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The act of defaecation, although a ubiquitous human experience, requires the coordinated actions of the anorectum and colon, pelvic floor musculature, and the enteric, peripheral and central nervous systems. Defaecation is best appreciated through the description of four phases, which are, temporally and physiologically, reasonably discrete. However, given the complexity of this process, it is unsurprising that disorders of defaecation are both common and problematic; almost everyone will experience constipation at some time in their life and many will develop faecal incontinence. A detailed understanding of the normal physiology of defaecation and continence is critical to inform management of disorders of defaecation. During the past decade, there have been major advances in the investigative tools used to assess colonic and anorectal function. This Review details the current understanding of defaecation and continence. This includes an overview of the relevant anatomy and physiology, a description of the four phases of defaecation, and factors influencing defaecation (demographics, stool frequency/consistency, psychobehavioural factors, posture, circadian rhythm, dietary intake and medications). A summary of the known pathophysiology of defaecation disorders including constipation, faecal incontinence and irritable bowel syndrome is also included, as well as considerations for further research in this field. Defaecation is a coordinated process that requires a morphologically intact gastrointestinal tract and the integration of multiple physiological systems (neuromuscular, hormonal and cognitive). This Review describes the physiology of human defaecation and continence, providing insights into the pathophysiology of defaecation and evacuation disorders. Key points Defaecation is a fundamental physiological process resulting in the evacuation of faeces; it is dependent on the coordination of neural, muscular, hormonal and cognitive systems. Several factors influence defaecation, including gastrointestinal transit, stool volume and/or consistency, and dietary intake. Defaecation can be described in terms of four reasonably discrete temporal phases: basal phase, pre-expulsive phase, expulsive phase and end phase. The latest imaging and technological advances (such as high-resolution colonic and anorectal manometry, cine-MRI and magnetic resonance defaecography and wireless capsules) have improved our knowledge of defaecatory mechanisms. Knowledge of the physiology of normal defaecation could inform management of common disorders of defaecation such as constipation and faecal incontinence; however, future research needs are highlighted in this article.

Intra-operative electrode placement for sacral neuromodulation (SNM) relies on visual observation of motor contractions alone, lacking complete information on neural activation from stimulation. This study aimed to determine whether electrophysiological responses can be recorded directly from the S3 sacral nerve during therapeutic SNM in patients with fecal incontinence, and to characterize such responses in order to better understand the mechanism of action (MOA) and whether stimulation is subject to changes in posture. Eleven patients undergoing SNM were prospectively recruited. A bespoke stimulating and recording system was connected (both intraoperatively and postoperatively) to externalized SNM leads, and electrophysiological responses to monopolar current sweeps on each electrode were recorded and analyzed. The nature and thresholds of muscle contractions (intraoperatively) and patient-reported stimulation perception were recorded. We identified both neural responses (evoked compound action potentials) as well as myoelectric responses (far-field potentials from muscle activation). We identified large myelinated fibers (conduction velocity: 36–60 m/s) in 5/11 patients, correlating with patient-reported stimulation perception, and smaller myelinated fibers (conduction velocity <15 m/s) in 4/11 patients (not associated with any sensation). Myoelectric responses (observed in 7/11 patients) were attributed to pelvic floor and/or anal sphincter contraction. Responses varied with changes in posture. We present the first direct electrophysiological responses recorded from the S3 nerve during ongoing SNM in humans, showing both neural and myoelectric responses. These recordings highlight heterogeneity of neural and myoelectric responses (relevant to understanding MOA of SNM) and confirm that electrode lead position can change with posture.

Background Faecal incontinence (FI) is a substantial health problem with a prevalence of approximately 8% in community-dwelling populations. Sacral neuromodulation (SNM) is considered the first-line surgical treatment option in adults with FI in whom conservative therapies have failed. The clinical efficacy of SNM has never been rigorously determined in a trial setting and the underlying mechanism of action remains unclear. Methods/design The design encompasses a multicentre, randomised, double-blind crossover trial and cohort follow-up study. Ninety participants will be randomised to one of two groups (SNM/SHAM or SHAM/SNM) in an allocation ratio of 1:1. The main inclusion criteria will be adults aged 18–75 years meeting Rome III and ICI definitions of FI, who have failed non-surgical treatments to the UK standard, who have a minimum of eight FI episodes in a 4-week screening period, and who are clinically suitable for SNM. The primary objective is to estimate the clinical efficacy of sub-sensory SNM vs. SHAM at 32 weeks based on the primary outcome of frequency of FI episodes using a 4-week paper diary, using mixed Poisson regression analysis on the intention-to-treat principle. The study is powered (0.9) to detect a 30% reduction in frequency of FI episodes between sub-sensory SNM and SHAM stimulation over a 32-week crossover period. Secondary objectives include: measurement of established and new clinical outcomes after 1 year of therapy using new (2017 published) optimised therapy (with standardised SNM-lead placement); validation of new electronic outcome measures (events) and a device to record them, and identification of potential biological effects of SNM on underlying anorectal afferent neuronal pathophysiology (hypothesis: SNM leads to increased frequency of perceived transient anal sphincter relaxations; improved conscious sensation of defaecatory urge and cortical/subcortical changes in afferent responses to anorectal electrical stimulation (main techniques: high-resolution anorectal manometry and magnetoencephalography). Discussion This trial will determine clinical effect size for sub-sensory chronic electrical stimulation of the sacral innervation. It will provide experimental evidence of modifiable afferent neurophysiology that may aid future patient selection as well as a basic understanding of the pathophysiology of FI. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN98760715 . Registered on 15 September 2017.

