Meta-Analysis Open Access
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 26, 2021; 9(15): 3607-3622
Published online May 26, 2021. doi: 10.12998/wjcc.v9.i15.3607
Effect of antifoaming agent on benign colorectal tumors in colonoscopy: A meta-analysis
Hu Zhang, Jing Gong, Lin-Song Ma, Ting Jiang, Heng Zhang, Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China
Hu Zhang, Department of Gastroenterology, The Eighth Hospital of Wuhan, Wuhan 430014, Hubei Province, China
ORCID number: Hu Zhang (0000-0002-5615-7109); Jing Gong (0000-0003-1193-0927); Lin-Song Ma (0000-0001-7464-064X); Ting Jiang (0000-0002-5293-7220); Heng Zhang (0000-0002-6964-7537).
Author contributions: Heng Z designed this study and critically revised the manuscript; Hu Z and JL were responsible for data acquisition and extraction; Hu Z drafted the manuscript, analyzed the data, and interpreted the results; Hu Z, Ma LS, Jiang T, and Gong J were involved in editing the manuscript; All authors read and approved the final manuscript.
Supported by the Natural Science Foundation of Wuhan, No. WX18Y04.
Conflict-of-interest statement: All of the authors declare that they have no conflicts of interest regarding this paper.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist statement, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Heng Zhang, MA, MD, Chief Doctor, Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No. 26 Shengli Street, Jiangan District, Wuhan 430014, Hubei Province, China. 653262549@qq.com
Received: January 3, 2021
Peer-review started: January 3, 2021
First decision: February 11, 2021
Revised: February 25, 2021
Accepted: March 12, 2021
Article in press: March 12, 2021
Published online: May 26, 2021

Abstract
BACKGROUND

Although several trials have shown that the addition of antifoaming agents to polyethylene glycol (PEG) can improve bowel preparation, whether PEG plus antifoaming agents have a beneficial role in the detection of benign tumors during colonoscopy has yet to be confirmed. Our aim was to clarify whether adding simethicone to PEG solution could improve the detection of benign colorectal tumors.

AIM

To clarify whether adding simethicone to PEG solution could improve the detection of benign colorectal tumors.

METHODS

The PubMed, EMBASE, and Cochrane Library databases were searched for articles published prior to September 2019. The outcomes included the detection rates of colorectal adenomas and polyps.

RESULT

Twenty studies were eligible. Although there was no difference in the colorectal adenoma detection rate (ADR), a significant effect of simethicone for diminutive adenomas (< 10 mm) was revealed in the group taking simethicone. We also found that simethicone could significantly improve the ADR in the proximal colon but did not affect the colorectal polyp detection rate. Furthermore, the subgroup analyses revealed a beneficial effect of simethicone on the ADR among Asians (P = 0.005) and those with an ADR < 25% (P = 0.003). Moreover, it was a significant finding that the low dose simethicone was as effective as the high dose one with respect to the detection of benign colorectal tumors.

CONCLUSION

In summary, the addition of simethicone to PEG might improve the detection of diminutive adenomas in the right colon by colonoscopy in Asia. Low-dose simethicone was recommended for the detection of benign colorectal tumors. However, large clinical trials are necessary to validate our results and determine the ideal dose of simethicone.

Key Words: Antifoaming agent, Simethicone, Polyethylene glycol, Colonoscopy, Meta-analysis

Core Tip: The addition of simethicone to polyethylene glycol might improve the detection of diminutive adenomas in the right colon by colonoscopy in Asia. Low-dose simethicone was recommended for the detection of benign colorectal tumors.
INTRODUCTION

Colorectal cancer (CRC) is a common cancer worldwide. The incidence and mortality of CRC have been rapidly increasing in Asian countries[1,2]. Early diagnosis is associated with better survival and quality of life. Currently, colonoscopy is a standard first-line tool for the screening, surveillance, and prevention of colorectal tumors[3,4]. The colorectal adenoma detection rate (ADR) is regarded as the most important indicator of colonoscopy. Polyethylene glycol (PEG) is recommended as the preferred choice for bowel preparation[5]. However, up to a quarter of patients have shown inadequate bowel preparation[6]. Inadequate bowel preparation is related to an increased risk of missed benign colorectal tumors and more discomfort for patients[7-9].

