Efficacy and safety of endoscopic submucosal dissection for early gastric cancer and precancerous lesions in elderly patients

BACKGROUND With advancements in the development of endoscopic technologies,the endo-scopic submucosal dissection(ESD)has been one of the gold-standard therapies for early gastric cancer.AIM To investigate the efficacy and safety ESD in the treatment of early gastric cancer and precancerous lesions in the elderly patients.METHODS Seventy-eight elderly patients with early gastric cancer and precancerous lesions admitted to the Third Affiliated Hospital of Qiqihar Medical University were se-lected and classified into two groups according to the different surgical therapies they received between January 2021 and June 2022.Among them,39 patients treated with ESD were included in an experimental group,and 39 patients treated with endoscopic mucosal resection(EMR)were included in a control group.We compared the basic intraoperative conditions,postoperative short-term recovery,long-term recovery effects and functional status of gastric mucosa between the two groups;the basic intraoperative conditions included lesion resection,intra-operative bleeding and operation time;the postoperative short-term recovery assessment indexes were length of hospital stay and incidence of surgical complic-ations;and the long-term recovery assessment indexes were the recurrence rate at 1 year postoperatively and the survival situation at 1 year and 3 years postoper-atively;and we compared the preoperative and predischarge serum pepsinogen I(PG I)and PG II levels and PG I/PG II ratio in the two groups before surgery and discharge.RESULTS The curative resection rate and the rate of en bloc resection were higher in the experimental group than in the control group.The intraoperative bleeding volume was higher in the experimental group than in the control group.The operation time was longer in the experimental group than that in the control group,and the rate for base residual focus was lower in the experimental group than that of the control group,and the differences were all statistically significant(all P<0.05).The length of hospital stay was longer in the experi-mental group than in the control group,and the incidence of surgical complications,1-year postoperative recu-rrence rate and 3-year postoperative survival rate were lower in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,the difference in the 1-year postoperative survival rate was not statistically significant between the two groups(P>0.05).Before discharge,PG I and PG I/PG II ratio were elevated in both groups compared with the preoperative period,and the above indexes were higher in the experimental group than those in the control group,and the differences were statistically significant(both P<0.05).Moreover,before discharge,PG II level was lower in both groups compared with the preoperative period,and the level was lower in the experimental group than in the control group,and the differences were all statistically significant(all P<0.05).CONCLUSION Compared with EMR,ESD surgery is more thorough.It reduces the rate of base residual focus,recurrence rate,surgical complications,and promotes the recovery of gastric cells and glandular function.It is safe and suitable for clinical application.

Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection

BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD.AIM To analyze the features of gastric mucosal tumors at different differentiation levels,and to explore the prognostic factors of ESD.METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021,according to the latest Japanese guidelines(sixth edition),and divided them into low-grade intrae-pithelial neoplasia(LGIN),high-grade intraepithelial neoplasia(HGIN),and computed tomography at 3,6 and 12 months after ESD.We compared clinicopathologic characteristics,ESD efficacy,and complications with different degrees of differentiation,and analyzed the related factors associated with ESD.RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients(P<0.001)and accounted for more 0-IIc(P<0.001),atrophic gastritis was common(P<0.001),and irregular microvascular patterns(IMVPs)and demarcation lines(DLs)were more obvious(P<0.001).There was more infiltration in the undifferentiated carcinoma tissue(P<0.001),more abnormal folds and poorer mucosal peristalsis(P<0.001),and more obvious IMVPs,irregular microsurface patterns and DLs(P<0.05)than in the LGIN and HGIN tissues.The disease-free survival rates at 2,5,and 8 years after ESD were 95.0%,90.1%,and 86.9%,respectively.Undifferen-tiated lesions(HR 5.066),white moss(HR 7.187),incomplete resection(HR 3.658),and multiple primary cancers(HR 2.462)were significantly associated with poor prognosis.CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics,which are closely related to the safety and efficacy of ESD.

