Clinical outcomes of endoscopic resection for the treatment of intermediate- or high-risk gastric small gastrointestinal stromal tumors: a multicenter retrospective study.

BACKGROUND AND AIMS: Many studies of gastric gastrointestinal stromal tumors (g-GISTs) following endoscopic resection (ER) have typically focused on tumor size, with most tumors at low risk of aggressiveness after risk stratification. There have been few systematic studies on the oncologic outcomes of intermediate- or high-risk g-GISTs after ER. METHODS: From January 2014 to January 2020, we retrospectively collected patients considered at intermediate- or high-risk of g-GISTs according to the modified NIH consensus classification system. The primary outcome was overall survival (OS). RESULTS: Six hundred and seventy nine (679) consecutive patients were diagnosed with g-GISTs and treated by ER between January 2014 and January 2020 in three hospitals in Shanghai, China. 43 patients (20 males and 23 females) were confirmed at intermediate-or high-risk. The mean size of tumors was 2.23 ± 1.01 cm. The median follow-up period was 62.02 ± 15.34 months, with a range of 28 to 105 months. There were no recurrences or metastases, even among patients having R1 resections. The 5-year OS rate was 97.4% (42/43). CONCLUSION: ER for intermediate- or high-risk gastric small GISTs is a feasible and safe method, which allows for a wait-and-see approach before determining the necessity for imatinib adjuvant or surgical treatment. This approach to g-GISTs does require that patients undergo close follow-up.

Automatically optimized radiomics modeling system for small gastric submucosal tumor (<2 cm) discrimination based on EUS images.

BACKGROUND AND AIMS: The clinical management of small gastric submucosal tumors (SMTs) (<2 cm) faces a non-negligible challenge because of the lack of guideline consensus and effective diagnostic tools. This article develops an automatically optimized radiomics modeling system (AORMS) based on EUS images to diagnose and evaluate SMTs. METHODS: A total of 205 patients with EUS images of small gastric SMTs (<2 cm) were retrospectively enrolled in the development phase of AORMS for the diagnosis and the risk stratification of GI stromal tumor (GIST). A total of 178 patients with images from different centers were prospectively enrolled in the independent testing phase. The performance of AORMS was compared to that of endoscopists in the development set and evaluated in the independent testing set. RESULTS: AORMS demonstrated an area under the curve (AUC) of 0.762 for the diagnosis of GIST and 0.734 for the risk stratification of GIST, respectively. In the independent testing set, AORMS achieved an AUC of 0.770 and 0.750 for the diagnosis and risk stratification of small GISTs, respectively. In comparison, the AUCs of 5 experienced endoscopists ranged from 0.501 to 0.608 for diagnosing GIST and from 0.562 to 0.748 for risk stratification. AORMS outperformed experienced endoscopists by more than 20% in diagnosing GIST. CONCLUSIONS: AORMS implements automatic parameter selection, which enhances its robustness and clinical applicability. It has demonstrated good performance in the diagnosis and risk stratification of GISTs, which could aid endoscopists in the diagnosis of small gastric SMTs (<2 cm).

Validation and update of a clinical score model to predict technical difficulty of colorectal endoscopic submucosal dissection: a multicenter prospective cohort study.

BACKGROUND AND AIMS: The Zhongshan colorectal endoscopic submucosal dissection (CR-ESD) score model was proposed to grade the technical difficulty of CR-ESD. The objective of this study was to prospectively validate and update the score model. METHODS: A multicenter prospective cohort analysis of CR-ESD was conducted. Individual data on patients, lesions, and outcomes of CR-ESD were used to validate the original model and further refine the difficulty of the prediction model. Data were randomly divided into discovery and internal validation cohorts. A multivariate Cox regression analysis was conducted on the discovery cohort to develop an updated risk-scoring system, which was then validated. RESULTS: Five hundred forty-eight patients with 565 colorectal lesions treated by ESD from 4 hospitals were included. In the prospective validation cohort, the area under the receiver-operating characteristic (ROC) curve for the original model was .707. Six risk factors were identified and assigned point values: tumor size (2 points for 30-50 mm, 3 points for ≥50 mm), at least two-thirds circumference of the lesion (3 points), tumor location in the cecum (2 points) or flexure (2 points), laterally spreading tumor-nongranular lesions (1 point), preceding biopsy sampling (1 point), and NBI International Colorectal Endoscopic type 3 (3 points). The updated model had an area under the ROC curve of .738 in the discovery cohort and of .782 in the validation cohort. Cases were categorized into easy (score = 0-1), intermediate (score = 2-3), difficult (score = 4-6), and very difficult (score ≥7) groups. Satisfactory discrimination and calibration were observed. CONCLUSIONS: The original model achieved an acceptable level of prediction in the prospective cohort. The updated model exhibited superior performance and can be used in place of the previous version. (Clinical trial registration number: ChiCTR2100047087.).

