Malignant glomus tumor of the intestinal ileum with multiorgan metastases:A case report and review of literature

BACKGROUND Glomus tumors(GTs)are rare mesenchymal neoplastic lesions derived from cells of the glomus body.GTs rarely occurs in the visceral organs,where there may be few or no glomus bodies,and the majority of GTs are benign,rarely demonstrating aggressive or malignant behavior and histological features.CASE SUMMARY We report a patient with malignant GTs of the intestinal ileum with multiorgan metastases who was admitted due to moderate anemia.Capsule endoscopy revealed a bleeding mass in the intestinal ileum,and the patient underwent segmental ileal resection through laparoscopic surgery.The histopathological and immunohistochemical diagnoses were consistent with malignant GT.Longterm follow-up showed that the GT had metastasized to multiple organs such as the colon,brain,and possibly the lung.CONCLUSION This case was characterized by the highest degree of malignancy and by multiorgan metastases,and it was the first case of intestinal GT uncovered by capsule endoscopy.

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

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

Development and validation of an online calculator to predict the pathological nature of colorectal tumors

BACKGROUND No single endoscopic feature can reliably predict the pathological nature of colorectal tumors(CRTs).AIM To establish and validate a simple online calculator to predict the pathological nature of CRTs based on white-light endoscopy.METHODS This was a single-center study.During the identification stage,530 consecutive patients with CRTs were enrolled from January 2015 to December 2021 as the derivation group.Logistic regression analysis was performed.A novel online calculator to predict the pathological nature of CRTs based on white-light images was established and verified internally.During the validation stage,two series of 110 images obtained using white-light endoscopy were distributed to 10 endoscopists[five highly experienced endoscopists and five less experienced endoscopists(LEEs)]for external validation before and after systematic training.RESULTS A total of 750 patients were included,with an average age of 63.6±10.4 years.Early colorectal cancer(ECRC)was detected in 351(46.8%)patients.Tumor size,left semicolon site,rectal site,acanthosis,depression and an uneven surface were independent risk factors for ECRC.The C-index of the ECRC calculator prediction model was 0.906(P=0.225,Hosmer-Lemeshow test).For the LEEs,significant improvement was made in the sensitivity,specificity and accuracy(57.6%vs 75.5%;72.3%vs 82.4%;64.2%vs 80.2%;P<0.05),respectively,after training with the ECRC online calculator prediction model.CONCLUSION A novel online calculator including tumor size,location,acanthosis,depression,and uneven surface can accurately predict the pathological nature of ECRC.

Prediction of lymph node metastasis in early esophageal cancer

BACKGROUND Given the poor prognosis of patients with lymph node metastasis,estimating the lymph node status in patients with early esophageal cancer is crucial.Indicators that could be used to predict lymph node metastasis in early esophageal cancer have been reported in many recent studies,but no recent studies have included a review of this subject.AIM To review indicators predicting lymph node metastasis in early esophageal squamous cell carcinoma(ESCC)and early esophageal adenocarcinoma(EAC).METHODS We searched PubMed with“[early esophageal cancer(Title/Abstract)]and[lymph node(Title/Abstract)]”or“[early esophageal carcinoma(Title/Abstract)]and[lymph node(Title/Abstract)]”or“[superficial esophageal cancer(Title/Abstract)]and[lymph node(Title/Abstract)].”A total of 29 studies were eligible for analysis.RESULTS Preoperative imaging(size),serum markers(microRNA-218),postoperative pathology and immunohistochemical analysis(depth of invasion,tumor size,differentiation grade,lymphovascular invasion,neural invasion,expression of PIM-1<30%)were predictive factors for lymph node metastasis in both early ESCC and EAC.Serum markers(thymidine kinase 1≥3.38 pmol/L;cytokeratin 19 fragment antigen 21-1>3.30 ng/mL;stathmin-1)and postoperative pathology and immunohistochemical analysis(overexpression of cortactin,mixed-lineage leukaemia 2,and stanniocalcin-1)were predictive for lymph node metastasis in early ESCC.Transcription of CD69,myeloid differentiation protein 88 and toll-like receptor 4 and low expression of olfactomedin 4 were predictive of lymph node metastasis in early EAC.A total of 6 comprehensive models for early ESCC,including logistic regression model,nomogram,and artificial neural network(ANN),were reviewed.The areas under the receiver operating characteristic curve of these models reached 0.789-0.938,and the ANN performed best.As all these models relied on postoperative pathology,further models focusing on serum markers,imaging and immunohistochemical indicators are still needed.CONCLUSION Various factors were predictive of lymph node metastasis in early esophageal cancer,and present comprehensive models predicting lymph node metastasis in early ESCC mainly relied on postoperative pathology.Further studies focusing on serum markers,imaging and immunohistochemical indicators are still in need.

