Simultaneous Colonic Pressure Waves in Children and Young Adults with Gastrointestinal Motility Disorders: Artefact or Colonic Physiology?

BACKGROUND: Simultaneous pressure waves (SPW) spanning all recording sites in colonic manometry studies have been described as a potential biomarker of normal gas transit and extrinsic neural reflexes. In pediatric studies utilizing combined antroduodenal and colonic manometry, it was noted that most colonic SPWs appeared to also span all sensors in the gastric and small bowel regions. This suggests that a proportion of colonic SPWs may represent an artefact caused by forces extrinsic to the colon. Our aim was to characterize colonic SPWs and determine how many of these spanned most of the digestive tract. METHODS: In 39 combined high-resolution antroduodenal and colonic manometry traces from 27 pediatric patients, we used our purpose-built software to identify all SPWs that spanned either (i) all recording sites in the digestive tract or (ii) those restricted to the colon. RESULTS: A total of 14,565 SPWs were identified (364 ± 316 SPWs/study), with 14,550 (99.9%) spanning the entire antroduodenal and colonic recording sites. Only 15 SPWs (0.1% of the total) were restricted to the colon (all in one recording). CONCLUSIONS: Based on these findings, we suggest that, in pediatric studies, SPWs should not form part of any diagnostic criteria, as these events appear to be an artefact caused by factors outside the colon (abdominal strain, body motion).

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: A randomized controlled trial.

AIM: The aim was to determine whether specialist-led habit training using Habit Training with Biofeedback (HTBF) is more effective than specialist-led habit training alone (HT) for chronic constipation and whether outcomes of interventions are improved by stratification to HTBF or HT based on diagnosis (functional defaecation disorder vs. no functional defaecation disorder) by radio-physiological investigations (INVEST). METHOD: This was a parallel three-arm randomized single-blinded controlled trial, permitting two randomized comparisons: HTBF versus HT alone; INVEST- versus no-INVEST-guided intervention. The inclusion criteria were age 18-70 years; attending specialist hospitals in England; self-reported constipation for >6 months; refractory to basic treatment. The main exclusions were secondary constipation and previous experience of the trial interventions. The primary outcome was the mean change in Patient Assessment of Constipation Quality of Life score at 6 months on intention to treat. The secondary outcomes were validated disease-specific and psychological questionnaires and cost-effectiveness (based on EQ-5D-5L). RESULTS: In all, 182 patients were randomized 3:3:2 (target 384): HT n = 68; HTBF n = 68; INVEST-guided treatment n = 46. All interventions had similar reductions (improvement) in the primary outcome at 6 months (approximately -0.8 points of a 4-point scale) with no statistically significant difference between HT and HTBF (-0.03 points; 95% CI -0.33 to 0.27; P = 0.85) or INVEST versus no-INVEST (0.22; -0.11 to 0.55; P = 0.19). Secondary outcomes showed a benefit for all interventions with no evidence of greater cost-effectiveness of HTBF or INVEST compared with HT. CONCLUSION: The results of the study at 6 months were inconclusive. However, with the caveat of under-recruitment and further attrition at 6 months, a simple, cheaper approach to intervention may be as clinically effective and more cost-effective than more complex and invasive approaches.

Gastrointestinal Transit Times in Health as Determined Using Ingestible Capsule Systems: A Systematic Review.

BACKGROUND: Ingestible capsule (IC) systems can assess gastrointestinal (GI) transit times as a surrogate for gut motility for extended periods of time within a minimally invasive, radiation-free and ambulatory setting. METHODS: A literature review of IC systems and a systematic review of studies utilizing IC systems to measure GI transit times in healthy volunteers was performed. Screening for eligible studies, data extraction and bias assessments was performed by two reviewers. A narrative synthesis of the results was performed. RESULTS: The literature review identified 23 different IC systems. The systematic review found 6892 records, of which 22 studies were eligible. GI transit time data were available from a total of 1885 healthy volunteers. Overall, seventeen included studies reported gastric emptying time (GET) and small intestinal transit time (SITT). Colonic transit time (CTT) was reported in nine studies and whole gut transit time (WGTT) was reported in eleven studies. GI transit times in the included studies ranged between 0.4 and 15.3 h for GET, 3.3-7 h for SITT, 15.9-28.9 h for CTT and 23.0-37.4 h for WGTT. GI transit times, notably GET, were influenced by the study protocol. CONCLUSIONS: This review provides an up-to-date overview of IC systems and reference ranges for GI transit times. It also highlights the need to standardise protocols to differentiate between normal and pathological function.

