A pharmacological challenge predicts reversible rectal sensorimotor dysfunctions in women with fecal incontinence.

BACKGROUND: In order to understand the pathophysiology of rectal sensorimotor dysfunctions in women with fecal incontinence (FI) and rectal urgency, we evaluated the effects of a muscarinic antagonist and an adrenergic α2 agonist on these parameters. METHODS: Firstly, rectal distensibility and sensation were evaluated with a barostat and sinusoidal oscillation at baseline and after randomization to intravenous saline or atropine in 16 healthy controls and 44 FI patients. Thereafter, FI patients were randomized to placebo or clonidine for 4 wk; rectal compliance and sensation were revaluated thereafter. The effect of atropine and clonidine on rectal functions and the relationship between them were evaluated. RESULTS: At baseline, compared to controls, rectal capacity was lower (P = .03) while the mean pressure (P = .02) and elastance (P = .01) during sinusoidal oscillation were greater, signifying reduced distensibility, in FI. Compared to placebo, atropine increased (P ≤ .02) the heart rate in controls and FI and reduced (P = .03) the variability in rectal pressures during sinusoidal oscillation in controls. Clonidine increased rectal compliance (P = .04) and reduced rectal capacity (P = .03) in FI. The effects of atropine and clonidine on compliance (r = .44, P = .003), capacity (r = .34, P = .02), pressures during sinusoidal oscillation (r = .3, P = .057), pressure (r = .6, P < .0001), and volume sensory thresholds (r = .48, P = .003) were correlated. CONCLUSIONS: The effects of atropine and clonidine on rectal distensibility and sensation were significantly correlated. A preserved response to atropine suggests that reduced rectal distensibility is partly reversible, mediated by cholinergic mechanisms, and may predict the response to clonidine, providing a pharmacological challenge.

Reproducibility of gastric emptying assessed with scintigraphy in patients with upper GI symptoms.

BACKGROUND: The reproducibility of gastric emptying (GE) measured with scintigraphy in patients is poorly understood. Our aims were to assess the intra and inter-individual reproducibility of these parameters in patients with upper gastrointestinal symptoms. METHODS: Sixty patients (21 diabetics, 39 non-diabetics) with upper gastrointestinal symptoms underwent scintigraphic-assessment of GE of a solid meal (296 kcal, 30% fat) over 4 hours on two occasions at an average interval of 15 days. The concordance correlation coefficient (CCC), intra and inter-individual coefficients of variation (COV) of GE endpoints were analyzed. RESULTS: The GE t1/2 was 134 ± 8 minutes (mean ± SEM) for the first and 128 ± 6 minutes for the second study. The mean (95% CI) CCC between the two studies was 0.79 (0.67, 0.87) for GE at 1 hour, 0.83 (0.75, 0.9) for GE at 2 hours, 0.54 (0.34, 0.7) for GE at 4 hours, and 0.79 (0.68, 0.86) for GE t1/2 . However, in 18 of 60 patients (30%), the characterization of GE as normal, delayed, or rapid differed between the first and second studies. For gastric empting t1/2 , the inter-individual coefficients of variation was 40%; the intra-individual COV was 20%, comparable in diabetics and non-diabetics, and greater in patients with rapid (28%) than delayed (18%) or normal GE (12%). CONCLUSIONS & INFERENCES: Among patients with upper gastrointestinal symptoms, GE measured with scintigraphy is relatively reproducible. In 30% of cases, the interpretation was different between the two assessments. Hence, a diagnosis of gastroparesis based on a single study may occasionally be inaccurate.

When all seems lost: management of refractory constipation-Surgery, rectal irrigation, percutaneous endoscopic colostomy, and more.

