Analysis of the potential risk factors for defecation problems and their bowel management based on the long-term bowel function in patients with persistent cloaca: Results of a nationwide survey in Japan

doi:10.21203/rs.3.rs-2497698/v1

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Analysis of the potential risk factors for defecation problems and their bowel management based on the long-term bowel function in patients with persistent cloaca: Results of a nationwide survey in Japan

https://doi.org/10.21203/rs.3.rs-2497698/v1

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published 30 Jan, 2023

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Aim of the Study: We conducted a nationwide survey of persistent cloaca (PC) to determine its current status in Japan. This study clarifies the potential risk factors for defecation problems in patients with PC.

Methods: Patient information was obtained via questionnaire, and a total of 213 PC patients who responded to a questionnaire on defecation problems and their bowel functions were enrolled in this study. We evaluated the constipation, incontinence, and soiling as bowel functions. Univariate and multivariate analyses were performed using a logistic regression analysis to clarify the risk factors for defecation problems.

Results: Of 213 patients with PC, 55 (25.8%) had defecation problems. A multivariate logistic regression analysis showed that sacral agenesis, as an associated anomaly, was significantly associated with defecation problems (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.11–9.16, p = 0.03). The other multivariate logistic regression analysis showed that the PC patients who underwent antegrade continence enema and regularly took laxatives after anorectoplasty had defecation problems (OR 12.4, 95% CI 2.35–65.6, p = 0.003, OR 2.84, 95% CI 1.24–6.55, p = 0.01).

Conclusion: Sacral agenesis is the potential risk factor of defecation problems in the patients with PC who underwent anorectoplasty. Those patients require vigorous defecation management.

persistent cloaca

bowel function

defecation problem

sacral agenesis

nationwide survey

Persistent cloaca (PC) malformation is the most severe type of anorectal and urogenital malformation. PC is associated with many kinds of complications, and comprehensive and long-term follow-up is important for PC patients. Management of the bowel function is also important for patients with anorectal malformation.

PC is a type of anorectal malformation, however, there are few cases and few reports on the bowel function. Similarly to intermediate- and high-type imperforate anus, PC patients may have some trouble in bowel management, but there are few reports on the long-term bowel function of these patients. Moreover, few reports have described the details of the defecation problem.

Kubota et al. conducted a nationwide survey of PC in 2014 to determine the current status of this disease in Japan [1]. In that survey, the incidence of defecation problems was 28%. We performed a subgroup analysis of the data of our nationwide survey. The present study clarified the potential risk factors for defecation problems in patients with PC following their bowel management based on a nationwide survey.

1.1. Study population

A nationwide survey was conducted, entitled “Establishment of treatment guidelines for smooth transitional care of persistent cloaca, cloacal exstrophy and Mayer-Rokitansky-Kuster-Hauser syndrome” [1, 2]. We analyzed the relationship between defecation problems and background factors in PC patients. Patient information was obtained by sending a questionnaire to 244 university hospitals and children’s hospitals in our country to investigate the etiologic events and clinical outcomes in patients with PC. Responses on 466 cases of PC were obtained from 113 institutions (46.3%). A total of 213 PC patients (45.7%) who responded to the questionnaire on defecation problems and their bowel functions were enrolled in the present study.

1.2. Data collection

To clarify the potential risk factors for defecation problems in patients with PC, we investigated their associated anomalies, the timing of anorectoplasty, and anorectoplasty procedures that were related to the bowel function. Associated anomalies included spinal cord meningeal syndrome and sacral agenesis. The timing of anorectoplasty was divided into 2 periods: ≤12 months of age or > 12 months, and ≤ 24 months of age or > 24 months of age. The types of operative procedure for anorectoplasty were classified as posterior sagittal anorectoplasty (PSARP) or other procedures.

The relationship between defecation problems and the current status of bowel management was also evaluated, with the following bowel managements analyzed: regular oral administration of laxatives, antegrade continence enema, and regular glycerin enema.

1.3. The evaluation of the bowel function

The bowel function was evaluated based on the latest evaluation using the evacuation score of the Japan Society of Anorectal Malformation Study Group [3]. In this study, we evaluated three scores: constipation, incontinence, and soiling. The detailed responses to the content on constipation were “absent”, “accidental”, “require enema or suppository every day” and “require colonic irrigation or stool extraction”. The responses to the content on incontinence were “absent”, “incontinence with diarrhea”, “accidental”, “more than twice a week”, and “frequent”. The responses to the content on soiling were “absent”, “accidental”, and “frequent”.

