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Background: Our objective was to evaluate long-term outcomes of sacral nerve stimulation (SNS) for children with functional and organic defecation disorders., Methods: We performed a prospective study of children <21 years of age who started SNS treatment between 2012 and 2018. We recorded demographics, medical history, and diagnostic testing. We obtained measures of symptom severity and quality of life at baseline and follow up at 1, 6, 12, 24, 36, 48, and ≥60 months. Successful response was defined as bowel movements >2 times/week and fecal incontinence (FI) <1 time/week. Families were contacted to administer the Glasgow Children's Benefit Inventory and to evaluate patient satisfaction., Key Results: We included 65 patients (59% female, median age at SNS 14 years, range 9-21) with median follow-up of 32 months. Thirty patients had functional constipation (FC), 15 had non-retentive FI (NRFI), and 16 had an anorectal malformation (ARM). The percentage with FI <1 time/week improved from 30% at baseline to 64% at 1 year (p < 0.001) and 77% at most recent follow-up (p < 0.001). Patients with FC, NRFI, and ARM had sustained improvement in FI (p = 0.02, p < 0.001, p = 0.02). Patients also reported fewer hard stools (p = 0.001). Bowel movement frequency did not improve after SNS. At most recent follow-up, 77% of patients with a functional disorder and 50% with an organic disorder had responded (p = 0.03). Nearly all families reported benefit., Conclusions and Inferences: SNS led to sustained improvement in FI regardless of underlying etiology, but children with functional disorders were more likely to respond than those with organic disorders., (© 2024 John Wiley & Sons Ltd.)

Background: Disruption of external anal sphincter muscle (EAS) is an important factor in the multifactorial etiology of fecal incontinence (FI)., Objectives: We categorize FI patients into four groups based on the location of lesion in neuromuscular circuitry of EAS to determine if there are differences with regards to fecal incontinence symptoms severity (FISI) score, age, BMI, obstetrical history, and anal sphincter muscle damage., Methods: Female patients (151) without any neurological symptoms, who had undergone high-resolution manometry, anal sphincter EMG, and 3D ultrasound imaging of the anal sphincter were assessed. Patients were categorized into four groups: Group 1 (normal)-normal cough EMG (>10 μV), normal squeeze EMG (>10 μV), and normal anal squeeze pressure (>124 mmHg); Group 2 (cortical apraxia, i.e., poor cortical activation)-normal cough EMG, low squeeze EMG, and low anal squeeze pressure; Group 3 (muscle damage)-normal cough EMG, normal squeeze EMG, and low anal squeeze pressure; and Group 4 (pudendal nerve damage)-low cough EMG, low squeeze EMG, and low anal squeeze pressure., Results: The four patient groups were not different with regards to the patient's age, BMI, parity, and FISI scores. 3D ultrasound images of the anal sphincter complex revealed significant damage to the internal anal sphincter, external anal sphincter, and puborectalis muscles in all four groups., Conclusion: The FI patients are a heterogeneous group; majority of these patients have significant damage to the muscles of the anal sphincter complex. Whether biofeedback therapy response is different among different patient groups requires study., (© 2024 John Wiley & Sons Ltd.)

Background: The functional lumen imaging probe (FLIP) is a test of anal sphincter distensibility under evaluation by specialist centers. Two measurement protocols termed "stepwise" and "ramp" are used, risking a lack of standardization. This study aims to compare the performance of these protocols to establish if there are differences between them., Methods: Patients with fecal incontinence were recruited and underwent measurement with both protocols at a tertiary pelvic floor referral unit. Differences in minimum diameter, FLIP bag pressure, and distensibility index (DI) at rest and during squeeze were calculated at various FLIP bag volumes., Key Results: Twenty patients (19 female, mean age 61 [range: 38-78]) were included. The resting minimum diameter at 30 and 40 mL bag volumes were less in the stepwise protocol (mean bias: -0.55 mm and -1.18 mm, p < 0.05) along with the DI at the same bag volumes (mean bias: -0.37 mm 2 /mmHg and -0.55 mm 2 /mmHg, p < 0.05). There was also a trend towards greater bag pressures at 30 mL (mean bias: +2.08 mmHg, p = 0.114) and 40 mL (mean bias: +2.81 mmHg, p = 0.129) volumes in the stepwise protocol. There were no differences between protocols in measurements of minimum diameter, maximum bag pressure, or DI during voluntary squeeze (p > 0.05)., Conclusion and Inferences: There are differences between the two commonly described FLIP measurement protocols at rest, although there are no differences in the assessment of squeeze function. Consensus agreement is required to agree the most appropriate FLIP measurement protocol in assessing anal sphincter function., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Even if understanding of neuronal enteropathies, such as Hirschsprung's disease and functional constipation, has been improved, specialized therapies are still missing. Sacral neuromodulation (SNM) has been established in the treatment of defecation disorders in adults. The aim of the study was to investigate effects of SNM in children and adolescents with refractory symptoms of chronic constipation., Methods: A two-centered, prospective trial has been conducted between 2019 and 2022. SNM was applied continuously at individually set stimulation intensity. Evaluation of clinical outcomes was conducted at 3, 6, and 12 months after surgery based on the developed questionnaires and quality of life analysis (KINDL R ). Primary outcome was assessed based on predefined variables of fecal incontinence and defecation frequency., Key Results: Fifteen patients enrolled in the study and underwent SNM (median age 8.0 years (range 4-17 years)): eight patients were diagnosed with Hirschsprung's disease (53%). Improvement of defecation frequency was seen in 8/15 participants (53%) and an improvement of fecal incontinence in 9/12 patients (75%). We observed stable outcome after 1 year of treatment. Surgical revision was necessary in one patient after electrode breakage. Urinary incontinence was observed as singular side effect of treatment in two patients (13%), which was manageable with the reduction of stimulation intensity., Conclusions: SNM shows promising clinical results in children and adolescents presenting with chronic constipation refractory to conservative therapy. Indications for patients with enteral neuropathies deserve further confirmation., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Aim: To determine if a biofeedback therapy that includes concentric resistance exercise for the anal sphincter muscles can improve muscle strength/function and improve AI symptoms compared to the traditional/non-resistance biofeedback therapy., Background: Biofeedback therapy is the current gold standard treatment for patients with anal incontinence (AI). Lack of resistance exercise biofeedback programs is a limitation in current practice., Methods: Thirty-three women with AI (mean age 60 years) were randomly assigned to concentric (resistance) or isometric (non-resistance) biofeedback training. Concentric training utilized the Functional Luminal Imaging Probe to provide progressive resistance exercises based on the patient's ability to collapse the anal canal lumen. Isometric training utilized a non-collapsible 10 mm diameter probe. Both groups performed a biofeedback protocol once per week in the clinic for 12 weeks and at home daily. High definition anal manometry was used to assess anal sphincter strength; symptoms were measured using FISI and UDI-6. 3D transperineal ultrasound imaging was used to assess the anal sphincter muscle integrity., Results: Concentric and isometric groups improved FISI and UDI-6 scores to a similar degree. Both the concentric and isometric groups showed small improvement in the anal high-pressure zone; however, there was no difference between the two groups. Ultrasound image analysis revealed significant damage to the anal sphincter muscles in both patient groups., Conclusions: Concentric resistance biofeedback training did not improve the anal sphincter muscle function or AI symptoms beyond traditional biofeedback training. Anal sphincter muscle damage may be an important factor that limits the success of biofeedback training., (© 2021 John Wiley & Sons Ltd.)

Background: Biofeedback therapy is useful for treatment of fecal incontinence (FI), but is not widely available and labor intensive. We investigated if home biofeedback therapy (HBT) is non-inferior to office biofeedback therapy (OBT)., Methods: Patients with FI (≥1 episode/week) were randomized to HBT or OBT for 6 weeks. HBT was performed daily using novel device that provided resistance training and electrical stimulation with voice-guided instructions. OBT consisted of six weekly sessions. Both methods involved anal strength, endurance, and coordination training. Primary outcome was change in weekly FI episodes. FI improvement was assessed with stool diaries, validated instruments (FISI, FISS, and ICIQ-B), and anorectal manometry using intention-to-treat analysis., Key Results: Thirty (F/M = 26/4) FI patients (20 in HBT, 10 in OBT) participated. Weekly FI episodes decreased significantly after HBT (Δ ± 95% confidence interval: 4.7 ± 1.8, compared with baseline, p = 0.003) and OBT (3.7 ± 1.6, p = 0.0003) and HBT was non-inferior to OBT (p = 0.2). The FISI and FISS scores improved significantly in HBT group (p < 0.02). Bowel pattern, bowel control, and quality of life (QOL) domains (ICIQ-B) improved significantly in HBT arm (p < 0.023). Resting and maximum squeeze sphincter pressures significantly improved in both HBT and OBT groups and sustained squeeze pressure in HBT, without group differences., Conclusions & Inferences: Home biofeedback therapy is non-inferior to OBT for FI treatment. Home biofeedback is safe, effective, improves QOL, and through increased access could facilitate improved management of FI., (© 2021 John Wiley & Sons Ltd.)

