The clinical features of patients who underwent bladder augmentation of cloacal exstrophy and their functional outcomes: The results of a nationwide survey in Japan

doi:10.21203/rs.3.rs-3115437/v1

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The clinical features of patients who underwent bladder augmentation of cloacal exstrophy and their functional outcomes: The results of a nationwide survey in Japan

https://doi.org/10.21203/rs.3.rs-3115437/v1

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Journal Publication

published 11 Jul, 2023

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PURPOSE

Cloacal exstrophy (CE) patients may need bladder reconstruction after initially undergoing surgery to obtain continence and improve their quality of life. This study attempts to clarify the clinical features of CE patients who underwent bladder augmentation (BA) and their urinary functional outcomes based on a nationwide survey in Japan.

METHODS

A questionnaire survey was conducted, and 150 CE patients were enrolled. Their clinical characteristics and urinary outcomes were reviewed.

RESULTS

BA was performed in 52 patients (34.7%). Most cases underwent early bladder closure at initial surgery in neonate period. The age at the BA was performed 6.4 [6–9.0] years old. Among them, the most used organ for BA was ileum (n = 30, 57.7%). Regarding the outcomes, the age when the renal function was evaluated was 14.0 [10.0–20.5] years old and the serum creatinine level was 0.44 [0.36–0.60] (mg/dl). Clean intermittent catheterization was required in 37 (71.2%) patients. On the other hand, no dialysis or kidney transplantation was necessary in any of these patients.

CONCLUSION

The renal function and conditions of patients who underwent BA were relatively well preserved. Individualized management with a stepwise surgical approach for CE patients should thus be considered in the future.

cloacal exstrophy

bladder augmentation

renal function

quality of life

nationwide survey

Cloacal exstrophy (CE) is an extremely rare congenital anomaly of the anorectum and urogenital tract. The prevalence of CE is estimated to be approximately 1 in 200,000 live births [1]. According to a 2014 nationwide survey of CE in Japan, the incidence of CE from 1980 to 2012 was 0.49 per 100,000 which is much lower than that of the major congenital anomaly of anorectal malformation, which is 1 per 4000–5000 [2, 3]. CE is the most severe form of cloaca-related anomaly, and it is characterized by a failure of lower abdominal wall closure, resulting in exstrophy of the intestines, as well as the urinary and genital organs. It has also been reported that a combination of defects may sometimes occur in combination with CE, consisting of omphalocele, exstrophy of the cloaca, imperforate anus, and spinal defects as “OEIS complex” [4].

These multiple anomalies of other organs normally have a major influence on the treatment outcome of such patients [2]. On the other hand, because it is an extremely rare and complicated condition, it is difficult to determine the optimal treatment strategies based on the findings of cases that have been treated at a single institution. Most patients with CE require multiple reconstructive urinary procedures to achieve continence [5], which often consists of bladder augmentation (BA) in addition to bladder neck reconstruction and continent catheterized channel creation after the initial approximation of the bladder halves to improve their quality of life (QOL). However, the outcomes after BA remain unclear. The aim of this study was to investigate the clinical features of patients with CE who underwent BA and to clarify their renal functional outcomes after BA based on a nationwide survey in Japan.

2.1. Study population

A nationwide survey was conducted, entitled “Establishment of the treatment guidelines for smooth transitional care of persistent cloaca, cloacal exstrophy and Mayer-Rokitansky-Kuster-Hauser syndrome” [2, 3]. A total of 229 CE patients were collected. After excluding 24 deceased patients and 55 patients whom surgical treatment for bladder exstrophy were unknown, 150 CE patients were enrolled in the present study.

2.2 Data collection

Data were collected by a questionnaire survey at 244 university hospitals and children’s hospitals in Japan. We had responses by 113 (46.3%) hospitals. The patients’ background, surgical treatment for bladder exstrophy, the details of BA procedure, and long-term outcomes for CE patients were summarized.

