Targeting the HSP47-collagen axis inhibits brain metastasis by reversing M2 microglial polarization and restoring anti-tumor immunity.

Brain metastases (BrMs) are the leading cause of death in patients with solid cancers. BrMs exhibit a highly immunosuppressive milieu and poor response to immunotherapies; however, the underlying mechanism remains largely unclear. Here, we show that upregulation of HSP47 in tumor cells drives metastatic colonization and outgrowth in the brain by creating an immunosuppressive microenvironment. HSP47-mediated collagen deposition in the metastatic niche promotes microglial polarization to the M2 phenotype via the α2ß1 integrin/nuclear factor κB pathway, which upregulates the anti-inflammatory cytokines and represses CD8+ T cell anti-tumor responses. Depletion of microglia reverses HSP47-induced inactivation of CD8+ T cells and abolishes BrM. Col003, an inhibitor disrupting HSP47-collagen association restores an anti-tumor immunity and enhances the efficacy of anti-PD-L1 immunotherapy in BrM-bearing mice. Our study supports that HSP47 is a critical determinant of M2 microglial polarization and immunosuppression and that blocking the HSP47-collagen axis represents a promising therapeutic strategy against brain metastatic tumors.

Application of the convolution neural network in determining the depth of invasion of gastrointestinal cancer: a systematic review and meta-analysis.

BACKGROUND: With the development of endoscopic technology, endoscopic submucosal dissection (ESD) has been widely used in the treatment of gastrointestinal tumors. It is necessary to evaluate the depth of tumor invasion before the application of ESD. The convolution neural network (CNN) is a type of artificial intelligence that has the potential to assist in the classification of the depth of invasion in endoscopic images. This meta-analysis aimed to evaluate the performance of CNN in determining the depth of invasion of gastrointestinal tumors. METHODS: A search on PubMed, Web of Science, and SinoMed was performed to collect the original publications about the use of CNN in determining the depth of invasion of gastrointestinal neoplasms. Pooled sensitivity and specificity were calculated using an exact binominal rendition of the bivariate mixed-effects regression model. I2 was used for the evaluation of heterogeneity. RESULTS: A total of 17 articles were included; the pooled sensitivity was 84% (95% CI, 0.81-0.88), specificity was 91% (95% CI, 0.85-0.94), and the area under the curve (AUC) was 0.93 (95% CI, 0.90-0.95). The performance of CNN was significantly better than that of endoscopists (AUC: 0.93 vs 0.83, respectively; P = .0005). CONCLUSION: Our review revealed that CNN is one of the most effective methods of endoscopy to evaluate the depth of invasion of early gastrointestinal tumors, which has the potential to work as a remarkable tool for clinical endoscopists to make decisions on whether the lesion is feasible for endoscopic treatment.

Design and Experimental Study of an Improved Pressure Core Sampler for Marine Gas Hydrates.

A pressure core sampler (PCS) is considered an effective tool to retrieve marine gas hydrate cores from hydrate-bearing sediments. However, according to the sampling application statistics, the success rate of pressure coring changed from 30% to 85% in different drilling wells. Such severe fluctuation will cause huge uncertainty in the practical application of technology and economic benefits. Herein, we present a new PCS designed to improve pressure-retaining reliability. The work principle, design and calculations, and structure composition were described. Through the laboratory tests and drilling experiments, the maximum holding pressure in the pressure chamber was 32.1 MPa, and the pressure loss rates of holding pressure after 2 h changed from 1.96% to 2.46%. The maximum temperature-rising value in the pressure chamber was 0.96 °C under a temperature of 23.5 °C in 2 h. Furthermore, the success rate of the pressure core reached 87.5% and the core recovery was not less than 80%, which were verified by 8 pressure core runs in three different offshore wells. Therefore, we conclude that this new and improved PCS has great application value in gas hydrate exploration that seeks to recover more accurate cores in situ, especially in the silt and sand layers.

