Can patients at high risk for significant colorectal neoplasms and having normal quantitative faecal occult blood test postpone elective colonoscopy?

BACKGROUND: Common reasons for elective screening and surveillance colonoscopy, at predetermined intervals, are family or personal history of colorectal cancer (CRC) or advanced adenoma (AAP). Quantified, human haemoglobin (Hb)-specific, immunochemical faecal occult blood tests (I-FOBT) detect bleeding. AIM: To determine I-FOBT sensitivity for CRC or AAP before elective colonoscopy in patients at high-risk of cancer or advanced adenoma. METHODS: Prospective double-blind study of 1000 ambulatory asymptomatic high-risk patients (555 family history of CRC, 445 surveillance for past neoplasm), who prepared three I-FOBTs before elective colonoscopy. I-FOBTs quantified as ngHb/mL of buffer by OC-MICRO instrument and results >or=50 ngHb/mL considered positive. RESULTS: At colonoscopy, eight patients had CRC, 64 others had AAP. Sensitivity for CRC and/or AAP was the highest, 65.3% (95% CI 54.3, 76.3), when any of the three I-FOBTs was >or=50 ngHb (15.4%), with specificity of 87.5% (95% CI 86.4, 90.5) identifying all CRCs and 62% of AAPs. CONCLUSIONS: All cancers or an AAP were detected every third I-FOBT-positive colonoscopy (47/154), so colonoscopy was potentially not needed at this time in 84.6% (846 patients). I-FOBT screening might provide effective supervision of high-risk patients, delaying unnecessary elective colonoscopies. This favourable evaluation needs confirmation and cost-benefit study by risk-group.

Identification of colorectal adenomas by a quantitative immunochemical faecal occult blood screening test depends on adenoma characteristics, development threshold used and number of tests performed.

BACKGROUND: Faecal occult blood tests (FOBT) are faulted by low sensitivity for advanced adenomatous polyps (AAP). Quantified, immunochemical, haemoglobin (Hb)-specific immunochemical FOBT (I-FOBT) measurements are now used for colorectal screening. AIMS: To correlate adenoma characteristics to amount of faecal Hb lost and to evaluate sensitivity and specificity for AAP by faecal Hb development threshold used and number of I-FOBTs collected. METHODS: Three daily I-FOBTs were collected and analysed in 1221 patients scheduled for colonoscopy. Faecal Hb was analysed as ngHb/mL of buffer and the highest result related to colonoscopy findings. RESULTS: In 1204 patients without cancer, colonoscopy identified adenomas in 294, 99 with AAPs. Adenoma patients had elevated faecal Hb increasing with advanced histology, size, pedunculated shape and multiplicity (P < 0.001 for all). At 50 ngHb/mL threshold, sensitivity and specificity for AAPs were 54.5% (95%CI 44.7, 64.7) and 88.1% (95%CI 86.2, 90.1) for three tests. At higher thresholds, sensitivity decreased, but was significantly higher with more samples collected. Conversely, specificity increased at higher thresholds, but decreased with more samples. CONCLUSIONS: Faecal Hb loss from adenomas is significantly associated with size, number and advanced features. Sensitivity and specificity for AAPs are determined by test threshold chosen and number of samples collected; these determine the number of colonoscopies needed for positive tests.

Quantitative colonoscopic evaluation of relative efficiencies of an immunochemical faecal occult blood test and a sensitive guaiac test for detecting significant colorectal neoplasms.

