Small intestinal bacterial overgrowth in diabetic gastroenteropathy.

BACKGROUND: Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test, which may be affected by altered transit in DGE. The risk factors for the consequences of SIBO in DGE are poorly understood. We aimed to evaluate the prevalence of, risk factors for, and gastrointestinal symptoms associated with SIBO in patients with DGE. METHODS: In 75 patients with DGE and dyspepsia, we tested for SIBO (≥105 colony forming units /mL of aerobic and/or anaerobic bacteria in a duodenal aspirate) and assessed gastric emptying (GE) of solids, symptoms during a GE study and during an enteral lipid challenge (300 kcal/2 h), and daily symptoms with a Gastroparesis Cardinal Symptom Index diary for 2 weeks. Symptoms and GE were compared in patients with versus without SIBO. KEY RESULTS: Of 75 patients, 34 (45%) had SIBO, which was not associated with the use of proton pump inhibitors, daily symptoms, GE, or symptoms during a GE study. During enteral lipid challenge, severe nausea (p = 0.006), fullness (p = 0.02) and bloating (p = 0.009) were each associated with SIBO. Twenty patients (59%) with versus 13 (32%) without SIBO had at least one severe symptom during the lipid challenge (p = 0.006). CONCLUSIONS & INFERENCES: Among patients with DGE 45% had SIBO, which was associated with symptoms during enteral lipid challenge but not with delayed GE, symptoms during a GE study, or daily symptoms. Perhaps bacterial products and even fatty acids are recognized by and activate mast cells that drive the increased lipid sensitivity in SIBO.

Defecatory disorders are a common cause of chronic constipation in Parkinson disease.

BACKGROUND AND AIMS: Up to 50% of patients with Parkinson disease have constipation (PD-C), but the prevalence of defecatory disorders caused by rectoanal dyscoordination in PD-C is unknown. We aimed to compare anorectal function of patients with PD-C versus idiopathic chronic constipation (CC). METHODS: Anorectal pressures, rectal sensation, and rectal balloon expulsion time (BET) were measured with high-resolution anorectal manometry (HR-ARM) in patients with PD-C and control patients with CC, matched for age and sex. RESULTS: We identified 97 patients with PD-C and 173 control patients. Eighty-six patients with PD-C (89%) had early PD, and 39 (40%) had a defecatory disorder, manifest by a prolonged rectal balloon expulsion time (37 patients) or a lower rectoanal pressure difference during evacuation (2 patients). PD-C patients with a prolonged BET had a greater anal resting pressure (p = 0.02), a lower rectal pressure increment (p = 0.005), greater anal pressure (p = 0.047), and a lower rectoanal pressure difference during evacuation (p < 0.001). Rectal sensory thresholds were greater in patients with abnormal BET. In the multivariate model comparing CC and PD-C (AUROC = 0.76), PD-C was associated with a lower anal squeeze increment (odds ratio [OR] for PD-C, 0.93 [95% CI, 0.91-0.95]), longer squeeze duration (OR, 1.05 [95% CI, 1.03-1.08]), lower rectal pressure increment (OR per 10 mm Hg, 0.72 [95% CI, 0.66-0.79]), and negative rectoanal gradient during evacuation (OR per 10 mm Hg, 1.16 [95% CI, 1.08-1.26]). CONCLUSIONS: Compared with CC, PD-C was characterized by impaired squeeze pressure, longer squeeze duration, lower increase in rectal pressure, and a more negative rectoanal gradient during evacuation.

Most patients with disorders of gut-brain interaction receive pharmacotherapy with major or moderate drug-gene interactions.

BACKGROUND: How variations predicted by pharmacogenomic testing to alter drug metabolism and therapeutic response affect outcomes for patients with disorders of gut- brain interaction is unclear. AIMS: To assess the prevalence of pharmacogenomics-predicted drug-gene interactions and symptom outcomes for patients with disorders of gut-brain interaction. METHODS: Patients who were treated in our clinical practice for functional dyspepsia/bowel disorder underwent pharmacogenomic testing. The change in symptoms from baseline to 6 months was compared for patients with variations in CYP2D6 and CYP2C19, which metabolize neuromodulators, and SLC6A4, which encodes the sodium- dependent serotonin transporter. RESULTS: At baseline, 79 of 94 participants (84%) had at least one predicted major drug- gene interaction, and all 94 (100%) had at least one predicted moderate interaction. For the 44 participants who completed a survey of their symptoms at 6 months, the mean (SD) irritable bowel syndrome-symptom severity score decreased from 284 (71) at baseline to 231 (95) at 6 months (p < 0.001). Among patients taking selective serotonin reuptake inhibitors, the decrease in symptom severity (p = 0.03) and pain (p = 0.002) scores from baseline to 6 months was greater for patients with a homozygous SLC6A4 long/long genotype (n = 30) (ie, increased serotonin transporter activity) than for patients with homozygous short/short or heterozygous long/short genotypes (n = 64). Symptom outcomes were not affected by CYP2D6 or CYP2C19 variations. CONCLUSIONS: The homozygous SLC6A4 long/long genotype confers better symptom resolution for patients with disorders of gut-brain interaction who take selective serotonin reuptake inhibitors than do the homozygous short/short or heterozygous long/short genotypes.