While the pharmacological armamentarium for chronic constipation has expanded over the past few years, a substantial proportion of constipated patients do not respond to these medications. This review summarizes the pharmacological and behavioral options for managing constipation and details the management of refractory constipation. Refractory constipation is defined as an inadequate improvement in constipation symptoms evaluated with an objective scale despite adequate therapy (ie, pharmacological and/or behavioral) that is based on the underlying pathophysiology of constipation. Minimally invasive (ie, rectal irrigation and percutaneous endoscopic colostomy) and surgical therapies are used to manage refractory constipation. This review appraises these options, and in particular, percutaneous endoscopic colostomy, which as detailed by an article in this issue, is a less invasive option for managing refractory constipation than surgery. While these options benefit some patients, the evidence of the risk: benefit profile for these therapies is limited.

Normal values for assessment of anal sphincter morphology, anorectal motion, and pelvic organ prolapse with MRI in healthy women.

BACKGROUND: Endoanal MRI and MR defecography are used to identify anal sphincter injury and disordered defecation. However, few studies have evaluated findings in asymptomatic healthy people. The effects of BMI and parity on rectoanal motion and evacuation are unknown. METHODS: In 113 asymptomatic females (age 50 ± 17 years, Mean ± SD) without risk factors for anorectal trauma, anal sphincter appearance, anorectal motion, and pelvic organ prolapse were evaluated with MRI. The relationship between age, BMI, and parity and structural findings were evaluated with parametric and non-parametric tests. RESULTS: The anal sphincters and puborectalis appeared normal in over 90% of women. During dynamic MRI, the anorectal angle was 100 ± 1º (Mean ± SEM) at rest, 70 ± 2° at squeeze, and 120 ± 2° during defecation. The change in anorectal angle during squeeze (r = -.25, P < .005), but not during evacuation (r = .13, P = .25) was associated with age. In the multivariable models, BMI (P < .01) and parity (P < .01) were, respectively, independently associated with the intersubject variation in the anorectal angle at rest and the angle change during squeeze. Ten percent or fewer women had had descent of the bladder base or uterus 4 cm or more below the pubococcygeal line or a rectocele measuring 4 cm or larger. Only 5% had a patulous anal canal. CONCLUSIONS: In addition to age, BMI and parity also affect anorectal motion in asymptomatic women. These findings provide age-adjusted normal values for rectoanal anatomy and pelvic floor motion.

Relationship between symptoms and quality of life in fecal incontinence.

BACKGROUND: Most measures of fecal incontinence (FI) severity assess the frequency of solid and liquid FI, but may incorporate other features. We compared two scales-the Fecal Incontinence Severity Score (FISS) and Fecal Incontinence Severity Index (FISI)-to determine which questionnaire and which individual questions predict FI Quality of Life (FIQOL). METHODS: A national sample of American adults completed a health questionnaire, and 234 with monthly FI were selected. Participants completed assessments of FI severity, FIQOL, and somatization. Stepwise linear regression models evaluated whether FISS and FISI total scores, or individual items on the FISS and FISI predicted FIQOL after adjusting for gender, age, income, and somatization (Brief Symptom Inventory-18). KEY RESULTS: Reliable responses were provided by 186. Age was 49 years, and 52% were women. The mean FISS score was 8.4 (95% confidence interval [CI] 8.0-8.9, 13 questions) and mean FISI was 29.9 (95% CI 27.4-32.4, 62 questions), indicating moderate FI severity. The mean FIQOL was 2.6 (95% CI 2.4-2.7, 5 questions). Lower income, greater somatization, and total FISS and FISI scores explained 69% of FIQOL; and total FISS and FISI scores were independent predictors. On the FISS, frequency, amount, and urgency to defecate were independently associated with FIQOL. After adding somatization, all but amount remained significant. For the FISI scale, solid and liquid FI and gas were significant predictors, but adjusting for somatization excluded solid FI. CONCLUSIONS AND INFERENCES: Five variables independently explained FIQOL: overall frequency of FI, frequency of liquid and gas leakage, urgency, and somatization.