BACKGROUND: The guaiac faecal occult blood test (G-FOBT), HemoccultSENSA, is sensitive for significant neoplasms [colorectal cancer (CRC), advanced adenomatous polyps (AAP)], but faulted by non-specificity for human haemoglobin (Hb). Quantified, Hb- specific, immunochemical faecal occult blood tests (I-FOBT) are now used. AIMS: To (i) compare I-FOBT and G-FOBT efficacy in identifying significant neoplasms and colonoscopy needs for positive tests and (ii) examine number of I-FOBTs needed and test threshold to use for equivalent or better sensitivity than G-FOBT and fewest colonoscopies for positive tests. METHODS: Three daily G-FOBTs and I-FOBTs were collected and analysed in 330 patients scheduled for colonoscopy. RESULTS: Colonoscopy found significant neoplasms in 32 patients, 6 CRC, 26 AAP. G-FOBT, sensitivity and specificity were 53.1% (17 neoplasms) and 59.4%, resulting in 8.1 colonoscopies/neoplasm. One I-FOBT having >or=50 ngHb/mL of buffer provided equivalent sensitivity but 94.0% specificity, resulting in 2.1 colonoscopies/neoplasm. By analysing the higher of two I-FOBTs at 50 ngHb/mL threshold, sensitivity increased to 68.8% (22 neoplasms, P = 0.063), specificity fell to 91.9% (P < 0.001), but still required 2.1 colonoscopies/neoplasm. CONCLUSIONS: In this population, quantified I-FOBT had significantly better specificity than G-FOBT for significant neoplasms, reducing the number of colonoscopies needed/neoplasm detected. Results depend on the number of I-FOBTs performed and the chosen development threshold.

Can quantification of faecal occult blood predetermine the need for colonoscopy in patients at risk for non-syndromic familial colorectal cancer?

BACKGROUND: Patients at risk for non-syndromic (Lynch or polyposis) familial colorectal neoplasia undergo colonoscopic surveillance at intervals determined by clinically ascertained protocols. The quantitative immunochemical faecal occult blood test for human haemoglobin is specific and sensitive for significant colorectal neoplasia (cancer or advanced adenomatous polyp). AIM: To determine immunochemical faecal occult blood test efficacy for identifying significant neoplasia in at-risk patients undergoing elective colonoscopy. METHODS: We retrospectively identified consecutive at-risk patients who provided three immunochemical faecal occult blood tests before colonoscopy. Quantitative haemoglobin analysis was performed by the OC-MICRO automated instrument using the 100 ng Hb/mL threshold to determine positivity. RESULTS: In 252 at-risk patients undergoing colonoscopy; five had cancer, 14 an advanced adenoma and 46 a non-advanced adenoma. The immunochemical faecal occult blood test was positive in 31 patients (12.3%). Sensitivity, specificity, positive and negative predictive values for cancer were: 100%, 90%, 16% and 100%, and for all significant neoplasia: 74%, 93%, 45% and 98%. With 88% fewer colonoscopies, all colorectal cancers and 74% of all significant neoplasia would have been identified by this one-time immunochemical faecal occult blood test screening. CONCLUSIONS: A sensitive, non-invasive, interval screening test might be useful to predetermine the need for colonoscopy in this at-risk population and minimize unnecessary examinations. This favourable retrospective evaluation will be extended to a prospective study.

Seroprevalence of Helicobacter pylori and length of stay in a nursing home.

BACKGROUND: Helicobacter pylori infection appears to be contracted mainly in childhood, and it is associated with disadvantaged socioeconomic conditions, overcrowding, and living in institutions. In this study we determined the seroprevalence of H. pylori among elderly patients (age > or = 70 years) admitted to a major medical center in Israel, and studied the relationship between seroprevalence of H. pylori and the duration of stay in a nursing home prior to the admission. PATIENTS AND METHODS: Whole blood from 182 consecutive patients hospitalized at the Rabin Medical Center was tested for the presence of anti-H. pylori IgG using Helisal Rapid Blood Test kit (Cortecs Diagnostics). Multivariate logistic regression analysis was used to study the relation between H. pylori seropositivity and possible predictive factors such as age, gender and duration of stay in a nursing home. RESULTS: Of the 182 patients included in the study, 80 (44%) were living in nursing homes (NH) and 102 (56%) were living in their own homes (H) prior to admission. Subjects that stayed in nursing homes for more than 15 months were significantly more likely to be seropositive than subjects with a shorter duration of stay (84% and 63% respectively, p = 0.03). Using a multivariate logistic regression analysis on both the NH group and the whole group, seropositivity was found to be significantly associated with duration of stay in a nursing home (p = 0.03 and p = 0.01 respectively). Seropositivity was not associated with age in either group. CONCLUSIONS: Living in a nursing home is associated with increased risk for H. pylori infection in the elderly. There is a strong correlation between the duration of stay in a nursing home and the prevalence of H. pylori infection.