Global Prevalence of Fecal Incontinence in Community-Dwelling Adults: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Fecal incontinence (FI) can considerably impair quality of life. Through a systematic review and meta-analysis, we sought to determine the global prevalence and geographic distribution of FI and to characterize its relationship with sex and age. METHODS: We searched PubMed, Web of Science, and Cochrane Library databases to identify population-based surveys of the prevalence of FI. RESULTS: Of the 5175 articles identified, the final analysis included 80 studies; the median response rate was 66% (interquartile range [IQR], 54%-74%). Among 548,316 individuals, the pooled global prevalence of FI was 8.0% (95% confidence interval [CI], 6.8%-9.2%); by Rome criteria, it was 5.4% (95% CI, 3.1%-7.7%). FI prevalence was greater for persons aged 60 years and older (9.3%; 95% CI, 6.6%-12.0%) compared with younger persons (4.9%; 95% CI, 2.9%-6.9%) (odds ratio [OR], 1.75; 95% CI, 1.39-2.20), and it was more prevalent among women (9.1%; 95% CI, 7.6%-10.6%) than men (7.4%; 95% CI, 6.0%-8.8%]) (OR, 1.17; 95% CI, 1.06-1.28). The prevalence was highest in Australia and Oceania, followed by North America, Asia, and Europe, but prevalence could not be estimated in Africa and the Middle East. The risk of bias was low, moderate, and high for 19 (24%), 46 (57%), and 15 (19%) studies, respectively. Exclusion of studies with high risk of bias did not affect the prevalence of FI or heterogeneity. In the meta-regression, the high study heterogeneity (I2 = 99.61%) was partly explained by age. CONCLUSIONS: Approximately 1 in 12 adults worldwide have FI. The prevalence is greater among women and older people.

A randomized double-blind trial of clonidine and colesevelam for women with fecal incontinence.

BACKGROUND: Diarrhea and rectal urgency are risk factors for fecal incontinence (FI). The effectiveness of bowel modifiers for improving FI is unclear. METHODS: In this double-blind, parallel-group, randomized trial, women with urge FI were randomly assigned in a 1:1 ratio to a combination of oral clonidine (0.1 mg twice daily) with colesevelam (1875 mg twice daily) or two inert tablets for 4 weeks. The primary outcome was a ≥50% decrease in number of weekly FI episodes. KEY RESULTS: Fifty-six participants were randomly assigned to clonidine-colesevelam (n = 24) or placebo (n = 32); 51 (91%) completed 4 weeks of treatment. At baseline, participants had a mean (SD) of 7.5 (8.2) FI episodes weekly. The primary outcome was met for 13 of 24 participants (54%) treated with clonidine-colesevelam versus 17 of 32 (53%) treated with placebo (p = 0.85). The Bristol stool form score decreased significantly, reflecting more formed stools with clonidine-colesevelam treatment (mean [SD], 4.5 [1.5] to 3.2 [1.5]; p = 0.02) but not with placebo (4.2 [1.9] to 4.1 [1.9]; p = 0.47). The proportion of FI episodes for semiformed stools decreased significantly from a mean (SD) of 76% (8%) to 61% (10%) in the clonidine-colesevelam group (p = 0.007) but not the placebo group (61% [8%] to 67% [8%]; p = 0.76). However, these treatment effects did not differ significantly between groups. Overall, clonidine-colesevelam was well tolerated. CONCLUSIONS AND INFERENCES: Compared with placebo, clonidine-colesevelam did not significantly improve FI despite being associated with more formed stools and fewer FI episodes for semiformed stools.

Hypoxia-Inducible Factor 1α Stabilization Restores Epigenetic Control of Nitric Oxide Synthase 1 Expression and Reverses Gastroparesis in Female Diabetic Mice.

