Evaluating the risk factors for the development of benign disorders of defaecation: a surgical perspective.

PURPOSE: There remains uncertainty as to which risk factors are important for the development of defaecatory problems as a result of heterogeneity of published evidence. Understanding the impact of risk factors may be important in selecting targets for disease prevention or reversal. The aim of this study was to identify and evaluate risk factors for faecal incontinence and chronic constipation. METHODS: Risk factors for chronic constipation and faecal incontinence were long-listed from scientific literature, then anonymously evaluated (by 50 predominantly colorectal surgical experts from the UK Pelvic Floor Society) using a Delphi technique. Each risk factor was rated as independent, a co-factor, or not a risk factor. Independent risk factors were rated between 1 (not important) and 10 (critically important) with mean (± standard deviation) calculated. RESULTS: Thirty-eight risk factors for chronic constipation were evaluated. Eighteen were classed as independent and 16 as co-factors. Opioid analgesia (7.87 ± 2.05), eating disorders (7.80 ± 1.72), and history of abuse (7.70 ± 1.89) were scored as most important independent risk factors. Female sex (6.60 ± 2.02) was considered an independent risk factor but increasing age was rated a co-factor. Thirty-three risk factors for faecal incontinence were evaluated. Twenty were classed as independent and eight as co-factors. Third- or fourth-degree tear (8.88 ± 1.57), instrumental delivery (8.47 ± 1.58), and grand multiparity (8.00 ± 1.63) were rated most important. Increasing age (7.41 ± 2.14) and female sex (7.58 ± 2.05) were both considered independent risk factors. CONCLUSIONS: Several risk factors for chronic constipation and faecal incontinence were selected by Delphi approach. These factors will feed forward into Bayesian models of disease prediction that combine data and expert knowledge.

Stepped-wedge randomized controlled trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation.

BACKGROUND: The effectiveness of laparoscopic ventral mesh rectopexy (LVMR) in patients with defecatory disorders secondary to internal rectal prolapse is poorly evidenced. A UK-based multicenter randomized controlled trial was designed to determine the clinical efficacy of LVMR compared to controls at medium-term follow-up. METHODS: The randomized controlled trial was conducted from March 1, 2015 TO January 31, 2019. A stepped-wedge RCT design permitted observer-masked data comparisons between patients awaiting LVMR (controls) with those who had undergone surgery. Adult participants with radiologically confirmed IRP refractory to conservative treatment were randomized to three arms with different delays before surgery. Efficacy outcome data were collected at equally stepped time points (12, 24, 36, 48, 60, and 72 weeks). Clinical efficacy of LVMR compared to controls was defined as ≥ 1.0-point reduction in Patient Assessment of Constipation-Quality of Life and/or Symptoms (PAC-QOL and/or PAC-SYM) scores at 24 weeks. Secondary outcome measures included 14-day diary data, the Generalized Anxiety Disorder scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), St Marks incontinence score, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), the chronic constipation Behavioral Response to Illness Questionnaire (CC-BRQ), and the Brief Illness Perception Questionnaire (BIPQ). RESULTS: Of a calculated sample size of 114, only 28 patients (100% female) were randomized from 6 institutions (due mainly to national pause on mesh-related surgery). Nine were assigned to the T0 arm, 10 to T12, and 9 to T24. There were no substantial differences in baseline characteristics between the three arms. Compared to baseline, significant reduction (improvement) in PAC-QOL and PAC-SYM scores were observed at 24 weeks post-surgery (- 1.09 [95% CI - 1.76, - 0.41], p = 0.0019, and - 0.92 [- 1.52, - 0.32], p = 0.0029, respectively) in the 19 patients available for analysis (9 were excluded for dropout [n = 2] or missing primary outcome [n = 7]). There was a clinically significant long-term reduction in PAC-QOL scores (- 1.38 [- 2.94, 0.19], p = 0.0840 at 72 weeks). Statistically significant improvements in PAC-SYM scores persisted to 72 weeks (- 1.51 [- 2.87, - 0.16], p = 0.0289). Compared to baseline, no differences were found in secondary outcomes, except for significant improvements at 24 and 48 weeks on CC-BRQ avoidance behavior (- 14.3 [95% CI - 23.3, - 5.4], and - 0.92 [- 1.52, - 0.32], respectively), CC-BRQ safety behavior (- 13.7 [95% CI - 20.5, - 7.0], and - 13.0 [- 19.8, - 6.1], respectively), and BIPQ negative perceptions (- 16.3 [95% CI - 23.5, - 9.0], and - 10.5 [- 17.9, - 3.2], respectively). CONCLUSIONS: With the caveat of under-powering due to poor recruitment, the study presents the first randomized trial evidence of short-term benefit of LVMR for internal rectal prolapse. TRIAL REGISTRATION: ISRCTN Registry (ISRCTN11747152).