1.4. Statistical analyses

Our primary objective was to investigate risk factors associated with defecation problems in PC patients based on the questionnaire. Our secondary objective was to clarify specific problems with the defecation status of patients with PC.

Univariate and multivariate logistic regression analysis were performed. We first performed logistic regression model analyses to obtain the crude odds ratios (ORs) for risk factors for defecation problems. We then used logistic regression to adjust for the covariates used in our primary analysis. Factors that showed a p value of < 0.05 in the univariate logistic regression analysis were included in a multivariate logistic regression analysis to obtain the adjusted ORs for defecation problems.

In all analyses, tests were 2-sided, and p values of < 0.05 were considered to indicate statistical significance. Data are expressed as the mean ± standard deviation. All statistical analyses were performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, it is a modified version of R commander designed to add statistical functions frequently used in biostatistics [4].

1.5. Ethical Approval

This research project entitled, “Establishment of treatment guidelines for smooth transitional care of persistent cloaca, cloacal exstrophy and Mayer-Rokitansky-Küster-Häuser syndrome,” was supported by the Health and Labour Sciences Research Grants for Research on Rare and Intractable Diseases from 2014 to 2016 in Japan (registration number: general-068). This study was performed in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects by the Ministry of Health, Labour, and Welfare of Japan in 2014 and was in compliance with the 1964 Declaration of Helsinki (revised in 2013). This study was approved by the Research Ethics Committee of Kagoshima University Hospital (registration number: 170347).

2.1. Patients’ characteristics

The clinical characteristics of the patients with defecation problems (n=55, 25.8%) and patients without defecation problems (n=158, 74.2%) are shown in Table 1. The age at anorectoplasty of patients with defecation problems was significantly younger in comparison to patients without problems (19.1 ± 19.4 vs. 28.2 ± 41.0 months, p=0.03). No significant differences were observed between the two groups with regard to the gestational age, body weight at birth, or follow-up period.

2.2. The defecation status of PC patients

The bowel functions at the latest evaluation of the PC patients were shown in Figure 1. The details of constipation are shown in Figure 1a. Thirty (21.2%) patients indicated “absent”, 45 (31.9%) patients indicated “accidental”, 42 (29.8%) patients indicated “require enema or suppository every day”, and 24 (17.0%) patients indicated “require colonic irrigation or stool extraction”. The details of incontinence are shown in Figure 1b. Seventy-three (51.7%) patients indicated “absent”, 37 (26.2%) patients indicated “incontinence with diarrhea”, 24 (17.0%) patients indicated “accidental”, 5 (3.5%) patients indicated “more than twice a week”, and 2 (1.4%) patients indicated “frequent”. The details of soiling are shown in Figure 1c. Seventy- three (51.7%) patients indicated “absent”, 64 (45.4%) patients indicated “accidental”, and 4 (2.8%) patients indicated “frequent”.

The content of the defecation problems in 55 patients was as follows (Table 2): 8 (14.5%) patients suffered from fecal incontinence, patients (9.0%) suffered from soiling, 3 patients (5.5%) suffered from constipation, 3 patients (5.5%) felt that frequent bowel movements were a problem, and one patient (1.8%) felt that it took a long time to defecate after enema.

2.3. Logistic regression analysis of potential risk factors of the patients with or without defecation problems

We performed a logistic regression analysis to clarify the relationship between defecation problems and potential risk factors for bowel dysfunction in PC patients (Table 3). A multivariate logistic analysis showed that the associated anomaly of sacral agenesis (adjusted OR 3.19, 95% confidence interval [CI] 1.11-9.16, p=0.03) independently increased the risk of defecation problems. The other parameters, spinal cord meningeal syndrome, the timing of anorectoplasty and the type of anorectoplasty were not statistically associated with defecation problems.

2.4 Logistic regression analysis of bowel management the patients with or without defecation problems

We conducted a multivariate logistic regression analysis of factors associated with bowel management in PC patients with defecation problems that showed p values of < 0.05 in a univariate logistic regression analysis (Table 4). This analysis further clarified that PC patients who underwent the regular oral administration of laxatives (adjusted OR 2.84, 95% CI 1.24-6.55, p=0.01) and antegrade continence enema (adjusted OR 12.4, 95% CI 2.35-65.6, p=0.003) independently had the defecation problems.

