Attenuation of Colitis-Induced Visceral Hypersensitivity and Pain by Selective Silencing of TRPV1-Expressing Fibers in Rat Colon.

BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) cation channels, expressed on nociceptors, are well established as key contributors to abdominal pain in inflammatory bowel disease (IBD). Previous attempts at blocking these channels have been riddled with side effects. Here, we propose a novel treatment strategy, utilizing the large pore of TRPV1 channels as a drug delivery system to selectively inhibit visceral nociceptors. METHODS: We induced colitis in rats using intrarectal dinitrobenzene sulfonic acid. Visceral hypersensitivity, spontaneous pain, and responsiveness of the hind paws to noxious heat stimuli were examined before and after the intrarectal application of membrane-impermeable sodium channel blocker (QX-314) alone or together with TRPV1 channel activators or blockers. RESULTS: Intrarectal co-application of QX-314 with TRPV1 channel activator capsaicin significantly inhibited colitis-induced gut hypersensitivity. Furthermore, in the model of colitis, but not in naïve rats, QX-314 alone was sufficient to reverse gut hypersensitivity. The blockade of TRPV1 channels prevented this effect of QX-314. Finally, applying QX-314 alone to the inflamed gut inhibited colitis-induced ongoing pain. CONCLUSIONS: Selective silencing of gut nociceptors by a membrane-impermeable sodium channel blocker entering via exogenously or endogenously activated TRPV1 channels diminishes IBD-induced gut hypersensitivity. The lack of effect on naïve rats suggests a selective analgesic effect in the inflamed gut. Our results suggest that in the colitis model, TRPV1 channels are tonically active. Furthermore, our results emphasize the role of TRPV1-expressing nociceptive fibers in colitis-induced pain. These findings provide proof of concept for using charged activity blockers for the blockade of IBD-associated abdominal pain.

Here, we show that the selective silencing of a specific subtype of nociceptive neurons innervating the gut mitigates colitis-induced visceral hypersensitivity and pain. Our results provide a basis for developing effective and selective treatments for inflammatory bowel disease pain.

Faecal incontinence with concurrent disorders of gut-brain interaction: A worse outcome.

BACKGROUND: Faecal incontinence is a common debilitating condition associated with poor quality of life that generates substantial economic strain on healthcare systems. OBJECTIVES: We aimed to evaluate, in a tertiary referral population presenting with faecal incontinence, the impact of suffering additional disorders of gut-brain interaction (DGBI) on symptom severity, anxiety, depression and quality of life. METHODS: Design: Retrospective cohort study. SETTING: Tertiary referral Neurogastroenterology centre. PATIENTS: All patients presenting with faecal incontinence from 2007 to 2020 were included. MAIN OUTCOME MEASURES: The results from structured medical and surgical questionnaires including Rome III Integrative Questionnaire, Faecal Incontinence Severity Index, Hospital Anxiety and Depression Scale, SF-36, and anorectal physiology were analysed using Stata version 17. Patients were categorised into 3 groups: 0-1 additional DGBI, 2 DGBIs, and 3+ DGBI. Statistical significance was defined as p < 0.05 (two-tailed). KEY RESULTS: Faecal incontinence patients (n = 249; mean age 63.4 ± 12.6 years; 93.6% female, 48.1% urge subtype) met diagnostic criteria for mean 2.2 additional DGBI each, mostly affecting bowel (n = 231, 42.4%) and anorectal (n = 150, 27.5%) regions. A greater number of DGBIs was associated with higher faecal incontinence symptom severity (p < 0.001), higher anxiety (p = 0.002) and depression (p = 0.003), and worse quality of life in areas of mental health (p = 0.037) and social effect (p < 0.001). Patients with a greater number of concurrent DGBI demonstrated a greater family history of gastrointestinal problems (p = 0.004). There were no associations found between a greater amount of DGBIs and anorectal physiology. CONCLUSIONS AND INFERENCES: A greater number of additional DGBIs in faecal incontinence patients was associated with worse faecal incontinence symptoms, higher anxiety and depression scores, and worse quality of life but was unrelated to physiology. This highlights the need to proactively search for comorbid DGBI in patients presenting with faecal incontinence.