2.3. Statistical analyses

The data are expressed as the median [interquartile range]. 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 which is designed to add statistical functions that are frequently used in biostatistics [6].

2.4. Ethical approval

This study was performed in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects established by the Ministry of Health, Labor, and Welfare of Japan in 2014 and complies with the 1964 Declaration of Helsinki revised in 2013. This study was approved by the Research Ethics Committee of Kagoshima University Hospital (Registration No. 210329).

3.1. Patients’ background

The total number of patients who underwent BA was 52 (34.7%) (BA group), and who had not undergone was 98 (65.3%) (NBA group). The patients’ background of the two groups are compared in Table 1; the number of unknown data are also shown in each category. There are no significant differences in Body weight at birth (BA: 2489 ± 371 vs. NBA: 2417 ± 411, p=0.307) and Gestational weeks (BA: 36.1 ± 1.7 vs. NBA: 35.9 ± 2.2, p=0.563) between the two groups. There was significant difference between the two groups in Defined sex (Male: Female: Unknown) (BA; 13:35:4 vs. NBA; 54:41:2, p<0.05). In the associated anomalies, Chromosome abnormality (BA; Yes=0 (0.0%), No=24 (46.2%), Unknown=28 (53.8%) vs. NBA; Yes=7 (7.1%), No=67 (68.4%), Unknown=28 (24.5%), p<0.05), Central nervous system anomalies (BA; Yes=1 (1.9%), No=38 (73.1%), Unknown=13 (25.0%) vs. NBA; Yes=12 (12.2%), No=77 (78.6%), Unknown=9 (9.2%), p<0.05), Omphalocele (BA; Yes=40 (76.9%), No=4 (7.7%), Unknown=8 (15.4%) vs. NBA; Yes=81 (82.7%), No=15 (15.3%), Unknown=2 (2.0%), p<0.05), and Spinal defect (BA; Yes=26 (50.0%), No=12 (23.1%), Unknown=14 (26.9%) vs. NBA; Yes=41 (41.8%), No=41 (41.8%), Unknown=16 (16.3%), p<0.05) were significantly difference between the two groups. There are no significant differences in Cardiac anomalies (BA; Yes=3 (5.8%), No=37 (71.1%), Unknown=12 (23.1%) vs. NBA; Yes=5 (5.1%), No=82 (83.7%), Unknown=11 (11.2%), p=0.147) and Myelomeningocele (BA; Yes=19 (36.5%), No=23 (44.2%), Unknown=10 (19.2%) vs. NBA; Yes=52 (53.1%) No=37 (37.8%), Unknown=9 (9.1%), p=0.08).

3.2. Surgical treatment for bladder exstrophy

The surgical treatment for bladder exstrophy between BA group and NBA group and age at surgery of each category were shown in Table 2. They are categorized as follows, Early ladder closure, Bladder reconstruction (including before late bladder closure in multistage closure), Late bladder closure, Urinary diversion, and No procedure (including the patients who were diagnosed “covered cloacal exstrophy”). There were significant differences in ratio of each category between the two groups as follows, Early bladder closure (BA; 33 (63.5%) vs. NBA; 31 (31.6%), age at surgery (days) (BA; 1.0 [1.0 – 6.0] vs. NBA; 1.0 [0.5 – 2.5])), Bladder reconstruction (BA; 15 (28.8%) vs. NBA; 45 (45.9%), age at surgery (days) (BA; 2.0 [0.5 – 10.0] vs. NBA; 8.0 [1.0 – 213])), Late bladder closure (BA; 0 (0.0%) vs. NBA; 12 (12.2%), age at surgery (days) (NBA; 363 [184 – 1020])), Urinary diversion (BA; 1 (1.9%) vs. NBA; 4 (4. %), age at surgery (days) (BA; 1095 vs. NBA; 3.5 [1.5 – 210])),and No procedure (BA; 3 (5.8%) vs. NBA; 6 (6.1%).