Efficacy of image-enhanced endoscopy for colorectal adenoma detection: A multicenter, randomized trial.

BACKGROUND: Improved adenoma detection at colonoscopy has decreased the risk of developing colorectal cancer. However, whether image-enhanced endoscopy (IEE) further improves the adenoma detection rate (ADR) is controversial. AIM: To compare IEE with white-light imaging (WLI) endoscopy for the detection and identification of colorectal adenoma. METHODS: This was a multicenter, randomized, controlled trial. Participants were enrolled between September 2019 to April 2021 from 4 hospital in China. Patients were randomly assigned to an IEE group with WLI on entry and IEE on withdrawal (n = 2113) or a WLI group with WLI on both entry and withdrawal (n = 2098). The primary outcome was the ADR. The secondary endpoints were the polyp detection rate (PDR), adenomas per colonoscopy, adenomas per positive colonoscopy, and factors related to adenoma detection. RESULTS: A total of 4211 patients (966 adenomas) were included in the analysis (mean age, 56.7 years, 47.1% male). There were 2113 patients (508 adenomas) in the IEE group and 2098 patients (458 adenomas) in the WLI group. The ADR in two group were not significantly different [24.0% vs 21.8%, 1.10, 95% confidence interval (CI): 0.99-1.23, P = 0.09]. The PDR was higher with IEE group (41.7%) than with WLI group (36.1%, 1.16, 95%CI: 1.07-1.25, P = 0.01). Differences in mean withdrawal time (7.90 ± 3.42 min vs 7.85 ± 3.47 min, P = 0.30) and adenomas per colonoscopy (0.33 ± 0.68 vs 0.28 ± 0.62, P = 0.06) were not significant. Subgroup analysis found that with narrow-band imaging (NBI), between-group differences in the ADR, were not significant (23.7% vs 21.8%, 1.09, 95%CI: 0.97-1.22, P = 0.15), but were greater with linked color imaging (30.9% vs 21.8%, 1.42, 95%CI: 1.04-1.93, P = 0.04). the second-generation NBI (2G-NBI) had an advantage of ADR than both WLI and the first-generation NBI (27.0% vs 21.8%, P = 0.01; 27.0% vs 21.2.0%, P = 0.01). CONCLUSION: This prospective study confirmed that, among Chinese, IEE didn't increase the ADR compared with WLI, but 2G-NBI increase the ADR.

Lesion-Decoupling-Based Segmentation With Large-Scale Colon and Esophageal Datasets for Early Cancer Diagnosis.

Lesions of early cancers often show flat, small, and isochromatic characteristics in medical endoscopy images, which are difficult to be captured. By analyzing the differences between the internal and external features of the lesion area, we propose a lesion-decoupling-based segmentation (LDS) network for assisting early cancer diagnosis. We introduce a plug-and-play module called self-sampling similar feature disentangling module (FDM) to obtain accurate lesion boundaries. Then, we propose a feature separation loss (FSL) function to separate pathological features from normal ones. Moreover, since physicians make diagnoses with multimodal data, we propose a multimodal cooperative segmentation network with two different modal images as input: white-light images (WLIs) and narrowband images (NBIs). Our FDM and FSL show a good performance for both single-modal and multimodal segmentations. Extensive experiments on five backbones prove that our FDM and FSL can be easily applied to different backbones for a significant lesion segmentation accuracy improvement, and the maximum increase of mean Intersection over Union (mIoU) is 4.58. For colonoscopy, we can achieve up to mIoU of 91.49 on our Dataset A and 84.41 on the three public datasets. For esophagoscopy, mIoU of 64.32 is best achieved on the WLI dataset and 66.31 on the NBI dataset.

Porphyromonas gingivalis predicts local recurrence after endoscopic submucosal dissection of early esophageal squamous cell carcinoma or precancerous lesion.