Reproducibility of assessing fecal microbiota in chronic constipation.

BACKGROUND: While limited data suggest that the fecal microbiota in healthy people is stable over time, the intraindividual variability of the fecal microbiota in constipated patients is unknown. METHODS: This study evaluated the intraindividual reproducibility of fecal microbiota analyzed with 16S rRNA gene sequencing in two stool samples collected without and after a laxative, respectively, in 25 healthy people and 25 constipated women. Participants completed a food record for 3 d before the stool collection. Colonic transit was measured with scintigraphy. KEY RESULTS: The constipated patients were older (48±15 vs 39±10 y, P=.02) than healthy participants but had a similar BMI. The total daily caloric intake was less (P=.005) in constipated (1265±350 kcal) than healthy participants (1597±402 kcal). Fourteen patients but only two controls (P<.005), had delayed colonic transit. For most measures of alpha (eg, Observed OTU number, Shannon index) and beta diversity (eg, Bray-Curtis dissimilarity, UniFrac, phyla level abundance), the ICCs between two stool samples were high, indicating moderate or strong agreement, and similar in healthy people and constipated patients. The ICC for the weighted UniFrac distance, which is weighted by abundance, was lower than its unweighted counterpart, indicating that the unweighted measure is more robust and reproducible. CONCLUSIONS AND INFERENCES: The intraindividual reproducibility of fecal microbiota in constipated patients is high and comparable to healthy participants. For most purposes, evaluating the fecal microbiota in a single stool sample should generally suffice in adequately powered studies of healthy and constipated patients.

High-resolution anorectal manometry: An expensive hobby or worth every penny?

Introduced approximately 10 years ago, high-resolution manometry catheters have fostered interest in anorectal manometry. This review, which accompanies two articles in this issue of Neurogastroenterology and Motility, reviews the methods, clinical indications, utility, and pitfalls of anorectal manometry and revisits the American Gastroenterological Association (AGA) Medical Position Statement on Anorectal Testing Techniques, which was last published in 1999. High-resolution manometry provides a refined assessment of the anorectal pressure profile, obviates the need for station pull-through maneuvers, and minimizes movement artifacts. In selected cases, this refined assessment may be useful for identifying structural abnormalities or anal weakness. However, many manometry patterns that were previously regarded as abnormal are also observed in a majority of healthy patients, which substantially limits the utility of manometry for identifying defecatory disorders. It is our impression that most conclusions of the AGA medical position statement from 1999 remain valid today. High-resolution techniques have not substantially affected the number of publications on or management of anorectal disorders. The ongoing efforts of an international working group to standardize techniques for anorectal manometry are welcome. Although high-resolution manometry is more than an expensive hobby, improvements in catheter design and further research to rigorously define and evaluate these techniques are necessary to determine if they are worth every penny.

Assessing the colonic microbiome, hydrogenogenic and hydrogenotrophic genes, transit and breath methane in constipation.

BACKGROUND: Differences in the gut microbiota and breath methane production have been observed in chronic constipation, but the relationship between colonic microbiota, transit, and breath tests remains unclear. METHODS: In 25 healthy and 25 constipated females we evaluated the sigmoid colonic mucosal and fecal microbiota using 16S rRNA gene sequencing, abundance of hydrogenogenic FeFe (FeFe-hydA) and hydrogenotrophic (methyl coenzyme M reductase A [mrcA] and dissimilatory sulfite reductase A [dsrA]) genes with real-time qPCR assays, breath hydrogen and methane levels after oral lactulose, and colonic transit with scintigraphy. KEY RESULTS: Breath hydrogen and methane were not correlated with constipation, slow colon transit, or with abundance of corresponding genes. After adjusting for colonic transit, the abundance of FeFehydA, dsrA, and mcrA were greater (P<.005) in colonic mucosa, but not stool, of constipated patients. The abundance of the selected functional gene targets also correlated with that of selected taxa. The colonic mucosal abundance of FeFe-hydA, but not mcrA, correlated positively (P<.05) with breath methane production, slow colonic transit, and overall microbiome composition. In the colonic mucosa and feces, the abundance of hydrogenogenic and hydrogenotrophic genes were positively correlated (P<.05). Breath methane production was not associated with constipation or colonic transit. CONCLUSIONS & INFERENCES: Corroborating our earlier findings with 16S rRNA genes, colonic mucosal but not fecal hydrogenogenic and hydrogenotrophic genes were more abundant in constipated vs. healthy subjects independent of colonic transit. Breath gases do not directly reflect the abundance of target genes contributing to their production.

