Estrogen regulates the expression of small-conductance Ca-activated K+ channels in colonic smooth muscle cells.

AIM: This study aimed to determine the effects of small-conductance Ca(2+)-activated K(+) (SK) channels in colonic relaxation and the regulation of SK channels by estrogen. METHODS: The contractile activity of muscle strips from male rats was estimated, and drugs including vehicle (DMSO), 17ß-estradiol (E2), or apamin (SK blocker) were added, respectively. In a further experiment, muscle strips were preincubated with apamin before exposure to E2. The levels of the SK2 and SK3 protein expression in the colonic smooth muscle cells (SMCs) were detected. SMCs were treated with ICI 182780 (estrogen receptor [ER] antagonist) plus E2, BSA-E2, PPT (ERα agonist), or DPN (ERß agonist). SK3 mRNA and protein expression levels were detected. RESULTS: The muscle strips responded to E2 with a decrease and to apamin with a transient increase in tension. Preincubation with apamin partially prevented E2-induced relaxation. Two SK channel subtypes, SK2 and SK3, were coexpressed with α-actin in colonic SMCs. The quantitative ratio of the SK transcriptional expression in colonic SMCs was SK3 > SK2. The SK3 expression was upregulated by E2, and was downregulated by ICI 182780, but was not influenced by BSA-E2. Furthermore, the effect of PPT on the expression of SK3 was almost the same as that of E2, while DPN did not influence the protein expression of SK3. CONCLUSION: These findings indicate that SK3 is involved in the E2-induced relaxing effect on rat colonic smooth muscle. Furthermore, E2 upregulates the expression of SK3 in rat SMCs, and that this effect is mediated via the ERα receptor.

Characteristics of reflux and gastric electrical activity in gastroesophageal reflux disease with ineffective esophageal motility.

OBJECTIVES: The impact of ineffective esophageal motility (IEM) on gastroesophageal reflux disease (GERD) remains unknown, and abnormal esophageal motility often coexists with abnormal gastric motility. We aimed to investigate the role of IEM in GERD and its relationship with gastric electrical activity. METHODS: Patients diagnosed as GERD based on GERD-questionnaire score ≥8 in our hospital from January 2020 to June 2022 were included. All patients underwent 24-h multichannel intraluminal impedance-pH monitoring, high-resolution manometry, and electrogastrogram and were categorized into the normal esophageal motility (NEM) and IEM groups, respectively. Reflux characteristics and gastric electric activity were compared between the two groups, and the correlation between gastric electric activity and reflux was analyzed. RESULTS: Acid exposure time, total reflux episodes, and DeMeester score in the IEM group were higher than those in the NEM group. Distal mean nocturnal baseline impedance was significantly lower in the IEM group. Compared with the NEM group, the power ratio (PR) of fundus, antrum and pylorus and premeal and postmeal normal wave ratio of antrum were significantly lower in IEM. The total reflux episodes were negatively correlated with the PR of fundus and pylorus, and the DeMeester score was negatively correlated with the PR of corpus and pylorus. CONCLUSIONS: IEM may lead to increased reflux, resulting in esophageal mucosal damage. There may be consistency between abnormal esophageal motility and gastric motility.

Endoscopic detection of esophageal low-grade squamous dysplasia: How to predict pathologic upgrades before treatment?

OBJECTIVE: In this study we aimed to predict the risk factors related to histopathologic upgrade after endoscopic submucosal dissection (ESD) in patients with pre-ESD esophageal squamous low-grade intraepithelial neoplasm (LGIN). METHODS: A training cohort of 201 patients with biopsy-confirmed esophageal squamous LGIN and underwent ESD at a tertiary medical center between January 2017 and July 2019 were included. Risk factors for histological upgrade were identified using the least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then established. Internal validation was evaluated by discrimination, calibration plot, and decision-curve analysis. Another cohort of 48 patients were prospectively collected from July 2019 to June 2021 for external validation of the nomogram. RESULTS: The rate of histological upgrade was 34.8% (70/201) and 27.1% (13/48) in the training and validation sets, respectively. LASSO regression identified that tumor area (mm2 ) per biopsy, Lugol's staining pattern, background coloration, and the circumferential range of the lesion were significantly associated with histological upgrade. The final nomogram attained favorable prediction efficacy in the training cohort (area under the receiver operating curve [AUROC] 0.96, 95% confidence interval [CI] 0.94-0.98) and validation cohort (AUROC 0.92, 95% CI 0.79 -0.99). This model generated well-fitted calibration and clinical-decision curves in both cohorts. CONCLUSIONS: The nomogram may better guide clinical decision on whether performing EDS or follow-up for suspicious lesions in patients with biopsy-confirmed esophageal squamous LGIN.