Factors associated with gastric adenocarcinoma and dysplasia in patients with chronic gastritis:a population-based study

Objective： Gastric cancer （GC） is one of the leading causes of death in China and other Asian countries. Recently, gastric endoscopy has become the main approach for GC screening, but the identification of high-risk individuals remains a challenge in GC screening programs. Methods： There were 7,302 patients with chronic gastritis involved in this study. Endoscopic examinations were performed, and their demographic characteristics and lifestyle data were collected. Each possible associated factor of GC/premalignant and precursor lesions was evaluated by univariate and multivariate logistic regressions. Nomograms were used for visualization of those models, and receiver operating characteristic （ROC） curve analysis was used to present the predictive accuracy. Resu Its： We detected 8 （0.11% ） gastric adenocarcinomas, 17 （0.23 %） dysplasia cases, 14 （0.19%） hyperplasia cases, 52 （0.71%） intestinal metaplasia cases, 217 （2.97%） inflammatory lesions, 141 （1.93%） gastric ulcers, 10 （0.14%） atrophic gastritis cases, 1,365 （18.69%） erosive gastritis cases, and 5,957 （81.58%） superficial gastritis cases in 7,302 patients. The age （P〈0.001）, gender （P=0.086）, labor intensity （P=0.018） and leek food intake （P=0.143） were identified as independent predictive factors of GC/premalignant lesions possibility. The corresponding nomogram exhibited an area under the curve （AUC） [95% confidence interval （95% CI）] of 0.82 （0.74-0.89） for the modeling group and 0.80 （0.75-0.85） for the validation group. The age （P=0.002）, gender （P=0.024）, smoldng （P=0.002） and leek food intake （P=0.039） were independent predictive factors of precursor lesions possibility. The corresponding nomogram exhibited an AUC （95% CI） of 0.62 （0.60-0.65） for the modeling group and 0.61 （0.59-0.63） for the validation group. Conclusions： We identified several potential associated factors and provided a preclinical nomogram with the potential to predict the possibility of GC/premalignant and precursor lesions.

Non-alcoholic fatty liver degree and long-term risk of incident inflammatory bowel disease:A large-scale prospective cohort study