Reproducibility of high-definition (3D) manometry and its agreement with high-resolution (2D) manometry in women with fecal incontinence.

BACKGROUND: While widely used in clinical practice, the reproducibility of high-definition anorectal manometry (HD-ARM) remains unclear. We evaluated the intra-individual reproducibility of HD-ARM and compared pressures measured with HD-ARM and high-resolution anorectal manometry (HR-ARM). METHODS: Thirty-six women with fecal incontinence had an initial HD-ARM (HD-ARM1); on the same day, after randomization, 21 had a second (HD-ARM2). Sixteen women had a third (HD-ARM3) 4 weeks later. Twenty-five had also been evaluated by HR-ARM previously. Rectoanal pressures were assessed at rest, during squeeze and simulated evacuation. Concordance among pressures was assessed with Lin's concordance correlation coefficient (CCC). KEY RESULTS: Anal resting and squeeze pressures measured with HD-ARM were reproducible on the same and different days; for average resting pressures of HD-ARM1 vs HD-ARM2, CCC = 0.73 (95% confidence interval [CI]: 0.53-0.94), and for HD-ARM1 vs HD-ARM3, CCC = 0.60 (95% CI: 0.28-0.93). For maximum squeeze pressures of HD-ARM1 vs HD-ARM2, CCC = 0.86 (95% CI: 0.75-0.97), and for HD-ARM1 vs HD-ARM3, CCC = 0.56 (95% CI: 0.21-0.91). The rectoanal gradient during evacuation was significantly concordant between HD-ARM1 and HD-ARM2 but not HD-ARM1 and HD-ARM3. Resting (CCC = 0.38 [95% CI: 0.14-0.62]) and squeeze pressures (CCC = 0.73 [95% CI: 0.57-0.89]) measured with HD-ARM1 and HR-ARM were also concordant. CONCLUSIONS & INFERENCES: Among women with fecal incontinence, measurements with HD-ARM were reproducible on the same (anal resting and squeeze pressures and rectoanal gradient during evacuation) and different days (anal resting and squeeze pressures) and correlated with HR-ARM measurements. These findings support use of HD-ARM and HR-ARM for longitudinal assessments of anal resting and squeeze pressures.

Effects of hemin on heme oxygenase-1, gastric emptying, and symptoms in diabetic gastroparesis.

BACKGROUND: Therapeutic options for management of diabetic gastroparesis are limited. Failure to maintain upregulation of heme oxygenase (HO1) leads to loss of interstitial cells of Cajal and delayed gastric emptying (GE) in non-obese diabetic mice. Our hypothesis was that hemin upregulation of HO1 would restore normal GE in humans with gastroparesis. AIMS: To compare effects of hemin and placebo infusions on HO1 activity and protein, GE, autonomic function, and gastrointestinal symptoms in diabetic gastroparesis. METHODS: In a single-center, double-blind, placebo-controlled, randomized clinical trial, we compared intravenous hemin, prepared in albumin, or albumin alone (placebo) in 20 patients, aged 41 ± 5 (SEM) years with diabetic gastroparesis. After infusions on days 1, 3, and 7, weekly infusions were administered for 7 additional weeks. Assessments included blood tests for HO1 protein and enzyme activity levels, GE with 13 C-spirulina breath test, autonomic functions (baseline and end), and gastrointestinal symptoms every 2 weeks. KEY RESULTS: Nine of 11 patients randomized to hemin completed all study procedures. Compared to placebo, hemin increased HO1 protein on days 3 (p = 0.0002) and 7 (p = 0.008) and HO1 activity on day 3 (p = 0.0003) but not after. Gastric emptying, autonomic functions, and symptoms did not differ significantly in the hemin group relative to placebo. CONCLUSIONS & INFERENCES: Hemin failed to sustain increased HO1 levels beyond a week and did not improve GE or symptoms in diabetic gastroparesis. Further studies are necessary to ascertain whether more frequent hemin infusions or other drugs would have a more sustained effect on HO1 and improve GE.