Rapid Endoscopic Diagnosis of Benign Ulcerative Colorectal Diseases With an Artificial Intelligence Contextual Framework.

BACKGROUND & AIMS: Benign ulcerative colorectal diseases (UCDs) such as ulcerative colitis, Crohn's disease, ischemic colitis, and intestinal tuberculosis share similar phenotypes with different etiologies and treatment strategies. To accurately diagnose closely related diseases like UCDs, we hypothesize that contextual learning is critical in enhancing the ability of the artificial intelligence models to differentiate the subtle differences in lesions amidst the vastly divergent spatial contexts. METHODS: White-light colonoscopy datasets of patients with confirmed UCDs and healthy controls were retrospectively collected. We developed a Multiclass Contextual Classification (MCC) model that can differentiate among the mentioned UCDs and healthy controls by incorporating the tissue object contexts surrounding the individual lesion region in a scene and spatial information from other endoscopic frames (video-level) into a unified framework. Internal and external datasets were used to validate the model's performance. RESULTS: Training datasets included 762 patients, and the internal and external testing cohorts included 257 patients and 293 patients, respectively. Our MCC model provided a rapid reference diagnosis on internal test sets with a high averaged area under the receiver operating characteristic curve (image-level: 0.950 and video-level: 0.973) and balanced accuracy (image-level: 76.1% and video-level: 80.8%), which was superior to junior endoscopists (accuracy: 71.8%, P < .0001) and similar to experts (accuracy: 79.7%, P = .732). The MCC model achieved an area under the receiver operating characteristic curve of 0.988 and balanced accuracy of 85.8% using external testing datasets. CONCLUSIONS: These results enable this model to fit in the routine endoscopic workflow, and the contextual framework to be adopted for diagnosing other closely related diseases.

Comparison of the Efficacy of Endoscopic Radial Incision and Cutting Procedure and Endoscopic Balloon Dilation for Benign Anastomotic Stricture After Low Anterior Resection Combined With Preventive Loop Ileostomy in Rectal Cancer.

BACKGROUND: Endoscopic radial incision and cutting procedure is a notable technique in the treatment of benign anastomotic strictures after low anterior resection in rectal cancer. However, the efficacy and safety of the endoscopic radial incision and cutting procedure and traditional endoscopic balloon dilation remain unknown. OBJECTIVE: To compare the efficacy and safety of the endoscopic radial incision and cutting procedure and endoscopic balloon dilation in patients with anastomotic stricture after low anterior resection. DESIGN: Rectal cancer patients with anastomotic stricture after low anterior resection combined with synchronous preventive loop ileostomy between January 2014 and June 2021 were retrospectively collected. These patients underwent the endoscopic radial incision and cutting procedure or endoscopic balloon dilation as an initial treatment. The clinicopathological baseline data of the patients, endoscopic surgery success rate, complications, and restricture rate were analyzed. SETTINGS: This study was conducted at Nanfang Hospital in China. PATIENTS: A total of 30 patients were eligible after reviewing the medical records. Twenty patients underwent endoscopic balloon dilation, and 10 patients underwent endoscopic radial incision and cutting procedure. MAIN OUTCOME MEASURES: The adverse event rate and stricture recurrence rate. RESULTS: There were no significant differences in patient demographics or clinical features. No adverse events occurred in either of the 2 groups. The mean operation time was 18.9 ± 3.6 minutes in the endoscopic balloon dilation group and 10.2 ± 3.3 minutes in the endoscopic radial incision and cutting procedure group ( p < 0.001). The stricture recurrence rates between the endoscopic balloon dilation group and the endoscopic radial incision and cutting procedure group were significantly different (44.4% vs 0%; p = 0.025). LIMITATIONS: This was a retrospective study. CONCLUSIONS: The endoscopic radial incision and cutting procedure is safe and more efficacious than endoscopic balloon dilation for anastomotic stricture after low anterior resection combined with synchronous preventive loop ileostomy in rectal cancer.

