Neurogastroenterology and Motility最新文献

Introduction: High-resolution manometry (HRM) allows assessment of esophagogastric junction (EGJ) disruption. While type 3 EGJ predicts definitive gastroesophageal reflux disease (GERD), type 2 EGJ is less clearly implicated in GERD pathogenesis. This study aimed to characterize physiologic findings in type 2 EGJ to determine if the HRM-based Milan Score can define GERD within type 2 EGJ.

Methods: 535 patients with suspected GERD who underwent HRM and reflux monitoring were retrospectively analyzed. Clinical, HRM, and reflux study data were compared between the EGJ morphology subtypes, with objective GERD defined according to Lyon Consensus 2.0. The Milan Score, a novel metric that integrates ineffective esophageal motility, EGJ-contractile integral, EGJ morphology, and straight leg raise response, was abnormal when ≥ 137 (risk rate 50% for GERD). Receiver operating characteristic (ROC) curve analysis was performed to assess the accuracy of the Milan Score to predict objective GERD.

Results: Type 3 EGJ was associated with the highest rate of objective GERD, followed by type 2 and type 1 EGJ (p < 0.001), with a corresponding stepwise increase in AET from type 1 to 3 EGJ (p < 0.001). Type 2 EGJ with Milan Score < 137 resembled type 1 EGJ (objective GERD in 23.6% vs. 33.2%, p = 0.09), and type 2 EGJ with score ≥ 137 resembled type 3 EGJ (objective GERD in 88.2% vs. 78.8%, p = 0.11). On ROC analysis, the Milan Score had an area under the curve of 0.858.

Conclusion: While type 2 EGJ includes varying GERD severity, the Milan Score can segregate patients at risk for objective GERD.

Background: The gut, the ureter, or the Fallopian tube all transport biological fluids by generating trains of propagating smooth muscle constrictions collectively known as peristalsis. These tubes connect body compartments at different pressures. We extend here Poiseuille's experiments on liquid flow in inert tubes to an active, mechanosensitive tube: the intestine.

Methods: We use as a miniature myogenic peristaltic pump model, the fetal chicken gut, and measured the flow and contractile wave propagation as a function of the initially applied pressures and pressure gradients. We dissect the molecular pathways of smooth muscle mechanosensitivity by measuring the force generated by gut rings in different pharmacological conditions.

Results: We demonstrate that smooth muscle contractions in response to stretch or pressure is mediated by L-type Ca²⁺ channels and IP3 receptors. We show that this positive-feedback mechanosensitive behavior can spontaneously generate pressure gradients across gut segments initially subject to equal pressure; this same mechanism tends to stabilize initially applied pressure gradients; it can act jointly or compete with the pressure gradient induced by directional peristaltic waves. We demonstrate that high pressure differentials can reverse the physiological propagation direction of contractile waves imparted by interstitial cell of Cajal pacemaker activity. We find that flow rate increases with tube length, but that the maximum pressure differential generated depends solely on smooth muscle contractile force and on the initial resting pressure applied inside the organ.

Conclusions: We provide fundamental mechanical and hydrodynamic insight into the myogenic mechanisms of transport in the gastrointestinal tract. We scale up our results to other human peristaltic organs and discuss their implications for pathophysiology of intestinal obstruction, vesicoureteral reflux and endometriosis.

Introduction: Gastrointestinal (GI) magnetic resonance imaging (MRI) enables simultaneous assessment of gastric peristalsis, emptying, and intestinal filling and transit. However, GI MRI in animals typically requires anesthesia, which complicates physiology and confounds interpretation and translation to humans. This study aimed to establish GI MRI in conscious rats, and for the first time, characterize GI motor functions in awake versus anesthetized conditions.

Methods: Fourteen Sprague-Dawley rats were acclimated to remain awake, still, and minimally stressed during MRI. GI MRI was performed under both awake and anesthetized conditions following voluntary consumption of a contrast-enhanced test meal.