The incidence rate and characteristics of clinically diagnosed defecatory disorders in the community.

BACKGROUND: Defecatory disorders (DD) are defined by clinical and objective features of impaired rectal evacuation. The epidemiology of DD in the population is unknown, partly because many constipated patients do not undergo anorectal tests. Our objectives were to estimate the incidence rate and clinical features of DD in the community. METHODS: We reviewed the medical records of all patients older than 16 years in Olmsted County, MN, who had constipation and underwent anorectal manometry from 1999 through 2008. Criteria for diagnosing DD were constipation for 6 months or longer and one of the following: (i) abnormal rectal balloon expulsion test; (ii) reduced or increased perineal descent; or (iii) two or more abnormal features with defecography or surface electromyography. KEY RESULTS: Of 11 112 constipated patients, 516 had undergone anorectal tests; 245 of these (209 women, 36 men) had a DD. The mean (±SD) age at diagnosis was 44 years (±18) among women and 49 years (±19) among men. The overall age- and sex-adjusted incidence rate per 100 000 person-years was 19.3 (95% CI: 16.8-21.8). The age-adjusted incidence per 100 000 person-years was greater (p < 0.0001) in women (31.8, 95% CI: 27.4-36.1) than in men (6.6, 95% CI: 4.4-8.9). Prior to the diagnosis of DD, nearly 30% of patients had irritable bowel syndrome (IBS), 48% had a psychiatric diagnosis, 18% had a history of abuse, and 21% reported urinary and/or fecal incontinence. CONCLUSIONS & INFERENCES: Among constipated patients, DD are fourfold more common in women than men and often associated with IBS and psychiatric diagnoses.

Diagnostic disagreement between tests of evacuatory function: a prospective study of 100 constipated patients.

BACKGROUND: Evacuatory dysfunction (ED) is a common cause of constipation and may be sub-classified on the basis of specialist tests. Such tests may guide treatment e.g., biofeedback therapy for 'functional' defecatory disorders (FDD). However, there is no gold standard, and prior studies have not prospectively and systematically compared all tests that are used to diagnose forms of ED. METHODS: One hundred consecutive patients fulfilling Rome III criteria for functional constipation underwent four tests: expulsion of a rectal balloon distended to 50 mL (BE50 ) or until patients experienced the desire to defecate (BEDDV ), evacuation proctography (EP) and anorectal manometry. Yields and agreements between tests for the diagnosis of ED and FDD were assessed. KEY RESULTS: Positive diagnostic yields for ED were: BEDDV 18%, BE50 31%, EP 38% and anorectal manometry (ARM) 68%. Agreement was substantial between the two balloon tests (k = 0.66), only fair between proctography and BE50 (k = 0.27), poor between manometry and proctography (k = 0.01), and there was no agreement between the balloon tests and manometry (k = -0.07 for both BE50 and BEDDV ). For the diagnosis of FDD, there was only fair agreement between ARM and EP (k = 0.23), ARM ± BE50 and EP (k = 0.18), ARM and EP ± BE50 (k = 0.30) and ARM ± BE50 and EP ± BE50 (k = 0.23). CONCLUSIONS & INFERENCES: There is considerable disagreement between the results of various tests used to diagnose ED and FDD. This highlights the need for a reappraisal of both diagnostic criteria, and what represents the 'gold standard' investigation.