Editorial article to:Animal experimental study on magnetic anchor technique-assisted endoscopic submucosal dissection of early gastric cancer

In this editorial we comment on the article published in the recent issue of the World Journal of Gastrointestinal Endoscopy 2023;15(11):634-680.Gastric cancer(GC)remains the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide.The overall prevalence of GC has declined,although that of proximal GC has increased over time.Thus,a significant proportion of GC cases and deaths can be avoided if preventive interventions are taken.Early GC(EGC)is defined as GC confined to the mucosa or submucosa.Endoscopic resection is considered the most appropriate treatment for precancerous gastrointestinal lesions improving patient quality of life,with reduced rates of complications,shorter hospitalization period,and lower costs when compared to surgical resection.Endoscopic mucosal resection(EMR)and endoscopic sub-mucosal dissection(ESD)are representative endoscopic treatments for EGC and precancerous gastric lesions.Standard EMR implies injection of a saline solution into the sub-mucosal space,followed by excision of the lesion using a snare.Complete resection rates vary depending on the size and severity of the lesion.When using conventional EMR methods for lesions less than 1 cm in size,the complete resection rate is approximately 60%,whereas for lesions larger than 2 cm,the complete resection rate is low(20%-30%).ESD can be used to remove tumors exceeding 2 cm in diameter and lesions associated with ulcers or submucosal fibrosis.Compared with EMR,ESD has higher en bloc resection rates(90.2%vs 51.7%),higher complete resection rates(82.1 vs 42.2%),and lower recurrence rates(0.65%vs 6.05%).Thus,innovative techniques have been introduced.

Prospective randomized study correlating intra-operative urethral mucosal injury with early period after transurethral resection of the prostate stricture urethra: A novel concept

Objective:To investigate the incidence of urethral stricture during the early period after transurethral resection of the prostate(TURP)and correlate its incidence with intra-operative urethral mucosal injury during TURP.Also to compare the other established risk factors affecting the development of urethral stricture among patients undergoing monopolar or bipolar TURP over a period of 6 months follow-up as the prospective randomized study.Methods:One hundred and fifty men older than 50 years with lower-urinary tract symptoms associated with benign prostatic hyperplasia were randomized to undergo either standard monopolar TURP with glycine as the irrigation fluid or bipolar TURP with normal saline as irrigant.The prostate size,operative time,intra-operative mucosal rupture,catheter time,catheter traction duration,uroflowmetry,and post-operative stricture rate were compared.Results:A total of 150 patients underwent TURP,including 74 patients undergoing monopolar TURP(one patient was excluded as his post-operative histopathological examination report was of adenocarcinoma prostate)and 75 patients undergoing bipolar-TURP,all of which were performed using a 26 Fr sheath resectoscope.The mean International Prostate Symptom Score and maximum urinary flow rate score at post-operative 3 months and 6 months were comparable between the groups.Out of 149 patients,nine patients(6.0%)developed urethral stricture.The severity of the injury(urethral mucosal injury)correlated with the likelihood of developing a subsequent complication(stricture urethra).Patients with stricture had significantly larger prostate volume than patients without stricture(65.0 mL vs.50.0 mL;p=0.030).Patients with stricture had longer operative time than patients without stricture(55.0 min vs.40.0 min;p=0.002).In both procedures,formation of post-operative stricture urethra was independently associated with intra-operative mucosal injury.Conclusion:Intra-operative recognition of urethral mucosal injury helps in prediction of stricture urethra formation in early post-operative period.