Simethicone, which prevents bubble formation and gas retention to alleviate bloating, is an effective and safe antifoaming agent for use during endoscopic procedures. A combination of simethicone and PEG has been shown to improve the visualization of the bowel for colonoscopy. Thus, simethicone could have a theoretical benefit in the detection of benign tumors in colonoscopy, especially diminutive lesions.

A large number of previous studies have evaluated the effect of simethicone in ADR during colonoscopy, but the results have been inconsistent. Hence, a recent meta-analysis is necessary. However, whether simethicone plus PEG has a beneficial role in the detection of benign tumors during colonoscopy has yet to be confirmed. Therefore, we performed a meta-analysis to investigate its effect on the detection of benign colorectal tumors.

MATERIALS AND METHODS
Literature search

The PubMed, EMBASE, and Cochrane Central databases (up to September 1, 2019) were searched using the keywords “colonoscopy”, “antifoaming agent” or “simethicone”, and “randomized”. We also performed a manual search of the reference lists of the published articles.

Inclusion criteria

(1) Study design: randomized studies as full manuscripts; (2) Language: limited to English; (3) Population: patients who underwent a colonoscopy; (4) Controls: PEG without simethicone for bowel preparation; (5) Intervention: PEG with simethicone for bowel preparation; and (6) Outcomes: primary endpoints: colorectal ADR and polyp detection rate (PDR) and secondary endpoint: adverse events.

Exclusion criteria

(1) Bowel preparation without PEG or simethicone; (2) Nonhuman studies; (3) Duplicate publications; and (4) Studies without available data.

Data extraction

The data were extracted by 3 investigators (HZ, JG, and LM) independently. Disagreements were resolved by consensus. The data included the author, year, number of patients, country or region, detailed information on interventions and controls (ADR and PDR), and adverse events.

Assessment of study quality

The Cochrane Collaboration’s risk of bias tool[10] was used to evaluate the quality of the randomized studies. The quality scale was assessed as “low risk of bias”, “unclear risk of bias”, and “high risk of bias”.

Data syntheses and statistical analysis

The odds ratio (OR) was used for discrete variables, and the mean difference and standardized difference in mean were used for continuous variables. The pooled ORs and 95% confidence intervals (CIs) were calculated from the studies using either a fixed-effects model or a random-effects model. When the heterogeneity was significant, the random-effects model was used for the pooled data; otherwise, a fixed-effects model was used. Heterogeneity among the studies was assessed using the I2 statistic or the χ2 test. I2 > 50% or P < 0.10 was considered to indicate heterogeneity. Publication bias was evaluated by Egger’s test, where P < 0.10 in a two-tailed test was regarded as positive. In the subgroup analyses, P < 0.05 for the χ2 test indicated statistically significant heterogeneity. By excluding one or more studies each time, sensitivity analysis was conducted to evaluate the robustness of the pooled results[11]. All of the statistical analyses and plots were performed using Review Manager statistical software, version 5.0 (the Cochrane Collaboration, Copenhagen, Denmark) and Stata software, version 12.0 (Stata Corp LLC, Texas, United States).

RESULTS
Study selection

The literature search retrieved 169 citations, 96 of which were excluded due to duplication. Of the 73 eligible studies, 53 studies were excluded, and 20 studies focused on comparing PEG with and without simethicone to evaluate the effects on ADR and PDR. This meta-analysis was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis[12] (Figure 1).

Figure 1
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Figure 1 Flowchart of the study selection. PEG: Polyethylene glycol.
Study characteristics

The 20 studies[13-32] included 6306 patients, of whom 3162 and 3144 patients were assigned to the PEG plus simethicone group and PEG group, respectively (Tables 1 and 2). These studies were performed in five countries (China, South Korea, Italy, United States, and Netherlands).