Background:Non-alcoholic fatty liver disease(NAFLD)and inflammatory bowel disease(IBD)have shown similar worsening epidemic patterns globally and shared various overlapping pathophysiological mechanisms.However,evidence on the relationship between NAFLD and IBD risk is lacking.We aimed to investigate the associations between long-term risk of incident IBD and NAFLD in a large prospective cohort.Methods:Participants from the United Kingdom Biobank cohort(https://biobank.ndph.ox.ac.uk/)who were free of IBD and alcoholic liver disease at baseline were enrolled.Baseline non-alcoholic fatty liver degree was measured by the well-established fatty liver index(FLI).The outcomes of interest included incident IBD,ulcerative colitis(UC),and Crohn’s disease(CD).Multivariable Cox proportional hazard regression was used to calculate hazard ratios(HRs)and 95%confidence intervals(CIs).Results:Among 418,721 participants(mean FLI:48.11±30.11),160,807(38.40%)participants were diagnosed as NAFLD at baseline.During a median of 12.4 years’follow-up,2346 incident IBD cases(1545 UC,653 CD,and 148 IBD-unclassified)were identified.Due to limited events,those IBD-unclassified were combined in UC or CD when examining the associated risk of UC or CD,separately.Compared with the lowest quartile of FLI,the highest quartile showed a separately 36.00%,25.00%,and 58.00%higher risk of incident IBD(HR_(Q4 vs.Q1)=1.36,95%CI:1.19-1.55,P_(trend)<0.001),UC(HR_(Q4 vs.Q1)=1.25,95%CI:1.07-1.46,P_(trend)=0.047),and CD(HR_(Q4 vs.Q1)=1.58,95%CI:1.26-1.97,P_(trend)<0.001)after multivariable adjustment.Compared with non-NAFLD,NAFLD participants had a significantly higher risk of incident IBD(HR=1.13,95%CI:1.04-1.24)and CD(HR=1.36,95%CI:1.17-1.58).Conclusions:Higher degree of non-alcoholic fatty liver is associated with increased risk of incident IBD.Interventions aimed at improving NAFLD may be a potential targeted strategy for the detection and treatment of IBD.

Comparative outcomes of endoscopic ultrasound-guided lumen-apposing mental stents drainage for pancreatic pseudocysts and walled-off necrosis:Case series and meta-analysis

Background:Endoscopic ultrasound(EUS)-guided transmural drainage for pancreatic fluid collections(PFCs)has become the first-line treatment with quicker recovery and more minor injury compared with surgery and percutaneous drainage.The efficacy of stents implantation and drainage for different PFCs remains controversial,especially lumen-apposing metal stents(LAMS).This study aimed to compare the efficacy and safety of LAMS drainage for pancreatic pseudocysts(PPC)and walled-off necrosis(WON).Methods:A meta-analysis was performed for LAMS drainage for WON and PPC by systematically searching PubMed,Cochrane,and Embase databases from January 2010 to January 2020.From 2017 to 2019,12 patients who were treated with LAMS drainage for PFCs in our medical center were also reviewed and included in this study.Results:Combining 11 copies of documents with the data from our medical center,a total of 585 patients with PFCs were enrolled in this meta-analysis,including 343 patients with WON and 242 with PPC.The technical success rate in WON is not significantly different from that of PPC(P=0.08>0.05).The clinical success of LAMS placement was achieved in 99%vs 89%in PPC and WON,respectively(RR=0.92,95%CI:0.86-0.98,P=0.01<0.05).The further intervention of direct endoscopic necrosectomy was required by 60%of patients in WON group.There was no significant difference in the incidence of adverse events,including infection,bleeding,stent migration and stent occlusion,after LAMS placement between WON and PPC.Conclusions:Endoscopic ultrasound-guided LAMS for PFCs are feasible,effective with preferable technical and clinical success rates.The clinical effect of LAMS on PPC is slightly better than that of WON,but its adverse reactions still need to be verified in a large-sample prospective study.

Modifiable risk factors for esophageal cancer in endoscopic screening population:A modeling study

To the Editor:Esophageal cancer,one of the most common cancer types in China,with an estimated 346,633 new cases and 323,600 deaths in 2022,is becoming an increasingly serious clinical and public health problem.^([1])The successful promotion of the self-management strategy has indicated that lifestyle modifications can be valuable in the primary prevention of cancer development.Adopting a healthy lifestyle has become a novel strategy for primary prevention and risk reduction in high-risk areas.Previous epidemiological studies have identified several lifestyle-related risk factors for esophageal cancer,including smoking and diet.^([2])Each factor can typically explain a modest proportion of cancer risk.However,when combined,these known risk factors may substantially affect the risk of esophageal cancer.Nevertheless,some risk factors for esophageal cancer are non-modifiable,including age,low socioeconomic status,and family history.Whether and how these non-modifiable risk factors affect primary cancer prevention by intervening with modifiable risk factors remain unclear.

