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

Aliment Pharmacol Ther 31 , 523–533

Summary

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 ≥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 ≥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.     

Colonoscopy‐controlled intra‐individual comparisons to screen relevant neoplasia: faecal immunochemical test vs. guaiac‐based faecal occult blood test

Aliment Pharmacol Ther 31 , 432–439

Summary

Background Guaiac‐based faecal occult blood tests (g‐FOBTs) are most commonly used in colorectal cancer (CRC) screening programmes. Faecal immunochemical tests (FITs) are thought to be superior. Aim To compare performance of a g‐FOBT and a quantitative FIT for detection of CRCs and advanced adenomas in a colonoscopy‐controlled population. Methods We assessed sensitivity and specificity of both FIT (OC‐sensor) and g‐FOBT (Hemoccult‐II) prior to patients’ scheduled colonoscopies. Results Of the 62 invasive cancers detected in 1821 individuals, g‐FOBT was positive in 46 and FIT in 54 (74.2% vs. 87.1%, P = 0.02). Among 194 patients with advanced adenomas, g‐FOBT was positive in 35 and FIT in 69 (18.0% vs. 35.6%, P < 0.001). Sensitivity for screen relevant tumours (197 advanced adenomas and 28 stage I or II cancers) was 23.0% for g‐FOBT and 40.5% for FIT (P < 0.001). Specificity of g‐FOBT compared to FIT for the detection of cancer was 95.7% vs. 91.0%, P < 0.001) and for advanced adenomas (97.4% vs. 94.2%, P < 0.001). Conclusions Faecal immunochemical test is more sensitive for CRC and advanced adenomas. Sensitivity of FIT for screen relevant tumours, early‐stage cancers and advanced adenomas, is significantly higher. Specificity of g‐FOBT is higher compared with FIT.     

Comparative evaluation of a new bedside faecal occult blood test in a prospective multicentre study

BACKGROUND: Faecal occult blood testing is an established method of colorectal neoplasia screening. Guaiac-based tests are limited by poor patient compliance, low sensitivity, specificity and positive predictive value. Newer immunochemical-based tests, accurate but tedious, require a well-established laboratory set up. There is need for simpler immunochemical tests that can be performed at the out-patient clinic. AIM: To compare the performance characteristics of a new bedside immunological test strip device with a sensitive Guaiac-based and established immunochemical test for detection of faecal occult blood in patients undergoing colonoscopy. METHODS: A total of 389 consecutive patients from four centres who were referred for colonoscopy also provided the stool samples for detection of occult blood without dietary restrictions. Stool tests performed were (i) Guaiac-based, (ii) immunochemical enzyme-linked immunosorbent assay and (iii) bedside immunochemical strip test. RESULTS: At the optimal threshold level, the sensitivity and specificity of the beside immunochemical strip test for detection of significant colorectal neoplasia (adenomas >1.0 cm and carcinomas) were 60% and 95%, respectively. CONCLUSIONS: This bedside immunochemical strip test proved to be a simple, convenient, non-cumbersome and accurate tool with similar performance characteristics for detection of any bleeding lesion including colorectal neoplasia when compared with an established immunochemical faecal occult blood test.     

A quantitative immunochemical faecal occult blood test is more efficient for detecting significant colorectal neoplasia than a sensitive guaiac test