BACKGROUND & AIMS: Although depletion of neuronal nitric oxide synthase (NOS1)-expressing neurons contributes to gastroparesis, stimulating nitrergic signaling is not an effective therapy. We investigated whether hypoxia-inducible factor 1α (HIF1A), which is activated by high O2 consumption in central neurons, is a Nos1 transcription factor in enteric neurons and whether stabilizing HIF1A reverses gastroparesis. METHODS: Mice with streptozotocin-induced diabetes, human and mouse tissues, NOS1+ mouse neuroblastoma cells, and isolated nitrergic neurons were studied. Gastric emptying of solids and volumes were determined by breath test and single-photon emission computed tomography, respectively. Gene expression was analyzed by RNA-sequencing, microarrays, immunoblotting, and immunofluorescence. Epigenetic assays included chromatin immunoprecipitation sequencing (13 targets), chromosome conformation capture sequencing, and reporter assays. Mechanistic studies used Cre-mediated recombination, RNA interference, and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated epigenome editing. RESULTS: HIF1A signaling from physiological intracellular hypoxia was active in mouse and human NOS1+ myenteric neurons but reduced in diabetes. Deleting Hif1a in Nos1-expressing neurons reduced NOS1 protein by 50% to 92% and delayed gastric emptying of solids in female but not male mice. Stabilizing HIF1A with roxadustat (FG-4592), which is approved for human use, restored NOS1 and reversed gastroparesis in female diabetic mice. In nitrergic neurons, HIF1A up-regulated Nos1 transcription by binding and activating proximal and distal cis-regulatory elements, including newly discovered super-enhancers, facilitating RNA polymerase loading and pause-release, and by recruiting cohesin to loop anchors to alter chromosome topology. CONCLUSIONS: Pharmacologic HIF1A stabilization is a novel, translatable approach to restoring nitrergic signaling and treating diabetic gastroparesis. The newly recognized effects of HIF1A on chromosome topology may provide insights into physioxia- and ischemia-related organ function.

Optimizing the Utility of Anorectal Manometry for Diagnosis and Therapy: A Roundtable Review and Recommendations.

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

Defecatory disorders in patients with type 1 diabetes and chronic constipation.

BACKGROUND AND OBJECTIVES: Chronic constipation (CC) may be caused by defecatory disorders (DDs) and associated with reduced rectal sensation. Among patients with type 1 diabetes (T1D) and CC (T1DCC patients), the prevalence of DDs and reduced rectal sensation is unknown. We sought to compare complications of T1D, anorectal dysfunction, and CC symptoms, among T1DCC patients with versus without a DD. METHODS: Anorectal pressures at rest and during squeeze and evacuation, as well as rectal sensation and rectal balloon expulsion time (BET) were measured with high-resolution anorectal manometry in 114 consecutive T1DCC patients. RESULTS: Thirty-seven patients (32%) had prolonged BET, suggestive of a DD. Complications of T1D included peripheral neuropathy (n = 67, 59%), retinopathy (n = 42, 37%), and nephropathy (n = 26, 23%). Among these complications, only retinopathy was associated with, that is, more prevalent in patients with normal (45%) than prolonged BET (19%). Compared with patients with normal BET, patients with prolonged BET had a lower rectal pressure (mean [SD], 32 [23] mm Hg vs. 23 [19] mm Hg, p = 0.03), greater anal pressure (91 [23] mm Hg vs. 68 [36] mm Hg, p < 0.001), and lower rectoanal gradient (-67 [30] mm Hg vs. -36 [32] mm Hg, p < 0.0001) during evacuation. Anal resting pressure and anal squeeze increment were below normal in 14 (13%) and 32 (29%) of patients and one or more rectal sensory thresholds were above normal in 34 (30%) patients; these abnormalities affected similar proportions in the normal and prolonged BET cohorts. CONCLUSIONS: Among T1DCC patients, 37 (32%) had prolonged BET, which was associated with anorectal pressures indicative of a DD but was not associated with reduced rectal sensation, suggesting that DDs are more likely explained by abdomino-anal dyscoordination than visceral disturbance.

Lifelong constipation in Parkinson's disease and other clinically defined alpha-synucleinopathies: A population-based study in Southeast Minnesota.

