Diagnostic performance of fecal immunochemical test and sigmoidoscopy for advanced right-sided colorectal neoplasms.

BACKGROUND: Colorectal cancer screening effect on right-sided colorectal neoplasia is limited. We compared fecal immunochemical test and simulated sigmoidoscopy diagnostic accuracy for advanced right-sided neoplasia detection. METHODS: We analyzed 1,292 individuals with complete screening colonoscopy with a fecal immunochemical test determination before colonoscopy. Sigmoidoscopy and "hybrid strategy" (sigmoidoscopy or fecal hemoglobin concentration ≥ 20 µg hemoglobin/g) diagnostic yield were simulated according to UK Flexible Sigmoidoscopy, Screening for COlon REctum (SCORE), and Norwegian Colorectal Cancer Prevention (NORCCAP) trials criteria to complete colonic examination. We compared sensitivity and specificity of both strategies and of "hybrid strategy" for advanced right-sided neoplasia with McNemar test. RESULTS: An advanced right-sided neoplasia was detected in 47 (3.6 %) subjects. A fecal hemoglobin concentration ≥ 20 µg hemoglobin/g was determined in 6.6 % of the subjects and 10.1, 12.7, and 23.5 % met UK, SCORE, and NORCCAP criteria, respectively. Fecal immunochemical test was statistically more specific than sigmoidoscopy strategies (93.8 %, UK 90.3 %, SCORE 87.7 %, NORCCAP 77.8 %; p < 0.001). In contrast, fecal immunochemical test sensitivity for advanced right-sided neoplasia (17 %) was not statistically different than UK (21.3 %; p = 0.7) or SCORE (23.4 %; p = 0.5), although it was inferior than NORCCAP strategy (42.5 %; p < 0.001). Adding fecal immunochemical test to sigmoidoscopy increased number of positives (8.5-25.7 %), sensitivity (10-30 %), and significantly reduced advanced right-sided neoplasia specificity (p < 0.001). CONCLUSIONS: Fecal immunochemical test and sigmoidoscopy diagnostic yield for advanced right-sided neoplasia are low. Fecal immunochemical test is more specific than sigmoidoscopy but less sensitive than sigmoidoscopy according to NORCCAP criteria.

Novel equation to determine the hepatic triglyceride concentration in humans by MRI: diagnosis and monitoring of NAFLD in obese patients before and after bariatric surgery.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is caused by abnormal accumulation of lipids within liver cells. Its prevalence is increasing in developed countries in association with obesity, and it represents a risk factor for non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Since NAFLD is usually asymptomatic at diagnosis, new non-invasive approaches are needed to determine the hepatic lipid content in terms of diagnosis, treatment and control of disease progression. Here, we investigated the potential of magnetic resonance imaging (MRI) to quantitate and monitor the hepatic triglyceride concentration in humans. METHODS: A prospective study of diagnostic accuracy was conducted among 129 consecutive adult patients (97 obesity and 32 non-obese) to compare multi-echo MRI fat fraction, grade of steatosis estimated by histopathology, and biochemical measurement of hepatic triglyceride concentration (that is, Folch value). RESULTS: MRI fat fraction positively correlates with the grade of steatosis estimated on a 0 to 3 scale by histopathology. However, this correlation value was stronger when MRI fat fraction was linked to the Folch value, resulting in a novel equation to predict the hepatic triglyceride concentration (mg of triglycerides/g of liver tissue = 5.082 + (432.104 * multi-echo MRI fat fraction)). Validation of this formula in 31 additional patients (24 obese and 7 controls) resulted in robust correlation between the measured and estimated Folch values. Multivariate analysis showed that none of the variables investigated improves the Folch prediction capacity of the equation. Obese patients show increased steatosis compared to controls using MRI fat fraction and Folch value. Bariatric surgery improved MRI fat fraction values and the Folch value estimated in obese patients one year after surgery. CONCLUSIONS: Multi-echo MRI is an accurate approach to determine the hepatic lipid concentration by using our novel equation, representing an economic non-invasive method to diagnose and monitor steatosis in humans.

Phenotype characteristics of patients with colonic serrated polyposis syndrome: a study of 23 cases.

