Neurogastroenterology and Motility最新文献

Background: Evaluation of gut motility in clinical practice is currently limited. A novel medical system (MoPill™) consisting of a capsule that wirelessly transmits radiofrequency signals to assess motility via 3D location, was used to conduct this study. The objectives were to: (1) confirm the safety of the MoPill™ system; (2) compare the 3D location transmitted by the capsule to its location captured by abdominal x-rays; 3 determine gastric emptying (GE), whole gut transit time (WGTT) and segmental transit times.

Methods: The MoPill™ system consists of an electronic capsule (2 × 1.2 cm), eight color-coded adhesive sensors (6 × 5.5 cm), a recorder (15 × 11 × 2 cm), and software on a laptop. Four sensors were applied to the abdomen and four to the back. Healthy subjects who had fasted overnight ingested a 250-calorie protein bar, 17 oz. of water, followed by an activated capsule. No further caloric contents were permitted for the next 5 h. At 1, 5, and 24 h (if the capsule had not been expelled), upright abdominal X-rays (AP and lateral) were obtained to assess the location of the capsule, which was compared to the gastrointestinal positioning system (GPS) location determined by the MoPill™ system. Identification of the capsule's anatomical location by the MoPill™ system was based on (1) the 3D (x, y, z) location; (2) time; (3) trajectory (e.g., going up the right side of the body signified ascending colon); (4) frequency of contractions (e.g., 3 cycles/min for the stomach); and (5) milestone relationship (e.g., pyloric passage must follow the end of gastric contractions). GE was determined first by the end of the 3 cycles/min rhythmic movement of the stomach and then again by pyloric expulsion on 3D location. Small intestine transit was taken as the duration from pyloric expulsion to arrival in the cecum. Colon transit time was determined by calculating the duration from 3D arrival in the cecum to passage of the capsule out of the body (i.e., loss of signal accompanying a bowel movement).

Key results: Ten healthy subjects (five women; mean age 34; mean BMI 24) were enrolled, and nine provided reliable data. The variation between the x-ray and the estimated (i.e., identified by the MoPill™ system) location of the capsule was within an average of 3.5 cm (range 0.9-9.4 cm). The mean GE was 3.1 h. The small intestine's mean transit time was 4.3 h. The mean colonic transit time was 17.6 h. There were no adverse events recorded during the study.

Conclusions & inferences: MoPill™ is a novel gastrointestinal positional system that accurately identifies the location of a capsule compared to an X-ray. MoPill™ system also recognizes GE, small bowel, colonic, and WGTT as well as segmental gut location and movement characteristics. MoPill™ offers the potential for new insights into GI motility disorders not attainable by current modalities.

Background: Our objective was to evaluate long-term outcomes of sacral nerve stimulation (SNS) for children with functional and organic defecation disorders.

Methods: We performed a prospective study of children <21 years of age who started SNS treatment between 2012 and 2018. We recorded demographics, medical history, and diagnostic testing. We obtained measures of symptom severity and quality of life at baseline and follow up at 1, 6, 12, 24, 36, 48, and ≥60 months. Successful response was defined as bowel movements >2 times/week and fecal incontinence (FI) <1 time/week. Families were contacted to administer the Glasgow Children's Benefit Inventory and to evaluate patient satisfaction.

Key results: We included 65 patients (59% female, median age at SNS 14 years, range 9-21) with median follow-up of 32 months. Thirty patients had functional constipation (FC), 15 had non-retentive FI (NRFI), and 16 had an anorectal malformation (ARM). The percentage with FI <1 time/week improved from 30% at baseline to 64% at 1 year (p < 0.001) and 77% at most recent follow-up (p < 0.001). Patients with FC, NRFI, and ARM had sustained improvement in FI (p = 0.02, p < 0.001, p = 0.02). Patients also reported fewer hard stools (p = 0.001). Bowel movement frequency did not improve after SNS. At most recent follow-up, 77% of patients with a functional disorder and 50% with an organic disorder had responded (p = 0.03). Nearly all families reported benefit.

