Current research on the interaction between Helicobacter pylori and macrophages.

Helicobacter pylori (H. pylori) is a gram-negative bacteria with a worldwide infection rate of 50%, known to induce gastritis, ulcers and gastric cancer. The interplay between H. pylori and immune cells within the gastric mucosa is pivotal in the pathogenesis of H. pylori-related disease. Following H. pylori infection, there is an observed increase in gastric mucosal macrophages, which are associated with the progression of gastritis. H. pylori elicits macrophage polarization, releases cytokines, reactive oxygen species (ROS) and nitric oxide (NO) to promote inflammatory response and eliminate H. pylori. Meanwhile, H. pylori has developed mechanisms to evade the host immune response in order to maintain the persistent infection, including interference with macrophage phagocytosis and antigen presentation, as well as induction of macrophage apoptosis. Consequently, the interaction between H. pylori and macrophages can significantly impact the progression, pathogenesis, and resolution of H. pylori infection. Moreover, macrophages are emerging as potential therapeutic targets for H. pylori-associated gastritis. Therefore, elucidating the involvement of macrophages in H. pylori infection may provide novel insights into the pathogenesis, progression, and management of H. pylori-related disease.

Recovery of driving skills after endoscopy under propofol sedation: a prospective pilot study to assess the driving skills after endoscopic sedation using driving simulation.

BACKGROUND: Patients are recommended not to drive for at least the first 24 h after endoscopy with propofol sedation. However, the evidence underlying these recommendations is scarce. We hypothesized that after endoscopic procedures performed under propofol sedation, the subject's driving ability was restored in less than 24 h. METHODS: We prospectively enrolled thirty patients between 20 and 70 years possessing a legitimate driver's license scheduled for endoscopy at our hospital. The sample chosen was a convenience sample. Gastroscopy or colonoscopy was performed with propofol sedation. Before and after endoscopy, the investigator drove the subjects to the laboratory to assess their driving skills using a driving simulation system, which employs 3 driving scenarios designed by professional transportation researchers. The blood propofol concentration was estimated before endoscopy, and 2 and 4 h after endoscopy. The primary outcome was the time required for subjects to recover their driving ability after propofol sedation. The secondary outcome was the blood propofol concentration before and after endoscopic procedures under propofol anesthesia. RESULTS: Thirty volunteers participated in the study and 18 of them completed all the interventions. In the low-risk S-curve scene, the mean acceleration, lane deviation, and number of deviations from the path at baseline (0.016 cm/s2, 42.50 cm, and 0.83, respectively) were significantly less than that at post-2 h (0.029 cm/s2, P = 0.001; 53.80 cm, P = 0.014; 2.06, P = 0.022). In the moderate-(overtaking) and high-risk (emergency collision avoidance) scenes, the tested parameters at baseline and post-2 h were statistically comparable. In the low-, moderate-, and high-risk scenes the tested parameters at baseline and post-4 h were statistically comparable. The total range of propofol was 120-280 mg.The mean blood concentration of propofol at post-2 h was 0.81 ± 0.40 µg/mL, and at post-4 h was below the limit of detection. CONCLUSION: After endoscopy performed under propofol sedation, subjects' driving abilities were completely restored at 4 h when tested on a simulator.

Predictors for malignant potential and deep submucosal invasion in colorectal laterally spreading tumors.

BACKGROUND: Colorectal laterally spreading tumors (LSTs) with malignant potential require en bloc resection by endoscopic submucosal dissection (ESD), but lesions with deep submucosal invasion (SMI) are endoscopically unresectable. AIM: To investigate the factors associated with high-grade dysplasia (HGD)/carcinoma and deep SMI in colorectal LSTs. METHODS: The endoscopic and histological results of consecutive patients who underwent ESD for colorectal LSTs in our hospital from June 2013 to March 2019 were retrospectively analyzed. The characteristics of LST subtypes were compared. Risk factors for HGD/carcinoma and deep SMI (invasion depth ≥ 1000 µm) were determined using multivariate logistic regression. RESULTS: A total of 323 patients with 341 colorectal LSTs were enrolled. Among the four subtypes, non-granular pseudodepressed (NG-PD) LSTs (85.5%) had the highest rate of HGD/carcinoma, followed by the granular nodular mixed (G-NM) (77.0%), granular homogenous (29.5%), and non-granular flat elevated (24.2%) subtypes. Deep SMI occurred commonly in NG-PD LSTs (12.9%). In the adjusted multivariate analysis, NG-PD [odds ratio (OR) = 16.8, P < 0.001) and G-NM (OR = 7.8, P < 0.001) subtypes, size ≥ 2 cm (OR = 2.2, P = 0.005), and positive non-lifting sign (OR = 3.3, P = 0.024) were independently associated with HGD/carcinoma. The NG-PD subtype (OR = 13.3, P < 0.001) and rectosigmoid location (OR = 8.7, P = 0.007) were independent risk factors for deep SMI. CONCLUSION: Because of their increased risk for malignancy, it is highly recommended that NG-PD and G-NM LSTs are removed en bloc through ESD. Given their substantial risk for deep SMI, surgery needs to be considered for NG-PD LSTs located in the rectosigmoid, especially those with positive non-lifting signs.

