Neurogastroenterology and Motility最新文献

Background: We aim to investigate the long-term clinical anorectal outcomes and anorectal physiology in patients treated non-surgically for minor types of anorectal malformations (ARM).

Methods: We retrospectively included 79 non-surgically treated patients born with minor types of ARM. We investigated constipation and fecal incontinence according to the Rome IV criteria, as well as anorectal physiology using anorectal manometry.

Key results: Of all patients, 60% reported no constipation and no fecal incontinence, 38% experienced constipation, and 2% had fecal incontinence. All patients could contract the external anal sphincter and the puborectal muscle, both voluntarily and involuntarily, and 94% possessed a functional internal anal sphincter. The mean anal sensibility was 2.5 mA.

Conclusions and inferences: The long-term anorectal outcomes of non-surgically treated patients diagnosed with minor types of ARM seem optimal. Most of these patients experience no constipation and fecal incontinence; some experience constipation and relatively seldom fecal incontinence. Furthermore, most patients possess all the known fecal continence mechanisms. This study demonstrates that patients with minor ARM who received non-surgical treatment can achieve optimal anorectal function outcomes.

Background: Gastroparesis (GP) is a chronic gastrointestinal motility disorder marked by delayed gastric emptying in the absence of mechanical obstruction. Despite its debilitating nature and high unmet therapeutic need, the clinical research landscape in GP remains underexplored. This study aimed to assess the trends, characteristics, and funding patterns of GP-related clinical trials registered on ClinicalTrials.gov (CTG).

Methods: A cross-sectional analysis was conducted using data from CTG between September 27, 2007, and April 30, 2024. Trials were identified using specific search terms and categorized by study type, phase, funding source, and status. Comparisons were made between GP trials and all registered trials on CTG. Statistical analyses included frequency distributions and odds ratios (OR) with 95% confidence intervals (CI).

Results: A total of 249 GP studies were registered, comprising only 0.059% of all CTG studies, with 68 ongoing as of April 2024. Interventional studies represented 77.1% of all GP trials, but this proportion declined significantly in ongoing studies (OR 0.23; 95% CI: 0.13-0.41). Registry-based studies increased significantly among ongoing trials (OR 3.4; 95% CI: 1.56-7.57). Industry and NIH-funded trials accounted for 27.3% and 8.4%, respectively, while the majority (77.1%) were funded by other sources. Completion rates for GP studies were significantly lower (39.8%) than the overall CTG average (50.3%), and GP trials had higher discontinuation (18.5% vs. 8.8%) and unknown status rates (41.8% vs. 14.8%). Ongoing GP studies also showed a marked decline in early-phase trials, particularly Phase 1 (OR 0.05; 95% CI: 0.03-0.08), while Phase 2 studies were more common when compared with all CTG studies.

Conclusion: Despite increasing overall research activity on CTG, clinical trials in GP have remained relatively stagnant, with fewer interventional and early-phase trials in recent years. The high discontinuation and low completion rates, along with limited industry sponsorship, highlight significant barriers to advancing GP therapeutics. Attention is needed from the industry and policymakers to bring focus on the development of therapeutic solutions for improved clinical outcomes.

Aim: To clarify the function of transient receptor potential vanilloid 4 (TRPV4)-prostaglandin E2 (PGE₂) signaling in the colon of rats with irritable bowel syndrome (IBS) induced by water-avoidance stress (WAS). On this basis, to explore whether colonic TRPV4-PGE₂ signaling is involved in the mechanism of action of Chinese herbal formula Shugan Decoction (SGD) on IBS.

Methods: The rat model of IBS was induced by chronic WAS, and the number of fecal pellets was counted. Meanwhile, the visceral pain pressure threshold was measured using colorectal distension. Western blot or immunofluorescence was used to measure the protein expressions of TRPV4, EP1, and EP3 in the colon. ELISA was used to determine the contents of PGE₂ in colonic tissue. The contractile activities of the colonic longitudinal muscle strips were observed via an organ bath experiment.

Results: Compared with the control group, the content of PGE₂, the expressions of TRPV4, EP1, and EP3 receptors in the colon of the rats in the WAS group increased, accompanied by enhanced fecal pellet output and reduced visceral pain pressure threshold; meanwhile, the tension and the amplitude of the spontaneous contraction of the colonic longitudinal muscle were significantly enhanced. These parameter values in the SGD group were significantly restored compared with those in the WAS group. The suppression of contractile tension and amplitude by the TRPV4 inhibitor HC-067047 in the WAS group was greater than that in the control and SGD groups. The enhancement of contractile amplitude by PGE₂ in the WAS group was weaker than that in the control group but was stronger than that in the SGD group. Interestingly, the suppression of contractile tension by the EP1 antagonist ONO-8711 in the SGD group was less than that in the WAS group.

Conclusion: SGD can ameliorate dysmotility of colonic longitudinal muscle and visceral hypersensitivity caused by WAS maybe by reducing the release of PGE₂ and decreasing the expression of TRPV4 and EP1.