Evaluation of a novel disposable esophagogastroduodenoscopy system in emergency, bedside, and intraoperative settings: Pilot study (with videos).

OBJECTIVES: The disposable esophagogastroduodenoscopy (EGD) system is a novel endoscopic device which is highly portable and is designed to eliminate the risk of cross-infection caused by reusable EGD. This study aimed to investigate the feasibility and safety of disposable EGD in emergency, bedside, and intraoperative settings. METHODS: This was a prospective, single-center, noncomparative study. Disposable EGD was used for emergency, bedside, and intraoperative endoscopies in 30 patients. The primary end-point was the technical success rate of the disposable EGD. Secondary end-points included technical performance indicators including clinical operability, image quality score, procedure time, the incidence of device malfunction and/or failure, and the incidence of adverse events. RESULTS: A total of 30 patients underwent diagnosis and/or treatment with disposable EGD. Therapeutic EGD was performed on 13/30 patients, including hemostasis (n = 3), foreign body retrieval (n = 6), nasoenteric tube placement (n = 3), and percutaneous endoscopic gastrostomy (n = 1). The technical success rate was 100%: all procedures and indicated interventions were completed without changing to a conventional upper endoscope. The mean image quality score obtained immediately after procedure completion was 3.72 ± 0.56. The mean (± SD) procedure time was 7.4 (± 7.6) min. There were no device malfunctions or failures, device-related adverse events, or overall adverse events. CONCLUSION: The disposable EGD may be a feasible alternative to the traditional EGD in emergency, bedside, and intraoperative settings. Preliminary data show that it is a safe and effective tool for diagnosis and treatment in emergency and bedside upper gastrointestinal cases. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Trial ID: ChiCTR2100051452, https://www.chictr.org.cn/showprojen.aspx?proj=134284).

Intensive Systematic "Train-the-Trainer" Course as an Effective Strategy to Improve Detection of Early Gastric Cancer: A Multicenter Retrospective Study.

BACKGROUND: To improve the diagnosis of early gastric cancer (EGC), a train-the-trainer (TTT) course was developed. This trial aimed to investigate whether TTT courses from trained trainers could improve trainees' EGC detection. METHODS: In this multi-center, retrospective study, the training was carried out 8 times in one year. Clinical records one year before ("2016"), during ("2017"), and after ("2018") the course were collected. The primary endpoint was the improvement of EGC detection rate after TTT courses. RESULTS: Twenty-four trainees from 17 hospitals were included in this study. A total of 123,416 esophagogastroduodenoscopy and 65,570 colonoscopy procedures were analyzed. The early gastric cancer detection rate (EDR) was 0.101% in 2016, which significantly increased to 0.338% in 2018 (p = 0.015). The early gastric cancer ratio (ECR, ratio of newly detected EGCs to all newly detected gastric cancers) in 2016 was 8.440%, which consistently increased to 11.853% and 19.778% in 2017 and 2018 (p = 0.006), respectively. In contrast, the advanced gastric cancer detection rate (ADR) was similar before, during, or after the course (p = 0.987). The 3-year EDR, ECR, and ADR in esophageal and colorectal cancer were not significantly different. CONCLUSIONS: The systematic training course can improve EGC detection rate and may be an effective educational strategy to reduce gastrointestinal cancers mortality.

Modified Cap-Assisted Endoscopic Mucosal Resection Versus Endoscopic Submucosal Dissection for the Treatment of Rectal Neuroendocrine Tumors ≤10 mm: A Randomized Noninferiority Trial.