Esophagogastric junction contractile integral abnormalities in patients with proton pump inhibitor-refractory symptoms.

OBJECTIVES: Esophagogastric junction contractile integral (EGJ-CI) is a novel indicator to evaluate quantitatively the esophagogastric junction (EGJ) barrier function. We aimed to assess the role of EGJ-CI in patients with refractory gastroesophageal reflux disease (GERD) symptoms and the correlation between EGJ-CI and impedance-pH monitoring characteristics. METHODS: In total 82 patients with proton pump inhibitors (PPIs)-refractory gastroesophageal reflux symptoms (heartburn or regurgitation) were enrolled. These patients were further divided into two groups based on their EGJ-CI value (39 mmHg·cm). The mean nocturnal baseline impedance (MNBI) was measured to explore its association with EGJ-CI. RESULTS: The median EGJ-CI in patients with PPI-refractory symptoms was 30.8 mmHg·cm. EGJ-CI was inversely correlated with acid exposure time and reflux episodes; while it was positively correlated with MNBI, distal contractile integral, lower esophageal sphincter basal pressure and integrated relaxation pressure. Patients were further divided into the high (n = 27) and low (n = 55) EGJ-CI groups using a cut-off value of 39.0 mmHg·cm. Patients with a low EGJ-CI had a lower MNBI level than those with a high EGJ-CI (2703 Ω vs 3545 Ω, P = 0.034). CONCLUSIONS: In patients with PPIs-refractory symptoms, EGJ-CI is associated with acid exposure and conventional high-resolution manometry parameters. EGJ-CI may play an important role in the diagnosis and treatment of patients with refractory GERD.

Sex differences in symptoms, high-resolution manometry values and efficacy of peroral endoscopic myotomy in Chinese patients with achalasia.

OBJECTIVE: We aimed to identify the differences in symptoms, high-resolution manometry (HRM) characteristics, and the efficacy of peroral endoscopic myotomy (POEM) regarding patients' sex in achalasia. METHODS: All patients diagnosed with achalasia by HRM who underwent POEM and were followed up for more than 6 months were included. The individual characteristics, symptoms and signs, POEM findings, HRM results and potentially related complications in male and female patients were reviewed. RESULTS: Prior to POEM, dysphagia was more severe in female than male patients (P = 0.044), while regurgitation was more severe (P = 0.013) and heartburn was more common in male patients (P = 0.003). Regarding HRM characteristics, the lower esophageal sphincter pressure (LESP) was higher (P = 0.01) and length of esophagus was shorter in female patients than in male patients. Eckardt scores, LESP and integrated relaxation pressure were significantly improved after the POEM procedure (P < 0.001). No significant difference was observed between the sexes regarding the efficacy of POEM, reflux symptoms, HRM data and complications after POEM. CONCLUSIONS: Before they seek treatment, female patients with achalasia may experience severe dysphagia and male patients are more likely to experience heartburn and more severe regurgitation. POEM is a safe and effective option for treating both male and female patients with achalasia.

Acid exposure in patients with gastroesophageal reflux disease is associated with esophageal dysmotility.