The patient with obstructed defecatory symptoms: Management differs considerably between physicians and surgeons.

BACKGROUND: Patients with obstructed defecatory symptoms (ODS) are commonly referred to either gastroenterologists (GE) or colorectal surgeons (CS). Further management of these patients may be impacted by this choice of referral. METHODS: An online survey of specialist practice was disseminated to GE and CS in Australia and New Zealand. A case vignette of a patient presenting with ODS was described, with multiple subsequent scenarios designed to delineate the responder's preferred approach to management of this patient. KEY RESULTS: A total of 107 responders participated in the study, 62 CS and 45 GE. For a female patient with ODS not responding to pharmacological treatment, GE were more likely than CS to refer patients for anorectal manometry, while CS were more likely to refer for dynamic imaging. A quarter of CS and GE referred patients directly to pelvic floor physiotherapy, without any pre-treatment testing. Knowing the result of dynamic imaging, especially if a rectocele was demonstrated, substantially influenced management for both of the specialties: GE became more likely to refer the patients for CS consultation and less likely to refer directly for biofeedback or physiotherapy and CS were more likely to opt for an operative pathway over conservative management than they were prior to knowledge of the imaging findings. The majority (>75%) of GE and CS did not find it necessary to obtain a gynecological consultation, even in the presence of a rectocele. CONCLUSIONS & INFERENCES: Practice variation across medical specialties affects diagnostic and management recommendations for patients with ODS, impacting treatment pathways. Our findings provide an incentive toward establishing interdisciplinary, uniform, management guidelines.

Using a footstool does not aid simulated defecation in undifferentiated constipation: A randomized trial.

INTRODUCTION: The use of a footstool has been advocated to optimize posture when sitting on the toilet and thus facilitate bowel evacuation. We aimed to assess the alterations in defecatory posture, and the changes in simulated defecation with use of a footstool in patients with constipation. METHODS: Forty-one patients (female 93%, mean 52 year, SD 14 year) with constipation referred to a tertiary neurogastroenterology unit were enrolled. A bowel questionnaire, Hospital Anxiety and Depression Scale, and Rome questionnaire were administered prior to anorectal manometry. Each patient underwent three rectal balloon expulsion tests in randomized order with no footstool, a 7-inch, and a 9-inch footstool. Additional assessments included angle between spine and femur, and visual analogue scales assessing ease of evacuation, urge to defecate, and discomfort with expulsion. KEY RESULTS: Defecatory posture was significantly altered by footstool use, with progressive narrowing of the angle between the spine and femur as footstool height increased (p < 0.001 for all comparisons). Compared with no footstool, the use of a footstool was not associated with a change in balloon expulsion time and there was no difference between the two footstool heights. Subjectively, no significant change was identified in any of the three perceptions of balloon expulsion between no footstool and footstool use. CONCLUSIONS AND INFERENCES: Although the use of a footstool led to changes in defecatory posture, it did not improve subjective or objective measures of simulated defecation in patients with undifferentiated constipation. Therefore, the recommendation for its use during evacuation cannot be applied to all patients with constipation.

Structural plasticity of axon initial segment in spinal cord neurons underlies inflammatory pain.

