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.

Can a Defecation Posture Modifying Device Correct an Abnormal Balloon Expulsion Test in Chronically Constipated Patients?

Evacuation disorders are common among chronically constipated (CC) patients who fail to respond to laxatives and are typically diagnosed by anorectal manometry (ARM) and/or balloon expulsion testing (BET).1,2 Recently, there has been emerging interest in the use of defecation posture-modifying devices (DPMDs) to improve constipation symptoms, presumably by replicating the physiologic benefits of squatting on stool evacuation, such as straightening of the anorectal angle and relaxing the pelvic floor. However, the ability of DPMDs to normalize anorectal function in adult patients with CC has not been studied.

An Office-Based, Point-of-Care Test Predicts Treatment Outcomes With Community-Based Pelvic Floor Physical Therapy in Patients With Chronic Constipation.

BACKGROUND & AIMS: Rectal evacuation disorders are common among constipated patients. We aimed to evaluate the accuracy of an investigational point-of-care test (rectal expulsion device [RED]) to predict outcomes with community-based pelvic floor physical therapy. METHODS: We enrolled patients meeting Rome IV criteria for functional constipation failing fiber/laxatives for more than 2 weeks. RED was inserted and self-inflated, and then time-to-expel was measured in a left lateral position. All patients underwent empiric community-based pelvic floor physical therapy in routine care with outcomes measured at 12 weeks. The primary end point was global clinical response (Patient Assessment of Constipation Symptoms score reduction, >0.75 vs baseline). Secondary end points included improvement in health-related quality-of-life (Patient Assessment of Constipation Quality of Life score reduction, >1.0) and complete spontaneous bowel movement frequency (Food and Drug Administration complete spontaneous bowel movement responder definition). RESULTS: Thirty-nine patients enrolled in a feasibility phase to develop the use-case protocol. Sixty patients enrolled in a blinded validation phase; 52 patients (mean, 46.9 y; 94.2% women) were included in the intention-to-treat analysis. In the left lateral position, RED predicted global clinical response (generalized area under the curve [gAUC], 0.67; 95% CI, 0.58-0.76]), health-related quality-of-life response (gAUC, 0.67; 95% CI, 0.58-0.77; P < .001), and complete spontaneous bowel movement response (gAUC, 0.63; 95% CI, 0.57-0.71; P < .001). As a screening test, a normal RED effectively rules out evacuation disorders (expected clinical response, 8.9%; P = .042). Abnormal RED in the left lateral position (defined as expulsion within 5 seconds or >120 seconds) predicted 48.9% clinical response to physical therapy. A seated maneuver enhanced the likelihood of clinical response (71.1% response with seated RED retained >13 seconds) but likely is unnecessary in most settings. CONCLUSIONS: RED offers an opportunity to disrupt the paradigm by offering a personalized approach to managing chronic constipation in the community (Clinicaltrials.gov: NCT04159350).

Utility of Anorectal Testing to Predict Outcomes With Pelvic Floor Physical Therapy in Chronic Constipation: Pragmatic Trial.

BACKGROUND & AIMS: We performed a clinical trial that aimed to inform the clinical utility of anorectal manometry (ARM) and balloon expulsion time (BET) as up-front tests to predict outcomes with community-based pelvic floor physical therapy as the next best step to address chronic constipation after failing an empiric trial of soluble fiber supplementation or osmotic laxatives. METHODS: We enrolled 60 treatment-naïve patients with Rome IV functional constipation failing 2 weeks of soluble fiber supplementation or osmotic laxatives. All patients underwent ARM/BET (London protocol) followed by community-based pelvic floor physical therapy. Outcomes were assessed at baseline and 12 weeks. The primary end point was clinical response (Patient Assessment of Constipation-Symptoms instrument). RESULTS: Fifty-three patients completed pelvic rehabilitation and the post-treatment questionnaire. Contemporary frameworks define dyssynergia on balloon expulsion time and dyssynergic patterns (ARM), but these parameters did not inform clinical outcomes (area under the curve [AUC], <0.6). Squeeze pressure (>192.5 mm Hg on at least 1 of 3 attempts; sensitivity, 47.6%; specificity, 83.9%) and limited squeeze duration (inability to sustain 50% of squeeze pressure for >20 seconds; sensitivity, 71.4%; specificity, 58.1%) were the strongest predictors of clinical outcomes. Combining BET with squeeze duration (BET greater than 6.5 seconds and limited squeeze duration) improved predictive accuracy (AUC, 0.75; 95% CI, 0.59-0.90). BET poorly predicted outcomes as a single test (AUC, 0.54; 95% CI, 0.38-0.69). CONCLUSIONS: Using ARM to evaluate squeeze profiles, rather than dyssynergia, appears useful to screen patients with chronic constipation for up-front pelvic floor physical therapy based on likelihood of response. BET appears noninformative as a single screening test (ClinicalTrials.gov: NCT04159350).

