Comparison of interventions for Barrett's esophagus: A network meta-analysis.

BACKGROUND AND OBJECTIVE: Barrett's esophagus (BE) is a precancerous condition that has the potential to develop into esophageal cancer (EC). Currently, there is a wide range of management options available for individuals at different pathological stages in Barrett's esophagus (BE). However, there is currently a lack of knowledge regarding their comparative efficacy. To address this gap, we conducted a network meta-analysis of published randomized controlled trials to examine the comparative effectiveness of all regimens. METHODS: Data extracted from eligible randomized controlled trials were utilized in a Bayesian network meta-analysis to examine the relative effectiveness of BE's treatment regimens and determine their ranking in terms of efficacy. The ranking probability for each regimen was assessed using the surfaces under cumulative ranking values. The outcomes under investigation were complete ablation of BE, neoplastic progression of BE, and complete eradication of dysplasia. RESULTS: We identified twenty-three RCT studies with a total of 1675 participants, and ten different interventions. Regarding complete ablation of non-dysplastic BE, the comparative effectiveness ranking indicated that argon plasma coagulation (APC) was the most effective regimen, with the highest SUCRA value, while surveillance and PPI/H2RA were found to be the least efficacious regimens. For complete ablation of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, photodynamic therapy (PDT) had the highest SUCRA value of 94.1%, indicating it as the best regimen. Additionally, for complete eradication of dysplasia, SUCRA plots showed a trend in ranking PDT as the highest with a SUCRA value of 91.2%. Finally, for neoplastic progression, radiofrequency ablation (RFA) and surgery were found to perform significantly better than surveillance. The risk of bias assessment revealed that 6 studies had an overall high risk of bias. However, meta-regression with risk of bias as a covariate did not indicate any influence on the model. In terms of the Confidence in Network Meta-Analysis evaluation, a high level of confidence was found for all treatment comparisons. CONCLUSION: Endoscopic surveillance alone or PPI/H2RA alone may not be sufficient for managing BE, even in cases of non-dysplastic BE. However, APC has shown excellent efficacy in treating non-dysplastic BE. For cases of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, PDT may be the optimal intervention as it can induce regression of BE metaplasia and prevent future progression of BE to dysplasia and EC.

Helicobacter pylori and Gastrointestinal Cancers: Recent Advances and Controversies.

Helicobacter pylori (H pylori), a gastric bacterium, has been extensively studied for its association with gastritis, peptic ulcers, and gastric cancer. However, recent evidence suggests its potential implications beyond the stomach, linking it to other gastrointestinal malignancies, such as esophageal cancer, liver cancer, pancreatic cancer, gallbladder cancer, and colorectal cancer. In light of the expanding research landscape and the increasing interest in exploring H pylori broader role in gastrointestinal tumorigenesis, this comprehensive review aims to elucidate the relationship between H pylori and gastrointestinal tumors. This review encompasses recent epidemiological studies, research progress, and emerging perspectives, providing a comprehensive assessment of the relationship between H pylori and gastrointestinal tumors. The findings highlight the captivating world of H pylori and its intricate involvement in gastrointestinal malignancies.

CAPG is a novel biomarker for early gastric cancer and is involved in the Wnt/ß-catenin signaling pathway.

Past studies have shown that the Gelsolin-like actin-capping protein (CAPG) regulates cell migration and proliferation and is strongly associated with tumor progression. We present the first study of the mechanism of action of CAPG in early gastric cancer (EGC). We demonstrate that CAPG expression is upregulated in gastric cancer (GC) especially EGC. CAPG promotes GC proliferation, migration, invasion, and metastasis in vivo and in vitro. More importantly, CAPG plays a role in GC by involving the Wnt/ß-catenin signaling pathway. Our findings suggest that CAPG may function as a novel biomarker for EGC.

Nomogram based on clinical characteristics for predicting overall survival in gastric cancer patients with preoperative anemia.

