Participant satisfaction with fecal occult blood test screening for colorectal cancer.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
Graeme P Young
Publications and source records attributed to Graeme P Young.
Effect of dietary resistant starch and protein on colonic fermentation and intestinal tumourigenesis in rats.
Protein as well as starch is fermented in the colon, but the interaction between protein and starch fermentation and the impact on colonic oncogenesis is unknown. High-protein diets increase delivery of protein to the colon and might promote oncogenesis through generation of toxic products. We investigated the interaction of resistant starch (RS) with digestion-resistant potato protein (PP) on colonic fermentation events and their relationship to intestinal tumourigenesis. Male Sprague-Dawley rats were fed an AIN-76A-based diet for 4 weeks and intestinal neoplasms were induced by azoxymethane. Experimental diets included the following: no added RS or PP, 10% high amylose maize starch (source of RS) replacing digestible starch, 15% PP replacing casein and 10% high amylose maize starch+15% PP. Rats were maintained on diets until killed at 30 weeks. Feeding RS significantly increased short-chain fatty acid (SCFA) levels (P<0.001) in the caecum and colon. Importantly, butyrate concentration was significantly increased in the distal colon with RS (P<0.001). Feeding PP increased protein fermentation products, but this effect was reduced by adding RS to the diet. Intestinal neoplasms and colorectal adenocarcinomas were reduced by feeding RS (P<0.01) regardless of whether PP was fed, whereas PP alone increased the incidence and number of small intestinal neoplasms including the adenocarcinomas (P<0.01). In conclusion, RS altered the colonic luminal environment by increasing the concentration of SCFAs including butyrate and lowering production of potentially toxic protein fermentation products. These effects of RS not only protected against intestinal tumourigenesis but also ameliorated the tumour-enhancing effects of feeding indigestible protein.
Animals↗
Comparison of a brush-sampling fecal immunochemical test for hemoglobin with a sensitive guaiac-based fecal occult blood test in detection of colorectal neoplasia.
BACKGROUND: Fecal immunochemical tests (FIT) are an advanced fecal occult blood test (FOBT) technology that reduces barriers to population screening by simplifying the logistics of stool-sampling. The current study was conducted to undertake a paired comparison of a sensitive guaiac FOBT (GFOBT; Hemoccult II Sensa, Beckman Coulter, Fullerton, CA) with a brush-sampling FIT (InSure; Enterix, North Ryde, NSW, Australia), to determine whether this FIT improves detection of significant neoplasia. METHODS: Individuals sampled consecutive stools, at home, with both FIT and GFOBT sampling devices while following dietary restrictions appropriate for GFOBT. Study populations included a screening cohort (n = 2351) and a symptomatic diagnostic group (n = 161). Paired comparison of positivity rates was undertaken in those found to have cancer and/or significant adenoma (high-grade dysplasia, villous change, > or =10 mm, serrated histology or > or =3 polyps), benign pathology, or no pathology. RESULTS: Combined results for both cohorts showed that the FIT returned a true-positive result significantly more often in cancer (n = 24; 87.5% vs. 54.2%) and in significant adenomas (n = 61; 42.6% vs. 23.0%). Of all UICC Stage I cancers, the FIT was positive in 12 of 13 compared with 4 of 13 with the GFOBT (P = .002). In analyses of just the screening cohort, the FIT remained significantly better at detecting cancers and significant adenomas; the false-positive rate for any neoplasia was marginally higher with the FIT than the GFOBT (3.4% vs. 2.5%; 95% CI of difference, 0-1.8%), whereas positive predictive values were 41.9% and 40.4%, respectively. CONCLUSIONS: This brush-sampling FIT is more sensitive for cancers and significant adenomas than a sensitive GFOBT. As such, it should deliver greater reductions in colorectal cancer mortality and incidence than the GFOBT.
Adenoma↗
Defective acute apoptotic response to genotoxic carcinogen in small intestine of APC(Min/+) mice is restored by sulindac.
