung reaction). RESULTS: The study population consisted of 5901 patients. The overall rate of occult bacteremia was 1.9% (95% confidence interval [CI]: 1.5-2.3). S pneumoniae accounted for 92 of 111 isolates (82.9%; 95% CI: 74.6-89.4) in children with occult bacteremia. Eight pneumococcal serotypes were represented: 6A (2%), 9V (6%), 19F (6%), 18C (8%), 4 (9%), 6B (13%), 23F (15%), and 14 (42%). Serotypes 14, 6B, and 23F accounted for 69.3% (95% CI: 58.6-78.7) of typed isolates. In the cohort, 97.7% (95% CI: 92-99.7) of isolated serotypes are represented in the newly licensed heptavalent pneumococcal conjugate vaccine. The single isolated serotype that would not have been covered by the currently licensed heptavalent pneumococcal conjugate vaccine was 6A. CONCLUSIONS: S pneumoniae accounts for the vast majority of bacterial pathogens in children with occult bacteremia. As indicated by the results of this study, the heptavalent pneumococcal conjugate vaccine may prevent the majority of occult pneumococcal bacteremia episodes. The 2 cases of bacteremia with a serotype that would not have been included in the vaccine both were due to serotype 6A. It has been noted that there is potential nonvaccine serotype and subgroup cross-protection (6A from 6B) afforded to children who are immunized with the heptavalent vaccine. The high potential efficacy of the heptavalent pneumococcal conjugate vaccine for strains that cause occult bacteremia in our population may have a profound effect on the treatment of children with fever without a source. There has been an alarming and rapid emergence of antibiotic-resistant pneumococcal strains. Less pressure to use broad-spectrum antibiotics, which in turn causes further antibiotic resistance, should result. Laboratory testing and hospitalization also should be reduced. The prevalence rates determined by this study may be used as baseline data for comparison of serotype rates of occult pneumococcal bacteremia after widespread use of the heptavalent vaccine.

Bacteremia↗

[The occurrence of occult malignancy in patients less than 50 years of age with venous thromboembolism: which diagnostic screening methods to use?].

Trousseau was the first who describe an association of venous thromboembolism (VTE) with malignancy. The prevalence of occult cancer in patients with secondary VTE is comparable with the prevalence of cancer in general population (2-3%), while the prevalence of occult cancer in patients with idiopathic VTE is 4-10%. It has been demonstrated that the frequency of malignancy is higher in the first 6 to 12 months after diagnosis of VTE. 113 consecutive patients (50 males, 63 females) with first or recurrent VTE before the age 50, mean age (mean age 34.1 at time of VTE diagnosis) were followed retrospectively. Patients with known cancer were excluded for follow-up. The presence of known malignancy and concomitant cancer at the time of diagnosis of VTE and during follow-up (average 29 months) was investigated. The use of routine or extensive screening detection of occult cancer was also assessed. Extensive screening was performed in 61% of patients and compared with 39 % of routine screening. Overall of occult cancer was 1.8 %. The incidence of occult cancer was 1.2% during one year follow-up, and the prevalence at the time of diagnosis of VTE was 0.9%. The authors confirmed the low prevalence of occult cancer in cohort of consecutive young patients with VTE under the age of 50. It seems that only routine investigation with careful history taking, physical examination and simple laboratory tests are sufficient to detect of occult cancer in this age population. The authors recommend the follow-up of these patients, mainly those with idiopathic VTE. Inherited thrombophilia much more prevails in this young thrombophilia patients but risk of occult malignancy exists as well.

Adolescent↗

Occult hepatitis B in Mexican patients with HIV, an analysis using nested polymerase chain reaction.

Hepatitis B virus infection (HBV) with undetectable levels of HBsAg, has been named occult HBV infection and observed in immunosuppressed patients. The aim of this study was to determine the frequency of occult HBV infection in patients with HIV from the West of México, using a combination of serological markers and nPCR. Thirty eight HIV/AIDS patients, 32 men (84.2%) and 6 (5.8%) women, without liver damage related symptoms were studied. HBV coinfection was observed in 10 (26.3%) patients; while only 3 (7.9%) of them were positive to HBsAg. Thus, 7 (18.4%) occult HBV infected patients could be assessed in this population. One (10%) patient with occult HBV infection was positive to anti-HBs, in spite of the reinfection protection attributed to this serological marker. Anti-HBc was detected only in 2 (20%) patients with occult HBV infection. No significant association could be established between occult HBV infection and CD+4 cell count, biochemical, clinical parameters, AIDS stage, or any other risk factor. This study suggest that determination of HBV DNA utilizing highly sensitive techniques, as nPCR, should be performed to detect occult HBV infection, even in the absence of anti-HBc in HIV/ AIDS patients, in order to have a reliable diagnosis, prevent HBV dissemination and acute exacerbation of chronic hepatitis B or even fulminant hepatitis. To our knowledge this is the first study of occult HBV infection in Mexican patients with HIV. However, further studies are necessary in order to determine HBV genotypes and its relationship with evolution and clinical manifestation of the disease.