New traction method (traction ring) for colorectal endoscopic submucosal dissection.

OBJECTIVES: Colorectal endoscopic submucosal dissection (ESD) is challenging because of the difficulty in adequately visualizing the submucosal layer. Many traction methods have been developed to facilitate submucosal dissection; however, they are not widely applied. Therefore, we designed a new traction device, a traction ring, and conducted this pilot study to evaluate its feasibility and safety for colorectal ESD. METHODS: Twenty patients with colorectal lesions who underwent traction ring-assisted ESD were retrospectively included. The main outcomes included en bloc resection rate, R0 resection rate, procedure time, resection time, and intraoperative and postoperative complications. RESULTS: The median procedure time was 74.5 min (range 35-269 min). The median resection time was 55 min (range 25-209 min). Application of the traction system accounted for only 2.7% of the entire procedure time. The en bloc resection rate was 95.0% (19/20), whereas the R0 resection rate was 90.0% (18/20). All traction rings were successfully set and retrieved. Significant intraoperative bleeding was not observed. One patient experienced perforation after treatment, but no further intervention was required. No delayed complications were observed within 1 month post-ESD. CONCLUSION: Traction ring is an effective and safe method for colorectal ESD and can be used at any location in the colorectum.

Endoscopic submucosal dissection for colorectal laterally spreading tumors: Clinical outcomes and predictors of technical difficulty.

OBJECTIVE: We aimed to investigate the clinical outcomes of endoscopic submucosal dissection (ESD) for the treatment of colorectal laterally spreading tumors (LSTs) and the factors related to technical difficulty. METHODS: Consecutive patients who underwent ESD for colorectal LSTs between June 2013 and January 2019 were retrospectively included. Factors associated with difficult ESD procedures (defined as conversion to piecemeal resection or discontinuation of endoscopic procedure), and dissection with a slow speed (<8 mm2 /min), were determined using the logistic regression analysis. RESULTS: A total of 325 patients with 342 colorectal LSTs (median size 20.0 mm) were enrolled. The proportions of granular (LST-G) and non-granular LST (LST-NG) were 62.9% and 37.1%, respectively. The overall en bloc and complete resection rates were 89.8% and 81.9%, respectively. The endoscopic procedure was discontinued in four lesions (1.2%), and 31 (9.1%) converted to piecemeal resection because of technical difficulty. Using multivariate analysis, positive non-lifting sign (odds ratio [OR] 19.9, P < 0.001), tumor size ≥20 mm (OR 10.0, P < 0.001), and less experienced endoscopists (OR 3.7, P = 0.005) were independent factors for technically difficult procedure. Positive non-lifting sign (OR 3.7, P = 0.004), lesion size <20 mm (OR 3.7, P < 0.001), LST-NG type (OR 1.8, P = 0.034), and less colorectal ESD experience (OR 1.9, P = 0.016) were independent factors of slow-speed dissection. CONCLUSIONS: ESD was feasible and safe for treating colorectal LSTs. Positive non-lifting sign and tumor ≥20 mm indicated difficult ESD procedures. Technical failure was more likely to occur in lesions resected by less-experienced endoscopists. Dissection speed might be improved with more experienced operators.

Expression and Significance of N-myc downstream regulated gene 2 in the process of Esophageal Squamous Cell Carcinogenesis.