A distance to the galaxy NGC4258 from observations of Cepheid variable stars.

Cepheid variable stars pulsate in a way that is correlated with their intrinsic luminosity, making them useful as 'standard candles' for determining distances to galaxies; the potential systematic uncertainties in the resulting distances have been estimated to be only 8-10%. They have played a crucial role in establishing the extragalactic distance scale and hence the value of the Hubble constant. Here we report observations of Cepheids in the nearby galaxy NGC4258; the distance calculated from the Cepheids is 8.1 +/- 0.4 Mpc, where the uncertainty does not include possible systematic errors. There is an independently determined geometric distance to this galaxy of 7.2 +/- 0.5 Mpc, based on the observed proper motions of water masers orbiting the central black hole; the distances differ by 1.3sigma. If the maser-based distance is adopted and the Cepheid distance scale revised accordingly, the derived value of the Hubble constant would increase by 12 +/- 9%, while the expansion age of the Universe would decrease by the same amount.

A comparison of new rapid urease tests for detection of Helicobacter pylori: test characteristics and factors affecting positivity and time to positivity.

We assessed two new rapid urease tests, the Helicobacter Urease Test (HUT, Astra, Sweden) and the Polish test, for accuracy, reaction time, and the effect of biopsy site and bacterial density on test characteristics and time to positivity. A prospective study was conducted in two groups of patients: 64 consecutive patients undergoing upper endoscopy for dyspepsia and 61 consecutive patients with duodenal ulcer on upper endoscopy. In the first group, test accuracy, time to positivity, and possible associations with biopsy site and bacterial density were assessed between the tests. In the second group, the two new tests were compared with the CLOtest for time to positivity and effect of bacterial density on test outcome. The Polish and HUT test had similar specificities (97%), but the Polish test was more sensitive (90.3% vs. 80.7%). The Polish test was positive within 10 minutes in 55% of the positive patients compared with 10% for the HUT test. There was no association between bacterial density (by histologic count) and reaction time in either test or in the CLOtest in the second group. The Polish test was more accurate and had a quicker time interval to positivity than the HUT. There was no significant association between bacterial density and reaction time in any of the urease tests assessed, and the biopsy site did not affect test accuracy in the HUT test.

Comparison of two bowel preparations for colonoscopy: sodium picosulphate with magnesium citrate versus sulphate-free polyethylene glycol lavage solution.

OBJECTIVES: Adequate preparation of the bowel is essential for accurate colonoscopic examination. We compared colonic preparation with sodium picosulphate plus magnesium citrate (SPS-Mg) with sulphate-free polyethylene glycol electrolyte lavage (PEG-EL) solution before colonoscopy, for quality of bowel cleansing, patient discomfort, and side effects. METHODS: Sixty-eight consecutive patients were randomly assigned to receive either 3 sachets of SPS-Mg (16.5 g each) (n = 39) or 3 L of PEG-EL (n = 29) on the day before colonoscopy. Shortly before the procedure each patient was interviewed to determine the degree of discomfort (1 = none or mild, 2 = moderate, 3 = severe) and side effects. The quality of bowel cleansing was graded by a gastroenterologist who was unaware of the method of preparation (from 1 = poor to 4 = excellent). RESULTS: Of the 29 PEG-EL patients, four (14%) did not complete the preparation because of side effects. The degree of discomfort was significantly greater with PEG-EL (mean score, 2.3 +/- 0.7) than with SPS-Mg (mean score, 1.4 +/- 0.5; p < 0.01). Nausea and vomiting were significantly more common in the PEG-EL group (38% vs 13%; p < 0.05). Using intention-to-treat analysis, bowel cleansing proved to be significantly better with SPS-Mg than with PEG-EL (mean score +/- SD, 3.05 +/- 0.9 and 2.57 +/- 1.0, respectively; p = 0.036). CONCLUSIONS: Colonic preparation with SPS-Mg is better tolerated, associated with significantly fewer side effects, and results in higher quality bowel cleansing than preparation with PEG-EL.