BACKGROUND: Preoperative anemia is associated with increased postoperative morbidity and mortality and increased perioperative transfusion risk. For surgical patients, this affects physical and cognitive ability and quality of life, but it is an important and modifiable risk factor. AIM: To determine the effect of preoperative anemia on the prognosis of gastric cancer (GC) patients and generate a prognostic nomogram to predict the postoperative overall survival (OS) of GC patients with preoperative anemia. METHODS: Clinicopathological and follow-up data of GC patients treated at Zhejiang Provincial People's Hospital (China) from 2010 to 2015 were collected. Independent prognostic factors were screened by univariate and multivariate Cox regression analyses. Then, these factors were used to construct a nomogram to predict 1-, 3-, and 5-year postoperative OS in preoperative anemic GC patients. The nomogram was assessed by calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). RESULTS: Nine hundred and sixty GC patients were divided into two groups (preoperatively anemic and nonanemic), and postoperative survival analysis was performed on both groups, yielding a shorter postoperative survival for preoperatively anemic patients than for nonanemic patients. A total of 347 GC patients with preoperative anemia were included. Age, preoperative alpha-fetoprotein level, monocyte count, lymphocyte count, clinicopathological stage, liver metastasis, and GC type were identified as independent prognostic factors for OS. The area under the ROC curve (AUC) of the nomogram for predicting 1-, 3-, and 5-year OS was 0.831, 0.845, and 0.840, respectively, for the training cohort, and the corresponding AUC values in the validation cohort were 0.827, 0.829, and 0.812, respectively. Calibration curves and DCA indicated good performance of the nomogram. CONCLUSION: In all, we have successfully produced and verified a useful nomogram for predicting OS in GC patients with preoperative anemia. This nomogram based on a variety of clinicopathological indices can provide an effective prognostic assessment and help clinicians choose an appropriate treatment strategy for GC patients with preoperative anemia.

Immunotherapy in combination with chemotherapy for Peutz-Jeghers syndrome with advanced cervical cancer: A case report.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder, and female patients may develop gynecologic tumours. The prognosis for such patients is poor and the specific pathogenesis remains uncertain. Therefore, there are currently no uniform treatment options. CASE SUMMARY: Herein, we introduce the case of a 45-year-old female who was diagnosed with PJS for 45 years and cervical cancer for 3 years. Postoperative pathological examination showed metastases in the right external iliac lymph nodes. The patient was initially treated with a combination of doxorubicin and carboplatin chemotherapy and pelvic magnetic resonance showed that the metastases had grown. Subsequently, we performed whole exome sequencing in this patient and identified the relevant causative gene. In addition to the chemotherapy regimen, sindilizumab was administered and the patient was followed up. After 4 cycles of treatment, the metastases were substantially reduced and were not enlarged after six months of follow-up. This case report suggests that patients with PJS combined with cervical cancer may have a sustained response to immune-combination chemotherapy regimens. CONCLUSION: Clinicians should be aware of the importance of immunotherapy in patients with PJS combined with advanced cervical cancer.

Helicobacter pylori Infection as a Predictor of Treatment Outcomes of Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Helicobacter pylori infection is strongly associated with gastric cancer. However, there is currently no consensus on the association between H. pylori and gastric cancer prognosis. METHODS: A systematic search was conducted on studies in PubMed, EMBASE, and Web of Science up to March 10, 2022. The quality of all included studies was assessed using the Newcastle-Ottawa Scale. The hazard ratio (HR) and its 95% confidence interval (95% CI) were extracted to analyze the association between H. pylori infection and prognosis of gastric cancer. In addition, subgroup analysis and publication bias were performed. RESULTS: A total of 21 studies were involved. The pooled HR was 0.67 (95% CI, 0.56-0.79) for overall survival (OS) in H. pylori-positive patients, with the control (HR = 1) being the H. pylori-negative group. In the subgroup analysis, the pooled HR was 0.38 (95% CI, 0.24-0.59) for OS in H. pylori-positive patients who received surgery combined with chemotherapy. The pooled HR for disease-free survival was 0.74 (95% CI, 0.63-0.8) and 0.41 (95% CI, 0.26-0.65) in patients who received surgery combined with chemotherapy. CONCLUSION: H. pylori-positive gastric cancer patients have a better overall prognosis than H. pylori-negative patients. H. pylori infection has improved the prognosis of patients undergoing surgery or chemotherapy, among which the improvement was most obvious in patients undergoing surgery combined with chemotherapy.