Slow-transit constipation and criteria for colectomy: a cross-sectional study of 1568 patients.

BACKGROUND: Colectomy remains a treatment option for a minority of patients with slow-transit constipation (STC) refractory to conservative treatment. However careful patient selection is essential to maximize benefits and minimize risk of adverse outcome. This study determined the proportion of patients with chronic constipation that would meet criteria for colectomy based on recent European graded practice recommendations derived by expert consensus. METHODS: Retrospective application of graded practice recommendations was undertaken on a prospectively maintained data set of consecutive adult patients with chronic constipation who underwent whole-gut transit studies using radio-opaque markers. Primary analysis applied contraindications achieving high level of expert consensus (normal whole-gut transit as an absolute contraindication and faecal incontinence as a relative contraindication for colectomy). Secondary analysis applied contraindications with less certain consensus. RESULTS: Primary analysis of 1568 patients undergoing a whole-gut transit study between January 2004 and March 2016 found 208 (13.3 per cent) met published criteria to be selected for colectomy, with 974 excluded for normal whole-gut transit and 386 for faecal incontinence. Secondary analysis demonstrated high prevalence of other relative contraindications to colectomy: 165 concomitant upper gastrointestinal symptoms, 216 abdominal pain (including 126 irritable bowel syndrome), and 446 evacuation disorder. The majority of patients (416 of 594) had two or more relative contraindications. If these patients were excluded, only 26 (1.7 per cent) chronically constipated patients retrospectively met selection criteria for colectomy. CONCLUSIONS: The retrospective application of selection criteria is a limitation. However, the data highlight the high prevalence of factors associated with poor postoperative outcome and provide further caution to surgeons undertaking colectomy for STC.

Initial experience with SphinKeeper™ intersphincteric implants for faecal incontinence in the UK: a two-centre retrospective clinical audit.

AIM: The SphinKeeper™ artificial bowel sphincter implant is a relatively new surgical technique for the treatment of refractory faecal incontinence. This study presents the first experience in two UK tertiary centres. METHOD: This is a retrospective audit of prospectively collected clinical data in relation to technique, safety, feasibility and short-term effectiveness from patients undergoing surgery from January 2016 to April 2019. Baseline data, intra-operative and postoperative complications, symptoms [using St Mark's incontinence score (SMIS)] and radiological outcomes were analysed. RESULTS: Twenty-seven patients [18 women, median age 57 years (range 27-87)] underwent SphinKeeper. In 30% of the patients, the firing device jammed and not all prostheses were delivered. There were no intra-operative complications and all patients were discharged the same or the following day. SMIS significantly improved from baseline [median -6 points (range -12 to +3); P < 0.00016] with 14/27 (51.9%) patients achieving a 50% reduction in the SMIS score. On postoperative imaging, a median of seven prostheses (range 0-10) were identified with a median of five (range 0-10) optimally placed. There was no relationship between number of well-sited prostheses on postoperative imaging and categorical success based on 50% reduction in SMIS (χ2 test, P = 0.79). CONCLUSION: SphinKeeper appears to be a safe procedure for faecal incontinence. Overall, about 50% patients achieved a meaningful improvement in symptoms. However, clinical benefit was unrelated to the rate of misplaced/migrated implants. This has implications for confidence in proof of mechanism and also the need for technical refinement.

Botulinum toxin type A for the treatment of dyssynergic defaecation in adults: a systematic review.