Background: There is wide variation in the clinical use of diagnostic tools for children with chronic constipation and functional/structural fecal incontinence (CCFSFI). Anorectal manometry (ARM) is a well-recognized technique to assess the function of the anorectum., Purpose: Our aim was to perform an up-to-date review on ARM in pediatric patients with CCFSFI, with specific focus on the indication of use and protocol. Variation of its use in pediatrics will be explored., Methods: A systematic search was conducted for empirical studies utilizing ARM with a pediatric sample. A keyword search of literature published in English before July 2018 was conducted and updated to October 2019. Data on demographics, clinical information, study aims, ARM parameters and use of sedation/anesthesia were collected., Key Results: A total of 227 studies were included in this systematic review. The age of study participants at the time of ARM ranged from birth to 18 years. ARM was most commonly used in patients with organic conditions (65%) compared to functional constipation (41%). In almost half [108/227 (48%)] of the studies, ARM was performed awake. The ARM parameters most frequently assessed were the rectoanal inhibitory reflex, which was evaluated in 198/227 studies (87%) and the anal resting pressure [166/227 studies (73%)]., Conclusions and Inferences: This systematic review has highlighted the vast variation of ARM use within pediatrics and the need to strive toward standardization and use of consensus guidelines. We anticipate this will further advance our understanding of the pathophysiological mechanisms involved in children with defecation disorders., (© 2020 John Wiley & Sons Ltd.)

Background: Anorectal manometry is the most commonly performed test of anorectal function. The cough-anorectal response is frequently assessed as part of a routine manometric investigation but has not previously been the subject of detailed analysis. This study systematically examined anorectal pressure responses to cough in health and evaluated the impact of parity and symptoms of fecal incontinence (FI) on measurements., Methods: High-resolution anorectal manometry (HR-ARM) traces from nulliparous (n = 25) and parous (n = 25) healthy volunteers (HV: aged 41, range 18-64), and 57 parous patients with FI (age 47, range 28-72) were retrospectively reviewed. Cough-anorectal pressure responses were analyzed between groups by qualitative and quantitative approaches., Key Results: In health, traditional anal pressure measurements ("rest" and "squeeze") were similar between nulliparous and parous women. In contrast, incremental anal-rectal pressure difference during cough significantly differed: nulliparous 42 mm Hg (95% CI: 21-64) vs. parous 6 mm Hg (-14-25), P < 0.036). This measure also differed significantly between nulliparous HVs and patients with FI (-2 mm Hg (95% CI: -15-12), P < 0.001), but not between parous HVs and FI. Qualitatively, a color-contour trace resembling a "spear" in the upper anal canal was observed uniquely in FI. Of 25 patients with normal anal function by traditional measures, cough parameters were abnormal in 52%., Conclusions and Inferences: Novel HR-ARM measures during coughing revealed differences in anal function between nulliparous and parous HV, and patients with FI, which were not detected by traditional measures. Cough-anorectal measurements may improve manometric yield, though clinical utility would require assessment by longitudinal studies., (© 2020 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Pathophysiology of fecal incontinence (FI) in children with anorectal malformations (AM) is not well understood. Standard or high-resolution anorectal manometry (ARM) does not identify radial asymmetry or localize abnormal sphincter function. 3D high-definition anorectal manometry (HDARM) provides detailed topographic and 3D pressure gradient representation of anal canal., Aims: To compare intra-anal pressure profiles between children with AM and controls using HDARM and to determine the association between manometric properties and reported predictors of fecal continence (AM type, spinal anomaly, and sacral integrity)., Methods: HDARM tracings of 30 children with AM and FI referred for ARM were compared with 30 age and sex-matched children with constipation. 2D pressure profiles were used to measure length of high-pressure zone (HPZ). Longitudinal and radial measurements of sphincter pressure at rest and squeeze were taken along each segment in 3D topographic views and compared between groups., Key Results: 3D measurements demonstrated longitudinal and radial differences between groups along all quadrants of HPZ. At rest, intra-anal pressures were lower along the four segments longitudinally across the anal canal and radially along the quadrants in AM group (P < .01). At squeeze, all quadrant pressures were lower in segments 1-4 in AM group (P < .01). Sensation was abnormal in AM group (P < .01). Intra-anal pressures longitudinally and radially were not associated with predictors of fecal continence., Conclusions and Inferences: Children with AM had abnormal sensation and lower pressures longitudinally and radially along all quadrants of anal canal. Manometric properties at rest were not associated with reported predictors of fecal continence., (© 2020 John Wiley & Sons Ltd.)

Background: Diagnostic investigations for fecal incontinence (FI) assess the structure and sensorimotor function of the anorectum. Investigations include anorectal manometry, anorectal sensory testing, pudendal nerve terminal motor latencies (PNTML), and endoanal sonography. The severity of FI and results of investigations are often discordant and the rate of symptom resolution following treatment remains <40%. High-resolution anorectal manometry (HRAM) and three-dimensional endoanal ultrasound (3D-US) have been introduced during the last decade. This study aims to assess the strength of relationships between contemporary investigation results and FI severity., Methods: Adults presenting for investigation of FI were assessed using the St Mark's FI severity score (SMIS), HRAM, anorectal sensory testing, PNTML, and 3D-US., Key Results: 246 patients were included. There were significant relationships between the SMIS and HRAM (resting pressure r s = -0.23, 95% CI = (-0.34, -0.11), P < .001; squeeze pressure (r s  = -0.26, 95% CI = (-0.37, -0.14), P < .001) and 3D-US (anterior EAS length r s = -0.22, 95% CI = (-0.34, -0.09), P = .001). The relationships between SMIS and HRAM had a greater effect size in those with urge-predominant symptoms (resting pressure: r s = -0.40, 95% CI = (-0.57, -0.20), P < .001, squeeze pressure: r s = -0.34, 95% CI = (-0.52, -0.12), P = .003). Overall, the variance in SMIS accounted for by anorectal investigations was 8.6% (R 2 = 0.098, adjusted R 2 = 0.086, P < .001)., Conclusions and Inferences: Anorectal investigations are not strong predictors of FI severity. These findings may reflect the multifactorial, heterogeneous pathophysiology of FI, the limitations of the SMIS and anorectal investigations, and contributing factors extrinsic to the anorectum., (© 2020 John Wiley & Sons Ltd.)

Background: High-resolution anorectal manometry (HR-ARM) is expected to be better than conventional manometry. Our aim was to characterize HR-ARM pressures in children with functional constipation (FC), with or without fecal incontinence (FI)., Methods: Children with diagnosis of FC, with or without FI, according to Rome-IV criteria, were enrolled. All patients underwent HR-ARM using 24-channel water-perfused catheter., Results: Twenty-nine consecutive children (M/F: 21/8; mean age ± SD: 9.5 ± 3.1 years; range 4-15), of whom 21 affected by FC without FI (mean age ± SD: 9.3 ± 3.23 years) and 8 affected by FC with FI (mean age ± SD: 10.2 ± 3.08 years), were enrolled. No significant differences were found regard to gender and age. The analysis of HR-ARM 3D plots demonstrated asymmetry of the anal canal, with higher pressures in distal halves. Comparing pressures between the two groups, we found lower values in FC with FI than in FC without FI group, with a statistically significance for maximum and mean resting pressures (P = .032 and P = .008, respectively). When evaluating our study population respect to asymptomatic children, we found lower resting pressures, lower maximum squeeze pressure, and higher rectoanal inhibitory reflex (RAIR) values., Conclusions: Our data demonstrate that HR-ARM pressures at rest and during squeezing in FC with FI children are lower than FC without FI subjects, particularly in anteroposterior quadrants. Compared to children without lower gastrointestinal symptoms, children with FC with or without FI show lower pressures and higher values of RAIR., (© 2020 John Wiley & Sons Ltd.)

Background: Accurate measurement of anal sphincter function is potentially of value in defining treatment of common pelvic floor disorders. The aim of this study was to establish repeatability and validate high-resolution anorectal manometry (HRAM) by comparison to conventional manometry (CM). Arising from this work would be definitive normal range data., Methods: Eighty healthy volunteers (40 female) underwent a test-retest repeatability study. A 16-channel water-perfused HRAM catheter was compared to an 8-channel conventional catheter using a station pull-through technique., Key Results: High-resolution anorectal manometry had similar precision to conventional manometry when measuring resting pressure (intraclass correlation coefficient [ICC] 0.73 vs 0.68, HRAM vs CM) and squeeze increment (ICC 0.90 vs 0.94, HRAM vs CM). HRAM measured resting pressures 10% lower than CM and squeeze pressure 27% higher than CM., Conclusions and Inferences: High-resolution anorectal manometry is a valid technique with comparable precision to CM. HRAM measurements differ considerably to CM, and a new set of normal values must be used., (© 2019 John Wiley & Sons Ltd.)

