The impact of transcutaneous electrical acustimulation (TEA) on rectal distension-induced pain in patients with irritable bowel syndrome (IBS)-A study to determine the optimal TEA delivery modalities and effects on rectal sensation and autonomic function.

BACKGROUND: Treatment options for abdominal pain in IBS are inadequate. TEA was reported effective treatment of disorders of gut-brain interaction but its mechanism of action and optimal delivery method for treating pain in IBS are unknown. This study aims to determine the most effective TEA parameter and location to treat abdominal pain in patients with IBS-Constipation and delineate the effect of TEA on rectal sensation and autonomic function. METHODS: Nineteen IBS-C patients underwent TEA at acupoints ST36 (leg), PC6 (wrist), or sham-acupoint. Each patient was studied in five randomized sessions on separate days: (1) TEA/ST36-100 Hz; (2) TEA/ST36-25 Hz; (3) TEA/PC6-100 Hz; (4) TEA/PC6-25 Hz; (5) TEA/Sham-25 Hz. In each session, barostat-guided rectal distention (RD) was performed before and after TEA. Patients graded the RD-induced pain and recorded three rectal sensation thresholds. A heart rate variability (HRV) signal was derived from the electrocardiogram for autonomic function assessment. KEY RESULTS: Studied patients were predominantly female, young, and Caucasian. Compared with baseline, patients treated with TEA/ST36-100 Hz had significantly decreased pain scores at RD pressure-points 20-50 mmHg (p < 0.04). The average pain reduction was 40%. Post-treatment scores did not change significantly with other TEA modalities except with sham-TEA (lesser degree compared to ST36-100 Hz, p = 0.04). TEA/ST36-100, but not other modalities, increased the rectal sensation threshold (first sensation: p = 0.007; urge to defecate: p < 0.026). TEA/ST36-100 Hz was the only treatment that significantly decreased sympathetic activity and increased parasympathetic activity with and without RD (p < 0.04). CONCLUSIONS & INFERENCES: TEA at ST36-100 Hz is superior stimulation point/parameter, compared to TEA at PC-6/sham-TEA, to reduce rectal distension-induced pain in IBS-C patients. This therapeutic effect appears to be mediated through rectal hypersensitivity reduction and autonomic function modulation.

Endoscopic severity of gastric sleeve stenosis can be quantified using impedance planimetry.

BACKGROUND: Gastric sleeve stenosis (GSS) is an adverse event following sleeve gastrectomy for which objective tools are needed for diagnosis and treatment. Endoscopic treatment with serial pneumatic balloon dilation may relieve symptoms and prevent the need for conversion to Roux-en-Y gastric bypass. Endoluminal functional impedance planimetry (EndoFLIP) is an endoscopic tool that measures luminal diameter and distensibility indices (DI) and could be used to characterize severity of GSS. METHODS: This was a retrospective analysis of a prospective database of patients referred for symptoms suggestive of GSS. Severity was determined at each endoscopy by a bariatric endoscopist blinded to EndoFLIP measurements. Successive pneumatic balloon dilations were performed until symptoms resolved; failure was defined as referral for conversion. EndoFLIP measurements of stenosis diameter and DI were obtained pre- and post-dilation. Primary outcomes were pre- and post-dilation luminal diameter and DI of GSS. Secondary outcomes were endoscopic severity of GSS, patient characteristics, and need for surgical revision. RESULTS: 26 patients were included; 23 (85%) were female. Mean age was 45.3 (± 9.9) years. Mean number of dilations was 2.4 (± 1.3) and 10 (38%) patients were referred for conversion. Mild, moderate, and severe GSS was found in 10 (38%), 6 (23%), and 10 (38%) patients, respectively. Moderate and severe GSS underwent more dilations (2.5 ± 1.0 and 3.2 ± 1.6) than mild GSS (1.8 ± 0.8) and were more likely to be referred for conversion. Both pre- and post-dilation diameters were significantly larger in mild versus moderate or severe GSS. Additionally, pre- and post-dilation DI at 30 ml were significantly higher for mild compared to moderate and severe GSS. DISCUSSION: EndoFLIP measurements correlate well with endoscopic assessment of GSS. While more data are needed to determine ideal balloon size and threshold measurements, our results suggest EndoFLIP may help expedite diagnosis and treatment of GSS.

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.

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.

Objective assessment of luminal diameter and distensibility by an impedance planimetry system before and after pneumatic dilation in gastric sleeve stenosis.

Video 1Endoscopic impedance planimetry system measurement and pneumatic balloon dilation of a sleeve gastrectomy stricture.

Pneumatic Balloon Dilation of Gastric Sleeve Stenosis Is Not Associated with Weight Regain.