Hsa_circ_0072309 is a prognostic biomarker and is correlated with immune infiltration in gastric cancer.

Background: Hsa_circ_0072309 has been identified as a tumor suppressor in several carcinomas. However, its precise role in gastric cancer (GC) remains largely unknown. This study was aimed to explore the precise role of Hsa_circ_0072309 in GC. Methods: The transcriptional and clinical data of stomach adenocarcinoma were downloaded using the University of California SantaCruz (UCSC) Xena browser. The circular RNA (circRNA) datasets were obtained from the Gene Expression Omnibus (GEO) database. The expression profile and survival analysis of differentially expressed micro RNAs (DEMIs) and differentially expressed messenger RNAs (DEMs) were performed. Correlations between the expression and immune infiltration of the DEMS were studied. Additionally, the expression of hsa_circ_0072309 in GC tissues and cell lines were validated, and the relationship between its expression and clinical features was investigated. Gain- and loss-of function experiments and molecular interaction experiments were also conducted. Results: Overall, 7 differentially expressed circRNAs, 13 DEMIs, and 17 DEMs were screened. Two DEMIs (hsa_miR-34a-3p and hsa_miR-326) and five DEMs (C7, MARCKSL1, UBE2T, OLR1, and HOXC11) showed significant differences in the high- and low-risk groups. The most significantly enriched Gene Ontology terms were the circadian regulation of gene expression and protein binding. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were the PI3K-Akt and Ras signal pathways. Additionally, six genes were significantly correlated with immune infiltration. The real-time quantitative PCR (RT-qPCR) results revealed a significant downregulation of hsa_circ_0072309 in GC tissues related to tumor size, vascular invasion, and lymph node metastasis. A hsa_circ_0072309 overexpression suppressed whereas a hsa_circ_0072309 knockdown promoted GC cells proliferation and migration in vitro; in addition, hsa_circ_0072309 could directly bind to has-miR-34a-3p and has-miR-330-5p. Conclusions: Hsa_circ_0072309 is a potential diagnostic biomarker for GC, and complement component 7 may be a tumor suppressor. These may potentially predict the prognosis of patients with GC and may become new therapeutic targets.

Intestinal natural killer/T-cell lymphoma presenting as a pancreatic head space-occupying lesion: A case report.

BACKGROUND: Intestinal natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive non-Hodgkin's lymphoma, and its occurrence is closely related to Epstein-Barr virus infection. In addition, the clinical symptoms of NKTCL are not obvious, and the specific pathogenesis is still uncertain. While NKTCL may occur in any segment of the intestinal tract, its distinct location in the periampullary region, which leads clinicians to consider mimics of a pancreatic head mass, should also be addressed. Therefore, there remain huge challenges in the diagnosis and treatment of intestinal NKTCL. CASE SUMMARY: In this case, we introduce a male who presented to the clinic with edema of both lower limbs, accompanied by diarrhea, and abdominal pain. Endoscopic ultrasound (EUS) showed well-defined homogeneous hypoechoic lesions with abundant blood flow signals and compression signs in the head of the pancreas. Under the guidance of EUS- fine needle biopsy (FNB) with 19 gauge or 22 gauge needles, combined with multicolor flow cytometry immunophenotyping (MFCI) helped us diagnose NKTCL. During treatments, the patient was prescribed the steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide chemotherapy regimen. Unfortunately, he died of leukopenia and severe septic shock in a local hospital. CONCLUSION: Clinicians should enhance their understanding of NKTCL. Some key factors, including EUS characteristics, the right choice of FNB needle, and combination with MFCI, are crucial for improving the diagnostic rate and reducing the misdiagnosis rate.