Background: Using high-resolution anorectal manometry, we aimed to evaluate the: (a) optimal threshold to measure functional anal canal length (FACL) with intra- and inter-observer variability; (b) relationship between abnormal FACL and other phenotypic findings; and (c) utility of FACL measurement to discriminate between healthy volunteers (HV) and patients with fecal incontinence (FI) or chronic constipation (CC)., Methods: Consecutive patients referred for investigation of FI or CC in isolation were included. FACL was calculated at 5, 10, 20, 30, and 50 mm Hg above rectal pressure. 5th-95th percentile in HV defined limits of normality., Key Results: FACL was analyzed in 192 patients with FI (154 females), 204 patients with CC (175 females), and 134 HV (101 females). The optimal threshold for measurement of FACL was 20 mm Hg. Using this threshold, observer reproducibility was very high (ICC 0.99, P < 0.0001). FACL was shorter in females with FI and longer in females with CC compared to HV (2.3 vs 2.9 cm; and 3.4 cm vs 2.9 cm; both P < 0.0001). Twenty percent of females and 13% males with FI had a short FACL, associated with older age, anal hypotonia or hypocontractility, and a atrophic internal anal sphincter. However, abnormal FACL in isolation was only found in 1/190 FI (0.5%) and 2/201 CC (1%) patients; all other patients had other abnormal manometric findings., Conclusions and Inferences: Considering overlap with other routinely evaluated manometric parameters, FACL measurement does not provide additional information in the diagnostic assessment of FI or CC., (© 2019 John Wiley & Sons Ltd.)

Background: In order to understand the pathophysiology of rectal sensorimotor dysfunctions in women with fecal incontinence (FI) and rectal urgency, we evaluated the effects of a muscarinic antagonist and an adrenergic α 2 agonist on these parameters., Methods: Firstly, rectal distensibility and sensation were evaluated with a barostat and sinusoidal oscillation at baseline and after randomization to intravenous saline or atropine in 16 healthy controls and 44 FI patients. Thereafter, FI patients were randomized to placebo or clonidine for 4 wk; rectal compliance and sensation were revaluated thereafter. The effect of atropine and clonidine on rectal functions and the relationship between them were evaluated., Results: At baseline, compared to controls, rectal capacity was lower (P = .03) while the mean pressure (P = .02) and elastance (P = .01) during sinusoidal oscillation were greater, signifying reduced distensibility, in FI. Compared to placebo, atropine increased (P ≤ .02) the heart rate in controls and FI and reduced (P = .03) the variability in rectal pressures during sinusoidal oscillation in controls. Clonidine increased rectal compliance (P = .04) and reduced rectal capacity (P = .03) in FI. The effects of atropine and clonidine on compliance (r = .44, P = .003), capacity (r = .34, P = .02), pressures during sinusoidal oscillation (r = .3, P = .057), pressure (r = .6, P < .0001), and volume sensory thresholds (r = .48, P = .003) were correlated., Conclusions: The effects of atropine and clonidine on rectal distensibility and sensation were significantly correlated. A preserved response to atropine suggests that reduced rectal distensibility is partly reversible, mediated by cholinergic mechanisms, and may predict the response to clonidine, providing a pharmacological challenge., (© 2018 John Wiley & Sons Ltd.)

Background: Voluntary anal sphincter function is driven by an extended network of brain structures, most of which are still unknown. Disturbances in this function may cause fecal incontinence. The aim of this study was to characterize the cerebral areas involved in voluntary contraction of the anorectal sphincter in healthy women and in a group of patients with fecal incontinence by using a standardized functional magnetic resonance imaging (fMRI) protocol., Methods: This comparative study included 12 healthy women (mean age 53.17 ± 4.93 years) and 12 women with fecal incontinence (56.25 ± 6.94 years). An MRI-compatible anal manometer was used to register voluntary external anal sphincter contraction. During brain fMRI imaging, participants were cued to perform 10-s series of self-paced anal sphincter contractions at an approximate rate of 1 Hz. Brain structures linked to anal sphincter contractions were mapped and the findings were compared between the 2 study groups., Key Results: There were no differences in the evoked brain activity between the 2 groups. In healthy women, group fMRI analysis revealed significant activations in medial primary motor cortices, supplementary motor area, bilateral putamen, and cerebellum, as well as in the supramarginal gyrus and visual areas. In patients with fecal incontinence, the activation pattern involved similar regions without significant differences with healthy women., Conclusions & Inferences: This brain fMRI-anorectal protocol was able to map the brain regions linked to voluntary anal sphincter function in healthy and women with fecal incontinence., (© 2018 John Wiley & Sons Ltd.)

Background: The functional lumen imaging probe (EndoFLIP ® ) is a new technology that measures the distensibility of the anal canal represented by the anal distensibility index. The aims of this study were (i) to compare the anal distensibility index to anal pressure in a cohort of patients with fecal incontinence (FI) and (ii) to compare the diagnostic value of the EndoFLIP ® to that of high-resolution anorectal manometry (HRAM) in the same cohort of patients., Methods: Eighty-three consecutive patients with FI who underwent EndoFLIP ® and HRAM assessments were enrolled. The diagnostic value of the EndoFLIP ® was compared to that of HRAM and agreement between EndoFLIP ® and HRAM data was assessed., Key Results: More than 70% of the patients diagnosed with anal deficiency at rest and/or during voluntary contractions by HRAM had the same diagnosis using the EndoFLIP ® . Two patients with higher distensibility indexes at rest had normal anal resting pressures. Sixteen patients with a normal EndoFLIP ® index (ie, normal distensibility index at rest and during voluntary contractions) had an abnormal HRAM result. Seven of these 16 patients (44%) had no sphincter lesion or neuropathic disorder that could explain an abnormal anal sphincter function., Conclusions & Inferences: We demonstrated that the anal distensibility index and HRAM results are largely in agreement. We did, however, identify several discrepancies between the two techniques, indicating that they may be complementary., (© 2018 John Wiley & Sons Ltd.)

Background: Fecal incontinence (FI) has a multifactorial pathophysiology with a severe social impact. The most common cause for FI is pudendal nerve damage, which mostly occurs in women during or after labor. A better understanding of the pathophysiology is required to optimize treatment of FI. In this study, we evaluate the use of a novel pelvic nerve damage rat model of FI., Methods: This new model simulates the forces on the pelvic floor during labor by prolonged transvaginal, retro-uterine intrapelvic balloon distention in female rats. Number of fecal pellets produced per day and defecation pattern was compared between the experimental and control group for 2 weeks. The cages of the rats were divided in food, nesting and latrine areas to evaluate changes in defecation pattern. The FI Index (FII) was calculated to assess the ratio of fecal pellets between the non-latrine areas and the total number of pellets. A higher score represents more random distribution of feces outside the latrine area., Results: Total number of fecal pellets was higher in the experimental group as compared with the controls. In both groups most fecal pellets were deposited in the nesting area, which is closest to the food area. The experimental group deposited more fecal pellets in the latrine area and had a lower FII indicating less random distribution of feces outside the latrine area., Conclusion: Transvaginal, retro-uterine intrapelvic balloon distention is a safe and feasible animal model simulating the human physiologic impact of labor by downwards pressure on the pelvic floor., (© 2017 John Wiley & Sons Ltd.)

Background: Decreased sensation of urge to defecate is often reported by children with functional constipation (FC) and functional nonretentive fecal incontinence (FNRFI). The aim of this cross-sectional study was to evaluate cerebral activity in response to rectal distension in adolescents with FC and FNRFI compared with healthy controls (HCs)., Methods: We included 15 adolescents with FC, 10 adolescents with FNRFI, and 15 young adult HCs. Rectal barostat was performed prior to functional magnetic resonance imaging (fMRI) to determine individual pressure thresholds for urge sensation. Subjects received 2 sessions of 5 × 30 seconds of barostat stimulation during the acquisition of blood oxygenation level-dependent fMRI. Functional magnetic resonance imaging signal differences were analyzed using SPM8 in Matlab., Key Results: Functional constipation and FNRFI patients had higher thresholds for urgency than HCs (P < .001). During rectal distension, FC patients showed activation in the anterior cingulate cortex, dorsolateral prefrontal cortex, inferior parietal lobule, and putamen. No activations were observed in controls and FNRFI patients. Functional nonretentive fecal incontinence patients showed deactivation in the hippocampus, parahippocampal gyrus, fusiform gyrus (FFG), lingual gyrus, posterior parietal cortex, and precentral gyrus. In HCs, deactivated areas were detected in the hippocampus, amygdala, FFG, insula, thalamus, precuneus, and primary somatosensory cortex. In contrast, no regions with significant deactivation were detected in FC patients., Conclusions & Inferences: Children with FC differ from children with FNRFI and HCs with respect to patterns of cerebral activation and deactivation during rectal distension. Functional nonretentive fecal incontinence patients seem to resemble HCs when it comes to brain processing of rectal distension., (© 2017 John Wiley & Sons Ltd.)

