Impaired expression of myogenic regulatory molecules in the pelvic floor muscles of murine embryos with anorectal malformations

Background/Purpose

Recent biological studies have elucidated the molecular mechanism of muscle development, in which various regulatory factors (myogenic regulatory factors [MRFs]) play key roles during embryogenesis. To investigate the development of anorectal malformations (ARMs), we studied MRF expressions in myogenic cells in the pelvic floor using murine embryos affected with ARM.

Methods

Anorectal malformation embryos were obtained from the 10.5th embryonal day (E10.5) to the 7.0th postnatal day (D7.0) in a natural mutant strain (Sd/+, RSV/Le). Serial frozen sections were prepared for immunohistochemistry using specific antibodies to M-cadherin, myoD, Myogenin, myosin heavy chain, and alfa-actin molecule.

Results

In normal mice, embryonal caudal somites differentiated into myogenic stem cells and migrated to the pelvic floor between E11.0 and E14.0. In the ARM mice, however, caudal somites were irregularly arranged and MRF expressions in myogenic cells were markedly decreased in the dorsocaudal region at E11.5 to E13.0, leading to hypoplastic pelvic floor muscles.

Conclusions

The maldevelopment of pelvic floor muscles in ARM is derived from a deficient supply of myogenic stem cells, with impaired MRF expression. These results suggest that myogenic stem cells, available from bone marrow contents, may be used for postnatal muscle regeneration to reinforce the pelvic floor muscle function in children with ARM.     

Aberrations of the intrinsic innervation of the anorectum in fetal rats with anorectal malformations

Background

Fecal accumulation, constipation, soiling, and incontinence are common sequelae after repair of anorectal malformations (ARMs) in children. It is believed that besides the abnormalities of sacral roots, certain inherent abnormalities of the myenteric plexuses may play an important role in the final outcome after definitive repair.

Methods

This study was conducted to investigate the distribution of neuron-specific enolase (NSE), vasoactive intestinal peptide (VIP), and substance P (SP)-100 neurotransmitters in the rectosigmoid and fistulous tract of the ethylenethiourea-treated rat with ARMs.

Results

ARMs were induced by administering 1% ethylenethiourea (125 mg/kg) on gestational day 10, and the litter was harvested on gestational day 21 by cesarean section. Forty-eight controls and 63 with ARMs (46 high-type and 17 low-type) were recovered. Whole-mount preparations of each rectosigmoid and fistulous communication between the rectum and genitourinary tract were stained with fluorescent antibodies against NSE, VIP, and SP-100. The tissues were counterstained with Eriochrome black-T and methyl green dyes to improve the visualization of the myenteric plexuses.

Conclusions

The immunoreactivity of NSE, VIP, and SP-100 was markedly reduced in the rectum and fistulous tract of high-type ARMs and slightly reduced in low-type ARMs compared with controls. Intramural nerves stained by VIP and SP-100 antisera were decreased in both types of ARM, indicating that both inhibitory and excitatory motor neural elements were affected, and this may explain the distal colonic dysmotility seen postoperatively in both high and low ARMs.     

Validation of the Baylor Continence Scale in children with anorectal malformations

Background

Anorectal malformations (ARMs) often result in lifelong problems with defecation. There have been no studies performed to develop scoring systems in children with fecal incontinence following repair of ARM. This study was designed to develop and validate a tool (Baylor Continence Scale [BCS]) to measure social continence in children after surgical correction of ARMs.

Methods

The BCS is a 23-question survey, was administered to children who have had repair of an ARM, children with enuresis, and normal children.

Results

Children in the ARM group had an average BCS score of 28.0, which was statistically different from an enuresis control group (16.5) and normal controls (11.5) (P < .05). A significantly greater proportion of children in the ARM group had higher Impact on Family Scores (>30) than either the enuresis or normal control group (P < .05).

Conclusions

The BCS tool should be useful in prospective studies of interventions to improve incontinence after repair of an ARM. An important secondary result of this study was to demonstrate the effect on families of caring for a child with imperforate anus, even years after the repair.     

