The value of LCI-based modified Kyoto classification risk scoring system in predicting the risk of early gastric cancer.

OBJECTIVE: To study and compare the value of the Kyoto classification risk scoring system and the modified Kyoto classification risk scoring system based on linked color imaging (LCI) in predicting the risk of early gastric cancer. METHODS: One hundred and fifty patients with pathologically confirmed non-cardia early gastric cancer by endoscopic LCI and 150 non-gastric cancer patients matched for age and gender were included. Basic patient data and whole gastric endoscopic images under LCI were collected, and the images were scored according to the LCI-based Kyoto classification risk scoring system and the LCI-based modified Kyoto classification risk scoring system. RESULTS: Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based modified Kyoto classification risk scoring system had a higher AUC for predicting the risk of early gastric cancer (0.723 vs. 0.784, p = 0.023), with a score of ≥3 being the best cutoff value for predicting the risk of early gastric cancer (sensitivity 61.33%, specificity 86.00%), and scores of 3 to 5 were significantly associated with early gastric carcinogenesis significantly (OR = 9.032, 95% CI: 4.995-16.330, p < 0.001). CONCLUSIONS: Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based Kyoto modified classification risk scoring system has a better value for predicting the risk of early gastric cancer, and the score of 3 to 5 is a high-risk factor for the risk of early gastric cancer development, which is more strongly correlated with the risk of early gastric cancer.

Linked color imaging-based endoscopic grading of gastric intestinal metaplasia and histological gastritis staging in the assessment of gastric cancer risk.

OBJECTIVE: To evaluate the value and compare the effectiveness of linked color imaging-based endoscopic grading of gastric intestinal metaplasia (LCI-EGGIM) and operative link on gastric intestinal metaplasia (OLGIM) in risk stratification of early gastric cancer (EGC). METHODS: Eighty-one patients with EGC who underwent endoscopic submucosal dissection were included. The general data and EGC-related risk factors of all participants were recorded. LCI-EGGIM and OLGIM were used for both groups. RESULTS: The number of patients with LCI-EGGIM score ≥ 5 was significantly higher in the EGC group than in the control group (58.02% vs. 12.35%, p < .001). Furthermore, the number of patients with OLGIM stage III/IV in the EGC group was significantly higher than that in the control group (56.79% vs. 7.41%, p < .001). Multivariate analysis showed that OLGIM stage III/IV (adjusted odds ratio [AOR]: 29.74, 95% CI: 7.49-117.94) and LCI-EGGIM score ≥ 5 (AOR: 12.33, 95% CI: 3.71-41.02) were significantly associated with EGC. There was no significant difference in the area under the receiver operating characteristic curve between LCI-EGGIM and OLGIM in predicting the risk of EGC (0.74 vs. 0.77, p = .1116). CONCLUSION: OLGIM and LCI-EGGIM can be used and have the same value for predicting the risk stratification of EGC in patients with gastric intestinal metaplasia.

Gastric intestinal metaplasia assessment between linked color imaging based on endoscopy and pathology.

OBJECTIVE: Cumulative evidence suggests that linked color imaging (LCI) can be used to identify gastric intestinal metaplasia (GIM). We aimed to develop endoscopic grading for GIM (EGGIM) with LCI. METHODS: Two hundred and seventy-seven patients who underwent high-resolution white-light gastroscopy followed by LCI for EGGIM estimation were included. LCI was performed for the entire mucosa, and images of five areas each were recorded from the lesser and greater curvatures of the antrum and corpus, and for the incisura. For each area, scores of 0 (no GIM), 1 (focal GIM, ≤30% of the area), and 2 (extensive GIM, >30% of the area) were attributed for 10 points. If GIM was suspected based on endoscopy findings, targeted biopsies were performed; if GIM was not evident, random biopsies were performed according to the Sydney system to estimate the operative link on GIM (OLGIM). RESULTS: GIM was staged as OLGIM 0, I, II, III, and IV in 136, 70, 37, 28, and 6 patients, respectively. For OLGIM III/IV diagnosis, the area under the receiver operating curve was 0.949 (95% CI 0.916-0.972). EGGIM of 4, with sensitivity and specificity of 94.12% (95% CI 80.3%-99.3%) and 86.42% (95% CI 81.5%-90.5%), respectively, was determined the best cut-off value for identifying OLGIM III/IV patients. CONCLUSIONS: Our findings demonstrated the ability of EGGIM for diagnosing the extent of intestinal metaplasia and showed that EGGIM is related to OLGIM staging. EGGIM of 4 was the best cut-off value for identifying OLGIM III/IV patients.