BACKGROUND: Porphyromonas gingivalis plays an oncogenic role in development and progression of esophageal squamous cell carcinoma (ESCC). However, the impact of P. gingivalis on local recurrence of early ESCC or precancerous lesion after ESD treatment remains unknown. The present study aimed to evaluate the impact of P. gingivalis on local recurrence after ESD treatment of early ESCC or high-grade dysplasia (HGD). METHODS: The amount of P. gingivalis was assessed by immunohistochemistry in 205 patients with early ESCC or HGD. Univariate and multivariate Cox regression analyses were performed to determine the effect of P. gingivalis on local recurrence. Propensity score matching analysis was performed to reduce the imbalance of baseline characteristics. A nomogram integrating significant prognostic factors was built for local recurrence prediction. RESULTS: The amount of P. gingivalis increased significantly in neoplasms that invaded up to muscularis mucosa and submucosa compared with lesions confined to epithelium or lamina propria. Overabundance of P. gingivalis was positively associated with invasion depth, post-ESD stricture and local recurrence. Univariate and multivariate Cox regression analyses revealed that P. gingivalis, longitudinal length of lesion and lymphovascular invasion were independent predictors for post-ESD recurrence. A nomogram comprising P. gingivalis, lymphovascular involvement, and lesion length performed well for prediction of post-ESD local recurrence with the concordance indices of 0.72 (95%CI, 0.62 to 0.80), 0.72 (95%CI, 0.63 to 0.80), and 0.74 (95%CI, 0.65 to 0.83) in the validation cohort, the entire cohort, and the subcohort after PSM, respectively. CONCLUSION: P. gingivalis overabundance is a risk factor and a potential predictor for local recurrence of early ESCC or HGD after ESD treatment. Thus, clearance of P. gingivalis represents an attractive strategy for prognosis improvement and for prevention of ESCC.

ClusterNet: a clustering distributed prior embedded detection network for early-stage esophageal squamous cell carcinoma diagnosis.

BACKGROUND: Early and accurate diagnosis of esophageal squamous cell carcinoma (ESCC) is important for reducing mortality. Analyzing intrapapillary capillary loops' (IPCLs) patterns on magnification endoscopy with narrow band imaging (ME-NBI) has been demonstrated effective in the diagnosis of early-stage ESCC. However, even experienced endoscopists may face difficulty in finding and classifying countless IPCLs on ME-NBI. PURPOSE: We propose a novel clustering prior embedded detection network: ClusterNet. ClusterNet is capable of analyzing the distribution of IPCLs on ME-NBI automatically and enables endoscopists to overview multiple types of visualization. With ClusterNet assisting, endoscopists may observe ME-NBI images more efficiently, thus they may also predict the pathology and make medical decisions more easily. METHODS: We propose the first large-scale ME-NBI dataset with fine-grained annotations by consensus of expert endoscopists. The dataset is splitted into a training set and an independent testing set based on patients. With two strategies for embedding, ClusterNet can automatically take the clustering effect into consideration. Prior to this work, none of the existing approaches take the clustering effect, which is rather important in classifying the IPCLs, into account. RESULTS: ClusterNet achieves an average precision of 81.2% and an average recall of 90.0% for the detection of IPCLs patterns on each patient of the independent testing set. We also compare ClusterNet with other state-of-the-art detection approaches. The performance of ClusterNet with embedding strategies is consistently superior to that of other approaches in terms of average precision, recall and F2-Score. CONCLUSIONS: Experiments demonstrate that our proposed method is able to detect almost all the IPCLs patterns on ME-NBI and classify them according to the Japanese Endoscopic Society (JES) classification accurately.

Long-term clinical outcomes of endoscopic submucosal dissection in rectal neuroendocrine tumors based on resection margin status: a real-world study.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been widely adopted in treating rectal neuroendocrine tumors (NETs). However, clinical outcomes in rectal NETs after ESD with different resection margin status remain scanty, particularly in patients with positive resection margins. This study aimed to evaluate the long-term clinical outcomes of ESD in rectal NET based on the resection margin status. METHODS: This retrospective study included 436 patients diagnosed with rectal NET who had undergone ESD. Clinical data, including age, sex, tumor size, stage, invasion, and the resection margin status, were collected. Further, the patients were assessed for complications, recurrence, distant metastasis, and long-term outcomes. RESULTS: Among all 436 patients, 395 patients had their primary ESD in our hospital. Complete resection was achieved in 319 patients. Patients who did not achieve complete resection opted for follow-up (n = 73), salvage surgery (n = 1) and salvage ESD (n = 2). Another 41 had their primary ESD in other hospital with incomplete resection and had salvage ESD in our hospital. All 436 patients had a median follow-up period of 61.4 months (range 33.4-125.3 months). During the follow-up period, two patients developed recurrences, while three patients developed metastasis. There were no significant differences in the 5-year progression-free survival and overall survival between patients with incomplete resection opting for follow-up compared to the other two groups (P = 0.5/0.8). However, the complication rates were significantly higher in patients who received salvage ESD. CONCLUSION: This study demonstrated that positive resection margins have no influence on survival in patients with rectal NET treated using ESD.