Determinants and clinical impact of pressure drift in manoscan anorectal high resolution manometry system.

BACKGROUND: Pressure drift (PD), resulting from differences between room and body temperature, reduces the accuracy of pressure measurements with the Manoscan high resolution manometry (HRM) system. Our aims were to assess PD during anorectal HRM. METHODS: Defined as the residual pressure measured immediately after the catheter was removed, PD was calculated for each sensor and averaged across all 12 sensors in 454 anorectal consecutive studies recorded with 3 HRM catheters. The relationship between PD and study duration, number of prior uses of a catheter, and peak and average pressure exposure during a study were evaluated. The correction of PD with a software algorithm (thermal compensation) was evaluated in 76 studies where the most distal sensor was outside the body. KEY RESULTS: The PD varied among sensors and across catheters. The average PD (7.3 ± 0.2 mmHg) was significantly greater for newer catheters, during longer studies, or when sensors were exposed to higher pressures. Together, these factors explained 81% of the variance in overall PD. After thermal compensation, the uncorrected median PD for the most distal sensor was 2.5-5 mmHg over the study duration. Correcting this changed the interpretation (e.g., as abnormal instead of normal) of at least 1 anorectal parameter in eight of 76 studies. CONCLUSIONS & INFERENCES: During anorectal HRM, PD declines with catheter use and is greater for newer catheters, when sensors are exposed to higher pressures, and for studies of longer duration. While PD is partially corrected with thermal compensation algorithms, the impact on interpretation is modest.

Validating endpoints for therapeutic trials in fecal incontinence.

BACKGROUND: A 50% or greater reduction in the frequency of fecal incontinence (FI) recorded with daily bowel diaries is the primary endpoint in clinical trials of FI. Whether this difference is clinically important is unknown. The relationship between FI symptoms recorded with daily and weekly instruments is unknown. The contribution of psychological factors to quality of life (QOL) in FI is unclear. METHODS: Fecal incontinence severity was assessed with daily bowel diaries and periodic questionnaires (fecal incontinence severity score [FISS], FIQOL, 36-Item Short Form Health Survey [SF-36], and hospital anxiety and depression scales) for 4 weeks before and during double-blind randomization to placebo or clonidine in 44 women with FI. The reduction in FI frequency was compared to the minimal clinically important difference (MCID) computed from the FISS. Endpoints of FI were compared between daily and weekly diaries. KEY RESULTS: The FISS exceeded the MCID in 75% and 83% of patients in whom the FI frequency declined by 50-74% and ≥75% respectively. Parameters of FI measured with daily and weekly instruments were significantly correlated. The daily parameters explained 71% of the inter-patient variation in the FISS. The SF-36 health scores, rather than the FISS rating, explained a majority of the inter-subject variation in FIQOL. CONCLUSIONS & INFERENCES: Most patients who report a ≥50% reduction in FI frequency experience a clinically important improvement. Weekly questionnaires accurately assess the severity of FI. Self-reported physical and mental health explained a greater proportion of the variance in FIQOL than FI symptom severity.

Evaluating the safety and the effects on colonic compliance of neostigmine during motility testing in patients with chronic constipation.