Results: Awake rats remained physiologically stable during MRI, giving rise to gastric emptying of 23.7% ± 1.4% at 48 min and robust peristaltic contractions propagating through the antrum at 0.72 ± 0.04 mm/s, with a relative amplitude of 40.7% ± 2.3% and a frequency of 5.1 ± 0.1 cycles per minute. Under anesthesia, gastric emptying was approximately halved, mainly due to a significant reduction in peristaltic contraction amplitude, rather than the change in propagation speed, whereas the contraction frequency remained unchanged. Additionally, the small intestine showed faster filling and stronger motility in awake rats.

Conclusion: This study demonstrates the feasibility of GI MRI in awake rats and highlights notable differences in gastric and intestinal motility between awake and anesthetized states. Our protocol provides a novel and valuable framework for preclinical studies of GI physiology and pathophysiology.

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are associated with gastrointestinal (GI) immune-related adverse events (IrAEs). GI dysautonomia is a rare IrAE due to enteric nervous system dysfunction with/without generalized autonomic failure. Here, we present a case series of GI dysautonomia following ICI therapy and conduct a systematic review of the literature.

Methods: We present three patients with ICI-induced GI dysautonomia referred to our tertiary ICI-neurotoxicity service. A systematic review was conducted in OVID, Cochrane, and Scopus until December 2024 for studies evaluating ICI-induced GI dysautonomia, including clinical presentation, treatment choice, and mortality.

Key results: Three male patients were treated with ICIs for melanoma (n = 2) and chondrosarcoma. Severe GI symptoms developed at seven years, two months, and three weeks from treatment initiation at ages 77, 60, and 57 years old, respectively. All three had panenteric involvement with additional autonomic dysfunction. Two patients had poor outcomes with enteral and parenteral nutrition dependence, respectively, and died from GI complications. The third case responded well to prolonged high-dose corticosteroids and mycophenolate maintenance. On systematic review, 18 individual cases were reported in 15 publications, with the onset of GI dysautonomia at a mean time of 13.6 weeks (SD 14.3) from ICI exposure. Corticosteroids were the primary treatment in 72% (n = 13), with a limited duration and low (< 1 mg/kg/day prednisolone equivalent) dose used in 46.2% (n = 6/13). There was GI recovery in 38.5% (n = 5) and mortality in 47.0% (n = 8; 1 missing).

Conclusion: ICI-induced GI dysautonomia is a potentially life-threatening IrAE requiring early recognition and effective immunosuppression to optimize outcome.

Background: Colon displays structural and functional diversity. However, the region-specific motility effects of spinal nerves on the colon are unclear. We mapped the regional colonic motor response to thoracolumbar (T12-L1) (TLNS) and sacral (S1-S4) (SNS) roots nerve electrical stimulation (ES) in an anesthetized porcine model, with or without concomitant afferent (AB) or efferent (EB) transmission block.

Methods: Adult male Yucatan pigs (n = 16) underwent a laminectomy followed by unilateral (left root) SNS (S1-S4, 30 Hz, 0.3 ms, 0.5 mA, PT, 30 s ON/90 s OFF) or with concomitant AB or EB (40 kHz, 0.1 ms, 2 mA). In a separate group (n = 7), TLNS (T12-L1, 10 Hz, 0.3 ms, 0.5 mA, continuous or 30 Hz, 0.3 ms, 0.5 mA, PT, 30 s ON/90 s OFF) of the left root concomitant with or without EB was applied. Proximal (pC), transverse (tC), distal (dC) colon and anal canal (AC) luminal manometry were monitored before, during and after stimulation. Area under the curve of contraction (AUC), luminal pressure heat maps, and contraction spectral analysis were analyzed.

Key results: S2 ES increased the power of the contraction frequency spectrum in both dC and AC during stimulation and increased the AUC of contraction in dC and AC during and post-stimulation. AB and EB partially reduced dC, while EB abolished the increase in AC. In contrast, S1, S3, or S4 ES as well as TLNS had little effect on motility.

Conclusions: In anesthetized male pigs, S2 ES induces a robust motility response in the distal colon via the central network while in the anal canal via efferent pathways.

Background: Gastroparesis is a debilitating disorder with limited treatment options, and metoclopramide remains the only FDA-approved pharmacologic therapy. Concerns about metoclopramide-induced tardive dyskinesia (TD) are based on older studies with inconsistent incidence estimates (1%-15%). A reassessment of metoclopramide's TD risk is needed.