The effect of APC loss on azoxymethane (AOM)-induced apoptosis and cell proliferation, as well as their regulation by sulindac was examined in colon and small intestine in APC(Min/+) mice. APC(Min/+) mice showed increased epithelial proliferation in all regions, with significant impairment of apoptosis in small intestine, but not in colon. Sulindac administration restored defective apoptosis to normal. As the apoptotic defect occurred at the major site of intestinal tumor formation in APC(Min/+) mice and as it was restored to normal by a proven chemopreventive agent, this defect in apoptosis might be a key biological consequence of APC dysfunction contributing to tumor formation.
Animals↗
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↗
Amylase-resistant starch as adjunct to oral rehydration therapy in children with diarrhea.
BACKGROUND: Oral rehydration solution (ORS) for treatment of diarrhea relies on enhancement of small intestinal sodium and fluid absorption to correct dehydration. Amylase-resistant starch added to ORS significantly reduced the duration and severity of diarrhea in adults with cholera, presumably by generation of short-chain fatty acids in the colon and enhancement of colonic sodium and fluid absorption. The present study was initiated to determine whether addition of amylase-resistant starch to standard World Health Organization glucose-ORS (G-ORS) would reduce the duration of diarrhea and fecal fluid losses in children with acute diarrhea. METHODS: One hundred eighty-three children (6 months to 3 years) with acute watery diarrhea were randomized to receive either standard treatment with G-ORS or G-ORS with additional amylase-resistant starch, HAMS (HAMS-ORS, 50g/L). Stool weight and consistency were monitored serially until development of formed stool or development of treatment failure defined as either the need for unscheduled intravenous fluid therapy or diarrhea longer than 72 hours. RESULTS: Five of the subjects were lost to follow up. In 178 remaining children (87 HAMS-ORS and 91 G-ORS) with evaluable data, time from enrolment to last unformed stool was significantly less in children receiving HAMS-ORS (median, 6.75 hours; 95% confidence interval, 4.27-9.22) than in children treated with G-ORS (12.80 hours, 8.69-16.91) (P = 0.0292). Time to first formed stool was also significantly shorter in children receiving HAMS-ORS (median, 18.25 hours; 95% confidence interval, 13.09-23.41) compared with children receiving G-ORS (median, 21.50 hours; 95% confidence interval, 17.26-25.74) (P = 0.0440). The total amount of ORS consumed was similar in both groups. There was a trend toward lower mean stool weight in first 24 hours (P = 0.0752) as well as total diarrheal stool weight (P = 0.0926) in patients in the HAMS group compared with the G-ORS group. CONCLUSION: In children with acute diarrhea, the addition of amylase-resistant starch to glucose ORS significantly shortened duration of diarrhea compared with standard treatment.
Acute Disease↗
Evaluation of oral rehydration solution by whole-gut perfusion in rats: effect of osmolarity, sodium concentration and resistant starch.
BACKGROUND: Reduced osmolarity oral rehydration solution (ORS) improved small bowel absorption of fluid and electrolytes in segmental perfusion in experimental animals; this was borne out in clinical practice. Adding amylase-resistant starch (RS) to ORS is expected to increase colonic fluid absorption. This study used combined small and large bowel perfusion to evaluate combinations of reduced osmolarity and starch in ORS. METHODS: Single-pass steady-state perfusions of the whole gut at 30 mL/h, using the nonabsorbable marker C-polyethylene glycol 4000, were performed in Wistar rats after exposure to cholera toxin or Escherichia coli heat-stable enterotoxin (STa). RESULTS: Steady state was established within 90 minutes after commencing perfusion. Net secretion of water, sodium and chloride induced by cholera toxin was partially reversed by standard glucose-ORS (G-ORS). Substituting glucose in G-ORS with RS (RS-ORS) substantially increased net water absorption (P < 0.001) as did reduced osmolarity ORS (RO-ORS) (P < 0.001); addition of RS to RO-ORS further increased water absorption (P < 0.001). In STa-treated intestine, RO-ORS and RS-ORS significantly improved water absorption compared to G-ORS (P < 0.005). RO- and RS-RO-ORS did not significantly augment net electrolyte absorption compared with G-ORS. RS-ORS was associated with highest net absorption of sodium and chloride compared with all other groups. CONCLUSIONS: RS increased net water (and sodium) absorption from isosmolar and reduced osmolar ORS consistent with increased absorption by the colon. RS in reduced osmolar ORS may have advantages to reduce severity of diarrhea and prevent hyponatremia in severe diarrhea and may be applicable to diarrhea of different etiologies.