Background: Elevated integrated relaxation pressure (IRP) on high-resolution manometry (HRM) could signify outflow obstruction, but could be artifactually elevated in the presence of a hiatus hernia (HH). We hypothesized that separate IRP measurements across the lower esophageal sphincter (LES) and crural diaphragm (CD) would differ from conventional IRP in the context of a hiatus hernia.

Methods: Esophageal tests from 467 patients were analyzed for differential IRP measurement across LES or CD separately in the presence of a HH. Patients were required to have undergone HRM and ambulatory reflux monitoring off antisecretory therapy for the investigation of esophageal symptoms presumed to be of reflux etiology to be considered for inclusion. A comparison cohort of 19 achalasia patients with HH was also analyzed. Supine IRP > 15 mmHg was considered abnormal.

Results: Median IRP was higher across both LES and CD compared to either LES or CD alone (p < 0.001). Among 158 patients with differential LES-CD IRP measurements, conventional median IRP > 15 mmHg was seen in 11 patients (7.0%), but only in 3 patients (2.0%) across either LES or CD (p = 0.03), and only one (0.6%) across the LES (p = 0.003). Although IRP across the LES was significantly higher in achalasia compared to patients with HH (p < 0.001), IRP across the CD alone was not abnormal in both cohorts.

Conclusions: Differential IRP measurement in HH reduces overdiagnosis of outflow obstruction.

Background: In previous studies, abnormal changes in the enteric nervous system (ENS) were often found in intestinal specimens from patients with slow transit constipation (STC). However, there are no clear pathological diagnostic criteria for STC due to the lack of accurate quantitative data references. The association of ENS alterations with STC remains unanswered.

Methods: Full-thickness colon specimens were obtained from 10 STC patients who underwent subtotal colectomy and 20 colon cancer patients who underwent radical colectomy. Using stereoscopic imaging combined with tissue clearing, immunohistochemistry, and confocal imaging techniques, the differences in ENS quantitative data between STC patients and controls were observed, and the correlation between this change and the clinical symptoms of STC was analyzed.

Key results: Quantitative analysis demonstrated significant reductions in both myenteric plexus density (descending: control: Mean ± SD = 27.0% ± 3.0% vs. STC: 22.2% ± 3.5%, p = 0.004; sigmoid: 26.1% ± 5.6% vs. 20.3% ± 4.1%, p = 0.018) and ganglion density (descending: 8.7% ± 2.6% vs. 5.9% ± 2.1%, p = 0.015; sigmoid: 11.5% ± 2.3% vs. 8.7% ± 3.3%, p = 0.042) in STC patients compared to controls. After stretch correction, we observed significant decreases in both neuronal populations (descending: 205.2 ± 23.2 vs. 180.3 ± 18.6, p = 0.016; sigmoid: 168.3 ± 20.0 vs. 137.2 ± 18.0, p = 0.002) and ganglion volumes (descending: 1.53 ± 0.42 vs. 1.19 ± 0.24, p = 0.045; sigmoid: 1.74 ± 0.42 vs. 1.36 ± 0.30, p = 0.031) in STC patients compared to controls. Furthermore, the proportion of neuronal subtypes in STC patients was significantly altered. Notably, several of these neuropathological changes correlated significantly with STC symptom severity.

Conclusions and inferences: This study revealed abnormal changes in colonic ENS in STC patients through three-dimensional imaging and quantitative analysis of ENS. There was a certain correlation between ENS changes and constipation symptoms in STC patients, and further studies of other components of ENS are needed to clarify the correlation between STC and ENS.

Background: Patients with IBS often report meal-related symptoms, which may negatively affect IBS-related quality of life, psychological health, and lead to food-avoidant behaviors. However, the understanding of the epidemiology of these symptoms is limited.

Methods: We compared characteristics of adult patients with Rome IV-defined IBS with and without meal-related abdominal discomfort or pain ≥ 50% of the time. Participants were recruited from the ContactME-IBS research register. We collected data concerning demographics, IBS symptoms, psychological health, quality of life, and impact on work and daily activities using validated questionnaires. We used logistic regression to explore independent predictors of meal-related discomfort or pain ≥ 50% of the time in IBS.

Key results: Of 752 respondents with Rome IV IBS, 561 (74.6%) reported meal-related abdominal discomfort or pain ≥ 50% of the time. 89.3% of individuals with meal-related discomfort or pain ≥ 50% of the time were female vs. 80.6% of those without (p = 0.002). Those with meal-related discomfort or pain ≥ 50% of the time were younger (43.7 years vs. 50.1 years, p < 0.001), had a higher prevalence of symptoms meeting criteria for functional dyspepsia (FD), especially postprandial distress syndrome (49.1% vs. 30.2%, p < 0.001), and reported higher gastrointestinal symptom-specific anxiety scores, lower IBS-related quality of life scores, and higher levels of activity impairment (p < 0.001 for all analyses). After logistic regression analysis, females, those meeting criteria for FD, younger individuals, and those reporting higher gastrointestinal symptom-specific anxiety scores were more likely to report meal-related discomfort or pain ≥ 50% of the time.