ABSTRACT: Physiological or pathology-mediated changes in neuronal activity trigger structural plasticity of the action potential generation site-the axon initial segment (AIS). These changes affect intrinsic neuronal excitability, thus tuning neuronal and overall network output. Using behavioral, immunohistochemical, electrophysiological, and computational approaches, we characterized inflammation-related AIS plasticity in rat's superficial (lamina II) spinal cord dorsal horn (SDH) neurons and established how AIS plasticity regulates the activity of SDH neurons, thus contributing to pain hypersensitivity. We show that in naive conditions, AIS in SDH inhibitory neurons is located closer to the soma than in excitatory neurons. Shortly after inducing inflammation, when the inflammatory hyperalgesia is at its peak, AIS in inhibitory neurons is shifted distally away from the soma. The shift in AIS location is accompanied by the decrease in excitability of SDH inhibitory neurons. These AIS location and excitability changes are selective for inhibitory neurons and reversible. We show that AIS shift back close to the soma, and SDH inhibitory neurons' excitability increases to baseline levels following recovery from inflammatory hyperalgesia. The computational model of SDH inhibitory neurons predicts that the distal shift of AIS is sufficient to decrease the intrinsic excitability of these neurons. Our results provide evidence of inflammatory pain-mediated AIS plasticity in the central nervous system, which differentially affects the excitability of inhibitory SDH neurons and contributes to inflammatory hyperalgesia.

Flatus Incontinence and Fecal Incontinence: A Case-Control Study.

BACKGROUND: Incontinence to gas can be a troublesome symptom impacting quality of life for patients even in the absence of fecal incontinence. Whether isolated flatus incontinence represents part of the spectrum of true fecal incontinence or a separate condition with a different pathophysiology remains unclear. OBJECTIVE: This study aimed to evaluate the clinical features and anorectal physiology in women presenting with severe isolated flatus incontinence compared to women with fecal incontinence and healthy asymptomatic women. DESIGN: This was a retrospective case-control study of prospectively collected data. SETTINGS: Data from participants were obtained from a single tertiary Neurogastroenterology Unit in Sydney, Australia. PATIENTS: Data from 34 patients with severe isolated flatus incontinence, 127 women with fecal incontinence' and 44 healthy women were analyzed. MAIN OUTCOME MEASURES: The primary outcomes were clinical (including demographic, obstetric, and symptom variables) and physiological differences across the 3 groups. RESULTS: Patients with flatus incontinence were significantly younger (mean 39 versus 63 years; p = 0.0001), had a shorter history of experiencing their symptoms ( p = 0.0001), and had harder stool form than patients with fecal incontinence ( p = 0.02). Those with flatus incontinence had an adverse obstetric history and impaired anorectal physiology (motor and sensory, specifically rectal hypersensitivity) but to a lesser extent than patients with fecal incontinence. LIMITATIONS: This study was limited by its retrospective design and modest sample size. CONCLUSIONS: Anorectal physiology was impaired in patients with flatus incontinence compared to healthy controls, but to a lesser extent than in those with fecal incontinence, raising the possibility that flatus incontinence could be a precursor to fecal incontinence. As clinical and physiological findings are different from healthy controls (including the presence of visceral hypersensitivity), isolated flatus incontinence should be considered a distinct clinical entity (like other functional GI disorders), or possibly part of an incontinence spectrum rather than purely a normal phenomenon. See Video Abstract at http://links.lww.com/DCR/B946 . INCONTINENCIA DE FLATOS E INCONTINENCIA FECAL UN ESTUDIO DE CASOS Y CONTROLES: ANTECEDENTES:La incontinencia de gases puede ser un síntoma molesto que afecta la calidad de vida de los pacientes incluso en ausencia de incontinencia fecal. Aún no está claro si la incontinencia de flatos aislada representa parte del espectro de la incontinencia fecal verdadera o una condición separada con una fisiopatología poco clara.OBJETIVO:Evaluar las características clínicas y la fisiología anorrectal en mujeres que presentan incontinencia grave aislada de flatos, en comparación con la incontinencia fecal y mujeres sanas asintomáticas.DISEÑO:Este fue un estudio retrospectivo de casos y controles de datos recolectados prospectivamente.AJUSTE:Los datos de los participantes se obtuvieron de una sola Unidad de Neurogastroenterología terciaria en Sydney, Australia.PACIENTES:Se analizaron los datos de 34 pacientes con incontinencia grave aislada de flatos, junto con 127 mujeres con incontinencia fecal y 44 mujeres sanas.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron clínicos (incluidas las variables demográficas, obstétricas y de síntomas), así como las diferencias fisiológicas entre los tres grupos.RESULTADOS:Los pacientes con incontinencia de flatos eran significativamente más jóvenes (media de 39 años frente a 63 años, p = 0,0001), tenían un historial más corto de experimentar sus síntomas (p = 0,0001) y tenían heces más duras que los pacientes con incontinencia fecal (p = 0,02). Aquellos con incontinencia de flatos tenían antecedentes obstétricos adversos y fisiología anorrectal alterada (motora y sensorial, específicamente hipersensibilidad rectal); aunque en menor medida que las pacientes con incontinencia fecal.LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo y tamaño de muestra modesto.CONCLUSIONES:La fisiología anorrectal se vio afectada en las pacientes con incontinencia de flatos en comparación con las controles sanos, pero en menor medida que en aquellas con incontinencia fecal, lo que plantea la posibilidad de que la incontinencia de flatos pueda ser un precursor de la incontinencia fecal. Dado que los hallazgos clínicos y fisiológicos son diferentes a los de los controles sanos (incluida la presencia de hipersensibilidad visceral), la incontinencia de flatos aislada debe considerarse como una entidad clínica distinta (al igual que otros trastornos gastrointestinales funcionales), o posiblemente como parte de un espectro de incontinencia en lugar de un trastorno puramente a un fenómeno normal. Consulte Video Resumen en http://links.lww.com/DCR/B946 . (Traducción-Dr Yolanda Colorado ).