The efficacy of full-thickness endoscopic resection of subepithelial tumors in the gastric cardia.

BACKGROUND: Gastric subepithelial tumors (SETs) may harbor potential malignancy. Although it is well recognized that large SETs should be resected, the precise treatment strategy remains controversial. Compared to surgical resection, endoscopic resection (ER) has many advantages; however, ER of SETs in the cardia is challenging. AIM: To evaluate the safety and efficacy of endoscopic full-thickness resection (EFTR) for the treatment of gastric cardia SETs. METHODS: We retrospectively reviewed data from all patients with SETs originating from the muscularis propria layer in the gastric cardia that were treated by EFTR or submucosal tunneling ER (STER) at Zhongshan Hospital Fudan University between November 2014 and May 2022. Baseline characteristics and clinical outcomes, including procedure times and complications rates, were compared between groups of patients receiving EFTR and STER. RESULTS: A total of 171 tumors were successfully removed [71 (41.5%) tumors in the EFTR and 100 (58.5%) tumors in the STER group]. Gastrointestinal stromal tumors (GISTs) were the most common SET. The en bloc resection rate was 100% in the EFTR group vs 97.0% in STER group (P > 0.05). Overall, the EFTR group had a higher complete resection rate than the STER group (98.6% vs 91.0%, P < 0.05). The procedure time was also shorter in the EFTR group (44.63 ± 28.66 min vs 53.36 ± 27.34, P < 0.05). The most common major complication in both groups was electrocoagulation syndrome. There was no significant difference in total complications between the two groups (21.1% vs 22.0%, P = 0.89). CONCLUSION: EFTR of gastric cardia SETs is a very promising method to facilitate complete resection with similar complications and reduced operative times compared to STER. In cases of suspected GISTs or an unclear diagnosis, EFTR should be recommended to ensure complete resection.

Simultaneous endoscopic submucosal dissection for synchronous multiple early esophageal squamous cell carcinoma: a propensity score-matched analysis.

BACKGROUND: The clinical effect of endoscopic submucosal dissection (ESD) in the treatment of early esophageal squamous cell carcinoma (EESCC) is widely recognized. However, the long-term treatment outcome of simultaneous ESD for multiple EESCC currently remained unknown. Hence, this study was aimed at further evaluating the long-term outcome of simultaneous ESD for synchronous multiple EESCC by comparing with ESD for single EESCC. METHODS: Consecutive patients who underwent ESD for EESCC from June 2008 to June 2018 were included. Propensity score-matched analysis was used to compensate for the differences in age, sex, tumor location, tumor size, and tumor invasion depth between simultaneous and single ESD groups. Treatment outcomes including en bloc resection rate, curative resection rate, complication rate, and long-term outcomes including overall survival (OS), recurrence-free survival (RFS), metachronous recurrence were compared between the 2 groups after matching. RESULTS: The propensity score-matched analysis included 332 lesions (166 patients) and 332 lesions (332 patients) in simultaneous and single ESD groups, respectively. Among all the outcomes, en bloc resection, curative resection, 5-year OS, and 5-year RFS rates were comparable. Complications were more common in the simultaneous ESD group (15.06% vs. 9.64%, P = 0.073). The 5-year metachronous recurrence rates were significantly high in the simultaneous ESD groups (24.28% vs. 6.99%). CONCLUSIONS: Simultaneous ESD is an effective and safe methodology for synchronous multiple EESCC; it also reduces hospital stay and medical expenses. The risk of metachronous recurrence is higher for patients with synchronous multiple EESCC; thus, more intensive strategies are required.