Spontaneous expulsion of a duodenal lipoma after endoscopic biopsy: A case report.

BACKGROUND: Gastrointestinal (GI) lipomas are benign submucosal tumors of mature adipocytes that arise mainly in the colon and stomach, sometimes in the ileum and jejunum, and rarely in the duodenum. Patients with symptomatic lipomas require endoscopic or surgical treatment. Spontaneous expulsion of lipomas after biopsy is a rare condition that has limited case reports. CASE SUMMARY: A 56-year-old man presented to our hospital with intermittent postprandial epigastric fullness. Esophagogastroduodenoscopy (EGD) revealed a 10-mm soft yellowish submucosal lesion with the "pillow sign," located in the second portion of duodenum. Endoscopic ultrasonography (EUS) using a 12-MHz catheter probe showed a hyperechoic, homogenous, and round solid lesion (OLYMPUS EUS EU-ME2, UM-DP12-25R, 12-MHz radial miniprobe, Olympus Corporation, Tokyo, Japan). Deep biopsy was performed using the bite-on-bite technique with forceps. Histological examination was compatible with submucosal lipoma. The lesion spontaneously expelled 12 d after the biopsy. Follow-up EUS performed after 2 mo confirmed this condition. CONCLUSION: Deep biopsy could lead to spontaneous GI lipoma expulsion. This might be the first step in lipoma diagnosis and treatment.

Proposal of minimum elements for screening and diagnosis of gastric cancer by an international Delphi consensus.

The World Endoscopy Organization Stomach and Duodenal Diseases Committee extracted minimum elements for screening and diagnosis of gastric cancer (GC) in aim to support countries that do not have national guidelines on screening and diagnosis of GC. Current national or international guidelines were collected worldwide and recommendations were classified according to the quality of evidence and were finalized through a modified Delphi method. The minimum elements consist of seven categories: [1] Extraction of high-risk patients of GC before esophagogastroduodenoscopy (EGD), [2] Patients who need surveillance of GC, [3] Method to ensure quality of EGD for detection of GC, [4] Individual GC risk assessment by EGD, [5] Extraction of high-risk patients of GC after EGD [6] Qualitative or differential diagnosis of GC by EGD, and [7] Endoscopic assessment to choose the therapeutic strategy for GC. These minimum elements will be a guide to promote the elimination of GC among countries with a high incidence of GC who lack national guidelines or screening programs.

Endoscopic Therapy of Small Bowel Polyps by Single-Balloon Enteroscopy in Patients with Peutz-Jeghers Syndrome.

Background: Little is known about the efficacy and safety of single-balloon enteroscopy (SBE) in patients with Peutz-Jeghers syndrome (PJS). The aim of this study was to assess the efficacy and safety of SBE for the treatment of small bowel polyps in patients with PJS. Methods: We conducted a single-center observational study, which included all patients diagnosed with PJS who underwent SBE for polypectomy between January 2018 and March 2021. Complete treatment was defined as the absence of polyps ≥10 mm after SBE resection. The clinical records were retrospectively reviewed. Results: 102 patients (including 40 men and 62 women) with a mean age of 28.7 years (range 13-55 y) were enrolled in our study. The intubation depth via the oral approach of patients with a history of laparotomy was significantly shorter than that of the patients without a history of laparotomy ([241.6 ± 64.2] cm vs [280.9 ± 40.2] cm, P=0.008). The maximum size of the resected polyps via anus during the second hospitalization was significantly smaller than that during the first hospitalization ([2.25 ± 1.29] cm vs [4.26 ± 3.51] cm, P=0.032). For patients with total enteroscopy, the complete treatment rate was 98% (49/50). For patients without total enteroscopy, all polyps larger than 10 mm in the examined segment of small bowel were resected successfully. Complications occurred in 10 of 129 hospitalizations (delayed bleeding in 4, perforation in 3, and acute pancreatitis in 3). Conclusions: SBE is effective and safe for resection of small bowel polyps in patients with PJS.