BACKGROUND: Gastric sleeve stenosis (GSS) occurs in up to 4% of patients after laparoscopic sleeve gastrectomy (LSG). Typical symptoms include reflux, abdominal pain, dysphagia, and regurgitation. Serial pneumatic balloon dilation (PBD) is a successful treatment in many cases obviating the need for revisional surgery, but the potential for weight regain is unknown. The aim of the current study was to assess weight trends following serial pneumatic dilation for GSS. METHODS: Retrospective analysis of a prospectively maintained database of patients undergoing serial PBD for GSS at one institution. Primary outcome was change in BMI before and after serial PBD. Secondary outcomes included complication rates and need for revisional surgery. Sub-group analyses were performed to determine the relationship of patient and procedural factors to BMI after PBD. RESULTS: Forty-four patients met inclusion criteria, 34 (84.1%) women. Mean age was 46.7 (SD 11.9). Mean pre-sleeve BMI was 47.8 (SD 9.2), and mean BMI prior to first dilation was 34.2 (SD 6.8). Median follow-up was 395 days (range 48-571). Mean BMI at time of last follow up was 33.7 (SD 6.7). There was no statistical difference in BMI pre- or post-PBD (p 0.980). The lowest 10th and highest 90th BMI percentile trended toward a higher and lower BMI after PBD, respectively, though not significant. DISCUSSION: As the prevalence of sleeve gastrectomy continues to rise, an increasing number of patients will require treatment for GSS. Stenosis is effectively treated with serial PBD in most patients without any impact on weight gain, making this an effective and appealing option for many patients.

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.

Changes in impedance planimetry metrics predict clinical response to flexible endoscopy in Zenker's diverticulotomy.

Background and study aims Various techniques have been described for flexible endoscopic therapy for Zenker's diverticulum (ZD). Objective methods to assess myotomy effectiveness are lacking. We assessed the utility of impedance planimetry in flexible endoscopic ZD therapies and correlation with a validated symptom score. Patients and methods Patients undergoing endoscopic therapy for symptomatic ZD from February 2019 to March 2020 were included. Intraprocedural impedance planimetry was performed pre- and post-myotomy to assess esophageal diameter and distensibility index (DI). Eating Assessment Tool (EAT)-10 scores were assessed preintervention and post-intervention. Descriptive statistics were calculated. Results Thirteen patients (46 % women; mean age 80 years; 77 % peroral endoscopic myotomy technique) were included. Technical and clinical success was 100 %. No adverse events occurred. At 40 mL and 50 mL, the diameter improved (mean 2.3 mm and 2.6 mm, respectively). At 40 mL and 50 mL, the DI improved (mean 1.0 mm 2 /mmHg and 1.8 mm 2 /mmHg, respectively). EAT-10 scores improved by a mean of 15 points. Mean follow-up was 97 days. Conclusions Intraprocedural impedance planimetry may provide objective data to define success for flexible endoscopic ZD. Further research is required to corroborate these results.

Quantification of gastric sleeve stenosis using endoscopic parameters and image analysis.

BACKGROUND AND AIMS: Sleeve gastrectomy has quickly become the most commonly performed bariatric surgery. In light of its increasing popularity, the prevalence of gastric sleeve stenosis (GSS) continues to rise. Management with serial pneumatic dilation is highly successful but underused because of a lack of quantitative diagnostic criteria. We aimed to develop quantifiable endoscopic criteria to characterize GSS based on the (1) ratio of narrowest to widest gastric lumen diameter, (2) endoscope angulation/trajectory required for passage, and (3) presence of bilious fluid pooling in the proximal sleeve and compare it with endoluminal functional lumen imaging probe (EndoFLIP) diameter and distensibility indices (DIs) and endoscopic documentation of gastric lumen morphology. METHODS: We retrospectively reviewed a prospectively maintained database of patients undergoing endoscopy to assess for GSS. Endoscopic images were reviewed in a blinded fashion by 2 bariatric endoscopists. The narrowest and widest part of the gastric lumen diameters were noted on each image, in addition to a hypothetical trajectory required for endoscope passage. Using image processing software, we calculated the the ratio of diameters (ie, narrowest divided by widest) and angle of endoscope trajectory. The presence of bilious fluid pooling in the proximal gastric lumen was noted. These values were then compared with EndoFLIP parameters and endoscopic documentation of gastric lumen morphology. RESULTS: Thirty patients met inclusion criteria, and 26 (87%) were found to have a stenosis on endoscopy. Of those, 9 (35%) were characterized as mild, 11 (42%) as moderate, and 6 (23%) as severe. There was no difference in demographic information between patients with and without stenosis. In patients with stenosis, mean EndoFLIP diameters and DIs were 12.9 ± 3.9 mm and 11.0 ± 6.8 mm2/mm Hg, respectively. In patients without stenosis, mean EndoFLIP diameters and DIs were 19.9 ± 2.9 mm and 21.5 ± 1.0 mm2/mm Hg, respectively. Patients with stenosis had significantly lower diameter ratios compared with those without stenosis (.27 ± .14 vs .48 ± .77, P = .01). Diameter ratios were also inversely related to severity of sleeve stenosis (ß = -.08, P = .01). Patients with stenosis were also more likely to have fluid pooling (96.2% vs 25%, P < .001). There was no significant difference in the trajectory of endoscope passage between the 2 groups. CONCLUSIONS: Endoscopic criteria for diagnosis of GSS are lacking. Our data suggest the ratio between the narrowest and widest gastric lumen diameters and presence of pooled fluid is associated with diagnosis of stenosis by EndoFLIP and gastric lumen morphology. Future studies to validate these criteria are needed.