AIM: Dyssynergic defaecation (DD) is characterized by inappropriate coordination of the pelvic floor muscles during defaecation, resulting in impaired stool expulsion. The mainstay of treatment is biofeedback and alternative therapies are limited in those who do not respond. This systematic review evaluated botulinum toxin type A injection (BTXA) as a treatment option for dyssynergia. METHODS: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for studies evaluating adult patients with DD treated with BTXA injection into the puborectalis and/or external anal sphincter. All study designs, except case reports, were included in the review with no language restriction. Studies limited to patients with specific neurological diagnoses or with a follow-up period under 1 month were excluded. Study selection, assessment and data extraction were performed by two reviewers and results were synthesized narratively. RESULTS: Eleven studies (three randomized control trials) involving 248 participants were included. All studies used the transanal approach to deliver the injection, most commonly at the 3 and 9 o'clock positions using digital palpation for guidance. The most commonly used patient position was left lateral, and most studies did not use any anaesthesia. The dose of BTXA varied (Botox 12-100 units, Dysport 100-500 units), and outcomes measured were heterogeneous (global rating ± up to five investigations). Symptomatic improvement varied between 29.2% and 100% and adverse effects occurred in 0% to 70%. CONCLUSION: The evidence to support using BTXA for DD is poor and only covers a transanal approach. Future studies should redress these limitations: heterogeneity of design, dose and outcome measures.

Technology as a tool in teaching quantitative biology at the secondary and undergraduate levels: a review.

Since the publication of the National Research Councils Report BIO2010, e orts have increased to better integrate mathematics and biology in undergraduate education. Unfortunately, equivalent e orts to introduce these quantitative topics at the secondary level have been seldom. This could cause differential success of undergraduate students who come from diverse secondary science backgrounds. Undergraduate courses regularly use technology to integrate these two disciplines, and we believe that technology can similarly be used at the secondary level to prevent quantitative achievement mismatch in undergraduate biology programs. In this paper, we review the current uses of technology to teach quantitative biology at the secondary and undergraduate levels, propose needs for further implementation, and address potential barriers to integrating mathematics and biology using technology.

Regional gastrointestinal pH profile is altered in patients with type 1 diabetes and peripheral neuropathy.

BACKGROUND: Gastrointestinal (GI) symptoms, such as nausea and bloating, are common in people with type 1 diabetes (T1DM). Autonomic dysfunction can lead to changes in the GI secreto-motor function which can be associated with GI symptom development. We hypothesized that regional pH profiles in T1DM differs from health and would be associated with objective physiological/clinical markers. METHODS: Forty-seven T1DM with confirmed diabetic sensory peripheral neuropathy and 41 healthy age-matched subjects underwent standardized wireless motility capsule testing. T1DM completed the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale. Disease duration, glycemic control, insulin usage, and 24-hour heart rate variability testing were evaluated. KEY RESULTS: In comparison to healthy subjects, gastric, and large bowel median pH were lower in T1DM (1.8 ± 1.6 vs 2.9 ± 1.5, P = 0.001 and 6.7 ± 0.6 vs 7.0 ± 0.5, P = 0.003, respectively). Additionally, change in pH across the pylorus was lower while change in pH across the ileocecal junction was higher in T1DM (5.2 ± 1.5 vs 5.8 ± 0.5, P = 0.003 and 1.8 ± 0.4 vs 1.3 ± 0.4, P < 0.0001, respectively). No difference was found in small bowel median pH. Gastric median pH was associated with small bowel transit time (r = 0.30, P = 0.049). Change in pH across the pylorus was negatively associated with fasting glycose (r = -0.35, P = 0.027). Small bowel median pH was associated with nausea (r = 0.42, P = 0.005) and small bowel transit time (r = 0.48, P = 0.0007). Large bowel median pH was associated with nausea (r = 0.35, P = 0.018) and the total GCSI score (r = 0.34, P = 0.023). CONCLUSIONS AND INFERENCES: The GI pH profile in T1DM with DSPN is different from healthy subjects. Changes in pH profile may have important therapeutic implications and influence pharmacotherapeutic bioavailability.

Technical report: Inter- and intra-rater reliability of regional gastrointestinal transit times measured using the 3D-Transit electromagnet tracking system.