Gastrodin From Gastrodia elata Enhances Cognitive Function and Neuroprotection of AD Mice via the Regulation of Gut Microbiota Composition and Inhibition of Neuron Inflammation.

Gastrodin (Gas) is known to exhibit neuroprotective effects in Alzheimer's disease (AD). However, the detailed mechanism of action is still unclear. In the present study, we focused on the microbiome-gut-brain axis to investigate the mechanism of action of Gas using a D-galactose (Dgal)-induced AD model. Gas reversed the memory dysfunction of Dgal-administered mice. Neurons in the cerebral cortex and hippocampus were reduced in the Dgal-administered group, and the decrease of neurons was suppressed in 90 and 210 mg/kg Gas treatment groups. 16S rRNA sequence analysis was carried out to explore the composition of gut microbiota in fecal samples of mice. Gas treatment had a positive correlation with Firmicutes and had a negative correlation with Cyanobacteria, Proteobacteria, and Deferribaceters. Importantly, the LPS and proinflammatory cytokines in the brain increased in Dgal-administered mice, but these parameters recovered to normal levels after oral administration of Gas. To determine whether the microbiota-gut-brain axis is involved in the neuroprotective effect of Gas, the mice were given antibiotic cocktail before and during the trial period to decrease the gut microbiota of mice. The antibiotic cocktail partially eliminated the neuroprotective effect of Gas by changing the gut microbiome composition. These results indicated that Gas improves the memory of the AD mouse model via partly targeting the microbiota-gut-brain axis and mitigating neuron inflammation.

Synergistic effects of ISL1 and KDM6B on non-alcoholic fatty liver disease through the regulation of SNAI1.

BACKGROUND: The increasing incidence of non-alcoholic fatty liver disease (NAFLD) has been reported worldwide, which urges understanding of its pathogenesis and development of more effective therapeutical methods for this chronic disease. In this study, we aimed to investigate the effects of a LIM homeodomain transcription factor, islet1 (ISL1) on NAFLD. METHODS: Male C57BL/6J mice were fed with a diet high in fat content to produce NAFLD models. These models were then treated with overexpressed ISL1 (oe-ISL1), oe-Lysine-specific demethylase 6B (KDM6B), oe-SNAI1, or short hairpin RNA against SNAI1. We assessed triglyceride and cholesterol contents in the plasma and liver tissues and determined the expressions of ISL1, KDM6B and SNAI1 in liver tissues. Moreover, the in vitro model of lipid accumulation was constructed using fatty acids to explore the in vitro effect of ISL1/KDM6B/SNAI1 in NAFLD. RESULTS: The results showed that the expressions of ISL1, KDM6B, and SNAI1 where decreased, but contents of triglyceride and cholesterol increased in mice exposed to high-fat diet. ISL1 inhibited lipogenesis and promoted lipolysis and exhibited a synergizing effect with KDM6B to upregulate the expression of SNAI1. Moreover, both KDM6B and SNAI1 could inhibit lipogenesis and induce lipolysis. Importantly, the therapeutic effects of ISL1 on in vitro model of lipid accumulations was also confirmed through the modulation of KDM6B and SNAI1. CONCLUSIONS: Taken together, these findings highlighted that ISL1 effectively ameliorated NAFLD by inducing the expressions of KDM6B and SNAI1, which might be a promising drug for the treatment of NAFLD.

A computer-aided diagnosis system using white-light endoscopy for the prediction of conventional adenoma with high grade dysplasia.