Table 1 Characteristics of the studies included in the meta-analysis.
Ref.GroupsnDose of simethicone in mgBubble scoreInsertion time in minWithdraw time in minAdverse events
Bloating
Nausea
Vomiting
Abdominal pain
Sleep disorder
Rishi et al[32] (2019)NS2L842001.77 ± 1.005.48 ± 2.8211.23 ± 3.99NR20612NR
S2L + Sim841.20 ± 0.606.06 ± 3.5511.73 ± 5.52NR13410NR
Morave et al[31] (2019)NS4L1394802.10 ± 2.156.19 ± 4.626.65 ± 1.28NRNRNRNRNR
S4L + Sim1290.10 ± 0.156.06 ± 3.716.60 ± 1.15NRNRNRNRNR
Zhang et al[13] (2018)NS2L29012002.5 ± 0.77.5 ± 5.1NR5957202457
S2L + Sim2892.8 ± 0.56.3 ± 3.1NR3461242153
Bai et al[14] (2018)NS2L28612003.98 ± 2.507.55 ± 4.196.87 ± 2.035738279NR
S2L + Sim2901.00 ± 1.267.84 ± 5.126.47 ± 1.8023393011NR
Yoo et al[15] (2016)NS2L130400NR6.75 ± 5.1317.29 ± 13.177151153139
S2L + Sim130NR6.78 ± 3.7813.35 ± 7.8631548736
Zorzi et al[16] (2016)NS2L924NRNRNR10.4 ± 29.9NRNRNRNRNR
S2L + Sim940NRNR10.6 ± 30.0NRNRNRNRNR
Kump et al[17] (2018)NS2L193NRNRNRNR2826337NR
S2L + Sim194NRNRNR2626134NR
Parente et al[18] (2015)NS4L189NRNR12 ± 710 ± 3NRNRNRNR43
S2L + Sim193NR13 ± 711 ± 6NRNRNRNR37
Mussetto et al[19] (2015)NS4L60NRNR7.8 ± 5.113.8 ± 9.62120NR626
S2L + Sim60NR6.5 ± 3.511.4 ± 9.41523NR917
Leone et al[20] (2013)NS4L79NRNR9.8 ± 3.6NR17223
S2L + Sim78NR10.9 ± 6.1NR15657
Valiante et al[21] (2013)NS4L126160NRNRNR3326NR5NR
S2L + Sim138NRNRNR1127NR13NR
Cesaro et al[22] (2013)NS4L51160NR9.5 ± 5.87.0 ± 1.81223NR2NR
S2L + Sim50NR8.1 ± 3.87.6 ± 2.4410NR6NR
Gentile et al[23] (2013)NS2L60160NRNRNRNR6310
S4L + Sim60NRNRNRNR12410
Matro et al[24] (2012)NS2L61400NRNRNR321832116
S2L + Sim62NRNRNR252231716
Repici et al[25] (2012)NS2L190160NR7.3 ± 3.5NR4357NR30NR
S2L + Sim187NR7.9 ± 3.7NR4760NR34NR
Jansen et al[26] (2011)NS2L102NRNRNRNRNRNRNR12NR
S2L + Sim86NRNRNRNRNRNR9NR
Pontone et al[27] (2011)NS2L72160NRNRNRNR7421
S4L + Sim72NRNRNRNR16511
Lazzaroni et al[28] (1993)NS4L48120NRNRNR2623NR1521
S4L + Sim57NRNRNR2620NR1311
McNally et al[29] (1989)NSNR121600.778 ± 0.278NRNRNRNRNRNRNR
SNR140.180 ± 0.054NRNRNRNRNRNRNR
McNally et al[30] (1988)NSNR48800.696 ± 0.112NRNRNRNRNRNRNR
SNR 490.114 ± 0.050NRNRNRNRNRNRNR
N: Total number of patients included; NR: Not reported; NS: Polyethylene glycol group only; S: Polyethylene glycol with simethicone group; Sim: Simethicone.
Table 2 Adenoma detection rate and polyp detection rate of the studies included in the meta-analysis.