BACKGROUND: The 3D-Transit electromagnet tracking system is an emerging tool for the ambulatory assessment of gastrointestinal (GI) transit times and motility patterns, based on the anatomical localization of ingestible electromagnetic capsules. Currently, 3D-Transit recordings are manually analyzed to extract GI transit times. As this is a subjective method, there is some inherent variability in the measurements, which may be experience-dependent. We therefore assessed inter- and intra-rater reliability of GI transit times from 3D-Transit recordings. METHODS: Thirty-six 3D-Transit recordings (17 female; median age: 34 years [range: 21-80]) were analyzed twice by 3 raters with varying experience. Each rater manually identified the timestamps when a capsule progressed from antrum to duodenum, and from ileum to right colon. These timestamps, along with the ingestion and expulsion times, were used to determine whole gut (WGTT), gastric emptying (GET), small intestinal (SITT) and colonic (CTT) transit times. Reliability was determined using interclass correlation coefficients (ICCs). KEY RESULTS: For capsule progression timestamps, the most and mid-experienced raters had fair to good inter- and excellent intra-rater reliability (ICCmin-max  = 0.61-1.00), whereas the inexperienced rater had poor to fair inter- and poor intra-rater reliability (ICCmin-max  = 0.28-0.55). GET and SITT reliability between the most and mid-experienced raters was fair (ICCmin-max  = 0.61-0.73), while reliability between these raters and the inexperienced rater was poor to fair (ICCmin-max  = 0.28-0.55). CTT reliability was excellent between and within all raters (ICCmin-max  = 0.92-0.99). CONCLUSIONS & INFERENCES: Inexperienced raters provide the least reliable measurements from 3D-Transit recordings, which confirms requirement for adequate training. Automation may improve the reliability of measurements.

Regional gastrointestinal contractility parameters using the wireless motility capsule: inter-observer reproducibility and influence of age, gender and study country.

BACKGROUND: The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. AIMS: To describe normative values for motility/contractility parameters across age, gender and testing centres. METHODS: Healthy participants underwent a standardised wireless motility capsule assessment following an overnight fast and consumption of a meal of known nutritional content. Traces were divided into regions of interest and analysed using 2 software packages (MotiliGI and GIMS Data Viewer). Inter-observer agreement was independently assessed by 2 investigators. RESULTS: Normative data for motility/contractility parameters (maximum amplitude, mean peak amplitude, contraction frequency and motility index) are presented for 107 individuals (62 male, median age 40 years, range 18-78). MotiliGI-Gastric, small bowel and colonic maximal contraction amplitude correlated with age (r = .24, P = .01; r = .22, P = .02; and r = .2, P = .04 respectively). Small bowel motility index was higher in females than males (150.4 ± 12 vs 122 ± 7.6, P = .04). Inter-observer agreement was excellent for transit times, pH and contractility/motility parameters. GIMS Data viewer-Gastric, small bowel and colonic loge motility index correlated with the respective area under the contraction curve, total contractions, sum of amplitudes and contraction frequency (all r>.35, P < .0003) but not with transit times. CONCLUSIONS: Our analysis provides normative data for motility/contractility parameters. Log motility index summarises a number of measures. In future, the measurement of contractile activity with the wireless motility capsule may potentially aid in the diagnosis of disease states such as visceral myopathic disorders.

Assessment of colorectal length using the electromagnetic capsule tracking system: a comparative validation study in healthy subjects.

AIM: We aimed to determine colorectal length with the 3D-Transit system by describing a 'centreline' of capsule movement and comparing it with known anatomy, as determined by magnetic resonance imaging (MRI). Further, we aimed to test the day-to-day variation of colorectal length assessed with the system. METHOD: The 3D-Transit system consists of electromagnetic capsules that can be tracked as they traverse the gastrointestinal tract. Twenty-five healthy subjects were examined with both 3D-Transit and MRI. Another 21 healthy subjects were examined with 3D-Transit on two consecutive days. RESULTS: Computation of colorectal length from capsule passage was possible for 60 of the 67 3D-Transit recordings. The length of the colorectum measured with MRI and 3D-Transit was 95 (75-153) cm and 99 (77-147) cm, respectively (P = 0.15). The coefficient of variation (CV) between MRI and 3D-Transit was 7.8%. Apart from the caecum/ascending colon being 26% (P = 0.002) shorter on MRI, there were no other differences in total or segmental colorectal lengths between methods (all P > 0.05). The length of the colorectum measured with 3D-Transit on two consecutive days was 102 (73-119) cm and 103 (75-123) cm (P = 0.67). The CV between days was 7.3%. CONCLUSION: The 3D-Transit system allows accurate and reliable determination of colorectal length compared with MRI-derived colorectal length and between days. Antegrade or retrograde capsule movement relative to this centreline, as well as the length and speed of movements, may be determined by future studies to allow better classification and treatment in patients with dysmotility.