AIDS Serodiagnosis↗

Accuracy of immunological fecal occult blood testing for colorectal cancer screening.

BACKGROUND: The present study was carried out to assess the accuracy of immunological fecal occult blood testing as a means for colorectal cancer screening. METHODS: Two hundred patients with colorectal cancer and 100 healthy controls served as subjects of the study. A total of 300 subjects were tested by immunological and chemical fecal occult blood tests. As a further test of diagnostic accuracy, mass screening for colorectal cancer using immunological fecal occult blood testing was conducted on 3,365 residents within the Nagano prefecture, and all of the subjects were followed for 1 year through verification from cancer registration of colorectal cancer patients. RESULTS: Sensitivity and specificity of immunological fecal occult blood testing were 67 and 96%, respectively, values significantly higher than those obtained by chemical fecal occult blood testing. Also, sensitivity and specificity in mass screening were 91 and 96%, respectively, indicating an accuracy higher than that achieved by chemical occult testing. CONCLUSION: These findings suggest that immunological fecal occult blood testing is a useful strategy for colorectal cancer screening.

Colorectal Neoplasms↗

Occult gastrointestinal bleeding.

Occult gastrointestinal bleeding commonly manifests as iron deficiency anemia or fecal occult blood. Iron deficiency anemia results from chronic occult gastrointestinal bleeding. Evaluation of asymptomatic patients who have iron deficiency anemia or fecal occult blood usually should begin with investigation of the colon. Colonoscopy is preferred, but flexible sigmoidoscopy plus air contrast barium enema, or computed tomographic colonography may be acceptable in certain circumstances. If evaluation of the colon does not reveal a bleeding site, evaluation of the upper gastrointestinal tract is mandatory in patients who have iron deficiency anemia, and this should be considered in those who have fecal occult blood. In patients who have gastrointestinal symptoms, evaluation of the portion of the gastrointestinal tract from which the symptoms is derived should be pursued initially. The role of small intestinal investigation is controversial, and this probably should be reserved for patients who have iron deficiency anemia and persistent gastrointestinal symptoms or those who fail to respond to appropriate therapy. Celiac sprue should be considered as a potential cause of iron deficiency anemia in all patients. The treatment and prognosis of patients who have iron deficiency anemia or fecal occult blood depends on the gastrointestinal tract abnormality(ies) identified. Those without identifiable bleeding sites generally respond to conservative management and have a favorable prognosis. On the other hand, the outlook is poorer for patients with refractory occult blood loss or those who have vascular ectasias. Both groups of patients are clinically challenging and require a focused and experienced team approach to diagnosis and therapy.

Algorithms↗

Immunochemical fecal occult blood test is not suitable for diagnosis of hemorrhoids.

PURPOSE: This study was conducted to clarify the diagnostic value of an immunochemical fecal occult blood test for hemorrhoids. PATIENTS AND METHODS: In a case-control study, an immunochemical fecal occult blood test with a 2-day method was carried out on 82 subjects with hemorrhoids, on 82 subjects with colorectal cancer, and on 82 healthy subjects. In a population-based cross-sectional study, 29,714 subjects who received an immunochemical occult blood screening with a 2-day method were divided into two groups, according to the results of a questionnaire on hemorrhoids, and the positivity rate of an immunochemical test as well as the predictive value for colorectal cancer were compared in the two groups. Moreover, both an immunochemical occult blood test with a 2-day method and colonoscopy were conducted at the same time on asymptomatic subjects during a medical checkup. RESULTS: In the case-control study, the test was positive in 13.4% subjects with hemorrhoids, in 84.1% subjects with colorectal cancer, and in 4.9% healthy subjects, respectively, showing a significant difference in the detection rate between the two diseases (P < 0.001). In the population screening program, the test was positive in 6.9% subjects with hemorrhoids and in 6.5% subjects without hemorrhoids, and the predictive value was 3.2% in subjects with and without hemorrhoids, respectively, indicating no significant difference in the positivity rate as well as the predictive value between the two groups. Among 232 subjects in a medical checkup, 28 patients with hemorrhoids and 21 patients with colorectal polyp 1 cm or larger were diagnosed by colonoscopy, and the occult blood test was positive in 16.7% patients with hemorrhoids and in 52.4% patients with colorectal polyp, respectively. There was a significant difference in the sensitivity between the two disease groups (P < 0.05). CONCLUSIONS: These findings indicate that the immunochemical fecal occult blood is unsuitable for the diagnosis of the patients with hemorrhoids and an examination of the colorectum is necessary in cases where the occult blood test is positive but there is a sign of hemorrhoids.