Magnetic resonance imaging of the pelvic floor in the postpartum patient

Magnetic resonance imaging (MRI) was used to assess anatomical changes in the pelvic floor after childbirth. Six women underwent serial MRI examination within 30 hours and at 1 week, 2 weeks, 6 weeks and 6 months after delivery; 8 additional women were studied only within 30 hours of delivery. T-1 and T-2-weighted images of the pelvis in the transverse and sagittal planes with a 1.5-T MR imager were obtained. In the sagittal section we assessed the urethrovesical angle, urethral length, distance from the symphysis to the proximal and distal vagina, vaginal length, width and length of the sphincters, and the presence of sphincter defects. Axial sections were assessed for sphincter defects for the distance between the symphysis and midurethra, vagina and rectum. Only one parameter (distance between symphysis and distal vagina) changed significantly over time, without a clear trend in direction. Interobserver variation was reasonable (<15%) except for anal canal length, urethral length and distance between symphysis and anus. There were no significant correlations between birthweight and MRI parameters. There was a non-significant association (P=0.09) between the sole combined sphincter defect and rectal injury, but not with episiotomy or parity. We concluded that it is feasible to determine multiple measurements on MR images to evaluate structures of the pelvic floor.EDITORIAL COMMENT: Although the presented study has multiple limitations — i.e. small sample size, no control group, static images, lack of correlated symptomatology — the investigators show that magnetic resonance imaging can be used to follow the natural course of pelvic floor changes after vaginal delivery. Hopefully this work will be continued and expanded, shedding more light on the effects of childbirth on pelvic floor anatomy and function.     

三维动态超声对盆底失弛缓综合征的诊断

目的探讨三维动态超声诊断盆底失弛缓综合征（PFD）的可行性。方法对符合PFD诊断的30例女性便秘患者行三维动态超声检查,比较其静息状态下与模拟排粪状态（Valsalva动作）时经会阴动态超声测量的指标饯角、经肛管三维超声测量的β角、γ角和H线的差异;同时,对超声各测量指标诊断盆底失弛缓综合征的检出率进行分析。结果三维动态超声检测出30例患者中直肠前突13例（43．3％）,直肠黏膜内套叠14例（46．7％）,子宫脱垂11例（36．7％）,膀胱脱垂1例（3．3％）。与静息状态相比,Valsalva动作时α角、β角和H线显著缩小,γ角显著增大,差异均有统计学意义（均P〈0．01）。α角、β角、γ角和H线对PFD的检出率分别是93．3％（28／30）、96．7％（29／30）、96．7％（29／30）和86．7％（26／30）。结论经会阴超声测量的仅角和经肛管超声测量的β角、γ角和H线都可以为临床上诊断PFD提供可行的指标数据。     

Impact of spinal cord malformation on bladder function in children with anorectal malformations

Purpose

Risk factors for the presence of neurogenic bladder dysfunction (NBD) in children born with high anorectal malformations (ARMs), were investigated, to identify the need for urodynamics in these patients.

Material and Methods

The study included 37 patients with high ARMs (21 boys and 16 girls). Bladder function was evaluated with urodynamics both before and after anorectoplasty (posterior sagittal anorectoplasty [PSARP]). All patients were investigated with spinal radiograph. Spinal ultrasound was performed in the neonatal period, and magnetic resonance imaging was added in case of abnormal ultrasound or urodynamics and in case of cloacal malformation.

Results

In ARM patients with rectourethral and vestibular fistulas and cloacas, NBD was identified in 9 children (25%). The bladder dysfunction was innate in all cases except in one girl with cloaca, indicating that the risk of iatrogenic denervation seems minimal using the PSARP technique. All children with innate NBD had a spinal cord malformation either as spinal cord regression or tethering with or without a lipoma. Concerning vertebral status, almost all children with NBD had partial sacral agenesis. Abnormal perineal appearance was highly correlated to NBD in boys, especially in those with a spinal cord regression malformation. Innate NBD was not found in any child with normal spinal cord.

Conclusion

From these results, we suggest that spinal ultrasound and perineal inspection are used as screening procedures for NBD in children with ARM. Urodynamic investigation is recommended only when spinal cord anomalies or other signs indicative of NBD are present. In case of spinal cord malformation, repeated urodynamics during follow-up is mandatory because of the risk for developing tethered cord syndrome.     