High-resolution anorectal manometry: A comparison of solid-state and water-perfused catheters.

BACKGROUND: Anorectal manometry is the most commonly performed investigation for assessment of anorectal dysfunction. Findings from previous studies comparing water-perfused (WP) and solid-state (SS) techniques in the anorectum are conflicting. We compared anal sphincter pressure at rest and during dynamic maneuvers (squeezing and coughing) in healthy volunteers using SS and WP high-resolution anorectal manometry (HR-ARM) employing equivalent catheter configurations, a standardized protocol, and identical data acquisition and analysis software. METHODS: Sixty healthy volunteers (40F; median age: 40; range: 18-74) underwent WP and SS HR-ARM in randomized order. Anal resting pressure, and squeeze and cough increments were measured. Median pressure and 5th and 95th percentiles were calculated for each maneuver and compared using Wilcoxon signed-rank test. Bland and Altman plots were used to assess agreement between the systems. The impact of gender and parity was also explored. KEY RESULTS: Anal sphincter pressure measurements during squeeze (P<.001) and cough (P<.001) were significantly higher using SS HR-ARM than WP HR-ARM. No differences were seen at rest between the two types of catheter (nulliparous: P=.304; parous: P=.390; males: P=.167). Normal ranges for SS and WP manometry from this small group of healthy volunteers are presented. CONCLUSIONS & INFERENCES: Greater sensitivity to rapid pressure change is one of the advantages associated with SS HR-ARM. This is reflected in the differences observed during dynamic maneuvers performed during this study. Catheter type should be taken into consideration when selecting normal ranges for comparison to disease states.

Altered defaecatory behaviour and faecal incontinence in a video-tracked animal model of pudendal neuropathy.

AIM: The aim was to develop a behavioural animal model of faecal continence and assess the effect of retro-uterine balloon inflation (RBI) injury. RBI in the rat causes pudendal neuropathy, a risk factor for obstetric related faecal incontinence in humans. METHOD: Video-tracking of healthy rats (n = 12) in a cage containing a latrine box was used to monitor their defaecatory behaviour index (DBI) over 2 weeks. The DBI (range 0-1) was devised by dividing the defaecation rate (pellets per hour) outside the latrine by that of the whole cage. A score of 0 indicates all pellets were deposited in the latrine. Subsequently, the effects of RBI (n = 19), sham surgery (n = 4) and colostomy (n = 2) were determined by monitoring the DBI for 2 weeks preoperatively and 3 weeks postoperatively. RESULTS: The DBI for healthy rats was 0.1 ± 0.03 with no significant change over 2 weeks (P = 0.71). In the RBI group, 13 of 19 rats (68%) showed no significant change in DBI postoperatively (0.08 ±  -0.05 vs 0.11 ±  -0.07) while in six rats the DBI increased from 0.16 ±  -0.09 to 0.46 ± 0.23. The negative control, sham surgery, did not significantly affect the DBI (0.09 ± 0.06 vs 0.08 ± 0.04, P = 0.14). The positive control, colostomy, increased the DBI from 0.26 ± 0.03 to 0.86 ± 0.08. CONCLUSIONS: This is the first study showing a quantifiable change in defaecatory behaviour following injury in an animal model. This model of pudendal neuropathy affects continence in 32% of rats and provides a basis for research on interventions for incontinence.

Methods of anorectal manometry vary widely in clinical practice: Results from an international survey.

BACKGROUND: Ano-rectal manometry (ARM) is the most commonly performed investigation for assessment of anorectal dysfunction. Its use is supported by expert consensus documents and international guidelines. Variation in technology, data acquisition, and analysis affect results and clinical interpretation. This study examined variation in ARM between institutions to establish the status of current practice. METHODS: A 50-item web-based questionnaire assessing analysis and interpretation of ARM was distributed by the International Anorectal Physiology Working Group via societies representing practitioners that perform ARM. Study methodology and performance characteristics between institutions were compared. KEY RESULTS: One hundred and seven complete responses were included from 30 countries. Seventy-nine (74%) institutions performed at least two studies per week. Forty-nine centers (47%) applied conventional ARM (≤8 pressure sensors) and 57 (53%) high-resolution ARM (HR-ARM). Specialist centers were most likely to use HR-ARM compared to regional hospitals and office-based practice (63% vs 37%). Most conventional ARM systems used water-perfused technology (34/49); solid-state hardware was more frequently used in centers performing HR-ARM (44/57). All centers evaluated rest and squeeze. There was marked variation in the methods used to report results of maneuvers. No two centers had identical protocols for patient preparation, setup, study, and data interpretation, and no center fully complied with published guidelines. CONCLUSIONS & INFERENCES: There is significant discrepancy in methods for data acquisition, analysis, and interpretation of ARM. This is likely to impact clinical interpretation, transfer of data between institutions, and research collaboration. There is a need for expert international co-operation to standardize ARM.