Background: Obesity is an emerging risk factor for fecal incontinence (FI). The aim of this study was to characterize pathophysiologic mechanisms of FI in obese patients compared with non-obese patients in a prospective case-matched study., Methods: The general characteristics and data of the anorectal manometry and endosonography of patients who were evaluated for FI at a single institution from 2005 to 2015 were prospectively assessed. Fecal incontinence was defined by a Cleveland Clinic Incontinence Score (CCIS) >4. Obesity was defined by a body mass index ≥30 kg/m 2 . Obese patients were case-matched with two age- and sex-matched non-obese patients., Key Results: A total of 201 patients were included (67 obese matched with 134 non-obese). The CCIS, Knowles-Eccersley-Scott Symptom Constipation Score and quality of life score were comparable between obese and non-obese patients with FI. Factors significantly associated with obesity in FI patients were cholecystectomy (odds ratio [OR]=3.45 [1.19-10.32], P=.0230), irritable bowel syndrome - diarrhea (OR=2.94 [1.22-7.19], P=.0158), upper part of the anal canal resting pressure ≥22 mm Hg (OR=3.45 [1.45-8.76], P=.0045), maximum rectal tolerable volume ≥240 mL (OR=3.14 [1.34-7.54], P=.0082), and abdominal pressure ≥28 mm Hg (OR=2.75 [1.13-7.33], P=.0248) by multivariate analysis., Conclusions & Inferences: Obese patients with FI had a comparable severity of FI to that of non-obese patients with FI. Regarding obesity in patients with FI, physicians should focus on stool consistency., (© 2017 John Wiley & Sons Ltd.)

Background: 3D-high definition anorectal manometry (3DARM) may aid the diagnosis of functional anorectal disorders, but data comparing asymptomatic and symptomatic subjects are scarce. We aimed to describe 3DARM values in asymptomatic volunteers and those with fecal incontinence (FI) or chronic constipation (CC), and identify which variables differentiate best these groups., Methods: Asymptomatic subjects were stratified by sex, age, and parity. Those with FI or CC were included according to anorectal symptom questionnaires. Endoanal ultrasound examination and 3DARM were performed the same day. Anal pressures were analyzed at rest, during voluntary squeeze, and during push maneuver, and compared between the 3 groups. Anal pressure defects were defined and compared to ultrasound defects., Key Results: A total of 126 subjects (113 female, mean age 52 years, range 18-83) were included; 36 asymptomatic, 38 FI, 42 CC. Anal resting and squeeze pressures, and rectal sensitivity values were lower in FI women than in the other groups. Typical anal sphincter asymmetry during squeezing was less frequently observed in FI women. A dyssynergic pattern during push maneuver was found in 70% of asymptomatic subjects, and with a similar frequency in the 2 symptomatic groups. There was slight concordance between 3D-pressure defects and ultrasound defects., Conclusions & Inferences: 3D anal pressures in asymptomatic women were significantly lower than in men, and in FI compared to asymptomatic women. The classical dyssynergic pattern during push maneuver was found as frequently in asymptomatic and symptomatic patients. Further studies should try to identify 3DARM variables that could reliably identify dyssynergic defecation., (© 2017 John Wiley & Sons Ltd.)

Introduced approximately 10 years ago, high-resolution manometry catheters have fostered interest in anorectal manometry. This review, which accompanies two articles in this issue of Neurogastroenterology and Motility, reviews the methods, clinical indications, utility, and pitfalls of anorectal manometry and revisits the American Gastroenterological Association (AGA) Medical Position Statement on Anorectal Testing Techniques, which was last published in 1999. High-resolution manometry provides a refined assessment of the anorectal pressure profile, obviates the need for station pull-through maneuvers, and minimizes movement artifacts. In selected cases, this refined assessment may be useful for identifying structural abnormalities or anal weakness. However, many manometry patterns that were previously regarded as abnormal are also observed in a majority of healthy patients, which substantially limits the utility of manometry for identifying defecatory disorders. It is our impression that most conclusions of the AGA medical position statement from 1999 remain valid today. High-resolution techniques have not substantially affected the number of publications on or management of anorectal disorders. The ongoing efforts of an international working group to standardize techniques for anorectal manometry are welcome. Although high-resolution manometry is more than an expensive hobby, improvements in catheter design and further research to rigorously define and evaluate these techniques are necessary to determine if they are worth every penny., (© 2017 John Wiley & Sons Ltd.)

Background: Three-dimensional high-resolution anorectal manometry (3DHRAM), used for exploring anorectal disorders, was recently developed, providing interesting topographic data for the diagnosis of pelvic floor disorders such as excessive perineal descent. The aim of our study was to define a diagnostic strategy based on selected 3DHRAM parameters to identify rectal intussusceptions (RI), considering conventional defecography (CD) as the gold standard., Methods: All patients referred to our center in the previous 6 months for 3DHRAM to explore fecal incontinence or constipation, and who previously achieved CD, were eligible. 3DHRAM results were obtained for all classical parameters and the presence of a narrow band of high pressure in the anal canal during attempted defecation, which was recently found to be associated with RI in some studies. The sensitivity, specificity, and positive and negative predictive values were calculated for various 3DHRAM criterion in order to propose a diagnostic strategy for RI., Key Results: Twenty-six patients (66%) presented with RI on CD. On 3DHRAM, according to our diagnostic strategy, the most relevant manometric criterion for the diagnosis of RI was the association of an anterior additional high-pressure area and an excessive perineal descent, with a positive predictive value of 100% [81.5-100], a specificity of 100% [75.3-100] and a sensibility of 69.2% [48.2-85.7]., Conclusions & Inferences: In this study, 3DHRAM was used to diagnose RI, and we confirmed its use in the diagnosis of pelvic floor disorders. Further studies will be necessary to define classifications for these new anatomic data from 3DHRAM., (© 2016 John Wiley & Sons Ltd.)

Background: While widely used in clinical practice, the reproducibility of high-definition anorectal manometry (HD-ARM) remains unclear. We evaluated the intra-individual reproducibility of HD-ARM and compared pressures measured with HD-ARM and high-resolution anorectal manometry (HR-ARM)., Methods: Thirty-six women with fecal incontinence had an initial HD-ARM (HD-ARM1); on the same day, after randomization, 21 had a second (HD-ARM2). Sixteen women had a third (HD-ARM3) 4 weeks later. Twenty-five had also been evaluated by HR-ARM previously. Rectoanal pressures were assessed at rest, during squeeze and simulated evacuation. Concordance among pressures was assessed with Lin's concordance correlation coefficient (CCC)., Key Results: Anal resting and squeeze pressures measured with HD-ARM were reproducible on the same and different days; for average resting pressures of HD-ARM1 vs HD-ARM2, CCC = 0.73 (95% confidence interval [CI]: 0.53-0.94), and for HD-ARM1 vs HD-ARM3, CCC = 0.60 (95% CI: 0.28-0.93). For maximum squeeze pressures of HD-ARM1 vs HD-ARM2, CCC = 0.86 (95% CI: 0.75-0.97), and for HD-ARM1 vs HD-ARM3, CCC = 0.56 (95% CI: 0.21-0.91). The rectoanal gradient during evacuation was significantly concordant between HD-ARM1 and HD-ARM2 but not HD-ARM1 and HD-ARM3. Resting (CCC = 0.38 [95% CI: 0.14-0.62]) and squeeze pressures (CCC = 0.73 [95% CI: 0.57-0.89]) measured with HD-ARM1 and HR-ARM were also concordant., Conclusions & Inferences: Among women with fecal incontinence, measurements with HD-ARM were reproducible on the same (anal resting and squeeze pressures and rectoanal gradient during evacuation) and different days (anal resting and squeeze pressures) and correlated with HR-ARM measurements. These findings support use of HD-ARM and HR-ARM for longitudinal assessments of anal resting and squeeze pressures., (© 2016 John Wiley & Sons Ltd.)

Background: Sacral nerve stimulation (SNS) is a well-established treatment for fecal incontinence but its mode of action remains obscure. Anal sphincter function is usually evaluated with manometry but resistance to distension may be a more appropriate parameter than luminal pressure. The functional lumen imaging probe allows detailed description of distension properties of the anal canal. Our objective in this study was to characterize the impact of SNS on distension properties of the anal canal in patients with idiopathic fecal incontinence., Methods: We studied 10 women (median age 64 [44-79] years) with idiopathic fecal incontinence at baseline and during SNS. The luminal geometry of the anal canal was examined with the FLIP at rest and during squeeze and the distensibility of the anal canal was investigated during filling of the bag., Key Results: All patients were successfully treated with SNS and the mean Wexner Incontinence Score was reduced from 14.9 ± 4 to 7.1 ± 4.8 (P<.001). The pressure required to open the narrowest point of the anal canal during distension (yield pressure) increased from 14.5 ± 12.2 mmHg at baseline to 20.5 ± 13.3 mmHg during SNS (P<.01). The pressure-strain elastic modulus increased non-significantly from 2.2 ± 0.5 to 2.9 ± 1.6 kPa, indicating increased stiffness of the anal canal., Conclusion and Inferences: The yield pressure and the resistance to distension increased in response to SNS for idiopathic fecal incontinence. This will inevitably increase the resistance to flow through the anal canal, which may contribute to the benefits of sacral nerve stimulation., (© 2016 John Wiley & Sons Ltd.)