BACKGROUND: The sensitive guaiac faecal occult blood test, Haemoccult SENSA (HOS; Beckman Coulter, Fullerton, CA, USA), is our standard screening test for significant colorectal neoplasia. We evaluated an automatically-developed, quantified human haemoglobin immunochemical faecal test, OC-MICRO (Eiken Chemical Co., Tokyo, Japan), to improve test specificity and so reduce the colonoscopy burden. AIM: To compare guaiac faecal occult blood test and immunochemical faecal test diagnostic efficacy and costs for identifying significant neoplasia. METHODS: Colonoscopies were performed on patients who prepared three daily guaiac faecal occult blood tests with or without immunochemical faecal tests. RESULTS: Total colonoscopy was performed on 151 subjects who prepared both guaiac and immunochemical faecal tests (group 1) and the positive predictive values (PPV) were also compared to those of 162 subjects undergoing colonoscopy for positive guaiac faecal occult blood tests (group 2). In group 1, comparative sensitivity, specificity, and PPVs for significant neoplasia with guaiac faecal occult blood test were 75%, 34%, and 12% (PPV, 18% for group 2) and with immunochemical faecal test were 75%, 94% and 60% (P < 0.01 for specificity). The number of colonoscopy examinations needed to detect a significant neoplasm because of positive faecal occult blood tests was six to eight with HOS and two with OC-MICRO at 21-31% the cost of evaluating a positive guaiac faecal occult blood test. CONCLUSION: An immunochemical faecal test maintains the high sensitivity of guaiac faecal occult blood test, but significantly reduces the colonoscopy burden and screening costs.     

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.     

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.     

As tests evolve and costs of cancer care rise: reappraising stool-based screening for colorectal neoplasia

Background Colorectal cancer screening and treatment are rapidly evolving. Aims To reappraise stool‐based colorectal cancer screening in light of changing test performance characteristics, lower test cost and increasing colorectal cancer care costs. Methods Using a Markov model, we compared faecal DNA testing every 3 years, annual faecal occult blood testing or immunochemical testing, and colonoscopy every 10 years. Results In the base case, faecal occult blood testing and faecal immunochemical testing gained life‐years/person and cost less than no screening. Faecal DNA testing version 1.1 at $300 (the current PreGen Plus test) gained 5323 life‐years/100 000 persons at $16 900/life‐year gained and faecal DNA testing version 2 (enhanced test) gained 5795 life‐years/100 000 persons at $15 700/life‐year gained vs. no screening. In the base case and most sensitivity analyses, faecal occult blood testing and faecal immunochemical testing were preferred to faecal DNA testing. Faecal DNA testing version 2 cost $100 000/life‐year gained vs. faecal immunochemical testing when per‐cycle adherence with faecal immunochemical testing was 22%. Faecal immunochemical testing with excellent adherence was superior to colonoscopy every 10 years. Conclusions As novel biological therapies increase colorectal cancer treatment costs, faecal occult blood testing and faecal immunochemical testing could become cost‐saving. The cost‐effectiveness of faecal DNA testing compared with no screening has improved, but faecal occult blood testing and faecal immunochemical testing are preferred to faecal DNA testing when patient adherence is high. Faecal immunochemical testing may be comparable to colonoscopy every 10 years in persons adhering to yearly testing.     

Cost-effectiveness analysis on screening for colorectal neoplasm and management of colorectal cancer in Asia

Background  Faecal occult blood testing (FOBT), flexible sigmoidoscopy (FS) and colonoscopy are recommended for subjects above 50 years of age for screening for colorectal cancer (CRC).
Aim  To evaluate the cost-effectiveness of FOBT, FS and colonoscopy on the basis of disease prevalence, compliance rate and cost of screening procedures in Asian countries.
Methods  A hypothetical population of 100 000 persons aged 50 undergoes either FOBT annually, FS every 5 years or colonoscopy every 10 years until the age of 80 years. Patients with positive FOBT or polyp in FS are offered colonoscopy. Surveillance colonoscopy is repeated every 3 years. The treatment cost of CRC, including surgery and chemotherapy, was evaluated. A Markov model was used to compare the cost-effectiveness of different screening strategies.
Results  Assuming a compliance rate of 90%, colonoscopy, FS and FOBT can reduce CRC incidence by 54.1%, 37.1% and 29.3% respectively. The incremental cost-effectiveness ratio (ICER) for FOBT (US$6222 per life-year saved) is lower than FS (US$8044 per life-year saved) and colonoscopy (US$7211 per life-year saved). When the compliance rate drops to 50% and 30%, FOBT still has the lowest ICER.
Conclusion  FOBT is cost-effective compared to FS or colonoscopy for CRC screening in average-risk individuals aged from 50 to 80 years.     