Systematic review with meta-analysis: effect of fibre supplementation on chronic idiopathic constipation in adults.

BACKGROUND: Chronic idiopathic constipation is a common symptom-based gastrointestinal disorder responsible for a substantial economic health service burden. Current guidelines recommend the use of fibre as a first-line treatment. AIM: To investigate the effect of fibre (including prebiotic) supplementation on global symptom response, stool output, gut microbiota composition and adverse events in adults with chronic idiopathic constipation. METHODS: Medline, EmBase, Web of Science, Scopus and the Cochrane central register of controlled trials were searched through to February 2016. Conference proceedings from 2003 to 2015 were hand-searched. There were no language restrictions. Forest plots with 95% CIs were generated using a random-effects model. RESULTS: The search strategy generated 1072 citations, of which seven individual randomised controlled trials were eligible. Overall, 113 of 147 (77%) patients assigned to fibre responded to therapy, compared with 61 of 140 (44%) allocated to placebo (RR of success to respond 1.71, 95% CI 1.20-2.42, P = 0.003). Fibre significantly increased stool frequency (SMD, standardised mean difference = 0.39; 95% CI 0.03-0.76; P = 0.03) and softened stool consistency (SMD = 0.35; 95% CI 0.04-0.65; P = 0.02) compared with placebo. Flatulence was significantly higher with fibre compared to placebo (SMD 0.56, 0.12-1.00, P = 0.01). Overall quality of evidence was low. CONCLUSIONS: This meta-analysis demonstrates that fibre is moderately effective, but also causes moderate gastrointestinal side effects. However, these findings need to be treated with caution due to a high risk of bias. Accordingly, further large, methodologically rigorous trials are required, before any definitive recommendation regarding its risk-benefit profile can be made. PROSPERO registration number CRD42014007005.

Diagnostic disagreement between tests of evacuatory function: a prospective study of 100 constipated patients.

BACKGROUND: Evacuatory dysfunction (ED) is a common cause of constipation and may be sub-classified on the basis of specialist tests. Such tests may guide treatment e.g., biofeedback therapy for 'functional' defecatory disorders (FDD). However, there is no gold standard, and prior studies have not prospectively and systematically compared all tests that are used to diagnose forms of ED. METHODS: One hundred consecutive patients fulfilling Rome III criteria for functional constipation underwent four tests: expulsion of a rectal balloon distended to 50 mL (BE50 ) or until patients experienced the desire to defecate (BEDDV ), evacuation proctography (EP) and anorectal manometry. Yields and agreements between tests for the diagnosis of ED and FDD were assessed. KEY RESULTS: Positive diagnostic yields for ED were: BEDDV 18%, BE50 31%, EP 38% and anorectal manometry (ARM) 68%. Agreement was substantial between the two balloon tests (k = 0.66), only fair between proctography and BE50 (k = 0.27), poor between manometry and proctography (k = 0.01), and there was no agreement between the balloon tests and manometry (k = -0.07 for both BE50 and BEDDV ). For the diagnosis of FDD, there was only fair agreement between ARM and EP (k = 0.23), ARM ± BE50 and EP (k = 0.18), ARM and EP ± BE50 (k = 0.30) and ARM ± BE50 and EP ± BE50 (k = 0.23). CONCLUSIONS & INFERENCES: There is considerable disagreement between the results of various tests used to diagnose ED and FDD. This highlights the need for a reappraisal of both diagnostic criteria, and what represents the 'gold standard' investigation.

Pathophysiology of fecal incontinence differs between men and women: a case-matched study in 200 patients.

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.

Reversal of sensory deficit through sacral neuromodulation in an animal model of fecal incontinence.