Normal bowel function requires intact sensory pathways. Diminished rectal sensation (rectal hyposensitivity [RH]) is associated with constipation, although its clinical importance remains unclear. Consecutive patients (aged 18-80) attending a tertiary center (2004-2016) for investigation of refractory functional constipation (Rome IV core criteria defined, applied post hoc) were included. Patients completed a clinical symptom questionnaire and underwent anorectal physiologic investigations, including rectal sensory testing (balloon distension) to determine 3 well-established sensory thresholds. Multivariate regression analyses were performed to evaluate associations between RH, symptomology, and allied physiologic investigations. Of 2,876 patients meeting inclusion criteria, 722 (25%) had RH based on ≥1 elevated sensory thresholds (0: n = 2,154 [74.9%]; 1: n = 327 [11.4%]; 2: n = 209 [7.3%]; and 3: n = 186 [6.5%]). A linear relationship existed between increasing number of elevated sensory thresholds and constipation severity (Cleveland Clinic constipation score: mean difference per threshold [95% confidence interval] 0.69 [0.48-0.90]; P < 0.001). Several symptoms were significantly (P < 0.05) associated with RH including: infrequent defecation (odds ratio 1.29 [1.17-1.42]), painful evacuation (1.15 [1.05-1.27]), prolonged toileting (1.14 [1.05-1.24]), and digitation or enema use (1.18 [1.08-1.30]). On defecography, a \"functional\" evacuation disorder was also associated with RH (1.37 [1.25-1.50], P < 0.001), as was megarectum (2.52 [2.08-3.05], P < 0.001). RH occurs in 25% of patients with refractory functional constipation. Increased number of elevated sensory thresholds is associated with more severe constipation phenotype. These data, in the largest study to date, provide for the first time evidence to show that RH is a major pathophysiologic mechanism in constipation, with recognized clinical impact (http://links.lww.com/AJG/B765).(Equation is included in full-text article.).

Obesity is a global epidemic. Its clinical impact on symptoms of fecal incontinence (FI) and/or constipation and underlying anorectal pathophysiology remains uncertain. This is a cross-sectional study of consecutive patients meeting Rome IV criteria for FI and/or functional constipation, with data on body mass index (BMI), attending a tertiary center for investigation between 2017 and 2021. Clinical history, symptoms, and anorectal physiologic test results were analyzed according to BMI categories. A total of 1,155 patients (84% female) were included in the analysis (33.5% normal BMI; 34.8% overweight; and 31.7% obese). Obese patients had higher odds of FI to liquid stools (69.9 vs 47.8%, odds ratio [OR] 1.96 [confidence interval: 1.43-2.70]), use of containment products (54.6% vs 32.6%, OR 1.81 [1.31-2.51]), fecal urgency (74.6% vs 60.7%, OR 1.54 [1.11-2.14]), urge FI (63.4% vs 47.3%, OR 1.68 [1.23-2.29]), and vaginal digitation (18.0% vs 9.7%, OR 2.18 [1.26-3.86]). A higher proportion of obese patients had Rome criteria-based FI or coexistent FI and functional constipation (37.3%, 50.3%) compared with overweight patients (33.8%, 44.8%) and patients with normal BMI (28.9%, 41.1%). There was a positive linear association between BMI and anal resting pressure (β 0.45, R 2 0.25, P = 0.0003), although the odds of anal hypertension were not significantly higher after Benjamini-Hochberg correction. Obese patients more often had a large clinically significant rectocele (34.4% vs 20.6%, OR 2.62 [1.51-4.55]) compared with patients with normal BMI. Obesity affects specific defecatory (mainly FI) and prolapse symptoms and pathophysiologic findings (higher anal resting pressure and significant rectocele). Prospective studies are required to determine whether obesity is a modifiable risk factor of FI and constipation.