Experiencing multiple concurrent functional gastrointestinal disorders is associated with greater symptom severity and worse quality of life in chronic constipation and defecation disorders.

BACKGROUND: Recent community-based studies have demonstrated that experiencing multiple concurrent functional gastrointestinal disorders (FGIDs) is associated with increased somatization, worse quality of life (QoL), and greater health care utilization. However, the presence of multiple overlapping FGIDs is unstudied specifically in chronic constipation and functional defecation disorders (FDD). We investigated the prevalence and impact of additional nonconstipation FGIDs on constipation severity, anorectal physiology, anxiety and depression, and QoL, in patients with chronic constipation and FDD. METHODS: One-hundred and forty-six consecutive patients with functional constipation or irritable bowel syndrome (IBS-C/IBS-M) presenting to a tertiary referral Neurogastroenterology Clinic were studied. In addition, 90/146 (62%) qualified for FDD due to abnormal defecatory physiology. Patients underwent comprehensive baseline assessment comprising anorectal physiology, Bristol Stool Chart, Rome questionnaire, Knowles-Eccersley-Scott-Symptom (KESS) constipation score, Hospital Anxiety, and Depression Scale, and modified 36-Item Short Form Health Survey (SF-36) for QoL. Additional FGIDs were diagnosed using Rome III criteria. KEY RESULTS: Additional nonconstipation FGIDs occurred in 85% of patients, with a mean of 2.1 (SD 1.6) additional FGIDs. Patients with four or more additional FGIDs experienced greater constipation severity compared to those with no additional FGIDs (p = 0.004). Comorbid FGIDs were associated with worse SF-36 scores for physical functioning (p < 0.001), role-physical (p = 0.005), bodily pain (p < 0.001), vitality (p = 0.008), social functioning (p = 0.004), and mental health index (p = 0.031). CONCLUSIONS AND INFERENCES: Functional gastrointestinal disorders comorbidity is highly prevalent in chronic constipation and defecatory disorders, and this is associated with greater symptom severity and worse QoL. Multimodal treatments targeting comorbid FGIDs may lead to superior outcomes.

Volumetric Rectal Perception Testing: Is It Clinically Relevant? Results From a Large Patient Cohort.