Development of a Simple, Point-of-Care Device to Test Anorectal Function in Patients with Constipation: Randomized Clinical Trial.

Functional constipation (FC) is one of the most frequently encountered gastrointestinal conditions in practice.1 Practice guidelines universally recommend that patients with typical constipation symptoms and no alarm features be treated empirically with dietary/lifestyle interventions and laxative therapy.2,3 Unfortunately, by the time a patient reaches a gastroenterologist, these treatments frequently have already been tried. Anorectal function testing (anorectal manometry [ARM] and balloon expulsion test [BET]) is the next best step in management guidelines in this all-too-common scenario, because treatment can then be targeted toward pelvic floor dysfunction or colon transit abnormalities. Unfortunately, more than 95% of patients continue to take only over-the-counter laxatives and receive empirical dietary advice, whereas fewer than 2% undergo physiologic evaluation to ascertain the cause of their symptoms.4 Indeed, more than 90% of patients desire more effective treatment options. These observations call into question the wisdom of a management strategy that fails to recognize the intrinsic diversity of the constipation universe and reinforces the misguided "one size fits all" empirical treatment strategy.

Video-Based Deep Learning to Detect Dyssynergic Defecation with 3D High-Definition Anorectal Manometry.

BACKGROUND: We developed a deep learning algorithm to evaluate defecatory patterns to identify dyssynergic defecation using 3-dimensional high definition anal manometry (3D-HDAM). AIMS: We developed a 3D-HDAM deep learning algorithm to evaluate for dyssynergia. METHODS: Spatial-temporal data were extracted from consecutive 3D-HDAM studies performed between 2018 and 2020 at Dartmouth-Hitchcock Health. The technical procedure and gold standard definition of dyssynergia were based on the London consensus, adapted to the needs of 3D-HDAM technology. Three machine learning models were generated: (1) traditional machine learning informed by conventional anorectal function metrics, (2) deep learning, and (3) a hybrid approach. Diagnostic accuracy was evaluated using bootstrap sampling to calculate area-under-the-curve (AUC). To evaluate overfitting, models were validated by adding 502 simulated defecation maneuvers with diagnostic ambiguity. RESULTS: 302 3D-HDAM studies representing 1208 simulated defecation maneuvers were included (average age 55.2 years; 80.5% women). The deep learning model had comparable diagnostic accuracy [AUC 0.91 (95% confidence interval 0.89-0.93)] to traditional [AUC 0.93(0.92-0.95)] and hybrid [AUC 0.96(0.94-0.97)] predictive models in training cohorts. However, the deep learning model handled ambiguous tests more cautiously than other models; the deep learning model was more likely to designate an ambiguous test as inconclusive [odds ratio 4.21(2.78-6.38)] versus traditional/hybrid approaches. CONCLUSIONS: Deep learning is capable of considering complex spatial-temporal information on 3D-HDAM technology. Future studies are needed to evaluate the clinical context of these preliminary findings.

Age- and Gender-Based Differences in Anorectal Function, Gastrointestinal Symptoms, and Constipation-Specific Quality of Life in Patients with Chronic Constipation.

BACKGROUND: The effect of age and gender differences on anorectal function, symptoms severity, and quality of life (QoL) in patients with chronic constipation (CC) is not well studied. This study examines the impact of age and gender on anorectal function testing (AFT) characteristics, symptoms burden, and QoL in patients with CC. METHODS: This is a retrospective analysis of prospectively collected data from 2550 adults with CC who completed AFT. Collected data include demographics, sphincter response to simulated defecation during anorectal manometry (ARM), balloon expulsion testing (BET), and validated surveys assessing constipation symptoms and QoL. DD was defined as both the inability to relax the anal sphincter during simulated defecation and an abnormal BET. RESULTS: 2550 subjects were included in the analysis (mean age = 48.6 years). Most patients were female (81.6%) and Caucasian (82%). 73% were < 60 years old (mean = 41) vs. 27% ≥ 60 years old (mean = 69). The prevalence of impaired anal sphincter relaxation on ARM, abnormal BET, and DD in patients with CC was 48%, 42.1%, and 22.9%, respectively. Patients who were older and male were significantly more frequently diagnosed with DD and more frequently had impaired anal sphincter relaxation on ARM, compared to patients who were younger and female (p < 0.05). Conversely, CC patients who were younger and female reported greater constipation symptoms severity and more impaired QoL (p ≤ 0.004). CONCLUSION: Among patients with CC referred for anorectal function testing, men and those older than 60 are more likely to have dyssynergic defecation, but women and patients younger than 60 experience worse constipation symptoms and QoL.