Animals↗
Sulindac corrects defective apoptosis and suppresses azoxymethane-induced colonic oncogenesis in p53 knockout mice.
The acute apoptotic response to genotoxic carcinogens (AARGC) might be important for controlling the subsequent colonic mutational load and progression through oncogenesis. We have found previously that AARGC is p53-dependent with a gene-dosage effect, and that decreased AARGC in p53(+/-) and p53(-/-) mice is associated with increased susceptibility to carcinogen-induced oncogenesis. We tested the ability of sulindac to reverse these defects. The effect of sulindac on azoxymethane (AOM)-induced apoptosis was measured in colonic epithelium in wild-type, p53(+/-) and p53(-/-) mice, 8 hr after a single AOM injection. Sulindac supplementation (0.5 +/- 0.1 mg/day) restored defective AARGC in p53(+/-) but not in p53(-/-) mice. For effect on colon tumor development, sulindac treatment was started at age 4 weeks in wild-type, p53(+/-) and p53(-/-) mice; three weekly AOM injections were commenced at 6 weeks of age to induce tumors. Sulindac reduced significantly tumor incidence and multiplicity in wild-type mice (17% and 0.3 tumors/mouse compared to 36% and 0.8 respectively without drug), in p53(+/-)mice (38% and 0.8 compared to 64% and 1.63) and in p53(-/-) mice (63% and 1.0 compared to 90% and 1.74). Although loss of p53 function impairs the apoptotic response to AOM-induced DNA damage, sulindac is capable of partly restoring this defect. As sulindac also reverses the increased risk of oncogenesis due to p53 dysfunction, its enhancement of the apoptotic response to initiating mutations might act to reduce mutational load driving oncogenesis. Sulindac is an effective chemopreventive agent in the presence of p53 dysfunction.
Animals↗
Absence of acute apoptotic response to genotoxic carcinogens in p53-deficient mice is associated with increased susceptibility to azoxymethane-induced colon tumours.
Acute apoptotic response to genotoxic carcinogens (AARGC) might be important for controlling the consequences of mutational load in the colon. It has been shown to occur in parallel with activation of DNA repair mechanisms. Inadequate AARGC might allow development of mutated clones with the potential to progress to cancer. In this study, we tested if p53 levels were important for AARGC in the colon and whether defective AARGC was associated with increased risk for colorectal oncogenesis. Apoptosis was measured in colonic epithelium of mice from each p53 genotype (p53-/-, p53+/-, wild-type) without and 8 hr following a single injection of azoxymethane (AOM). To determine risk for carcinogen-induced colorectal cancer (CRC), groups of mice from each p53 genotype received 3 weekly injections of AOM and colons were examined for tumour 20 weeks later. Rates of spontaneous apoptosis in colon were not affected by p53 level. However, AARGC was absent in p53-/- mice and reduced by 50% in p53+/- mice (both p < 0.01) compared to wild-type mice. AOM induced tumours in 30% of wild-type mice (average multiplicity 1.0 tumours/mouse) compared to 72% of p53+/- mice (2.0 tumours/mouse, p < 0.01) and 100% of p53-/- mice (2.8 tumours/mouse, p < 0.01). Without AOM, significantly fewer mice in all groups had tumours. Rates of apoptosis in tumours were independent of p53 status. p53 dysfunction puts intestinal epithelia at increased risk of genotoxin-induced oncogenesis due to impairment of apoptotic response mechanisms. p53 levels do not appear, however, to be important for spontaneous apoptosis in normal epithelium or apoptosis in tumours. Subsequent studies are now warranted to test the converse, namely, that enhanced apoptotic response to carcinogen reduces risk for colorectal oncogenesis.