It has been reported that the expression of tumor suppressor gene N-myc downstream-regulated gene 2 (NDRG2) was significantly reduced in human solid tumors, including esophageal squamous cell carcinoma (ESCC). This study aimed to explore whether the difference of NDRG2 expression exists in different stages of ESCC and provides a basis for the early diagnosis and prognosis of ESCC. Immunohistochemical staining was used to investigate the expression level of NDRG2 in samples from 91 patients with mild-to-moderate dysplasia, early ESCC, and advanced ESCC. The relationship between the expression of NDRG2 and clinicopathological characteristics of the patients was analyzed. The results showed that positive expression rates of NDRG2 in tissues adjacent to early ESCC (76.7%), or from mild-to-moderate dysplasia (74.1%), and early ESCC (83.3%) were significantly higher than in tissue from advanced ESCC (55.9%). The positive expression rate in advanced ESCC was significantly lower than in the other three tissue types (p < 0.05). There was a significant difference (p < 0.05) and correlation (Cramer's V = 0.351, p = 0.019, <0.05) between the expression of NDRG2 and the clinical stage in the 64 patients with ESCC. In conclusion, this study found that the expression of NDRG2 gradually decreased with the progression of esophageal lesions into advanced ESCC. This difference in positive expression rate was more obvious in male patients and patients under 60 years of age. Therefore, the detection of NDRG2 plays an important role in differentiating early ESCC from advanced ESCC.

Feasibility of standardized procedures of white light gastroscopy for clinical practice: A multicenter study in China.

OBJECTIVE: We aimed to establish a standardized procedure for white light gastroscopy (WLG) to screen gastric lesions including early gastric cancer (EGC) in China and to verify its efficacy and feasibility in clinical practice. METHODS: A standardized WLG procedure for outpatients at nine tertiary hospitals in Beijing was established. Clinical information of the participants and details of the endoscopic procedures were recorded. RESULTS: A total of 1051 participants were enrolled in a baseline conventional endoscopic survey between March 2014 and December 2015, while 2156 patients were enrolled in the standardized WLG operation from January 2016 to June 2017. The procedure time of the standardized procedure was significantly longer than that of the baseline conventional procedure (P = 0.003). More images were obtained during the standardized procedure compared with the baseline conventional procedure (P < 0.001). The overall detection rate of gastric lesions in the standardized procedure group was significantly higher than that in the baseline procedure group (52.5% vs 38.4%, P < 0.01). The satisfaction scores of both participants and endoscopists in the standardized procedure group were significantly higher than in the baseline procedure group. CONCLUSIONS: Compared with the conventional procedure, standardized WLG procedure significantly improves the detection rate of gastric lesions as well as the satisfaction score of participants and endoscopists despite its longer procedure time. It is effective and feasible in clinical practice in China for the use of currently available endoscopic equipment.

Accuracy of artificial intelligence-assisted detection of esophageal cancer and neoplasms on endoscopic images: A systematic review and meta-analysis.

OBJECTIVE: To investigate systematically previous studies on the accuracy of artificial intelligence (AI)-assisted diagnostic models in detecting esophageal neoplasms on endoscopic images so as to provide scientific evidence for the effectiveness of these models. METHODS: A literature search was conducted on the PubMed, EMBASE and Cochrane Library databases for studies on the AI-assisted detection of esophageal neoplasms on endoscopic images published up to December 2020. A bivariate mixed-effects regression model was used to calculate the pooled diagnostic efficacy of AI-assisted system. Subgroup analyses and meta-regression analyses were performed to explore the sources of heterogeneity. The effectiveness of AI-assisted models was also compared with that of the endoscopists. RESULTS: Sixteen studies were included in the systematic review and meta-analysis. The pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio and area under the summary receiver operating characteristic curve regarding AI-assisted detection of esophageal neoplasms were 94% (95% confidence interval [CI] 92%-96%), 85% (95% CI 73%-92%), 6.40 (95% CI 3.38-12.11), 0.06 (95% CI 0.04-0.10), 98.88 (95% CI 39.45-247.87) and 0.97 (95% CI 0.95-0.98), respectively. AI-based models performed better than endoscopists in terms of the pooled sensitivity (94% [95% CI 84%-98%] vs 82% [95% CI 77%-86%, P < 0.01). CONCLUSIONS: The use of AI results in increased accuracy in detecting early esophageal cancer. However, most of the included studies have a retrospective study design, thus further validation with prospective trials is required.

Modulation of gut microbiota protects against viral respiratory tract infections: a systematic review of animal and clinical studies.