Organizing and Developing a GI Motility Lab in Community Practice: Challenges and Rewards.

PURPOSE OF REVIEW: Neurogastroenterology and motility is a rapidly evolving subspecialty that encompasses over 33% of gastroenterological disorders, and up to 50% of referrals to gastroenterology practice. It includes common problems such as dysphagia, gastroesophageal reflux disease, irritable bowel syndrome, chronic constipation, gastroparesis, functional dyspepsia, gas/bloating, small intestinal bacterial overgrowth, food intolerance and fecal incontinence Standard diagnostic tests such as endoscopy or imaging are normal in these conditions. To define the underlying mechanism(s)/etiology of these disorders, diagnostic motility tests are often required. These are best performed by well-trained personnel in a dedicated motility laboratory. Our purpose is to provide an up-to-date overview on how to organize and develop a motility laboratory based on our collective experiences in setting up such facilities in academia and community practice. RECENT FINDINGS: A lack of knowledge, training and facilities for providing diagnostic motility tests has led to suboptimal patient care. A motility laboratory is the hub for diagnostic and therapeutic motility procedures. Common procedures include esophageal function tests such as esophageal manometry and pH monitoring, anorectal function tests suchlike anorectal manometry, neurophysiology and balloon expulsion, dysbiosis and food intolerance tests such as hydrogen/methane breath tests, and gastrointestinal transit assessment. These tests provide an accurate diagnosis and guide clinical management including use of medications, biofeedback therapy, neuromodulation, behavioral therapies, evidence-based dietary interventions and endoscopic or surgical procedures. Further, there have been recent developments in billing and coding of motility procedures and training requirements that are not well known. This review provides a stepwise approach on how to set-up a motility laboratory in the community or academic practice and includes the rationale, infrastructure, staffing needs, commonly performed motility tests and their clinical utility, billing and coding strategies, training needs and economic considerations for setting up this service.

Diffusion of an innovation: growth in video capsule endoscopy in the U.S. Medicare population from 2003 to 2019.

BACKGROUND: Video capsule endoscopy (VCE), approved by the U.S. Food and Drug Administration (FDA) in 2001, represented a disruptive technology that transformed evaluation of the small intestine. Adoption of this technology over time and current use within the U.S. clinical population has not been well described. METHODS: To assess the growth of capsule endoscopy within the U.S. Medicare provider population (absolute growth and on a population-adjusted basis), characterize the providers performing VCE, and describe potential regional differences in use. Medicare summary data from 2003 to 2019 were used to retrospectively analyze capsule endoscopy use in a multiple cross-sectional design. In addition, detailed provider summary files were used from 2012 to 2018 to characterize provider demographics. RESULTS: VCE use grew rapidly from 2003 to 2008 followed by a plateau from 2008 to 2019. There was significant variation in use of VCE between states, with up to 10-fold variation between states (14.6 to 156.1 per 100,000 enrollees in 2018). During this time, the adjusted VCE use on a population-adjusted basis declined, reflecting saturation of growth. CONCLUSIONS: Growth of VCE use over time follows an S-shaped diffusion of innovation curve demonstrating a successful diffusion of innovation within gastroenterology. The lack of additional growth since 2008 suggests that current levels of use are well matched to overall population need within the constraints of reimbursement. Future studies should examine whether this lack of growth has implications for access and healthcare inequities.

A Randomized Pilot Study to Compare the Effectiveness of a Low FODMAP Diet vs Psyllium in Patients With Fecal Incontinence and Loose Stools.