INTRODUCTION: Epidemiological studies show correlations between constipation and development of Parkinson's disease (PD); however, few studies have explored the association between constipation and dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and multiple system atrophy (MSA). We sought to explore the lifelong association of constipation and PD, DLB, PDD, and MSA (α-Synucleinopathies), compared to age- and sex-matched controls. METHODS: Using the Rochester Epidemiology Project (REP), we established an incident cohort of clinically defined α-synucleinopathies. A movement-disorder specialist reviewed all medical charts to establish clinical diagnoses. RESULTS: We identified 453 incident cases of clinically diagnosed α-synucleinopathies and an identical number of age- and sex-matched controls in Olmsted County (MN), 1991-2010. There were 303 cases of PD; 80, DLB; 54, PDD; and 16, MSA. Approximately 50% of α-synucleinopathies of all types reported constipation, compared to 27% in controls. The earliest pre-motor onset constipation was in DLB (median, 3.76 years prior to α-synucleinopathies motor-symptom onset); latest onset post-motor constipation was in PD (median, 5.15 years after motor-symptom onset). PD also had the highest longstanding constipation rate (18.2%). All α-synucleinopathies had higher odds of constipation compared to controls, except for MSA (p = 0.09), likely due to a limited sample size. CONCLUSION: PD, DLB, and PDD had higher odds of constipation compared to controls; PD had the most widespread onset of lifelong constipation, both longstanding and pre- or post-motor onset symptoms. Our results indicate that constipation rates do not differ among α-synucleinopathies but do differ in terms of temporal onset compared to disease onset.

Effect of endoscopic sleeve gastroplasty on gastric emptying, motility and hormones: a comparative prospective study.

OBJECTIVE: Endoscopic sleeve gastroplasty (ESG) has gained global adoption but our understanding of its mechanism(s) of action and durability of efficacy is limited. We sought to determine changes in gastric emptying (GE), gastric motility (GM), hormones and eating behaviours after ESG. DESIGN: A priori-designed single-centre substudy of a large US randomised clinical trial, adults with obesity were randomised to ESG or lifestyle interventions (LS) alone. We measured GE, hormones and weight loss and assessed eating behaviours. In a subset of ESG patients, we assessed GM. The primary outcome was the change in T1/2 (min) at 3 months, and secondary outcomes were changes in weight, GE, GM, hormones and eating behaviours. We used t-test analyses and regression to determine the association between GE and weight loss. RESULTS: 36 (ESG=18; LS=18) participated in this substudy. Baseline characteristics were similar between the two groups. At 3 months, T1/2 was delayed in the ESG group (n=17) compared with the LS group (n=17) (152.3±47.3 vs 89.1±27.9; p<0.001). At 12 months, T1/2 remained delayed in the ESG group (n=16) vs control group (n=14) (137±37.4 vs 90.1±23.4; p<0.001). Greater delays in GE at 3 months were associated with greater weight loss. GM was preserved and fasting ghrelin, glucagon-like peptide 1 and polypeptide YY significantly increased 18 months after ESG. CONCLUSION: ESG promotes weight loss through several key mechanistic pathways involving GE and hormones while preserving GM. These findings further support clinical adoption of this technique for the management of obesity. TRIAL REGISTRATION NUMBER: NCT03406975.

Higher Cell-Mediated Immune Responses in Patients With Inflammatory Bowel Disease on Anti-TNF Therapy After COVID-19 Vaccination.

BACKGROUND: Some patients with inflammatory bowel disease (IBD) on immunosuppressive therapies may have a blunted response to certain vaccines, including the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines. However, few studies have evaluated the cell-mediated immune response (CMIR), which is critical to host defense after COVID-19 infection. The aim of this study was to evaluate the humoral immune response and CMIR after mRNA COVID-19 vaccination in patients with IBD. METHODS: This prospective study (HERCULES [HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD] study) evaluated humoral immune response and CMIR after completion of 2 doses of mRNA COVID-19 vaccines in 158 IBD patients and 20 healthy control (HC) subjects. The primary outcome was the CMIR to mRNA COVID-19 vaccines in patients with IBD. The secondary outcomes were a comparison of (1) the CMIR in patients with IBD and HC subjects, (2) CMIR and humoral immune response in all participants, and (3) correlation between CMIR and humoral immune response. RESULTS: The majority (89%) of patients with IBD developed a CMIR, which was not different vs HC subjects (94%) (P = .6667). There was no significant difference (P = .5488) in CMIR between immunocompetent (median 255 [interquartile range, 146-958] spike T cells per million peripheral blood mononuclear cells) and immunosuppressed patients (median 377 [interquartile range, 123-1440]). There was no correlation between humoral and cell-mediated immunity after vaccination (P = .5215). In univariable analysis, anti-tumor necrosis factor therapy was associated with a higher CMIRs (P = .02) and confirmed in a multivariable model (P = .02). No other variables were associated with CMIR. CONCLUSIONS: Most patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.