BACKGROUND: Earlier studies suggest that probiotics have protective effects in the prevention of respiratory tract infections (RTIs). Whether such benefits apply to RTIs of viral origin and mechanisms supporting the effect remain unclear. AIM: To determine the role of gut microbiota modulation on clinical and laboratory outcomes of viral RTIs. METHODS: We conducted a systematic review of articles published in Embase and MEDLINE through 20 April 2020 to identify studies reporting the effect of gut microbiota modulation on viral RTIs in clinical studies and animal models. The incidence of viral RTIs, clinical manifestations, viral load and immunological outcomes was evaluated. RESULTS: We included 58 studies (9 randomized controlled trials; 49 animal studies). Six of eight clinical trials consisting of 726 patients showed that probiotics administration was associated with a reduced risk of viral RTIs. Most commonly used probiotics were Lactobacillus followed by Bifidobacterium and Lactococcus. In animal models, treatment with probiotics before viral challenge had beneficial effects against influenza virus infection by improving infection-induced survival (20/22 studies), mitigating symptoms (21/21 studies) and decreasing viral load (23/25 studies). Probiotics and commensal gut microbiota exerted their beneficial effects through strengthening host immunity. CONCLUSION: Modulation of gut microbiota represents a promising approach against viral RTIs via host innate and adaptive immunity regulation. Further research should focus on next generation probiotics specific to viral types in prevention and treatment of emerging viral RTIs.

Advancements in the endoscopic treatment of pancreatic fluid collections.

Endoscopic drainage of pancreatic fluid collections (PFCs) with fewer complications and less trauma has gradually replaced surgery or percutaneous drainage to become the first-line treatment for PFCs. In recent years, the differential efficacy of various stent techniques to drain different types of PFCs has been controversial. This review summarizes the clinical applications of endoscopic ultrasound-guided stent placement for PFCs drainage.

The role of a transparent cap in the endoscopic removal of foreign bodies in the esophagus: A propensity score-matched analysis.

OBJECTIVE: To investigate the effectiveness and safety of transparent cap-assisted endoscopy in removing foreign bodies in the esophagus. METHODS: Patients with foreign body lodged in the esophagus who received a transparent cap-assisted or conventional endoscopy between October 2004 and July 2018 were retrospectively enrolled. Propensity score matching was performed. The success rate of the endoscopic procedure, procedure time, clearness of endoscopic view and adverse event rate were compared between the two groups. RESULTS: Of the 838 patients who had a foreign body lodged in the esophagus, 728 (86.9%) underwent endoscopic intervention. After matched by prospensity score, 224 patients each received either transparent cap-assisted endoscopy or conventional endoscopy. No difference was noted between the two groups in terms of the success rate (100% vs 99.1%, P = 0.499). Transparent cap-assisted endoscopy was associated with shorter procedure time for removing jujube pits ([4.24 ± 2.81] min vs [7.62 ± 8.15] min, P = 0.001), fish bones ([2.99 ± 2.15] min vs [6.49 ± 6.54] min, P < 0.001) and other sharp objects ([4.29 ± 3.36] min vs [10.60 ± 19.79 min], P = 0.027) and higher rates of clear endoscopic views in extracting jujube pits, fish bones, poultry bones and other sharp objects (98% vs 43.4%, 97.5% vs 74.1%, 100% vs 81.3% and 100% vs 82.7%; all P < 0.05). No significant differences in the rates of adverse event were observed between the groups (P = 1.000). CONCLUSION: Transparent cap-assisted endoscopic technique is effective and safe for removing sharp foreign bodies in the esophagus.

Incidence, risk factors, and a predictive model for lymph node metastasis of submucosal (T1) colon cancer: A population-based study.

OBJECTIVE: This study aimed to assess the incidence, identify independent factors, and develop a lymph node metastasis (LNM) prediction model for patients with T1 colon cancer. METHODS: Statistics were drawn from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. A multivariate logistic regression analysis was performed to determine independent predictors of LNM. A nomogram for predicting the possibility of LNM was developed based on those factors. RESULTS: A total of 5397 patients with T1 colon cancer were identified. The overall LNM rate was 15.0% (808/5397). A multivariate analysis showed that age (odds ratio [OR] 0.97, P < 0.001), tumor size (OR 1.01, P < 0.001), moderate (OR 1.77, P = 0.001) or poorly differentiated/undifferentiated tumor (OR 5.60, P < 0.001), right colon cancer (OR 1.39, P = 0.008), and a positive carcinoembryonic antigen level (OR 1.51, P = 0.004) were independent predictive factors for LNM. The area under the receiver operating characteristic curve was 0.68 (95% confidence interval [CI] 0.65-0.71) in the training set and 0.65 (95% CI 0.61-0.67) in the validation set. A calibration plot showed good consistency between the bias-corrected prediction and the ideal reference line with 1000 additional bootstraps (mean absolute error = 0.007). CONCLUSIONS: The incidence of LNM was high in patients with T1 colon cancer. A nomogram for predicting the probability of LNM for T1 colon cancer may be used to help determine the optimal treatment for these patients.

