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Abstract

Background

Few well-designed studies have investigated water exchange colonoscopy (WE). We performed a meta-analysis to comprehensively evaluate the clinical utility of WE based on high-quality randomized controlled trials (RCTs) and to compare the impacts of WE, water immersion colonoscopy (WI), and gas-insufflation colonoscopy.

Methods

We searched the Cochrane Library, MEDLINE, Embase, PubMed, Elsevier, CNKI, VIP, and Wan Fang Data for RCTs on WE. We analyzed the results using fixed- or random-effect models according to the presence of heterogeneity. Publication bias was assessed by funnel plots.

Results

Thirteen studies were eligible for this meta-analysis. The colonoscopic techniques included WE as the study group, and WI and air- or CO₂-insufflation colonoscopy as control groups. WE was significantly superior to the control procedures in terms of adenoma detection rate, proportion of painless unsedated colonoscopy procedures, and cecal intubation rate according to odds ratios. WE was also significantly better in terms of maximal pain score and patient satisfaction score according to mean difference.

Conclusions

WE can remarkably improve the adenoma detection rate, proportion of painless unsedated colonoscopy procedures, patient satisfaction, and cecal intubation rate, as well as reducing the maximal pain score in patients undergoing colonoscopy.

Keywords

Water exchange water immersion air insufflation colonoscopy randomized controlled trial meta-analysis

Introduction

Colonoscopy plays an important role in the diagnosis and treatment of colorectal diseases, especially in screening for colorectal cancer.^1–3 Conventional air-insufflation colonoscopy (AI) often causes abdominal distension, abdominal pain, and other discomfort during the procedure;^4,5 however, technical developments have led to the introduction of water exchange (WE) and water immersion (WI) techniques.⁶ In WE, the cecal intubation process proceeds more slowly with the infused water suctioned during insertion rather than during withdrawal, and the suctioning of any retained gas pockets as they are encountered. WI involves infusing water solely for the purpose of expanding the lumen and intubating the cecum, with suctioning of the water during withdrawal. WE has been reported to be clinically more valuable than WI,^7–9 especially in terms of the adenoma detection rate (ADR) and cecal intubation rate.^10,11 One report showed that the cecal intubation time of WE was longer than either WI and AI,¹² while WI has also been suggested to have better diagnostic and therapeutic performances than AI.^6,10,13 Recent studies of CO₂-insufflation colonoscopy, which uses CO₂ instead of air to achieve minimal distension of the lumen throughout the insertion phase and during withdrawal, demonstrated superiority of CO₂ in reducing postprocedural pain. Three previous meta-analyses have analyzed the use of WE;^14–16 however, Chen et al.¹⁴ only analyzed WE versus WI, Zhang et al.¹⁵ compared any two of AI, CO₂-insufflation colonoscopy, WI, and WE, and did not focus on WE, while Fuccio et al.¹⁶ separately compared WI and/or WE with AI and/or CO₂-insufflation colonoscopy. In contrast, in the current meta-analysis, we set WE as the experimental group and the three other methods (WI, AI, CO₂-insufflation colonoscopy) as the control groups, and compared the subgroups. This meta-analysis thus comprehensively evaluated the clinical utility of WE based on high-quality RCTs.

Methods

Inclusion and exclusion criteria

Inclusion criteria

Studies were included if they met the following criteria: 1) contained case inclusion criteria, and the study design was an RCT with a quality level of A or B (see ‘Quality assessment’ below); 2) were designed to study WE; 3) had a study group that received WE and a control group that received AI, CO₂-insufflation colonoscopy, or WI; and 4) included one or more of the following indicators for comparing efficacy between WE and other colonoscopic techniques: cecal intubation rate, ADR, proportion of painless unsedated colonoscopy, maximal pain score, and patient satisfaction.

Exclusion criteria

Studies were excluded if they met any of the following criteria: 1) incomplete data; 2) duplicate publications (only those with credible data were included); 3) had a control group that underwent WE combined with other colonoscopic techniques; or 4) were a RCT without WE as one of the methods.

Literature retrieval and data collection

We searched the Cochrane Library, MEDLINE, Embase, PubMed, Elsevier and Technological Periodical Database, and Wanfang Data prior to July 2018. The search excluded studies involving children or pregnant women, and review articles. References in the included articles were checked to identify any study that might have been omitted. The articles were screened by two reviewers independently, according to the steps for preliminary screening and full-text screening, and any disagreements were resolved by discussion or consultation with a third evaluator.