Animals↗
Fecal DNA for colorectal-cancer screening.
Explore the source record for details and available documents.
Colorectal Neoplasms↗
Dietary fibre and colorectal cancer: a model for environment--gene interactions.
As environmental factors are clearly associated with risk for colorectal cancer, we set out to model how dietary fibre, or the effects of its ingestion, might impact upon the complex events that characterise colorectal oncogenesis. The diverse nature of dietary fibre and its resultant fate in the gut is outlined. The evidence indicates that different types of fibre create different conditions in different regions of the gut. This is reflected in different effects on oncogenesis especially in animal models. Data from animal models show that insoluble fibre is protective. Evidence from human studies are not consistent, especially considering the interventional studies. However, all such studies have been dependent on biomarkers short of cancer formation, for measurement of an effect. The biological and molecular events characteristic of colorectal oncogenesis are reviewed in an effort to identify how fibre ingestion might regulate oncogenesis. While several mechanisms might account for protection, the results of fermentation and especially butyrate production provide examples of how genomic instability might be controlled. Activation of apoptosis and cell cycle arrest seem likely to be mechanisms that would enable correction of genomic events that drive oncogenesis. Butyrate itself can regulate gene expression by both epigenetic and direct effects.
Adenoma↗
Screening with a fecal multitarget DNA test.
Explore the source record for details and available documents.
Cohort Studies↗
A synbiotic combination of resistant starch and Bifidobacterium lactis facilitates apoptotic deletion of carcinogen-damaged cells in rat colon.
Recent reports suggest that combinations of prebiotics and probiotics may be protective against colorectal cancer. We examined in rats the effects of probiotic bacteria, resistant starch (RS), and their interaction on luminal and epithelial events of relevance to the development of colorectal cancer. Lyophilized cultures (1 x 10(10) cfu/g) of Lactobacillus acidophilus and/or Bifidobacterium lactis were added at a concentration of 1% by weight to a semipurified diet containing either low-RS (no supplemented RS) or moderate-RS (10% Hi-maize) and fed to male Sprague-Dawley rats for 4 wk. Experimental end-points included cecal bacterial enumeration, fecal and cecal pH, SCFA levels, cell proliferation, and the acute apoptotic response to a genotoxic carcinogen (AARGC; measured 6 h after a single azoxymethane injection). A significant interaction between dietary RS and supplemental bacteria was observed for the AARGC in the colon and fecal pH (P < 0.01). Rats fed the moderate-RS diet in combination with B. lactis had a significantly greater AARGC in the colon than those fed that diet without B. lactis. Fecal pH was elevated in the moderate-RS fed rats supplemented with bacteria. The moderate-RS diet increased cell proliferation and crypt column height (P < 0.001) compared with the low-RS diet. SCFA levels and numbers of bifidobacteria and lactobacilli species were also increased (P < 0.001) by the moderate-RS diet, whereas pH levels and total coliforms were lowered (P < 0.001). The synbiotic combination of RS and B. lactis significantly facilitated the apoptotic response to a genotoxic carcinogen in the distal colon of rats. It appears likely that ingested RS acts as a metabolic substrate, thus creating the right conditions for B. lactis to exert its proapoptotic action. Because the synbiotic combination of these agents facilitates the apoptotic response to DNA damage by a cancer initiator in the colon of rats, it warrants further study for its capacity to protect against colorectal cancer.
Animals↗
Effect of resistant starch on genotoxin-induced apoptosis, colonic epithelium, and lumenal contents in rats.