Conclusions: Meal-related abdominal discomfort or pain ≥ 50% of the time was associated with female sex, younger age, and comorbid FD. Better characterization and recognition of patients affected by meal-related discomfort or pain may allow more personalized dietary and psychological interventions.

Background: Several genetic syndromes that affect nerve development and functioning may involve the enteric nervous system and present clinically as dysmotility syndromes, typically in childhood.

Aim: To review the enteric neuromuscular manifestations, predominantly observed in adults, of neurofibromatosis type I at a tertiary referral center.

Methods: We conducted a medical records review at the Mayo Clinic and documented clinical manifestations and findings on radiology, pathology, and specialized motility tests of the esophagus, stomach, colon, and rectal evacuatory functions. The tests included scintigraphic gastrointestinal and colonic transit measurements, intraluminal esophageal, gastrointestinal, colonic, and anorectal manometry, and balloon expulsion test.

Results: Among 2406 with documented NF1, the gastrointestinal manifestations were obstruction or dysmotility, seen in 2% of the cohort. Thirteen patients had small bowel or colonic obstructions: 4 gastrointestinal stromal tumors, 3 malignant peripheral nerve sheath tumors, 3 neurofibromas, 1 diffuse ganglioneuromatosis, 1 schwannoma, and 1 inflammatory fibroid polyp. In addition, 38 patients had abnormal gut motility, including esophageal achalasia or spasm, delayed gastric emptying, slow colonic transit, and dyssynergic defecation. Gastric, small bowel, and colonic manometry were characterized by normal amplitude incoordinated contractions suggestive of neuropathy. In the few resected specimens, myenteric plexus proliferation or diffuse ganglioneuromatosis was identified histologically.

Conclusions: In addition to mechanical obstruction, typically due to benign tumors affecting smooth muscle or components of nerve (sheath or nerve fiber), patients with NF1 may present with dysmotility syndromes such as gastroparesis, slow colonic transit, or global dysmotility. Neuropathic dysmotility in NF1 can be identified by manometry and by histological evidence of myenteric plexus proliferation or diffuse ganglioneuromatosis.

Background: Dysphagia after laparoscopic Nissen fundoplication (LNF) is common and may be due to post-fundoplication outflow obstruction (PFOO) as defined by high-resolution manometry (HRM) using the Padova Classification. This study aimed to compare clinical and HRM parameters between patients with manometric PFOO and those with a functioning, effective fundoplication (FELF), and to evaluate treatment outcomes in PFOO patients.

Methods: This retrospective study from two international centers included patients who underwent LNF and postoperative HRM between January 2000 and January 2025. Patients were categorized into PFOO (manometric PFOO) and FELF (manometric FELF and normal reflux study) groups. HRM parameters including LES basal pressure, integrated relaxation pressure (IRP), and esophageal body function were compared. Postoperative dysphagia was assessed clinically, and treatment outcomes in PFOO patients were evaluated.

Results: Among 106 patients (62 PFOO, 44 FELF), the PFOO group showed significantly higher median LES basal pressure (41.2 vs. 23.7 mmHg, p < 0.01), IRP (19.3 vs. 10.3 mmHg, p < 0.01), and LES lengths (p = 0.01). PFOO patients had an increased incidence of elevated intrabolus pressure and premature swallows (p < 0.01). Dysphagia was reported in 89% of PFOO patients versus 5% in FELF (p < 0.01). Of symptomatic PFOO patients undergoing retreatment (pneumatic dilation, redo surgery, or both), 89% achieved symptom improvement.

Conclusions: This first study applying the Padova Classification confirms HRM can distinguish obstructive from functional fundoplications post-LNF, supporting its diagnostic role in managing postoperative dysphagia.

Background: The article by Martín-Domínguez V et al. proposes genetic testing as the first diagnostic test for lactose malabsorption, given its high concordance with the lactose breath test (LBT). We think that conceptual and methodological inconsistencies undermine this conclusion.

Methods: The genetic test, LBT, and Gaxilose test measure different physiological aspects such as genetic predisposition, lactose malabsorption, and lactase enzymatic activity, respectively, so the three tests cannot be used interchangeably. Diagnostic bias is introduced by the study's limited use of biopsy confirmation, disregard for secondary hypolactasia, and reliance on genotype as a reference standard.

Results: Additionally, the clinical validity of the results is compromised by the high variability in genetic polymorphisms across populations, unreported comorbidities like SIBO or IBS, and dubious symptom assessment during testing. Evidence from multicenter studies demonstrates that the Gaxilose test offers high sensitivity and specificity and is well tolerated.

Conclusions: We conclude that genetic testing alone cannot replace functional or structural assessments and warn that the study's conclusions may lead to misleading diagnostic recommendations in real-world clinical practice.