Futuristic Developments and Applications in Endoluminal Stenting

Endoscopic stenting is a well-established option for the treatment of malignant obstruction, temporary management of benign strictures, and sealing transmural defects, as well as drainage of pancreatic fluid collections and biliary obstruction. In recent years, in addition to expansion in indications for endoscopic stenting, considerable strides have been made in stent technology, and several types of devices with advanced designs and materials are continuously being developed. In this review, we discuss the important developments in stent designs and novel indications for endoluminal and transluminal stenting. Our discussion specifically focuses on (i) biodegradable as well as (ii) irradiating and drug-eluting stents for esophageal, gastroduodenal, biliary, and colonic indications, (iii) endoscopic stenting in inflammatory bowel disease, and (iv) lumen-apposing metal stent.

Nursing Value Analysis and Risk Assessment of Acute Gastrointestinal Bleeding Using Multiagent Reinforcement Learning Algorithm

Gastrointestinal bleeding (GIB) indicates an issue in the digestive system. Blood can be found in feces or vomiting; however, it is not always visible, even if it makes the stool appear darkish or muddy. The bleeding can range in harshness from light to severe and can be dangerous. It is advised that nursing value analysis and risk assessment of patients with GIB is essential, but existing risk assessment techniques function inconsistently. Machine learning (ML) has the potential to increase risk evaluation. For evaluating risk in patients with GIB, scoring techniques are ineffective; a machine learning method would help. As a result, we present а unique machine learning-based nursing value analysis and risk assessment framework in this research to construct a model to evaluate the risk of hospital-based interventions or mortality in individuals with GIB and make a comparison to that of other rating systems. Initially, the dataset is collected, and preprocessing is done. Feature extraction is done using local binary patterns (LBP). Classification is performed using a fuzzy support vector machine (FSVM) classifier. For risk assessment and nursing value analysis, machine learning-based prediction using a multiagent reinforcement algorithm is employed. For improving the performance of the proposed system, we use spider monkey optimization (SMO) algorithm. The performance metrics like classification accuracy, area under the receiver-operating characteristic curve (AUROC), area under the curve (AUC), sensitivity, specificity, and precision are analyzed and compared with the traditional approaches. In individuals with GIB, the suggested technique had a good–excellent prognostic efficacy, and it outperformed other traditional models.

Development and Application of Magnetically Controlled Capsule Endoscopy in Detecting Gastric Lesions

In the past 20 years, several magnetically controlled capsule endoscopes (MCCE) have been developed for the evaluation of gastric lesions, including NaviCam (ANKON), MiroCam-Navi (Intromedic), Endocapsule MGCE (Olympus and Siemens), SMCE (JIFU), and FAMCE (Jinshan). Although limited to observing esophageal and duodenal lesions and lacking the ability of biopsy, MCCE has the advantages of comfort, safety, no anesthesia, no risk of cross-infection, and high acceptability. Several high-quality RCTs showed that the diagnostic accuracy of MCCE is comparable to the traditional gastroscopy. Due to the nonnecessity of anesthesia, MCCE may be more suitable for the elderly with obvious comorbidities as well as children. With more evidences accumulated and more innovative technologies developed, MCCE is expected to be an important tool for screening of early gastric cancer or the diagnosis of gastric diseases.

Exploration of the Potential Mechanisms of Wumei Pill for the Treatment of Ulcerative Colitis by Network Pharmacology