INTRODUCTION: Although recent guidelines recommend endoscopic resection of rectal neuroendocrine tumors (NET) ≤10 mm, there is no consensus on which endoscopic modality should be performed. We aimed to compare the safety and efficacy of modified cap-assisted endoscopic mucosal resection (mEMR-C) and endoscopic submucosal dissection (ESD) methods for the treatment of rectal NET ≤10 mm. METHODS: A randomized noninferiority trial comparing mEMR-C and ESD was conducted. The primary outcome was the histological complete resection rate; the secondary outcomes included en bloc resection rate, operation time, complications, and so on. Subgroup analyses and follow-up were also performed. RESULTS: Ninety patients were enrolled, and 79 patients with pathologically confirmed rectal NET were finally analyzed, including 38 cases of mEMR-C and 41 cases of ESD. Histological complete resection rate was 97.4% in the mEMR-C group and 92.7% in the ESD group. The noninferiority of mEMR-C compared with that of ESD was confirmed because the absolute difference was 4.7% (2-sided 90% confidence interval, -3.3% to 12.2%; P = 0.616). En bloc resection and successful removal of rectal NET were achieved in all patients. Advantages of mEMR-C over ESD included shorter operation time (8.89 ± 4.58 vs 24.8 ± 9.14 minutes, P < 0.05) and lower hospitalization cost ($2,233.76 ± $717.70 vs $2,987.27 ± $871.81, P < 0.05). Postoperative complications were recorded in 4 patients who received mEMR-C and 2 patients in the ESD group (11.5% vs 4.9%, P = 0.509), which were all well managed using endoscopy. Similar findings were observed when subgroup analysis was performed. DISCUSSION: mEMR-C is noninferior to ESD with a similar complete resection rate. In addition, mEMR-C had shorter procedure duration time and lower hospitalization costs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03982264.

Derepression of the USP22-FASN axis by p53 loss under oxidative stress drives lipogenesis and tumorigenesis.

Overproduction of reactive oxygen species (ROS) and aberrant lipid metabolism are established hallmarks of cancer; however, the role of ROS in lipid synthesis during tumorigenesis is almost unknown. Herein, we show that ROS regulates lipid synthesis and thus controls colorectal tumorigenesis through a p53-dependent mechanism. In p53 wild-type colorectal cancer (CRC) cells, hydrogen peroxide (H2O2)-induced p53 expression represses the transcription of deubiquitinase USP22, which otherwise deubiquitinates and stabilizes Fatty Acid Synthase (FASN), and thus inhibits fatty acid synthesis. Whereas, in p53-deficient CRC cells, ROS-mediated inhibition of USP22 is relieved, leading to FASN stabilization, which thus promotes lipid synthesis and tumor growth. In human CRC specimens, USP22 expression is positively correlated with FASN expression. Our study demonstrates that ROS critically regulates lipid synthesis and tumorigenesis through the USP22-FASN axis in a p53-dependent manner, and targeting the USP22-FASN axis may represent a potential strategy for the treatment of colorectal cancer.

Pan-Cancer Analysis of the Oncogenic and Immunological Role of RCN3: A Potential Biomarker for Prognosis and Immunotherapy.

Despite emerging publications have elucidated a functional association between RCN3 and tumors, no evidence about a pan-cancer analysis of RCN3 is available. Our study first conducted a comprehensive assessment of its expression profiles, prognosis value, immune infiltration, and relevant cellular pathways via bioinformatics techniques based on the public database of TCGA (The Cancer Genome Atlas). RCN3 is highly expressed in most tumors, and it is associated with poor prognosis. Kaplan-Meier analysis and Cox regression analysis suggested that the high expression of RCN3 was associated with poor overall survival (OS) in pan-cancer, Cox regression analysis also indicated high RCN3 expression was correlated with disease-specific survival (DSS) and progression-free interval (PFI) in most tumors. We observed a regulation function of RCN3 at genetic and epigenetic levels through CNA and DNA methylation using cBioPortal database. Based on Gene Set Enrichment Analysis, we first identified related pathways of RCN3 and its potential biological functions in pan-cancer, RCN3 was implicated in oncogenic pathways, and was related to extracellular matrix and immune regulation. We found that RCN3 positively correlated with the levels of infiltrating cells such as TAMs and CAFs, but negatively correlated with CD8+ T-cells by analyzing immune cell infiltration data we downloaded from published work and online databases, further investigation of the correlation between immunosuppressive genes, chemokines, chemokines receptors, and high RCN3 expression showed a significant positive association in the vast majority of TCGA cancer types. These results indicated its role as an immune regulatory in cancers and suggested that RCN3 is a potential biomarker for immunotherapy. Also, we found that expression of RCN3 was much higher in CRC tissues than in normal tissues with a higher expression level of RCN3 closely correlating to advanced American Joint Committee on Cancer (AJCC) stage, poor differentiation, increased tumor size, and poor prognosis of CRC. Biological function experiments showed that RCN3 regulated CRC cells' proliferation and metastasis ability. Upregulation of RCN3 in CRC cells increased the expression of immune related factor, including TGFß1, IL-10, and IL-6. Thus, our pan-cancer analysis offers a deep understanding of potential oncogenic roles of RCN3 in different cancers.