The evolution to stool DNA testing for colorectal cancer

Despite a variety of screening strategies and recent trends showing death rate stabilization, colorectal cancer still remains the second leading cause of overall cancer death. Current screening tools suffer from performance limitations, low patient acceptability, and marginal reliable access within the health care system. Noninvasive strategies present the lowest risk with the highest potential for patient satisfaction. However, serious implementation barriers exist requiring consistent programmatic screening, strict patient adherence, and poor sensitivity for adenomas. Colonoscopy remains an invasive screening test with the best sensitivity and specificity, but faces large financial costs, manpower requirements, patient access and adherence. Development of advanced molecular techniques identifying altered DNA markers in exfoliated colonocytes signify early or precancerous growth. Stool-based DNA testing provides an entirely noninvasive population-based screening strategy which patients can perform easier than faecal occult blood testing (FOBT). Large-scale prospective randomized control trials currently pending should help characterize accurate test performance, screening intervals, cost-effectiveness, direct comparison to FOBT and analysis of patient adherence. As tumour development pathways and potential target genes are further elucidated, refinements in multi-assay stool-based DNA testing portend enhanced test characteristics to detect and treat this genetically heterogeneous disease.     

Review article: balancing the ideal versus the practical-considerations of colorectal cancer prevention and screening

Colorectal cancer is responsible for over 500 000 deaths annually world-wide. Death from colorectal cancer is preventable, primarily through early diagnosis of disease that has not metastasized. The disease itself may be prevented by the detection and removal of colorectal adenomas, from which more than 95% of colorectal cancers arise. Currently there are several screening methods for the disease. These include faecal occult blood tests, sigmoidoscopy, barium enema and colonscopy as well as emerging methods of virtual colonoscopy and faecal DNA testing. While direct and indirect evidence support the efficacy of these tests they differ from each other in their sensitivity, specificity, cost, and safety. Various professional organizations in different geographical regions of the world have published recommendations on which screening methods to use and when in patients at average- or high-risk. The challenge in reducing the incidence and mortality of this disease lies in increasing accessibility to and compliance with screening and delivery within a quality assured programme.     

The role of calprotectin in predicting endoscopic post-surgical recurrence in asymptomatic Crohn's disease: a comparison with ultrasound

BACKGROUND AND OBJECTIVES: Faecal calprotectin is predictive of clinical relapse in inflammatory bowel disease and ultrasound is sensitive in detecting its post-surgical recurrence. However, no data regarding the role of calprotectin in predicting post-surgical recurrence in asymptomatic Crohn's disease are available. The aim of this study was to prospectively evaluate the role of calprotectin as a predictive marker for one year post-surgical endoscopic recurrence in comparison with ultrasound in patients with asymptomatic Crohn's disease. MATERIAL AND METHODS: We consecutively enlisted 50 patients who had undergone a resection for Crohn's disease. Faecal calprotectin was analysed and ultrasound were performed at the third month, and a colonoscopy after one year. The sensitivity and specificity of these two techniques were evaluated using endoscopic findings as a golden standard. A Receiver Operator Curve (ROC) curve was plotted, in order to identify the best-cut off value for calprotectin. RESULTS: 39 out of 50 patients were evaluated by performing a colonoscopy after one year; 19 patients had an endoscopic recurrence after one year. Calprotectin sensitivity and specificity were calculated for 5 different cut-off values; the best cut-off value for calprotectin sensitivity (63%) and specificity (75%) was > 200 mg/L. The US sensitivity and specificity at the third month were 26% and 90% respectively. CONCLUSIONS: When performed three months after surgery ultrasound is more specific than calprotectin in predicting endoscopic recurrence. Faecal calprotectin at a dosage > 200 mg/L seems to have a better sensitivity than ultrasound. Values of calprotectin > 200 mg can be an indication to colonoscopy in the group of patients with negative ultrasound in order to detect early recurrence.     