OBJECTIVES: We developed a computer-aided diagnosis system called ECRCCAD using standard white-light endoscopy (WLE) for predicting conventional adenomas with high-grade dysplasia (HGD) to optimise the patients' management decisions during colonoscopy. METHODS: Pretraining model was used to fine-tune the model parameters by transfer learning. 2,397 images of HGD and 2,487 low-grade dysplasia (LGD) images were randomly assigned (8:1:1) to the training, optimising, and internal validation dataset. The prospective validation dataset is the frames accessed from colonoscope videoes. One independent rural hospital provided an external validation dataset. Histopathological diagnosis was used as the standard criterion. The capability of the ECRCCAD to distinguish HGD was assessed and compared with two expert endoscopists. RESULTS: The accuracy, sensitivity and specificity for diagnosis of HGD in the internal validation set were 90.5%, 93.2%, 87.9%, respectively. While 88.2%, 85.4%, 89.8%, respectively, for the external validation set. For the prospective validation set, ECRCCAD achieved an AUC of 93.5% in diagnosing HGD. The performance of ECRCCAD in diagnosing HGD was better than that of the expert endoscopist in the external validation set (88.2% vs. 71.5%, P < 0.0001). CONCLUSION: ECRCCAD had good diagnostic capability for HGD and enabled a more convenient and accurate diagnosis using WLE.

Identification of three immune subtypes characterized by distinct tumor immune microenvironment and therapeutic response in stomach adenocarcinoma.

BACKGROUND: In primary stomach adenocarcinoma (STAD), the tumor immune microenvironment (TIME) is important for cancer occurrence and progression; however, its clinical significance remains unclear. This study investigated the association between patient survival, TIME, and therapeutic response to STAD. METHODS: Gene expression profiles of STAD cases were collected from the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus. Molecular subtypes were explored with consistent clustering methods according to 119 immune signatures and the infiltrating scores of 22 immune cells using the Multi-Omics Immuno-Oncology Biological Research algorithm. We determined IFNγ scores and immune cytolytic activity (CYT) scores on the basis of corresponding gene signatures via single-sample Gene Set Enrichment Analysis. Comparisons of survival, TIME, 10 immunity-related oncogenic pathways, immune checkpoint expression, and therapeutic response were conducted among the three subtypes. We further applied linear discriminant analysis to construct a characteristic index to classify the subtypes, and the Pearson correlation coefficient for the relationship between the index and immune checkpoint genes. Weighted Correlation Network Analysis (WGCNA) was used to mine the associated modules and specific genes. RESULTS: We collected gene expression profiles from 352 STAD cases in the TCGA database, 300 in GSE62254, and 344 in GSE84437. Three STAD subtypes (IS1-IS3) were established according to the TIME signatures. The IS3 subtype had the highest immune score and the best prognosis, as well as markedly increased immune T-cell CYT, Th1/IFNγ scores, and immune checkpoint gene expression, compared to the other two subtypes. It was highly similar to the PD-1 response group in the previous study samples of GSE91061. The established TIME classification index performed well in classifying subtypes and was directly proportional to immune checkpoint-related gene expression levels. WGCNA explored 6 modules and 14 genes, namely DYSF, MAN1C1, HTRA3, EMCN, RFLNB, KANK3, MAGEH1, CD93, PCAT19, FUT11, BMP1, FOSB, DCHS1, and TCF3, which were associated with the established TIME classification index and STAD patient prognosis. CONCLUSION: TIME phenotypes of STAD patients could be divided into three different molecular subtypes, which displayed different prognoses, immune features, and therapeutic responses. Our results shed new light on predicting patient outcomes and the discovery of new anti-STAD therapeutic strategies according to the TIME.