Quality assessment

Study quality was evaluated according to the quality evaluation criteria recommended in the Cochrane Reviewers’ Handbook 5.1.0. Briefly, study quality was rated as A, B, or C based on its randomization method, allocation concealment, blinding method, incomplete outcome data, selective outcome data, and other bias sources. The results are shown in Figures 1 and 2. All studies^12,17–28 described the process of randomization, whereas only seven^{12,17,18,20,24,26,28} studies described appropriate allocation concealment. Nine studies^{18–20,22–25,27,28} did not clearly describe other biases. Reference blinding was similar in all the included studies. The only study²⁵ with a guaranteed low risk of bias was a study in which the colonoscopists were blinded to the insertion method (double-blinded).

Figure 1.

Summary of the risk of bias assessment (1).

Figure 2.

Graph of the risk of bias assessment (2).

Data analysis

The data were analyzed statistically using Review Manager 5.3. Odds ratios (ORs) were used to analyze the heterogeneity of numerical data such as ADR, proportion of painless unsedated colonoscopy, and cecal intubation rate between the two groups in each study. Maximal pain score and patient satisfaction were analyzed by weighted mean difference (MD) and the effect variables were expressed by 95% confidence intervals (CI). Each study was considered to be homogeneous when the P value was > 0.1 or the I² statistic was < 50%; otherwise the study was regarded as non-homogenous. A fixed-effect model was used to estimate the overall effect if the OR was homogenous and a random-effect model if it was non-homogenous. A symmetrical funnel plot that was narrow at the top and wide at the bottom indicated no publication bias in relation to the analyzed index (Figure 3).

Figure 3.

Funnel plots of the risk of publication bias (according to cecal intubation rate). SE: standard error, WI: water immersion colonoscopy, AI: air-insufflation colonoscopy, WE: water-exchange colonoscopy, CO₂: CO₂-insufflation colonoscopy.

Results

Literature search and information retrieval of included studies

A total of 76 articles were extracted, of which 63 were excluded after reading the titles and abstracts and 13 RCTs were eventually included in the final analysis (Figure 4). Of the included articles, 11 were rated as grade A and two as grade B in terms of methodological quality. The included studies contained a total of 8780 patients, and the colonoscopic techniques used in these studies included WE, AI or CO₂-insufflation colonoscopy, and WI (Table 1).

Figure 4.

Diagram of article screening and selection. RCT: randomized controlled trial, WI: water immersion colonoscopy, AI: air-insufflation colonoscopy, WE: water-exchange colonoscopy.

Table 1.

Clinical characteristics of studies included in the meta-analysis.

	Water-exchange group						Control group
Reference	Total number (n)	Method	Male/female (n)	Age (years)	BMI	Previous abdominal/pelvic surgery (%)	Male/female (n)	Age (years)	Method	BMI	Previous abdominal/pelvic surgery (%)	Quality
Arai M 2016^[17]	403	WE	125/81	65.6 ± 12.0	22.9 ± 3.8	24.8%	122/75	63.1 ± 12.6	AI	23.3 ± 4.2	28.8%	A
Azevedo R 2018^[18]	141	WE	41/29	61.6 ± 13.4	26.4 ± 5.2	42.9%	40/31	63.6 ± 13.3	AI	25.8 ± 7	39.4%	A
Cadoni S 2014^[19]	672	WE	201/137	58 ± 12.4	–	29.9%	204/130	60 ± 12.3	AI	–	21.0%	A
Cadoni S 2015^[20]	576	WE	110/76	59 ± 11.3	26.5 ± 4.9	33.3%	112/81116/81	59 ± 11.360 ± 10.8	AIWI	26.0 ± 5.025.9 ± 4.2	30.1%27.4%	A
Cadoni S 2015-1^[21]	520	WE-CO₂	–	–	–	–	–	–	CO₂	–	–	B
		WE							AI
									WI
Cadoni S 2016-1^[22]	240	WE-CO₂	48/31	58.3 ± 13.6	27.3 ± 4.4	36.7%	50/31	58 ± 13.7	CO₂	26.3 ± 4.1	40.7%	A
Cadoni S 2016^[23]	1224	WE	224/184	61.4 ± 6.2	26.4 ± 4.1	36.8%	225/183223/185	60.9 ± 6.261.0 ± 6.3	AIWI	26.6 ± 4.426.4 ± 4.4	37.7%30.9%	A
Garborg K 2014^[24]	473	WE-CO₂	49/114	60 ± 4.5	26.9 ± 3.8	25%	49/118	61 ± 3.7	CO₂	26.7 ± 4.1	30%	A
Hsieh YH 2014^[12]	270	WE	55/35	58	24.9 ± 2.9	27.8%	59/3153/37	5953	AIWI	25.3 ± 3.225.0 ± 3.3	27.8%23.3%	A
Hsieh YH 2016^[25]	651	WE	121/96	55.7 ± 10.6	24.1 ± 3.2	38.2%	105/112110/107	54.8 ± 10.555.9 ± 10.2	AIWI	24.1 ± 4.224.3 ± 3.3	29.5%36.9%	B
Jia H 2016^[26]	3303	WE	830/823	50.2 ± 13.7	22.8 ± 3.5	23.7%	855/795	50.2 ± 13.9	AI	23.3 ± 3.8	26.1%	A
Luo H 2013^[27]	110	WE	18/37	55.8 ± 11.0	22.0 ± 3.4	100%	16/39	56.6 ± 12.0	AI	21.3 ± 3.6	100%	A
Wang X 2015^[28]	197	WE	51/48	46.4 ± 11.8	23.0 ± 2.9	28%	46/52	48.6 ± 13.2	AI	22.8 ± 3.1	19%	A