Benefit of concomitant gastrointestinal and gynaecological evaluation in premenopausal women with iron deficiency anaemia

Background  Iron-deficiency anaemia (IDA) is common in premenopausal women and menorrhagia is often considered responsible.
Aim  To evaluate prospectively the occurrence of bleeding and iron malabsorption related gastrointestinal (GI) diseases likely responsible of IDA in premenopausal women regardless of their menstrual flow.
Methods  One hundred and eighty-seven premenopausal women [median age 39 (20–56) years] irrespective of their menstrual flow underwent gastroscopy with gastric and duodenal biopsies and faecal occult blood test (FOBT). Patients over 50 years, positive 1st degree family history for colonic cancer and/or positive FOBT underwent colonoscopy too.
Results  Menorrhagia was present in 67.4% of premenopausal women. A possible GI cause of IDA was found in 129/187 patients; in 65.2% the cause of IDA was possibly related to iron malabsorption diseases. GI bleeding as a cause of IDA was found in seven patients. An exclusive GI cause of IDA was found in 26.7% of premenopausal women, whereas a possible GI cause was observed in 34.2% of menorrhagic premenopausal women. The main risk factor for the presence of likely GI causes was the presence of upper GI symptoms (OR 5.2: 95% CI = 1.6–16.4).
Conclusions  Most premenopausal women had a possible upper GI cause of IDA because of diseases related to iron malabsorption. Menorrhagia and a GI cause coexist in one-third of women with iron-deficiency anaemia.     

The utility of flexible sigmoidoscopy after a computerized tomographic colonography revealing only rectosigmoid lesions

Background  Identifying polyps by computerized tomographic colonography typically prompts colonoscopy, increasing its cost, risk and inconvenience. Many polyps are confined to the rectosigmoid and theoretically amenable to resection via flexible sigmoidoscopy.
Aim  To determine the prevalence of advanced proximal colonic neoplasia when computerized tomographic colonography reveals only rectosigmoid polyps, and characterize the yield of polypectomy via flexible sigmoidoscopy in such patients.
Methods  Subjects underwent computerized tomographic colonography and colonoscopy with segmental unblinding. Patients with only rectosigmoid findings by computerized tomographic colonography were identified retrospectively. Flexible sigmoidoscopy findings were estimated by including lesions distal to the descending/sigmoid colon junction during colonoscopy. Proximal lesions were also reviewed. Advanced lesions were defined as: adenocarcinoma, tubular adenoma >1 cm, ≥3 tubular adenomas, tubulovillous histology or high-grade dysplasia.
Results  By computerized tomographic colonography, 15% (203 of 1372) had only rectosigmoid polyps. Concomitant lesions in the proximal colon were seen in 32% (64 of 203) during colonoscopy. Advanced proximal neoplasia occurred in 2% (three of 203) with only rectosigmoid polyps on computerized tomographic colonography.
Conclusions  Using flexible sigmoidoscopy to follow-up computerized tomographic colonography demonstrating only rectosigmoid polyps would eliminate 15% of subsequent colonoscopies. This strategy carries a small risk of missed proximal advanced neoplasia. This miss rate appears comparable to that of colonoscopy alone. Further study on the cost-effectiveness of this approach is warranted.     

A comparison of the acceptance of immunochemical faecal occult blood test and colonoscopy in colorectal cancer screening: a prospective study among Chinese