INTRODUCTION: Serrated polyposis syndrome (SPS) is a rare entity characterized by the presence of multiple hyperplastic polyps in the colon and an increased risk of presentation and development of colorectal cancer (CRC). OBJECTIVE: To evaluate the clinical and phenotypical characteristics of patients that present one of the 3 WHO criteria for the diagnosis of SPS diagnosed and treated a tour hospital. PATIENTS AND METHODS: Patients with the diagnosis of SPS during 2005-2012 were revised; 24.208 colonoscopies were performed during this period. Age, sex, family history of CRC (APC/MYH), proximal/mixed/distal phenotype, indication for colonoscopy, number, size, location of the hyperplastic polyps, presence of mixed/adenomatous polyps, CRCI, follow-up and endoscopio/surgical treatment. RESULTS: A total of 23 cases were included (19 male). The median age was 51. A total of 34% had a prior family history of CRC or polpyps. Distal phenotype was more frequent (48%). Another 73% presented synchronous adenomatous polyps, and 26% a CRC. A total of 57% were asymptomatic. Surgery was performed in 9 cases (6 for cancer and 3 for polyposis), and 14 were treated by polypectomy and observation. Eleven patients (47%) presented recurrent/persistent lesions after initial surgical/endoscopic treatment. CONCLUSION: SPS is an heterogeneous syndrome that is variable in the type, size, distribution and number of polyps, and is more common in male smokers with a distal phenotype. The majority of patients also present synchronous adenomatous polyps. These patients require an organized multidisciplinary evaluation.

Diagnosis of Whipple's disease using molecular biology techniques.

The diagnosis of Whipple's disease (WD) is based on the existence of clinical signs and symptoms compatible with the disease and in the presence of PAS-positive diastase-resistant granules in the macrophages of the small intestine. If there is suspicion of the disease but no histological findings or only isolated extraintestinal manifestations, species-specific PCR using different sequences of the T. whippleii genome from different tissue types and biological fluids is recommended.This study reports two cases: the first patient had diarrhea and the disease was suspected after an endoscopic examination of the ileum, while the second patient had multi-systemic manifestations,particularly abdominal, thoracic, and peripheral lymphadenopathies. In both cases, the diagnosis was confirmed using molecular biology techniques to samples from the small intestine or from a retroperineal lymph node, respectively.

Food groups, diet quality and colorectal cancer risk in the Basque Country.

BACKGROUND: The results obtained to date concerning food groups, diet quality and colorectal cancer (CRC) risk vary according to criteria used and the study populations. AIM: To study the relationships between food groups, diet quality and CRC risk, in an adult population of the Basque Country (North of Spain). METHODS: This observational study included 308 patients diagnosed with CRC and 308 age- and sex-matched subjects as controls. During recruitment, dietary, anthropometric, lifestyle, socioeconomic, demographic and health status information was collected. Adherence to the dietary recommendations was evaluated utilizing the Healthy Eating Index for the Spanish Diet and the MedDietScore. Conditional logistic regressions were used to evaluate the associations of food group intakes, diet quality scores, categorized in tertiles, with CRC risk. RESULTS: The adjusted models for potential confounding factors showed a direct association between milk and dairy products consumption, in particular high-fat cheeses [odds ratio (OR) third tertile vs first tertile = 1.87, 95% confidence intervals (CI): 1.11-3.16], and CRC risk. While the consumption of fiber-containing foods, especially whole grains (OR third tertile vs first tertile = 0.62, 95%CI: 0.39-0.98), and fatty fish (OR third tertile vs first tertile = 0.53, 95%CI: 0.27-0.99) was associated with a lower risk for CRC. Moreover, higher MD adherence was associated with a reduced CRC risk in adjusted models (OR third tertile vs first tertile = 0.40, 95%CI: 0.20-0.80). CONCLUSION: Direct associations were found for high-fat cheese, whereas an inverse relation was reported for fiber-containing foods and fatty fish, as well as adherence to a Mediterranean dietary pattern.

Gene-Diet Interactions in Colorectal Cancer: Survey Design, Instruments, Participants and Descriptive Data of a Case-Control Study in the Basque Country.

