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).

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.

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.

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.

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.

Effects of stimulation frequency and intensity in sacral neuromodulation on anorectal inputs to the somatosensory cortex in an experimental model.

INTRODUCTION: Although sacral neuromodulation (SNM) is an established treatment for faecal incontinence, stimulation parameters have been derived empirically and only one frequency (14 Hz) is employed clinically. The aim of this study was to test a range of stimulation frequencies to establish an optimal frequency of SNM for maximum augmentation of anal canal cortical evoked potentials (EPs) in an animal model. METHODS: In female Wistar rats, anal canal EPs were recorded over the primary somatosensory cortex using a flexible multielectrode array, and the effect of SNM was studied. SNM was applied at 0·1-100 Hz and a frequency response curve plotted. The data were fitted to a quadratic equation. RESULTS: The magnitude of potentiation of anal canal EPs caused by SNM depended significantly on stimulation frequency (P < 0·001). The frequency-potentiation relationship was parabolic in form, with a clear optimum at 2 Hz. The SNM must be applied for at least 3 min. The theoretical maximal potentiation predicted by the model was not found to be statistically different to actual data recorded (P = 0·514-0·814). The response depended on stimulation amplitude in an 'all-or-nothing' fashion. EPs were augmented when the SNM intensity was 0·5 times the motor threshold to tail twitch or greater, but values below this intensity failed to affect the EPs. CONCLUSION: The effect of SNM in this animal model is governed principally by frequency, with an optimum of 2 Hz. If animal data can be translated to humans, optimization of SNM frequency may offer a clinically relevant improvement in the efficacy of SNM. Surgical relevance Sacral neuromodulation (SNM) for faecal incontinence currently employs stimulation parameters that have been derived empirically and may not be optimal. This study used an animal model of SNM and focused on its acute effect on anal canal cortical evoked potentials (EPs). It was found that SNM potentiated EPs, with a clear optimum at a frequency of 2 Hz. If this finding is applicable to the mechanism of action of human SNM, this suggests that there may be a clinically relevant improvement by reducing stimulus frequency from its typical value of 14 Hz to 2 Hz.

Evacuation proctography: a reappraisal of normal variability.

AIM: Interpretation of evacuation proctography (EP) images is reliant on robust normative data. Previous studies of EP in asymptomatic subjects have been methodologically limited. The aim of this study was to provide parameters of normality for both genders using EP. METHOD: Evacuation proctography was prospectively performed on 46 healthy volunteers (28 women). Proctograms were independently analysed by two reviewers. All established and some new variables of defaecatory structure and function were assessed objectively: anorectal dimensions; anorectal angle changes; evacuation time; percentage contrast evacuated; and incidence of rectal wall morphological 'abnormalities'. RESULTS: Normal ranges were calculated for all main variables. Mean end-evacuation time was 88 s (95% CI: 63-113) in male subjects and 128 s (95% CI: 98-158) in female subjects; percentage contrast evacuated was 71% (95% CI: 63-80) in male subjects and 65% (95% CI: 58-72) in female subjects. Twenty-six (93%) of 28 female subjects had a rectocoele with a mean depth of 2.5 cm (upper limit = 3.9 cm). Recto-rectal intussusception was found in nine subjects (approximately 20% of both genders); however, recto-anal intussusception was not observed. Only rectal diameter differed significantly between genders. Qualitatively, three patterns of evacuation were present. CONCLUSION: This study defines normal ranges for anorectal dimensions and parameters of emptying, as well as the incidence and characteristics of rectal-wall 'abnormalities' observed or derived from EP. These ranges can be applied clinically for subsequent disease comparison.

Attitudes of patients with metastatic breast cancer toward research biopsies.

BACKGROUND: Research studies involving human tissue are increasingly common. However, patients' attitudes toward research biopsies are not well characterized, particularly when the biopsies are carried out outside the context of therapeutic trials. PATIENTS AND METHODS: One hundred sixty patients with metastatic breast cancer (MBC) from two academic (n = 80) and two community (n = 80) hospitals completed a 29-item self-administered survey to evaluate their willingness to consider providing research purposes only biopsies (RPOBs) (as a stand-alone procedure) and additional biopsies (ABs) (additional needle passes at the time of a clinically indicated biopsy). RESULTS: Eighty-two (51%) of 160 patients would consider having RPOBs, of which 42 (53%) and 40 (50%) patients were from academic and community hospitals, respectively. Patients who had more prior biopsies were less likely to consider RPOBs (RR = 0.6, 95% CI: 0.4-1.0, P = 0.03). Of 160 patients, 115 (72%) patients would consider having ABs. Of these, 64 (80%) and 51 (64%) patients from academic and community hospitals, respectively, would consider ABs (RR = 1.2, 95% CI: 1.0-1.5, P = 0.03). CONCLUSIONS: Many patients with MBC in both academic and community settings report willingness to consider undergoing biopsies for research. Further research is needed to understand ethical, logistical and provider-based barriers to broader participation in such studies.

