Prediction of advanced colonic neoplasm in symptomatic patients: a scoring system to prioritize colonoscopy (COLONOFIT study).

BACKGROUND: Fast-track colonoscopy to detect patients with colorectal cancer based on high-risk symptoms is associated with low sensitivity and specificity. The aim was to derive a predictive score of advanced colonic neoplasia in symptomatic patients in fast-track programs. METHODS: All patients referred for fast-track colonoscopy were evaluated. Faecal immunological haemoglobin test (3 samples; positive> 4 µg Hb/g), and a survey to register clinical variables of interest were performed. Colorectal cancer and advanced adenoma were considered as advanced colonic neoplasia. A sample size of 600 and 500 individuals were calculated for each phase 1 and phase 2 of the study, respectively (Phase 1, derivation and Phase 2, validation cohort). A Bayesian logistic regression analysis was used to derive a predictive score. RESULTS: 1495 patients were included. Age (OR, 21), maximum faecal-Hb value (OR, 2.3), and number of positive samples (OR, 28) presented the highest ORs predictive of advanced colonic neoplasia. The additional significant predictive variables adjusted for age and faecal-Hb variables in Phase 1 were previous colonoscopy (last 5 years) and smoking (no, ex/active). With these variables a predictive score of advanced colonic neoplasia was derived. Applied to Phase 2, patients with a Score > 20 had an advanced colonic neoplasia probability of 66% (colorectal cancer, 32%), while those with a Score ≤ 10, a probability of 10% (colorectal cancer, 1%). Prioritizing patients with Score > 10, 49.4% of patients would be referred for fast-track colonoscopy, diagnosing 98.3% of colorectal cancers and 77% of advanced adenomas. CONCLUSIONS: A scoring system was derived and validated to prioritize fast-track colonoscopies according to risk, which was efficient, simple, and robust.

Capsule endoscopy capture rate: has 4 frames-per-second any impact over 2 frames-per-second?

AIM: To compare the current capsule and a new prototype at 2 and 4 frames-per-second, respectively, in terms of clinical and therapeutic impact. METHODS: One hundred patients with an indication for capsule endoscopy were included in the study. All procedures were performed with the new device (SB24). After an exhaustive evaluation of the SB24 videos, they were then converted to "SB2-like" videos for their evaluation. Findings, frames per finding, and clinical and therapeutic impact derived from video visualization were analyzed. Kappa index for interobserver agreement and χ (2) and Student's t tests for qualitative/quantitative variables, respectively, were used. Values of P under 0.05 were considered statistically significant. RESULTS: Eighty-nine out of 100 cases included in the study were ultimately included in the analysis. The SB24 videos detected the anatomical landmarks (Z-line and duodenal papilla) and lesions in more patients than the "SB2-like" videos. On the other hand, the SB24 videos detected more frames per landmark/lesion than the "SB2-like" videos. However, these differences were not statistically significant (P > 0.05). Both clinical and therapeutic impacts were similar between SB24 and "SB2-like" videos (K = 0.954). The time spent by readers was significantly higher for SB24 videos visualization (P < 0.05) than for "SB2-like" videos when all images captured by the capsule were considered. However, these differences become non-significant if we only take into account small bowel images (P > 0.05). CONCLUSION: More frames-per-second detect more landmarks, lesions, and frames per landmark/lesion, but is time consuming and has a very low impact on clinical and therapeutic management.

Novel methylation panel for the early detection of neoplasia in high-risk ulcerative colitis and Crohn's colitis patients.

