Colonoscopy Preparation in Low-Risk People

Colonoscopy has been established as the gold standard procedure for the diagnosis, detection and surveillance of colorectal cancer (CRC). Adequate bowel preparation (BP) is the basis for the success of the procedure and the accurate diagnosis of colorectal lesions. High-volume (3-4 L) polyethylene glycol (PEG) -based regimens have been established as standard regimens for BP in unselected patients.

However, the large volume and unpleasant taste lead to suboptimal patient compliance and acceptability, hampering its clinical application. To address these disadvantages, optimized methods using lower volume PEG combined with additional intestinal purgatives have been developed, which showed comparable efficacy with improved compliance compared to high volume regimens.

Several risk factors have been identified as predictors of colonoscopy preparation failure such as advanced age, constipation, diabetes mellitus, history of inadequate blood pressure, use of narcotics and tricyclic antidepressants. Although low-volume regimens appear to be less effective in these high-risk patients, they may be attractive alternatives for low-risk patients that are relatively easy to prepare. As awareness of colonoscopy for CRC screening is increasing, more low-risk patients are likely to participate in colonoscopy screening. However, data on BP performance in low-risk patients are limited.

A further reduction in volume without compromising the efficacy of bowel cleansing could represent a promising strategy to improve tolerability and compliance, especially in low-risk patients.

Linaclotide , a guanylate acid peptide cyclase-C agonist, could increase luminal fluid secretion and mediate visceral analgesia, thereby inducing a laxative effect and improving abdominal symptoms. It has been reported that 290 μg linaclotide exerted a comparable effect compared to 2L PEG on blood pressure for capsule endoscopy. Another study also showed that 290 μg linaclotide combined with 2 L PEG was comparably effective and associated with better tolerability compared to 4 L PEG regimens. Based on these results, we hypothesize the additional use of linaclotide, which may not only reduce the total PEG volume while maintaining the desired efficacy, but also improve the patients’ experience during colonoscopy.

The efficacy and tolerability of a new BP regimen using 1L PEG and linaclotide (1L PEG+L) versus a single dose of 2L PEG was investigated in low-risk patients.

M In this prospective, randomized, observer-blind, multicenter study, low-risk adult patients scheduled for colonoscopy were enrolled and randomized (1:1) to receive 1L PEG+L or 2L PEG regimen. The primary outcome was the effectiveness of bowel cleansing according to the Boston Bowel Preparation Scale (BBPS). Secondary outcomes included cecal intubation rate, cecal insertion time, removal time, polyp detection rate (PDR) and adenoma detection rate (ADR), tolerability, adverse events, and willingness to repeat bowel preparation. The full analysis set (FAS) and per-protocol set (PPS) were used for statistical analyses.

A total of 548 patients comprised the FAS while 522 patients comprised the PPS. Non-inferiority in adequate intestinal cleansing of 1 L of PEG+L versus 2 L of PEG was established in both FAS (90.5% vs 91.6%, P = 0.644) and PPS (90.3% vs 92.4%, P =0.390).

There were no significant differences regarding the total and each segment of BBPS scores, cecal intubation rate, cecal insertion time, removal time, PDR and ADR. However, patients in the 1L PEG+L group reported less nausea (7.7% vs 17.1%, P < 0.01), vomiting (4.0% vs 10.9%, P < 0.01 ) and had a greater willingness to repeat (95.2% vs 82.2%, P < 0.01).

This multicenter randomized controlled trial recommended 1L PEG+L as an alternative to the single-dose 2L PEG regimen for low-risk individuals. Not only did the new regimen show high intestinal cleansing efficacy, but it also improved patient tolerability and willingness to repeat the preparation.

Additional use of adjuvants (e.g., ascorbic acid or bisacodyl) combined with 2L PEG has been validated and recommended for routine BP with comparable efficacy and increased tolerability. However, the 2L dose is still large to ingest. Several ultra-volume regimens have been developed to promote improved patient experience with either hyperosmotic solution or laxative stimulant. In the present study, 1L PEG+L was highly effective, achieving adequate BP in more than 90% of patients with a similar safety profile compared to 2L PEG.

Linaclotide, a minimally absorbed guanylate cyclase-C agonist, accelerated colonic transit and improved abdominal and intestinal symptoms in patients with IBS-C. Regarding its laxative effect, linaclotide has been used in capsule BP and colonoscopy to improve intestinal cleansing with minimal side effects.

Consistent with these results, the study also suggested that the combination of 1L PEG with linaclotide showed similar efficacy to 2L PEG without serious adverse events. It is noted that the use of linaclotide shortened the time of the first desertion after consuming PEG (22.66 ± 14.70 min vs. 31.89 ± 21.06 min, which may contribute to adequate preparation in the 1L PEG group +L.

Interestingly, it was hoped that linaclotide would reduce abdominal discomfort during colonoscopy preparation, but in this it failed. Given the increasing awareness of colonoscopy for CRC screening, the proportion of low-risk individuals who may benefit from lower intensity bowel cleansing compared to high-risk individuals is increasing. Recently, numerous studies have been carried out in high-risk patients to improve the quality of intestinal cleansing while the current evidence in “easy to prepare” patients is scarce.

Consistent with previous work, this study reported that 52.1% of patients were at low risk. Therefore, we estimated that almost half of patients undergoing colonoscopy would benefit from this novel ultra-low volume regimen, which emphasized the importance of improved instructions, intensive diet restriction, and better compliance.

The overall ADRs in both groups in this study (ranging from 18.3% to 21.5%) appeared to be lower than that recommended for a population not selected for colonoscopy. Patient characteristics such as age, BMI, diabetes mellitus, and personal history of adenoma were risk factors associated with colorectal adenoma. The relatively low ADRs in this study could be attributed to data obtained from low-risk patients with relatively younger age (around 45 years), lower BMI (around 22 kg/m2), and lower comorbidity (diabetes), similar to those reported in another study of low-risk patients

There are several strengths to this study. First, the results have considerable clinical implication. Given the growing awareness and accessibility of colonoscopy for CRC screening, the percentage of screening among low-risk individuals would increase. The 1L PEG+L regimen provided high-quality bowel cleansing with safety and better tolerability for “easy-to-prep” patients, who might benefit more from less intensive regimens.

Second, the multicenter design and large sample size provided highly generalizable results. Third, the rigorous methodology: randomization until enrollment and blinding of endoscopists was used. to reduce both conscious and unconscious bias. Fourth, the primary evaluation was based on the well-validated BBPS, which was performed by two independent blinded observers. The analyzes based on FAS and PPS were consistent, which further supported the validity of the results in this study.

Several limitations must be recognized. First, the regimen in this study was performed for procedures performed in the afternoon and its effectiveness for morning procedures were uncertain. Second, a split-dose regimen was not used for bowel cleansing, which was commonly used in high-volume preparations. However, it is still unclear whether split dosing is feasible with ultra-low volume fluids. Consistent with the study, the combined efficacy of ultra-low-volume regimens with same-day adjustment was reported to be nearly 90%, suggesting that the same-day regimen was a viable option.

Third, there are no uniform criteria for the low-risk population at present. BP-related factors are used as exclusion criteria in this study based on high-quality RCTs, meta-analyses, and guidelines. Fourth, although the 1 L PEG+L regimen was an effective, well-tolerated and safe treatment for low-risk patients, several essential prerequisites were needed for its success, including improved instructions, strict dietary restriction, and high adhesion. Additionally, more studies are needed to establish the optimal dose and timing of taking linaclotide for colonoscopy. Fifth, the analysis was restricted to low-risk individuals and generalization of these findings to the general population should be taken with caution.