盆底松弛综合征的病理生理与外科治疗的研究

目的研究盆底松弛综合征（ＲＰＦＳ）的病理生理特征，并探讨盆腔紧固术对本征的治疗价值。方法对１１例诊断为ＲＰＦＳ患者的临床症状进行了分析，并行标准化盆腔紧固术，术后平均随访１９个月。结果患者的主要症状与体征为排便困难、排便不全、会阴坠胀、排便时会阴下凸、子宫后倾及直肠松弛。肛肠动力学检测有静息压、收缩压下降，收缩时间缩短，直肠感觉功能减退。排粪造影示盆腔多种松弛性病变同时存在。术中可见结肠、直肠、子宫的固定松弛及腹腔位置降低。术后７例症状完全消失；４例明显改善。结论ＲＰＦＳ的病理生理特征是以盆腔脏器为主的多部位、多系统、多脏器松弛性改变。盆腔紧固手术对本征的治疗具有一定价值     

Functional outcome and quality of life in anorectal malformations

Background/Purpose

The aim of this study was to assess the early functional outcome and quality of life (QOL) in children with anorectal malformations.

Methods

Children treated for anorectal malformations (ARMs) from 1994 to 2000 were evaluated if 4 years or older. Primary outcome measures were bowel function score, assessed by functional outcome questionnaire, and QOL using the Pediatric Quality of Life Inventory (PedsQL 4). The secondary outcome measure was age at potty training. Twenty healthy children were used as controls for functional outcome and age at potty training. Data are reported as mean (SD) unless otherwise stated.

Results

Eighty children were evaluated during the study period. The mean age at follow-up was 82 months (18.7). The response rate was 76.3% (58/76) for bowel function and 77.5% (62/80) for QOL questionnaires. Functional outcome score (maximum 20) decreased significantly with increasing severity of the ARM (male perineal fistula, 16 [3]; female perineal fistula, 15 [3]; rectourethral fistula, 12 [4]; vestibular fistula, 13 [3.5]; bladder neck fistula, 6 [2]; analysis of variance, P = .001). However, there was no difference in QOL between patients with ARM and controls. There was no correlation between age and either bowel function score (Pearson r² = 0.06) or QOL (Pearson r² = 0.12). Affected children took significantly longer to achieve potty training for bladder (35 [13.8] months vs 26 [8.7] months for controls [t test, P = .005]) and bowels (38 [16] months vs 25 [7] months [t test, P = .001]).

Conclusion

Children with ARMs have significantly worse bowel function than their peers, depending on the type of lesion. Despite these findings, QOL was not significantly impaired. No correlation was demonstrated between age and either functional outcome or QOL.     

Dynamic assessment of pelvic floor function in women using the intravaginal device test

The aim of the study was to assess pelvic floor function and dysfunction using intravaginal devices (IVD test). One hundred and eighty-five patients were evaluated, 65 (35.1%) in the control group without genital prolapse and 120 (64.9%) in the study group, with prolapse. Anatomic changes were evaluated on a scale described by Halban, and functional classification based on palpation of the muscles of the pelvic floor during contraction. Additionally, weighted vaginal devices were used to assess pelvic floor function. Statistic analysis was performed with the Spearman-Pearson correlation coefficient, the ² test and the response/ operator characteristic curve. There was an acceptable correlation between the IVD test and the functional classification of 0.75. Using this classification, the IVD test showed 86.58% sensitivity, 75.72% specificity, and had a positive predictive value 73.95% and a negative predictive value of 87.64%. Significant differences between pelvic floor muscle activity in those patients with and without genital prolapse were observed (X²=58.28, P=<0.005). It was concluded that pelvic floor assessment can be done through the evaluation of active muscle strength or pelvic floor integrity using the functional classification and the IVD test.EDITORIAL COMMENT: In 1988, Peattie and Plevnick introduced the use of weighted vaginal cones to exercise the pelvic floor muscles and treat stress urinary incontinence [1]. Contreras-Ortiz and Nuñez build on this earlier work, using a similar technique to assess pelvic floor muscle function and integrity. Specifically, pelvic floor function is assessed by a combination of digital palpation of the pubococcygeus muscle at rest and during contraction; pelvic floor integrity is assessed by the patient's ability to retain a weighted cone vaginally for 1 minute. Scoring of these two parameters can then be objectively followed for therapeutic response to treatment for urinary incontinence or pelvic relaxation. Many of us forget to palpate the pubococcygeus muscle at rest and during an elicited contraction during baseline or follow-up examination. As this study indicates, simple assessment of pelvic floor function and integrity is possible, and should be used both clinically and in research.     