Normal bowel function requires intact sensory pathways. Diminished rectal sensation (rectal hyposensitivity [RH]) is associated with constipation, although its clinical importance remains unclear. Consecutive patients (aged 18-80) attending a tertiary center (2004-2016) for investigation of refractory functional constipation (Rome IV core criteria defined, applied post hoc) were included. Patients completed a clinical symptom questionnaire and underwent anorectal physiologic investigations, including rectal sensory testing (balloon distension) to determine 3 well-established sensory thresholds. Multivariate regression analyses were performed to evaluate associations between RH, symptomology, and allied physiologic investigations. Of 2,876 patients meeting inclusion criteria, 722 (25%) had RH based on ≥1 elevated sensory thresholds (0: n = 2,154 [74.9%]; 1: n = 327 [11.4%]; 2: n = 209 [7.3%]; and 3: n = 186 [6.5%]). A linear relationship existed between increasing number of elevated sensory thresholds and constipation severity (Cleveland Clinic constipation score: mean difference per threshold [95% confidence interval] 0.69 [0.48-0.90]; P < 0.001). Several symptoms were significantly (P < 0.05) associated with RH including: infrequent defecation (odds ratio 1.29 [1.17-1.42]), painful evacuation (1.15 [1.05-1.27]), prolonged toileting (1.14 [1.05-1.24]), and digitation or enema use (1.18 [1.08-1.30]). On defecography, a \"functional\" evacuation disorder was also associated with RH (1.37 [1.25-1.50], P < 0.001), as was megarectum (2.52 [2.08-3.05], P < 0.001). RH occurs in 25% of patients with refractory functional constipation. Increased number of elevated sensory thresholds is associated with more severe constipation phenotype. These data, in the largest study to date, provide for the first time evidence to show that RH is a major pathophysiologic mechanism in constipation, with recognized clinical impact (http://links.lww.com/AJG/B765).

Background Perianal fistula surgery can damage the anal sphincters which may cause faecal incontinence. By measuring regional pressures, 3D-HRAM potentially provides better guidance for surgical strategy in patients with perianal fistulas. The aim was to measure regional anal pressures with 3D-HRAM and to compare these with 3D-EUS findings in patients with perianal fistulas. Methods Consecutive patients with active perianal fistulas who underwent both 3D-EUS and 3D-HRAM at a clinic specialised in proctology were included. A group of 30 patients without fistulas served as controls. Data regarding demographics, complaints, previous perianal surgical procedures and obstetric history were collected. The mean and regional anal pressures were measured with 3D-HRAM. Fistula tract areas detected with 3D-EUS were analysed with 3D-HRAM by visual coding and the regional pressures of the corresponding and surrounding area of the fistula tract areas were measured. The study was granted by the VUmc Medical Ethical Committee. Results Forty patients (21 males, mean age 47) were included. Four patients had a primary fistula, 19 were previously treated with a seton/abscess drainage and 17 had a recurrence after previously performed fistula surgery. On 3D-HRAM, 24 (60%) fistula tract areas were good and 8 (20%) moderately visible. All but 7 (18%) patients had normal mean resting pressures. The mean resting pressure of the fistula tract area was significantly lower compared to the surrounding area (47 vs. 76 mmHg; p  < 0.0001). Only 2 (5%) patients had a regional mean resting pressure < 10 mmHg of the fistula tract area. Using a Δ mean resting pressure ≥ 30 mmHg difference between fistula tract area and non-fistula tract area as alternative cut-off, 21 (53%) patients were identified. In 6 patients 3D-HRAM was repeated after surgery: a local pressure drop was detected in one patient after fistulotomy with increased complaints of faecal incontinence. Conclusions Profound local anal pressure drops are found in the fistula tract areas in patients normal mean resting pressures. Fistulotomy may affect local sphincter pressure. This might influence surgical decision making in future.

Although the association of absent or attenuated \"call to stool\" with constipation is well-recognized, no studies have systematically evaluated the perception of urge to defecate in a well-defined cohort of patients with chronic constipation (CC). A prospective study of 43 healthy adult women and 140 consecutive adult women attending a tertiary center for investigation of CC. All participants completed a 5-day viscerosensory questionnaire, and all women with CC also underwent anorectal physiologic investigations. Normal urge perception and abnormal urge perception were defined using a Naive Bayes model trained in healthy women (95% having normal urge). In total, 181 toilet visits in healthy women and 595 in women with CC were analyzed. Abnormal urge perception occurred in 70 (50.0%) women with CC. In this group, the urge to defecate was more often experienced as abdominal sensation (69.3% vs 41.4%; P < 0.0001), and the viscerosensory referral area was 81% larger (median pixels anterior: 1,849 vs 1,022; P < 0.0001) compared to women with CC and normal urge perception. Abnormal (vs normal) urge in women with CC was associated with more severe constipation (Cleveland Clinic constipation score: 19 vs 15 P < 0.0001), irritable bowel syndrome (45.7% vs 22.9% P < 0.0001), and a functional evacuation disorder on defecography (31.3% vs 14.3% P = 0.023). A distinct pattern of abnormal urge was found in women with CC and rectal hyposensitivity. Abnormal urge perception was observed in 50% of women with CC and was frequently described as abdominal sensation, supporting the concept that sensory dysfunction makes an important contribution to the pathophysiology of constipation.