Journal of Neurogastroenterology and Motility最新文献

Background/aims: Disruptions in tight junction (TJ) protein expression leading to duodenal epithelial barrier impairment may contribute to increased intestinal permeability, potentially playing a role in functional dyspepsia (FD) pathophysiology. Currently published studies evaluated the role of several TJ proteins in FD patients with inconsistent results. Therefore, we conducted this systematic review and metaanalysis to evaluate the duodenal mucosal expression of several TJ proteins in FD.

Methods: We performed a systematic electronic search on PubMed, EMBASE, and Scopus using predefined keywords. Diagnosis of FD by Rome III or Rome IV criteria was considered acceptable. Full articles satisfying our inclusion and exclusion criteria were included. The principal summary outcome was the mean difference of several TJ proteins in FD patients and control subjects.

Results: A total of 8 and 5 studies were included in our qualitative and quantitative synthesis, respectively, with a total population of 666 participants, out of which 420 were FD patients. No significant differences were observed between FD patients and controls in the expression of claudin-1 (-0.102 [95% CI, -0.303, 0.099]), claudin-2 (0.161 [95% CI, -0.134, 0.456)], claudin-3 (0.278 [95% CI, -0.280, 0.837]), claudin-4 (0.045 [95% CI, -0.264, 0.354]), ZO-1 (-0.221 [95% CI, -0.683, 0.241]), ZO-2 (-0.070 [95% CI, -0.147, 0.007]), ZO-3 (-0.129 [95% CI, -0.376, 0.118]), β-catenin (-0.135 [95% CI, -0.484, 0.214]), E-cadherin (-0.083 [95% CI, -0.229, 0.063]), and occludin (-0.158 [95% CI, -0.409, 0.093]).

Conclusions: The expressions of all evaluated proteins including claudin-1, claudin-2, claudin-3, claudin-4, ZO-1, ZO-2, ZO-3, β-catenin, E-cadherin, and occludin did not significantly differ between FD patients and controls. However, due to the limited number of included studies, results should be interpreted with caution.

Background/aims: Cholecystokinin (CCK) administration has been shown to reduce lower esophageal sphincter (LES) pressure in normal subjects in manometric studies. Functional luminal imaging probe (FLIP) panometry offers a method to assess esophageal motility in response to sustained distension though mechanisms related to this response remain unexplored. The aim of this study is to evaluate the effect of CCK-8 on the esophageal response to distension in asymptomatic volunteers using FLIP.

Methods: Esophageal response to distension was studied in 7 asymptomatic volunteers (mean age ± SD [27 ± 2]; 86% female) before and after CCK-8 administration in a crossover study design. During sedated endoscopy, FLIP was performed twice with CCK-8 administered via intravenous push in one of 2 protocols: during filling (n = 4) or during emptying (n = 3). Esophagogastric junction distensibility index (EGJ-DI) at 60 mL fill volume and esophageal body contractile response patterns were analyzed.

Results: During the baseline FLIP study, all subjects had a contractile response with repetitive antegrade contractions both before and after CCK-8 administration. However, a sustained LES contraction or a sustained occluding contraction with esophageal shortening was observed in all subjects in the filling protocol, but in none during the emptying protocol. EGJ-DI was similar before and after CCK-8 during both filling (4.7 ± 1.9 mm²/mmHg vs 4.3 ± 1.8 mm²/mmHg) and emptying protocol (7.5 ± 1.4 mm²/mmHg vs 6.9 ± 0.6 mm²/mmHg).

Conclusion: While EGJ-DI appeared unaffected by CCK-8 administration in asymptomatic volunteers, CCK induced spastic-reactive contractions of the LES during distention suggesting that exogenous CCK interferes with normal LES relaxation during secondary peristalsis.

Background/aims: Diagnosing gastroesophageal reflux disease (GERD) is sometimes challenging because the performance of available tests is not entirely satisfactory. This study aims to directly measure the esophageal mucosal impedance during upper gastrointestinal endoscopy for the diagnosis of GERD.