Conclusions and inferences: SNS led to sustained improvement in FI regardless of underlying etiology, but children with functional disorders were more likely to respond than those with organic disorders.

Background: This study compared the effects of ondansetron and placebo in patients with diabetes mellitus and symptoms of dyspepsia (diabetic gastroenteropathy [DGE]).

Methods: We performed a randomized, double-blinded, placebo-controlled study of ondansetron tablets (8 mg) three times daily for 4 weeks in DGE patients. Symptoms were assessed with the Gastroparesis Cardinal Symptom Index daily diaries. Gastric emptying (GE) of solids (scintigraphy) and duodenal lipid infusions (300 kcal over 2 h) were each assessed twice, with placebo and ondansetron. Drug effects on GE, symptoms during the GE study and during lipid infusion, and daily symptoms were analyzed.

Key results: Of 41 patients, 37 completed both GE studies and one completed 1; 31 completed both lipid infusions and four only placebo; and all 35 randomized patients completed 4 weeks of treatment. Compared to placebo, ondansetron reduced the severity of fullness (p = 0.02) and belching (p = 0.049) during lipid infusion but did not affect GE T_1/2. Both ondansetron and placebo improved daily symptoms versus the baseline period (p < 0.05), but the differences were not significant. In the analysis of covariance of daily symptoms during the treatment period, the interaction term between treatment and the acute effect of ondansetron on symptoms during lipid challenge was significant (p = .024).

Conclusions & inferences: Ondansetron significantly reduced fullness during enteral lipid infusion in patients with DGE. Overall, ondansetron did not improve daily symptoms versus placebo. But patients in whom ondansetron improved symptoms during enteral lipid challenge were perhaps more likely to experience symptom relief during daily treatment.

Background: Recently, radio-frequency ablation has been used to modulate slow-wave activity in the porcine stomach. Gastric ablation is, however, still in its infancy compared to its history in the cardiac field, and electrophysiological studies have been restricted to temperature-controlled, non-irrigated ablation. Power-controlled, irrigated ablation may improve lesion formation at lower catheter-tip temperatures that produce the desired localized conduction block.

Methods and results: Power-controlled, irrigated radio-frequency ablation was performed on the gastric serosal surface of female weaner pigs (n = 5) in vivo. Three combinations of power (10-15 W) and irrigation settings (2-5 mL min^-1) were investigated. A total of 12 linear lesions were created (n = 4 for each combination). Slow waves were recorded before and after ablation using high-resolution electrical mapping.

Key results: Irrigation maintained catheter-tip temperature below 50°C. Ablation induced a complete conduction block in 8/12 cases (4/4 for 10 W at 2 mL min^-1, 1/4 for 10 W at 5 mL min^-1, 3/4 for 15 W at 5 mL min^-1). Blocks were characterized by a decrease in signal amplitude at the lesion site, along with changes in slow-wave propagation patterns, where slow waves terminated at and/or rotated around the edge of the lesion.

Conclusions and inferences: Power-controlled, irrigated ablation can successfully modulate gastric slow-wave activity at a reduced catheter-tip temperature compared to temperature-controlled, non-irrigated ablation. Reducing the irrigation rate is more effective than increasing power for blocking slow-wave activity. These benefits suggest that irrigated ablation is a suitable option for further translation into a clinical intervention for gastric electrophysiology disorders.

Background: Serving as a reservoir, the gastric fundus can expand significantly, with an initial receptive and a following adaptive relaxation, controlled by extrinsic and intrinsic reflex circuits, respectively. We hypothesize that mechanosensitive enteric neurons (MEN) are involved in the adaptive relaxation, which is initiated when a particular gastric volume and a certain stretch of the stomach wall is reached. To investigate whether the responsiveness of MEN in the gastric fundus is dependent on tissue stretch, we performed mechanical stimulations in stretched versus ganglia "at rest".

