Publications by authors named "Adil E Bharucha"

153 Publications

Presentation of the Julius M. Friedenwald Medal to Michael Camilleri, MD, AGAF.

Gastroenterology 2021 Jun;160(7):2563-2571

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

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http://dx.doi.org/10.1053/j.gastro.2021.04.039DOI Listing
June 2021

Relationship between symptoms during a gastric emptying study, daily symptoms and quality of life in patients with diabetes mellitus.

Neurogastroenterol Motil 2021 Apr 8:e14154. Epub 2021 Apr 8.

Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic, Rochester, MN, USA.

Aims: Gastric emptying is of limited utility for predicting the severity of symptoms in patients with diabetes mellitus and gastrointestinal symptoms. We evaluated the extent to which symptoms recorded during a C-spirulina-based gastric emptying breath test (GEBT) or scintigraphy predicting the severity of daily symptoms in diabetes mellitus.

Methods: Gastric emptying, symptoms during a gastric emptying study, either scintigraphy (n = 38) or GEBT (n = 111), and daily gastrointestinal symptoms were evaluated in 149 patients with diabetes mellitus and variably severe gastrointestinal symptoms.

Key Results: Gastric emptying was normal, delayed, and rapid in 37%, 52%, and 9% measured with the GEBT and 55%, 34%, and 11% of patients measured with scintigraphy; differences between GEBT and scintigraphy were not significant. Daily symptoms were moderately severe or more intense in 58% and 21% of patients undergoing scintigraphy and GEBT (P < 0.0001). Symptoms during the GEBT (46%) and emptying t (3%) explained 50% of the variance in daily symptoms in the GEBT group. In the scintigraphy group, symptoms explained 29% of this variance; the t was insignificant. Patients who reported that one or more symptoms were more severe than the others during the GE study were more likely (OR 3.98, 95% CI 2.16, 7.33) to report the same symptom(s) as being the most severe in the daily diary.

Conclusions: Symptoms during a GEBT and to a lesser extent during scintigraphy, but not gastric emptying predict the severity of daily symptoms and may serve as a biomarker in patients with diabetes mellitus.
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http://dx.doi.org/10.1111/nmo.14154DOI Listing
April 2021

Sex- and Gender-Related Differences in Common Functional Gastroenterologic Disorders.

Mayo Clin Proc 2021 04;96(4):1071-1089

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. Electronic address:

Functional gastrointestinal (GI) disorders (FGIDs) result from central and peripheral mechanisms, cause chronic remitting-relapsing symptoms, and are associated with comorbid conditions and impaired quality of life. This article reviews sex- and gender-based differences in the prevalence, pathophysiologic factors, clinical characteristics, and management of functional dyspepsia (FD) and irritable bowel syndrome (IBS) that together affect approximately 1 in 4 people in the United States. These conditions are more common in women. Among patients with IBS, women are more likely to have severe symptoms and coexistent anxiety or depression; constipation or bloating and diarrhea are more common in women and men, respectively, perhaps partly because defecatory disorders, which cause constipation, are more common in women. Current concepts suggest that biological disturbances (eg, persistent mucosal inflammation after acute gastroenteritis) interact with other environmental factors (eg, abuse) and psychological stressors, which influence the brain and gut to alter GI tract motility or sensation, thereby causing symptoms. By comparison to a considerable understanding of sex-based differences in the pathogenesis of visceral hypersensitivity in animal models, we know less about the contribution of these differences to FGID in humans. Slow gastric emptying and colon transit are more common in healthy women than in men, but effects of gonadal hormones on colon transit are less important than in rodents. Although increased visceral sensation partly explains symptoms, the effects of sex on visceral sensation, colonic permeability, and the gut microbiome are less prominent in humans than rodents. Whether sex or gender affects response to medications or behavioral therapy in FD or IBS is unclear because most patients in these studies are women.
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http://dx.doi.org/10.1016/j.mayocp.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075061PMC
April 2021

A comparison of rectoanal pressures during Valsalva maneuver and evacuation uncovers rectoanal discoordination in defecatory disorders.

Neurogastroenterol Motil 2021 Apr 2:e14126. Epub 2021 Apr 2.

Division of Gastroenterology and Hepatology (Drs Srinivasan and Sharma, Ms. Feuerhak, and Dr. Bharucha) and Division of Biomedical Statistics and Informatics (Dr Bailey), Mayo Clinic, Rochester, MN, USA.

Background: It is suggested that patients with defecation disorders (DD) strain excessively or do a Valsalva maneuver (VM) during evacuation, resulting in rectoanal discoordination, which hinders rectal evacuation. However, definitive data are lacking.

Methods: Rectoanal pressures during evacuation and a VM were measured with seated high-resolution manometry (HRM) in 64 healthy and 136 constipated women with a normal (84 women, C-normal) or prolonged (52 women, C-abnormal) balloon expulsion time (BET). The number of abnormal rectoanal parameters during evacuation and the joint distribution of pressures during evacuation and a VM were used to discriminate between controls and C-abnormal BET patients.

Key Results: The peak anal pressure (5 s) during a VM accounted for 0%, 26%, and 49% of the variance in anal pressure during evacuation in healthy women, C-normal BET, and C-abnormal BET. The association between anal pressure during a VM and evacuation was stronger in C-abnormal BET than in healthy women and C-normal BET (p for interaction <0.001). Fifty-eight of 64 controls and 33 of 52 C-abnormal BET patients had no or one abnormal parameter during evacuation; hence, the probability of C-abnormal BET was 33/91 (36%). In patients with no or one abnormal parameter during evacuation, a logistic model based on anal pressures during evacuation and a VM discriminated between controls and patients with C-abnormal BET with a sensitivity and a specificity of 67% and 75%.