盆底肌电图在出口梗阻性便秘中的诊断价值

目的:探讨各类型出口梗阻型便秘的盆底肌电图诊断价值.方法:对90例出口梗阻型便秘患者,进行盆底肌电图检查,并分析其结果.结果:①静息相:5种出口梗阻型便秘均可出现异常电位,以松弛性盆底疾病多见,尤以会阴下降患者居多.松弛性疾病表现出内外括约肌的异常静息电位居多,痉挛性疾病表现出耻骨直肠肌的异常电位居多.②轻度收缩相:5种出口梗阻型便秘疾病的动作电位电压下降,波幅缩短,表明肌源性损伤.③重度收缩相松弛性盆底疾病多见异常,痉挛性盆底疾病相对较少.④模拟排便相以痉挛性盆底疾病多见反常收缩,并以耻骨直肠肌异常居多,松弛性盆底疾病相对较少.⑤总体评价出口梗阻型便秘的盆底肌电图异常率高达95.56%.结论:盆底肌电图应作为便秘的常规检查方法,不仅方便综合评定盆底功能,更能早期发现异常,还可以鉴别出松弛性盆底疾病和痉挛性盆底疾病.出口梗阻型便秘耻骨直肠肌的自制功能保存良好.松弛性出口梗阻型便秘患者内、外括约肌收缩障碍;痉挛性出口梗阻型便秘症状多由于耻骨直肠肌松弛障碍引起.     

Comparison of clinical outcomes and anorectal manometry in patients with congenital anorectal malformations treated with posterior sagittal anorectoplasty and laparoscopically assisted anorectal pull through

Purpose

The objective of this study is to analyze the clinical outcomes and anorectal manometry (AM) in infants with congenital high anorectal malformations treated with posterior sagittal anorectoplasty (PSARP) and laparoscopically assisted anorectal pull through (LAARP).

Materials and Methods

From August 2005 to December 2008, 23 patients with congenital high anorectal malformations were randomly distributed into PSARP and LAARP groups. All of them underwent LAARP (11 cases) or PSARP (12 cases) at 2 or 3 months old. Clinical outcomes and results of anorectal manometry were compared between patients at the age of 17.4 ± 4.9 and 19.3 ± 6.2 months (P = .4270), respectively.

Results

Kelly's clinical score for patients in LAARP and PSARP groups was 3.91 ± 1.14 and 3.83 ± 1.40 (P = .8827), respectively. Anal canal resting pressure and high-pressure zone length were 29.4 ± 7.2 vs 23.4 ± 6.5 mm Hg (P = .0479) and 14.9 ± 3.0 vs 13.9 ± 3.1 mm (P = .4414), respectively. Rectal anal inhibitory reflex was observed in 81.8% (9/11) and 83.3% (10/12) patients (P = 1.0000), respectively. The mean length of stay during the second hospitalization was 10.6 ± 0.9 and 14.3 ± 1.4 days (P < .0001), respectively.

Conclusions

Although no significant difference can be noted in clinical scoring between both groups, the results of anorectal manometry indicate that LAARP can significantly improve anal canal resting pressure and reduce the length of stay.     

Pelvic floor muscle function in women presenting with pelvic floor disorders

Introduction and hypothesis  This observational study was undertaken to determine knowledge, prior instruction, frequency of performance, and ability to perform pelvic floor muscle exercises in a group of women presenting for evaluation of pelvic floor disorders. Methods  Three hundred twenty-five women presenting for evaluation of pelvic floor disorders were questioned concerning knowledge and performance of pelvic floor muscle exercises (PMEs) and then examined to determine pelvic floor muscle contraction strength. Results  The majority of women (73%) had heard of PMEs, but only 42% had been instructed to perform them and 62.5% stated they received verbal instruction only. Only 23.4% of patients could perform pelvic muscle contractions with Oxford Scale 3, 4, or 5 strengths. Increased age, parity, and stage of prolapse were associated with lower Oxford scores. Conclusions  Although most women with pelvic floor disorders are familiar with PMEs, less than one fourth could perform adequate contractions at the time of initial evaluation.     