Methods: Responses of myenteric neurons in the guinea pig gastric fundus were recorded with membrane potential imaging using Di-8-ANEPPS. MEN were identified by small-volume intraganglionic injection in ganglia stretched to different degrees using a self-constructed stretching tool. Immunohistochemical staining identified the neurochemical phenotype of MEN. Hexamethonium and capsaicin were added to test their effect on recruited MEN.

Key results: In stretched compared to "at rest" ganglia, significantly more MEN were activated. The change in the ganglionic area correlated significantly with the number of additional recruited MEN. The additional recruitment of MEN was independent from nicotinic transmission and the ratio of active MEN in stretched ganglia shifted towards a nitrergic phenotype.

Conclusion and inferences: The higher number of active MEN with increasing stretch of the ganglia and their greater share of nitrergic phenotype might indicate their contribution to the adaptive relaxation. Further experiments are necessary to address the receptors involved in mechanotransduction.

Background: Patients with chronic laryngopharyngeal symptoms, with or without pathologic reflux, frequently have poor response to standard therapies, which may be a result of overlapping cognitive-affective processes. Therefore, the aims of this study included measuring psychosocial distress and laryngeal-specific cognitive distress in patients with chronic laryngopharyngeal symptoms (LPS) as well as comparing these among laryngeal symptomatic patients with and without conclusive gastroesophageal reflux disease (GERD).

Methods: This prospective, single-center study enrolled adults with chronic LPS from 9/22 to 6/23. Patients completed eight questionnaires on quality of life, symptom burden, and psychosocial distress. The laryngeal cognitive affective tool (LCAT) assessed laryngeal-specific hypervigilance and anxiety; LCAT scores ≥33 were elevated. All patients underwent objective testing with endoscopy and/or ambulatory reflux monitoring and were categorized as proven GERD (GER+) or no proven GERD (GER-).

Key results: One hundred twenty-nine patients were included: 66% female, mean age 54.1 (17.5) years, mean BMI 27.6 (6.8) kg/m², 66% Caucasian, 57% with an elevated LCAT, and 53% GER+. Moderate-to-severe anxiety was found in 39% and moderate-to-severe depression in 19%. An elevated LCAT alone or with an elevated anxiety/depression score was found in 58%. Patient-reported outcomes scores, including LCAT scores (32.9 (13.8) GER- vs. 33.1 (12.6) GER+, p = 0.91), were similar between patients with and without GER+.

Conclusions and inferences: Patients with chronic LPS experience heightened levels of hypervigilance, symptom-specific anxiety, and psychosocial distress, regardless of the presence of pathologic GER.

Background: Gastric sensorimotor disorders (functional dyspepsia [FD] and gastroparesis [GP]) are prevalent and burdensome. Prolonged ambulatory recording using a wireless patch may provide novel information in these patients.

Methods: Consecutive adult patients (age ≥ 18 years) referred for gastric emptying scintigraphy (GES) were eligible for study inclusion. Patients were excluded if they had prior foregut surgery; were taking opioids or other medications known to affect gastric emptying; had a HgbA1C > 10; or were recently hospitalized. Three wireless motility patches were applied to the skin prior to GES. Patients wore the patches for 6 days while recording meals, symptoms, and bowel movements using an iPhone app.

Key results: Twenty-three consecutive adults (87% women; mean age = 43.9 years; mean BMI = 26.7 kg/m²) were enrolled. A gastric histogram revealed three levels of gastric myoelectric activity: weak, moderate, and strong. Patients with delayed gastric emptying at 4 h had weak gastric myoelectrical activity. Patients with nausea and vomiting had strong intestinal activity. Those with FD had weak gastric and intestinal myoelectric activity, and a weak meal response in the stomach, intestine, and colon compared to those with nausea alone or vomiting alone.