Conclusions: Assessment of rectoanal pressures during evacuation and a VM uncovers rectaoanal discoordination and facilitates the diagnosis of DD in selected patients.
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http://dx.doi.org/10.1111/nmo.14126DOI Listing
April 2021

Duodenal mucosal mitochondrial gene expression is associated with delayed gastric emptying in diabetic gastroenteropathy.

JCI Insight 2021 01 25;6(2). Epub 2021 Jan 25.

Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Hindered by a limited understanding of the mechanisms responsible for diabetic gastroenteropathy (DGE), management is symptomatic. We investigated the duodenal mucosal expression of protein-coding genes and microRNAs (miRNA) in DGE and related them to clinical features. The diabetic phenotype, gastric emptying, mRNA, and miRNA expression and ultrastructure of duodenal mucosal biopsies were compared in 39 DGE patients and 21 controls. Among 3175 differentially expressed genes (FDR < 0.05), several mitochondrial DNA-encoded (mtDNA-encoded) genes (12 of 13 protein coding genes involved in oxidative phosphorylation [OXPHOS], both rRNAs and 9 of 22 transfer RNAs) were downregulated; conversely, nuclear DNA-encoded (nDNA-encoded) mitochondrial genes (OXPHOS) were upregulated in DGE. The promoters of differentially expressed genes were enriched in motifs for transcription factors (e.g., NRF1), which regulate mitochondrial biogenesis. Seventeen of 30 differentially expressed miRNAs targeted differentially expressed mitochondrial genes. Mitochondrial density was reduced and correlated with expression of 9 mtDNA OXPHOS genes. Uncovered by principal component (PC) analysis of 70 OXPHOS genes, PC1 was associated with neuropathy (P = 0.01) and delayed gastric emptying (P < 0.05). In DGE, mtDNA- and nDNA-encoded mitochondrial genes are reduced and increased - associated with reduced mitochondrial density, neuropathy, and delayed gastric emptying - and correlated with cognate miRNAs. These findings suggest that mitochondrial disturbances may contribute to delayed gastric emptying in DGE.
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http://dx.doi.org/10.1172/jci.insight.143596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934845PMC
January 2021

A multicenter study of anorectal pressures and rectal sensation measured with portable manometry in healthy women and men.

Neurogastroenterol Motil 2021 Jun 18;33(6):e14067. Epub 2021 Jan 18.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Background: The equipment and methods for performing anorectal manometry and biofeedback therapy are different and not standardized. Normal values are influenced by age and sex. Our aims were to generate reference values, examine effects of gender and age, and compare anorectal pressures measured with diagnostic and biofeedback catheters and a portable manometry system.

Methods: In this multicenter study, anorectal pressures at rest, during squeeze, and evacuation were measured with diagnostic and biofeedback catheters using Mcompass portable device in healthy subjects. Balloon expulsion time and rectal sensation were evaluated. The effects of age and gender were assessed.

Results: The final dataset comprised 108 (74 women) of 124 participants with normal rectal balloon expulsion time (less than 60 s). During squeeze, anal resting pressure increased by approximately twofold in women and threefold in men. During evacuation, anal pressure exceeded rectal pressure in 87 participants (diagnostic catheter). The specific rectoanal pressures (e.g., resting pressure) were significantly correlated and not different between diagnostic and biofeedback catheters. With the diagnostic catheter, the anal squeeze pressure and rectal pressure during evacuation were greater in men than women (p ≤ 0.02). Among women, women aged 50 years and older had lower anal resting pressure; rectal pressure and the rectoanal gradient during evacuation were greater in older than younger women (p ≤ 0.01).

Conclusions: Anal and rectal pressures measured with diagnostic and biofeedback manometry catheters were correlated and not significantly different. Pressures were influenced by age and sex, providing reference values in men and women.
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http://dx.doi.org/10.1111/nmo.14067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169521PMC
June 2021

Translumbosacral Neuromodulation Therapy Is a Promising Option for Fecal Incontinence.

Am J Gastroenterol 2021 01;116(1):80-81

Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.

Abstract: Fecal incontinence is a common symptom that can significantly impair quality of life. The treatment options range from conservative measures (e.g., Kegel exercises, pelvic floor biofeedback therapy, fiber supplementation, or medications) to noninvasive nerve stimulation (e.g., posterior tibial nerve stimulation and transcutaneous tibial nerve stimulation), implanted neurostimulation (i.e., sacral nerve stimulation), perianal injection of dextranomer, and anal sphincteroplasty. In this issue of the journal, a promising, uncontrolled study suggests that noninvasive, repetitive magnetic stimulation of the lumbosacral nerves significantly improved symptoms, increased anal squeeze pressure, and increased rectal compliance in patients with fecal continence. Sham-controlled studies are necessary to confirm these findings.
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http://dx.doi.org/10.14309/ajg.0000000000001069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775327PMC
January 2021

Effects of Diaphragmatic Breathing on the Pathophysiology and Treatment of Upright Gastroesophageal Reflux: A Randomized Controlled Trial.

Am J Gastroenterol 2021 01;116(1):86-94

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Introduction: Uncontrolled results suggest that diaphragmatic breathing (DB) is effective in gastroesophageal reflux disease (GERD) but the mechanism of action and rigor of proof is lacking. This study aimed to determine the effects of DB on reflux, lower esophageal sphincter (LES), and gastric pressures in patients with upright GERD and controls.