Antibody and T cell responses to coronavirus disease 2019 vaccines in patients with inflammatory bowel disease do not correlate. Most patients with inflammatory bowel disease mount a T cell response despite being on biologic therapies, those on anti-tumor necrosis factor may have a higher T cell response. Anti-tumor necrosis factor therapy has been associated with a lower antibody response to coronavirus disease 2019 vaccines, but the T cell response is augmented.

Imaging Review of Gastrointestinal Motility Disorders.

The motor function of the gastrointestinal tract relies on the enteric nervous system, which includes neurons spanning from the esophagus to the internal anal sphincter. Disorders of gastrointestinal motility arise as a result of disease within the affected portion of the enteric nervous system and may be caused by a wide array of underlying diseases. The etiology of motility disorders may be primary or due to secondary causes related to infection or inflammation, congenital abnormalities, metabolic disturbances, systemic illness, or medication-related side effects. The symptoms of gastrointestinal dysmotility tend to be nonspecific and may cause diagnostic difficulty. Therefore, evaluation of motility disorders requires a combination of clinical, radiologic, and endoscopic or manometric testing. Radiologic studies including fluoroscopy, CT, MRI, and nuclear scintigraphy allow exclusion of alternative pathologic conditions and serve as adjuncts to endoscopy and manometry to determine the appropriate diagnosis. Additionally, radiologist understanding of clinical evaluation of motility disorders is necessary for guiding referring clinicians and appropriately imaging patients. New developments and advances in imaging techniques have allowed improved assessment and diagnosis of motility disorders, which will continue to improve patient treatment options. Online supplemental material is available for this article. ©RSNA, 2022.

Rectocele: Incidental or important? Observe or operate? Contemporary diagnosis and management in the multidisciplinary era.

BACKGROUND: More common in older women than younger women, rectoceles may be secondary to pelvic floor weakness and/or pelvic floor dysfunction with impaired rectal evacuation. Rectoceles may be small (<2 cm), medium (2-4 cm), or large (>4 cm). Arguably, large rectoceles are more likely to be associated with symptoms (e.g., difficult defecation). It can be challenging to ascertain the extent to which a rectocele is secondary to pelvic floor dysfunction and/or whether a rectocele, rather than associated pelvic floor dysfunction, is responsible for symptoms. Surgical repair should be considered when initial treatment measures (e.g., bowel modifying agents and pelvic floor biofeedback therapy) are unsuccessful. PURPOSE: We summarize the clinical features, diagnosis, and management of rectoceles, with an emphasis on outcomes after surgical repair. This review accompanies a retrospective analysis of outcomes after multidisciplinary, transvaginal rectocele repair procedures undertaken by three colorectal surgeons in 215 patients at a large teaching hospital in the UK. A majority of patients had a large rectocele. Some patients also underwent an anterior levatorplasty and/or an enterocele repair. All patients were jointly assessed, and some patients underwent surgery by colorectal and urogynecologic surgeons. In this cohort, the perioperative data, efficacy, and harms outcomes are comparable with historical data predominantly derived from retrospective series in which patients had a good outcome (67%-78%), symptoms of difficult defecation improved (30%-50%), and patients had a recurrent rectocele 2 years after surgery (17%). Building on these data, prospective studies that rigorously evaluate outcomes after surgical repair are necessary.

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.

Comparison of Anorectal Manometry, Rectal Balloon Expulsion Test, and Defecography for Diagnosing Defecatory Disorders.

