According to the increase of the proportions of colon disease year after year, the importance of colonoscopy examinations is growing. Besides, the general use of colonoscopies has been suggested for colon cancer screening. Thorough bowel preparation is necessary for the safe and accurate completion of the colonoscopy examination. Actually, diagnostic accuracy and therapeutic safety of the colonoscopy relies on the quality of the bowel preparation [1-5].

Though appropriate preparation is generally defined as one that allows the detection of colonic polyps 5 mm or larger [6], this definition does not consider the shape of the lesions, and it is well known that flat lesions are more difficult to detect. The cecal intubation rate and adenoma detection rate are two of the chief quality colonoscopic indices. Those have close relation with the quality of bowel preparation [7].

Inappropriate bowel cleaning can cause low detection rates of incipient and advanced adenomas, flat lesions, and flat adenomas [7-10]; it can also cause a higher rate of canceled procedures with increased costs, prolonged procedures, and a higher risk of complications [11].

Bowel preparation is one of the concerns that negatively affect the willingness of patients to receive the colonoscopy procedure [12,13]. Compliance to the preparation process is a main important factor for success colonoscopy, as compliance affects the quality of the bowel preparation. But, the preparation process has limitations due to side effects, and the low tolerance for the taste and the large amount of solution, which are the leading causes for avoiding the complete bowel preparation [14]. Polyethylene glycol (PEG) solution has been the favored bowel preparation agent to use prior to performing diagnostic and therapeutic colonoscopy procedures on the colon and rectum.

Ramosetron is a selective serotonergic 5-hydroxy-tryptamine (HT) receptor-3 antagonist that is used to prevent and treat postoperative or chemotherapy-induced nausea and vomiting [15,16]. The author supposes that ramosetron can improve a patient’s tolerance and satisfaction regarding the PEG solution. However, the efficacy and tolerability of PEG with or without ramosetron has not been investigated. Based on that, we conducted a prospective, pilot study to evaluate the tolerability, and efficacy of ramosetron as an adjuvant in the PEG solution for colonoscopy preparation who had difficulty taking PEG due to side effects and large volume.

The baseline characteristics of current PEG+ramosetron group are presented in Table 1. The mean age of enrolled patients was 48.79±14.97 years old. Male to female ratio was 1:1.54. Of the 28 patients, 11 patients had underlying diseases such as 5 diabetes mellitus (17.9%), 6 hypertension (21.4%), 5 cancer (17.9%), 2 asthma (7.1%), and 3 heart failure (10.7%). Of the total patients, 13 patients (46.4%) had a previous history of abdominal surgery. The mean previous colonoscopy interval time was 26.3±17.7 months. The mean cecal intubation time and withdrawal time were 4.1±2.1 and 6.7±2.4 min, respectively.

Concerning the PEG volume, 12 of the 28 patients (42.9%) were able to finish 100% (4 L) of the PEG solution in the previous PEG only group. However 22 of the 28 patients (78.6%) were able to finish 100% of the PEG solution in the PEG+ramosetron group (p=0.019). The number of patients who finished less than half the amount of the PEG solution are 5 (17.8%) and 1 (3.5%) in previous PEG only group and PEG+ramosetron group, respectively. The patients’ acceptability in these two groups was significantly different (Table 2).

With regard to side effects of the bowel preparation, several symptoms were assessed in the questionnaire, including nausea, vomiting, abdominal discomfort and abdominal pain. Side effects were more frequently found in the previous PEG only group than in the PEG+ramosetron group (p<0.001). Of the total 28 patients, 18 (64.3%) patients did not complain of any side effects in PEG+ramosetron group (Table 2).

The authors investigated the satisfaction of patients with the bowel preparation method. The proportion of excellent satisfaction in the PEG+ramosetron group (64.3%) was higher than that in the previous PEG only group (64.3% vs. 19.7%, p<0.001, respectively) (Table 2).

The efficacy of the bowel preparation was categorized into four groups as clear, fluid that can be sucked away, small amount of feces and large amount of feces. As much as 78.6% of bowel preparation in the previous PEG only group was optimal and 89.3% of bowel preparation in PEG+ramosetron group was optimal (p=0.052). Although not statistically significant, both groups showed a comparable overall assessment of bowel preparation (p=0.175) (Table 2).