Ref.CountryGroupsNAdenoma
Polyp
n
%
Left colon
Right colon
< 10 mm
≥ 10 mm
n
%
Left colon
Right colon
< 10 mm
≥ 10 mm
Rishi et al[32] (2019)United StatesNS2L84NRNRNRNRNRNR4654.8NRNRNRNR
S2L + Sim84NRNRNRNRNRNR4756.0NRNRNRNR
Morave et al[31] (2019)United StatesNS4L1395438.8NRNRNRNR6949.6NRNRNRNR
S4L + Sim1294333.3NRNRNRNR6046.5NRNRNRNR
Zhang et al[13] (2018)ChinaNS2L2904515.522304669332.16446NRNR
S2L + Sim2896422.136487869833.96762NRNR
Bai et al[14] (2018)ChinaNS2L2864114.335326078529.7NRNRNRNR
S2L + Sim2906121.049851221210937.6NRNRNRNR
Yoo et al[15] (2016)KoreaNS2L1306046.2NRNRNRNRNRNRNRNRNRNR
S2L + Sim1306550.0NRNRNRNRNRNRNRNRNRNR
Zorzi et al[16] (2016)ItalyNS2L92434637.4NRNRNRNR56961.6NRNR403166
S2L + Sim94032234.3NRNRNRNR54257.7NRNR380162
Kump et al[17] (2018)AustriaNS2L193NRNRNRNRNRNRNRNRNRNRNRNR
S2L + Sim194NRNRNRNRNRNRNRNRNRNRNRNR
Parente et al[18] (2015)ItalyNS4L189NRNRNRNRNRNR8949.2NRNR61NR
S2L + Sim193NRNRNRNRNRNR9148.1NRNR59NR
Mussetto et al[19] (2015)ItalyNS4L60NRNRNRNRNRNRNRNRNRNRNRNR
S2L + Sim60NRNRNRNRNRNRNRNRNRNRNRNR
Leone et al[20] (2013)ItalyNS4L793444.7NRNRNRNRNRNRNRNRNRNR
S2L + Sim783443.6NRNRNRNRNRNRNRNRNRNR
Valiante et al[21] (2013)ItalyNS4L126NRNRNRNRNRNR7156.3NRNR5516
S2L + Sim138NRNRNRNRNRNR10576.1NRNR8421
Cesaro et al[22] (2013)ItalyNS4L511734.7NRNRNRNRNRNRNRNRNRNR
S2L + Sim501732.7NRNRNRNRNRNRNRNRNRNR
Gentile et al[23] (2013)ItalyNS2L60NRNRNRNRNRNRNRNRNRNRNRNR
S4L + Sim60NRNRNRNRNRNRNRNRNRNRNRNR
Matro et al[24] (2012)United StatesNS2L612032.8NRNRNRNR2947.5NRNRNRNR
S2L + Sim621524.2NRNRNRNR2337.1NRNRNRNR
Repici et al[25] (2012)ItalyNS2L190NRNRNRNRNRNRNRNRNRNRNRNR
S2L + Sim187NRNRNRNRNRNRNRNRNRNRNRNR
Jansen et al[26] (2011)NetherlandsNS2L102NRNRNRNRNRNR1413.7NRNRNRNR
S2L + Sim86NRNRNRNRNRNR2326.7NRNRNRNR
Pontone et al[27] (2011)ItalyNS2L72912.581NRNR1318.1NRNRNRNR
S4L + Sim721216.757NRNR2230.6NRNRNRNR
Lazzaroni et al[28] (1993)ItalyNS4L48NRNRNRNRNRNRNRNRNRNRNRNR
S4L + Sim57NRNRNRNRNRNRNRNRNRNRNRNR
McNally et al[29] (1989)United StatesNSPEG12NRNRNRNRNRNRNRNRNRNRNRNR
SPEG + Sim14NRNRNRNRNRNRNRNRNRNRNRNR
McNally et al[30] (1988)United StatesNSPEG48NRNRNRNRNRNRNRNRNRNRNRNR
SPEG + Sim49NRNRNRNRNRNRNRNRNRNRNRNR
N: Total number of patients included; NR: Not reported; NS: Polyethylene glycol group only; PEG: Polyethylene glycol; S: Polyethylene glycol with simethicone group; Sim: Simethicone.
Quality assessment