3.3 The details of BA procedure

The details of BA procedure are shown in Table 3. The age at BA (years old) was 6.4 [6 – 9.0]. The organs used for BA as follows; Ileum (n=30, 57.7%), Stomach (n=6, 11.5%), Colon (n=6, 11.5%), Stomach + Ileum (n=6, 11.5%), Cecum (n=3, 5.8%), and Hindgut (n=1, 2.0%). Simultaneous procedures that were performed at that same time of BA were as follows; route creation for conducting clean intermittent catheterization (CIC) (n=16, 30.7%), bladder neck reconstruction or closure (n=4, 7.7%), and ureterocystostomy (n=28, 53.8%).

3.4. Long-term outcomes of CE patients who underwent BA

Long-term outcomes between BA group and NBA group are compared in Table 4. Patients’ characteristics at the evaluation are as follows; Age (years) (BA: 14.0 [10.0 – 20.5] vs. NBA: 8.0 [3.0 – 16.0], p<0,05), Height (cm) (BA: 138.0 [126.1 – 149.8] vs. NBA: 114.0 [87.4 – 138.0], p<0,05), and Body weight (kg) (BA: 33.5 [24.3 – 41.4] vs. NBA: 19.6 [10.6 – 35.1], p<0,05). Regarding the renal function, the serum creatinine level (mg/dl) in BA was significantly higher than that of NBA (0.44 [0.36 – 0.60] vs. 0.33 [0.24 – 0.45], p<0,05). The percentage of patients needed CIC in BA group was higher than that of NBA group (BA: 37 (71.2%) vs. NBA: 18 (28.8%), p<0,05).

Regarding complications of urinary tract, there were no significant differences between two groups as follows; bladder disorder (BA: 32 (61.5%) vs. NBA: 71 (72.4%), p=0.197), history of urinary infection (BA: 14 (26.9%) vs. NBA: 38 (32.7%), p=0.577), bladder stone (BA: 6 (11.5%) vs. NBA: 5 (5.1%), p=0.191), and vesicoureteral reflux (BA: 16 (30.8%) vs. NBA: 37 (37.8%), p=0.474). Only 1 case in NBA group required dialysis, and no cases required kidney transplantation in both group.

This study focused on the clinical features of CE patients who underwent BA and their long-term outcomes after BA based on a nationwide survey in Japan [2,3] . The major findings of this study were as follows: (1) 34.7% CE patients underwent BA. (2) They had significantly lower rate of associated anomalies than the patients who had not undergone BA. (3) Surgical treatment for bladder exstrophy were numerous variations and there is significant difference between BA and NBA group. (4) Most BA group (65.3%) had underwent early bladder closure in neonate. (5) Most CE patients underwent BA in childhood using ileum (57.7%). (6) The renal function after BA tended to be preserved. (7) After BA, most patients required CIC (71.2%).

In our present study, similar to the findings of previous reports [7], 34.7% CE patients in Japan normally undergo BA in childhood. Most of them had lower rate of associated anomalies and they had longer follow-up in comparison the patients who had not undergone BA. The most of them (63.5%) undergone early bladder closure for bladder exstrophy in neonate period. About the percentage of the patients with BA, there was a report that 57% of patients who underwent primary closure of the bladder within 48 h after birth had undergone BA in childhood [8]. On the other hand, Shah BB et al. suggested that the average age at operation in the failure bladder closure was earlier than success closure [9]. These reviewed the time of the initial early bladder closure is not contributed to the renal function or need of secondary surgery. Regarding another factor for renal function, it was also reported that urinary continence after bladder neck reconstruction was observed in 40% of patients without spinal anomalies, but in only 7% of patients with spinal anomalies [8]. In present study, spinal anomalies were recognized in 50.0% of the patients who underwent BA similar to previous article. It is thought that the long-term outcomes and renal function and the need for a BA were determined by multiple factors such as the age at primary surgery and associated anomalies of the patients.

