Impact of inadequate bowel cleansing in sigmoidoscopy screening.

BACKGROUND AND STUDY AIMS: Long-time follow-up of sigmoidoscopy screening trials has shown reduced incidence and mortality of colorectal cancer (CRC), but inadequate bowel cleansing may hamper efficacy. The aim of this study was to assess the impact of bowel cleansing quality in sigmoidoscopy screening. PATIENTS AND METHODS: Individuals 50 to 74 years old who had a screening sigmoidoscopy in a population-based Norwegian, randomized trial between 2012 and 2019, were included in this cross-sectional study. The bowel cleansing quality was categorised as excellent, good, partly poor, or poor. The effect of bowel cleansing quality on adenoma detection rate (ADR) and referral to colonoscopy was evaluated by fitting multivariable logistic regression models. RESULTS: 35,710 individuals were included. The bowel cleansing at sigmoidoscopy was excellent in 20,934 (58.6%) individuals, good in 6580 (18.4%), partly poor in 7097 (19.9%) and poor in 1099 (3.1%). The corresponding ADRs were 17.0%, 16.6%, 14.5%, and 13.0%. Compared to participants with excellent bowel cleansing, those with poor bowel cleansing had an odds ratio for adenoma detection of 0.66 (95% confidence interval 0.55-0.79). We found substantial differences in the assessment of bowel cleansing quality among endoscopists. CONCLUSIONS: Inadequate bowel cleansing reduces the efficacy of sigmoidoscopy screening, by lowering ADR. A validated rating scale and improved bowel preparation are needed to make sigmoidoscopy an appropriate screening method.Trial registration Clinicaltrials.gov (NCT01538550).

Women require routine opioids to prevent painful colonoscopies: a randomised controlled trial.

BACKGROUND: Women are at high risk for painful colonoscopy. Pain, but also sedation, are barriers to colorectal cancer (CRC) screening participation. In a randomised controlled trial, we compared on-demand with pre-colonoscopy opioid administration to control pain in women at CRC screening age. METHODS: Women, aged 55-79 years, attending colonoscopy at two Norwegian endoscopy units were randomised 1:1:1 to (1) fentanyl on-demand, (2) fentanyl prior to colonoscopy, or (3) alfentanil on-demand. The primary endpoint was procedural pain reported by the patients on a validated four-point Likert scale and further dichotomized for the study into painful (moderate or severe pain) and non-painful (slight or no pain) colonoscopy. Secondary endpoints were: willingness to repeat colonoscopy, adverse events, cecal intubation time and rate, and post-procedure recovery time. RESULTS: Between June 2017 and May 2020, 183 patients were included in intention-to-treat analyses in the fentanyl on-demand group, 177 in the fentanyl prior to colonoscopy group, and 179 in the alfentanil on-demand group. Fewer women receiving fentanyl prior to colonoscopy reported a painful colonoscopy compared to those who were given fentanyl on-demand (25.2% vs. 44.1%, p < .001). There was no difference in the proportion of painful colonoscopies between fentanyl on-demand and alfentanil on-demand (44.1% vs. 39.5%, p = .40). No differences were observed for adverse events or any of the other secondary endpoints between the three groups. CONCLUSIONS: Fentanyl prior to colonoscopy provided better pain control than fentanyl or alfentanil on-demand. Fentanyl before colonoscopy should be recommended to all women at screening age. Trial registration: Clinicaltrials.gov (NCT01538550). Norwegian Medicines Agency (16/16266-13). EU Clinical Trials Register (EUDRACTNR. 2016-005090-13).

Performance of Faecal Immunochemical Testing for Colorectal Cancer Screening at Varying Positivity Thresholds.

BACKGROUND: The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries. AIMS: To explore the trade-off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial. METHODS: We included first participation in biennial FIT screening for 47,265 individuals aged 50-74 years. Individuals with FIT > 15 µg Hb/g faeces were referred for colonoscopy. We estimated the number of colonoscopies, adverse events, screen-detected CRCs, advanced adenomas and serrated lesions expected at FIT thresholds currently or recently used in other European countries ranging between 20 and 150 µg/g. RESULTS: At the 15 µg/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47 µg/g threshold, 1826 (49.3%) individuals would have undergone colonoscopy, and 154 (75.9%) would have been diagnosed with CRC, 702 (62.7%) with advanced adenoma and 128 (50.0%) with advanced serrated lesion compared to the 15 µg/g threshold. At 150 µg/g, the corresponding figures would have been 838 (22.6%) undergoing colonoscopy, 114 (56.2%) with CRC, 345 (30.8%) advanced adenoma and 54 (21.1%) advanced serrated lesions. The detection rate of stage I CRC was 0.22% at 15 µg/g and 0.11% at 150 µg/g. Post-colonoscopy bleeding rates were 0.8% and 1.7%, respectively. CONCLUSIONS: Increasing the FIT threshold reduces colonoscopy demand, but substantially decreases lesion detection and unfavourably changes CRC stage distribution. The risk of adverse events at colonoscopy increased with FIT threshold, requiring country-specific information on adverse events. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01538550.

Colonoscopy quality improvement after initial training: A cross-sectional study of intensive short-term training.