Background. Wumei pill (WMP) has a long history of colitis treatment in China, but the protective mechanisms have not been elucidated. To uncover the potential mechanisms of WMP against ulcerative colitis (UC), the network pharmacology approach was utilized in this study. Methods. Public databases were utilized to identify the potential targets of WMP and genes related to UC. Based on the identified overlapping common targets, drug-ingredient-target gene network, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-protein interaction (PPI) analysis were conducted. Molecular docking was carried out to verify the selected key active ingredients and core targets. Results. 129 active ingredients and 622 target genes were obtained. The drug-ingredient-target gene network revealed 52 active ingredients of WMP acting on 73 targets related to UC. GO analysis revealed that biological processes were mainly associated with oxidative stress, such as, reactive oxygen species metabolic processes, response to oxidative stress, cellular response to oxidative stress, response to reactive oxygen species, and regulation of reactive oxygen species metabolic processes. KEGG analysis revealed that the immune- and inflammation-related pathways, tumor-related signaling pathways, and microbial infection-related signaling pathways were the most significant. PPI network identified 13 core target genes. The molecular docking results indicated the formation of stable bonds between the active ingredients and core target genes. Conclusions. The approach of network pharmacology reveals the key ingredients, potential core targets, and biological process of WMP in the treatment of UC. The mechanisms of action of WMP involve anti-inflammation, antioxidation, and modulation of immunity, which provides evidence for the therapeutic role of WMP in UC.

TAS-102 Monotherapy and Combination Therapy with Bevacizumab for Metastatic Colorectal Cancer

Objective. To evaluate the effectiveness and safety of TAS-102 monotherapy and combination therapy with bevacizumab in the treatment of metastatic colorectal cancer. Methods. The PubMed, Web of Science, MEDLINE, and Cochrane Library databases were searched for the literature on TAS-102 treatment of metastatic colorectal cancer. Extracted data include median overall survival (mOS), median progression-free survival (mPFS), and the incidence of adverse events for meta-analysis. Results. Our study found that the mOS of patients treated with TAS-102 monotherapy was 6.95 (95% CI: 6.26-7.72) months and the mPFS was 2.53 (95% CI: 2.31-2.78) months. The mOS in patients treated by TAS-102 combined with bevacizumab was 10.41 (95% CI: 8.40-12.89) months, and the mPFS is 4.35 (95% CI: 3.05-6.20) months. In the control experiment, the patients’ mOS and mPFS were improved. TAS-102+B vs. TAS-102 ( OR = 0.41 , 95% CI: 0.18-0.93; OR = 0.72 , 95% CI: 0.63-0.83) and TAS-102 vs. placebo ( OR = 0.44 , 95% CI: 0.29-0.67; OR = 0.51 , 95% CI: 0.42-0.62) were studied to actively prevent the occurrence of neutropenia, leukopenia, febrile neutropenia, anemia, and vomiting. Conclusion. TAS-102 monotherapy and combination therapy with bevacizumab can significantly improve the survival of patients and prevent specific adverse events from happening.

Risk of Bleeding after Colorectal Endoscopic Resection in Patients with Continued Warfarin Use Compared to Heparin Replacement: A Propensity Score Matching Analysis

The Japan Gastroenterological Endoscopy Society (JGES) guidelines recommend continued warfarin treatment during gastroenterological endoscopic procedures with a high risk of bleeding as an alternative to heparin replacement in patients on warfarin therapy. However, there is insufficient evidence to support the use of warfarin in colorectal endoscopic resection (ER). The present study is aimed at verifying the risk of bleeding after ER for colorectal neoplasia (CRN) in patients with continued warfarin use. This was a single-center retrospective cohort study using clinical records. We assessed 126 consecutive patients with 159 CRNs who underwent ER (endoscopic mucosal resection, 146 cases; endoscopic submucosal dissection, 13 cases) at Hiroshima University Hospital between January 2014 and December 2019. Patients were divided into two groups: the heparin replacement group (79 patients with 79 CRNs) and the continued warfarin group (47 patients with 80 CRNs). One-to-one propensity score matching was performed to compare the bleeding rate after ER between the groups. The rate of bleeding after ER was significantly higher in the heparin replacement group than in the continued warfarin group for both before (10.1% vs. 1.3%, respectively; P = 0.0178 ) and after (11.9% vs. 0%, respectively; P = 0.0211 ) propensity score matching. None of the patients experienced thromboembolic events during the perioperative period. The risk of bleeding after colorectal ER was significantly lower in patients with continued warfarin use than in those with heparin replacement. Our data supports the recommendations of the latest JGES guidelines for patients receiving warfarin therapy.