Methods: A retrospective cohort study using the MarketScan Research database analyzed TD incidence in adults (2011-2020) with at least 12 months of medical and pharmacy benefits. TD rates were compared among metoclopramide-treated gastroparesis patients, those untreated, and the general population. Poisson regression models adjusted for person-years (p-yrs) at risk.

Key results: The incidence of TD among metoclopramide-treated gastroparesis patients was 159.4 per 100,000 p-yrs (0.37%), notably lower than guideline estimates (1%-15%). Comparatively, TD incidence was 121.3 (0.26%) in untreated gastroparesis patients, 51.4 (0.12%) among all metoclopramide users, and 7.6 (0.02%) in the general population. Higher TD rates were observed in older adults (≥ 65 years), females, and in patients with prolonged metoclopramide use, diabetes, psychiatric conditions, Parkinson's disease, or concurrent use of dopamine receptor-blocking agents. Adjusted analyses found no significant independent association between metoclopramide use and increased TD risk in gastroparesis patients.

Conclusions & inferences: TD incidence is uncommon with metoclopramide use and lower than previously estimated in gastroparesis patients. These findings suggest metoclopramide may be a viable treatment option and warrant a reassessment of its risk-benefit profile in gastroparesis management.

Introduction: A significant, yet often overlooked, complication of subarachnoid hemorrhage (SAH) is the development of acidosis. Denervation atrophy is a recognized cause of neural ganglion damage following primary motor neuron damage, but the effect of tissue pH changes has not been thoroughly investigated.

Aim: This study investigates whether acidosis causes Auerbach ganglia damage following SAH.

Methods: Twenty-four hybrid rabbits were selected, and five (GI; n = 5) were used for the analysis of the Auerbach ganglia. Six animals (GII; n = 6) were allocated to the SHAM group, receiving 1 cc of saline. The remaining 13 animals (GIII; n = 13) were allocated to the study group, receiving 1 cc of autologous arterial blood injected into the cisterna magna to induce subarachnoid hemorrhage under general anesthesia. Blood pH values were recorded before the experiment, on the seventh day, and immediately before sacrifice. Animals were sacrificed after 1 week, and the degenerated neuron density of the Auerbach ganglia in 1 cm segments of the ascending colon was estimated. The pH values and degenerated Auerbach ganglia neuron densities (n/mm³) were compared using the Mann-Whitney U test.

Results: The presurgical blood pH values of all animals were 7.431 ± 0.032. On the seventh day, pH values were 7.403 ± 0.052 in GI; 7.395 ± 0.024 in GII; and 7.264 ± 0.045 in GIII. At the end of the experiment, pH values were 7.431 ± 0.037 in GI; 7.395 ± 0.062 in GII; and 7.330 ± 0.035 in GIII. Degenerated neuron densities of Auerbach ganglia neurons were 13 ± 4 in GI, 34 ± 6 in the SHAM group, and 87 ± 15 in GIII. The p values were: p < 0.005 for GII/GI; p < 0.0001 for GII/GIII; and p < 0.00005 for GI/GIII.

Conclusion: Acidosis is a potential causative factor of Auerbach ganglia degeneration following SAH, a phenomenon not previously described.

Background: Clinical non-response to peroral endoscopic myotomy (POEM) is a major clinical challenge of achalasia. Four-dimensional high-resolution impedance manometry (4D-HRIM) enables evaluation of both esophageal motility and bolus clearance. This study investigated whether 4D-HRIM could predict outcomes of POEM in achalasia patients.

Methods: Achalasia patients who underwent preoperative 4D-HRIM evaluation and POEM were retrospectively included. The baseline characteristics, myotomy metrics, traditional preoperative examinations metrics, and 4D-HRIM metrics were compared between clinical response and non-response patients. Statistically significant parameters were selected to deliver receiver operating characteristic curve (ROC) analysis, with stepwise regression constructing optimal prediction models.