Methods: Adult patients with pH proven upright GERD were studied. During a high-resolution impedance manometry, study patients received a standardized pH neutral refluxogenic meal followed by LES challenge maneuvers (Valsalva and abdominal hollowing) while randomized to DB or sham. After that, patients underwent 48 hours of pH-impedance monitoring, with 50% randomization to postprandial DB during the second day.

Results: On examining 23 patients and 10 controls, postprandial gastric pressure was found to be significantly higher in patients compared with that in controls (12 vs 7 mm Hg, P = 0.018). Valsalva maneuver produced reflux in 65.2% of patients compared with 44.4% of controls (P = 0.035). LES increased during the inspiratory portion of DB (42.2 vs 23.1 mm Hg, P < 0.001) in patients and healthy persons. Postprandial DB reduced the number of postprandial reflux events in patients (0.36 vs 2.60, P < 0.001) and healthy subjects (0.00 vs 1.75, P < 0.001) compared with observation. During 48-hour ambulatory study, DB reduced the reflux episodes on day 2 compared with observation on day 1 in both the patient and control groups (P = 0.049). In patients, comparing DB with sham, total acid exposure on day 2 was not different (10.2 ± 7.9 vs 9.4 ± 6.2, P = 0.804). In patients randomized to DB, esophageal acid exposure in a 2-hour window after the standardized meal on day 1 vs day 2 reduced from 11.8% ±6.4 to 5.2% ± 5.1, P = 0.015.

Discussion: In patients with upright GERD, DB reduces the number of postprandial reflux events pressure by increasing the difference between LES and gastric pressure. These data further encourage studying DB as therapy for GERD.
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http://dx.doi.org/10.14309/ajg.0000000000000913DOI Listing
January 2021

Constipation and Fecal Incontinence in the Elderly.

Curr Gastroenterol Rep 2020 Aug 24;22(11):54. Epub 2020 Aug 24.

Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street, Rochester, MN, 55905, USA.

Purpose Of Review: To review the epidemiology, pathogenesis, clinical features, and management of primary constipation and fecal incontinence in the elderly.

Recent Findings: Among elderly people, 6.5%, 1.7%, and 1.1% have functional constipation, constipation-predominant IBS, and opioid-induced constipation. In elderly people, the number of colonic enteric neurons and smooth muscle functions is preserved; decreased cholinergic function with unopposed nitrergic relaxation may explain colonic motor dysfunction. Less physical activity or dietary fiber intake and postmenopausal hormonal therapy are risk factors for fecal incontinence in elderly people. Two thirds of patients with fecal incontinence respond to biofeedback therapy. Used in combination, loperamide and biofeedback therapy are more effective than placebo, education, and biofeedback therapy. Vaginal or anal insert devices are another option. In the elderly, constipation and fecal incontinence are common and often distressing symptoms that can often be managed by addressing bowel disturbances. Selected diagnostic tests, prescription medications, and, infrequently, surgical options should be considered when necessary.
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http://dx.doi.org/10.1007/s11894-020-00791-1DOI Listing
August 2020

A new method for assessing anal distensibility with a barostat and magnetic resonance imaging in healthy and constipated women.

Neurogastroenterol Motil 2021 02 19;33(2):e13972. Epub 2020 Aug 19.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

Objectives: Defecation requires relaxation of the internal and external anal sphincters. High anal resting pressure is associated with painful constipation, defecatory disorders, and increased healthcare utilization in constipated patients; the mechanisms are unclear. Perhaps patients with a high anal resting pressure have a less distensible canal, which impedes defecation.

Methods: In 50 of 64 participants (33 healthy and 17 constipated women), anal pressures and distensibility were measured, respectively, with manometry and balloon distention combined with magnetic resonance imaging; rectal balloon expulsion time (BET) was also studied.

Results: The BET (P = .006) was longer, and the mean (SD) rectoanal pressure gradient (-58[40] vs -34[26] mm Hg, P = .03) was more negative in constipated than healthy women; anal resting pressure was not different. During anal distention, the balloon expanded rapidly at an opening pressure of 49 (18) mm Hg, which was lower (P < .0001) than resting pressure (90 [25] mm Hg). The resting pressure was correlated with the opening pressure (r = 0.57, P < .0001) and inversely (r = -0.38, P = .007) with maximum volume but not with anal distensibility (volume-pressure slope). In healthy women, the difference (opening-resting pressure) was correlated with anal relaxation during evacuation (r = 0.35, P = .04). Anal distensibility and sensory thresholds were not different between constipated and healthy women.

Conclusions: Among healthy and constipated women, a greater anal resting pressure is correlated with greater opening pressure and lower maximum volume during distention, and, hence, provides a surrogate marker of anal distensibility. The difference (opening-resting pressure), which reflects anal relaxation during distention, is correlated with anal relaxation during evacuation. Anal resting pressure and distensibility were comparable in healthy and constipated women.
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http://dx.doi.org/10.1111/nmo.13972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864861PMC
February 2021

Duodenal mucosal secretory disturbances in functional dyspepsia.

Neurogastroenterol Motil 2021 01 9;33(1):e13955. Epub 2020 Aug 9.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

Background: There is increased recognition of duodenal disturbances (inflammation, altered mucosal protein expression, and chemosensitivity) in functional dyspepsia (FD). Besides sensorimotor functions, enteric submucosal neurons also regulate epithelial ion transport. We hypothesized that duodenal mucosal ion transport and expression of associated genes are altered in FD.

Methods: Duodenal mucosal ion transport (basal and acetylcholine- and glucose-evoked changes in short-circuit current [Isc]) and expression of associated genes and regulatory miRNAs were evaluated in 40 FD patients and 24 healthy controls.