Endoscopic Delivery Method Using a Retrieval Net for Patients with Small-Bowel Capsule Endoscopy Stagnation in the Stomach

With the increasing use of capsule endoscopy (CE), screening tests for the small bowel can be performed with minimal invasiveness. However, occasionally, the entire small bowel cannot be observed because of decreased peristalsis of the stomach. For such cases, we perform delivery of CE by an endoscope. We retrospectively examined the usefulness of the endoscopic delivery method using a retrieval net for patients with CE stagnation in the stomach. From 2,270 patients who underwent small-bowel CE at Hiroshima University Hospital from January 2013 to January 2020, 29 consecutive patients (1.3% of the total number) in whom the small bowel could not be observed due to CE stagnation in the stomach at the time of the initial CE underwent the endoscopic delivery method using a retrieval net for secondary small-bowel CE. This study included 16 male (55%) and 13 female (45%) patients with a mean age of 69.2 ± 13.2 years . 11 patients (38%) had a history of gastrointestinal surgical resection. The entire small bowel could be observed in 19 patients (66%), and CE reached the terminal ileum in the remaining patients. A history of gastrointestinal surgical resection was significantly more frequent in the group where the entire small bowel could not be observed. The rate of small-bowel lesion detection was 55% (16/29). There were no adverse events associated with our endoscopic delivery method. Thus, the endoscopic delivery method using a retrieval net for patients with initial CE stagnation in the stomach may be safe and useful for the detection of small-bowel lesions.

p53 Immunohistochemistry Patterns Are Surrogate Biomarkers for TP53 Mutations in Gastrointestinal Neuroendocrine Neoplasms

Aims. The aim of this study was to establish p53 immunohistochemistry (IHC) patterns to predict TP53 mutations in gastrointestinal neuroendocrine neoplasms (GI-NENs) and to determine whether p53 IHC patterns could be used for the differential diagnosis of neuroendocrine neoplasms. Methods. TP53 gene sequencing and p53 IHC were performed on formalin-fixed paraffin-embedded (FFPE) tissue samples from 92 patients diagnosed with GI-NENs from five medical centers. Results. The cohort included 35 well-differentiated neuroendocrine tumors and 57 poorly differentiated neuroendocrine carcinomas. Gene sequencing revealed 38 wild-type TP53 and 54 TP53 mutations. p53 expression was interpreted as follows: pattern A, p53 was absent from all tumor cells; pattern B, scattered and weak p53 expression in 1-20% of tumor cells; and pattern C was subclassified as pattern C1: variable p53 staining intensity in 21-60% of tumor cells and tumor cell nests with focal strong positive p53 staining and pattern C2: strong p53 staining in more than 60% of tumor cells. p53 IHC patterns were evaluated as a binary classifier where pattern B predicted wild-type TP53, and patterns A and C predicted TP53 mutations. The sensitivity, specificity, and overall accuracy of this binary classification to predict TP53 status were 0.963, 0.868, and 0.924, respectively. p53 IHC patterns were also correlated with TP53 mutation types. Most cases with pattern A harboured loss-of-function (LOF) mutations, whereas patterns B and C tended to indicate wild-type TP53 and gain-of-function (GOF) mutations, respectively. Furthermore, most of the well-differentiated NETs showed pattern B, whereas pattern C2 was more common in poorly differentiated NECs. Finally, staining interpretation between different observers also yielded high reproducibility. Conclusions. p53 IHC patterns may be used as predictors of TP53 gene mutations and therefore could be potential surrogate markers for TP53 mutations in GI-NENs and could distinguish between well-differentiated NETs and poorly differentiated NECs.