INTRODUCTION: Rectal perception testing is a recommended component of anorectal physiology testing. Although recent consensus (London) guidelines suggested criteria for categorizing hyporectal and hyper-rectal sensitivity, these were based on scant evidence. Moreover, data regarding diagnostic capabilities and clinical utility of rectal perception testing are lacking. The aims of this study were to determine the association between rectal perception testing and both clinical and physiological variables to enhance the analysis and interpretation of real-life test results. METHODS: Prospectively documented data from 1,618 (92% female) patients referred for anorectal physiology testing were analyzed for 3 rectal perception thresholds (first, urge, and maximal tolerated). Normal values derived from healthy female subjects were used to categorize each threshold into hyposensitive and hypersensitive to examine the clinical relevance of this categorization. RESULTS: There was poor to moderate agreement between the 3 thresholds. Older age, male sex, and constipation were associated with higher perception thresholds, whereas irritable bowel syndrome, fecal incontinence, connective tissue disease, and pelvic radiation were associated with lower perception thresholds to some, but not all, thresholds (P < 0.01 on multivariate analysis for all). The clinical utility and limitations of categorizing thresholds into "hypersensitivity" and "hyposensitivity" were determined. DISCUSSION: Commonly practiced rectal perception testing is correlated with several disease states and thus has clinical relevance. However, most disease states were correlated with 2 or even only 1 abnormal threshold, and agreement between thresholds was limited. This may suggest each threshold measures different pathophysiological pathways. We suggest all 3 thresholds be measured and reported separately in routine clinical testing.

Factors Associated With Response to Anorectal Biofeedback Therapy in Patients With Fecal Incontinence.

BACKGROUND & AIMS: Anorectal biofeedback (BF) is commonly used to treat patients with fecal incontinence (FI), but demand usually exceeds availability. It is therefore important to identify patients most likely to respond to BF treatment. We aimed to identify pre-treatment clinical or physiologic factors that might be used to predict completion and success of BF in women with FI. METHODS: We analyzed data from 400 women with FI (mean age, 61 ± 14 y) undergoing instrumental BF in a tertiary care setting from 2003 through 2016. All patients completed questionnaires before BF, including Rome and the hospital anxiety and depression scale questionnaires. Histories of medication use, surgery, medical conditions, and bowel pattern were recorded, urge was assessed, and patients kept stool diaries. Before and after treatment (6 weekly sessions with a gastroenterologist-supervised nurse specialist, 4 involving instrumented anorectal biofeedback), patients were examined by a physician and fecal incontinence severity index and visual analogue scale scores were recorded. The main outcome measure was response to therapy, defined as improvement of 50% or more in weekly FI episodes at the end of BF compared with before BF. RESULTS: The BF treatment was completed by 363 women (91%); of these, 62 had low baseline symptom frequency (no FI episodes in the 2 weeks before BF). Younger age was associated with failure to complete treatment. Of the 301 patients remaining, 202 patients (67%) had a response to therapy; among these women, urge FI was associated with response at end of BF, but not at follow up (6 months after therapy). Baseline severity of symptom scores and quality of life measures were associated with greater improvement in the same variable at the end of BF and after 6 months. Patients with low baseline symptom frequency improved in all secondary outcome measures, similar to patients with higher baseline symptom frequency. CONCLUSIONS: In an analysis of 363 women with FI, approximately two-thirds had a response to BF treatment. Urge FI was the only baseline variable associated with response. Baseline severity of symptoms and quality of life measures were associated with greater improvement in the same variable, but not overall response. It is therefore a challenge to select treatment for patients with FI.

A novel combined anorectal biofeedback and percutaneous tibial nerve stimulation protocol for treating fecal incontinence.