Endoscopic resection via antral submucosal tunneling for en bloc removal of tumors in the duodenal bulb.

To overcome difficulties in the removal of duodenal bulb lesions, especially those in anatomically challenging locations, we developed the endoscopic resection via antral submucosal tunneling (ERAST) technique. In this study, we evaluated the feasibility and safety of ERAST for the removal of superficial and subepithelial lesions in the duodenal bulb. This was a single-center retrospective study of 10 patients with lesions in the bulb. Submucosal tunneling from the gastric antrum to the duodenum was performed to facilitate en bloc tumor resection in the bulb. The en bloc resection rate, postoperative bleeding, and perforation were the primary endpoints. Ten lesions (four superficial and six subepithelial), with an average size of 19.1 ± 9.2 mm, were resected en bloc by ERAST. Esophagogastroduodenoscopy follow-up after 2 months indicated complete wound healing in all patients. In our primary experience, ERAST was found to be a feasible and safe endoscopic resection technique for the removal of lesions in the duodenal bulb, especially those that are difficult to access.

Regular diet is non-inferior to restricted diet after polypectomy with decreased hospitalization length of stay and cost: a randomized-controlled trial.

Background: There are no data comparing a regular diet with a restricted diet after endoscopic polypectomy in patients with colorectal polyps. The current guidelines also did not provide the detailed information of dietary patterns after polypectomy. In this study, we aimed to evaluate the safety and efficacy of different diets on post-polypectomy outcomes. Methods: A total of 302 patients with colorectal polyps who underwent polypectomy were prospectively enrolled between March 2019 and December 2019 in Nanfang Hospital (Guangzhou, China). Enrolled patients were then randomly assigned to a regular diet group or a restricted diet group after polypectomy. The study is a non-inferior design and the primary end point was the post-operative adverse events (AE) rate. Secondary end points included length of stay (LOS) and hospitalization cost. Results: Among all the included patients, 148 patients received a restricted diet and 154 patients received a regular diet after polypectomy. A total of 376 polyps were removed, with 183 polyps in the restricted diet group and 193 polyps in the regular diet group. Shorter LOS (4.0 ± 1.4 vs 4.8 ± 1.7, P < 0.001) and lower hospitalization costs (7,701.63 ± 2,579.07 vs 8,656.05 ± 3,138.53, P = 0.001) were observed in the regular diet group. In particular, there was no significant difference in 3-day AE rates between the restricted diet and the regular diet group (1.35% [2/148] vs 2.60% [4/154], P = 0.685). Subgroup analysis looking at the number of polyps removed in each patient and different treatment modalities also showed similar findings. Conclusion: Regular diet should be recommended after polypectomy for polyps <20 mm as it can shorten LOS and save hospitalization costs.

Tsc1 regulates tight junction independent of mTORC1.