The cecal intubation rate and adenoma detection rate, which are quality indexes of colonoscopy quality, did not differ between the two groups. The cecal intubation rate accounted for 96.4% of both two groups, except for one patient with stenosis with Crohn's disease. Adenoma detection rate were 28.6% in previous PEG only group and 25.0% in the PEG+ramosetron group, which are not statistical significantly (p=0.118).

Bowel preparation before colonoscopy is usually considered as uncomfortable by patients. It is common for patients to complain that the bowel preparation is harder than the actual colonoscopy procedure. Accordingly, many kinds of agents have been studied in order to achieve comfortable and effective bowel preparation. Many reports about PEG solution have concluded that PEG is more effective and better tolerated than the combination of diet and laxative regimens, high-volume balanced electrolyte solutions, and mannitol-based solutions [17-20]. Even if PEG is usually well-tolerated, 5-15% patients who take PEG do not complete the preparation because of the bad taste, large volume or side effects [21]. In particular, patients experiencing difficulty with PEG administration and side effects may have a negative willingness of colonoscopy, leading to poor compliance and avoidance of examination.

There are several studies that have evaluated the effects of prokinetics on bowel preparation. Abdullah et al. reported that the adjunct use of clebopride in PEG solution for bowel preparation tended to increase the acceptability, tolerability and efficacy [22]. Tajika et al. revealed that mosapride citrate can be an effective and safe adjunct to PEG solution which brings about improved bowel preparation status [23]. However, it has not been fully evaluated to add-on prokinetic agents with PEG in terms of the efficacy and safety of colonic cleansing. In addition, as the difficulty and side effects during PEG administration may increase the avoidance of colonoscopy, safer and more effective adjunctive agents are required.

Ramosetron (Nasea^®; Astellas), a new generation 5-HT3 antagonists developed newly in Japan, has a higher potency and longer lasting antiemetic effect than first-generation 5-HT3 antagonists [24,25]. Three-dimensional molecular modeling studies have revealed that ramosetron occupies the 5-HT binding site of 5-HT3 receptors with long lasting antagonism [26]. Ramosetron is commonly used to treat postoperative nausea and vomiting or chemotherapy-induced nausea and vomiting [27].

The present study showed that patient acceptability was superior in the PEG+ramosetron group compared to the previous PEG only group (p=0.019). With regard to side effects, ramosetron reduced the presence of nausea and vomiting (p<0.001). In regard to patient satisfaction, the proportion of excellent satisfaction in the PEG+ramosetron group was higher than that in the previous PEG only group (p<0.001). As to the efficacy of bowel preparation assessed by the colonoscopist, both groups showed comparable results (p=0.175). This was consistent with results of other reports that showed no statistically significant differences between the regimens for bowel preparation [28-32].

Although good bowel preparations and PEG doses are known to be interrelated, no difference in bowel preparation status revealed between two groups. The reasons for this are as follows. First, the PEG dosage is measured in quarters, making it difficult to accurately dose PEG. That is, the difference in the amount of 1 L of PEG in each quartile may have affected the difference in the degree of bowel preparation. Second, differences in the dosing interval may have affected the bowel preparation. Non-compliance of dosing interval was not checked. Third, the previous PEG dose is likely to be inaccurate due to a colonoscopy interval of 2 years or more.

Generally, the PEG solution is very effective for bowel preparation before colonoscopy. But patients show a somewhat low tolerance due to the large amount of solution and the side effects that include nausea, vomiting and abdominal pain. In the present study, ramosetron could increase the tolerance and decrease various side effects. In addition, ramosetron may help to reduce negative willingness about colonoscopy by increasing the satisfaction of taking PEG.

There are some limitations in this study. First, although it is a prospective study, it is a small population-pilot study without a definite control group. No appropriate control group to compare with PEG+ramosetron group only was established. Second, recall bias can occur. As I aforementioned, depending on the memory, the data was collected in a form that filled the questionnaire with total amount of PEG solution and the side effects that occurred during the previous colonoscopy. Third, the effect of ramosetron can be overestimated. Fourth, due to the chart review format, accurate assessment of previous patients' characteristics and quality of colonoscopy including cecal intubation time and withdrawal time may be insufficient. Finally, grading of side effects is not evaluated, although no severe adverse effects were found to stop colonoscopy. However, this study was the first to compare efficacy with previous PEG alone group using PEG+ramosteron for bowel preparation in patients with difficult taking PEG.

In conclusion, similar to several prokinetics that were reported at previous study, ramosetron can be a good adjunctive agent for bowel preparation when used with PEG solution.