Background: Over the last few years, the study of the colon and anorectal function has experienced great technical advances that have facilitated the performance of the tests and have allowed a more detailed characterization of reflexes and motor patterns. As a result, we have achieved a much better understanding of the pathophysiology of children with defecation problems. Anorectal and colonic manometry are now commonly used in all major pediatric referral centers as diagnostic tools and to guide the management of children with intractable constipation and fecal incontinence, particularly when a surgical intervention is being considered., Purpose: This review highlights some of the recent advances in pediatric colon and anorectal motility testing including indications and preparation for the studies, and how to perform and interpret the tests. This update has been endorsed by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN)., (© 2016 John Wiley & Sons Ltd.)

Background: Biofeedback therapy (BFT) is an established treatment for fecal incontinence (FI), with access often being restricted to tertiary centers due to resources and the perceived requirement for high-intensity regimes. However, the optimal regime remains unknown. We evaluated outcomes from our low-intensity integrated BFT program in a secondary care center., Methods: Outcomes of our BFT service for FI were evaluated retrospectively. Response was defined by ≥50% improvement in FI frequency from baseline or complete continence. Responders were compared to non-responders for factors including symptoms, manometry data, sphincter exercise technique and duration of practice, and the number and frequency of sessions. Where patients dropped out, outcomes and the reason for dropout were obtained retrospectively., Key Results: Fecal incontinence patients (n=205, median 62 years, 72% female) attended a median (IQR) 3 (2) BFT sessions with 55 (36) days between visits. Overall, 146/205 (71%) responded with 97/205 (47%) achieving continence. Fecal incontinence frequency improved dramatically in completed cases (P=0.000). While non-response was associated with males (P=0.03) and dropout (P=0.000), "good" anal sphincter exercise technique (P=0.008) and longer in-home practice (P=0.007) and more sessions (P=0.04) were associated with response. Dropout rate was 80/205 (39%), with the reason for dropout being obtained in 80%., Conclusions & Inferences: Despite low-intensity BFT, comparable outcomes to data from tertiary centers were achieved. Our data emphasize the importance of technique and in-home practice of anal sphincter exercises. Customizing BFT intensity based on predictive factors and encouraging in-home practice may optimize outcomes, reduce dropout rates, and rationalize resources., (© 2016 John Wiley & Sons Ltd.)

Background: Defecatory disorders (DD) are defined by clinical and objective features of impaired rectal evacuation. The epidemiology of DD in the population is unknown, partly because many constipated patients do not undergo anorectal tests. Our objectives were to estimate the incidence rate and clinical features of DD in the community., Methods: We reviewed the medical records of all patients older than 16 years in Olmsted County, MN, who had constipation and underwent anorectal manometry from 1999 through 2008. Criteria for diagnosing DD were constipation for 6 months or longer and one of the following: (i) abnormal rectal balloon expulsion test; (ii) reduced or increased perineal descent; or (iii) two or more abnormal features with defecography or surface electromyography., Key Results: Of 11 112 constipated patients, 516 had undergone anorectal tests; 245 of these (209 women, 36 men) had a DD. The mean (±SD) age at diagnosis was 44 years (±18) among women and 49 years (±19) among men. The overall age- and sex-adjusted incidence rate per 100 000 person-years was 19.3 (95% CI: 16.8-21.8). The age-adjusted incidence per 100 000 person-years was greater (p < 0.0001) in women (31.8, 95% CI: 27.4-36.1) than in men (6.6, 95% CI: 4.4-8.9). Prior to the diagnosis of DD, nearly 30% of patients had irritable bowel syndrome (IBS), 48% had a psychiatric diagnosis, 18% had a history of abuse, and 21% reported urinary and/or fecal incontinence., Conclusions & Inferences: Among constipated patients, DD are fourfold more common in women than men and often associated with IBS and psychiatric diagnoses., (© 2016 John Wiley & Sons Ltd.)

Background: One-third of patients with fecal incontinence (FI) do not have any anal dysfunction. The aim was to characterize patients with FI with normal anal function compared with patients with anal weakness., Methods: The general characteristics and data of anal manometry, endosonography, and defecography of patients who were evaluated for FI at a single institution from 2005 to 2015 were prospectively assessed. Fecal incontinence was defined by the Cleveland Clinic Incontinence Score (CCIS) >4. Anal weakness was defined by one or more of the three following parameters: <25 mmHg at the upper part of the anal canal, <26 mmHg at the lower part of the anal canal, and <60 mmHg for the mean squeeze pressure., Key Results: A total of 439 patients with FI were included (152 with normal anal function/287 with anal weakness). Severe constipation (Kess score ≥21) was predominant in patients with normal anal function (44/151 vs 50/284, respectively; p = 0.0054). Fecal incontinence with normal anal function was significantly associated with lower age (>63 years; odds ratio [OR] = 0.29), higher weight (>65 kg; OR = 1.69), fecal urgency (OR = 1.58), less severe FI score (CCIS score >10; OR = 0.52), higher abdominal pressure (>36 mmHg; OR = 2.15), and paradoxical puborectal contraction (OR = 2.07) in a multivariate analysis model., Conclusion & Inferences: Fecal incontinence with normal anal function is a specific phenotype that involves distal constipation and may be an early stage of FI with anal weakness. Physicians should adapt their management to focus on the treatment of constipation., (© 2016 John Wiley & Sons Ltd.)

Background: Fecal incontinence (FI) is a common and socially disabling condition with obstetric trauma considered the principal etiological factor. This study aimed to systematically evaluate symptom presentation and anorectal function in both females and males with FI., Methods: One hundred males (M) and 100 age-matched females (F) with FI presenting between 2012 and 2014 were identified from a prospectively collected database. Comparison of clinical (history, symptom profile, and severity using validated questionnaires) and anorectal physiological (manometry, rectal sensory testing, endoanal ultrasonography, and evacuation proctography) data between M and F was performed., Key Results: Incidence of prior anal surgery (M: 28% vs F: 18%, p = 0.13) and abdominal surgery (M: 25% vs F: 26%, p = 0.90) was similar between sexes, but females had a higher incidence of previous pelvic surgery (M: 4% vs F: 47%, p < 0.001). Eighty-five females were parous and 75% reported history of traumatic vaginal delivery. There was a trend toward higher St Mark's incontinence scores in females (mean ± SD; M: 13 ± 4 vs F: 14 ± 5, p = 0.06). In men, structural sphincter abnormalities were uncommon (M: 37% vs F: 77%, p < 0.001), while impaired rectal sensation (M: 24% vs F: 7%, p = 0.001) and functional disturbances of evacuation (M: 36% vs F: 13%, p = 0.001) were more common than in women. No abnormality on all tests performed was observed in twice as many males (M: 18% vs F: 9%, p = 0.10)., Conclusions & Inferences: Pathophysiological mechanisms of FI differ between sexes. Anal sphincter dysfunction was an uncommon finding in males, with impaired rectal sensation and functional disturbances of evacuation much more prominent than in the female cohort. These findings are likely to impact options for symptom management., (© 2016 John Wiley & Sons Ltd.)

Background: Multiple sclerosis (MS) is the commonest disabling neurological disease in young adults. A majority of patients experience bowel dysfunction, reporting a wide spectrum of bowel symptoms that significantly negatively impact social activities and emotional state. Transanal irrigation (TAI) is a method of managing such bowel symptoms. We aimed to investigate long-term efficacy of TAI, to measure health status-related quality of life and identify factors predictive of TAI outcome., Methods: Forty-nine consecutive MS patients (37 female; mean age 51, range 26-80) were studied. We investigated predominant symptoms, reason for beginning TAI and medical comorbidity. All patients underwent anorectal physiology testing. They completed Neurogenic Bowel Dysfunction and EQ-5D questionnaires at baseline and annual follow-up., Key Results: Mean follow-up was 40 months, at which there was 55% rate of continuation of TAI. Severe bowel dysfunction was present in 47% at baseline, falling to 18%. The EQ-5D scores at latest follow-up were not statistically significant, but 42% had improved visual analog scores. The only predictive factor for successful therapy was impaired anal electrosensitivity (p = 0.008)., Conclusions & Inferences: Long-term continuation of TAI, with improved bowel symptomatology, is seen in the majority of patients. The EQ-5D is insufficiently sensitive to show change in MS patients that using TAI., (© 2016 John Wiley & Sons Ltd.)