The Clinical Impact of Obesity in Patients With Disorders of Defecation: A Cross-Sectional Study of 1,155 Patients.

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

Regional gastrointestinal transit times in patients with chronic pancreatitis.

The mechanisms behind disrupted gastrointestinal (GI) motor function in patients with chronic pancreatitis (CP) have not been fully elucidated. We compared regional transit times in patients with CP to those in healthy controls, and investigated whether they were associated with diabetes mellitus, exocrine dysfunction, opioid treatment or quality of life. Twenty-eight patients with CP and 28 age- and gender-matched healthy controls were included. Regional GI transit times were determined using the 3D-Transit system, which consists of an ingestible electromagnetic capsule and a detector worn in an abdominal belt for 5 days. Exocrine function was assessed using the fecal elastase-1 test, and quality of life was assessed using the European Organization for Research and Treatment of Cancer questionnaire. Transit times were analyzed for associations with diabetes mellitus, exocrine pancreatic insufficiency (EPI), opioid treatment and quality of life. Compared with healthy controls, patients with CP had prolonged transit times in the small intestine (6.6 ±â€…1.8 vs 4.8 ±â€…2.2 hours, P = .006), colon (40 ±â€…23 vs 28 ±â€…26 hours, P = .02), and total GI tract (52 ±â€…26 vs 36 ±â€…26 hours, P = .02). There was no difference in gastric emptying time (4.8 ±â€…5.2 vs 3.1 ±â€…1.3 hours, P = .9). No associations between transit times and diabetes, EPI, or opioid consumption were found (all P > .05). Quality of life and associated functional and symptom subscales were not associated with transit times, except for diarrhea (P = .03). Patients with CP have prolonged small intestinal and colonic transit times. However, these alterations do not seem to be mediated by diabetes, EPI, or opioid consumption.

The impact of almonds and almond processing on gastrointestinal physiology, luminal microbiology, and gastrointestinal symptoms: a randomized controlled trial and mastication study.

BACKGROUND: Almonds contain lipid, fiber, and polyphenols and possess physicochemical properties that affect nutrient bioaccessibility, which are hypothesized to affect gut physiology and microbiota. OBJECTIVES: To investigate the impact of whole almonds and ground almonds (almond flour) on fecal bifidobacteria (primary outcome), gut microbiota composition, and gut transit time. METHODS: Healthy adults (n = 87) participated in a parallel, 3-arm randomized controlled trial. Participants received whole almonds (56 g/d), ground almonds (56 g/d), or an isocaloric control in place of habitual snacks for 4 wk. Gut microbiota composition and diversity (16S rRNA gene sequencing), SCFAs (GC), volatile organic compounds (GC-MS), gut transit time (wireless motility capsule), stool output and gut symptoms (7-d diary) were measured at baseline and endpoint. The impact of almond form on particle size distribution (PSD) and predicted lipid release was measured (n = 31). RESULTS: Modified intention-to-treat analysis was performed on 79 participants. There were no significant differences in mean ± SD abundance of fecal bifidobacteria after consumption of whole almonds (8.7% ± 7.7%), ground almonds (7.8% ± 6.9%), or control (13.0% ± 10.2%; q = 0.613). Consumption of almonds (whole and ground pooled) resulted in higher mean ± SD butyrate (24.1 ± 15.0 µmol/g) than control (18.2 ± 9.1 µmol/g; P = 0.046). There was no effect of almonds on gut microbiota at the phylum level or diversity, gut transit time, stool consistency, or gut symptoms. Almond form (whole compared with ground) had no effect on study outcomes. Ground almonds resulted in significantly smaller PSD and higher mean ± SD predicted lipid release (10.4% ± 1.8%) than whole almonds (9.3% ± 2.0%; P = 0.017). CONCLUSIONS: Almond consumption has limited impact on microbiota composition but increases butyrate in adults, suggesting positive alterations to microbiota functionality. Almonds can be incorporated into the diet to increase fiber consumption without gut symptoms.This trial was registered at clinicaltrials.gov as NCT03581812.

Faecal incontinence in adults.