Aged↗

Relationship of low-dose aspirin to GI injury and occult bleeding: a pilot study.

BACKGROUND: Low-dose aspirin is commonly used in patients with cardiovascular disease. However, little is known about the effect of aspirin on occult blood loss caused by gastrointestinal injury. Therefore, we studied endoscopic injury and fecal occult blood loss in patients ingesting different quantities of low-dose aspirin. METHODS: Forty healthy volunteers were enrolled in a randomized, double-blind, prospective, pilot endoscopic study. Each volunteer underwent 30 days of treatment with daily aspirin 30 mg, 81 mg, 325 mg, or placebo. Subjects completed fecal occult blood test cards before and at the end of treatment of two types: guaiac impregnated (Hemoccult and Hemoccult SENSA) and immunochemical (HemeSelect and FlexSure OBT). Each volunteer underwent upper endoscopy at baseline and after completing 30 days of study medication. RESULTS: Aspirin did not induce significant injury as determined by endoscopy when compared with placebo. Six of 30 volunteers taking aspirin developed erosions, whereas 1 of 10 subjects on placebo developed a new erosion (p = 0.66). Aspirin (325 mg) was associated with a higher mean symptom score than the lower aspirin dosages and the placebo group (p = 0.12). Only one subject taking aspirin (325 mg) had fecal occult blood on a single HemeSelect card. No subject had a positive fecal occult blood test with Hemoccult II, Hemoccult II SENSA, or FlexSure OBT cards. CONCLUSIONS: Aspirin in dosages commonly used for cardiovascular prophylaxis does not generally cause significant gastric or duodenal mucosal endoscopic lesions. In the absence of frank ulceration, low-dose aspirin does not result in positive fecal occult blood tests. Low-dose aspirin should not interfere with fecal occult blood testing and probably should not be stopped during stool collection.

Adult↗

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.

Adult↗

Many participants in fecal occult blood test population screening have a higher-than-average risk for colorectal cancer.

OBJECTIVES: Population-based colorectal cancer screening by fecal occult blood testing reduces cancer-specific mortality. Current guidelines recommend this strategy for average risk individuals. This study investigated the prevalence of higher-than-average risk characteristics, and rate of prior colonoscopy, in participants in fecal occult blood test screening programs. METHODS: Randomly selected individuals aged 50-74 years in urban Adelaide were offered free fecal occult blood test screening by mail, without prior knowledge of their medical status. Each invitation included a questionnaire to record the prevalence of higher-than-average risk characteristics related to symptoms, family history or comorbidity, as well as prior colonoscopy. The definition of average risk was taken from updated guidelines published by the US Multisociety Task Force on Colorectal Cancer. RESULTS: Of 2538 responses analyzed, 425 individuals had had a colonoscopy within the last 5 years, 106 fulfilled family history criteria for an initial screening colonoscopy, 209 had past polyps and 26 had had colorectal cancer. Eighty-three reported recent rectal bleeding. By current guidelines, 23% of the screened population did not warrant fecal occult blood test, because either prior colonoscopy rendered it unnecessary or particular patient characteristics made colonoscopy a more appropriate initial investigation. CONCLUSIONS: Fecal occult blood test screening programs capture a sizeable number of higher-than-average risk individuals that may warrant colonoscopic rather than fecal occult blood test screening. Other participants have had a recent colonoscopy and probably warrant a delay in screening. Mass population fecal occult blood test-based screening programs need to more effectively target those at average risk and should divert those of higher or lower risk to more individualized assessment.