Tuberous sclerosis complex 1 (Tsc1) is a tumor suppressor that functions together with Tsc2 to negatively regulate the mechanistic target of rapamycin complex 1 (mTORC1) activity. Here, we show that Tsc1 has a critical role in the tight junction (TJ) formation of epithelium, independent of its role in Tsc2 and mTORC1 regulation. When an epithelial cell establishes contact with neighboring cells, Tsc1, but not Tsc2, migrates from the cytoplasm to junctional membranes, in which it binds myosin 6 to anchor the perijunctional actin cytoskeleton to ß-catenin and ZO-1. In its absence, perijunctional actin cytoskeleton fails to form. In mice, intestine-specific or inducible, whole-body Tsc1 ablation disrupts adherens junction/TJ structures in intestine or skin epithelia, respectively, causing Crohn's disease-like symptoms in the intestine or psoriasis-like phenotypes on the skin. In patients with Crohn's disease or psoriasis, junctional Tsc1 levels in epithelial tissues are markedly reduced, concomitant with the TJ structure impairment, suggesting that Tsc1 deficiency may underlie TJ-related diseases. These findings establish an essential role of Tsc1 in the formation of cell junctions and underpin its association with TJ-related human diseases.

Artificial intelligence-enhanced white-light colonoscopy with attention guidance predicts colorectal cancer invasion depth.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) and EMR are applied in treating superficial colorectal neoplasms but are contraindicated by deeply invasive colorectal cancer (CRC). The invasion depth of neoplasms can be examined by an automated artificial intelligence (AI) system to determine the applicability of ESD and EMR. METHODS: A deep convolutional neural network with a tumor localization branch to guide invasion depth classification was constructed on the GoogLeNet architecture. The model was trained using 7734 nonmagnified white-light colonoscopy (WLC) images supplemented by image augmentation from 657 lesions labeled with histopathologic analysis of invasion depth. An independent testing dataset consisting of 1634 WLC images from 156 lesions was used to validate the model. RESULTS: For predicting noninvasive and superficially invasive neoplasms, the model achieved an overall accuracy of 91.1% (95% confidence interval [CI], 89.6%-92.4%), with 91.2% sensitivity (95% CI, 88.8%-93.3%) and 91.0% specificity (95% CI, 89.0%-92.7%) at an optimal cutoff of .41 and the area under the receiver operating characteristic (AUROC) curve of .970 (95% CI, .962-.978). Inclusion of the advanced CRC data significantly increased the sensitivity in differentiating superficial neoplasms from deeply invasive early CRC to 65.3% (95% CI, 61.9%-68.8%) with an AUROC curve of .729 (95% CI, .699-.759), similar to experienced endoscopists (.691; 95% CI, .624-.758). CONCLUSIONS: We have developed an AI-enhanced attention-guided WLC system that differentiates noninvasive or superficially submucosal invasive neoplasms from deeply invasive CRC with high accuracy, sensitivity, and specificity.

Laparoscopic versus open radical resection for transverse colon cancer: evidence from multi-center databases.

BACKGROUND: The role of laparoscopic approach is still a controversy for transverse colon cancer. Our investigation aimed to evaluate the perioperative and oncologic outcomes of laparoscopic versus open radical resection for transverse colon cancer based on evidence from multi-center databases. METHODS: 416 patients with transverse colon cancer undergoing radical surgery were analyzed including 181 laparoscopic resections and 235 open resections from January 2004 to May 2017 based on multi-center databases. Perioperative and oncologic outcomes were compared. RESULTS: No statistical differences regarding the baseline characteristics were observed between the two groups except the procedure type. Compared with open approach, laparoscopic approach was associated with statistically longer operation time (209.96 vs. 173.31 min, P = 0.002), significantly shorter time to soft food intake (4.73 vs. 6.01 days, P = 0.034), and shorter postoperative hospitalization (12.05 vs. 14.44 days, P = 0.001). In terms of oncologic outcomes, laparoscopic resection was correlated with statistically more lymph node retrieval (13.52 vs. 15.91, P = 0.002) and similar 5-year overall survival (91.2% vs. 89.1%, P = 0.356) and disease-free survival (89.6% vs. 86.0%, P = 0.873), compared with open resection. CONCLUSIONS: For patients with transverse colon cancer, laparoscopic approach can achieve several short-term advantages without decreasing long-term oncologic survival.