BACKGROUND/AIMS: Fecal incontinence (FI) is a common, debilitating condition that causes major impact on quality of life for those affected. Non-surgical treatment options include anorectal biofeedback therapy (BF) and percutaneous tibial nerve stimulation (PTNS), usually performed separately. The aims of the current study were to determine the feasibility, tolerability, safety, and efficacy of performing a combined BF and PTNS treatment protocol. METHODS: Female patients with urge FI were offered a novel pilot program combining BF with PTNS. The treatment protocol consisted of 13 weekly sessions: an educational session, followed by 5 combined BF and PTNS sessions, 6 PTNS and a final combined session. Anorectal physiology and clinical outcomes were assessed throughout the program. For efficacy, patients were compared with BF only historical FI patients matched for age, parity, and severity of symptoms. RESULTS: A total of 12/13 (93%) patients completed the full program. Overall attendance rate was 93% (157/169 sessions). Patient comfort score with treatment was rated high at 9.8/10 (SD 0.7) for PTNS and 8.6/10 (SD 1.7) for the BF component. No major side effects were reported. A reduction of at least 50% in FI episodes/week was achieved by 58% of patients by visit 6, and 92% by visit 13. No physiology changes were evident immediately following PTNS compared with before, but pressure during sustained anal squeeze improved by the end of the treatment course. Comparing outcomes with historical matched controls, reductions in weekly FI episodes were more pronounced in the BF only group at visit 6, but not week 13. CONCLUSIONS: In this pilot study, concurrent PTNS and anorectal biofeedback therapy has been shown to be feasible, comfortable, and low risk. The combined protocol is likely to be an effective treatment for FI, but future research could focus on optimizing patient selection.

Anorectal biofeedback: an effective therapy, but can we shorten the course to improve access to treatment?

BACKGROUND: Instrumented anorectal biofeedback (BF) improves symptoms and quality of life in patients with faecal incontinence and defecation disorder-associated chronic constipation. However, demand for BF greatly outweighs availability, so refinement of the BF protocol, in terms of the time and resources required, is of importance. Our aim was to evaluate the outcomes of an abbreviated BF protocol in patients with defecation disorder-associated chronic constipation and/or faecal incontinence compared to standard BF. METHODS: Data were collected from consecutive patients (n = 31; age 54 ± 15; 29 females; 61% functional constipation) undergoing an intentionally abbreviated BF protocol, and compared in a 1:2 ratio with 62 age, gender and functional anorectal disorder-matched control patients undergoing a standard BF. Outcomes included change in symptoms, physiology, patient satisfaction and quality of life. RESULTS: On intention to treat, patients in both protocols showed significant improvement in symptom scores and the magnitude did not differ between groups. Impact on quality of life, satisfaction and control over bowel movements improved in both protocols, but satisfaction improved to a greater extent in the standard BF protocol (p = 0.009). Physiological parameters were unchanged after BF apart from improvement in rectal sensation in the standard BF group compared to abbreviated BF (p ⩽ 0.002). CONCLUSIONS: Abbreviated anorectal BF offered to patients travelling from far away was not different to a standard BF in providing substantial, at least short term, improvements in symptoms of constipation and faecal incontinence, quality of life and feeling of control over bowel movements. Refinement of the standard BF protocol according to individual patient phenotypes and desired outcomes warrants further study in order to maximize efficacy and improve access for patients.

Risk Factors for Low Bone Density in Inflammatory Bowel Disease: Use of Glucocorticoids, Low Body Mass Index, and Smoking.