Upregulation of bile acid receptor TGR5 and nNOS in gastric myenteric plexus is responsible for delayed gastric emptying after chronic high-fat feeding in rats.

Chronic high-fat feeding is associated with functional dyspepsia and delayed gastric emptying. We hypothesize that high-fat feeding upregulates gastric neuronal nitric oxide synthase (nNOS) expression, resulting in delayed gastric emptying. We propose this is mediated by increased bile acid action on bile acid receptor 1 (TGR5) located on nNOS gastric neurons. To test this hypothesis, rats were fed regular chow or a high-fat diet for 2 wk. Rats fed the high-fat diet were subjected to concurrent feeding with oral cholestyramine or terminal ileum resection. TGR5 and nNOS expression in gastric tissue was measured by immunohistochemistry, PCR, and Western blot. Gastric motility was assessed by organ bath and solid-phase gastric emptying studies. The 2-wk high-fat diet caused a significant increase in neurons coexpressing nNOS and TGR5 in the gastric myenteric plexus and an increase in nNOS and TGR5 gene expression, 67 and 111%, respectively. Enhanced nonadrenergic, noncholinergic (NANC) relaxation, deoxycholic acid (DCA)-induced inhibition in fundic tissue, and a 26% delay in gastric emptying accompanied these changes. A 24-h incubation of whole-mount gastric fundus with DCA resulted in increased nNOS and TGR5 protein expression, 41 and 37%, respectively. Oral cholestyramine and terminal ileum resection restored the enhanced gastric relaxation, as well as the elevated nNOS and TGR5 expression evoked by high-fat feeding. Cholestyramine also prevented the delay in gastric emptying. We conclude that increased levels of circulatory bile acids induced by high-fat feeding upregulate nNOS and TGR5 expression in the gastric myenteric plexus, resulting in enhanced NANC relaxation and delayed gastric emptying.

NMDA and AMPA receptors in the anterior cingulate cortex mediates visceral pain in visceral hypersensitivity rats.

Several studies have shown that N-methyl-D-aspartate (NMDA)-receptor activation in anterior cingulate cortex (ACC) neurons plays critical roles in modulating visceral pain responses in visceral hypersensitivity (VH) rats. However, there are few reports about the expressions of NMDA and α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic-acid (AMPA) receptor subtypes in ACC of VH model rats at different time points. The current study was undertaken to investigate NR2A, NR2B and GluR2 expressions in ACC of VH rats that were induced by administration with 5% mustard oil. Our results indicated that NR2B, but not NR2A, was highly expressed in VH model group on day 15, 22, and 36 compared with normal group (p < 0.05). GluR2 expression was also higher in VH model group on day 15, 22, and 36 than that of normal group (p < 0.05). These findings suggested increased expression of NR2B and GluR2 might be key mechanisms for long-term synaptic plastic changes in VH rats.