BACKGROUND: Patients with ulcerative colitis and Crohn's colonic disease are at increased risk of developing colorectal cancer (CRC). The aim of the study was to analyze the methylation status of selected genes as a risk marker for CRC in inflammatory bowel disease (IBD) patients. METHODS: We evaluated the methylation status of four genes (TGFB2, SLIT2, HS3ST2, and TMEFF2) in biopsies of four groups of patients: 60 patients with sporadic CRC, 32 patients with IBD-associated neoplasia, 85 patients with IBD without associated neoplasia (20 at high risk and 65 at low risk), and 28 healthy controls. Methylation-specific melting curve analysis (MS-MCA) was used. Methylation status of these genes was also assessed in stool DNA from 60 IBD patients without neoplasia. RESULTS: Methylation of the panel of genes analyzed was a very common phenomenon (78%) in IBD-associated neoplasia. The prevalence of methylation in adjacent nonneoplastic mucosa was also high (12/30). This prevalence was higher than in mucosa from healthy controls (2/28;7.1%; P < 0.05). Methylation of SLIT2 and TMEFF2 was more frequently detected in the mucosa of IBD patients at high risk of dysplasia or cancer (15/20) than patients at low risk (32/63) (P = 0.05 and P = 0.03, respectively). When stool samples were assessed, only SLIT2 gene methylation was more frequently methylated in the group of patients at high risk of dysplasia or cancer (4/16) compared to low risk (0/37) (P = 0.006). CONCLUSIONS: Analysis of a panel of methylation markers may help in the early identification of colorectal dysplasia or cancer in high-risk IBD patients.

Nanofluidic digital PCR for KRAS mutation detection and quantification in gastrointestinal cancer.

BACKGROUND: Concomitant quantification of multiple mutant KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) alleles may provide information in addition to that provided by standard mutation-detection procedures. We assessed the feasibility of a nanofluidic digital PCR array platform to detect and quantify KRAS mutations simultaneously in clinically relevant samples. METHODS: We assessed 2 groups of patients (colorectal and pancreatic disease): Group 1 consisted of 27 patients with colorectal carcinomas, 14 patients with adenomas, and 5 control individuals; group 2 consisted of 42 patients with pancreatic carcinoma, 4 with adenocarcinomas of the ampulla, and 6 with chronic pancreatitis). Digital PCR was performed with the Digital Array Chip (Fluidigm). RESULTS: Nanofluidic digital PCR detected mutant alleles at 0.05% to 0.1%, depending on the variant analyzed. For the colorectal disease group, conventional PCR detected 9 (64%) of 14 adenomas that were positive for KRAS mutants, whereas digital PCR increased this number to 11 (79%) of 14. Sixteen (59%) of 27 carcinomas showed KRAS mutation with conventional PCR. Two additional cases were detected with digital PCR. In 5 cases (3 adenomas, 2 carcinomas), the total number of mutant alleles changed. For the pancreatic disease group, digital PCR increased the number of positive cases from 26 to 34 (81%) and identified ≥ 2 mutant alleles in 25 cases, compared with conventional PCR, which identified multiple KRAS mutant alleles in only 12 cases. A good correlation was observed between results obtained with tumor biopsies and those obtained with pancreatic juice. CONCLUSIONS: Digital PCR provides a robust, quantitative measure of the proportion of KRAS mutant alleles in routinely obtained samples. It also allows a better classification of tumors, with potential clinical relevance.

[Wireless capsule endoscopy: basic principles and clinical utility]. / Cápsula endoscópica: fundamentos y utilidad clínica.

Wireless capsule endoscopy (PillCam) represents a major advance in the study of small bowel disease since this procedure allows images of hitherto unreachable areas to be obtained. Approved for use by the Food and Drug Administration in August 2000, capsule endoscopy is currently a first line procedure in the study of small bowel disease. This technique consists of a non-reusable swallowable capsule (length 26 x 11 mm) that acquires video images while moving through the gastrointestinal tract propelled by natural peristalsis. The main indications of capsule endoscopy are evaluation of obscure gastrointestinal bleeding, chronic anemia, and inflammatory bowel disease. Contraindications are swallowing disorders and known or suspected small bowel strictures of any etiology. Consequently, small bowel follow through is useful prior to capsule endoscopy when these lesions are suspected.