BACKGROUND: Inflammatory bowel disease (IBD) patients are reported to have lower bone density compared to healthy controls. There is limited consensus regarding factors affecting bone density among these patients. Our aim, therefore, was to determine clinical and genetic variables that contribute to lower bone mineral density (BMD) in IBD patients. METHODS: A cross-sectional study of IBD patients treated in a tertiary referral center was performed. Epidemiological and clinical data were collected, and genetic testing for the common mutations in Nucleotide-binding Oligomerization Domain-containing protein (NOD)2 was performed. We examined correlations between the different variables and BMD in the total hip, femoral neck, and lumbar spine. RESULTS: Eighty-nine patients (49% males, 67 Crohn's disease [CD]) participated in the study. 42Forty-two (63%) of the CD and 13 (59%) of the ulcerative colitis patients met the criteria for osteoporosis/osteopenia. Factors associated with lower Z scores were low body mass index (BMI; r = -0.307, p = 0.005), use of glucocorticoids (likelihood ratio [LR] 5.1, p = 0.028), and a trend for male gender (LR = 3.4, p = 0.079). Among CD patients, low bone density showed borderline significance for association with gastrointestinal surgery (LR = 4.1, p = 0.07) and smoking (LR = 3.58, p = 0.06). Low levels of 25OHD were not associated with low BMD, nor were mutations in NOD2. No increased rate of fractures was seen among patients with osteopenia or osteoporosis. CONCLUSION: In addition to the generally accepted risk factors for osteoporosis (glucocorticoids, low BMI, smoking), male IBD patients had a trend toward lower BMD. Carrying a mutaticon in NOD2 did not confer a risk for bone loss.

Anorectal physiology in health: A randomized trial to determine the optimum catheter for the balloon expulsion test.

BACKGROUND: Anorectal manometry (ARM) and balloon expulsion test (BET) are pivotal in investigation of anorectal disorders. There is controversy, however, about normal values and optimum methodology for performing these tests. Our aims were to compare BET using three different balloons and to establish normal values for ARM and BET in health. METHODS: Forty-four female healthy subjects (mean age 56 ± 12 years) underwent ARM, followed by BET which was performed in a private toilet using three different catheters (party balloon, Foley catheter and a commercially available catheter) in a single-blinded randomized order. Outcome measures were time to balloon expulsion and comprehensive measures of anal sphincter function, the push maneuver and rectal sensation. KEY RESULTS: The Foley catheter took longer to expel compared to both party and commercial balloons (both pairwise P < 0.001) with a wider distribution of results (P < 0.001). Ten of 40 healthy subjects could not expel the Foley catheter within 120 seconds. On ARM, older age was associated with lower resting anal sphincter pressure (ρ = -0.3, P = 0.05) and lower anal squeeze pressure (ρ = -0.3, P = 0.05). Having at least one vaginal delivery (compared to none) was associated with lower anal squeeze pressures (P = 0.03) and a smaller difference between cough and squeeze pressures (P = 0.03). CONCLUSIONS & INFERENCES: A commercial balloon exhibited superior results in vivo compared to the Foley catheter without the concerns of latex allergy and quality control present with the use of a party balloon. Normal values for high-resolution water-perfused manometry have been established and an effect seen for age and parity.

Early histological findings may predict the clinical phenotype in Crohn's colitis.

BACKGROUND AND AIMS: Predicting the clinical course of Crohn's disease (CD) is relevant for treatment selection. Currently, such diagnostic tools are lacking. In a previous pilot study, morphometric tissue image analysis showed promise in predicting the clinical phenotype and need for surgery. In this study, we aimed to validate our previous results on a larger cohort. METHODS: Colonic biopsies from CD patients with colonic or ileocolonic disease and at least five years of post-biopsy clinical follow-up were analyzed. The results were used to predict post-biopsy clinical phenotypes and outcomes. Data analysis was performed using multivariate regression models, discriminant score (DS) computations and Neural Network (NNET). RESULTS: Multivariate analysis of morphometric variables differentiated between B1 and B2 phenotypes (sensitivity 81%, specificity 74%, accuracy on cross-validation 75%; area under the curve (AUC) of 0.74 (CI 0.6-0.84; NNET model sensitivity 87%, specificity 67% on the testing population)). Differentiation between B1 and B3 phenotypes was also possible (sensitivity 69%, specificity 76%, accuracy 70.5% on cross-validation; AUC 0.78 (CI 0.68-0.89); NNET model sensitivity 78%, specificity 77% on the testing population)). Differentiating between B2 and B3 phenotypes was not possible using morphometric variables. Multivariate analysis predicted surgery (sensitivity 67%, specificity 72.5%, accuracy 69%; AUC 0.72 (CI 0.61-0.82); NNET model sensitivity 80%, specificity 91% on the testing population)). CONCLUSIONS: This study validates previous results and suggests that morphometric image analysis of early biopsies from Crohn's colitis patients may contribute to the prediction of future outcomes such as clinical phenotype and surgery. Prospective validation on larger cohorts is still needed.