Consensus on the digestive endoscopic tunnel technique.

With the digestive endoscopic tunnel technique (DETT), many diseases that previously would have been treated by surgery are now endoscopically curable by establishing a submucosal tunnel between the mucosa and muscularis propria (MP). Through the tunnel, endoscopic diagnosis or treatment is performed for lesions in the mucosa, in the MP, and even outside the gastrointestinal (GI) tract. At present, the tunnel technique application range covers the following: (1) Treatment of lesions originating from the mucosal layer, e.g., endoscopic submucosal tunnel dissection for oesophageal large or circular early-stage cancer or precancerosis; (2) treatment of lesions from the MP layer, per-oral endoscopic myotomy, submucosal tunnelling endoscopic resection, etc.; and (3) diagnosis and treatment of lesions outside the GI tract, such as resection of lymph nodes and benign tumour excision in the mediastinum or abdominal cavity. With the increasing number of DETTs performed worldwide, endoscopic tunnel therapeutics, which is based on DETT, has been gradually developed and optimized. However, there is not yet an expert consensus on DETT to regulate its indications, contraindications, surgical procedure, and postoperative treatment. The International DETT Alliance signed up this consensus to standardize the procedures of DETT. In this consensus, we describe the definition, mechanism, and significance of DETT, prevention of infection and concepts of DETT-associated complications, methods to establish a submucosal tunnel, and application of DETT for lesions in the mucosa, in the MP and outside the GI tract (indications and contraindications, procedures, pre- and postoperative treatments, effectiveness, complications and treatments, and a comparison between DETT and other operations).

shRNA­mediated knockdown of KNTC1 suppresses cell viability and induces apoptosis in esophageal squamous cell carcinoma.

Kinetochore­associated proteins are critical components of mitotic checkpoints, which are essential for faithful chromosomal segregation and spindle assembly during cell division. Recent advances have demonstrated that kinetochore­associated proteins are upregulated and serve significant roles in the carcinogenesis of numerous types of cancer. However, the effects of kinetochore­associated protein 1 (KNTC1) on human cancer, particularly on esophageal squamous cell carcinoma (ESCC), remain unclear. The present study revealed that KNTC1 was highly expressed in ESCC cell lines. Subsequently, lentivirus­mediated short hairpin RNAs were used to knockdown KNTC1 expression in human ESCC cell lines. Cell growth and viability were measured using multiparametric high­content screening and the MTT assay, respectively. Cell apoptosis was assessed by staining cells with Annexin V­allophycocyanin and was detected using FACScan flow cytometry. The results demonstrated that knockdown of KNTC1 effectively inhibited cell viability and increased apoptosis. In addition, a gene set enrichment analysis of online ESCC datasets indicated that KNTC1 overexpression was associated with increases in the mitotic spindle and hypoxia pathways, and decreases in the DNA repair and mismatch repair pathways. The findings of the present study suggested that KNTC1 may have an essential role in mediating cell viability and apoptosis in human ESCC cells and may serve as a novel therapeutic target for ESCC.

Challenge in the new era: Translational medicine in gastrointestinal endoscopy and early cancer.

Translational medicine is a new medical model that has emerged over the past 20 years and is dedicated to bridging the gap between basic and clinical research. At the same time, the diagnosis and treatment of digestive diseases, especially gastrointestinal endoscopy, have been rapidly developed. The emergence of new techniques for gastrointestinal endoscopy has changed the therapeutic spectrum of some diseases and brought huge benefits to patients. Targeted therapy has positively affected the individualized and precise treatment of patients with advanced gastrointestinal cancer. The construction of a standardized biobank provides a strong guarantee for clinicians to conduct translational medical research. Translational medicine has brought good development opportunities, but it also faces challenges. The training of translational medicine researchers and the transformation of educational models require sufficient attention for further development.