Background: Sacral neuromodulation (SNM) is a treatment option for intractable fecal incontinence. The mechanism of action is unclear, however, increasing evidence for afferent somatosensory effects exists. This study's aim was to elucidate effects of acute SNM on the cerebral cortex in a rodent model of pudendal nerve injury., Methods: The effects of 14 Hz and 2 Hz SNM on sensory cortical activation were studied. In 32 anesthetized rats, anal canal evoked potentials (EPs) were recorded over the primary somatosensory cortex. Pudendal nerve injury was produced by 1-hour inflation of two intra-pelvic balloons. Four groups were studied: balloon injury, balloon injury plus either 14 Hz or 2 Hz SNM, sham operation. Immunohistochemistry for the neural plasticity marker polysialylated neural cell adhesion molecule (PSA-NCAM) positive cells (numerical density and location) in the somatosensory cortex was performed., Key Results: Anal EP amplitudes diminished during balloon inflation; 14 Hz SNM restored diminished anal EPs to initial levels and 2 Hz SNM to above initial levels. Evoked potential latencies were prolonged during balloon inflation. The numerical density of PSA-NCAM positive cells increased in the SNM groups, but not in sham or balloon injury without SNM. Stimulated cortices showed clusters of PSA-NCAM positive cells in layers II, IV, and V. Post SNM changes were similar in both SNM groups., Conclusions & Inferences: Sacral neuromodulation augments anal representation in the sensory cortex and restores afferent pathways following injury. PSA-NCAM positive cell density is increased in stimulated cortices and positive cells are clustered in layers II, IV, and V., (© 2016 John Wiley & Sons Ltd.)

Background: Anal manometry is the standard technique for evaluating anal sphincter function. However, the functional lumen imaging probe (EndoFLIP(®) ) can be used to measure sphincter distensibility during volume-controlled distensions. Our aims were (i) to assess anal distensibility in patients with fecal incontinence (FI) and in healthy subjects using the EndoFLIP(®) and (ii) to compare the results with anal pressures measured by 3D high-resolution manometry (3D-HRM) to determine whether the EndoFLIP(®) was more sensitive and specific for diagnosing FI than 3D-HRM., Methods: EndoFLIP(®) and 3D-HRM assessments of 34 female FI patients and 40 healthy female subjects were performed. Anal distensibility was measured as the median cross-sectional area at the narrowest point divided by the corresponding intra-bag pressure at rest and during peak voluntary contraction and was expressed in mm(2) /mmHg., Key Results: A 40-mL anal distensibility index was selected for further comparisons as it provided the best discrimination between the FI patients and the healthy subjects. The index was significantly higher in the FI patients than in the healthy subjects at rest (p = 1.10(-4) ) and during voluntary contraction (p = 1.10(-4) ). The index at rest and during voluntary contraction appeared to be more appropriate than anal pressures for discriminating between FI patients and healthy subjects., Conclusions & Inferences: The present study confirmed that FI is associated with an abnormally high distensibility index at rest and during voluntary contraction. The ability of the distensibility index to discriminate between FI patients and healthy subjects was significantly better than anal pressure., (© 2015 John Wiley & Sons Ltd.)

Background: Sacral nerve stimulation has become a first line treatment for fecal incontinence, however, its effect on the motor function of the anorectum is uncertain. The aim of this study was to apply acute lumbosacral nerve stimulation in an animal model and to determine its effect on the external and internal anal sphincter forces, the rectoanal inhibitory and excitatory reflexes, and the slow wave frequency of the internal anal sphincter., Methods: Lumbosacral nerve stimulation was applied to 16 nulliparous female rats. A novel in vivo preparation was designed to allow simultaneous monitoring of external and internal anal sphincter forces. The effect of rectal distension on the two anal sphincters was also studied., Key Results: Lumbosacral nerve stimulation delivered at either S1 or L6 in rodents did not affect sphincter forces, rectoanal reflexes or slow wave frequency of anal canal smooth muscle., Conclusions & Inferences: The absence of effect on the motor pathways of continence suggests that the mechanism of action is predominantly on sensory feedback mechanisms from the anorectum, thereby increasing cortical awareness of the pelvic floor., (© 2015 John Wiley & Sons Ltd.)

Background: Currently, anorectal manometry (ARM), which is used to diagnose defecatory disorders and identify anal weakness in fecal incontinence (FI) is generally conducted in specialized laboratories. Our aims were to compare anorectal functions measured with high-resolution manometry (HRM) and a novel portable manometry device., Methods: Anal pressures at rest, during squeeze, and simulated evacuation, and rectal sensation were evaluated with portable and HRM in 20 healthy women, 19 women with constipation, and 11 with FI. The relationship between anal pressures measured with portable and HRM was assessed by the concordance correlation coefficient (CCC), Bland Altman test, and paired t-tests., Key Results: Anal pressures at rest (CCC 0.45; 95% CI: 0.29, 0.58) and during squeeze (CCC 0.60; 95% CI: 0.46, 0.72) measured with portable and HRM were correlated and inversely associated with the risk of FI. During simulated evacuation, the CCC for rectal pressure (0.62; 95% CI: 0.43, 0.76) was greater than that for anal pressure (CCC 0.22; 95% CI: 0.04, 0.39) and the rectoanal gradient (CCC 0.22; 95% CI: 0.02, 0.41). Rectal sensory thresholds for first sensation, the desire to defecate, and urgency measured by portable and HRM were also significantly correlated between techniques. For several parameters, differences between portable and HRM were statistically significant and the Bland Altman test was positive., Conclusions & Inferences: Anorectal pressures and rectal sensation can be conveniently measured by portable manometry and are significantly correlated with high-resolution manometry., (© 2015 John Wiley & Sons Ltd.)

Background: Rectal disorders during ulcerative colitis (UC) drastically alter the quality of life and may result from an impairment of rectal perception and compliance. This study aims to assess anorectal disorders in patients with mild-to-moderate UC., Methods: Anal pressures and the rectal responses to phasic rectal isobaric distension in 10 patients with mild-to-moderate UC were prospectively compared with those in 10 healthy volunteers (HVs)., Key Results: The patients in each group were similar regarding age, gender, and delivery. In the resting state, the anal canal pressures were similar between the groups. Only the squeeze pressures of the lower anal canal were significantly lower in UC patients than in HVs. During phasic isobaric distension, rectal sensitivity was similar between the groups, whatever the step of distension. Isobaric rectal distension resulted in a significant decrease of the rectoanal inhibitory reflex and a decrease in rectal tone and a significant drop in rectal compliance in UC patients compared with HVs., Conclusions & Inferences: Patients showing mild-to-moderate UC experience rectal compliance and innervation disorders without a significant change in rectal sensitivity. The findings of this work suggest impairment not only of the properties of the rectal wall but also of intrinsic innervation. Repeated evaluation over time may be helpful for analyzing the reversibility of the process after healing., (© 2015 John Wiley & Sons Ltd.)

Background: The pathophysiology behind idiopathic fecal incontinence (IFI) is poorly understood. We hypothesized abnormal sensory pathways along the brain-gut axis as a key player in this disease, reflected in cortical evoked potentials (CEP) from mechanical stimuli of the rectum and the anal canal., Methods: CEPs were recorded during repeated rapid balloon distensions of the rectum and anal canal in 19 women with IFI (mean age: 60 ± 14, mean Wexner score: 14.7 ± 2.9) and in 19 healthy women (mean age: 56 ± 11, mean Wexner score: 1.1 ± 1.3). Latencies, amplitudes and topography of CEPs elicited by rectal distension were compared between the groups. CEPs from both rectal and anal distensions were examined using spectral band analysis of single sweeps determining the relative amplitude of five spectral bands as a proxy of neuronal processing., Key Results: Compared to controls IFI patients had prolonged latency of CEPs from rectal distension by up to 27% (p < 0.001) while amplitudes and topography were similar (all p > 0.7 and all p > 0.23). Spectral analysis of CEPs from rectal distensions showed no difference (all p > 0.1) between groups. However, analysis of CEPs following distension of the anal canal resulted in abnormally low activity in beta (8-12 Hz; p < 0.001) band and high activity in the gamma (32-70 Hz; p = 0.04) band in patients., Conclusions & Inferences: IFI seems to be associated with impaired ano-rectal sensory functions in both the afferent fibers to the brain and the cortical processing of anal sensory pathways. This may play a central role for the pathogenesis of IFI., (© 2015 John Wiley & Sons Ltd.)

Background: Measurements of anorectal function using high-resolution anorectal manometry (HR-ARM) and rectal barostat technology provide more reliable results than standard ARM with an elastic balloon; however, HR-ARM results have not been compared to ARM and standard barostat protocols are impractical in routine clinical practice. The aim of this study was to validate HR-ARM against standard ARM and standard barostat against a novel Rapid Barostat Bag (RBB) measurement and elastic balloon measurements of rectal function., Methods: Twenty-six healthy volunteers (15 female, 11 male, 19-52 years) were studied. Measurements of anal function and simulated defecation were compared for 12-sensor HR-ARM and 6-sensor standard ARM using line plots from the same recording. Rectal capacity, compliance, and sensation (volume threshold) were measured by elastic balloon, standard barostat, and RBB methods using stepwise inflation of a 700-mL polyethylene bag to 40 mmHg distension by electronic barostat and handheld syringe monitored by sphygmo-manometer, respectively. Results are reported as mean ± SD. Bland-Altman plots and correlation coefficients (r) for measurements were calculated., Key Results: There was excellent agreement between HR- and standard ARM measurements (r > 0.86, <25 mmHg difference) and between standard barostat and RBB measurements of rectal capacity (r = 0.97, <25 mL difference). Correlation coefficients of threshold volumes for initial perception, urgency and discomfort were 0.37, 0.71, and 0.95, respectively. No significant correlation was present with elastic balloon measurements. Time to complete studies was shorter for HR-ARM than standard ARM and for RBB than standard barostat in historical controls., Conclusions & Inferences: HR-ARM with RBB measurements of anorectal function provides quick and reasonably accurate measurements of continence function suitable for use in routine clinical practice (ClinicalTrial.gov NCT01456442)., (© 2014 John Wiley & Sons Ltd.)