Transcriptomic Analyses of the Adenoma-Carcinoma Sequence Identify Hallmarks Associated With the Onset of Colorectal Cancer.

The concept of the adenoma-carcinoma sequence in colorectal cancer (CRC) is widely accepted. However, the relationship between the characteristics of the transcriptome and the adenoma-carcinoma sequence in CRC remains unclear. Here, the transcriptome profiles of 15 tissue samples from five CRC patients were generated by RNAseq. Six specific dynamic expression patterns of differentially expressed genes (DEGs) were generated by mFuzz. Weighted correlation network analysis showed that DEGs in cluster 4 were associated with carcinoma tissues, and those in cluster 6 were associated with non-normal tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified metabolic dysregulation as a consistent finding throughout the transition process, whereas downregulation of the immune response occurred during normal to adenoma transition, and the upregulation of canonical pathways was associated with adenoma to carcinoma transition. Overall survival analysis of patients in cluster 6 identified TPD52L1 as a marker of poor prognosis, and cell proliferation, colony formation, wound healing, and Transwell invasion assays showed that high expression levels of TPD52L1 promoted malignant behaviors. In total, 70 proteins were identified as potential partners of hD53 by mass spectrometry. CRC formation was associated with three cancer hallmarks: dysregulation of metabolism, inactivation of the immune response, and activation of canonical cancer pathways. The TPD52L1 gene was identified as a potential marker to track tumor formation in CRC and as an indicator of poor patient prognosis.

NLRP7 deubiquitination by USP10 promotes tumor progression and tumor-associated macrophage polarization in colorectal cancer.

BACKGROUND: NOD-like receptors affect multiple stages of cancer progression in many malignancies. NACHT, LRR, and PYD domain-containing protein 7 (NLRP7) is a member of the NOD-like receptor family, although its role in tumorigenesis remains unclear. By analyzing clinical samples, we found that NLRP7 protein levels were upregulated in colorectal cancer (CRC). We proposed the hypothesis that a high level of NLRP7 in CRC may promote tumor progression. Here, we further investigated the role of NLRP7 in CRC and the underlying mechanism. METHODS: NLRP7 expression in human CRC and adjacent non-tumorous tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The effect of NLRP7 in CRC progression was investigated in vitro and in vivo. Proteins interacting with NLRP7 were identified by immunoprecipitation and mass spectrometry analysis while immunofluorescence staining revealed the cellular location of the proteins. Cellular ubiquitination and protein stability assays were applied to demonstrate the ubiquitination effect on NLRP7. Cloning and mutagenesis were used to identify a lysine acceptor site that mediates NLRP7 ubiquitination. Cytokines/chemokines affected by NLRP7 were identified by RNA sequencing, qRT-PCR, and enzyme-linked immunosorbent assay. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and immunohistochemistry. RESULTS: NLRP7 protein levels, but not mRNA levels, were upregulated in CRC, and increased NLRP7 protein expression was associated with poor survival. NLRP7 promoted tumor cell proliferation and metastasis in vivo and in vitro and interacted with ubiquitin-specific protease 10, which catalyzed its deubiquitination in CRC cells. NLRP7 stability and protein levels in CRC cells were modulated by ubiquitination and deubiquitination, and NLRP7 was involved in the ubiquitin-specific protease 10 promotion of tumor progression and metastasis in CRC. K379 was an important lysine acceptor site that mediates NLRP7 ubiquitination in CRC cells. In CRC, NLRP7 promoted the polarization of pro-tumor M2-like macrophages by inducing the secretion of C-C motif chemokine ligand 2. Furthermore, NLRP7 promoted NF-κB nuclear translocation and activation of C-C motif chemokine ligand 2 transcription. CONCLUSIONS: We showed that NLRP7 promotes CRC progression and revealed an as-yet-unidentified mechanism by which NLRP7 induces the polarization of pro-tumor M2-like macrophages. These results suggest that NLRP7 could serve as a biomarker and novel therapeutic target for the treatment of CRC.

A Triptolide Loaded HER2-Targeted Nano-Drug Delivery System Significantly Suppressed the Proliferation of HER2-Positive and BRAF Mutant Colon Cancer.