We conducted an analysis of potential risk factors for defecation problems and factors affecting bowel management based on the long-term bowel function in patients with PC who were identified in a nationwide survey in Japan. The major findings of this study were as follows: (1) Of 213 patients with PC who answered our questionnaire, 55 (25.8%) had defecation problems; (2) according to the constipation score, only 21% of the patients were free of constipation; (3) according to the incontinence and soiling score, 52% of the patients were asymptomatic, while the remaining patients had some symptoms; (4) a multivariate logistic analysis showed that associated anomalies of sacral agenesis was significantly associated with defecation problems; (5) the other multivariate logistic analysis showed that PC patients suffering defecation problems underwent antegrade continence enema and regularly took laxatives.

The incidence of fecal incontinence was reported to be at least 25–30% [5], and it was reported that appropriate bowel management overcame fecal incontinence in 90% of cases with fecal incontinence [6]. In our study, however, bowel management itself was found to be a burden on the patients themselves. Our multivariate logistic analysis showed that antegrade continence enema and the regular administration of laxatives independently increased the risk of suffering defecation problems. We suspected that it took time to perform antegrade continence enema, and there were some complications associated with stoma, such as stoma stenosis or stool leakage from the tract of the antegrade continence enema [7]. We also suspected that in patients who regularly took laxatives, the laxatives were likely taken daily and after each meal, and that in some cases, it may have been necessary to adjust the oral administration according to the defecation situation. Due to the above reasons, patients performing antegrade continence enema and those who regularly took laxatives felt that they had some problems with their bowel functions. On the other hand, glycerin enema was the preferred method of bowel management in our country, 37% of PC patients required enema daily. However, in our regression analysis the rate of regular glycerin enema in patients with or without defecation problems did not differ to a statistically significant extent. By performing glycerin enema, PC patients could defecate within one hour, and they could do it on their own time; thus, glycerin enema may be a relatively simple and useful defecation method for PC patients with defecation problems.

The incidence of constipation and soiling after anorectoplasty were reported to be 10–73% and 15–23%, respectively [8–11]. However, constipation and soiling were shown to improve chronologically with age [12, 13]. Rintala et al. and Borg et al. reported that the period of constipation improvement was closely related to physical growth and sexual maturation of puberty [13, 14]. In our study, however, although the mean follow-up period of PC patients was approximately 13 years, which was the age around puberty, the incidence rates of constipation and soiling of patients with PC were high in comparison to previous reports about patients with anorectal malformations. The poor bowel function of PC patients was related to the fact that PC had more associated anomalies and delayed radical surgery, as described below.

Sacral agenesis and spinal cord meningeal syndrome have been reported as anomalies associated with the bowel function [15, 16]. In our study, 24% of PC patients had sacral agenesis, and our multivariate logistic analysis showed that sacral agenesis was significantly associated with suffering defecation problems. In cases with imperforate anus, bowel management was less effective, and the same could be expected to be true for PC patients. The incidence of sacral abnormality in PC patients was reported to be 57% [17], which was higher than the incidence in this study. The reason for this was that 54.5% (116/213 cases) of cases could not be evaluated for sacral agenesis. In fact, it could be suggested that there may have been more cases of sacral agenesis. Sacral agenesis is an important factor in the management of bowel function after anorectoplasty in PC as well as in the imperforate anus, and a thorough evaluation of sacral malformations is necessary to obtain a better bowel function.

The performance of anorectoplasty at an early age is associated with some advantages [18, 19]. The performance of anorectoplasty at an early age allowed for the passage of stool earlier, with early establishment of the brain-defecation reflex [20, 21]. In this study, patients with or without defecation problems underwent anorectoplasty at around 2 years of age, and our regression analysis showed that there was no significant difference in the presence or absence of defecation problems. There were only 29 cases (19.6%) in which anorectoplasty was performed before 12 months of age. This is because PC patients had many comorbidities, and—in addition to anorectal malformations—urinary and gynecological diseases must be evaluated and treatment methods must be considered; thus, anorectoplasty was inevitably delayed. Although the defecation function in PC patients was poor with or without defecation problems, the performance of anorectoplasty as soon as possible could be expected to improve the defecation function.