Faecal incontinence, which is defined by the unintentional loss of solid or liquid stool, has a worldwide prevalence of ≤7% in community-dwelling adults and can markedly impair quality of life. Nonetheless, many patients might not volunteer the symptom owing to embarrassment. Bowel disturbances, particularly diarrhoea, anal sphincter trauma (obstetrical injury or previous surgery), rectal urgency and burden of chronic illness are the main risk factors for faecal incontinence; others include neurological disorders, inflammatory bowel disease and pelvic floor anatomical disturbances. Faecal incontinence is classified by its type (urge, passive or combined), aetiology (anorectal disturbance, bowel symptoms or both) and severity, which is derived from the frequency, volume, consistency and nature (urge or passive) of stool leakage. Guided by the clinical features, diagnostic tests and therapies are implemented stepwise. When simple measures (for example, bowel modifiers such as fibre supplements, laxatives and anti-diarrhoeal agents) fail, anorectal manometry and other tests (endoanal imaging, defecography, rectal compliance and sensation, and anal neurophysiological tests) are performed as necessary. Non-surgical options (diet and lifestyle modification, behavioural measures, including biofeedback therapy, pharmacotherapy for constipation or diarrhoea, and anal or vaginal barrier devices) are often effective, especially in patients with mild faecal incontinence. Thereafter, perianal bulking agents, sacral neuromodulation and other surgeries may be considered when necessary.

Rectal hyposensitivity: a common pathophysiological finding in patients with constipation and associated hypermobile Ehlers-Danlos syndrome.

BACKGROUND AND AIMS: To evaluate symptom presentation and underlying pathophysiology of colonic/anorectal dysfunction in females with functional constipation (FC) and hypermobile Ehlers-Danlos syndrome (hEDS)/hypermobility spectrum disorder (HSD) METHODS: Case-control study of 67 consecutive female patients with an established diagnosis of hEDS/HSD referred to a specialist centre for investigation of FC (Rome III criteria), age-matched (1:2 ratio) to 134 female controls with FC scoring 0 on the validated 5-point joint hypermobility questionnaire. Symptoms and results of colonic/anorectal physiology testing were compared. An independent series of 72 consecutive females with hEDS/HSD, referred to a separate hospital for investigation of FC, was used to validate physiological findings. RESULTS: Females with hEDS/HSD were more likely to report constipation for ≥ 5 years (76.1% vs. 61.2%, p = 0.035), and a greater proportion had a high Cleveland Clinic constipation score (≥12: 97.0% vs. 87.3%; p = 0.027). The proportions with delayed whole-gut transit were similar between groups (35.3% vs. 41.7%; p = 0.462), as were the proportions with functional or structural abnormalities on defaecography (functional: 47.8% vs. 36.6%; p = 0.127; structural: 65.7% vs. 66.4%; p = 0.916). However, rectal hyposensitivity was more common in those with hEDS/HSD (43.3% vs. 20.1%; p = 0.0006); this was confirmed in the validation cohort (rectal hyposensitivity: 45.8%). CONCLUSIONS: Rectal hyposensitivity is a common pathophysiological factor in females with FC and hEDS/HSD as confirmed in two separate cohorts. The rectal hyposensitivity may be due to altered rectal biomechanics/neuronal pathway dysfunction. Management may be better focused on enhancement of sensory perception (e.g., sensory biofeedback).

Abnormal Perception of Urge to Defecate: An Important Pathophysiological Mechanism in Women With Chronic Constipation.

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

Review of the indications, methods, and clinical utility of anorectal manometry and the rectal balloon expulsion test.

BACKGROUND: Anorectal manometry (ARM) comprehensively assesses anorectal sensorimotor functions. PURPOSE: This review examines the indications, techniques, interpretation, strengths, and weaknesses of high-resolution ARM (HR-ARM), 3-dimensional high-resolution anorectal manometry (3D-HR-ARM), and portable ARM, and other assessments (i.e., rectal sensation and rectal balloon expulsion test) that are performed alongside manometry. It is based on a literature search of articles related to ARM in adults. HR-ARM and 3D-HR-ARM are useful for diagnosing defecatory disorders (DD), to identify anorectal sensorimotor dysfunction and guide management in patients with fecal incontinence (FI), constipation, megacolon, and megarectum; and to screen for anorectal structural (e.g., rectal intussusception) abnormalities. The rectal balloon expulsion test is a useful, low-cost, radiation-free, outpatient assessment tool for impaired evacuation that is performed and interpreted in conjunction with ARM. The anorectal function tests should be interpreted with reference to age- and sex-matched normal values, clinical features, and results of other tests. A larger database of technique-specific normal values and newer paradigms of analyzing anorectal pressure profiles will increase the precision and diagnostic utility of HR-ARM for identifying abnormal mechanisms of defecation and continence.

Redundancy in the International Anorectal Physiology Working Group Manometry Protocol: A Diagnostic Accuracy Study in Fecal Incontinence.