BACKGROUND: Colon cancer (CRC) was a malignant tumor and there were about 25% of patients with tumor metastasis at diagnosis stage. Chemotherapeutic agents for metastatic CRC patients were with great side effects and the clinical treatment results of advanced CRC were still not satisfactory. Human epidermal growth factor receptor 2 (HER2) is overexpressed in some CRC patients and is an effective target for CRC patient treatment. Anti-HER2 therapy had a beneficial role in the treatment of HER2-positive metastatic CRC with fewer side effects. CRC patients with BRAF mutations were resistant to HER2 antibodies treatment. Therefore, there was an urgent need to develop new therapeutic agents. METHODS: HER2 targeted nanoparticles (TPLNP) drug delivery system loading triptolide (TPL) were prepared and identified. The effects of TPLNP and free TPL on cell viability, targeting and cell cycle progression on HT29 (BRAF mutation) with HER2 overexpression, were evaluated by Cell Counting Kit-8 (CCK8), Fluorescence Activating Cell Sorter (FACS) and immunofluorescence methods, respectively. The anti-tumor efficacies of TPLNP were evaluated in subcutaneous xenograft model of colon cancer and the survival rate, tumor volume, liver and kidney indexes of tumor-bearing mice were measured. RESULTS: TPLNP was small in nanosize (73.4±5.2nm) with narrow size distribution (PDI=0.15±0.02) and favorable zeta potential (pH=9.6, zeta potential: -57.3±6.69mV; pH=7.0, zeta potential: -28.7±5.1mV; pH=5.6, zeta potential: -21.1±4.73mV). Comparing with free TPL treatment group, TPLNP developed stranger colon cancer-killing efficiency in a dose- and time-dependent manner detected with CCK8 method; achieved good in vitro colon cancer targeting detected with flow cytometry and immunofluorescence experiments; enhanced more HT29-HER2 apoptosis and induced more cell cycle arrested in G1-S phase detected with FACS in vitro. As for in vivo antitumor response, TPLNP remarkably inhibited the growth of colon cancer in the colon cancer xenograft model, significantly improved the survival rate and did not exhibit significant liver and kidney toxicity in contrast with free TPL in vivo. CONCLUSION: TPLNP was effectively against colon cancer with HER2 overexpression and BRAF mutation in pre-clinical models. In summary, the TPLNP appeared to be a promising treatment option for CRC in clinical application based on improved efficacy and the favorable safety profile.

Comparative study on artificial intelligence systems for detecting early esophageal squamous cell carcinoma between narrow-band and white-light imaging.

BACKGROUND: Non-magnifying endoscopy with narrow-band imaging (NM-NBI) has been frequently used in routine screening of esophagus squamous cell carcinoma (ESCC). The performance of NBI for screening of early ESCC is, however, significantly affected by operator experience. Artificial intelligence may be a unique approach to compensate for the lack of operator experience. AIM: To construct a computer-aided detection (CAD) system for application in NM-NBI to identify early ESCC and to compare it with our previously reported CAD system with endoscopic white-light imaging (WLI). METHODS: A total of 2167 abnormal NM-NBI images of early ESCC and 2568 normal images were collected from three institutions (Zhongshan Hospital of Fudan University, Xuhui Hospital, and Kiang Wu Hospital) as the training dataset, and 316 pairs of images, each pair including images obtained by WLI and NBI (same part), were collected for validation. Twenty endoscopists participated in this study to review the validation images with or without the assistance of the CAD systems. The diagnostic results of the two CAD systems and improvement in diagnostic efficacy of endoscopists were compared in terms of sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. RESULTS: The area under receiver operating characteristic curve for CAD-NBI was 0.9761. For the validation dataset, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CAD-NBI were 91.0%, 96.7%, 94.3%, 95.3%, and 93.6%, respectively, while those of CAD-WLI were 98.5%, 83.1%, 89.5%, 80.8%, and 98.7%, respectively. CAD-NBI showed superior accuracy and specificity than CAD-WLI (P = 0.028 and P ≤ 0.001, respectively), while CAD-WLI had higher sensitivity than CAD-NBI (P = 0.006). By using both CAD-WLI and CAD-NBI, the endoscopists could improve their diagnostic efficacy to the highest level, with accuracy, sensitivity, and specificity of 94.9%, 92.4%, and 96.7%, respectively. CONCLUSION: The CAD-NBI system for screening early ESCC has higher accuracy and specificity than CAD-WLI. Endoscopists can achieve the best diagnostic efficacy using both CAD-WLI and CAD-NBI.

RNA binding protein CUGBP1 mediates the liver metastasis of colorectal cancer by regulating the ErbB signal pathway.