Conclusions and inferences: Patients with FD, and those with delayed gastric emptying, had unique gastrointestinal myoelectrical activity patterns. Reduced postprandial pan-intestinal myoelectric activity may explain the symptoms of FD in some patients. Recording gastrointestinal activity over a prolonged period in the outpatient setting has the potential to identify unique pathophysiologic patterns and meal-related activity that distinguishes patients with distinct gastric sensorimotor disease states.

Background: Esophagogastric junction outflow obstruction (EGJOO) is a heterogenous disorder in which the correct management strategy is unclear. We assessed whether functional lumen imaging probe (FLIP) topography data could select EGJOO, which would benefit from lower esophageal sphincter Botulinum toxin (Botox) injection.

Methods: This was a single-center prospective study of adult patients meeting Chicago Classification (CC) v3.0 criteria for EGJOO. We assessed differences in pretreatment physiologic measurements on high-resolution manometry (HRM) and FLIP and other relevant clinical variables in predicting Botox response (>50% in BEDQ at 2 months).

Key results: Sixty-nine patients were included (ages 33-90, 73.9% female). Of these, 42 (61%) were Botox responders. Majority of physiologic measures on HRM and FLIP and esophageal emptying were not different based on Botox response. However, a spastic-reactive (SR) FLIP contractile response (CR) pattern predicted a Botox response with OR 25.6 (CI 2.9-229.6) when compared to antegrade FLIP CR; and OR for impaired-disordered/absent CR was 22.5 (CI 2.5-206.7). Logistic regression model using backward elimination (p value = 0.0001, AUC 0.79) showed that a SRCR or IDCR/absent response and the upright IRP predicted Botox response. Response rates in tiered diagnostic groups were: (i) CCv3.0 EGJOO (60.9%), (ii) CCv4.0 EGJOO (73.1%), (iii) CCv4.0 + FLIP REO (80%), (iv) CCv4.0, FLIP REO, and abnormal FLIP CR (84.2%), and (v) CCv4.0, FLIP REO, and SR FLIP CR (90%).

Conclusions and inferences: FLIP helps identify patients with EGJOO who are likely to response to LES Botox therapy. An abnormal FLIP contractile response pattern is the single-most important predictor of a Botox response.

Background and purpose: Measurement of gastro-intestinal motility is increasingly performed under general anesthesia during endoscopic or surgical procedures. The aim of the present study was to review the impact of different anesthetic agents on digestive motility measurements in humans.

Methods: This systematic review was performed using the Medline-Pubmed and Web of Science databases. All articles published until October 2023 were screened by identification of key words. Studies were reviewed if patients had an assessment of digestive motility using conventional perfused manometry, high-resolution manometry, electronic barostat or functional lumen impedance planimetry with the use of inhaled or intravenous anesthetic anesthetic agents (propofol, ketamine, halogens, nitrous oxide, opioids, and neuromuscular blockades).

Results: Four hundred and eighty-eight unique citations were identified, of which 42 studies met the inclusion criteria and were included in the present review. The impact of anesthetics was mostly studied in patients who underwent esophageal manometry. There was a heterogeneity in both the dose and timing of administration of anesthetics among the studies. Remifentanil analgesia was the most studied anesthetic drug in the literature, showing a decrease in both distal latency and lower esophageal sphincter pressure after its administration, but the impact on Chicago classification was not studied. Inhaled anesthetics administration elicited a decrease in lower esophageal sphincter pressure, but contradictory findings were shown on esophageal motility following propofol or neuromuscular blocking agents administration.

Conclusion: Studies of the impact of anesthetics on digestive motility remain scarce in the literature, although some agents have been reported to profoundly affect gastro-intestinal motility.

Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction which has a wide clinical spectrum. Clinical action plans have been developed to address and to facilitate treatment in the setting of complex, chronic medical conditions. The CVS Action Plan was developed to meet the chronic and acute care needs of children and adults with CVS. While this tool has not been tested for clinical efficacy as was shown with action plans for functional constipation, anecdotal and indirect evidence supports its use. The CVS Action Plan has the potential to enhance outcomes by simplifying home management and streamlining disease recognition and acute care in the emergency department.