OBJECTIVE: To explore the correlation between reflux disease and abnormal esophageal motility in patients with gastroesophageal reflux disease (GERD). METHODS: Participants (patients with GERD and controls) who underwent 24-h impedance-pH monitoring (MII-pH monitoring) and high-resolution manometry between January 2012 and February 2017 were retrospectively studied. The patients were divided into two groups (acid reflux and nonacid reflux) based on their MII-pH monitoring data. Reflux episodes, endoscopic findings, and esophageal dynamic parameters were assessed and compared. RESULTS: A total of 142 patients were included (acid reflux [n = 58], nonacid reflux [n = 60], control group [n = 24]). There were more patients with esophagitis and more severe esophageal mucosal injury in the acid reflux group than in the nonacid reflux group. The acid reflux group had reduced lower esophageal sphincter (LES) basal pressure, shorter LES length, lower esophageal pressure and distal contractile integral index than the nonacid reflux group. Patients in the acid reflux group had more large breaks and a higher incidence of type II and III esophagogastric junction morphology than those in the nonacid reflux group. Acid exposure time, the incidence of long-term acid reflux, recumbent acid reflux, and the incidence of acid and nonacid reflux had a significant negative correlation with esophageal body motility or LES function. CONCLUSION: This study suggests that an increase in esophageal acid exposure is correlated with an increase in esophageal dysmotility in patients with GERD.

Reflux episodes and esophageal impedance levels in patients with typical and atypical symptoms of gastroesophageal reflux disease.

To determine the relationship between baseline impedance levels and gastroesophageal reflux, we retrospectively enrolled 110 patients (54 men and 56 female; mean age, 51 ±â€Š14 years) with suspected gastroesophageal reflux disease (GERD) who underwent 24-h multichannel intraluminal impedance and pH monitoring. Patients were stratified according to symptom (typical or atypical) and reflux types (acid reflux, nonacid reflux [NAR], or no abnormal reflux). Mean nocturnal baseline impedance (MNBI) were measured 3 cm (distal esophagus) and 17 cm (proximal esophagus) above the lower esophageal sphincter. Median distal esophageal MNBI was lower in the acid reflux group (1244 Ω; 647-1969 Ω) than in the NAR (2586 Ω; 1368-3666 Ω) or no abnormal reflux groups (3082 Ω; 2495-4472 Ω; all P < .05). Distal MNBI were negatively correlated with DeMeester score and acid exposure time. Atypical symptoms were more frequently associated with NAR than typical symptoms (P < .01). Among patients with positive symptom-association probability (SAP) for NAR, median proximal MNBI tended to be lower in patients with typical symptoms (median, 3013 Ω; IQR, 2535-3410 Ω) than in those with atypical symptoms (median, 3386 Ω; IQR, 3044-3730 Ω, P = .05). Thus, atypical GERD symptoms were more likely to be associated with NAR. The mucosal integrity of the proximal esophagus might be relatively impaired in GERD patients with typical symptoms for NAR.

Application of AJCC/UICC and WHO-2010 classifications for GEP-NEN in Chinese patients.

OBJECTIVE: To assess the prognostic value in Chinese patients of two new systems, the World Health Organization (WHO)-2010 and the American Joint Committee on Cancer and the Union for International Cancer Control (AJCC/UICC) systems, for the classification of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). METHODS: One hundred and three patients with GEP-NEN treated at the First Affiliated Hospital of Nanjing Medical University from January 2003 to December 2011 were included in the study. All patients were diagnosed pathologically and had complete follow-up data. Univariate and multivariate analyses of their clinicopathological characteristics were performed. RESULTS: The 5-year survival rates were 95%, 74%, 24% and 15% based on the AJCC/UICC stages I to IV, and 92%, 62% and 29% according to WHO-2010 grades 1 to 3, respectively, in patients with GEP-NEN. A higher mortality was observed in patients with AJCC/UICC stage III and IV tumors compared with those at stage I-II, and patients with stage II compared with those with stage I, whereas there was no difference in survival between stage IV and III patients. Based on the WHO-2010 grading classification, patients with grade 3 tumors had the lowest survival rate than those with grade 1 and 2 tumors, followed by patients with grade 2 tumors. CONCLUSION: The WHO-2010 and AJCC/UICC staging systems can effectively evaluate the prognosis of patients with GEP-NEN, although the latter might not accurately discriminate the prognosis of patients with local metastasis from those having distant metastasis.