Artificial Intelligence-Assisted Colonoscopy for Detection of Colon Polyps: a Prospective, Randomized Cohort Study.

BACKGROUND AND AIMS: Improving the rate of polyp detection is an important measure to prevent colorectal cancer (CRC). Real-time automatic polyp detection systems, through deep learning methods, can learn and perform specific endoscopic tasks previously performed by endoscopists. The purpose of this study was to explore whether a high-performance, real-time automatic polyp detection system could improve the polyp detection rate (PDR) in the actual clinical environment. METHODS: The selected patients underwent same-day, back-to-back colonoscopies in a random order, with either traditional colonoscopy or artificial intelligence (AI)-assisted colonoscopy performed first by different experienced endoscopists (> 3000 colonoscopies). The primary outcome was the PDR. It was registered with clinicaltrials.gov . (NCT047126265). RESULTS: In this study, we randomized 150 patients. The AI system significantly increased the PDR (34.0% vs 38.7%, p < 0.001). In addition, AI-assisted colonoscopy increased the detection of polyps smaller than 6 mm (69 vs 91, p < 0.001), but no difference was found with regard to larger lesions. CONCLUSIONS: A real-time automatic polyp detection system can increase the PDR, primarily for diminutive polyps. However, a larger sample size is still needed in the follow-up study to further verify this conclusion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT047126265.

Standing-type magnetically guided capsule endoscopy versus gastroscopy for gastric examination: multicenter blinded comparative trial.

AIM: To compare feasibility and safety after gastrointestinal checkup by standing-type magnetically controlled capsule endoscopy (SMCE) and conventional gastroscopy. METHODS: This was a prospective multicenter, blinded study that compared SMCE with gastroscopy in patients from April 2018 to July 2018. All patients first underwent SMCE and then subsequently had gastroscopy with i.v. anesthesia. We calculated the compliance rates of gastric lesion detection by SMCE using gastroscopy as the standard. Capsule retention rate, incidence of adverse events, and patient satisfaction were documented throughout the study. RESULTS: One hundred and sixty-one patients who completed SMCE and gastroscopy were included in the analysis. Positive compliance rate among SMCE and gastroscopy was 92.0% (95% CI: 80.77%-97.78%). Negative compliance rate was 95.5% (89.80%, 98.52%). Moreover, overall compliance rate was 94.41% (89.65%, 97.41%). Sixty-four pathological outcomes were identified. Of these 64 outcomes, 50 were detected by both procedures. The gastroscopy method neglected seven findings (such as five erosions, one polyp, and one ulcer). Furthermore, SMCE also overlooked seven lesions (i.e. one erosion, two polyps, one atrophy, and three submucosal tumors). Capsule retention or related adverse events were not reported. CONCLUSION: Standing-type magnetically controlled capsule endoscopy provides equivalent agreement with gastroscopy and may be useful for screening of gastric illnesses without any anesthesia.

Real-time in vivo optical biopsy using confocal laser endomicroscopy to evaluate distal margin in situ and determine surgical procedure in low rectal cancer.