Regarding the various types of BA procedures, all intestinal segments available, and have advantages and disadvantages, depending on their metabolic properties [7]. In general, the ileum might have larger segments which are available for use during BA in comparison with other parts of the intestines. However, it is associated with a higher risk for developing mucous production with stone formation and metabolic acidosis than when using other organs [10,11]. Moreover, most CE patients are also complicated with short bowel syndrome, and therefore the ileum and cecum should be preserved as much as possible [12]. In the present study, one factor associated with the use of the ileum was the fact that, a few patients with bladder stones were observed. When using several segments of the intestine for CE patients undergoing BA, such patients may be affected by multiple factors including their nutritional condition, defecation function, and associated complications. As a result, the optimal segments of the intestine for usage when performing BA remained still unclear in present study.

Previously, CE patients underwent urological surgery including BA to achieve urinary continence after surgery [13]. In the present study, the details of combined surgery and urinary continence were not described. The renal function of the patients several years after undergoing BA was evaluated by their serum creatinine levels, they had relatively higher levels than the patients who had not undergone BA, but their renal function was not concerned chronic renal failure. The characteristics of evaluation were differenced; however, it was explained that the patients who undergone BA had longer follow-up. Also no cases of dialysis or renal transplantation were recognized in BA. Similar to the findings of previous reports, the patients’ renal function was relatively well preserved. It is reported that when gastric segments were used during BA, it is lower incidence of reoperation and complications [14]. On the other hand, it is reported that the surgical method of achieving continence was not predictive of hydronephrosis or scarring. The difference in postoperative results may be due to the observation period.

Regarding the QOL for CE patients, more than half of all patients required CIC in the present study. Renal functional outcomes after BA tended to be preserved, however, the patients’ QOL was compromised. Teenagers and adults born with CE have well defined long-term problems compared to the general population [15], and many of these problems still remain to be solved. In the present study, the relationship between psychological problems and renal function has not been sufficiently investigated. To clarify the impact of surgical treatment for CE patients, additional research is needed.

Limitation

There are several limitations associated with this study. This study was performed based on a questionnaire survey sent to the departments of pediatric surgery and pediatric urology. Therefore, aggregated data were based on the information provided by all individual pediatric surgeons and pediatric urologists in each institution. And the response rate in our study may be low (113/244 institutions, 46.3%). Additional information or further details regarding the data were unknown.

Urinary tract management appears to have a large impact on the QOL, especially for CE patients. Although CE patients vary regarding their specific backgrounds, the conditions of the patients who underwent BA in this study were all deemed to be within the acceptable limits. Individualized management with a stepwise surgical approach for CE patients should thus be continued in the future.

Compliance with ethical standards

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

Acknowledgments

We thank all the members who participated in the questionnaire survey in Japan, and the appendix lists of al research members. We also thank Brian Quinn, Japan Medical Communication, for his comments and help with the manuscript.

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Table 1. 　The comparison of patients’ background between BA group and

NBA group

	BA group	NBA group	p-value
Total number of patients	52 (34.7%)	98 (65.3%)
Body weight at birth (g)	2489 ± 371	2417 ± 411	0.307
Gestational weeks	36.1 ± 1.7	35.9 ± 2.2	0.563
Defined sex (Male: Female: Unknown)	13: 35: 4	54: 41: 2	<0.05
Associated Anomalies
Chromosome abnormality			<0.05
Yes	0 (0.0%)	7 (7.1%)
No	24 (46.2%)	67 (68.4%)
Unknown	28 (53.8%)	28 (24.5%)
Cardiac anomalies			0.147
Yes	3 (5.8%)	5 (5.1%)
No	37 (71.1%)	82 (83.7%)
Unknown	12 (23.1%)	11 (11.2%)
Central nervous system anomalies			<0.05
Yes	1 (1.9%)	12 (12.2%)
No	38 (73.1%)	77 (78.6%)
Unknown	13 (25.0%)	9 (9.1%)
Myelomeningocele			0.08
Yes	19 (36.5%)	52 (53.1%)
No	23 (44.2%)	37 (37.8%)
Unknown	10 (19.2%)	9 (9.1%)
Omphalocele			<0.05
Yes	40 (76.9%)	81 (82.7%)
No	4 (7.7%)	15 (15.3%)
Unknown	8 (15.4%)	2 (2.0%)
Spinal defect			<0.05
Yes	26 (50.0%)	41 (41.8%)
No	12 (23.1%)	41 (41.8%)
Unknown	14 (26.9%)	16 (16.3%)