Developmental study of tethered spinal cord in murine embryos with anorectal malformations

Background/Purpose

Tethered spinal cord is frequently associated with anorectal malformations (ARMs). However, it remains unknown how the tethered spinal cord develops and relates to the severity of ARM. We studied the development of the spinal cord in ARM mouse embryos induced by all-trans retinoic acid (ATRA).

Methods

Pregnant ICR-Slc mice were administered 100 mg/kg of ATRA on the ninth embryonic day (E9.0). Embryonic specimens were obtained from the uteri between E11.0 and E18.5. Midsagittal histologic sections focusing on the spinal cord and pelvis were prepared for immuonhistochemistry specific for neurofilament and Protein Gene Product 9.5 molecules.

Results

More than 98% of ATRA-treated embryos demonstrated ARM with rectourethral or rectocloacal fistula. Normal embryos exhibited progressive ascent of the spinal cord from E14.5. However, in ARM embryos, the distal spinal cord ended with meningomyelocelelike or atypical hamartomatous lesions at E11.5 to E13.5, which later caused stretch force that damaged the spinal cord, resulting in tethered cord between E16.0 and E16.5.

Conclusions

In ATRA-induced ARM mouse embryos, tethered spinal cord was mostly established, accompanied by caudal neural maldevelopment, during early fetal development. This experimental model may be useful for researching detailed neuropathologic conditions in ARM children accompanied with tethered spinal cord.     

Social quality of life for adult patients with anorectal malformations

Background/Purpose

Pediatric surgeons who performed the initial surgery on anorectal malformations (ARM) lose contact with the patients as they become adults. In the present study, we examined 20- to 40-year-old adult patients with a history of surgery for ARM and analyzed them from the points of social quality of life.

Patients and Methods

Twenty-nine patients with ARM, aged 20 to 40, were surveyed by questionnaire or personal interview. Thirteen with high-type and 9 with intermediate-type anomalies underwent abdominoperineal rectoplasty, and 7 with low-type anomalies underwent perineoplasty between 1965 and 1985. Responses were analyzed from the perspectives of bowel, urinary, and sexual functions and social activity.

Results

One third of patients with high- or intermediate-type anomalies occasionally complained of fecal soiling. However, the other patients gained good bowel function and enjoyed occupational or student life without problems. Fecal soiling was the key factor disturbing occupational life, although the problem remained within a socially manageable level. All of the patients with ARM had normal urinary function. Three of the 18 male patients had sexual problems such as erectile or ejaculatory dysfunction because of associated genitourinary anomalies. Nine of the 11 female patients had regular menstruation and the other 2 had irregular menstrual periods. Five female patients were married and 4 of the 5 had children (1-5 children). Modes of delivery were normal vaginal delivery in 8 and cesarean section in 1. Only one of the 5 had a slight sacral anomaly. However, she had no apparent abnormality of bladder function and got through pregnancy and delivery without difficulty.

Conclusion

One third of adult patients with high- or intermediate-type anomalies after abdominoperineal rectoplasty had some problems in bowel function. Fecal soiling was the key factor that disturbed their occupational life. Most of the patients had normal urinary and sexual functions if they did not have associated genitourinary anomalies and enjoyed social activities.     