Our multivariate logistic analysis of potential risk factors for defecation problems in PC patients based on a nationwide survey showed that sacral agenesis was significantly associated with defecation problems. PC patients with defecation problems were managed with the regular administration of laxatives and antegrade continence enema. Those patients require vigorous defecation management.

Author contributions

H.T. and S.K. wrote the main manuscript text. Y.K., M.M and K.T. prepared tables and researched the literature. I.S .and K.M. gave conceptual advices. All authors reviewed the manuscript.

Conflict of interest

The authors declare no conflicts of interest in association with the present study.

Acknowledgments

We thank the members who participated in the nationwide survey in Japan, and the following researchers who are referenced in the manuscript [1]. We thank Mr. Brian Quinn for his comments and help with the manuscript. This study was supported by the Research Project for Rare and Intractable Diseases of the Ministry of Health, Labour and Welfare (MHLW), a research grant from The Mother and Child Health Foundation, and a research grant from the Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics.

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Harumatsu T, Sugita K, Ieiri S, Kubota M (2022) Risk factor analysis of irreversible renal dysfunction based on fetal ultrasonographic findings in patients with persistent cloaca: Results from a nationwide survey in Japan J Pediatr Surg 57(2):229–234
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Table 1 Clinical characteristics of the patients with or without defecation problems

	Defecation problems		p-value
	With problems (n = 55)	Without problems (n = 158)	p-value
Gestational week (weeks)	32.6 ± 12.5	35.5 ± 8.7	0.05
Body weight at birth (kg)	2.48 ± 0.8	2.66 ± 0.7	0.1
Age at anorectoplasty (months)	19.1 ± 19.4	28.2 ± 41.0	0.03
Follow up period (years)	13.0 ± 7.1	13.1 ± 7.1	0.9

Table 2 Details of problems related to defecation

	Number (%)
Fecal incontinence	8 (14.5)
Soiling	5 (9.0)
Constipation	3 (5.5)
Frequent defecation	3 (5.5)
Take time to defecate after enema	1 (1.8)

Table 3 Logistic regression analysis of potential risk factors of the patients with or without defecation problems

	Defecation problems		Univariable			Multivariable
Parameters	+	―	Crude OR	95% CI	p-value	Adjusted OR	95% CI	p-value
Associated anomalies
Spinal cord meningeal syndrome (+/-)	11/36	15/108	2.19	0.83 - 5.65	0.09	1.73	0.56 – 5.39	0.35
Sacral agenesis (+/-)	12/18	12/55	3.02	1.04 - 8.87	0.02	3.19	1.11 – 9.16	0.03
Timing of anorectoplasty
Anorectoplasty at ≦12 months of age (≦12/>12)	7/30	22/89	1.06	0.39 - 3.24	1.0
Anorectoplasty at ≦24 months of age (≦24/>24)	27/6	85/26	0.73	0.22 – 2.07	0.6
Type of anorectoplasty
Operative procedure for anorectoplasty (PSARP/others)	31/17	95/50	1.04	0.49 - 2.16	1.0

OR, odds ratio; CI, confidence interval; PSARP, posterior sagittal anorectoplasty.

Table 4 　Logistic regression analysis of bowel management the patients with or without defecation problems

	Defecation problems		Univariable			Multivariable
Parameters	+	―	Crude OR	95% CI	p-value	Adjusted OR	95% CI	p-value
Bowel management
regular administration of laxatives (+/-)	23/12	43/68	3.00	1.28 - 7.37	0.006	2.84	1.24 – 6.55	0.01
antegrade continence enema (+/-)	7/28	2/112	13.66	2.43 - 142.1	0.0006	12.4	2.35 – 65.6	0.003
regular glycerin enema (+/-)	16/19	36/73	1.70	0.72 - 3.97	0.22

OR, odds ratio; CI, confidence interval; PSARP, posterior sagittal anorectoplasty.

No competing interests reported.

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published 30 Jan, 2023

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Editorial decision: Accepted
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You are reading this latest preprint version

Analysis of the potential risk factors for defecation problems and their bowel management based on the long-term bowel function in patients with persistent cloaca: Results of a nationwide survey in Japan

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Materials And Methods

1.1. Study population

1.2. Data collection

1.3. The evaluation of the bowel function

1.4. Statistical analyses

1.5. Ethical Approval

Results

Discussion

Conclusion

Declarations

References

Tables

Additional Declarations

Status:

Journal Publication

Version 1