Budesonide versus prednisone in the treatment of active Crohn's disease. The Israeli Budesonide Study Group.

BACKGROUND & AIMS: Budesonide (BUD) is a potent steroid that undergoes extensive first-pass metabolism. BUD incorporated in a pH-dependent formulation has been proposed as an alternative treatment for Crohn's disease (CD). The aim of this study was to compare the efficacy and safety of BUD and prednisone (PRED) in the treatment of active CD involving the terminal ileum and/or the colon. METHODS: Patients with mild to moderately active CD were included in a randomized, double-blind, double-dummy controlled trial. Patients received either 9 mg BUD once daily for 8 weeks or 40 mg PRED once daily for the first 2 weeks tapered gradually to 5 mg/day by the end of the study. Disease activity, quality of life, and laboratory parameters were recorded. RESULTS: One hundred patients received BUD, and 101 patients received PRED. By intention-to-treat analysis, treatment efficacy defined as Crohn's Disease Activity Index of <150 at completion was 51% and 52.5% for the BUD and PRED groups, respectively. Twice as many responded to treatment with no side effects in the BUD compared with the PRED group (30% vs. 14%) (P = 0.006). Most of the decrease in CDAI scores occurred during the first 2 weeks. CONCLUSIONS: BUD is as effective as PRED in the treatment of CD involving the terminal ileum and right colon. BUD has significantly fewer steroid-related adverse reactions.

Cytomegalovirus infection associated with ulcerative colitis in immunocompetent individuals.

Gastrointestinal infection with cytomegalovirus (CMV) is usually found in immunocompromised patients and rarely affects immunocompetent subjects. We describe two immunocompetent patients who had primary CMV infection, and in both the disease was associated with ulcerative colitis. Both patients recovered from the CMV infection spontaneously.

Carbamazepine neurotoxic reaction after administration of diltiazem.

A patient with epilepsy controlled by carbamazepine developed a carbamazepine neurotoxic reaction after being given an increased dosage of diltiazem hydrochloride as adjunctive therapy. Abrupt withdrawal of diltiazem reduced the circulating carbamazepine concentration and resulted in an epileptic attack. Awareness of the interaction between diltiazem and carbamazepine and careful monitoring of carbamazepine blood levels is recommended to prevent the dangerous neurotoxic effect associated with this combination.

The role of atrial natriuretic peptide in natriuresis of fasting.

OBJECTIVE: To examine the relation between plasma atrial natriuretic peptide (ANP) and the natriuresis of fasting. DESIGN: ANP, aldosterone and renin were examined during natriuresis of fasting in 25 obese essential hypertensive patients and nine overweight normotensive subjects placed on a supervised 500-KCal diet composed of 50% carbohydrates, 30% fat and 20% protein, and unlimited salt. Twenty-four-hour urinary electrolytes were measured on days 0, 4, 7 and 10 of the diet. RESULTS: Urinary sodium concentration nearly doubled in the patients on day 4, and increased 1.4-fold in the normotensive controls. Plasma ANP rose nearly threefold in the hypertensives on day 4 and nearly doubled in the normotensives. Patients and controls showed similar patterns of natriuresis and ANP secretion during the diet. CONCLUSIONS: We conclude that there is a clear association between ANP levels and natriuresis of fasting.