Clinical and psychosocial functioning in adolescents and young adults with anorectal malformations and chronic idiopathic constipation.

BACKGROUND: Faecal incontinence (FI) and constipation occur following corrective surgery for anorectal malformations (ARMs) and in children or adults with chronic constipation without a structural birth anomaly (chronic idiopathic constipation, CIC). Such symptoms may have profound effects on quality of life (QoL). This study systematically determined the burden of FI and constipation in these patients in adolescence and early adulthood, and their effect on QoL and psychosocial functioning in comparison with controls. METHODS: Patients with ARMs or CIC were compared with age- and sex-matched controls who had undergone appendicectomy more than 1 year previously and had no ongoing gastrointestinal symptoms. Constipation and FI were evaluated using validated Knowles-Eccersley-Scott Symptom (KESS) and Vaizey scores respectively. Standardized QoL and psychometric tests were performed in all groups. RESULTS: The study included 49 patients with ARMs (30 male, aged 11-28 years), 45 with CIC (32 male, aged 11-30 years) and 39 controls (21 male, aged 11-30 years). The frequency of severe constipation among patients with ARMs was approximately half that seen in the CIC group (19 of 49 versus 31 of 45); however, frequencies of incontinence were similar (22 of 49 versus 21 of 45) (P < 0·001 versus controls for both symptoms). Physical and mental well-being were significantly reduced in both ARM and CIC groups compared with controls (P = 0·001 and P = 0·015 respectively), with generally worse scores among patients with CIC. Both were predicted by gastrointestinal symptom burden (P < 0·001). There were no statistically significant differences in state or trait psychiatric morbidity between groups. CONCLUSION: FI and constipation are major determinants of poor QoL in adolescents and young adults with ARMs and in those with CIC.

The effects of age and childbirth on anal sphincter function and morphology in 999 symptomatic female patients with colorectal dysfunction.

BACKGROUND AND OBJECTIVES: Conflicting data exist on the contributions of advancing age and childbirth on the structure and function of the anal sphincter. This study aimed to examine the relative contributions of age and childbirth in a large cohort of women referred for investigation of symptoms of colorectal dysfunction (fecal incontinence and constipation). SETTING: This study was conducted at a specialist surgical colorectal investigation unit in a university teaching hospital. PATIENTS: Retrospective analysis was performed on prospectively collected demographic, symptom profile, and physiologic data from 3686 female patients. Strict exclusion criteria were applied, leaving 999 patients for univariate, multivariate, and logistic statistical modeling. MAIN OUTCOME MEASURES: The effects of independent variables alone and in combination on anal sphincter pressures (resting and squeeze increment) and the presence of sphincter defects (internal and external) were expressed as regression coefficients and odds ratios. RESULTS: Median age was 42 years (range, 16-88), and parity was 2 (range, 0-11); 16% were nulliparous. Three hundred sixty patients had fecal incontinence, 352 had constipation, and 287 had combined symptoms. Anal resting tone decreased with age by 0.66 cm H2O per year, and by 4.3 cm H2O per birth, and was associated with both internal and external anal sphincter defects (p = 0.0001 for both). Squeeze increment pressures decreased by 0.3 cm H2O per year, and by 3.8 cm H2O per birth; decreased pressures were, however, only significantly associated with external anal sphincter defects (p = 0.0001) as a result of childbirth. Cesarean delivery was protective against both reduced anal pressures and sphincter defects. Pudendal nerve terminal motor latencies increased bilaterally with age and with vaginal delivery; the impact of both was greater on the left nerve. Rectal sensation was unaffected by age or parity. CONCLUSIONS: Aging predominantly affects anal resting pressures; childbirth, particularly instrumental delivery, is detrimental to the structure and function of the external sphincter.

Percutaneous tibial nerve stimulation (PTNS) in females with faecal incontinence: the impact of sphincter morphology and rectal sensation on the clinical outcome.

BACKGROUND: Percutaneous tibial nerve stimulation (PTNS) is an acceptable second line treatment for patients with faecal incontinence (FI) unresponsive to conservative measures. There is however a paucity of data in the literature regarding its efficacy. The aim of this prospective study was to evaluate the efficacy of PTNS in an exclusively female cohort of patients and to identify factors that may predict treatment response. METHOD: A prospective cohort of female patients with FI underwent evaluation of sphincter morphology, anorectal pressures and rectal sensation as part of their physiologic assessment prior to treatment. PTNS was performed according to a specific departmental protocol. The clinical outcomes measured were: (1) Cleveland Clinic incontinence scores, (2) deferment time and (3) weekly incontinence episodes. Outcomes were compared at baseline and following treatment using appropriate statistical tests. Clinical outcomes were correlated with the results of the anorectal physiology testing (i.e. sphincter morphology, rectal sensation). RESULTS: Eighty-eight female patients with a mean age of 58.0 ± 13.6 years were included in the analysis. FI was predominantly a late consequence of obstetric injury. The mean incontinence score improved from 12.2 ± 4.0 at baseline to 9.1 ± 4.6 following treatment (p < 0.0001). Statistically significant improvements were also seen in the median deferment time and median number of weekly incontinence episodes. Sphincter damage and altered rectal sensation did not appear to influence the outcomes. CONCLUSIONS: PTNS is an effective treatment in female patients with FI. Improvements in clinical outcomes were independent of damage to the anal sphincter complex in patients with normal rectal sensation.