BACKGROUND: Anorectal manometry (ARM) is essential for identifying sphincteric dysfunction. The International Anorectal Physiology Working Group (IAPWG) protocol and London Classification provide a standardized format for performing and interpreting ARM. However, there is scant evidence to support timing and number of constituent maneuvers. AIMS: To assess the impact of protocol modification on diagnostic accuracy in patients with fecal incontinence. METHODS: Retrospective analysis of high-resolution ARM recordings from consecutive patients based on the current IAPWG protocol and modifications thereof: (1) baseline rest period (60 vs. 30 vs. 10 s); (2) number of abnormal short squeezes (SS) out of 3 (SS1/SS2/SS3) based on maximal incremental squeeze pressures over 5 s; (3) resting anal pressures (reflecting recovery) at 25-30 versus 15-20 s after SS1. RESULTS: One hundred patients (86 F, median age 55 [IQR: 39-65]; median St. Mark's incontinence score 14 [10-17]) were studied. 26% and 8% had anal hypotonia and hypertonia, respectively. Compared with 60-s resting pressure, measurements had perfect correlation (κ = 1.0) over 30 s, and substantial correlation (κ = 0.85) over 10 s. After SS1, SS2, and SS3, 43%, 49%, and 46% had anal hypocontractility, respectively. Correlation was substantial between SS1 and SS2 (κ = 0.799) and almost perfect between SS2 and SS3 (κ = 0.9). Compared to resting pressure of 5 s before SS1, pressure recordings at 25-30 and 15-20 s after SS1 were significantly correlated. CONCLUSIONS: A 30-s resting anal pressure, analysis of 2 short-squeezes with a 20-s between-maneuver recovery optimizes study duration without compromising diagnostic accuracy. These findings indicate the IAPWG protocol has redundancy.

Understanding the physiology of human defaecation and disorders of continence and evacuation.

The act of defaecation, although a ubiquitous human experience, requires the coordinated actions of the anorectum and colon, pelvic floor musculature, and the enteric, peripheral and central nervous systems. Defaecation is best appreciated through the description of four phases, which are, temporally and physiologically, reasonably discrete. However, given the complexity of this process, it is unsurprising that disorders of defaecation are both common and problematic; almost everyone will experience constipation at some time in their life and many will develop faecal incontinence. A detailed understanding of the normal physiology of defaecation and continence is critical to inform management of disorders of defaecation. During the past decade, there have been major advances in the investigative tools used to assess colonic and anorectal function. This Review details the current understanding of defaecation and continence. This includes an overview of the relevant anatomy and physiology, a description of the four phases of defaecation, and factors influencing defaecation (demographics, stool frequency/consistency, psychobehavioural factors, posture, circadian rhythm, dietary intake and medications). A summary of the known pathophysiology of defaecation disorders including constipation, faecal incontinence and irritable bowel syndrome is also included, as well as considerations for further research in this field.

Clinical Impact of Rectal Hyposensitivity: A Cross-Sectional Study of 2,876 Patients With Refractory Functional Constipation.

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

Tapentadol results in less deterioration of gastrointestinal function and symptoms than standard opioid therapy in healthy male volunteers.

BACKGROUND: Tapentadol is a combined opioid agonist and norepinephrine reuptake inhibitor with fewer gastrointestinal side effects at equianalgesic doses compared with classical strong opioids. Previous studies on tapentadol have included multi-morbid patients in whom confounders exclude detailed assessment of the mechanistic effects and strict comparison with other opioids or placebo. This study aimed at investigating the effects of tapentadol and oxycodone on gastrointestinal motility and gastrointestinal side effects. METHODS: 21 healthy males participated in a randomized, double-blind, placebo-controlled, crossover study. Tapentadol (50 mg twice daily), oxycodone (10 mg twice daily), or placebo tablets were administered for 14 days. Segmental gastrointestinal transit times and colonic motility parameters were measured with electromagnetic capsules. Gastrointestinal side effects were assessed using questionnaires. KEY RESULTS: During dosing with tapentadol, gastrointestinal side effects and motility parameters were on placebo level. Compared with tapentadol, oxycodone increased whole gut transit time by 17.9 hours (p = .015) and rectosigmoid transit time by 6.5 hours (p = .005). Compared with tapentadol, oxycodone also reduced long, fast antegrade colonic movements (p = .001). In comparison with placebo, oxycodone prolonged whole gut transit time by 31.6 hours, (p < .001). Moreover, less long, fast antegrade colonic movements (p = .002) were observed during oxycodone. For oxycodone only, slow colonic movements were associated with gastrointestinal side effects. CONCLUSIONS & INFERENCES: In this mechanistic study, tapentadol caused significantly less colonic dysmotility and gastrointestinal side effects as compared with oxycodone in equianalgesic doses.