Aged↗

Effectiveness and economic impact of screening for colorectal cancer by mass fecal occult blood testing.

OBJECTIVES: Fecal occult blood testing has been shown to reduce mortality from colorectal cancer in large randomized, controlled trials conducted in the United States, Denmark, and the United Kingdom, and mathematical simulation modeling found it to be cost-effective relative to other health care services. Before making a concerted effort to implement mass fecal occult blood testing based on this evidence alone, however, we considered it prudent to critically re-evaluate the effectiveness and economic impact of screening in the US population as a whole. METHODS: To assess the effectiveness of screening, we projected published outcomes from each of the three large randomized controlled trials of fecal occult blood testing to the US population, as if each clinical trial had been done in the population as a whole. We then determined the resource costs of detection and treatment that would be associated with the outcomes predicted from each trial. RESULTS: More than 1 million colorectal cancers could be expected to arise over 10 yr in the cohort of US residents eligible to enter a screening program in 1997, and trial outcomes indicate that > or = 60% of these cancers would be fatal. If the 60-67% compliance rate of the population-based randomized controlled trials were achieved, a fecal occult blood testing program would detect 30% of known colorectal cancers and save 100,000 lives over 10 yr. Screening would incur total costs of $3-4 billion over 10 yr, or $2,500 per life-year saved. CONCLUSIONS: Mass fecal occult blood testing is cost-effective, and, although not inexpensive, many would consider the total cost acceptable. Even with a concerted effort to achieve compliance, however, the effectiveness of fecal occult blood testing would be limited to saving the lives of < or = 15% of those who otherwise would die from their cancer in the first 10 yr after beginning mass screening. The limitations of fecal occult blood testing suggest the need to further evaluate the role of endoscopy in screening, and to develop more effective, noninvasive screening tools.

Aged↗

Role of double-contrast barium enema in colorectal cancer screening based on fecal occult blood.

AIMS AND BACKGROUND: Screening for colorectal cancer by fecal occult-blood testing has been shown to be effective in reducing colorectal cancer mortality. Total colonoscopy is the test of choice for the assessment of fecal occult blood-positive subjects. Double-contrast barium enema is commonly employed to study the rest of the colon when colonoscopy is incomplete. The present study evaluated the contribution of double-contrast barium enema in detecting neoplastic lesions of the colon in fecal occult-blood-positive subjects with incomplete colonoscopy. METHODS: In the frame of a screening program for colorectal cancer in the Florence District, a new immunochemical fecal occult-blood test replaced the classic guaiac fecal occult-blood test in 1993. Subjects with a positive fecal occult-blood test were invited to undergo total colonoscopy. Incomplete colonoscopy prompted double-contrast barium enema. Type and rate of neoplastic lesions detected by endoscopy or double-contrast barium enema as single methods or combined were evaluated. RESULTS: A total of 38,829 subjects underwent fecal occult-blood testing in the period 1993-2000. Overall, 1,542 were positive. Assessment was refused by 235 subjects. Out of 1,307 subjects accepting assessment, total colonoscopy was attempted in 1,294: of these, it was not possible in 343 cases, and double-contrast barium enema was advised and performed in 261 subjects. Colorectal cancer was detected in 115 subjects, single or multiple adenomas in 323, hyperplastic polyps in 58, inflammatory, hamartomatous or not histologically confirmed polyps in 38, and other benign non-polypoid findings or no abnormality in 773. There were significant differences between the rates of detected colorectal cancers or adenomas of total and incomplete colonoscopy. There were also significant differences between incomplete colonoscopy and the combination of incomplete colonoscopy and double-contrast barium enema as regards rates of detected colorectal cancer, and between total colonoscopy and the combination of incomplete colonoscopy with double-contrast barium enema as regards rates of detected adenomas. Double-contrast barium enema associated to incomplete colonoscopy was responsible for an increase in detection rates of cancer or adenoma of 2.3/1000 or 3.8/1000, respectively. CONCLUSIONS: Double-contrast barium enema was useful in detecting colorectal cancer beyond the range reached by incomplete colonoscopy, whereas our data confirmed a lower sensitivity of double-contrast barium enema for polyps. The diagnostic contribution observed in the present survey confirms the opportunity of performing double-contrast barium enema as a routine adjunct to incomplete colonoscopy. Nevertheless, in order to maximize the detection rate of adenomas, the rate of total colonoscopy should be kept as high as possible.

Adenoma↗