AI: air-insufflation, BMI: body mass index, CO₂: CO₂-insufflation, WE, water exchange, WI: water immersion.

Efficacy indicators

Nine RCTs^{17–19,23–26,28} reported the ADR in the WE group, with a non-significant χ² value of 3.60 for heterogeneity, indicating homogeneity of effects among the trials. A fixed-effect model was therefore used, and the OR value in the WE group was 1.43 (95%CI: 1.30 to 1.59, P < 0.001). The OR values in the AI, WI, and CO₂-insufflation groups were 1.49 (95%CI: 1.32 to 1.68, P < 0.001), 1.36 (95%CI: 1.10 to 1.67, P = 0.004), and 1.18 (95%CI: 0.80 to 1.73), respectively, indicating that WE could significantly increase ADR (Figure 5).

Figure 5.

Comparison between WE and control groups in relation to ADR. Forest plot showing odds ratio (OR) with 95% confidence interval (CI). df: degrees of freedom, WI: water immersion colonoscopy, AI: air-insufflation colonoscopy, WE: water-exchange colonoscopy, CO₂: CO₂-insufflation colonoscopy, M-H: Mantel–Haenszel.

Three RCTs^19–21 reported the proportion of painless unsedated colonoscopy procedures in the WE group, with a non-significant χ² value of 0.97 for heterogeneity, indicating homogeneity of effects among the trials. A fixed-effect model was therefore used. The OR for WE was 2.43 (95%CI: 1.87 to 3.14, P < 0.001), and the OR values for the AI and WI groups were 2.52 (95%CI: 1.88 to 3.37, P < 0.001) and 2.11 (95%CI: 1.21 to 3.68, P < 0.001), respectively, indicating that WE could significantly increase the proportion of painless unsedated colonoscopy procedures (Figure 6).

Figure 6.

Comparison between WE and control groups in relation to painless unsedated colonoscopy. Forest plot showing odds ratio (OR) with 95% confidence interval (CI). df: degrees of freedom, WI: water immersion colonoscopy, AI: air-insufflation colonoscopy, WE: water-exchange colonoscopy, CO₂: CO₂-insufflation colonoscopy, M-H: Mantel–Haenszel.

Maximal pain score during insertion was investigated in the WE group in seven RCTs,^{12,20,21,25–28} with a χ² value for heterogeneity of 114.86 (P < 0.001), indicating significant heterogeneity of effect among the trials. The results were therefore analyzed using a random-effect model. The MD value for WE was −1.48 (95%CI: −1.98 to 0.98, P < 001), indicating that the maximal pain score during insertion was remarkably lower in the WE group compared with the AI (MD −1.84 [95%CI: −2.53 to 1.16, P < 0.001]) and WI groups (MD −0.62 [95%CI: −1.14 to 0.10, P = 0.02) (Figure 7).

Figure 7.

Comparison between WE and control groups in relation to maximal pain score during insertion. Forest plot showing mean difference (MD) with 95% confidence interval (CI). df: degrees of freedom, WI: water immersion colonoscopy, AI: air-insufflation colonoscopy, WE: water-exchange colonoscopy, CO₂: CO₂-insufflation colonoscopy, IV: inverse variance.

Eleven RCTs^12,19–28 reported the cecal intubation rate in the WE group, with a non-significant χ² value for heterogeneity of 17.39, indicating homogeneity of effects among the trials. A fixed-effect model was therefore used, and the OR value was 1.39 (95%CI: 1.08 to 1.79, P = 0.01). The equivalent ORs in the AI, WI, and CO₂-insufflation groups were 1.20 (95%CI: 0.86 to 1.66), 1.41 (95%CI: 0.87 to 2.26), and 2.85 (95%CI: 1.31 to 6.21, P = 0.008), indicating that WE could improve the cecal intubation rate relative to the control groups (Figure 8).

Figure 8.