Results: Basal Isc (FD: 88.2 [52.6] μA/cm vs healthy: 20.3 [50.2] μA/cm ; P ≤ .0001), acetylcholine-evoked Isc (FD: Emax 50.4 [35.8] μA/cm vs healthy: 16.6 [15] μA/cm ; P ≤ .001), and glucose-evoked Isc responses (FD: E 69.8 [42.1] μA/cm vs healthy: 40.3 [24.6] μA/cm ; P = .02) were greater in FD than in controls. The Emax for glucose was greater in FD patients on selective serotonin reuptake inhibitors. In FD, the mRNA expression of SLC4A7 and SLC4A4, which transport bicarbonate into cells at the basolateral surface, and the apical anion exchanger SLC26A3 were reduced (false discovery rate <0.05), the serotonin receptor HTR4 was increased, and the serotonin transporter SLC6A4 was decreased. Selected miRNAs (hsa-miR-590-3p, hsa-miR-32-5p) that target genes associated with ionic transport were upregulated in FD.

Conclusions: Compared to controls, FD patients had greater baseline and agonist-evoked duodenal mucosal secretory responses. These findings may be explained by reduced gene expression, which would be anticipated to reduce luminal bicarbonate secretion. The upregulated miRNAs may partly explain the downregulation of these genes in FD.
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http://dx.doi.org/10.1111/nmo.13955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772227PMC
January 2021

Improving the utility of high-resolution manometry for the diagnosis of defecatory disorders in women with chronic constipation.

Neurogastroenterol Motil 2020 10 1;32(10):e13910. Epub 2020 Jul 1.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

Background: We compared the utility of existing and modified versions of high-resolution manometry for diagnosing defecatory disorders (DD).

Methods: In 64 healthy and 136 constipated women, we compared left lateral (LL) and seated manometry, and analyzed with existing (ManoView™) and new methods, for discriminating between constipated patients with normal and prolonged rectal balloon expulsion time (BET). In both positions, the rectoanal gradient (RAG) and, for the new analysis, the pressure topography pattern during evacuation were used to discriminate between constipated patients without and with DD.

Key Results: The BET was prolonged, suggestive of a DD, in 52 patients (38%). During evacuation, rectoanal pressures and the RAG were greater in the seated than the LL position (P≤.001). The new analysis identified 4 rectoanal pressure patterns. In the seated position, the BET was associated with the pattern (P=.0001), being prolonged in, respectively, 45%, 15%, 53%, and 0% of patients with minimal change, anal relaxation, paradoxical contraction, and transmission. Within each pattern, the RAG was greater (ie, less negative, P<.0001) in patients with a normal than a prolonged BET. Compared to the ManoView™ RAG in the LL position, the integrated analysis (ie, pattern and new RAG) in the LL position (P<.01) and the seated ManoView™ gradient (P=.02) were more effective for discriminating between constipated patients without and with DD.

Conclusions & Inferences: Anorectal HRM ideally should be performed in the more physiological seated position and analyzed by a two-tier approach, which incorporates the overall pattern followed by the rectoanal gradient. These findings reinforce the utility of manometry for diagnosing DD.
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http://dx.doi.org/10.1111/nmo.13910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529936PMC
October 2020

COVID-19 Ethics and Research.

Mayo Clin Proc 2020 06 24;95(6):1119-1123. Epub 2020 Apr 24.

Department of Cardiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.

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http://dx.doi.org/10.1016/j.mayocp.2020.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180345PMC
June 2020

Epigenetic Alterations Are Associated With Gastric Emptying Disturbances in Diabetes Mellitus.

Clin Transl Gastroenterol 2020 03;11(3):e00136

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Introduction: Epigenetic modifications have been implicated to mediate several complications of diabetes mellitus (DM), especially nephropathy and retinopathy. Our aim was to ascertain whether epigenetic alterations in whole blood discriminate among patients with DM with normal, delayed, and rapid gastric emptying (GE).

Methods: Using the ChIP-seq (chromatin immunoprecipitation combined with next-generation sequencing) assays, we compared the genome-wide enrichment of 3 histone modifications (i.e., H3K4me3, H3K9ac, and H3K27ac) in buffy coats from 20 diabetic patients with gastrointestinal symptoms and normal (n = 6), delayed (n = 8), or rapid (n = 6) GE.

Results: Between patients with DM with delayed vs normal GE, there were 108 and 54 genes that were differentially bound (false discovery rate < 0.05) with H3K27ac and H3K9ac, respectively; 100 genes were differentially bound with H3K9ac in patients with rapid vs normal GE. The differentially bound genes with H3K27ac were functionally linked to the type 2 immune response, particularly Th2 cell activation and function (e.g., CCR3, CRLF2, CXCR4, IL5RA, and IL1RL1) and glucose homeostasis (FBP-1, PDE4A, and CMKLR1). For H3K9ac, the differentially occupied genes were related to T-cell development and function (e.g., ICOS and CCR3) and innate immunity (RELB, CD300LB, and CLEC2D). Compared with normal GE, rapid GE had differential H3K9ac peaks at the promoter site of diverse immunity-related genes (e.g., TNFRSF25 and CXCR4) and genes related to insulin resistance and glucose metabolism. Motif analysis disclosed enrichment of binding sites for transcription factors relevant to the pathogenesis and complications of DM.

Discussion: GE disturbances in DM are associated with epigenetic alterations that pertain to dysimmunity, glucose metabolism, and other complications of DM.
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http://dx.doi.org/10.14309/ctg.0000000000000136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145053PMC
March 2020

Clinical features and disturbances of gastrointestinal transit in patients with rapid gastric emptying.

Neurogastroenterol Motil 2020 04 20;32(4):e13779. Epub 2020 Jan 20.

Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Aims: Some patients with upper gastrointestinal symptoms have rapid gastric emptying (GE). We aimed to compare patients with normal and rapid GE and to identify phenotypes among patients with rapid GE.

Methods: Among 2798 patients who underwent GE scintigraphy, we compared patients with normal and rapid GE and separately, patients with rapid GE at 1 hour (GE1), 2 hours (GE2), or both (GE12).

Results: In 2798 patients, GE was normal (74%), delayed (18%), or rapid (8%). Among 211 patients with rapid GE, patterns were rapid GE1 (48%), 2 hours (17%), or 1 and 2 hours (35%); 42 (20%) had diseases that explain rapid GE. A combination of upper and lower gastrointestinal symptoms (54%) was more common that isolated upper (17%) or lower (28%) gastrointestinal symptoms (P < .001). Constipation was more prevalent in patients with rapid GE 2 (72%) than rapid GE 1 (47%) or rapid GE12 hours (67%) (P < .05). Among 179 diabetes mellitus (DM) patients, 15% had rapid GE, which was not associated with the DM phenotype. By multivariable analysis, insulin therapy (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.15-0.88), and weight loss (OR, 0.10; 95% CI, 0.01-0.78) were associated with a lower risk of rapid than normal GE in DM.

Conclusions: Eight percent of patients undergoing scintigraphy had rapid GE, which is most frequently associated with upper and lower gastrointestinal symptoms; constipation is common. Insulin therapy and weight loss were associated with a lower risk of rapid than normal GE in DM patients.
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http://dx.doi.org/10.1111/nmo.13779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085445PMC
April 2020

Mechanisms, Evaluation, and Management of Chronic Constipation.

Gastroenterology 2020 04 13;158(5):1232-1249.e3. Epub 2020 Jan 13.

Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.

With a worldwide prevalence of 15%, chronic constipation is one of the most frequent gastrointestinal diagnoses made in ambulatory medicine clinics, and is a common source cause for referrals to gastroenterologists and colorectal surgeons in the United States. Symptoms vary among patients; straining, incomplete evacuation, and a sense of anorectal blockage are just as important as decreased stool frequency. Chronic constipation is either a primary disorder (such as normal transit, slow transit, or defecatory disorders) or a secondary one (due to medications or, in rare cases, anatomic alterations). Colonic sensorimotor disturbances and pelvic floor dysfunction (such as defecatory disorders) are the most widely recognized pathogenic mechanisms. Guided by efficacy and cost, management of constipation should begin with dietary fiber supplementation and stimulant and/or osmotic laxatives, as appropriate, followed, if necessary, by intestinal secretagogues and/or prokinetic agents. Peripherally acting μ-opiate antagonists are another option for opioid-induced constipation. Anorectal tests to evaluate for defecatory disorders should be performed in patients who do not respond to over-the-counter agents. Colonic transit, followed if necessary with assessment of colonic motility with manometry and/or a barostat, can identify colonic dysmotility. Defecatory disorders often respond to biofeedback therapy. For specific patients, slow-transit constipation may necessitate a colectomy. No studies have compared inexpensive laxatives with newer drugs with different mechanisms. We review the mechanisms, evaluation, and management of chronic constipation. We discuss the importance of meticulous analyses of patient history and physical examination, advantages and disadvantages of diagnostic testing, guidance for individualized treatment, and management of medically refractory patients.
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http://dx.doi.org/10.1053/j.gastro.2019.12.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573977PMC
April 2020

Association between allelic variants in the glucagon-like peptide 1 and cholecystokinin receptor genes with gastric emptying and glucose tolerance.

Neurogastroenterol Motil 2020 01 5;32(1):e13724. Epub 2019 Nov 5.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background: Nutrient-mediated release of cholecystokinin and glucagon-like peptide-1 (GLP-1) regulates gastric emptying (GE) via duodenogastric feedback mechanisms; GLP-1 also regulates postprandial insulin secretion. Some patients with functional upper gastrointestinal symptoms have impaired glucose tolerance during enteral dextrose infusion. Our hypothesis was that variants in CCK, GLP-1, and TCF7L2 (transcription factor 7-like 2 locus), which is associated with greatest genetic risk for development of type 2 diabetes mellitus, are associated with GE and independently with glucose tolerance. Our aims were to evaluate the associations between these GE, glucose tolerance, and these single nucleotide polymorphisms (SNPs).

Methods: Genetic variants, scintigraphic GE of solids, plasma glucose, insulin, and GLP-1 during enteral dextrose infusion (75gm over 2 hours) were measured. GE and enteral dextrose infusion were, respectively, evaluated in 44 (27 controls and 17 patients with functional dyspepsia or nausea) and 42 (28 controls, 14 patients) participants; of these, 51 participants consented to assessment of SNPs. Four functional SNPs were studied: rs6923761 and rs1042044 at GLP-1 receptor, rs7903146 (TCF7L2), and rs1800857 (CCK receptor).

Key Results: Gastric emptying was normal in 38, rapid in 4, and delayed in two participants; 38 had normal, and four had impaired glucose tolerance. The T allele at rs7903146 (TCF7L2) was non-significantly associated (P = .14) with faster GE. The associations between SNPs and demographic variables, GE t , glucose tolerance and plasma GLP1 levels were not significant.

Conclusions & Inferences: There is a trend toward an association between faster GE and the diabetes-associated allele at rs7903146 in TCF7L2. However, these SNPs were not associated with plasma glucose or GLP1 concentrations during enteral dextrose infusion.
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http://dx.doi.org/10.1111/nmo.13724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923543PMC
January 2020

Utility of the plasma pancreatic polypeptide response to modified sham feeding in diabetic gastroenteropathy and non-ulcer dyspepsia.