Comparison of the Effectiveness and Safety of Different Methods of Colorectal Endoscopic Submucosal Dissection: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Traditional endoscopic submucosal dissection (ESD) has developed different methods, such as pocket method (P-ESD), traction-assisted method (T-ESD), and hybrid method (H-ESD). In this meta-analysis, the benefits and drawbacks of different ESD methods were discussed and ranked. STUDY DESIGN: Studies comparing different methods of colorectal ESD were searched by using PubMed, EMBASE, and Cochrane Library databases. The study was conducted for five endpoints: en bloc resection rate, R0 resection rate, operation time, dissection speed, and adverse events rate. Pairwise and network meta-analyses were performed through Rev Man 5.4 and Stata 16.0. The quality of all included studies was assessed using the Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale. RESULTS: Twenty-six studies met the inclusion criteria, including 7 RCTs and 19 non-RCTs, with a total of 3,002 patients. The pooled analysis showed that the en bloc resection rate of H-ESD was significantly lower than that of C-ESD, P-ESD, and T-ESD (RR = 0.28, 95% CI [0.12, 0.65]; RR = 0.11, 95% CI [0.03, 0.44]; RR = 8.28, 95% CI [2.50, 27.42]). Compared with C-ESD, the operation time of H-ESD and T-ESD was significantly shorter (MD = -21.83, 95% CI [-34.76, -8.90]; MD = -23.8, 95% CI [-32.55, -15.06]). Meanwhile, the operation time of T-ESD was also significantly shorter than that of P-ESD (MD = -18.74, 95% CI [-31.93, -5.54]). The dissection speed of T-ESD was significantly faster than that of C-ESD (MD = 6.26, 95% CI [2.29, 10.23]). CONCLUSION: P-ESD and T-ESD are probably the two best methods of colorectal ESD at present. The advantages of P-ESD are high en bloc resection rate and low incidence of adverse events. The advantages of T-ESD are rapid dissection and short operation time.

Clinical Impact of X-Ray Repair Cross-Complementary 1 (XRCC1) and the Immune Environment in Colorectal Adenoma-Carcinoma Pathway Progression.

PURPOSE: Colorectal cancer (CRC) can develop via a hypermutagenic pathway characterized by frequent somatic DNA base-pair mutations. Alternatively, the immunogenicity of tumor cells themselves may influence the anticancer activity of the immune effector cells. Impaired DNA repair mechanisms drive mutagenicity, which then increase the neoantigen load and immunogenicity. However, no studies have analyzed immune checkpoint protein expression, particularly programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), in adenoma-carcinoma progression and its relationship with the emergence of other DNA repair gene mutation. MATERIALS AND METHODS: We investigated mutations of 10 genes involved in DNA repair function: XRCC1, TP53, MLH1, MSH, KRAS, GSTP, UMP, MTHF, DPYD, and ABCC2. We performed sequencing to determine mutations and immunohistochemistry of immune checkpoints in clinical samples and determined changes in XRCC1 expression during progression through the adenoma-carcinoma pathway. We further investigated the prognostic associations of gene XRCC1 according to the expression, mutational profile, and immune profile using The Cancer Genome Atlas-colon adenocarcinoma (TCGA-COAD) dataset. RESULTS: From clinical samples, XRCC1 mutation demonstrated the strongest association with adenomas with a mutation frequency of 56.2% in adenomas and 34% in CRCs (p =0.016). XRCC1 was abnormally expressed and altered by mutations contributing to adenoma carcinogenesis. High expression of XRCC1, CD4, FOXP3, and PD-1/PD-L1 showed an overall upward trend with increased lesion severity (all p < 0.01). PD-1/PD-L1 expression and CD4+ intraepithelial lymphocytes (IELs) correlated with cytological dysplasia progression, specifically in patients with wild-type XRCC1 (all p < 0.01), whereas FOXP3 expression was independently associated with adenoma-carcinoma progression. From TCGA-COAD analysis, XRCC1 expression was associated with patients survival, tumor-infiltrating lymphocytes and immune marker expression. CONCLUSION: Increased IEL density and PD-1/PD-L1 expression correlate with cytological dysplasia progression and specifically with the XRCC1 mutation status in CRC. Our findings support a stepwise dysplasia-carcinoma sequence of adenoma carcinogenesis and an XRCC1 hypermutated phenotypic mechanism of lesions.