nhibitory Role of Pentraxin-3 in Esophageal Squamous Cell Carcinoma

Background： Esophageal cancer is the sixth leading cause of cancer-related death worldwide. Pentraxin-3 （PTX3） is a member of the PTX superfamily. Here, we investigated the role of PTX3 in esophageal squamous cell carcinoma （ESCC）. Methods： The effect of PTX3 on ESCC cell proliferation, colony formation, apoptosis, migration, and invasion was investigated using cell viability assays, colony formation assays, flow cytometry, and migration and invasion assays. The effect of PTX3 on the tumorigenicity of ESCC in vivo was investigated with xenograft studies in nude mice. Results： PTX3 overexpression in ESCC cells reduced cellular proliferation and colony formation （P 〈 0.05） and increased the rate of apoptosis （P 〈 0.05）. PTX3 expression had no significant effect on the migratory or invasive potential of ESCC cells. In our mouse model of human ESCC, we achieved 100% successful tumor establishment. Compared with the control and empty vector-expressing groups, the PTX3-expressing group formed significantly smaller tumors （P 〈 0.05）. Conclusions： This study indicates that PTX3 might play an inhibitory role in ESCC.

Matrix stiffness exacerbates the proinflammatory responses of vascular smooth muscle cell through the DDR1-DNMT1 mechanotransduction axis

Vascular smooth muscle cell (vSMC) is highly plastic as its phenotype can change in response to mechanical cues inherent to the extracellular matrix (ECM). VSMC may be activated from its quiescent contractile phenotype to a proinflammatory phenotype, whereby the cell secretes chemotactic and inflammatory cytokines, e.g. MCP1 and IL6, to functionally regulate monocyte and macrophage infiltration during the development of various vascular diseases including arteriosclerosis. Here, by culturing vSMCs on polyacrylamide (PA) substrates with variable elastic moduli, we discovered a role of discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that binds collagens, in mediating the mechanical regulation of vSMC gene expression, phenotype, and proinflammatory responses. We found that ECM stiffness induced DDR1 phosphorylation, oligomerization, and endocytosis to repress the expression of DNA methyltransferase 1 (DNMT1), very likely in a collagen-independent manner. The DDR1-to-DNMT1 signaling was sequentially mediated by the extracellular signal-regulated kinases (ERKs) and p53 pathways. ECM stiffness primed vSMC to a proinflammatory phenotype and this regulation was diminished by DDR1 inhibition. In agreement with the in vitro findings, increased DDR1 phosphorylation was observed in human arterial stiffening. DDR1 inhibition in mouse attenuated the acute injury or adenine diet-induced vascular stiffening and inflammation. Furthermore, mouse vasculature with SMC-specific deletion of Dnmt1 exhibited proinflammatory and stiffening phenotypes. Our study demonstrates a role of SMC DDR1 in perceiving the mechanical microenvironments and down-regulating expression of DNMT1 to result in vascular pathologies and has potential implications for optimization of engineering artificial vascular grafts and vascular networks.

Advancements in the endoscopic treatment of pancreatic fluid collections

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

Inhibition of Cancer Cell Migration and Glycolysis by Terahertz Wave Modulation via Altered Chromatin Accessibility

Metastasis and metabolic disorders contribute to most cancer deaths and are potential drug targets in cancer treatment. However, corresponding drugs inevitably induce myeloid suppression and gastrointestinal toxicity. Here, we report a nonpharmaceutical and noninvasive electromagnetic intervention technique that exhibited long-term inhibition of cancer cells. Firstly, we revealed that optical radiation at the specific wavelength of 3.6 μm (i.e., 83 THz) significantly increased binding affinity between DNA and histone via molecular dynamics simulations, providing a theoretical possibility for THz modulation- (THM-) based cancer cell intervention. Subsequent cell functional assays demonstrated that low-power 3.6 μm THz wave could successfully inhibit cancer cell migration by 50% and reduce glycolysis by 60%. Then, mRNA sequencing and assays for transposase-accessible chromatin using sequencing (ATAC-seq) indicated that low-power THM at 3.6 μm suppressed the genes associated with glycolysis and migration by reducing the chromatin accessibility of certain gene loci. Furthermore, THM at 3.6 μm on HCT-116 cancer cells reduced the liver metastasis by 60% in a metastatic xenograft mouse model by splenic injection, successfully validated the inhibition of cancer cell migration by THM in vivo. Together, this work provides a new paradigm for electromagnetic irradiation-induced epigenetic changes and represents a theoretical basis for possible innovative therapeutic applications of THM as the future of cancer treatments.