BACKGROUND: In low rectal cancer, a negative distal margin (DM) is necessary for R0 radical resection, and therefore, the choice of surgical procedure is dependent on whether the planned transection rectum has residual cancer or not. Currently, surgeons choose surgical procedures according to intraoperative in vitro DM frozen sections. This study aimed to investigate the feasibility of real-time in vivo optical biopsy using confocal laser endomicroscopy (CLE) to evaluate DM in situ and determine the surgical procedure in low rectal cancer. METHODS: Optical biopsy using CLE was performed when the rectum was dissected at the levator ani plane and rectum transection was ready. For negative DM, the surgical procedure of low anterior resection (LAR) was chosen. For positive DM, the surgical procedure of abdominoperineal resection (APR) was chosen. The specimen at the site of the planned transection rectum underwent intraoperative frozen section and routine pathological procedures. RESULTS: Eighteen patients underwent real-time in vivo optical biopsy using CLE in surgery. Eleven patients' CLE images of DM showed a regular, round crypt, and round luminal opening covered by a simple layer of columnar epithelial cells and goblet cells. LAR was then performed. Pathology revealed that the 11 DMs were negative, and the median length of the DMs was 2.0 cm. The remaining seven patients' CLE images of the planned transection rectum showed the loss of crypt architecture and irregular epithelial layer with loss of goblet cells. APR was then performed. Pathology confirmed cancer invasion, and the median distance from tumor to dentate line was 1.0 cm. The sensitivity, specificity, and accuracy of CLE optical biopsy of DM were 85.71%, 100%, and 94.44%, respectively. CONCLUSIONS: It is feasible to perform real-time in vivo optical biopsy using CLE to evaluate DM in situ and determine the surgical procedure in low rectal cancer.

Colonic epithelial mTORC1 promotes ulcerative colitis through COX-2-mediated Th17 responses.

The functional role of colonic epithelium in the pathogenesis of ulcerative colitis (UC) remains unclear. Here, we reveal a novel mechanism by which colonic epithelia recruit T helper-17 (Th17) cells during the onset of UC. mTOR complex 1 (mTORC1) was hyper-activated in colonic epithelia of UC mice. While colonic epithelial TSC1 (mTORC1 negative regulator) disruption induced constitutive mTORC1 activation in the colon epithelia and aggravated UC, RPTOR (essential mTORC1 component) depletion inactivated mTORC1 and ameliorated UC. TSC1 deficiency enhanced, whereas RPTOR ablation reduced the expression of cyclooxygenase 2 (COX-2), interleukin-1 (IL-1), IL-6, and IL-23, as well as Th17 infiltration in the colon. Importantly, inhibition of COX-2 reversed the elevation in the expression of these proinflammatory mediators induced by TSC1 deficiency, and subsequently reduced the symptoms and pathological characteristics of UC in mouse models. Mechanistically, mTORC1 activates COX-2 transcription via phosphorylating STAT3 and enhancing it's binding to the COX-2 promoter. Consistently, enhanced mTORC1 activity and COX2 expression, as well as strong positive correlation between each other, were observed in colonic epithelial tissues of UC patients. Collectively, our study demonstrates an essential role of epithelial mTORC1 in UC pathogenesis and establishes a novel link between colonic epithelium, Th17 responses, and UC development.

Endoscopic mucosa-sparing lateral dissection for treatment of gastric submucosal tumors: a prospective cohort study.

BACKGROUND: In our previous work, we developed a modified method for the removal of gastric submucosal tumors (SMTs), called endoscopic mucosa-sparing lateral dissection (EMSLD). This prospective study aimed to evaluate the efficacy and postoperative outcomes of EMSLD. METHODS: We prospectively enrolled 25 consecutive patients with gastric SMTs, who received EMSLD treatment. Clinicopathological characteristics and operation-related outcomes were analyzed. RESULTS: The mean age of patients was 49.3 ±â€Š9.7 years, and the mean tumor size was 14.6 ±â€Š6.1 mm. En bloc resection was achieved in all cases. The mean procedure time was 47.3 ± 25.9 minutes, and the estimated blood loss was 4.8 ±â€Š3.5 mL. Endoscopic full-thickness resection was performed in six patients (24 %) because the tumors originated from the deep muscularis propria layer. All perforations and resection defects were successfully closed by the retained mucosa and endoclips. No serious complications related to EMSLD were encountered during or after the procedure. CONCLUSIONS: EMSLD was reliable and effective for the removal of gastric SMTs. However, large-scale randomized controlled trials are needed.