BA bladder augmentation, NBA the patients who had not undergone bladder augmentation.

Table 2. The comparison of surgical treatment for bladder exstrophy between BA group and NBA group

	BA group	NBA group	p-value
Total number of patients	52 (34.7%)	98 (65.3%)
Surgical management for bladder exstrophy			< 0.05
Early bladder closure	33 (63.5％)	31 (31.6%)
age at surgery (days)	1.0 [1.0 -6.0]	1.0 [0.5 -2.5]
Bladder reconstruction*	15 (28.8%)	45 (45.9%)
age at surgery (days)	2.0 [0.5 -10.0]	8.0 [1.0 -213]
Late bladder closure	0 (0.0%)	12 (12.2%)
age at surgery (days)	–	363 [184 -1020]
Urinary diversion	1 (1.9%)	4 (4.1%)
age at surgery (days)	1095	3.5 [1.5 -210]
No procedure**	3 (5.8%)	6 (6.1%)

BA bladder augmentation, NBA the patients who had not undergone bladder augmentation.

* Including before late bladder closure in multistage closure

** Including the patients who were diagnosed “covered cloacal exstrophy”

Table 4. 　The comparison of long-term outcomes and renal function

between BA group and NBA group

	BA group	NBA group	p-value
Total number of patients	52 (34.7%)	98 (65.3%)
Patients’ characteristics at the evaluation
Age (years)	14.0 [10.0-20.5]	8.0 [3.0-16.0]	<0.05
Height (cm)	138.0 [126.1-149.8]	114.0 [87.4-138.0]	<0.05
Body weight (kg)	33.5 [24.3-41.4]	19.6 [10.6-35.1]	<0.05
Serum creatinine level (mg/dl)	0.44 [0.36-0.60]	0.33 [0.24-0.45]	<0.05
CIC	37 (71.2%)	18 (28.8%)	<0.05
Complication of urinary tract
Bladder disorders	32 (61.5%)	71 (72.4%)	0.197
History of urinary Infection	14 (26.9%)	38 (32.7%)	0.577
Bladder stone	6 (11.5%)	5 (5.1%)	0.191
Vesicoureteral reflux	16 (30.8%)	37 (37.8%)	0.474
Dialysis	0 (0.0%)	1 (1.0%)
Kidney transplantation	0 (0.0%)	0 (0.0%)

BA Bladder Augmentation, CIC Clean Intermittent catheterization, NBA the patients who had not undergone bladder augmentation.

No competing interests reported.

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Journal Publication

published 11 Jul, 2023

Read the published version in Pediatric Surgery International →

Editorial decision: Accepted
29 Jun, 2023
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Submission checks completed at journal
27 Jun, 2023
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27 Jun, 2023

You are reading this latest preprint version

The clinical features of patients who underwent bladder augmentation of cloacal exstrophy and their functional outcomes: The results of a nationwide survey in Japan

Status:

Journal Publication

Version 1

Abstract

PURPOSE

METHODS

RESULTS

CONCLUSION

Introduction

Patients and methods

2.1. Study population

2.2 Data collection

2.3. Statistical analyses

Results

Discussion

Conclusion

Declarations

References

Tables

Additional Declarations

Status:

Journal Publication

Version 1