BACKGROUND: The CUGBP1 (CELF1) is differentially expressed in liver metastasis and no liver metastasis colorectal cancers (CRC) tissues and the function of CUGBP1 in CRC is still unclear. METHODS: Five cases of colorectal adenocarcinoma and 6 cases of liver metastatic CRC lesions were collected and subjected to cDNA microarray and bioinformatical analyses. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm the result. Cell function assays were used to study the function of CUGBP1, and the western blot was used to discover the change of the downstream molecules. RESULTS: CUGBP1 was significantly elevated in liver metastatic CRC lesions. Besides, the CUGBP1 can promote proliferation, colony formation, invasion, metastasis abilities as well as increase the apoptosis rates of CRC cells. ERBB2 was positively related to the CUGBP1. Western blot results found that silence of CUGBP1 decreased the protein level of p-AKT and p-ERK without influence the expression level of total protein of AKT and ERK. CONCLUSIONS: CUGBP1 can promote liver metastasis of CRC by promoting the phosphorylation of AKT and ERK through the ErbB signaling pathway. CUGBP1 is a potential biomarker for early detection of CRC and maybe a novel therapeutic target of CRC treatment, especially in liver metastasis.

Strategy for Scanning Peptide-Coding Circular RNAs in Colorectal Cancer Based on Bioinformatics Analysis and Experimental Assays.

Background: Colorectal cancer (CRC) is the third most common cause of cancer deaths worldwide. Numerous studies have reported that circular RNAs (circRNAs) have important functions in CRC. It was first thought that circRNAs were non-coding RNA; however, more recently they were discovered to encode peptides and play a pivotal role in cancer development and progression. It was shown that most circRNAs possess coding potential; however, not all of them can truly encode peptides. Therefore, a practical strategy to scan for coding circRNAs is needed. Method: Sequence analyses included open reading frame (ORF) prediction, coding peptide prediction, and the identification of unique sequences. Then, experimental assays were used to verify the coded peptides, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was introduced to detect sequences of circRNAs with coding potential, and Western blot was used to identify the encoded peptides. Finally, the functions of the circRNAs were primarily explored. Result: An efficient strategy for searching circRNAs with coding potential was created. We verified this schedule using public databases and LC-MS/MS, then two of these circRNAs were selected for further verification. We used commercial antibodies that can also identify the predicted peptides to test the coded peptides. The functions of the circRNAs were explored primarily, and the results showed that they were mainly involved in the promotion of proliferation and invasion ability. Discussion: We have constructed an efficient strategy of scanning circRNAs with coding potential. Our strategy helped to provide a more convenient pathway for identifying circRNA-derived peptides, which can be a potential therapeutic target or a diagnostic biomarker.

Identifying early gastric cancer under magnifying narrow-band images with deep learning: a multicenter study.

BACKGROUND AND AIMS: Narrow-band imaging with magnifying endoscopy (ME-NBI) has shown advantages in the diagnosis of early gastric cancer (EGC). However, proficiency in diagnostic algorithms requires substantial expertise and experience. In this study, we aimed to develop a computer-aided diagnostic model for EGM (EGCM) to analyze and assist in the diagnosis of EGC under ME-NBI. METHODS: A total of 1777 ME-NBI images from 295 cases were collected from 3 centers. These cases were randomly divided into a training cohort (n = 170), an internal test cohort (ITC, n = 73), and an external test cohort (ETC, n = 52). EGCM based on VGG-19 architecture (Visual Geometry Group [VGG], Oxford University, Oxford, UK) with a single fully connected 2-classification layer was developed through fine-tuning and validated on all cohorts. Furthermore, we compared the model with 8 endoscopists with varying experience. Primary comparison measures included accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: EGCM acquired AUCs of .808 in the ITC and .813 in the ETC. Moreover, EGCM achieved similar predictive performance as the senior endoscopists (accuracy: .770 vs .755, P = .355; sensitivity: .792 vs .767, P = .183; specificity: .745 vs .742, P = .931) but better than the junior endoscopists (accuracy: .770 vs .728, P < .05). After referring to the results of EGCM, the average diagnostic ability of the endoscopists was significantly improved in terms of accuracy, sensitivity, PPV, and NPV (P < .05). CONCLUSIONS: EGCM exhibited comparable performance with senior endoscopists in the diagnosis of EGC and showed the potential value in aiding and improving the diagnosis of EGC by endoscopists.