Aspirin and esophageal squamous cell carcinoma： bedside to bench

Objective To review the advances of studies on clinical results of aspirin＇s chemopreventive effect against esophageal squamous cell carcinoma （ESCC） and evidences for mechanisms of the antitumoural effects of aspirin in experimental research.Data sources A comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as aspirin and esophageal cancer.Study selection Articles associated with aspirin and esophageal cancer are analyzed.Results This review focuses on the current evidence for use of aspirin as a chemopreventive agent in ESCC.Aspirin is the most widely used among all nonsteroidal anti-inflammatory drugs （NSAIDs）,which is cheap and acceptable to patients.Several observational results provide the further investigation of prevention and therapy of aspirin or similar drugs in esophageal cancer.Data from case control studies,cohort studies and randomized controlled trials （RCTs） also give some support of a beneficial role of aspirin on ESCC.Experimental data suggest that aspirin may prevent carcinogenesis of ESCC by favorably affecting proliferation,apoptosis,or other as yet unidentified growth-regulating processes.But the mechanism by which aspirin influence on esophageal squamous cell carcinoma needs further investigation.Conclusion A wealth of evidences ranging from clinical data to experimental results are building to suggest that aspirin has significant effects in reducing both the incidence and mortality of ESCC.

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

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

Reinfection rates among patients previously infected by SARS-CoV-2:systematic review and meta-analysis

Background:Asymptomatic or symptomatic infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)can be followed by reinfection.The protection conferred by prior infection among coronavirus disease 2019(COVID-19)patients is unclear.We assessed the incidence of SARS-CoV-2 reinfection and the protection effect of previous infection against reinfection.Methods:We searched PubMed,EMBASE,Cochrane,Scopus,Web of Science,and ClinicalTrials.gov for publications up until the end date of May 1,2021.The reinfection rate of recovered patients and the protection against reinfection were analyzed using meta-analysis.Results:Overall,19 studies of 1096 reinfection patients were included.The pooled reinfection rate was 0.65%(95%confidence interval[CI]0.39-0.98%).The symptomatic reinfection rate was a bit lower(0.37%[95%CI 0.11-0.78%],I^(2)=99%).The reinfection rate was much higher in high-risk populations(1.59%[95%CI 0.30-3.88%],I^(2)=90%).The protection against reinfection and symptomatic reinfection was similar(87.02%[95%CI 83.22-89.96%]and 87.17%[95%CI 83.09-90.26%],respectively).Conclusions:The rate of reinfection with SARS-CoV-2 is relatively low.The protection against SARS-CoV-2 after natural infection is comparable to that estimated for vaccine efficacy.These data may help guide public health measures and vaccination strategies in response to the COVID-19 pandemic.High-quality clinical studies are needed to establish the relevant risk factors in recovered patients.

Sentinel node navigation to treat early gastric cancer after non-curative endoscopic submucosal dissection: A case series

Dear Editor:Gastric cancer is a leading cause of cancer-related death.With the development and popularization of endoscopic techniques,early gastric cancer(EGC)is being diagnosed more frequently.EGC is a carcinoma that invades the submucosa regardless of the lymph node status.1 Endoscopic submucosal dissection(ESD)has been accepted as an optimal treatment for patients with EGC due to its low invasiveness and functional preservation.Guidelines indicate the curability of EGC after ESD based on the curative criteria.