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.

Mechanically evoked cortical potentials: A physiological approach to assessment of anorectal sensory pathways.

BACKGROUND: Normal defaecation involves activation of anorectal mechanoreceptors responsive to pressure and stretch. The aim of this study was to develop selective anal and rectal mucosal light-touch stimulation suitable for measurement of cortical evoked potentials (EPs) in order to explore the sensory arm of these pathways. NEW METHOD: A novel device was manufactured to deliver selective rectal and/or anal light-touch stimulation using a shielded inter-dental brush mounted on a rotating stepper motor (1Hz, 1ms, 15° rotation). Resultant somatosensory EPs recorded with a 32-channel cortical multi-electrode array were compared to those elicited by electrical anorectal stimulation (2mm anal plug electrode [1Hz, 1ms, 10V]). RESULTS: Eighteen anaesthetized female Wistar rats (body mass 180-250g) were studied. Electrical and mechanical stimulation provoked similar maximal response amplitudes (electrical anorectal 39.0µV[SEM 5.5], mechanical anal 42.2µV[8.1], mechanical rectal 45.8µV[9.0]). Response latency was longer following mechanical stimulation (electrical anorectal 8.8ms[0.5], mechanical anal 16.4ms[1.1], mechanical rectal 18.3ms[2.5]). The extent of activated sensory cortex was smaller for mechanical stimulation. Sensory inferior rectal nerve activity was greater during anal compared to rectal mechanical in a subgroup of 4 rats. Evoked potentials were reproducible over 40min in a subgroup of 9 rats. COMPARISON WITH EXISTING METHODS: Cortical EPs are typically recorded in response to non-physiological electrical stimuli. The use of a mechanical stimulus may provide a more localized physiological method of assessment. CONCLUSIONS: To the authors' knowledge these are the first selective brush-elicited anal and rectal EPs recorded in animals and provide a physiological approach to testing of anorectal afferent pathways.

Regional gastrointestinal transit and pH studied in 215 healthy volunteers using the wireless motility capsule: influence of age, gender, study country and testing protocol.

BACKGROUND: The wireless motility capsule (WMC) offers the ability to investigate luminal gastrointestinal (GI) physiology in a minimally invasive manner. AIM: To investigate the effect of testing protocol, gender, age and study country on regional GI transit times and associated pH values using the WMC. METHODS: Regional GI transit times and pH values were determined in 215 healthy volunteers from USA and Sweden studied using the WMC over a 6.5-year period. The effects of test protocol, gender, age and study country were examined. RESULTS: For GI transit times, testing protocol was associated with differences in gastric emptying time (GET; shorter with protocol 2 (motility capsule ingested immediately after meal) vs. protocol 1 (motility capsule immediately before): median difference: 52 min, P = 0.0063) and colonic transit time (CTT; longer with protocol 2: median 140 min, P = 0.0189), but had no overall effect on whole gut transit time. Females had longer GET (by median 17 min, P = 0.0307), and also longer CTT by (104 min, P = 0.0285) and whole gut transit time by (263 min, P = 0.0077). Increasing age was associated with shorter small bowel transit time (P = 0.002), and study country also influenced small bowel and CTTs. Whole gut and CTTs showed clustering of data at values separated by 24 h, suggesting that describing these measures as continuous variables is invalid. Testing protocol, gender and study country also significantly influenced pH values. CONCLUSIONS: Regional GI transit times and pH values, delineated using the wireless motility capsule (WMC), vary based on testing protocol, gender, age and country. Standardisation of testing is crucial for cross-referencing in clinical practice and future research.

The use of colonic and anorectal high-resolution manometry and its place in clinical work and in research.

BACKGROUND: In the esophagus, high-resolution manometry (HRM) has become a standard diagnostic tool in the investigation of suspected motility disorders. However, at the opposite end of the digestive tract (i.e., the colon and anorectum), the use of HRM still remains in its infancy, with relatively few published studies in the scientific literature. Further, the clinical utility of those studies that have been performed is largely undetermined. PURPOSE: This review assesses all of the HRM studies published to date from both the colon and anorectum, explores the catheter types used, and attempts to determine the worth of HRM over traditional 'low-resolution' recordings from the same regions. Ultimately, this review addresses whether HRM currently provides information that will benefit patient diagnosis and treatment.