Background and study aims High-quality is crucial for the effectiveness of colonoscopy and can be achieved by high-quality training and verified with assessment of key performance indicators (KPIs) for colonoscopy such as cecum intubation rate (CIR), adenoma detection rate (ADR) and adequate polyp resection. Typically, trainees achieve adequate CIR after 275 procedures, but little is known about learning curves for KPIs after initial training. Methods This cross-sectional study includes work-up colonoscopies after a positive screening test with fecal occult blood testing (FIT) or sigmoidoscopy, performed by either trainees after 300 training colonoscopies or by consultants. Outcome measures were KPIs. We assessed inter-endoscopist variation in trainees and learning curves for trainees as a group. We also compared KPIs for trainees and consultants as a group.  Results Data from 6,655 colonoscopies performed by 21 trainees and 921 colonoscopies performed by 17 consultants were included. Most trainees achieved target standards for main KPIs. With time, trainees shortened cecum intubation time and withdrawal time without decreasing their ADR, reduced the proportion of painful colonoscopies, and increased the adequate polyp resection rate (all P  < 0.01). Compared to consultants, trainees had higher CIR (97.7 % vs. 96.3 %, P  = 0.02), ADR after positive FIT (57.6 % vs. 50.3 %, P  < 0.01), and proximal ADR after sigmoidoscopy screening (41.1 % vs. 29.8 %; P  < 0.01), higher adequate polyp resection rate (94.9 % vs. 93.1 %, P  = 0.01) and fewer serious adverse events (0.65 % vs. 1.41 %, P  = 0.02). Conclusions Trainees performed high-quality colonoscopies and achieved international target standards. Several KPIs continuously improved after initial training. Trainees outperformed consultants on several KPIs.

Detection of cancers and advanced adenomas in asymptomatic participants in colorectal cancer screening: a cross-sectional study.

OBJECTIVES: To assess detection rates for colorectal cancer (CRC) and advanced adenomas in asymptomatic CRC screening participants and bowel symptoms in association with CRC and advanced adenoma. DESIGN: Cross-sectional study. SETTING: Two screening centres. PARTICIPANTS: 42 554 men and women, aged 50-74 years, participating in a randomised CRC screening trial. 36 059 participants underwent a sigmoidoscopy (and follow-up colonoscopy if positive sigmoidoscopy) and 6495 underwent a colonoscopy after a positive faecal immunochemical test (FIT). PRIMARY AND SECONDARY OUTCOME MEASURES: Proportion of asymptomatic participants diagnosed with CRC or advanced adenomas. Prevalence of bowel symptoms (rectal bleeding, change in bowel habits, diarrhoea, constipation, bloating, alternating bowel habits, general symptoms, other bowel symptoms) recorded by the endoscopist and their association with CRC and advanced adenomas. RESULTS: Among sigmoidoscopy participants, 7336 (20.3%) reported at least one symptom. 120 (60%) out of 200 individuals with screen-detected CRC and 1301 (76.5%) out of 1700 with advanced adenoma were asymptomatic. Rectal bleeding was associated with detection of CRC and advanced adenoma (OR 4.3, 95% CI 3.1 to 6.1 and 1.8, 95% CI 1.5 to 2.1, respectively), while change in bowel habits only with CRC detection (OR 3.8, 95% CI 2.4 to 6.1). Among the FIT positives, 2173 (33.5%) reported at least one symptom. Out of 299 individuals with screen-detected CRC and 1639 with advanced adenoma, 167 (55.9%) and 1 175 (71.7%) were asymptomatic, respectively. Detection of CRC was associated with rectal bleeding (OR 1.8, 95% CI 1.4 to 2.3), change in bowel habits (OR 2.2, 95% CI 1.4 to 3.5) and abdominal pain (OR 1.8, 95% CI 1.2 to 2.7). CONCLUSIONS: Some bowel symptoms increased the likelihood of being diagnosed with CRC or advanced adenoma. However, the majority of individuals with these findings were asymptomatic. Asymptomatic individuals should be encouraged to participate in CRC screening. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov Identifier: NCT01538550.

Complement C5 mediates experimental tubulointerstitial fibrosis.

Renal fibrosis is the final common pathway of most progressive renal diseases. C5 was recently identified as a risk factor for liver fibrosis. This study investigated the role of C5 in the development of renal tubulointerstitial fibrosis by (1) induction of renal fibrosis in wild-type and C5(-/-) mice by unilateral ureteral ligation (UUO) and (2) investigation of the effects of a C5a receptor antagonist (C5aRA) in UUO. In C5(-/-) mice, when compared with wild-type controls, markers of renal fibrosis (Sirius Red, type I collagen, fibronectin, alpha-smooth muscle actin, vimentin, and infiltrating macrophages) were significantly reduced on day 5 of UUO. On day 10, fibronectin mRNA and protein expression were still reduced in the C5(-/-) mice. Cortical mRNA of all PDGF isoforms and of TGF-beta(1) (i.e., central mediators of renal disease) were significantly reduced in C5(-/-) mice when compared with controls. Renal tubular cell expression of the C5aR was sparse in normal cortex but markedly upregulated after UUO. Treatment of wild-type UUO mice with C5aRA also led to a significant reduction of cortical Sirius Red staining, fibronectin protein expression, and PDGF-B mRNA expression on day 5. Neither genetic C5 deficiency nor C5aRA treatment caused any histologic changes in the nonobstructed kidneys. In cultured murine cortical tubular cells, C5a stimulated production of TGF-beta(1), and this was inhibited by C5aRA. Using a combined genetic and pharmacologic approach, C5, in particular C5a, is identified as a novel profibrotic factor in renal disease and as a potential new therapeutic target.