BACKGROUND: Neostigmine, an acetyl cholinesterase inhibitor, stimulates colonic motor activity and may induce vagally mediated cardiovascular effects. Our aim was to evaluate effects of i.v. neostigmine on colonic compliance and its safety in patients with chronic constipation. METHODS: We retrospectively reviewed medical records of a selected group of 144 outpatients with chronic constipation who were refractory to treatment. These patients had undergone intracolonic motility and compliance measurements with an infinitely compliant balloon linked to a barostat. Data abstracted included barostat balloon mean volumes with increases in pressure (4 mmHg steps from 0 to 44 mmHg) before and after i.v. neostigmine. Vital signs and oxygen saturation before and after neostigmine were recorded. KEY RESULTS: Of the 144 patients, 133 were female, mean age was 41.0 ± 15.4 years (SD), and duration of constipation was 12.9 ± 13.8 years. Among patients who had undergone colonic transit measurement by scintigraphy, the overall colonic transit at 24 h (geometric center, GC24 [n = 115]) was 1.5 ± 0.7 (normal >1.3), and at 48 h (GC48 [n = 75]) it was 2.3 ± 0.9 (normal >1.9). Neostigmine decreased colonic compliance at lower distension pressures (e.g., 12 and 20 mmHg [both p < 0.001]), but not at 40 mmHg. There were expected minor changes in vital signs in response to neostigmine in 144 patients; however, one patient developed unresponsiveness, significant bradycardia, hypotension, and muscular rigidity that responded to 400 mcg i.v. atropine. CONCLUSIONS & INFERENCES: Neostigmine significantly decreases colonic compliance in patients with refractory chronic constipation. Symptomatic bradycardia in response to neostigmine should be promptly reversed with atropine.

Diaphragmatic breathing for rumination syndrome: efficacy and mechanisms of action.

BACKGROUND: While high resolution esophageal manometry combined with impedancometry has demonstrated that gastric pressurizations lead to rumination, the contribution of upper esophageal sphincter (UES) and esophagogastric junction (EGJ) function to rumination is unclear. Behavioral therapy with diaphragmatic breathing (DB) can reduce rumination. We aimed to evaluate the pressures in the stomach, EGJ and UES during rumination and the effects of DB augmented with biofeedback therapy. METHODS: Sixteen patients with rumination were studied with manometry and impedancometry before and after a meal. The postprandial assessment comprised three periods: before, during, and after DB augmented with biofeedback therapy. KEY RESULTS: All patients had postprandial rumination, which was associated (p < 0.001) with increased gastric pressure and reversal of the postprandial gastroesophageal pressure gradient from -4 (-43 to 18) before to 20 (7-79) mmHg during rumination. The EGJ pressure was lower (p < 0.001) during gastric pressurizations that were associated with rumination vs those that were not. The UES also relaxed, almost completely, during rumination. Patients had a median (range) of 5 (2-10) rumination episodes before, 1 (0-2) (p < 0.001) during, and 3 (1-5) after (p < 0.001 vs during) diaphragmatic breathing. During manometry and impedancometry, DB was well-tolerated and learned within 5 min. Diaphragmatic breathing increased EGJ pressure (p < 0.001) and restored a negative gastroesophageal pressure gradient (-20 mmHg [-80 to 7]). CONCLUSIONS & INFERENCES: Diaphragmatic breathing aided with high resolution esophageal manometry is well-tolerated, effective and averts the gastroesophageal pressure disturbance that leads to rumination.

Effect of neostigmine on gastroduodenal motility in patients with suspected gastrointestinal motility disorders.