INTRODUCTION: The aim of the study was to compare the effectiveness of a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet (LFD) vs psyllium on the frequency and severity of fecal incontinence (FI) episodes in patients with loose stools. METHODS: This was a single-center, randomized pilot trial of adult patients with FI (Rome III) with at least 1 weekly FI episode associated with loose stool. Eligible patients were randomized to 4 weeks of either a dietitian-led LFD or 6 g/d psyllium treatment. RESULTS: Forty-three subjects were randomized from October 2014 to May 2019. Thirty-seven patients completed the study (19 LFD and 18 psyllium). There was no statistically significant difference in the proportion of treatment responders (>50% reduction in FI episodes compared with baseline) for treatment weeks 1-4 (LFD 38.9%, psyllium 50%, P = .33). Compared with baseline, mean fecal incontinence severity index score significantly improved with LFD (39.4 vs 32.6, P = .02) but not with psyllium (35.4 vs 32.1, P = .29). Compared with baseline values, the LFD group reported improvements in fecal incontinence quality of life coping/behavior, depression/self-perception, and embarrassment subscales. The psyllium group reported improvement in incontinence quality of life coping/behavior. DISCUSSION: In this pilot study, there was no difference in the proportion of patients who reported a 50% reduction of FI episodes with the LFD or psyllium. Subjects in the psyllium group reported a greater reduction in overall FI episodes, whereas the LFD group reported consistent improvements in FI severity and quality of life. Further work to understand these apparently discrepant results are warranted but the LFD and psyllium seem to provide viable treatment options for patients with FI and loose stools.

Utilization of Dietitians in the Management of Irritable Bowel Syndrome by Members of the American College of Gastroenterology.

INTRODUCTION: The aim of this study was to identify benefits and barriers to using a gastroenterology (GI) dietitian for irritable bowel syndrome (IBS) care. METHODS: A 25-question survey was electronically distributed to the members of the American College of Gastroenterology. Information pertaining to demographics, barriers, and values to using a GI dietitian for IBS patient care was collected. RESULTS: Two hundred seventy-nine survey responses were collected. Although 56% of the GI providers feel they are trained to provide nutrition education, almost half (46%) sometimes, rarely, or never provided information to aid menu planning, label reading, or grocery shopping, and 77% spent ≤10 minutes for nutrition counseling. Of those with access to a local dietitian, 91% strongly agreed or agreed that having access to a GI dietitian would help them manage their IBS patient care more effectively, but 42% lack access to a local GI dietitian. DISCUSSION: Our survey identified gaps in nutrition-based interventions for IBS care.

Phenotyping patients with borderline elevated esophageal acid exposure.

Acid exposure time (AET) <4% on ambulatory reflux monitoring definitively rules out pathologic gastroesophageal acid reflux, while AET >6% indicates pathologic reflux per the Lyon Consensus, leaving AET of 4-6% as borderline. We aimed to elucidate the borderline AET population and identify metrics that could help differentiate this group. A total of 50 subjects in each group, AET <4, 4-6, and >6% on pH-impedance monitoring between 2015 and 2019, were retrospectively reviewed. In addition to demographic and clinical information, the extracted data included mean nocturnal baseline impedance (MNBI) on reflux study and high-resolution manometry (HRM) parameters and diagnosis. After excluding patients with prior foregut surgery, major esophageal motility disorder, or unreliable impedance testing, a total of 89 subjects were included in the analysis (25 with normal AET < 4%, 38 with borderline 4-6%, 26 with abnormal >6%). MNBI in borderline AET patients was significantly lower compared to normal AET (1607.7 vs. 2524.0 ohms, P < 0.01), and higher than abnormal AET (951.5 ohms, P < 0.01). Borderline subjects had a greater frequency of ineffective esophageal motility (IEM) diagnosis per Chicago classification v3.0 (42.1 vs. 8.0%, P = 0.01), but did not demonstrate any differences compared to abnormal subjects (34.6%, P = 0.56). Patients with borderline AET had an average MNBI that was in between normal AET and abnormal AET. Borderline AET patients also commonly demonstrate IEM on HRM, similar to those with abnormal AET. Our findings can be potentially useful in assigning higher clinical significance for patients found to have borderline AET with concomitant low MNBI and IEM on manometry.

How the North American Consensus Protocol Affects the Performance of Glucose Breath Testing for Bacterial Overgrowth Versus a Traditional Method.