Comparison between WE and control groups in relation to cecal intubation rate. Forest plot showing odds ratio (OR) with 95% confidence interval (CI). df: degrees of freedom, WI: water immersion colonoscopy, AI: air-insufflation colonoscopy, WE: water-exchange colonoscopy, CO₂: CO₂-insufflation colonoscopy, M-H: Mantel–Haenszel.

Patient satisfaction score was assessed in the WE group in three RCTs,^12,21,22 and the χ² value for heterogeneity was 2.31, indicating homogeneity of effects among the trials. A fixed-effect model was therefore used. The MD value for WE was 0.20 (95%CI: 0.05 to 0.35, P = 0.01), indicating that WE could increase patient satisfaction compared with the AI (MD 0.19 [95%CI: 0.02 to 0.35, P = 0.03]) and CO₂-insufflation groups (MD0.20 [95%CI: −0.26 to 0.63]) (Figure 9).

Figure 9.

Comparison between WE and control groups in relation to patient satisfaction score. Forest plot showing mean difference (MD) with 95% confidence interval (CI). df: degrees of freedom, WI: water immersion colonoscopy, AI: air-insufflation colonoscopy, WE: water-exchange colonoscopy, CO₂: CO₂-insufflation colonoscopy, IV: inverse variance.

Discussion

ADR is known to be an important colonoscopy quality indicator related to the risk of interval cancer. The current meta-analysis showed that WE could significantly increase the ADR compared with other colonoscopy techniques, with a pooled OR of 1.43, in line with the results of previous studies.^12,19 However, only one study compared WE and CO₂-insufflation in relation to ADR,²⁴ and the result for this comparison was therefore not significant, probably due to the small sample size. Further clinical studies should therefore be conducted to compare the ADRs of these two techniques. We also compared WE with AI, WI, and CO₂-insufflation colonoscopy in terms of cecal intubation rate, and confirmed that WE had a higher cecal intubation rate than all the other insertion techniques. WE has consistently been shown to be the least-painful insertion technique,²⁹ and we verified that WE could significantly increase the proportion of painless unsedated colonoscopy procedures compared with AI and WI. Unsedated colonoscopy in the clinic could reduce medical costs and ensure postprocedural patient safety,^30,31 and the current analysis indicated that WE could be used to perform unsedated colonoscopy, especially in patients who cannot tolerate pain. Pain limits the cecal intubation rate from 67% to 83% worldwide among patients undergoing scheduled, unsedated colonoscopy.³² Our analysis indicated that WE significantly reduced the maximal pain on insertion, based on visual analog scale (0 = none,10 = maximum) pain scores. WE might thus allow the completion of difficult colonoscopy procedures, e.g., in patients with a history of abdominal surgery and those referred for prior incomplete colonoscopy, and may decrease the maximal discomfort during colonoscopy in these patients. This study thus further confirmed that WE was a relatively comfortable method in unsedated patients.³³ Finally, our meta-analysis also showed that WE was associated with higher patient satisfaction than the control techniques, suggesting that WE might be a popular choice for patients in the future .

All the studies included in this comprehensive meta-analysis were high-quality RCTs with consistent diagnostic criteria. However, there were still some limitations. Notably, the included studies were performed in different races and ethnic groups. Furthermore, differences in experimental design, numbers of patients in the control groups, and outcome measurements led to large heterogeneities among the included studies in terms of maximal pain score during insertion, necessitating the use of a random-effect model for this item, which might have affected the results. In addition, colonoscopy was divided into insertion and withdrawal phases, with some differences among studies in terms of withdrawal procedure. Finally, relatively few RCTs compared WE and CO₂-insufflation colonoscopy.

In summary, WE is a promising colonoscopic technique that can remarkably increase the ADR and thus improve the detection rate of interval cancer. WE can also significantly increase the proportion of painless unsedated colonoscopy procedures and cecal intubation rate, and lower the maximal pain score. However, there was some heterogeneity among the included studies, and more high-quality RCTs with consistent outcome measurements are needed to verify the clinical value of WE in terms of maximal pain score during insertion and to compare WE with CO₂-insufflation colonoscopy.

Declaration of conflicting interest

The authors declare that there is no conflict of interest.

Footnotes

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Diagnostic application of water exchange colonoscopy: A meta-analysis of randomized controlled trials

Abstract

Background

Methods

Results

Conclusions

Keywords

Introduction

Methods

Inclusion and exclusion criteria

Inclusion criteria

Exclusion criteria

Literature retrieval and data collection

Quality assessment

Data analysis

Results

Literature search and information retrieval of included studies

Efficacy indicators

Discussion

Declaration of conflicting interest

Footnotes

Funding

References