Risk factors for delayed bleeding after endoscopic submucosal dissection of colorectal tumors.

AIM: To investigate the risk factors for delayed bleeding following endoscopic submucosal dissection (ESD) for colorectal neoplasms. METHODS: We retrospectively reviewed the medical records of 991 consecutive patients who underwent ESD for colorectal neoplasms at our hospital from January 2007 to November 2016. Delayed post-ESD bleeding was defined as bleeding within 6 h to 30 days after ESD that resulted in either of the three situations: overt hematochezia, bleeding spots confirmed by repeat colonoscopy, or the requirement of a blood transfusion. Delayed bleeding was furtherly separated into early and late delayed bleeding by the end of post-ESD day 2. We analyzed the relationship between delayed bleeding and candidate factors including patient-, lesion-, and treatment-related details. RESULTS: Delayed post-ESD bleeding was found in 47 patients (4.7%), of which 18 cases were late delayed bleeding. Among all patients, 14 patients required a second colonoscopy, and 2 other patients were transferred to surgery. Univariate analysis revealed that patients with hypertension (p = 0.017) and using hot biopsy forceps for wound management (p = 0.028) were significantly associated with late delayed bleeding. Both risk factors remained significant after multivariate analysis: hypertension (OR 2.829, 95% CI 1.101-7.265, p = 0.031), hot biopsy forceps (OR 2.873, 95% CI 1.013-8.147, p = 0.047). Using hot biopsy forceps was also the significant risk factor for late delayed bleeding compared with early delayed bleeding. CONCLUSION: Patient with hypertension and using hot biopsy forceps for wound management during procedure call for attention on high risk of delayed post-ESD bleeding. Therefore, additional perioperative treatment is recommended in patients with these risk factors.

Prediction of technically difficult endoscopic submucosal dissection for large superficial colorectal tumors: a novel clinical score model.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is a promising technique for removing superficial GI tumors, but ESD is technically difficult. The aim of this study was to establish a clinical score model for grading technically difficult colorectal ESD. METHODS: Data on patients, lesions, and outcomes of colorectal ESD at 2 centers were analyzed. The objective parameter of successful ESD within 60 minutes was set as an endpoint to evaluate the difficulty. Independent predictors of difficulty in the derivation cohort were identified by multiple logistic regression analysis and used to develop a clinical score. We validated the score model in the validation cohort. RESULTS: The clinical score comprised tumor size of 30 to 50 mm (1 point) or ≥50 mm (2 points), at least two-thirds circumference of the lesion (2 points), location in the cecum (1 point), flexure (2 points) or dentate line (1 point), and laterally spreading tumor nongranular lesions (1 point). Areas under the receiver operator characteristic curves for the score model were comparable (derivation [.70] vs internal validation [.69] vs external validation [.69]). The probability of successful ESD within 60 minutes in easy (score = 0), intermediate (score = 1), difficult (score = 2-3), and very difficult (score ≥4) categories were 75.0%, 51.3%, 35.6%, and 3.4% in the derivation cohort; 73.3%, 47.9%, 31.8%, and 16.7% in the internal validation cohort; and 79.5%, 66.7%, 43.3%, and 20.0% in the external validation cohort, respectively. CONCLUSIONS: This clinical score model accurately predicts the probability of successful ESD within 60 minutes and can be applied to grade the technical difficulty before the procedure.

HDAC2 promotes the EMT of colorectal cancer cells and via the modular scaffold function of ENSG00000274093.1.

Histone deacetylase 2 (HDAC2), a member of the Histone deacetylase family, plays a vital role in various carcinomas. In this study, we identified that HDAC2 expression levels are associated with liver metastasis, higher T stages and poor prognosis in colorectal cancer. HDAC2 down-regulation via lentivirus-mediated expression of HDAC2-targeting shRNA reduced the in vitro migration and invasion ability of HCT116 cell as well as their liver metastasis in nude mouse xenografts. Mechanistically, HDAC2 promotes epithelial-mesenchymal transition (EMT) in colorectal cancer cells by combining HDAC1 with EZH2 (a key histone methyltransferase), possibly through the modular scaffold function of a new lncRNA, ENSG00000274093.1. HDAC2 thus appears to promote CRC cell migration and invasion through binding HDAC1 and EZH2 via ENSG00000274093.1.