The quality of the randomized studies was evaluated by the Cochrane Collaboration’s risk of bias tool. Although all of the studies were single-blind to the examiner, the blinding of outcome assessments was not affected. Therefore, the risk bias of selective reporting of each trial was considered low risk. The quality assessment of the randomized studies is shown in Supplementary Table 1.

Primary endpoints

ADR: For the primary endpoint, nine studies reported data on the ADR, including 4069 patients (2042 patients treated with PEG plus simethicone and 2027 patients treated with PEG). The overall ADR during colonoscopy was similar in both groups: 30.9% in the PEG group and 31.0% in the PEG plus simethicone group. The heterogeneity among the studies was not significant (I² = 41%; P = 0.10). According to the fixed-effects model, the pooled OR was not significant (OR = 1.01; 95%CI: 0.88-1.15; P = 0.94), suggesting that there was no statistically significant difference in the ADR during colonoscopy between the two groups (Figure 2). Begg’s funnel plots and Egger’s regression test revealed that there was no significant effect of publication bias on the overall ADR (P = 0.307).

Figure 2
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Figure 2 Forest plot of the effect of simethicone on overall adenoma detection rate. CI: Confidence interval; PEG: Polyethylene glycol; PEG+S: Polyethylene glycol plus simethicone.

PDR: Overall, the PDR was available in 10 studies, including 4544 patients (2279 patients treated with PEG plus simethicone and 2265 patients treated with PEG). The overall PDR was higher in the group treated with simethicone during colonoscopy (49.1% vs 48.0%). The heterogeneity among the studies was significant (I² = 64%; P = 0.003). The pooled OR, according to a random-effects model for PDR (OR = 1.13; 95%CI: 0.89-1.42; P = 0.31), was not significantly different between the two groups (Figure 3). Egger’s regression test revealed that there was no significant effect of publication bias on the overall PDR (P = 0.221).

Figure 3
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Figure 3 Forest plot of the effect of simethicone on overall polyp detection rate. CI: Confidence interval; PEG: Polyethylene glycol; PEG+S: Polyethylene glycol plus simethicone.
Secondary endpoints

Adverse events: Sixteen studies reported data on adverse events, including bloating, vomiting, nausea, abdominal pain, and sleep disturbance. Simethicone significantly reduced the incidence of bloating (15.8% vs 25.3%) (OR = 0.52; 95%CI: 0.44-0.63, P < 0.00001). There were no statistically significant differences in other adverse events. Egger’s regression test revealed that there was no significant effect of publication bias.

Sensitivity analyses: We performed further sensitivity analyses to assess the impact on the heterogeneity by the exclusion of one or more studies at a time. There was statistically significant heterogeneity for the ADR in the right colon (heterogeneity P = 0.09, I2 = 58%). When Bai et al[14] was excluded, it no longer showed heterogeneity for the ADR (heterogeneity P = 0.18, I² = 45%). The other two outcomes had significant heterogeneity, including the PDR and adverse events of bloating. When Valiante et al[21] was excluded, they no longer showed heterogeneity of the PDR. The studies associated with the heterogeneity of each outcome are listed in Table 3.

Table 3 Sensitivity analyses and subgroup analyses of the studies included in the meta-analysis.
Number of trials
Number of patients
OR/MD (95%CI)
P value
I2
Study associated with heterogeneity
Primary outcome
ADR940691.01 (0.88-1.15)0.9441%-
Proportion of ADR
< 25%312991.55 (1.16-2.07)0.0030%-
≥ 25%627700.88 (0.76-1.03)0.120%-
Dose of simethicone
≥ 400 mg518061.21 (0.97-1.50)0.0950%-
< 400 mg and NR422630.89 (0.75-1.06)0.200%
Size of adenoma
< 10 mm211552.36 (1.79-3.10)< 0.0000129%-
≥ 10 mm211551.39 (0.67-2.86)0.380%-
Location of adenoma
Right colon 312992.61 (1.43-4.76)0.00258%Bai 2018 (I2 = 45%)
Left colon 312991.44 (1.02-2.02)0.0423%-
Regions of the populations
Asia314151.45 (1.12-1.87)0.0050%-
Not-Asia523860.88 (0.74-1.04)0.140%-
PDR1045441.13 (0.89-1.42)0.3164%Valiante 2013 (I2 = 41%)
Dose of simethicone
≥ 400 mg415461.06 (0.80-1.41)0.6740%
< 400 mg and NR629981.23 (0.85-1.79)0.2874%Valiante 2013 (I2 = 41%)
Size of adenoma
< 10 mm324980.93 (0.79-1.09)0.3746%-
≥ 10 mm221280.98 (0.78-1.22)0.840%-
Proportion of PDR
< 40%414871.29 (0.97-1.72)0.0831%-
≥ 40%630571.03 (0.75-1.41)0.8667%Valiante 2013 (I2 = 0%)
Regions of the populations
Asia211551.24 (0.95-1.62)0.1114%-
Not-Asia833891.10 (0.82-1.47)0.5366%Valiante 2013 (I2 = 22%)
Secondary outcome
Adverse events
Bloating1130490.51 (0.36-0.73)0.000267%Repici 2012 (I² = 49%)
Nausea1433971.03 (0.87-1.22)0.6933%-
Vomiting925141.02 (0.75-1.40)0.890%-
Abdominal pain1536690.89 (0.72-1.10)0.2942%-
Sleep disturbance919900.81 (0.64-1.01)0.0625%-
ADR: Detection rate of colorectal adenoma; MD: Mean difference; NR: Not reported; OR: Odds ratio; PDR: Detection rate of colorectal polyp.