Epidemiologic studies have revealed inconsistent evidence of gene-diet interaction in relation to colorectal cancer (CRC). The aim of this study was to analyze them in a sample of cases and controls from the population-based bowel cancer screening program of the Osakidetza/Basque Health Service. This study analyzed dietetic, genetic, demographic, socioeconomic factors and lifestyles. In the present manuscript, the survey design, sampling, instruments, measurements and related quality management were presented. Moreover, we analyze differences between cases and controls in some data, especially those related to diet. The participants were 308 cases and 308 age- and sex-matched subjects as controls. Cases were more likely than controls to have overweight/obesity (67.5% vs. 58.1%, p < 0.05), a lower intake of vitamin B2 (0.86 ± 0.23 vs. 0.92 ± 0.23 mg/1000 kcal, p < 0.01) and calcium:phosphorus ratio (0.62 ± 0.12 vs. 0.65 ± 0.13, p < 0.01). A higher proportion of cases than controls did not meet the Nutritional Objectives for saturated fatty acids (85.7% vs. 67.5%, p < 0.001) or cholesterol (35.4% vs. 25.0%, p < 0.01). In conclusion, the present study provides valuable data for analyzing the complexity of gene-diet interaction in relation to CRC. The results presented here suggest that overweight/obesity and a high intake of certain dietary components, especially saturated fatty acids and cholesterol, are more frequent in cases than in controls.

Single nucleotide polymorphisms associated with susceptibility for development of colorectal cancer: Case-control study in a Basque population.

Given the significant population diversity in genetic variation, we aimed to investigate whether single nucleotide polymorphisms (SNPs) previously identified in studies of colorectal cancer (CRC) susceptibility were also relevant to the population of the Basque Country (North of Spain). We genotyped 230 CRC cases and 230 healthy controls for 48 previously reported CRC-susceptibility SNPs. Only the rs6687758 in DUPS10 exhibited a statistically significant association with CRC risk based on the crude analysis. The rs6687758 AG genotype conferred about 2.13-fold increased risk for CRC compared to the AA genotype. Moreover, we found significant associations in cases between smoking status, physical activity, and the rs6687758 SNP. The results of a Genetic Risk Score (GRS) showed that the risk alleles were more frequent in cases than controls and the score was associated with CRC in crude analysis. In conclusion, we have confirmed a CRC susceptibility locus and the existence of associations between modifiable factors and the rs6687758 SNP; moreover, the GRS was associated with CRC. However, further experimental validations are needed to establish the role of this SNP, the function of the gene identified, as well as the contribution of the interaction between environmental factors and this locusto the risk of CRC.

Resveratrol inhibits nonalcoholic fatty liver disease in rats.

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) is high. NAFLD is linked to obesity, diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with NAFLD will eventually develop cirrhosis. Our purpose was to investigate whether resveratrol decreased hepatic steatosis in an animal model of steatosis, and whether this therapeutic approach resulted in a decrease in tumor necrosis factor alpha (TNF-alpha) production, lipid peroxidation and oxidative stress. METHODS: Male Wistar CRL: Wi (Han) (225 g) rats were randomized into three groups. A control group (n = 12) was given free access to regular dry rat chow for 4 weeks. The steatosis (n = 12) and resveratrol (n = 12) groups were given free access to feed (a high carbohydrate-fat free modified diet) and water 4 days per week, and fasted for the remaining 3 days for 4 weeks. Rats in the resveratrol group were given resveratrol 10 mg daily by the oral route. All rats were killed at 4 weeks and assessed for fatty infiltration and bacterial translocation. Levels of TNF-alpha in serum, hepatic malondialdehyde (MDA), oxidative stress (superoxide dismutase, glutathione peroxidase, catalase and nitric oxide synthase) and biochemical parameters were measured. RESULTS: Fat deposition was decreased in the resveratrol group as compared to the steatosis group (Grade 1 vs Grade 3, P < 0.05). TNF-alpha and MDA levels were significantly increased in the steatosis group (TNF-alpha; 33.4 +/- 5.2 vs 26.24 +/- 3.47 pg/ml and MDA; 9.08 +/- 0.8 vs 3.17 +/- 1.45 muM respectively, P < 0.05). This was accompanied by increased superoxide dismutase, glutathione peroxidase and catalase and decreased nitric oxide synthase in the liver of resveratrol group significantly (P < 0.05 vs steatosis group). Bacterial translocation was not found in any of the groups. Glucose levels were decreased in the group of rats given resveratrol (P < 0.05). CONCLUSION: Resveratrol decreased NAFLD severity in rats. This effect was mediated, at least in part, by TNF-alpha inhibition and antioxidant activities.

Effect of resveratrol on alcohol-induced mortality and liver lesions in mice.