Orthodontic Rubber Band-Assisted Endoscopic Submucosal Dissection: An Efficient Method for Treating Superficial Colorectal Tumors.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is a complex operation. Effective traction is crucial. We have successfully used an orthodontic rubber band (ORB) combined with the clip traction method to assist ESD (ORB-ESD). The aim of this retrospective study is to describe the method and to compare the efficacy and safety of ORB-ESD versus conventional ESD in the treatment of superficial colorectal tumors. METHODS: We retrospectively analyzed the data of patients with superficial colorectal tumor (with diameter ≥ 20 mm) who received either ORB-ESD (n = 34) or conventional ESD (n = 90) between January 2019 and September 2020. Propensity score matching (PSM) was used to match the clinical data of 31 pairs of patients in each group. RESULTS: Operation time was significantly shorter for ORB-ESD than for conventional ESD (34.5 minutes vs. 56 minutes, P ≤ 0.001). In the propensity-matched cohorts, the operation time remained significantly shorter in the ORB-ESD patients (35 minutes vs. 50 minutes, P = 0.001). Postoperative adverse events, en bloc resection rate, and R0 resection rate were comparable between the two groups (P > 0.05), both before and after propensity score matching. In the ORB subgroup analysis, the trainee and expert ESD operation times were similar (37 (26-53) vs. 33.5 (26-37) minutes, respectively; P = 0.274). CONCLUSION: ORB-ESD appears to be an effective technique for ESD of colorectal cancer. Our findings need to be confirmed in large prospective multicenter studies.

Bile acid toxicity in Paneth cells contributes to gut dysbiosis induced by high-fat feeding.

High-fat feeding (HFF) leads to gut dysbiosis through unclear mechanisms. We hypothesize that bile acids secreted in response to high-fat diets (HFDs) may act on intestinal Paneth cells, leading to gut dysbiosis. We found that HFF resulted in widespread taxonomic shifts in the bacteria of the ileal mucosa, characterized by depletion of Lactobacillus and enrichment of Akkermansia muciniphila, Clostridium XIVa, Ruminococcaceae, and Lachnospiraceae, which were prevented by the bile acid binder cholestyramine. Immunohistochemistry and in situ hybridization studies showed that G protein-coupled bile acid receptor (TGR5) expressed in Paneth cells was upregulated in the rats fed HFD or normal chow supplemented with cholic acid. This was accompanied by decreased lysozyme+ Paneth cells and α-defensin 5 and 6 and increased expression of XBP-1. Pretreatment with ER stress inhibitor 4PBA or with cholestyramine prevented these changes. Ileal explants incubated with deoxycholic acid or cholic acid caused a decrease in α-defensin 5 and 6 and an increase in XBP-1, which was prevented by TGR5 antibody or 4PBA. In conclusion, this is the first demonstration to our knowledge that TGR5 is expressed in Paneth cells. HFF resulted in increased bile acid secretion and upregulation of TGR5 expression in Paneth cells. Bile acid toxicity in Paneth cells contributes to gut dysbiosis induced by HFF.

FODMAP diet modulates visceral nociception by lipopolysaccharide-mediated intestinal inflammation and barrier dysfunction.

Foods high in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) exacerbate symptoms of irritable bowel syndrome (IBS); however, their mechanism of action is unknown. We hypothesized that a high-FODMAP (HFM) diet increases visceral nociception by inducing dysbiosis and that the FODMAP-altered gut microbial community leads to intestinal pathology. We fed rats an HFM and showed that HFM increases rat fecal Gram-negative bacteria, elevates lipopolysaccharides (LPS), and induces intestinal pathology, as indicated by inflammation, barrier dysfunction, and visceral hypersensitivity (VH). These manifestations were prevented by antibiotics and reversed by low-FODMAP (LFM) diet. Additionally, intracolonic administration of LPS or fecal supernatant (FS) from HFM-fed rats caused intestinal barrier dysfunction and VH, which were blocked by the LPS antagonist LPS-RS or by TLR4 knockdown. Fecal LPS was higher in IBS patients than in healthy subjects (HS), and IBS patients on a 4-week LFM diet had improved IBS symptoms and reduced fecal LPS levels. Intracolonic administration of FS from IBS patients, but not FS from HS or LFM-treated IBS patients, induced VH in rats, which was ameliorated by LPS-RS. Our findings indicate that HFM-associated gut dysbiosis and elevated fecal LPS levels induce intestinal pathology, thereby modulating visceral nociception and IBS symptomatology, and might provide an explanation for the success of LFM diet in IBS patients.