Subgroup analyses: The results of the subgroup analyses for the ADR and PDR in relation to sites of colorectal adenomas or polyps (right or left colon), sizes of adenomas or polyps (≥ 10 mm or < 10 mm), populations (Asian or non-Asian), dose of simethicone (≥ 400 mg or < 400 mg and NR), and proportion of ADR (≥ 25% or < 25%) are shown in Table 3.

The analysis separately revealed that there was no significant difference (OR = 1.39, 95%CI: 0.67-2.86, P = 0.38) or heterogeneity (P = 0.48, I² = 0%) between the two groups for ADR ≥ 10 mm. However, our study displayed a significant increase in the ADR for small adenomas (< 10 mm) during colonoscopy in the group treated with simethicone (OR = 2.36; 95%CI: 1.79-3.10; P < 0.00001) (Figure 4A).

Figure 4
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Figure 4 Forest plots of subgroup analysis. A: Forest plot of subgroup analysis of the effect of simethicone on adenoma detection rate (ADR) in trials with small adenomas (< 1 cm); B: Forest plot of subgroup analysis of the effect of simethicone on ADR in trials with right-side adenomas; C: Forest plot of subgroup analysis of the effect of simethicone on ADR in trials of the population from Asia; D: Forest plot of subgroup analysis of the effect of simethicone on ADR in trials with the baseline ADR < 25%. CI: Confidence interval; PEG: Polyethylene glycol; PEG+S: Polyethylene glycol plus simethicone.

When analyzed separately, a significantly larger proportion of ADR in the right colon was present in the PEG plus simethicone group (21.5% vs 9.7%, OR = 2.61, 95%CI: 1.43-4.76, P = 0.002) (Figure 4B). In addition, the ADR in the left colon was also higher than that in the PEG group, with borderline statistical significance (13.8% vs 10.0%, P = 0.04).

The subgroup analysis revealed a significant increase in the ADR in the studies from Asia in the PEG with simethicone group (26.8% vs 20.7%, OR= 1.45, 95%CI: 1.12-1.87, P = 0.005) (Figure 4C), and a baseline ADR < 25% of the studies included was associated with a significant benefit of simethicone (OR = 1.55, 95%CI: 1.16-2.07, P = 0.003) (Figure 4D). In addition, our analysis revealed that there was no significant difference in ADR between the two groups with respect to the dose of simethicone, suggesting that the low dose of simethicone was as effective as the high dose with respect to the detection of benign colorectal tumors.

The comparison of PDR between the two groups showed no differences in the proportion of PDR, dose of simethicone, size of polyps, or populations when simethicone was added.

DISCUSSION

The effectiveness of colonoscopy could significantly reduce the incidence and mortality of CRC[33], depending on adequate bowel preparation and removal of colorectal precancerous lesions[34]. Inadequate bowel preparation increases economic costs, prolongs procedure times, and increases the likelihood of potential lesions being missed, especially those in the proximal colon[35].

Simethicone is an effective antifoaming agent used during endoscopic procedures. The Gastroenterological Society of Australia consensus panel found that the current evidence supported the use of simethicone for improving visibility and that it likely facilitates adenoma detection at colonoscopy[36]. Although simethicone addition to PEG solution could improve bowel cleanness and mucosal visibility[37], our results found that simethicone did not affect the total ADR or PDR. This outcome might be related to the possible explanation that solid stool was unlikely to be cleaned, although simethicone could improve the overall bowel cleanness.

The ADR has been recognized as the most important indicator of colonoscopy quality. The current international guidelines have recommended that the ADR should be ≥ 25% overall as the minimal requirement for surveillance colonoscopy[38]. In the subgroup analysis, we revealed a positive effect of simethicone with statistical significance in the low ADR group (< 25%). An interesting finding in our study was that the population of the low ADR group was Asian. This phenomenon might be related to the genes, diet, and/or microbiota of Asians.

The most important finding in our study was that simethicone could significantly improve detection of small adenomas (< 10 mm) of the proximal colon. The main reason is that simethicone can improve bowel preparation, especially in the right colon[39]. Because bubbles usually present in the ascending colon, bubble elimination could enhance the ability to detect smaller proximal adenomas. A previous study revealed that missed cancers in the proximal colon were more often found with poor bowel preparation[40]. A previous study reported that CRC in Eastern China has undergone a rightward change in the site distribution over the past two decades[41]. Therefore, improving the effectiveness of right-sided cleansing plays a key role in improving compliance with screening programs, which is crucial for screening efficiency in CRC prevention. However, simethicone did not significantly affect the ADR in the left colon, which might be associated with the small samples in the studies included. Therefore, further large clinical trials are necessary to confirm our results.