The effect of different doses of a type-2 resistant starch (RS) in the form of high amylose cornstarch (HAS) on the intralumenal environment and the acute-apoptotic response to a genotoxic carcinogen (AARGC) in the colon was assessed to determine if changes in lumenal conditions were associated with an enhanced apoptotic response to DNA damage. The control diet was a modified form of the AIN-76 diet containing fully digestible starch but no dietary fibre. HAS was added to the control diet at the expense of digestible starch to give 10% HAS, 20% HAS and 30% HAS. Rats were fed the different experimental diets for a period of 4 weeks, after which a single injection of azoxymethane was given to induce DNA damage in the colonic epithelium; 6 h later AARGC was measured. Other measures included fecal and cecal short chain fatty acids (SCFA) and pH, and cell proliferation in the colonic epithelium. In HAS-supplemented rats, fermentation events were significantly increased in both cecum and feces. There was a progressive decrease in pH in both the cecum and feces as the amount of HAS in the diet increased. SCFA concentrations, including butyrate, were significantly elevated by HAS with higher levels being observed in the cecum than in the feces. There was a significant increase in colonic AARGC with HAS doses of 20 and 30% (P < 0.01) but not with 10% HAS. Cell proliferation was not affected by any dose of HAS. Correlations with AARGC, independent of dietary group, were seen for fecal SCFAs and pH, suggesting that fermentation events, might explain the effect of RS on AARGC. Altering amounts of dietary RS changes fermentative activity in the colon. Increased RS is associated with enhanced AARGC. Changes in amount of fermentable substrate are capable of changing the biological response to DNA damage.
Amylose↗
Evaluation of an automated immunochemical fecal occult blood test for colorectal neoplasia detection in a Chinese population.
BACKGROUND: Most commercial fecal occult blood tests (FOBT) used for colorectal carcinoma screening of Western populations are guaiac-based, manually developed, subjective, and sensitive to dietary components. Preliminary studies demonstrated the unsuitability of these tests for screening a Chinese population. The goal of the current study was to evaluate the performance characteristics of a human hemoglobin-specific automated immunochemical FOBT, the Magstream 1000/Hem SP (Fujirebio, Inc., Tokyo, Japan), in a Chinese population referred for colonoscopy. METHODS: Two hundred fifty consecutive patients who were referred for colonoscopy and met the study inclusion criteria provided samples for the immunochemical FOBT (without dietary restrictions) from two successive stool specimens. Tests were developed with an automated instrument that had an adjustable sensitivity threshold. The sensitivity, specificity, and positive predictive value for detecting colorectal adenomas and carcinomas were calculated according to the manufacturer's instructions over a range of sensitivity levels. RESULTS: At the optimal threshold level, the sensitivity, specificity, and positive predictive value for detection of significant colorectal neoplasia (adenomas >or= 1.0 cm and carcinomas) were 62%, 93%, and 44%, respectively. The test was easy to use, and results did not depend on operator experience. CONCLUSIONS: The automated immunochemical FOBT used in the current study was a robust, convenient, and useful tool for colorectal carcinoma screening in the study population.
Adenoma↗
Reduced accumulation of specific microRNAs in colorectal neoplasia.
Short non-coding RNAs are known to regulate cellular processes including development, heterochromatin formation, and genomic stability in eukaryotes. Given the impact of these processes on cellular identity, a study was undertaken to investigate possible changes in microRNA (miRNA) levels during tumorigenesis. A total of 28 different miRNA sequences was identified in a colonic adenocarcinoma and normal mucosa, including 3 novel sequences and a further 7 that had previously been cloned only from mice. Human homologues of murine miRNA sequences, miR-143 and miR-145, consistently display reduced steady-state levels of the mature miRNA at the adenomatous and cancer stages of colorectal neoplasia.
Adenocarcinoma↗
Applying evidence-based guidelines improves use of colonoscopy resources in patients with a moderate risk of colorectal neoplasia.