Aliment Pharmacol Ther 2010; 32: 74–82

Summary

Background Preferences to choose immunochemical faecal occult blood test (FIT) and colonoscopy as colorectal cancer (CRC) screening modalities among asymptomatic Chinese subjects remain unknown. Aim To evaluate the preference of choosing colonoscopy vs. FIT among CRC screening participants. Methods From a community‐based CRC screening programme for asymptomatic Hong Kong Chinese aged 50–70 years, participants attended standardized educational sessions and chose the options of annual FIT for 5 years or direct colonoscopy once. Factors associated with choosing colonoscopy were evaluated by multivariate regression analysis. Results Among 3430 participants [mean age 56.8 years (s.d. 5.0); female 55.1%, male 44.9%], 51.3% chose colonoscopy and 48.7% chose FIT. Older participants (65–70 years) were less likely to choose colonoscopy [adjusted odds ratio (aOR) 0.731, P = 0.041]. Subjects who chose colonoscopy were those disagreed screening would lead to discomfort (aOR 1.356, P < 0.001), had relatives or friends who had CRC (first degree relatives aOR 1.679, P < 0.001; second degree relatives aOR 1.304, P = 0.019; friends or others aOR 1.252, P = 0.026) and those who self‐perceived their health as poor (aOR 1.529, P = 0.025). Conclusions Faecal occult blood test and direct colonoscopy were equally preferable to Chinese. Colonoscopy was preferred among the younger subjects, those with positive family history of CRC and self‐perceived poor health status.     

Faecal DNA and calprotectin as biomarkers of acute intestinal toxicity in patients undergoing pelvic radiotherapy

Background  Acute intestinal toxicity is a frequent complication that may lead to interruption of treatment in patients undergoing pelvic radiotherapy. Reliable, non-invasive biological markers to evidence their severity are not yet available.
Aim  To test faecal DNA and calprotectin as potential biomarkers of intestinal toxicity caused by pelvic radiotherapy.
Methods  Patients were categorized according to the location of the cancer as nonrectal ( n  = 25) and rectal ( n  = 27). Four stool samples were collected at weeks w0, w3, w5 (end of radiotherapy) and w7. Faecal DNA was determined by quantitative PCR and calprotectin by ELISA. Intestinal toxicity was scored according to the Common Toxicity Criteria.
Results  In the nonrectal group, acute diarrhoea toxicity was present in 80% of patients, faecal DNA increased 10-fold during radiotherapy (1.5 × 10³ copies/mg dry weight, 9.5 × 10²–8.8 × 10³ at w0, median and interquartile range vs. 1.3 × 10⁴, 1.9 × 10³–3.9 × 10⁴ at w5, P  < 0.01), but was not recovered at w7 (3.4 × 10³, 1.5 × 10³–4.1 × 10⁴) and calprotectin doubled during treatment at w3 and w5. No significant changes in faecal markers were found in the rectal group.
Conclusion  Faecal excretion of human DNA and calprotectin increased during pelvic radiotherapy treatment, and may be a good objective biomarker of intestinal damage in nonrectal cancer patients.     

The effect of a probiotic drink with Lactobacillus plantarum 299v on the bacterial composition in faeces and mucosal biopsies of rectum and ascending colon

BACKGROUND: Studies on probiotics mainly base their results on faecal samples, which may not represent the situation in the mucosa of distal and proximal colon. AIM: In a placebo-controlled study, to assess the effect of Lactobacillus plantarum 299v on the bacterial composition of faecal vs. mucosal samples. METHODS: Twenty-nine patients undergoing colonoscopic examination for polyps consumed a twice-daily drink with or without L. plantarum 299v (10(11) CFU/day) for 2 weeks. Faecal samples were collected before and after consumption. During colonoscopy, biopsies were collected from the ascending colon and rectum. The faecal and mucosal bacterial concentrations and prevalence were determined. RESULTS: L. plantarum 299v significantly increased the concentration of faecal lactic acid bacteria, lactobacilli and clostridia, and was identified in two rectal biopsies but not in the ascending colon biopsies of probiotic-treated subjects. Concentrations and prevalence in ascending colon and rectum biopsies were comparable, but were significantly lower compared with faecal samples. CONCLUSIONS: After probiotic consumption, a significant increase in the faecal concentration of lactobacilli was found but concentrations were low in biopsies. The bacterial composition in biopsies of the ascending colon and rectum did not differ based on culture techniques. To further elucidate the modes of action of probiotics, it might be necessary to study differences in colonization with molecular techniques.     