Management of idiopathic anal fistula using cross-linked collagen: a prospective phase 1 study.

AIM: Fibrin glue and porcine intestinal submucosa are used in novel sphincter-preserving techniques to heal anal fistulae. However, their success is highly variable and decreases with the length of follow up. The aim of this study was to assess the safety, feasibility and potential efficacy of another novel agent, cross-linked collagen, in two different physical formats, to heal anal fistulae. METHOD: Prospectively recruited patients underwent symptom, continence and anal physiology assessments and magnetic resonance imaging. Patients with secondary tracts or acute sepsis were excluded. At operation, participants were randomized to receiving a solid collagen implant or collagen fibres suspended in fibrin glue. Follow up included repeat symptom, continence and physiological assessments at 3 months, and regular clinical review thereafter. RESULTS: Twenty-nine of 43 entrants were eligible for inclusion. Thirteen patients received the collagen implant, and 16 collagen-fibrin glue. Three months postoperation, no patient experienced acute sepsis or continence disturbance, and sphincter function and integrity were unchanged. At 29 months, 12 of 15 (one lost to follow up) patients treated with collagen-fibrin glue were healed, compared with seven of 13 who received the implant. CONCLUSION: In the short-to-medium term, both techniques are safe and equally effective. The results justify continued research into the use of biomaterials to heal anal fistulae.

Combined vertical reduction rectoplasty and sacral nerve stimulation for rectal evacuatory dysfunction and faecal incontinence associated with previous anorectal malformation.

Functional outcomes following surgery for anorectal malformation are variable, with many children experiencing persisting anorectal dysfunction. We describe a 34-year-old female with previous vestibular fistula who experienced lifelong rectal evacuatory dysfunction and faecal incontinence; she was treated in a two stage process producing efficient defecation and almost total continence.

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.

Importance of extrasphincteric mechanisms in the pathophysiology of faecal incontinence in adults with a history of anorectal anomaly.

BACKGROUND: Although surgery for congenital anorectal anomalies (ARAs) aims to preserve anorectal function, faecal incontinence and constipation often result. Apart from the anal sphincters, continence is dependent on multiple anatomical and physiological factors. The aim of this study was to evaluate adults with a history of ARA to determine the role of such factors in functional outcome. METHODS: The study included 20 consecutive adult patients with faecal incontinence who had undergone anorectal surgery as infants. Comprehensive testing included anal manometry, endoanal ultrasonography, tests of pudendal nerve function and rectal sensory function, evacuation proctography and colonic transit studies. RESULTS: Anal resting tone and squeeze increments were both attenuated in 15 of 19 patients. Integrity of the internal and external anal sphincters was compromised in 16 and 15 of 18 patients respectively. Eleven of 13 had evidence of pudendal neuropathy. Rectal sensation was abnormal in 14 of 18 patients, of whom ten were hypersensitive and four hyposensitive. Rectal evacuation was abnormal in nine of 14. Colonic transit was delayed in five of eight patients with constipation. CONCLUSION: Faecal incontinence in adult patients with ARA is related to various pathophysiologies. Structural integrity of the anal sphincters is a major factor, but extrasphincteric mechanisms, notably rectal sensory function, may be as important.

Normalization of substance P levels in rectal mucosa of patients with faecal incontinence treated successfully by sacral nerve stimulation.

BACKGROUND: Sacral nerve stimulation (SNS) may improve faecal incontinence by modulating rectal sensation. This study measured changes in the peripheral expression of various neural epitopes in response to SNS. METHODS: Rectal mucosal biopsies were taken from 12 patients before and after temporary SNS, and from ten responders at 90 days after permanent stimulation. Sections were immunostained for substance P, transient receptor potential vanilloid (TRPV) 1, vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). Levels were compared with those in nine continent controls. RESULTS: Baseline levels of percentage area immunoreactivities of substance P (median 0.51 (95 per cent confidence interval 0.31 to 0.73) versus 0.13 (0.07 to 0.27) per cent; P < 0.001) and TRPV1 (0.76 (0.41 to 1.11) versus 0.09 (0.04 to 0.14) per cent; P < 0.001), but not of VIP (1.26 (0.37 to 2.15) versus 1.28 (0.39 to 2.17); P = 0.943), were significantly greater than in controls. Successful SNS resulted in a significant decrease in substance P immunostaining after temporary (0.15 (0.06 to 0.51) per cent; P = 0.051) and permanent (0.17 (0 to 0.46) per cent; P = 0.051) stimulation. Immunoreactivity of TRPV1, VIP, CGRP and neural markers showed no qualitative change. CONCLUSION: Patients with faecal incontinence demonstrate normalization of raised rectal mucosal substance P levels following successful SNS.

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.

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 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.