Methods: Sixty participants with typical symptoms of GERD underwent high-resolution esophageal manometry, 24-hour multichannel intraluminal impedance-pH monitoring, upper gastrointestinal endoscopy, and mucosal impedance measurement. Mucosal impedance measurement was performed at 2, 5, 10, and 18 cm above the esophagogastric junction during gastrointestinal endoscopy using a specific catheter developed based on devices described in the literature over the last decade. The patients were divided into groups A (acid exposure time < 4%) and B (acid exposure time ≥ 4%).

Results: The mucosal impedance was significantly lower in group B at 2 cm (2264.4 Ω ± 1099.0 vs 4575.0 Ω ± 1407.6 [group A]) and 5 cm above the esophagogastric junction (4221.2 Ω ± 2623.7 vs 5888.2 Ω ± 2529.4 [group A]). There was no significant difference in the mucosal impedance between the 2 groups at 10 cm and 18 cm above the esophagogastric junction. Mucosal impedance value at 2 cm > 2970 Ω resulted in a sensitivity of 96.4% and a specificity of 87.5% to exclude GERD.

Conclusions: Direct measurement of mucosal impedance during endoscopy is a simple and promising method for diagnosing GERD. Individuals with an abnormal acid exposure time have lower mucosal impedance measurements than those with a normal acid exposure time.

Background/aims: Functional dyspepsia (FD) overlapping with other gastrointestinal disorders are quite common. The characteristics of FD overlap in Chinese population with latest Rome IV criteria were unclear. This large-scale outpatient-based study assessed the characteristics of FD overlap in South China.

Methods: Consecutive FD patients visited the Gastroenterology Clinic at 2 tertiary medical centers in Hangzhou, China who fulfilled the Rome IV criteria were enrolled. Complete questionnaires related to the gastrointestinal symptoms (Rome IV criteria), Reflux Disease Questionnaire, anxiety and depression, quality of sleep and life, and demographic information were collected.

Results: Among the total of 3281 FD patients, 50.69% overlapped with gastroesophageal reflux disease, 21.46% overlapped with irritable bowel syndrome, 6.03% overlapped with functional constipation. FD overlap had higher proportion of single/divorced/widowed rate, high education level, being employed, drinking, night shift, unhealthy dietary habit than FD only (P < 0.05). They had higher frequency of consultation and economic burden, as well as lower scores in quality of life (P < 0.001). Multivariate logistic regression showed that increasing age, female, low body mass index, history of gastroenteritis, anxiety, depression, and poor sleep quality were independent risk factors for FD overlap.

Conclusions: FD overlap was quite common in China with high economic burden and poor quality of life, FD patients with history of gastroenteritis, anxiety, depression, and poor sleep quality were more likely to have overlap disorders. Awareness of the physical and psychosocial stressors in overlapping condition would help optimize the management of FD overlap in clinical practice.

Background/aims: Achalasia is a disorder characterized by impairment in lower esophageal sphincter relaxation and esophageal aperistalsis, caused primarily by loss of inhibitory innervation. However, little is known about associated changes in esophageal smooth muscle. We examined the contractile phenotype and innervation of the circular smooth muscle, as well as inflammatory status, and correlated these with patient-specific parameters.

Methods: Circular smooth muscle biopsies were obtained in consecutive patients with achalasia undergoing peroral endoscopic myotomy. Axonal innervation and neurotransmitter subtypes were determined with immunocytochemistry, and this was used with quantitative Polymerase Chain Reaction (qPCR) to characterize smooth muscle proliferation and cellular phenotype, as well as collagen expression. These were compared to control tissue obtained at esophagectomy and correlated with patient demographic factors including age, onset of symptoms, and Eckhardt score.

Results: Biopsies of smooth muscle were obtained from 25 patients with achalasia. Overall, there was increased mast cell number and collagen deposition but increased smooth muscle cell proliferation vs control. There was a striking drop in axon density over controls, with no differences among subtypes of achalasia. Immunocytochemical analysis showed increased expression of the contractile marker α-smooth muscle actin, principally in Type 1 achalasia, that increased with disease duration, while qPCR identified increased mRNA for smoothelin with decreased myosin heavy chain and collagen 3a1, but not collagen 1a1.

Conclusions: The thickened circular smooth muscle layer in achalasia is largely denervated, with an altered contractile phenotype and fibrosis. Biopsies obtained during peroral endoscopic myotomy provide a means to further study the pathophysiology of achalasia.