INTRODUCTION: The North American Consensus guidelines for glucose breath testing (GBT) for small intestinal bacterial overgrowth (SIBO) incorporated changes in glucose dosing and diagnostic cutoffs. We compared GBT positivity based on hydrogen and methane excretion and quantified symptoms during performance of the North American vs older modified Rome Consensus protocols. METHODS: GBT was performed using the North American protocol (75 g glucose, cutoffs >20 parts per million [ppm] hydrogen increase after glucose and >10 ppm methane anytime) in 3,102 patients vs modified Rome protocol (50 g glucose, >12 ppm hydrogen and methane increases after glucose) in 3,193 patients with suspected SIBO. RESULTS: Positive GBT were more common with the North American vs modified Rome protocol (39.5% vs 29.7%, P < 0.001). Overall percentages with GBT positivity using methane criteria were greater and hydrogen criteria lower with the North American protocol (P < 0.001). Peak methane levels were higher for the North American protocol (P < 0.001). Times to peak hydrogen and methane production were not different between protocols. With the North American protocol, gastrointestinal and extraintestinal symptoms were more prevalent after glucose with both positive and negative GBT (P < 0.04) and greater numbers of symptoms (P < 0.001) were reported. DISCUSSION: GBT performed using the North American Consensus protocol was more often positive for SIBO vs the modified Rome protocol because of more prevalent positive methane excretion. Symptoms during testing were greater with the North American protocol. Implications of these observations on determining breath test positivity and antibiotic decisions for SIBO await future prospective testing.

Anorectal manometry to diagnose dyssynergic defecation: Systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: Chronic constipation is a common condition, and dyssynergic defecation underlies up to 40% of cases. Anorectal manometry is recommended to assess for dyssynergic defecation among chronically constipated patients but remains poorly standardized. We aimed to evaluate the diagnostic accuracy of anorectal manometry and determine optimal testing parameters. METHODS: We performed a systematic review with meta-analysis of diagnostic test accuracy including cohort studies of chronically constipated patients and case-control studies of patients with dyssynergic defecation or healthy controls. Meta-analysis was performed to determine summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI). KEY RESULTS: A total of 15 studies comprising 2140 patients were included. Including all studies (estimating optimal diagnostic accuracy), the AUC was 0.78 [95% CI 0.72-0.82], summary sensitivity was 79% [61%-90%], and summary specificity was 64% [44%-79%] to diagnose dyssynergic defecation. In cohort studies only (estimating real-world diagnostic accuracy), the AUC was 0.72 [0.66-0.77], summary sensitivity was 86% [64%-95%], and summary specificity was 49% [30%-68%]. Employing three consecutive simulated defecation attempts improved sensitivity to 94%. A fourth simulated defecation maneuver with air insufflation may improve accuracy. Measuring anorectal pressures to identify complex dyssynergic patterns did not improve real-world diagnostic accuracy estimates over anal pressure measurement alone. Choice of manometry system did not impact diagnostic accuracy. CONCLUSIONS & INFERENCES: Following the current iteration of the London consensus protocol (three simulated defecation attempts measuring anal relaxation), the role of anorectal manometry in evaluating dyssynergic defecation appears limited. Future iterations of this protocol may improve diagnostic accuracy.

Provider Variability in the Management Patterns of Increased Nonacid Reflux.

INTRODUCTION: Increased nonacid reflux is diagnosed in a subgroup of patients with gastroesophageal reflux disease who often present with reflux symptoms refractory to proton-pump inhibitor therapy. Despite the prevalence of this condition, the management approach for patients with increased nonacid reflux can often be varied and unclear. AIMS: Our primary aim was to investigate physician management patterns for patients who had received a diagnosis of increased nonacid reflux on impedance-pH studies. METHODS: Reflux studies in patients with increased nonacid reflux per Lyon Consensus criteria and management approaches were retrospectively reviewed. Reflux symptom survey, manometry findings, reflux symptom association (RSA) on reflux testing, immediate posttesting management information, and managing provider information were assessed. RESULTS: A total of 43 subjects in total were analyzed. Management plan after a diagnosis of increased nonacid reflux was decided by a gastroenterologist in over 95% of cases and varied greatly with no changes being the most common. Even among subjects with + RSA on reflux monitoring, no change in management was the most common action, although this occurred much less frequently compared to subjects with - RSA (28.6% vs. 78.6%, p < 0.01). When change in therapy occurred, medical treatment with baclofen was the most common choice (21.4%). Other management changes included medications for visceral hypersensitivity and antireflux surgery, although these changes occurred rarely. CONCLUSIONS: Abnormally increased nonacid reflux is frequently encountered on impedance-pH studies; however, management decisions vary significantly among gastroenterologists. When treatment change is implemented, they are variable and can include lifestyle modifications, medication trials, or antireflux surgery. Future development of standardized management algorithms for increased nonacid reflux is needed.