Background: Despite the commonality of fecal incontinence (FI) in men, few studies have been carried out in this patient group. The aim of the study was to determine the contributions of clinical and physiological factors to symptom severity in males with fecal leakage (FL) and FI., Methods: The records of all male patients referred for evaluation of FI and FL over a 6-year period were analyzed. For each male case, the records of three age-matched female controls with FI or FL were retrieved. All patients completed symptom assessment questionnaires (Vaizey score) and standard anorectal manometry testing., Key Results: A total of 100 males and 300 age-matched female controls were included. Vaizey scores were similar between sexes. For all Vaizey strata, males had normal maximal resting pressures (MRP) as well as normal maximal squeeze pressure (MSP). Females had a significantly reduced MRP and MSP across all Vaizey strata. In the FL subgroup, males had higher MRP and MSP than females. A multivariable linear regression analysis in males did not identify any clinical factors predictive of symptoms severity. For females, increased symptom duration, abnormal Bristol score, and reduced MSP were associated with worsening in Vaizey score., Conclusions & Inferences: For females, FL represents one end of the severity spectrum of FI while in males FL has a distinct pathophysiology. Contributing factors to symptoms in males with FL are not identified by routine clinical tests; however, anorectal manometry may identify a subgroup of FL males with low anal sphincter pressures that may respond to targeted interventions., (© 2013 John Wiley & Sons Ltd.)

Background: Anatomical structures and their distensibility vary along the length of the anal canal. The anal sphincter muscles have dynamic properties that are not well-reflected by standard manometry. Abnormal distensibility of the anal canal may be of importance in idiopathic fecal incontinence (IFI). The functional lumen imaging probe (FLIP) allows detailed studies of the distensibility and axial variation of sphincters. We aimed at comparing segmental distensibility of the anal canal in patients with IFI and healthy subjects., Methods: The FLIP was used for distension of the anal canal in 22 patients with IFI (17 female, age 27-82 years) and 21 healthy volunteers (18 female, age 32-73 years). The distensibility was determined from changes in luminal diameter. Closure of the anal canal during voluntary squeeze was computed as the combined length of closed anal canal and time. Pressure-strain elastic modulus was computed at rest., Key Results: In all subjects, the proximal anal canal was the most distensible segment. During distension at rest and during squeeze the middle and distal anal canal became significantly larger in IFI than in healthy (F < 22.4, p < 0.05). The closure of the anal canal during voluntary squeeze did not differ between healthy (75.9 ± 92.9 mm s) and IFI patients (90.4 ± 105 mm s; p = 0.6). Compared with healthy, IFI patients had lower pressure-strain elastic modulus of the middle and distal (q > 4.5, p < 0.05) but not the proximal anal canal (q < 0.7, p > 0.05)., Conclusions & Inferences: Patients with IFI have increased distensibility of the middle and distal parts of the anal canal., (© 2013 John Wiley & Sons Ltd.)

Background: Transcutaneous electrical tibial nerve stimulation (TENS) is of growing interest for the treatment of fecal incontinence (FI), but its mechanism of action remains uninvestigated. We aimed to further assess the anorectal response to TENS in a dynamic model., Methods: We performed a placebo-controlled, randomized, double-blinded crossover study in 19 patients suffering from FI to assess the effects of TENS on anorectal function. Anorectal physiology and perception were recorded through two sequences of rectal isobaric distension using an electronic barostat device to measure anal and rectal pressures, rectal volumes, and perception scores., Key Results: Maximal rectal pressure and volume variation were affected by TENS, with higher mean maximal rectal pressure (5.33 and 4.06 mmHg in the active and sham TENS respectively, p < 0.0001) and lower volume variation (11.45 and 14.7 mL in the active and sham stimulation respectively, p < 0.05). Rectal compliance was not modified by active TENS. Pressure of the upper anal canal was significantly lower with raised isobaric distension in sequences assigned to active TENS., Conclusions & Inferences: Acute TENS modified anorectal physiology by strengthening the myogenic response to distension rather than increasing muscle relaxation and related rectal compliance in patients with FI., (© 2013 John Wiley & Sons Ltd.)

Background: Inter-observer variability limits the reproducibility of pelvic floor motion measured by magnetic resonance imaging (MRI). Our aim was to develop a semi-automated program measuring pelvic floor motion in a reproducible and refined manner., Methods: Pelvic floor anatomy and motion during voluntary contraction (squeeze) and rectal evacuation were assessed by MRI in 64 women with fecal incontinence (FI) and 64 age-matched controls. A radiologist measured anorectal angles and anorectal junction motion. A semi-automated program did the same and also dissected anorectal motion into perpendicular vectors representing the puborectalis and other pelvic floor muscles, assessed the pubococcygeal angle, and evaluated pelvic rotation., Key Results: Manual and semi-automated measurements of anorectal junction motion (r = 0.70; P < 0.0001) during squeeze and evacuation were correlated, as were anorectal angles at rest, squeeze, and evacuation; angle change during squeeze or evacuation was less so. Semi-automated measurements of anorectal and pelvic bony motion were also reproducible within subjects. During squeeze, puborectalis injury was associated (P ≤ 0.01) with smaller puborectalis but not pelvic floor motion vectors, reflecting impaired puborectalis function. The pubococcygeal angle, reflecting posterior pelvic floor motion, was smaller during squeeze and larger during evacuation. However, pubococcygeal angles and pelvic rotation during squeeze and evacuation did not differ significantly between FI and controls., Conclusion & Inferences: This semi-automated program provides a reproducible, efficient, and refined analysis of pelvic floor motion by MRI. Puborectalis injury is independently associated with impaired motion of puborectalis, not other pelvic floor muscles in controls and women with FI., (© 2012 Blackwell Publishing Ltd.)

Background: While bowel and bladder dysfunction are recognized consequences of a radical hysterectomy, the effects of a simple hysterectomy on anorectal sensorimotor functions, particularly rectal sensation, vary among studies and the effects on rectal compliance remain unknown. Our aims were to prospectively evaluate anorectal sensorimotor functions before and after a hysterectomy., Methods: Anal pressures, rectal compliance, capacity, sensation, and bowel symptoms were assessed before, at 2 months, and at 1 year after a simple vaginal hysterectomy for benign indications in 19 patients. Rectal staircase (0-44 mmHg, 4-mmHg steps), ramp (0-200 mL at 50, 200 and 600 mL min(-1)) and phasic distentions (8, 16, and 24 mmHg above operating pressure) were performed., Key Results: Anal resting (63 ± 4 before, 56 ± 4 mmHg after) and squeeze pressures (124 ± 12 before, 124 ± 12 mmHg after), rectal compliance and capacity (285 ± 12 before, 290 ± 11 mL 1 year after), and perception of phasic distentions were not different before vs after a hysterectomy. Sensory thresholds for first sensation and the desire to defecate were also not different, but pressure and volume thresholds for urgency were somewhat greater (Hazard ratio = 0.7, 95% CI [0.5, 1.0]) 1 year after (vs before) a hysterectomy. Rectal pressures were higher (P < 0.0001) during fast compared with slow ramp distention; this rate effect was greater at 1 year after a hysterectomy, particularly at 100 mL (P = 0.04)., Conclusions & Inferences: A simple vaginal hysterectomy has relatively modest effects (i.e., somewhat reduced rectal urgency and increased stiffness during rapid distention) on rectal sensorimotor functions., (© 2011 Blackwell Publishing Ltd.)

Background: The length at which a muscle/sarcomere operates in vivo (operational length) and the length at which it generates maximal stress (optimal length) can be quite different. In a previous study, we found that the rabbit external anal sphincter (EAS) operates on the ascending limb of the length-tension curve, in other words at lengths shorter than its optimal length (short sarcomere length). In this study, we tested whether the human EAS muscle also operates at a short sarcomere length., Methods: The length-tension relationship of the EAS muscle was studied in vivo in 10 healthy nullipara women. EAS muscle length was altered by anal distension using custom-designed probes of 5, 10, 15, and 20mm diameter. Probes were equipped with a sleeve sensor to measure anal canal pressure. The EAS muscle electromyograph (EMG) was recorded using wire electrodes. Ultrasound images of anal canal were obtained to measure EAS muscle thickness and anal canal diameter. EAS muscle stress was calculated from the anal canal pressure, inner radius, and thickness of the EAS muscle., Key Results: Rest and squeeze stress of the anal canal increased with the increase in probe size. Similarly, the change in anal canal stress, i.e. the difference between the rest and the squeeze, which represents the active contribution of EAS to the anal canal stress, increased with the increase in probe size. However, increase in probe size was not associated with an increase in the external anal sphincter EMG activity., Conclusions & Inferences: Increase in EAS muscle stress with the increase in probe size, in the presence of constant EMG (neural input), demonstrates that the human EAS muscle operates on the ascending limb of the length-tension curve or at low sarcomere lengths. We propose that surgically adjusting EAS sarcomere length may represent a novel strategy to treat fecal incontinence in humans., (© 2011 Blackwell Publishing Ltd.)