Review article: faecal occult blood testing for colorectal cancer

Major health organizations recommend colorectal cancer screening using faecal occult blood tests, sigmoidoscopy or both for patients 50 years of age or older who are at average risk for colorectal cancer. However, no specific recommendations have been made regarding choice of test from among the tests currently or soon to be available. Therefore, to aid clinicians in rationally choosing a particular test for faecal occult blood, published data are reviewed regarding the performance characteristics, strengths and weaknesses of the various faecal occult blood tests. New studies suggest that immunochemical tests (e.g. HemeSelect) or a combination of sensitive guaiac tests and immunochemical tests (e.g. Hemoccult Sensa and HemeSelect) are the most sensitive, specific tests for detecting colorectal carcinoma and colorectal polyps ≥ 1 cm.     

Off-label use of atypical antipsychotics: cause for concern?

Licensed indications for medicines were designed to regulate the claims that can be made about a medicine by a pharmaceutical company. Off-label prescribing (i.e. prescribing a drug for an indication outside of that for which it is licensed) is legal and an integral part of medical practice. In psychiatry, off-label prescribing is common and gives clinicians scope to treat patients who are refractory to standard therapy or where there is no licensed medication for an indication. However, efficacy or safety of such off-label use may not be established. There is a growing list of licensed indications for atypical antipsychotics (AAP) beyond schizophrenia and bipolar affective disorder, and also more evidence for other indications where pharmaceutical companies have not obtained a license. Pharmaceutical companies have promoted AAPs for off-label indications to increase sales and consequently have been fined by the US FDA for this. Since the 1990s, AAP use has expanded considerably, for example, the off-label use of quetiapine alone accounted for an estimated 17% of the AAP spend in New Zealand in 2010. There are a number of potential problems with the expanded use of AAPs outside of schizophrenia and related psychoses. A larger population will be exposed to their adverse effects, which include weight gain, type 2 diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. There are also concerns with the abuse of these agents, in particular quetiapine. Given that an increasing percentage of the population is being treated with these agents, off-label prescribing of AAPs is a cause for concern; they have a propensity to cause significant side effects and their efficacy and long-term safety for most off-label indications remains largely unknown, and therefore the risks and benefits of their use should be carefully weighed up prior to prescribing these agents off-label.     

Faecal microbiota profile of Crohn's disease determined by terminal restriction fragment length polymorphism analysis

Background  Terminal restriction fragment length polymorphism (T-RFLP) analyses are powerful tools to assess the diversity of complex microbiota. T-RFLPs permit rapid comparisons of microbiota from many samples.
Aim  To perform T-RFLP analyses of faecal microbiota in Crohn's disease (CD) patients to investigate potential alterations in faecal microbial communities and furthermore to analyse the effects of elemental diet on faecal microbiota profiles.
Methods  Thirty-four patients with CD and 30 healthy individuals were enrolled in the study. DNA was extracted from stool samples and 16S rRNA genes were amplified by PCR. PCR products were digested with Bsl I restriction enzymes and T-RF lengths were determined.
Results  Faecal microbial communities were classified into seven clusters. Almost all healthy individuals (28/30) were included in cluster I, II and III, but the majority of CD patients (25/34) could be divided into another four clusters (cluster IV–VII). Prediction of bacteria based on the Bsl I-digested T-RFLP database showed a significant decrease in Clostridium cluster IV, Clostridium cluster XI and subcluster XIVa in CD patients. In contrast, Bacteroides significantly increased in CD patients. Significant increases in Enterobacteriales were also observed in CD patients. Furthermore, elemental diets modulated faecal bacterial communities in CD patients.
Conclusions  Terminal restriction fragment length polymorphism analyses showed that the diversity of faecal microbiota in patients with CD differed from that of healthy individuals. Furthermore, elemental diets modulated faecal microbiota composition, and this effect may be involved in mechanisms of clinical effects of elemental diet.