Prediction of severity and outcomes of colon ischaemia using a novel prognostic model: a clinical multicenter study.

OBJECTIVE: To identify risk factors of disease severity and between mild and severe colon ischaemia (CI) patients and to improve clinical outcomes, this study aimed to explore a novel scoring model. METHODS: Retrospective analyses of hospital records between January 2009 and December 2019 were included. Clinical manifestations, mortality, Oakland score, laboratory tests, colonoscopy, and histopathology were collected. Risk factors of severe CI were determined by univariate and multivariate logistic regression and used for the predicting model. RESULTS: A total of 203 patients with CI were included. Serum C-reactive protein (CRP) and albumin ratio (CAR) were much higher in the severe CI group compared with that of the mild CI group (3.33 ± 1.78 versus 0.68 ± 0.97, p < .001). The Oakland score was much higher in the severe CI group (12.00 ± 3.02 versus 8.77 ± 1.63, p < .001). The histopathological finding of fibrin thrombi was an independent risk factor that predicted poor outcomes (20.00% versus. 1.09%, p < .001). Patients present with CAR ≥3.33, Oakland score ≥12, and histopathological fibrin thrombi were independent risk factors. In addition, the final scoring model was 0.042 × Oakland score + 1.040 × CAR + 3.412 × fibrin thrombi, the area under the curve (AUC) was 0.960 (95% confidence interval:0.930-0.990), and the sensitivity and specificity of the novel scoring model were 95% and 92%, respectively. CONCLUSIONS: The novel prognostic model was established to predict CI severity and clinical outcomes efficiently.Key messagesIn this article, we discuss the scoring model for clinical outcomes of colon ischaemia patients.In our study, the sensitivity and specificity of a novel scoring model are very high.Thus, laboratory tests (CRP albumin ratio), Oakland score, and histopathological findings (fibrin thrombi) can be assessed efficiently for colon ischaemia outcomes.

Circular RNA circCOL6A3_030 is involved in the metastasis of gastric cancer by encoding polypeptide.

Gastric cancer (GC) is a serious digestive tract disease that threatens human life worldwide, and the prognosis of gastric cancer accompanied by distant lymph node or the distant metastasis organs is worse. The purpose of this study was to investigate the role of circular RNA COL6A3_030 (circBase ID: hsa_circ_0006401; circRNADb ID: hsa_circ_28198; circBank ID: hsa_circCOL6A3_030) in GC metastasis. qRT-PCR analysis using back-splicing primers and Sanger sequencing of PCR products were performed to identify circCOL6A3_030 in GC tissues and cell lines; RNA-FISH assay was performed to validate the subcellular localization of circCOL6A3_030. Transwell and wound-healing assays were carried out to evaluate the migration ability of GC cells. Western blot was conducted to detect the polypeptide encoded by circCOL6A3_030 in cells. circCOL6A3_030 was down-regulated in GC tissues and cell lines, while circCOL6A3_030 was up-regulated in GC with distant lymph node metastasis. The migration of circCOL6A3_030 silenced GC cells was significantly inhibited in both SGC-7901 and BGC-823 cell lines. Importantly, in vivo assay, silencing circCOL6A3_030 could reduce liver metastases from gastric cancer cells. Meanwhile, further studies suggested that circCOL6A3_030 encoded a small peptide that had a function as a tumor-promoting metastasis factor and immunohistochemistry confirmed the presence of this polypeptide. To sum up, our study showed that circCOL6A3_030 promoted GC cell migration by encoding a small peptide called circCOL6A3_030_198aa. Therefore, our results highlight the potential role of circCOL6A3_030 for clinical diagnosis and treatment of GC with distant lymph node metastasis.