Neurogastroenterol Motil 2020 02 22;32(2):e13744. Epub 2019 Oct 22.

Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

Background: The relationship between cardiovascular and gastrointestinal (ie, plasma pancreatic polypeptide [PP] response to modified sham feeding [MSF]) indices of vagal function is unclear. Hyperglycemia inhibits PP secretion via vagally mediated mechanisms. Our aims were to (a) compare the PP response, (b) its relationship with glycemia, and (c) the relationship between PP response to MSF, gastric emptying (GE) of solids, and symptoms during GE study in healthy controls, patients with diabetic gastroenteropathy (DM), and non-ulcer dyspepsia (NUD).

Methods: In 24 healthy controls, 40 DM, and 40 NUD patients, we measured plasma PP concentrations during MSF, cardiovagal functions, GE, and symptoms during a GE study.

Key Results: Baseline PP concentrations were higher in DM than in controls and NUD (P = .01), and in type 2 than in type 1 DM patients (P < .01). The PP increment during MSF was normal (≥20 pg/mL) in 70% of controls, 54% of DM, and 47% of NUD patients. Overall, the PP response and cardiovagal tests were concordant (P = .01). Among patients with a reduced PP increment with MSF, 7/10 of T1DM and 1/7 of T2DM patients had moderate or severe cardiovagal dysfunctions (P < .05). The PP response to MSF was not associated with GE.

Conclusions & Inferences: Up to 30% of healthy controls have a reduced PP increment during MSF, limiting the utility of this test to detect vagal injury. The PP response is more useful when it is normal than abnormal. A reduced PP response is more likely to be associated with cardiovagal dysfunctions in T1DM than in T2DM.
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http://dx.doi.org/10.1111/nmo.13744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994387PMC
February 2020

The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function.

Neurogastroenterol Motil 2020 01 12;32(1):e13679. Epub 2019 Aug 12.

Queen Mary, University of London, London, UK.

Background: This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed.

Methods: Twenty-nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face-to-face and three remote meetings to derive consensus between 2014 and 2018.

Key Recommendations: The IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia.

Conclusions And Inferences: This framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much-needed standardization to these techniques.
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http://dx.doi.org/10.1111/nmo.13679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923590PMC
January 2020

Relationship between symptoms during a gastric emptying study and intestinal chemosensitivity with daily symptoms.

Neurogastroenterol Motil 2019 10 21;31(10):e13686. Epub 2019 Jul 21.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background: Non-ulcer dyspepsia (NUD) is a heterogeneous disorder, which is characterized by upper gastrointestinal symptoms and sensorimotor disturbances, including abnormal gastric emptying (GE) and increased intestinal chemosensitivity, and associated with greater plasma glucagon-like peptide-1 (GLP-1) levels during duodenal lipid infusion. However, the relationship(s) between these disturbances and daily symptoms in NUD is variable. We hypothesize that abnormal GE and symptoms during a GE study and during duodenal lipid infusion are associated with the severity of daily symptoms and that GLP-1 mediates symptoms during duodenal lipid infusion in NUD.

Methods: Gastric emptying of solids, symptoms during the GE study and duodenal lipid infusion, and daily gastrointestinal symptoms (2 week diary) were measured in 24 healthy controls and 40 NUD patients. During duodenal lipid infusion, participants received the GLP-1 antagonist exendin 9-39 or placebo.

Key Results: In controls and patients, GE of solids was normal in 75% and 75%, delayed in 8% and 12.5%, or rapid in 17% and 12.5%, respectively. No controls but 26 patients (65%) had severe symptoms during the GE study. During lipid infusion, gastrointestinal symptoms were greater (P = .001) in patients and not affected by exendin. Symptoms during GE study and lipid infusion accounted for respectively 62% and 37% of variance in daily symptom severity.

Conclusions: In NUD, symptoms during a GE study and to a lesser extent during lipid infusion explain the variance in daily symptoms. Intestinal chemosensitivity is not reduced by GLP-1 antagonist. Assessment of symptoms during a GE study may provide a useful biomarker for NUD in research and clinical practice.
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http://dx.doi.org/10.1111/nmo.13686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746577PMC
October 2019

First translational consensus on terminology and definitions of colonic motility in animals and humans studied by manometric and other techniques.

Nat Rev Gastroenterol Hepatol 2019 09 11;16(9):559-579. Epub 2019 Jul 11.

Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Centre, Amsterdam, Netherlands.

Alterations in colonic motility are implicated in the pathophysiology of bowel disorders, but high-resolution manometry of human colonic motor function has revealed that our knowledge of normal motor patterns is limited. Furthermore, various terminologies and definitions have been used to describe colonic motor patterns in children, adults and animals. An example is the distinction between the high-amplitude propagating contractions in humans and giant contractions in animals. Harmonized terminology and definitions are required that are applicable to the study of colonic motility performed by basic scientists and clinicians, as well as adult and paediatric gastroenterologists. As clinical studies increasingly require adequate animal models to develop and test new therapies, there is a need for rational use of terminology to describe those motor patterns that are equivalent between animals and humans. This Consensus Statement provides the first harmonized interpretation of commonly used terminology to describe colonic motor function and delineates possible similarities between motor patterns observed in animal models and humans in vitro (ex vivo) and in vivo. The consolidated terminology can be an impetus for new research that will considerably improve our understanding of colonic motor function and will facilitate the development and testing of new therapies for colonic motility disorders.
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http://dx.doi.org/10.1038/s41575-019-0167-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136172PMC
September 2019

Diabetic Gastroparesis.