American Neurogastroenterology and Motility Society Task Force Recommendations for Resumption of Motility Laboratory Operations During the COVID-19 Pandemic.

The American Neurogastroenterology and Motility Society Task Force recommends that gastrointestinal motility procedures should be performed in motility laboratories adhering to the strict recommendations and personal protective equipment (PPE) measures to protect patients, ancillary staff, and motility allied health professionals. When available and within constraints of institutional guidelines, it is preferable for patients scheduled for motility procedures to complete a coronavirus disease 2019 (COVID-19) test within 48 hours before their procedure, similar to the recommendations before endoscopy made by gastroenterology societies. COVID-19 test results must be documented before performing procedures. If procedures are to be performed without a COVID-19 test, full PPE use is recommended, along with all social distancing and infection control measures. Because patients with suspected motility disorders may require multiple procedures, sequential scheduling of procedures should be considered to minimize need for repeat COVID-19 testing. The strategies for and timing of procedure(s) should be adapted, taking into consideration local institutional standards, with the provision for screening without testing in low prevalence areas. If tested positive for COVID-19, subsequent negative testing may be required before scheduling a motility procedure (timing is variable). Specific recommendations for each motility procedure including triaging, indications, PPE use, and alternatives to motility procedures are detailed in the document. These recommendations may evolve as understanding of virus transmission and prevalence of COVID-19 infection in the community changes over the upcoming months.

Comparison of anorectal function measured using wearable digital manometry and a high resolution manometry system.

There is a need for a lower cost manometry system for assessing anorectal function in primary and secondary care settings. We developed an index finger-based system (termed "digital manometry") and tested it in healthy volunteers, patients with chronic constipation, and fecal incontinence. Anorectal pressures were measured in 16 participants with the digital manometry system and a 23-channel high-resolution anorectal manometry system. The results were compared using a Bland-Altman analysis at rest as well as during maximum squeeze and simulated defecation maneuvers. Myoelectric activity of the puborectalis muscle was also quantified simultaneously using the digital manometry system. The limits of agreement between the two methods were -7.1 ± 25.7 mmHg for anal sphincter resting pressure, 0.4 ± 23.0 mmHg for the anal sphincter pressure change during simulated defecation, -37.6 ± 50.9 mmHg for rectal pressure changes during simulated defecation, and -20.6 ± 172.6 mmHg for anal sphincter pressure during the maximum squeeze maneuver. The change in the puborectalis myoelectric activity was proportional to the anal sphincter pressure increment during a maximum squeeze maneuver (slope = 0.6, R2 = 0.4). Digital manometry provided a similar evaluation of anorectal pressures and puborectalis myoelectric activity at an order of magnitude less cost than high-resolution manometry, and with a similar level of patient comfort. Digital Manometry provides a simple, inexpensive, point of service means of assessing anorectal function in patients with chronic constipation and fecal incontinence.

Unraveling the behavior of oral drug products inside the human gastrointestinal tract using the aspiration technique: History, methodology and applications.

Fluid sampling from the gastrointestinal (GI) tract has been applied as a valuable tool to gain more insight into the fluids present in the human GI tract and to explore the dynamic interplay of drug release, dissolution, precipitation and absorption after drug product administration to healthy subjects. In the last twenty years, collaborative initiatives have led to a plethora of clinical aspiration studies that aimed to unravel the luminal drug behavior of an orally administered drug product. The obtained drug concentration-time profiles from different segments in the GI tract were a valuable source of information to optimize and/or validate predictive in vitro and in silico tools, frequently applied in the non-clinical stage of drug product development. Sampling techniques are presently not only being considered as a stand-alone technique but are also used in combination with other in vivo techniques (e.g., gastric motility recording, magnetic resonance imaging (MRI)). By doing so, various physiological variables can be mapped simultaneously and evaluated for their impact on luminal drug and formulation behavior. This comprehensive review aims to describe the history, challenges and opportunities of the aspiration technique with a specific focus on how this technique can unravel the luminal behavior of drug products inside the human GI tract by providing a summary of studies performed over the last 20 years. A section 'Best practices' on how to perform the studies and how to treat the aspirated samples is described. In the conclusion, we focus on future perspectives concerning this technique.