Although a recent study reported a 10% increase in the detection rate of colorectal polyps when simethicone was added to the water pump during colonoscopy[42], residual simethicone in biopsy channels could promote biofilm formation[43]. In addition, endoscopists with higher ADRs likely spent more time cleaning the colon. Simethicone addition to PEG solution could decrease the infection risk from endoscope transmission[31]. However, the optimal dose of simethicone has yet to be ascertained[44]. The addition of 2–3 mL of 120 mg/mL simethicone to lavage fluid was recommended [33]. In the subgroup analysis, we compared the effect of low-dose simethicone (< 400 mg) to that of high-dose simethicone (≥ 400 mg) for the ADR and PDR. Our results revealed that simethicone at a high or low dose made no significant difference in terms of ADR and PDR, suggesting that the low dose was not inferior to the high dose, similar to the study of Li et al[45]. Further research is required to determine the optimal dose of simethicone in clinical practice.

The strengths were as follows in our study. First, subgroup analyses and sensitivity analyses were conducted to seek potential reasons. To reduce possible bias, we conducted sensitivity analyses to assess the impact on the heterogeneity by excluding one or more studies at a time and performing subgroup analyses according to the site and size of colorectal benign tumors, the population included, and the proportion of ADR. There was no significant heterogeneity found in the meta-analysis of the ADR, except for right-side ADR. When Valiante et al[21] study was excluded, it no longer showed heterogeneity of the PDR. Second, our results of the subgroup analyses for the ADR and PDR included the population included and the dose of simethicone before colonoscopy. Third, 20 studies were included in our meta-analysis. This large number of studies allowed for firm conclusions and adequate subgroup analyses. Therefore, the results of our study are convincing.

There are several limitations to our meta-analysis. First, our meta-analysis was restricted to publications written in English, which might have produced potential selection bias. Second, all of the included studies were single blinded for outcome assessment; therefore, further double-blind randomized controlled trials should be conducted to confirm the positive effects of simethicone. Third, demographic and procedure data, such as race, diet, microbiota, and genes, might have been interesting to evaluate, but these data were not analyzed due to the limited condition. Fourth, although the endoscopists were trained adequately, the effects of observer bias cannot be ignored.

CONCLUSION

In conclusion, we believe that simethicone might improve small ADRs, especially in the proximal colon, for colonoscopy in Asians with low baseline ADRs. Simethicone at a low dose was not inferior to that at a high dose with respect to the detection of benign colorectal tumors. Additional large clinical trials are necessary to validate our results and to evaluate the ideal dose of simethicone.

ARTICLE HIGHLIGHTS
Research background

The incidence and mortality of colorectal cancer have been rapidly increasing in Asian countries, and inadequate bowel preparation is related to an increased risk of missed benign colorectal tumors and more discomfort for patients.

Research motivation

Simethicone is an effective and safe antifoaming agent for use during endoscopic procedures. A combination of simethicone and polyethylene glycol has been shown to improve the visualization of the bowel for colonoscopy.

Research objectives

We performed a meta-analysis to investigate its effect on the detection of benign colorectal tumors.

Research methods

The PubMed, EMBASE, and Cochrane Library databases were searched for articles published.

Research results

A significant effect of simethicone for diminutive adenomas (< 10 mm) and the adenoma detection rate in the proximal colon were revealed in the group taking simethicone. Moreover, it was a significant finding that the low dose simethicone was as effective as the high dose one with respect to the detection of colorectal benign tumors.

Research conclusions

The addition of simethicone to polyethylene glycol might improve the detection of diminutive adenomas in the right colon by colonoscopy in Asia. Low-dose simethicone was recommended for the detection of benign colorectal tumors.

Research perspectives

We believe that simethicone might improve small adenoma detection rates, especially in the proximal colon for colonoscopy in Asians with low baseline adenoma detection rates.

Footnotes

Manuscript source: Unsolicited manuscript

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: China

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Panteris V S-Editor: Zhang H L-Editor: Filipodia P-Editor: Wang LL

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