Background: Sacral nerve stimulation (SNS) is a well-established treatment for fecal incontinence of various etiologies. However, the mechanism of action remains unclear. The aim of the present study was to determine whether SNS affects gastric emptying, small intestinal transit or colonic transit times., Methods: Seven patients with a permanently implanted sacral nerve stimulator participated in a double-blind randomized cross-over study. The patients were allocated to stimulation ON or OFF for two 7-day periods separated by at least 1week. On days 4-7 of each 7-day period, the patients were examined by gamma camera imaging to measure gastric emptying, small intestinal transit and colonic transit parameters of a radiolabeled, 1600 kJ mixed solid and liquid meal ingested on day 4., Key Results: Sacral nerve stimulation did not change gastric retention at 15 min, gastric mean emptying time, gastric half emptying time, small intestinal mean transit time or colonic geometric center after 24, 48 and 72 h., Conclusions & Inferences:   Sacral nerve stimulation does not induce major changes in the propulsive capacity of the gastrointestinal tract in patients successfully treated for fecal incontinence with permanent sacral nerve stimulator., (© 2011 Blackwell Publishing Ltd.)

Background: Fecal incontinence (FI) is a major part of illness and physical discomfort in the general population. Since the 1990s, sacral nerve stimulation has been well established in the treatment of neurogenic FI. The precise placement of the electrode is crucial for the success of the procedure. Eighty percent of the patients benefit from permanent treatment, but in 10-20% of the patients tested electrode placement proves impossible due to anatomical variations of the sacral foramina. In this study, we describe the technical requirements and a new method of electrode placement with reference to the anatomical (bone) landmarks in an animal model., Methods: With a small endoscope (Verres needle), we accessed the perirectal space to identify the nervous structures. A stimulated sphincter EMG was obtained for the experimental animals and muscle action potential (MAP/M-wave), latency time [ms], and the amplitude of the motor response [μV] were recorded. Electrodes were placed, the animals killed and dissected leaving the pelvic cavity untouched. The specimens were examined in a magnetic resonance scanner and in a multi-slice computed tomography scanner to detect the electrode material and possible surgical complications. After that the specimens were dissected., Key Results: In all eight cases in the four animals tested, we were able to stimulate the sacral nerve as demonstrated by the EMG findings. No major surgical complications were observed for the procedure., Conclusions & Inferences: Endoscopic sacral nerve root stimulation is a safe and effective method for delivering stimulation material in the pelvis of the sheep. It is a promising procedure to be tested in humans., (© 2010 Blackwell Publishing Ltd.)

Unlabelled: The mechanisms of action of sacral nerve stimulation (SNS) to treat faecal incontinence remain poorly understood., The Aims of Our Study Were: (i) to measure the effect of SNS on rectal function and (ii) to evaluate rectal function as a predictive factor of clinical response to SNS. Rectal function was studied before and 3 months after permanent SNS in 18 patients (17 women, mean age 58.5 years) with faecal incontinence, using an electronic barostat. Rectal sensitivity and volume variations were recorded during isobaric distensions. Three months after SNS, 14 patients had a significant improvement of faecal incontience symptoms and four had not. Baseline 'maximal tolerated volume' was significantly lower in the positive response group (210 +/- 56 vs 286 +/- 30 mL, P = 0.02). Baseline rectal compliance was lower in patients with a positive response than those without, although this difference did not reach significance (6.2 +/- 3.2 vs 9.2 +/- 2.9 mL mmHg(-1),P = 0.10). Rectal compliance was not significantly modified by SNS. Our results suggest that an increased rectal capacity as measured by the maximal tolerated volume may be a predictive factor of poor response to SNS in faecal incontinence. SNS does not significantly modify rectal function.

Sacral nerve root stimulation (SNS) can produce dramatic symptomatic improvement in faecal incontinence (FI). However, the physiological mechanism behind this improvement remains unknown. One hypothesis is that SNS may modulate cortico-anal pathways and drive compensatory changes within the spinal cord or cerebral cortex that beneficially alter sphincter function. Our aim was to assess whether short-term experimental SNS can induce changes in the human cortico-anal pathway. Eight healthy volunteers (mean age 30 years) were studied. Subjects were investigated on three separate occasions and randomized to either active (5 and 15 Hz) or sham rapid-rate lumbosacral magnetic stimulation (rLSMS). Anal sphincter electromyograms (EMG) were recorded from an anal probe following single-pulse transcranial magnetic stimulation, at baseline, immediately, 30 and 60 min following rLSMS at either (i) 5 Hz for 15 min, (ii) 15 Hz for 15 min or (iii) sham stimulation for 15 min. In addition, manometry and anal sphincter sensation was measured in a subset of subjects. Interventions were compared to sham using anova. Fifteen hertz rLSMS increased cortico-anal EMG response amplitude in the 1 h postintervention (F(4, 28) = 3.2, P = 0.027), without a shift in response latency. This effect was not demonstrated with either 5 Hz or sham stimulation. rLSMS had no short-term effect on sensation or physiology. Short-term magnetic stimulation of the sacral nerve roots induces changes in cortico-anal excitability which is frequency specific. These data support the hypothesis that SNS produces some of its beneficial effect in patients with FI by altering the excitability of the cortico-anal pathway.

Oxidative stress is associated with skeletal muscle fatigue. This study tests the hypotheses that N-acetylcysteine (NAC) reduces fatigue and accelerates recovery of the rat external anal sphincter (EAS). Fifteen female Wistar rats were killed humanely. The EAS was mounted as a ring preparation and electrically stimulated with 50 Hz trains of 200 ms in duration every 4 s for three and a half minutes. Three groups were analysed: a control group (n = 5), a group pretreated with NAC (10(-4) mol L(-1); n = 5) and a group pretreated with NAC (10(-3) mol L(-1); n = 5). A novel fatigue index was formulated and was compared to a conventional method of expressing fatigue. There was no significant difference at concentrations of NAC (10(-4) mol L(-1); P > 0.05). At high concentrations of NAC (10(-3) mol L(-1)) there was a significant depression in peak twitch amplitude before fatigue (P = 0.04). N-acetylcysteine in both concentrations used, did not alter fatigue or recovery of the rat EAS. There was a significant positive correlation between the two methods of expressing fatigue but the conventional method produced a higher fatigue index (22.4% on average). N-acetylcysteine does not ameliorate fatigue or accelerate recovery of the EAS and may not be a useful medical therapy for faecal incontinence.

The aim of the present study was to determine the effects of selectively stimulating the afferent fibres running in the dorsal sacral roots (S1, S2, S3) and the somatic (radial and sciatic) nerves on colonic and internal anal sphincter (IAS) electromyographic (EMG) activity in anaesthetized cats to try to understand how sacral nerve stimulation can improve fecal continence in human. Electrically stimulating the afferent fibres present in the sacral dorsal roots and somatic nerves inhibited the colonic spike potential frequency (n = 97) and increased the slow variations in the sphincteric membrane potential (n = 76). These effects were found to have disappeared after administering an alpha-noradrenergic receptor blocker (n = 64) or sectioning the sympathetic efferent fibres innervating these organs (n = 69) suggesting the involvement of the sympathetic system in the effects observed. Moreover, no significant differences were observed between the effects of sacral dorsal root vs somatic nerve stimulation on colonic and sphincteric EMG activity. In conclusion, the data obtained here show that neurostimulation applied to the sacral spinal roots may improve fecal continence by inhibiting colonic activity and enhancing IAS activity via a somatosympathetic reflex.

Rectal hyposensitivity (RH) is commonly found in patients with intractable constipation, faecal incontinence or both. Anal sensation may also be blunted in these conditions. We aimed to determine whether RH is associated with anal hyposensitivity, which may reflect a combined viscero-somatic neuropathy. One hundred and fifty-eight female patients with chronic constipation underwent physiological investigation including rectal sensation to volumetric balloon distension, and distal anal mucosal sensation to electrostimulation. Data were also obtained from 32 healthy female volunteers. Anal mucosal electrosensory thresholds were significantly higher in patients compared with volunteers (median: 2.4 mA, range: 0.4-19.6 vs 1.1 mA, range: 0.1-4.2, respectively), although the patient group was older (P < 0.0001), but there was no difference (P = 0.572) in the incidence of blunted anal sensation between those with normal rectal sensation (n = 113, 20% abnormal) and RH (n = 45, 24% abnormal). Irrespective of rectal sensory function, there was a strong association between symptom duration (P = 0.012) and anal hyposensitivity. One-fifth of constipated female patients had evidence of diminished anal sensation. However, the presence of RH was not associated with an increased frequency of anal hyposensitivity, thereby suggesting that different aetiopathogenic mechanisms underlie the development of anal and rectal hyposensitivity. Further studies in carefully selected, homogenous patient populations are necessary to elucidate these mechanisms.