OBJECTIVES: To determine whether applying National Health and Medical Research Council (NHMRC) guidelines for colorectal cancer prevention would reduce the number of follow-up colonoscopies. DESIGN: A prospective audit of colonoscopic surveillance decisions before and after the intervention. SETTING: The endoscopy suite at a metropolitan tertiary hospital three months before and after January 2000. INTERVENTION: Dissemination of NHMRC guidelines, and supervision of application of the guidelines by a nurse coordinator. SUBJECTS: We compared colonoscopic surveillance decisions before and after the intervention in two groups of 100 consecutive patients after polypectomy and in two groups of 50 consecutive patients with a family history of colorectal cancer after a normal colonoscopy. MAIN OUTCOME MEASURES: Change in concordance of decisions with NHMRC guidelines; and effect on number of follow-up colonoscopies. RESULTS: After the intervention, the proportion of postpolypectomy surveillance decisions matching the guidelines increased from 37% to 96% (P < 0.05). The mean time to repeat colonoscopy after polypectomy increased from 2.7 to 3.5 years (P < 0.005) (ie, a 23% reduction in the number of postpolypectomy surveillance colonoscopies performed per year). Likewise, the proportion of family-history surveillance decisions matching the guidelines increased from 63% to 96%. Adhering to the guidelines resulted in a 17% reduction in colonoscopies performed on the basis of a family history of colorectal cancer. CONCLUSIONS: Supervised application of evidence-based guidelines to a colorectal cancer surveillance program significantly reduces the number of surveillance colonoscopies performed.
Adenoma↗
Preventing cancer: dietary lifestyle or clinical intervention?
In Australia, colorectal, prostate and breast cancers are the most frequently occurring cancers in our society, a pattern that is quite different from that of underdeveloped countries. While diet is largely responsible for these differences, technological advances mean that the solutions can be viewed as systematic, financial, lifestyle or technological. They range from those that require self-discipline and care for personal well-being through to those that are seemingly a quick technological fix that will work in spite of an unhealthy lifestyle. There are three main approaches available for prevention of these cancers: dietary lifestyle, chemoprevention and screening. It has been estimated that the potential for prevention by a healthy dietary lifestyle is excellent and might reduce the burden of breast, prostate and colorectal cancer by 33-55%, 10-20% and 66-75%, respectively. This should be safe and inexpensive and have collateral benefit such as reduced cardiovascular disease and osteoporosis. But, population compliance with more plant-based, less calorie dense foods is uncertain, the most healthy are likely to be the most compliant and evidence for effectiveness when interventional programs are undertaken is disappointing. It is not clear how dependable the dietary approach would be where inherited genetic factors determine risk for one of these cancers. Chemoprevention, the administration of natural or synthetic agents that delay, slow down or inhibit the process of tumorigenesis, are still under development and study. Hormone receptor modulators for breast and derivatives of non-steroidal anti-inflammatory drugs for colorectal cancers seem to have most promise and may reduce tumour incidence or death by as much as 50%. These agents are simpler to comply with than changing dietary lifestyle and they are more potent, hence they may be of particular value in high-risk settings. But they are likely to be more costly and run the risk of adverse effects with few collateral benefits. Screening, or the testing of an individual for a disease when that individual does not have any symptoms or signs suggesting that the disease is present, aims to prevent or delay the development of the cancer. Screening impacts on mortality more so than on incidence, reducing colorectal cancer mortality in the range 15-60% and breast cancer mortality by 23-37%. Screening has the advantage of being effective in high-risk as well as average-risk groups and is an 'easy' solution for the person who elects not to follow a healthy dietary lifestyle. Nonetheless, it is expensive, demanding on resources, provides no collateral benefits and does not have the same potential to reduce incidence of disease as does the dietary approach. With these Western cancers, we are fortunate that there are options for prevention. At least choices are available and some will suite certain circumstances and personalities more than others.
Australia↗