BACKGROUND & AIMS: The utility of high-resolution anorectal manometry (HR-ARM) for diagnosing defecatory disorders (DDs) is unclear because healthy people may have features of dyssynergia. We aimed to identify objective diagnostic criteria for DD and to ascertain the utility of HR-ARM for diagnosing DD. METHODS: Constipated patients were assessed with HR-ARM and rectal balloon expulsion time (BET), and a subset underwent defecography. Normal values were established by assessing 184 sex-matched healthy individuals. Logistic regression models evaluated the association of abnormal HR-ARM findings with prolonged BET and reduced rectal evacuation (determined by defecography). RESULTS: A total of 474 constipated individuals (420 women) underwent HR-ARM and BET, and 158 underwent defecography. BET was prolonged, suggesting a DD, for 152 patients (32%). Rectal evacuation was lower for patients with prolonged vs normal BET. A lower rectoanal gradient during evacuation, reduced anal squeeze increment, and reduced rectal sensation were independently associated with abnormal BETs; the rectoanal gradient was 36% sensitive and 85% specific for prolonged BET. A lower rectoanal gradient and prolonged BET were independently associated with reduced evacuation. Among constipated patients, the probability of reduced rectal evacuation was 14% when the gradient and BET were both normal, 45% when either was abnormal, and 75% when both variables were abnormal. CONCLUSIONS: HR-ARM, BET, and defecography findings were concordant for constipated patients, and reduced rectoanal gradient was the best HR-ARM predictor of prolonged BET or reduced rectal evacuation. Prolonged BET, reduced gradient, and reduced evacuation each independently supported a diagnosis of DD in constipated patients. We propose the terms probable DD for patients with an isolated abnormal gradient or BET and definite DD for patients with abnormal results from both tests.

Reproducibility of high-resolution manometry among healthy and constipated persons.

BACKGROUND AND AIMS: Although high-resolution manometry (HR_ARM) is commonly used to diagnose defecatory disorders, its intraindividual day-to-day reproducibility is unknown. Since these measurements entail voluntary effort, this study aimed to evaluate the intraindividual day-to-day reproducibility of HR_ARM. METHODS: In 22 healthy women (35 years [14] mean [SD]) and 53 constipated patients (42 years [13], 46 women), the rectal balloon expulsion time (BET), and anorectal pressures were measured with HR_ARM on 2 days separated by a median (interquartile range) of 15 days (11-53) in healthy and 40 days (8-75) in constipated patients. Anorectal pressures were evaluated at rest (20 s), during squeeze, and during evacuation. Rectal sensation was also evaluated in constipated patients. The agreement between both measurements was evaluated with Lin's concordance correlation coefficient (CCC) and other tests. RESULTS: Among constipated patients, the anal resting (mean CCC [95%CI] 0.62 [0.43-0.76]) and squeeze pressures (CCC 0.65 [0.47-0.79]), rectoanal gradient during evacuation (CCC 0.42 [0.17-0.62]), and rectal sensory thresholds (CCC for urgency 0.72 [0.52-0.84]) were concordant. Between days 1 and 2, one or more outcomes, characterized as normal or abnormal, differed in 79% of constipated patients, i.e., anal resting and squeeze pressures, the gradient, and the rectal BET differed in, respectively, 25%, 19%, 36%, and 10% of constipated patients. The rectal BET was prolonged in three healthy persons (both days) and either on 1 day (six patients) or 2 days (33 patients) in constipated patients. CONCLUSIONS: While HR_ARM variables and the BET are reproducible within healthy and constipated persons, the outcome on repeat testing differed in 79% of constipated patients.

Automated extraction of anorectal pressures from high-resolution manometry reports.

BACKGROUND: During high-resolution anorectal manometry (HR_ARM), the raw data are converted into software-derived summary variables (e.g., rectoanal gradient during evacuation) that capture only a snapshot of the data collected during HR_ARM and are less useful than newer indices, which are also derived from the raw data, for diagnosing defecatory disorders (DD). However, it is cumbersome and time-consuming to extract raw data from the program and calculate such indices. This study aimed to devise a user-friendly approach to extract anorectal pressures measured with HR_ARM. METHODS: Anorectal pressures at rest, during anal squeeze, and evacuation were measured with HR_ARM in 180 women, among whom 60 each were healthy, had DD, or fecal incontinence. A reverse engineering approach extracted pressure values from color images in HR_ARM reports. The summary variables generated by the software and a reverse engineering approach were compared with Lin's concordance correlation coefficient (CCC), paired t-tests, and Bland-Altman's tests. RESULTS: Anorectal pressures summarized by the software and a reverse engineering method were highly concordant for anal resting (CCC [95% CI], 0.98 [0.97, 0.99]) and squeeze pressures (0.99 [0.99, 0.99) and the rectoanal gradient during evacuation with an empty (0.98 [0.97, 0.98]) and a filled balloon (0.99 [0.99, 0.99]). For most variables, the paired t and Bland-Altman comparisons were not significant. CONCLUSIONS: Anorectal pressures can be accurately determined from pressure topography images in HR_ARM reports. In future, this reverse engineering approach can be harnessed to compile large HR_ARM datasets across centers and to uncover newer, potentially more useful summary rectoanal pressure variables.