Novel insights into fecal incontinence in men.

Fecal incontinence (FI) in men is common, yet data on sex differences in clinical features, physiology, and treatment are scarce. Our aim was to provide insights into FI in males compared with females. Prospectively collected data from 73 men and 596 women with FI in a tertiary referral center were analyzed. Anorectal physiology, clinical characteristics, and outcome of instrumented biofeedback (BF) were recorded. Thirty-one men with FI proceeded to BF and were matched with 62 age-matched women with FI who underwent BF. Men with FI had higher resting, squeeze, and cough anal sphincter pressures (P < 0.001) and were more able to hold a sustained squeeze compared with women (P = 0.04). Men with FI had higher rectal pressure and less inadequate rectal pressure on strain and higher sensory thresholds (P < 0.05). Men, but not women, with isolated soiling had higher anal resting and squeeze pressures compared with those with overt FI (P < 0.05). Men were less likely to undergo BF when offered compared with women. Baseline symptom severity did not differ between the groups. In men, the absence of an organic cause for the FI and the presence of overt FI, but not isolated soiling, were correlated with improvement in patient satisfaction following BF. The outcomes of 50% reduction in FI episodes, physician assessment, symptoms, and quality of life scores after BF all significantly improved in men similarly to women. We conclude that men, compared with women, with FI have unique clinical features and physiology and are less likely to have investigations and treatment despite successful outcome with BF. Future studies to customize treatment in males and determine barriers to therapy are warranted. NEW & NOTEWORTHY: Fecal incontinence in men is common, yet data on sex differences in clinical features, physiology, and treatment are scarce. We provide evidence that men, compared with women, with fecal incontinence have unique clinical features and physiology and are less likely to have investigations and treatment despite successful outcome with anorectal biofeedback therapy.

Efficacy of anorectal biofeedback in scleroderma patients with fecal incontinence: a case-control study.

OBJECTIVE: To determine whether anorectal biofeedback therapy can improve the symptoms of fecal incontinence (FI) in patients with scleroderma when compared to patients with functional FI, and also whether there is any effect on anorectal physiology or quality of life (QOL). FI in patients with scleroderma is highly prevalent and is associated with significant loss of QOL. Biofeedback has been proven to be an effective treatment for functional FI, but there are no data to support its use in scleroderma. MATERIALS AND METHODS: 13 consecutive female patients (median age 59, IQR 47-65 years) with scleroderma, and 26 age- and parity-matched female patients with functional FI (disease controls, 2:1), underwent biofeedback therapy for management of FI. Fecal incontinence severity index (FISI), anorectal physiology, feeling of control and QOL were collected before and after 6 weeks of biofeedback therapy, with additional scoring repeated at 6-month follow-up. RESULTS: After biofeedback treatment FISI, feeling of control and QOL significantly improved in both groups (p < 0.005). There was no difference in the degree in improvement in physiology, FISI or QOL between scleroderma patients and functional FI patients. Long-term improvement in FISI and control were seen in both groups and for QOL only in the scleroderma cohort (p < 0.05). CONCLUSIONS: Patients with scleroderma benefit from biofeedback therapy to the same extent as that achieved in patients with functional FI. There are significant improvements in symptoms, physiology and QOL. Biofeedback is an effective, low-risk treatment option in this patient group.