Impact of experience with a retrograde-viewing device on adenoma detection rates and withdrawal times during colonoscopy: the Third Eye Retroscope study group.

BACKGROUND: Colonoscopy has been adopted as the preferred method to screen for colorectal neoplasia in the United States. However, lesions can be missed because of numerous factors, including location on the proximal aspect of folds or flexures, where they may be difficult to detect with the forward-viewing colonoscope. The Third Eye Retroscope (TER) is a disposable device that is passed through the instrument channel of a standard colonoscope to provide a retrograde view that complements the forward view of the colonoscope during withdrawal. OBJECTIVE: To evaluate whether experience with the TER affects polyp detection rates and procedure times in experienced endoscopists who had not previously used the equipment. DESIGN, SETTING, PATIENTS: This was an open-label, prospective, multicenter study at 9 U.S. sites, involving 298 patients presenting for colonoscopy, evaluating the use of the TER in combination with a standard colonoscope. INTERVENTIONS: After cecal intubation, the TER was inserted through the instrument channel of the colonoscope. During withdrawal, the forward and retrograde video images were observed simultaneously on a wide-screen monitor. MAIN OUTCOME MEASUREMENTS: Primary outcome measures were the number and size of adenomas and all polyps detected with the standard colonoscope and with the colonoscope combined with the TER. Secondary outcome measures were withdrawal phase time and total procedure time. Each endoscopist examined 20 subjects, divided into quartiles according to the order of their procedures, and results were compared among quartiles. RESULTS: Overall, 182 polyps were detected with the colonoscope and 27 additional polyps with the TER, a 14.8% increase (P < .001). A total of 100 adenomas were detected with the colonoscope and 16 more with the TER, a 16.0% increase (P < .001). For procedures performed after each endoscopist had completed 15 procedures while using the TER, the mean additional detection rates with the TER were 17.0% for all polyps (P < .001) and 25.0% for adenomas (P < .001). For lesions 6 mm or larger, the overall additional detection rates with the TER for all polyps and for adenomas were 23.2% and 24.3%, respectively. For lesions 10 mm or larger, the overall additional detection rates with the TER for all polyps and for adenomas were 22.6% and 19.0%, respectively. The mean withdrawal times in the first and fourth quartiles were 10.6 and 9.2 minutes, respectively (P = .044). LIMITATIONS: There was no randomization or separate control group. The endoscopists judged whether each lesion could have been detected with the colonscope alone by using their standard technique. CONCLUSIONS: Polyp detection rates improved significantly with the TER, especially after 15 procedures, when the mean additional detection rate for adenomas was 25.0%. Additional detection rates with the TER for medium-size and large adenomas were greater than for smaller lesions. These results suggest that, compared with a colonoscope alone, a retrograde-viewing device can increase detection rates for clinically significant adenomas without detriment to procedure time or procedure complications. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00969124.).

Five-year efficacy and safety analysis of the Adenoma Prevention with Celecoxib Trial.

The Adenoma Prevention with Celecoxib Trial examined the efficacy and safety of the cyclooxygenase (Cox)-2 inhibitor, celecoxib, for sporadic colorectal adenoma prevention in patients at high risk for colorectal cancer. The trial randomized 2,035 subjects to receive either placebo, celecoxib 200 mg twice daily, or celecoxib 400 mg twice daily. The primary study safety and efficacy analyses involved 3 years of treatment. The results showed significant antitumor effect but also indicated increased cardiovascular adverse events in patients treated with celecoxib compared with placebo. A total of 933 patients participated in an extension of the Adenoma Prevention with Celecoxib Trial, with a planned total treatment and surveillance duration of 5 years. Study medication was stopped early, resulting in a median treatment duration of 3.1 years for those with a year 5 colonoscopy. Patients treated on the placebo arm had a cumulative adenoma incidence of 68.4% over 5 years of observation. This figure was 59.0% (P < 0.0001) for those receiving low-dose celecoxib, and 60.1% (P < 0.0001) for those receiving high-dose celecoxib. The cumulative incidence of advanced adenomas over 5 years was 21.3% of those taking placebo, 12.5% (P < 0.0001) of those taking low dose celecoxib and 15.8% (P < 0.0001) of those taking high-dose celecoxib. Investigator reported treatment emergent adverse events were similar across all treatment groups for categories including renal and hypertensive events and gastrointestinal ulceration and hemorrhage events. For a category composed of cardiovascular and thrombotic events, the risk relative to placebo was 1.6 (95% confidence interval, 1.0, 2.5) for those using 200 mg twice daily celecoxib and 1.9 (95% confidence interval, 1.2, 3.1) for those using 400 mg twice daily celecoxib. Secondary analysis showed an interaction between a baseline history of atherosclerotic heart disease and study drug use with respect to cardiovascular and thrombotic adverse events (P = 0.004). These results confirm the inhibitory effect of celecoxib on colorectal adenoma formation, and provide additional safety data indicating an elevated risk for cardiovascular and thrombotic adverse events, particularly for patients with preexisting atherosclerotic heart disease.

Celecoxib for the prevention of sporadic colorectal adenomas.

BACKGROUND: Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia. METHODS: We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin. Follow-up colonoscopies were performed at one and three years after randomization. The occurrence of newly detected colorectal adenomas was compared among the groups with the life-table extension of the Mantel-Haenszel test. RESULTS: Follow-up colonoscopies were completed at year 1 in 89.5 percent of randomized patients, and at year 3 in 75.7 percent. The estimated cumulative incidence of the detection of one or more adenomas by year 3 was 60.7 percent for patients receiving placebo, as compared with 43.2 percent for those receiving 200 mg of celecoxib twice a day (risk ratio, 0.67; 95 percent confidence interval, 0.59 to 0.77; P<0.001) and 37.5 percent for those receiving 400 mg of celecoxib twice a day (risk ratio, 0.55; 95 percent confidence interval, 0.48 to 0.64; P<0.001). Serious adverse events occurred in 18.8 percent of patients in the placebo group, as compared with 20.4 percent of those in the low-dose celecoxib group (risk ratio, 1.1; 95 percent confidence interval, 0.9 to 1.3; P=0.5) and 23.0 percent of those in the high-dose group (risk ratio, 1.2; 95 percent confidence interval, 1.0 to 1.5; P=0.06). As compared with placebo, celecoxib was associated with an increased risk of cardiovascular events (risk ratio for the low dose, 2.6; 95 percent confidence interval, 1.1 to 6.1; and risk ratio for the high dose, 3.4; 95 percent confidence interval, 1.5 to 7.9). CONCLUSIONS: These findings indicate that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication. (ClinicalTrials.gov number, NCT00005094 [ClinicalTrials.gov].).