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.

Impact of gastric per-oral endoscopic myotomy on static and dynamic pyloric function in gastroparesis patients.

BACKGROUND: Functional Lumen Imaging Probe (EndoFLIP) tests typically measure static pyloric parameters, but the pylorus exhibits phasic variations on manometry. Dynamic changes in pyloric function have not been quantified using EndoFLIP, and the impact of Gastric Per-Oral Endoscopic Myotomy (G-POEM) on static and dynamic pyloric activity in gastroparesis is unknown. METHODS: EndoFLIP balloon inflation to 30, 40, and 50 mL was performed to measure mean, maximum, and minimum values and variability in pyloric diameter and distensibility before and after G-POEM in 20 patients with refractory gastroparesis. The impact of phasic contractions on these pyloric measures was compared. KEY RESULTS: G-POEM increased mean (P < .0001) and maximum (P = .0002) pyloric diameters and mean (P = .02) and maximum (P = .02) pyloric distensibility on 50 mL EndoFLIP inflation but not intraballoon pressures or minimum diameters or distensibility. Temporal variability of pyloric diameter (P = .02) and distensibility (P = .02) also increased after G-POEM. Phasic coupled contractions propagating from the antrum through the pylorus were observed in 37.5% of recordings; other phasic activity including isolated pyloric contractions were seen in 23.3%. Variability of pyloric diameter and distensibility tended to be higher during recordings with phasic activity. Some pyloric responses to G-POEM were influenced by age, gastroparesis etiology, gastric emptying, and prior botulinum toxin injection. CONCLUSIONS & INFERENCES: Pyloric activity exhibits dynamic changes on EndoFLIP testing in gastroparesis. G-POEM increases maximal but not minimal diameter and distensibility with increased variations, suggesting this therapy enhances pyloric opening but may not impair pyloric closure. Phasic pyloric contractions contribute to variations in pyloric activity.

Functional Lumen Imaging Probe Is Useful for the Quantification of Gastric Sleeve Stenosis and Prediction of Response to Endoscopic Dilation: a Pilot Study.

BACKGROUND: Stenosis after sleeve gastrectomy (SG) is common though diagnostic criteria and predictors of treatment response is unknown. Endoluminal functional impedance planimetry (EndoFLIP) is a diagnostic tool for measuring lumen geometry. We aimed to use EndoFLIP to characterize SG stenosis. METHODS: We enrolled SG stenosis patients undergoing serial pneumatic dilations between May 2018 and November 2018. Outcomes of interest included pre- and post-dilation EndoFLIP measurements and post-dilation symptom response. RESULTS: We included 10 patients who underwent a mean of 1.8 ± 0.7 dilations. Pre-dilation EndoFLIP characteristics were similar for responders and non-responders. Responders had larger mean post-dilation diameter (19.9 ± 2.9 mm vs 13.1 ± 1.3 mm, p = 0.007) and DI (21.3 ± 1.0 mm2/Hg vs 4.0 ± 5.4 mm2/Hg, p = 0.04) than non-responders. CONCLUSION: Our pilot study supports the use of EndoFLIP in the management of SG stenosis.

Is Dyssynergic Defecation an Unrecognized Cause of Chronic Constipation in Patients Using Opioids?

OBJECTIVES: The impact of opioids on anorectal function is poorly understood but potentially relevant to the pathogenesis of opioid-induced constipation (OIC). To evaluate anorectal function testing (AFT) characteristics, symptom burden, and quality of life in chronically constipated patients prescribed an opioid (OIC) in comparison with constipated patients who are not on an opioid (NOIC). METHODS: Retrospective analysis of prospectively collected data on 3,452 (OIC = 588 and NOIC = 2,864) chronically constipated patients (Rome 3) who completed AFT. AFT variables included anal sphincter pressure and response during simulated defecation, balloon expulsion test (BET), and rectal sensation. Dyssynergic defecation (DD) was defined as an inability to relax the anal sphincter during simulated defecation and an abnormal BET. Patients completed Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires. RESULTS: The mean age of the study cohort was 49 years. Most patients were women (82%) and whites (83%). Patients with OIC were older than NOIC patients (50.7 vs 48.3, P = 0.001). OIC patients were significantly more likely to have DD (28.6% vs 21.4%, P < 0.001), an abnormal simulated defecation response on anorectal manometry (59% vs 43.8%, P < 0.001), and an abnormal BET (48% vs 42.5%, P = 0.02) than NOIC patients. OIC patients reported more severe constipation symptoms (P < 0.02) and worse quality of life (P < 0.05) than NOIC patients. DISCUSSION: Chronically constipated patients who use opioids are more likely to have DD and more severe constipation symptoms than NOIC.