Endocr Rev 2019 10;40(5):1318-1352

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.
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http://dx.doi.org/10.1210/er.2018-00161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736218PMC
October 2019

Chronic Constipation.

Mayo Clin Proc 2019 11 1;94(11):2340-2357. Epub 2019 May 1.

Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Constipation is a common symptom that may be primary (idiopathic or functional) or associated with a number of disorders or medications. Although most constipation is self-managed by patients, 22% seek health care, mostly to primary care physicians (>50%) and gastroenterologists (14%), resulting in large expenditures for diagnostic testing and treatments. There is strong evidence that stimulant and osmotic laxatives, intestinal secretagogues, and peripherally restricted μ-opiate antagonists are effective and safe; the lattermost drugs are a major advance for managing opioid-induced constipation. Constipation that is refractory to available laxatives should be evaluated for defecatory disorders and slow-transit constipation using studies of anorectal function and colonic transit. Defecatory disorders are often responsive to biofeedback therapies, whereas slow-transit constipation may require surgical intervention in selected patients. Both efficacy and cost should guide the choice of treatment for functional constipation and opiate-induced constipation. Currently, no studies have compared inexpensive laxatives with newer drugs that work by other mechanisms.
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http://dx.doi.org/10.1016/j.mayocp.2019.01.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829047PMC
November 2019

Effects of psychosensory stimulation on anal pressures: Effects of alfuzosin.

Neurogastroenterol Motil 2019 07 29;31(7):e13618. Epub 2019 Apr 29.

Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background: Our aim is to explain the lack of clarity in the ways in which anxiety and depression, which are common in defecatory disorders (DD), may contribute to the disorder. In this study, we evaluate the effects of mental stress and relaxation on anal pressures and the mechanisms thereof.

Methods: In 38 healthy women and 36 DD patients, rectoanal pressures were assessed at rest and during mental stressors (ie, word-color conflict [Stroop] and mental arithmetic tests) and mental relaxation, before and after randomization to placebo or the adrenergic α -antagonist alfuzosin.

Key Results: During the baseline Stroop test, the anal pressure increased by 6 ± 13 mm Hg (mean ± SD, P = 0.004) in healthy women and 9 ± 10 mm Hg (P = 0.0001) in constipated women. During mental arithmetic, the anal pressure increased in healthy (4 ± 8 mm Hg, P = 0.002) and constipated women (5 ± 9 mm Hg, P = 0.004). After relaxation, anal pressure declined (P = 0.0004) by 3 ± 4 mm Hg in DD patients but not in controls. Alfuzosin reduced (P = 0.0001) anal resting pressure (by 31 ± 19 mm Hg) vs placebo (16 ± 18 mm Hg). However, during the postdrug Stroop test, anal pressure increased (P = 0.0001) in participants who received alfuzosin but not placebo.

Conclusions & Inferences: In healthy controls and DD patients, mental stressors likely increased anal pressure by contracting the internal anal sphincter; relaxation reduced anal pressure in DD patients. Alfuzosin reduced anal resting pressure but did not block the Stroop-mediated contractile response, which suggests that this response is not entirely mediated by adrenergic α receptors.
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http://dx.doi.org/10.1111/nmo.13618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559834PMC
July 2019

Comparison of changes in rectal area and volume during MR evacuation proctography in healthy and constipated adults.

Neurogastroenterol Motil 2019 07 26;31(7):e13608. Epub 2019 Apr 26.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background: During proctography, rectal emptying is visually estimated by the reduction in rectal area. The correlation between changes in rectal area, which is a surrogate measure of volume, is unclear. Our aims were to compare the change in rectal area and volume during magnetic resonance (MR) proctography and to compare these parameters with rectal balloon expulsion time (BET).

Methods: In 49 healthy and 46 constipated participants, we measured BET and rectal area and volume with a software program before and after participants expelled rectal gel during proctography.

Key Results: All participants completed both tests; six healthy and 17 constipated patients had a prolonged (>60 seconds) BET. During evacuation, the reduction in rectal area and volume was lower in participants with an abnormal than a normal BET (P < 0.01). The reduction in rectal area and volume were strongly correlated (r = 0.93, P < 0.001) and equivalent for identifying participants with abnormal BET. Among participants with less evacuation, the reduction in rectal area underestimated the reduction in rectal volume. A rectocele larger than 2 cm was observed in eight of 18 (44%) participants in whom the difference between change in volume and area was ˃10% but only 14 of 77 (18%) participants in whom the difference was ≤10% (P = 0.03).

Conclusions: Measured with MR proctography, the rectal area is reasonably accurate for quantifying rectal emptying and equivalent to rectal volume for distinguishing between normal and abnormal BET. When evacuation is reduced, the change in rectal area may underestimate the change in rectal volume.
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http://dx.doi.org/10.1111/nmo.13608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559848PMC
July 2019

A Practical Guide to Biofeedback Therapy for Pelvic Floor Disorders.

Curr Gastroenterol Rep 2019 Apr 23;21(5):21. Epub 2019 Apr 23.

Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street, Rochester, MN, 55905, USA.

Purpose Of Review: Biofeedback therapy (BFT) is effective for managing pelvic floor disorders (i.e., defecatory disorders and fecal incontinence). However, even in controlled clinical trials, only approximately 60% of patients with defecatory disorders experienced long-term improvement. The review serves to update practitioners on recent advances and to identify practical obstacles to providing biofeedback therapy.