Key results: A total of 121 achalasia patients were included, of which 10 patients were assigned to the clinical non-response group. While no significant difference was found in HRM, endoscopy, and barium esophagram metrics, patients in the clinical non-response group presented higher phase-specific intrabolus pressure (IBP), increased pressure, and lower distensibility index (DI) of the esophageal body, higher pressure at EGJ, and lower retention ratio under 4D-HRIM evaluation. The area under the curve (AUC) for predicting poor outcomes using a single 4D-HRIM metric, such as phase-specific IBP or DI, ranged from 0.69 to 0.76. The combination of the median IBP at phase 2 and the retention ratio showed the best predictive performance, with an AUC of 0.817.

Conclusions and inferences: 4D-HRIM evaluation could help predict clinical outcomes after POEM in achalasia, thereby enabling us to develop personalized surgical strategies and establish more meticulous postoperative follow-up plans.

Background: Chronic gastroduodenal symptoms arise from heterogeneous gastric motor dysfunctions. This study applied multimodal physiological testing using gastric emptying scintigraphy (GES) with intragastric meal distribution (IMD) and Gastric Alimetry body surface gastric mapping (BSGM) to define motility and symptom associations.

Methods: Patients with chronic gastroduodenal symptoms underwent simultaneous supine GES and BSGM with a 30 m baseline, 99mTC-labeled egg meal, and 4 h postprandial recording. IMD (ratio of counts in the proximal half of the stomach to the total gastric counts) was calculated immediately after the meal (IMD0), with < 0.568 defining abnormal IMD. BSGM phenotyping followed a consensus approach, based on normative spectral reference intervals.

Results: Among 67 patients (84% female, median age 40 years, median BMI 24 kg/m²), median IMD0 was 0.76 (IQR: 0.69-0.86) with 5 (7.5%) meeting abnormal IMD criteria. Delayed gastric emptying (n = 18) was associated with higher IMD0 (median 0.9 vs. 0.7, p = 0.004). On BSGM, 15 patients had abnormal spectrograms (5 [7.5%] high frequency and 10 [14.9%] low rhythm stability and/or amplitude); and in these patients, higher IMD0 (proximal retention) strongly correlated to delayed BSGM meal responses (R = -0.71, p = 0.003). Lower IMD, indicating antral distribution, correlated with higher gastric frequencies (R = -0.27, p = 0.03). BSGM abnormalities paired with abnormal IMD were associated with worse dyspeptic symptoms.

Conclusion: Proximal retention of food as assessed by IMD correlated with delayed emptying, and in the presence of neuromuscular spectral abnormalities (abnormal frequencies or rhythms), delayed motility responses on BSGM. Patients with multiple motor abnormalities experience worse dyspeptic symptoms.

Background: This study aims to evaluate transverse rectal diameter (TRD) as a predictor of clinical severity and response to conventional treatment in children with chronic functional constipation (CFC).

Methods: This longitudinal prospective study enrolled 105 children aged 4-17 years with CFC at Fondazione Policlinico A. Gemelli (Rome, Italy) from December 2021 to April 2025. We used the Constipation Scoring System (CSS), pelvic ultrasound (TRD, anterior wall thickness [WT], detrusor thickness [DT]), and follow-up assessments at 2, 4, and 6 months. Patients without TRD or CSS improvement at 6 months underwent high-resolution anorectal manometry (HR-ARM). Statistical analysis included generalized linear mixed-effects models.

Results: Children with megarectum (TRD ≥ 3 cm) showed higher CSS scores (p = 0.002), TRD (p = 0.001), WT (p = 0.021), and longer constipation duration (p = 0.005) compared to controls. TRD positively correlated with age (p = 0.008) and CSS (β = 1.41, p = 0.043). A significant reduction in TRD and WT was observed at 2 months posttreatment (p < 0.001). Nine patients who failed to improve had type I dyssynergia confirmed on HR-ARM. DT showed no significant correlation with clinical severity.

Conclusion: TRD measured by pelvic ultrasound is a reliable noninvasive marker for assessing severity and monitoring treatment response in pediatric CFC. Persistence of rectal dilatation may suggest underlying defecatory dyssynergia and guide further evaluation. Integration of TRD into routine practice could improve personalized, outpatient-based care. Further multicentric studies are needed to validate TRD as a predictive biomarker in long-term management.