A novel classification of colorectal tumors based on microsatellite instability, the CpG island methylator phenotype and chromosomal instability: implications for prognosis.

BACKGROUND: We studied the overlap between the major (epi)genomic events microsatellite instability (MSI), the CpG island methylator phenotype (CIMP) and chromosomal instability (CIN) in colorectal cancer (CRC), and whether specific (epi)genotypes were associated with CRC-related deaths. PATIENTS AND METHODS: Molecular analyses using tumor DNA were successful in 509 CRC cases identified within the Netherlands Cohort Study in the period 1989-1993. Follow-up for the vital status until May 2005 was 100%. RESULTS: MSI (12.6%), CIMP-only (5.3%), CIMP + CIN (13.4%), CIN-only (58.2%) and triple-negative tumors (10.6%) differed significantly regarding tumor localization, differentiation grade, initial adjuvant therapy (AT) use and genetic characteristics (P ≤ 0.03). CIMP-only, CIMP + CIN and triple-negative tumors, compared with CIN-only tumors, were significantly associated with a 3.67, 2.44 and 3.78-fold risk of CRC-related deaths after 2-year follow-up (95% confidence intervals, CIs, 1.70-7.91, 1.35-4.41 and 1.97-7.25, respectively), but not after late follow-up. MSI tumors were borderline significantly associated with a 0.40-fold risk of CRC-related deaths after late follow-up (95% CI 0.15-1.03). CONCLUSION(S): This is the first study to show that specific (epi)genotypes may hold a differential prognostic value that may vary over time. Although no specific treatment data were available, an explanation for the differential findings over time might be that (epi)genotypes modify therapy response.

Opportunistic screening of hospital staff using primary colonoscopy: participation, discomfort and willingness to repeat the procedure.

BACKGROUND: Participation in and tolerability of primary colonoscopy screening are presumed to be relatively low. The present study aimed to test its feasibility in a well-informed population of hospital staff using an intensive information campaign, and to identify factors associated with screening colonoscopy rated as uncomfortable. METHODS: Data were collected using standardized forms. RESULTS: Out of 1,090 invited employees (50-65 years), 447 (41.0%) participated. Bowel preparation and colonoscopy were rated as 'somewhat to very uncomfortable' by 79.5 and 21.9%, respectively. 96.3% of participants were willing to repeat colonoscopy in the future. Participants rating colonoscopy as uncomfortable were more likely unwilling to repeat the procedure (OR 8.026, CI 2.667-24.154). Multivariate analysis (age- and gender-adjusted) showed an association of colonoscopy rated as uncomfortable with: abdominal pain during colonoscopy (OR 3.185, CI 1.642-6.178), other pain (OR 2.428, CI 1.335-4.416), flatulence (OR 2.175, CI 1.219-3.881), embarrassment (OR 2.843, CI 1.350-5.989), abdominal pain after colonoscopy (OR 1.976, CI 1.041-3.751), and a prolonged procedure time (OR 1.000, CI 1.000-1.001). CONCLUSIONS: Acceptance of primary colonoscopy screening for colorectal neoplasia was high, although participants with symptoms during and after colonoscopy were more likely to rate colonoscopy as uncomfortable. This type of opportunistic screening procedure is suitable for the introduction of screening programs and may be useful in areas that have no access to population-based screening.

Cardiopulmonary events during primary colonoscopy screening in an average risk population.

BACKGROUND: Large colorectal cancer screening studies using primary colonoscopy have reported a low risk of major complications. Studies on diagnostic and therapeutic colonoscopy have pointed to a frequent occurrence of(minor) cardiopulmonary events, and with the steady increase of colonoscopy screening, it is important to investigate their occurrence in colonoscopy screening. METHODS: This study describes the frequency of bradycardia(pulse rate <60 min-1), hypotension (systolic blood pressure(SB P) <90 mmHg), hypoxaemia (blood oxygenation, SaO2<90%) and ECG changes during colonoscopy screening in an average-risk population (hospital personnel, n=214,mean age 54.0±3.8, 39.3% male), without significant comorbidity) and aims at identifying subject-related and/or endoscopic factors associated with their occurrence. All data were collected prospectively. During 214 consecutive primary screening colonoscopies under conscious sedation(midazolam and pethidine), on top of pulse rate and SaO2,blood pressure and a three-channel ECG were recorded every five minutes. RESULTS: No major complications or relevant ECG changes occurred. Hypoxaemia occurred in 119 (55.6%),hypotension in 19 (8.9%) and bradycardia in 12 subjects(5.6%). In multivariate analysis, the sedation level 3 increased the risk of hypoxaemia (OR 4.8, CI 1.7-13.7), and incomplete colonoscopy (OR 5.3, CI 1.6-18.1) was associated with hypotension. Subjects with bradycardia had a longer mean procedure time (38±12 vs. 29±12 min, p<0.05), which did not turn out as a risk factor in a multivariate analysis. CONCLUSIONS: Mainly procedure-related and not subject-related factors were found to be associated with the occurrence of cardiopulmonary events in primary colonoscopy screening in this relatively healthy screening population.