女性盆底松弛综合征患者肛提肌裂隙的动态三维超声研究

目的探讨动态三维超声对盆底松弛综合征患者治疗前后肛提肌裂隙形态结构改变方面的评估价值。方法2011年10月到2012年9月间于南京市中医院便秘专病门诊筛选出盆底松弛综合征所致便秘的40例女性患者,填写克里夫兰便秘评分（CCS评分）量表,并在Valsalva动作时进行动态三维超声检查,测量患者肛提肌裂隙的前后径和左右径。经1个疗程（2周）的生物反馈和针灸治疗后,再次填写治疗后CCS评分量表并复查Valsalva动作时的动态三维超声。结果最终有25例盆底松弛综合征女性患者接受治疗前、后的动态三维超声检查并完成CCS评分量表。与治疗前相比,治疗后Valsalva动作时动态三维超声所测得的肛提肌裂隙纵轴[（5．13±0．82）cm比（4．89±0．89）cm,P〈O．01]、横轴[（4．86±0．74）cm比（4．62±0．75）cm,P〈0．01]和面积[（19．92±6．33）cm。比（18．16±6．42）cm2．P〈0．01]均明显减小,CCS评分亦明显下降[（15．80±3．42）比（9．52±2．50）,P〈0．01）。结论使用动态三维超声可以为女性盆底松弛综合征肛提肌裂隙的测定提供一种简单、无创并有效的影像学检测方法。     

Dynamic magnetic resonance imaging: reliability of anatomical landmarks and reference lines used to assess pelvic organ prolapse

The aim of this study was to determine the intra- and interobserver reliability of dynamic magnetic resonance (MR) staging in pelvic organ prolapse patients. In 30 patients with pelvic organ prolapse, dynamic MR images were assessed independently by two observers. Various anatomical landmarks to asses pelvic organ prolapse were used in relation to the pubococcygeal line, H-line, and mid-pubic line. Clinical measurement points were assessed in relation to the mid-pubic line. The intraclass correlation coefficients (ICC) were calculated to describe the intra- and interobserver reliability. Overall, the intra- and interobserver reliability of MR imaging measurements was excellent to good. The pubococcygeal line showed superior reliability (ICC range 0.70–0.99). The reliability of clinical measurement points, however, were only moderate (ICC range 0.20–0.96). The intra- and interobserver reliability of quantitative prolapse staging on dynamic MR imaging were good to excellent. The pubococcygeal line appears the most reliable to use.     

Augmentation of urethral pressure profile by voluntary pelvic floor contraction

The aim of the investigation was to study the repeatability of urethral pressure profile (UPP) and to quantify the influence of voluntary pelvic floor contraction on the UPP. Seventy-two patients underwent one UPP at rest and one UPP during a pelvic floor contraction. The functional urethral length (FUL) and the maximum urethral closure pressure (MUCP) were recorded. To establish repeatability the UPP was repeated twice in 18 patients in rest, and in 15 patients during a contraction. We used the repeatability coefficient instead of the correlation coefficient. Forty-eight patients, had no major anatomical abnormalities (group A); 24 had grade 2 or more prolapse (group B). In both groups we found a shortening of the FUL and an increase in MUCP during a contraction. The UPP was reproducible, both at rest and during a contraction. In conclusion, we found a significant and constant increase in MUCP and a shortening of the FUL during a contraction. Unlike other studies we found the UPP to have good reproducibility. However, we used the repeatability coefficient instead of the correlation coefficient.     

The effect of training with vaginal weighted cones and pelvic floor exercises on the strength of the pelvic floor muscles: A pilot study

A pretest-post-test design (n=14) was used to investigate pelvic floor muscle (PFM) strength over a 2-month training period using vaginal cones with pelvic floor exercises in the treatment of female stress incontinence, and to correlate any changes in muscle strength with objective and subjective measures of stress incontinence. PFM strength was assessed by vaginal examination and the ability to retain the cones. The symptom of stress incontinence was assessed using rating scales, and measured objectively by the extended pad test. The results showed a significant increase in muscle strength (P<0.05). An unexpected finding was that most of the improvement in PFM function occurred in a 1-week baseline assessment period before training was commenced. It is therefore suggested that the increase in force generation occurred due to a process of neural adaptation rather than muscle hypertrophy. No significant correlations were found between muscle strength and objective or subjective measures of stress incontinence.Editorial Comment: Vaginal cones are gaining in popularity as a method of therapy for stress incontinence. As in this study, the symptom of stress incontinence was enough to begin treatment and objective documentation of the diagnosis was not undertaken. The therapy has no side-effects and only requires that the patient is motivated enough to put the cone in the vagina and take it out after a prescribed time period. Everything else is automatic. Biofeedback from the perception of the cone falling out provides the stimulus for pelvic floor contraction. Success rates are high, with 21% cured and 29% improved for an overall improvement rate of 50%. Such therapies may be tried before diagnosis, and certainly before expensive surgical treatment.