BACKGROUND: Resveratrol is a polyphenol with important antiinflammatory and antioxidant properties. We investigated the effect of resveratrol on alcohol-induced mortality and liver lesions in mice. METHODS: Mice were randomly distributed into four groups (control, resveratrol-treated control, alcohol and resveratrol-treated alcohol). Chronic alcohol intoxication was induced by progressively administering alcohol in drinking water up to 40% v/v. The mice administered resveratrol received 10 mg/ml in drinking water. The animals had free access to standard diet. Blood levels were determined for transaminases, IL-1 and TNF-alpha. A histological evaluation was made of liver damage, and survival among the animals was recorded. RESULTS: Transaminase concentration was significantly higher in the alcohol group than in the rest of the groups (p < 0.05). IL-1 levels were significantly reduced in the alcohol plus resveratrol group compared with the alcohol group (p < 0.05). TNF-alpha was not detected in any group. Histologically, the liver lesions were more severe in the alcohol group, though no significant differences between groups were observed. Mortality in the alcohol group was 78% in the seventh week, versus 22% in the alcohol plus resveratrol group (p < 0.001). All mice in the alcohol group died before the ninth week. CONCLUSION: The results obtained suggest that resveratrol reduces mortality and liver damage in mice.

Biochemical determination of lipid content in hepatic steatosis by the Soxtec method.

AIM: To establish a quantitative method to measure the amount of lipids. METHODS: The livers of 53 male Wistar rats (225 g) with different degrees of hepatic steatosis were studied. This model of hepatic steatosis was based on a high carbohydrate, fat-free modified diet. Biopsies were classified into four grades depending on fat accumulation, using the Kleiner and Brunt classification. Total fat was studied by the Soxtec method (Soxtec 2050 Auto Fat Extraction System), and agreement between both assays was assessed by calculating the kappa coefficient. RESULTS: According to the histological classification, 38% of rats presented grade 0, 21% grade 1, 22% grade 2 and 20% grade 3. The amount of fat per 100 g tissue was 2.60 +/- 0.64 g for grade 0, 3.87 +/- 1.59 g for grade 1, 5.82 +/- 1.37 g for grade 2 and 8.68 +/- 2.30 g for grade 3. Statistically significant differences were found between the mean values for each of the histological grades (P < 0.05). The correlation for the quantification of fat in the liver between both assays was moderate (kappa = 0.60). CONCLUSION: The biochemical quantification of fat in liver tissue by the Soxtec method was correlated with the histological classification, although the agreement between the two tests was only moderate.

MSH6 and MUTYH deficiency is a frequent event in early-onset colorectal cancer.

PURPOSE: Early-onset colorectal cancer (CRC) is suggestive of a hereditary predisposition. Lynch syndrome is the most frequent CRC hereditary cause. The MUTYH gene has also been related to hereditary CRC. A systematic characterization of these two diseases has not been reported previously in this population. EXPERIMENTAL DESIGN: We studied a retrospectively collected series of 140 patients ≤50 years old diagnosed with nonpolyposis CRC. Demographic, clinical, and familial features were obtained. Mismatch repair (MMR) deficiency was determined by microsatellite instability (MSI) analysis, and immunostaining for MLH1, MSH2, MSH6, and PMS2 proteins. Germline MMR mutations were evaluated in all MMR-deficient cases. Tumor samples with loss of MLH1 or MSH2 protein expression were analyzed for somatic methylation. Germline MUTYH mutations were evaluated in all cases. BRAF V600E and KRAS somatic mutational status was also determined. RESULTS: Fifteen tumors (11.4%) were MSI, and 20 (14.3%) showed loss of protein expression (7 for MLH1/PMS2, 2 for isolated MLH1, 3 for MSH2/MSH6, 7 for isolated MSH6, and 1 for MSH6/PMS2). We identified 11 (7.8%) germline MMR mutations, 4 in MLH1, 1 in MSH2, and 6 in MSH6. Methylation analysis revealed one case with somatic MLH1 methylation. Biallelic MUTYH mutations were detected in four (2.8%) cases. KRAS and BRAF V600E mutations were present in 39 (27.9%) and 5 (3.6%) cases, respectively. CONCLUSIONS: Loss of MSH6 expression is the predominant cause of MMR deficiency in early-onset CRC. Our findings prompt the inclusion of MSH6 and MUTYH screening as part of the genetic counseling of these patients and their relatives.