Prognostic Value of TRPM7 Expression and Factor XIIIa-Expressing Tumor-Associated Macrophages in Gastric Cancer

Purpose. TRPM7 is known to play a key role in tumor progression by regulating cellular proliferation, migration, and invasion in various cancer cell lines. However, there are no comprehensive clinical studies about the effect of TRPM7 expression on gastric cancer (GC) prognosis. In this study, it was aimed at investigating the effect of TRPM7 expression on prognosis in GC patients. Additionally, for the first time, it was investigated whether the density of Factor XIIIa-expressing tumor-associated macrophages (TAMs) in GC has an effect on the biological behaviour of the tumor. Methods. TRPM7 expression and Factor XIIIa-expressing TAM density were immunohistochemically evaluated in paraffin-embedded tumor tissues of 204 GC patients undergoing surgery at a single institution. Results. Tumor size was clearly higher in cases with high TRPM7 expression than those with low expression ( p < 0.001 , Mann-Whitney U ). TRPM7 overexpression was closely related to high depth of tumor invasion ( p < 0.001 , ANOVA), increased lymph node metastasis ( p < 0.001 , ANOVA), and high distant metastasis rate ( p < 0.001 , Mann-Whitney U ). These findings exposed that high TRPM7 expression is effective in the progression and aggressiveness of GC. In addition, while high CD8+ TIL density affects the prognosis positively, it was determined that high Factor XIIIa+ TAM density negatively affects the prognosis of patients with GC. Furthermore, multivariate analyses revealed TRPM7 overexpression was independently related with short overall (HR 9.64, 95% CI 5.74–16.19, p < 0.001 ) and disease-free survival (HR 5.67, 95% CI 3.61-8.92, p < 0.001 ) in GC patients. Conclusions. Our data suggest that high TRPM7 expression is closely related to progressive tumor behaviour in GC and independently negatively affects survival in patients. In addition, it was determined that a high density of Factor XIIIa+ TAMs negatively affects the prognosis of patients with GC.

The Clinicopathological Characteristics and Prognoses of dMMR Gastric Adenocarcinoma Patients

Background. Few studies on the clinicopathological features and prognosis of DNA mismatch repair deficiency (dMMR) gastric cancer (GC) have been reported, and no clear conclusions have been drawn about the factors affecting the prognosis of dMMR GC. The aim of this study was to explore the clinicopathological characteristics and prognoses of dMMR GC patients. Methods. From May 2011 to November 2020, GC patients who underwent surgery with dMMR confirmed by immunohistochemistry (IHC) at the Affiliated Cancer Hospital of Shanxi Medical University were selected. The patients’ clinical and pathological data were collected. The recurrence-free survival (RFS) and overall survival (OS) rates of the patients were determined through follow-up. SPSS 26.0 was used to analyze the patients’ clinicopathological features and prognoses. Results. A total of 162 dMMR GC patients met the inclusion criteria, and the median age was 63.5 years (32–89 years). dMMR GC was more common in males (65% vs. 35%), and most of the cases were stage II (the prevalence of stage I was 22%, that of stage II was 43%, that of stage III was 30%, and that of stage IV was 5%). Most of the lesions were located in the antrum (49%), followed by the cardia (25%). PMS2 and MLH1 (57%) deficiency was most common. Kaplan–Meier analysis showed that factors related to OS were family history ( P = 0.048 ), number of lymph node (LN) metastases ( P < 0.001 ), vascular tumor thrombus ( P < 0.001 ), HER2 expression status ( P = 0.025 ), and clinical stage ( P < 0.001 ). The factors related to RFS included vascular tumor thrombus ( P < 0.001 ), number of LN metastases ( P < 0.001 ), and clinical stage ( P < 0.001 ). Conclusion. In this study, dMMR GC was more common in men, and the median age was 63.5 years. Most of the lesions were in the antrum and showed the combined deletion of MLH1 and PMS2. dMMR GC patients tended to be early stage, and the prognosis of those with early-stage GC was better. dMMR GC patients with vascular tumor thrombus or >6 LN metastases had a high recurrence rate and poor survival outcome.