BACKGROUND: Acetylcholinesterase inhibitors (ACIs), e.g., neostigmine, are known to increase upper and lower gastrointestinal (GI) motility and are used to treat acute colonic pseudoobstruction. However, their effects on gastroduodenal motility in humans are poorly understood. Our hypotheses were that, in patients with suspected GI motility disorders, neostigmine increases gastric and small intestinal motor activity, and these effects are greater in patients with cardiovagal neuropathy, reflecting denervation sensitivity. METHODS: In this open label study, the effects of neostigmine (1 mg intravenously) on gastroduodenal motor activity recorded with manometry were assessed in 28 patients with a suspected GI motility disorder. Cardiovagal function was assessed with the heart rate response to deep breathing and GI transit by scintigraphy. KEY RESULTS: The final diagnoses were gastroparesis (6 patients), gastroparesis with intestinal neuropathy (3 patients), intestinal neuropathy or pseudoobstruction (5 patients), functional dyspepsia (6 patients), chronic abdominal pain (3 patients), mechanical small intestinal obstruction (3 patients), and pelvic floor dysfunction (2 patients). Neostigmine increased both antral and intestinal phasic pressure activity (p < 0.001). Neostigmine increased antral and intestinal pressure activity in 81% and 50% of patients with reduced postprandial antral and intestinal contractile responses to meal, respectively. The antroduodenal pressure response to neostigmine was not higher in patients with cardiovagal dysfunction. CONCLUSIONS & INFERENCES: Neostigmine increased antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility. These responses to neostigmine were not greater in patients with cardiovagal dysfunction. The use of longer-acting ACIs for treating antroduodenal dysmotility warrant further study.

A novel technique for bedside anorectal manometry in humans.

BACKGROUND: Currently, anorectal manometry (ARM), which is used to diagnose defecatory disorders and identify anal weakness in fecal incontinence (FI) is generally conducted in specialized laboratories. Our aims were to compare anorectal functions measured with high-resolution manometry (HRM) and a novel portable manometry device. METHODS: Anal pressures at rest, during squeeze, and simulated evacuation, and rectal sensation were evaluated with portable and HRM in 20 healthy women, 19 women with constipation, and 11 with FI. The relationship between anal pressures measured with portable and HRM was assessed by the concordance correlation coefficient (CCC), Bland Altman test, and paired t-tests. KEY RESULTS: Anal pressures at rest (CCC 0.45; 95% CI: 0.29, 0.58) and during squeeze (CCC 0.60; 95% CI: 0.46, 0.72) measured with portable and HRM were correlated and inversely associated with the risk of FI. During simulated evacuation, the CCC for rectal pressure (0.62; 95% CI: 0.43, 0.76) was greater than that for anal pressure (CCC 0.22; 95% CI: 0.04, 0.39) and the rectoanal gradient (CCC 0.22; 95% CI: 0.02, 0.41). Rectal sensory thresholds for first sensation, the desire to defecate, and urgency measured by portable and HRM were also significantly correlated between techniques. For several parameters, differences between portable and HRM were statistically significant and the Bland Altman test was positive. CONCLUSIONS & INFERENCES: Anorectal pressures and rectal sensation can be conveniently measured by portable manometry and are significantly correlated with high-resolution manometry.

ANMS-ESNM position paper and consensus guidelines on biofeedback therapy for anorectal disorders.

BACKGROUND: Anorectal disorders such as dyssynergic defecation, fecal incontinence, levator ani syndrome, and solitary rectal ulcer syndrome are common, and affect both the adult and pediatric populations. Although they are treated with several treatment approaches, over the last two decades, biofeedback therapy using visual and verbal feedback techniques has emerged as an useful option. Because it is safe, it is commonly recommended. However, the clinical efficacy of biofeedback therapy in adults and children is not clearly known, and there is a lack of critical appraisal of the techniques used and the outcomes of biofeedback therapy for these disorders. PURPOSE: The American Neurogastroenterology and Motility Society and the European Society of Neurogastroenterology and Motility convened a task force to examine the indications, study performance characteristics, methodologies used, and the efficacy of biofeedback therapy, and to provide evidence-based recommendations. Based on the strength of evidence, biofeedback therapy is recommended for the short-term and long-term treatment of constipation with dyssynergic defecation (Level I, Grade A), and for the treatment of fecal incontinence (Level II, Grade B). Biofeedback therapy may be useful in the short-term treatment of Levator Ani Syndrome with dyssynergic defecation (Level II, Grade B), and solitary rectal ulcer syndrome with dyssynergic defecation (Level III, Grade C), but the evidence is fair. Evidence does not support the use of biofeedback for the treatment of childhood constipation (Level 1, Grade D).