Recent Findings: The efficacy and safety of biofeedback therapy have been evaluated in defecatory disorders, fecal incontinence, and levator ani syndrome. Recent studies looked at outcomes in specific patient sub-populations and predictors of a response to biofeedback therapy. Biofeedback therapy is effective for managing defecatory disorders, fecal incontinence, and levator ani syndrome. Patients who have a lower bowel satisfaction score and use digital maneuvers fare better. Biofeedback therapy is recommended for patients with fecal incontinence who do not respond to conservative management. A subset of patients with levator ani syndrome who have dyssynergic defecation are more likely to respond to biofeedback therapy.
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http://dx.doi.org/10.1007/s11894-019-0688-3DOI Listing
April 2019

Anorectal pressures measured with high-resolution manometry in healthy people-Normal values and asymptomatic pelvic floor dysfunction.

Neurogastroenterol Motil 2019 07 8;31(7):e13597. Epub 2019 Apr 8.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background: High-resolution manometry (HRM) is used to measure rectoanal pressures in defecatory disorders and fecal incontinence. This study sought to define normal values for rectoanal HRM, ascertain the effects of age and BMI on rectoanal pressures, and compare pressures in asymptomatic women with normal and prolonged balloon expulsion time (BET).

Methods: High-resolution manometry pressures and BET were measured in 163 asymptomatic healthy participants. Women (96) and men (47) with normal BET were used to estimate normal values and the effects of age/BMI on pressures using a Medtronic 4.2-mm-diameter rectoanal catheter.

Key Results: Age is associated with lower resting pressure, higher rectal pressure during evacuation, and a higher rectoanal gradient during evacuation in women and men. In women, the BET is also inversely correlated with age while the BMI is correlated with a higher threshold volume for discomfort and a longer BET. The anal squeeze pressure increment, squeeze duration, and HPZ length are higher in men than women. The rectoanal gradient during evacuation is also lower (ie, more negative) in asymptomatic women with an abnormal than a normal BET.

Conclusions & Inferences: These findings provide an expanded database of normal values for anorectal HRM in men and women. Age and sex affect anal resting and squeeze pressures, respectively; rectal pressure during evacuation is also higher in older people. Less than 15% of asymptomatic people have BET >60 seconds, which is associated with manometry features of impaired evacuation.
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http://dx.doi.org/10.1111/nmo.13597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559859PMC
July 2019

More movement with evaluating colonic transit in humans.

Neurogastroenterol Motil 2019 02;31(2):e13541

Université Paris V René Descartes, Paris, France.

Background: Colonic functions (ie, absorption of fluids and electrolytes, digestion of selected nutrients, harbor for microbes, and elimination of excreta) necessitate complex patterns of storage and transit. Indeed, colonic transit accounts for a major part of the mouth-to-anus transit time. Colonic transit assessments are useful for understanding the pathophysiology of disease, the pharmacodynamic effects of new medications and to diagnose slow transit constipation. Currently, radiopaque markers, scintigraphy, and a colonic pH-pressure capsule are used to measure overall colonic transit. Radioopaque markers, scintigraphy, and the electromagnetic capsule, which is a newer technique, also evaluate regional colonic transit. The pH-pressure capsule also measures colonic pressures. Magnetic resonance imaging and a radio-frequency identification-based device are evolving methods for assessing colonic transit.

Purpose: This mini-review, which accompanies a study evaluating the assessment of colon transit with the electromagnetic capsule, evaluates and compares existing and evolving methods for evaluating colonic transit in humans (Neurogastroenterol Motil. 2018; in press). In addition to overall and regional colonic transit, the electromagnetic capsule evaluates colonic motor patterns without radiation exposure. These patterns are summarized by analyzing the characteristics (ie, distance and velocity) of discrete antegrade and retrograde capsule movements as they travel in the colon. However, the electromagnetic capsule does not measure pressure or colonic wall movement (ie, contractions). The motor patterns identified by this capsule should be compared with motor patterns identified with manometry. The next challenge is to harness different techniques to evaluate the relationships between colonic pressures and transit or, even better, the trifecta of colonic contractions, pressure events, and transit.
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http://dx.doi.org/10.1111/nmo.13541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362846PMC
February 2019

Recent advances in understanding and managing chronic constipation.

F1000Res 2018 15;7. Epub 2018 Oct 15.

Clinical Enteric Neuroscience Translational and Epidemiological Research Program and Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA.

Constipation, a condition characterized by heterogeneous symptoms, is common in Western society. It is associated with reduced physical health, mental health, and social functioning. Because constipation is rarely due to a life-threatening disease (for example, colon cancer), current guidelines recommend empiric therapy. Limited surveys suggest that fewer than half of treated individuals are satisfied with treatment, perhaps because the efficacy of drugs is limited, they are associated with undesirable side effects, or they may not target the underlying pathophysiology. For example, although a substantial proportion of constipated patients have a defecatory disorder that is more appropriately treated with pelvic floor biofeedback therapy than with laxatives, virtually no pharmacological trials formally assessed for anorectal dysfunction. Recent advances in investigational tools have improved our understanding of the physiology and pathophysiology of colonic and defecatory functions. In particular, colonic and anorectal high-resolution manometry are now available. High-resolution anorectal manometry, which is increasingly used in clinical practice, at least in the United States, provides a refined assessment of anorectal pressures and may uncover structural abnormalities. Advances in our understanding of colonic molecular physiology have led to the development of new therapeutic agents (such as secretagogues, pro-kinetics, inhibitors of bile acid transporters and ion exchangers). However, because clinical trials compare these newer agents with placebo, their efficacy relative to traditional laxatives is unknown. This article reviews these physiologic, diagnostic, and therapeutic advances and focuses particularly on newer therapeutic agents.
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http://dx.doi.org/10.12688/f1000research.15900.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192438PMC
March 2019