Fecal calprotectin and endoscopic scores: The cornerstones in clinical practice for evaluating mucosal healing in inflammatory bowel disease

Managing inflammatory bowel disease(IBD)is becoming increasingly complex and personalized,considering the advent of new advanced therapies with distinct mechanisms of action.Achieving mucosal healing(MH)is a pivotal therapeutic goal in IBD management and can prevent IBD progression and reduce flares,hospitalization,surgery,intestinal damage,and colorectal cancer.Employing proactive disease and therapy assessment is essential to achieve better control of intestinal inflammation,even if subclinical,to alter the natural course of IBD.Periodic monitoring of fecal calprotectin(FC)levels and interval endoscopic evaluations are cornerstones for evaluating response/remission to advanced therapies targeting IBD,assessing MH,and detecting subclinical recurrence.Here,we comment on the article by Ishida et al Moreover,this editorial aimed to review the role of FC and endoscopic scores in predicting MH in patients with IBD.Furthermore,we intend to present some evidence on the role of these markers in future targets,such as histological and transmural healing.Additional prospective multicenter studies with a stricter MH criterion,standardized endoscopic and histopathological analyses,and virtual chromoscopy,potentially including artificial intelligence and other biomarkers,are desired.

Alkaline sphingomyelinase deficiency impairs intestinal mucosal barrier integrity and reduces antioxidant capacity in dextran sulfate sodium-induced colitis

BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.

Addressing mucosal ulcers during orthodontic treatment:An urgent call for preventive strategies

Mucosal ulcers are a common yet often overlooked complication during orthodontic treatment,significantly impacting patient comfort and compliance.This letter aims to highlight the prevalence,potential causes,and management strategies for mucosal ulcers in orthodontic patients.By reviewing recent literature and clinical observations,we underscore the necessity for proactive measures and tailored interventions to mitigate the incidence and severity of these lesions.Emphasizing the role of patient education and the use of protective devices,we call for a multidisciplinary approach to enhance patient care and treatment outcomes.This discussion is particularly relevant in the context of evolving orthodontic techniques and materials,which necessitate continuous adaptation of clinical practices to ensure patient safety and well-being.

Alteration of ascending colon mucosal microbiota in patients after cholecystectomy

BACKGROUND Cholecystectomy is a successful treatment option for gallstones,although the inci-dence of colorectal cancer(CRC)has notably increased in post-cholecystectomy(PC)patients.However,it remains uncertain whether the altered mucosal micro-biota in the ascending colon is related.In total,30 PC patients and 28 healthy controls underwent colonoscopies to collect mucosal biopsy samples.PC patients were divided based on their clinical features.Then,16S-rRNA gene sequencing was used to analyze the amplicon,alpha diversity,beta diversity,and composition of the bacterial communities.Addi-tionally,the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States(PICRUSt)database,sourced from the Kyoto Encyclopedia of Genes and Genomes,was used to predict the functional capabilities of the bac-teria.RESULTS PC patients were comparable with healthy controls.However,PC patients older than 60 years had a distinct composition compared to those under 60 years old.Bacteroidetes richness was considerably higher at the phylum level in PC patients.Bacteroides,Parabacteroides,and Bilophila were more abundant in the PC group than in the control group.Furthermore,PC patients exhibited greater enrichment in metabolic pathways,specifically those related to lipopolysaccharide biosynthesis and vancomycin group antibiotic production,than controls.CONCLUSION This study indicated that the mucosal microbiota in PC patients was altered,perhaps offering new perspectives on the treatment possibilities for CRC and diarrhea following cholecystectomy.

Giant Brunner's gland hyperplasia of the duodenum successfully resected en bloc by endoscopic mucosal resection: A case report

BACKGROUND Duodenal Brunner's gland hyperplasia(BGH)is a therapeutic target when complications such as bleeding or gastrointestinal obstruction occur or when malignancy cannot be ruled out.Herein,we present a case of large BGH treated with endoscopic mucosal resection(EMR).CASE SUMMARY An 83-year-old woman presented at our hospital with dizziness.Blood tests revealed severe anemia,esophagogastroduodenoscopy showed a 6.5 cm lesion protruding from the anterior wall of the duodenal bulb,and biopsy revealed the presence of glandular epithelium.Endoscopic ultrasonography(EUS)demonstr-ated relatively high echogenicity with a cystic component.The muscularis propria was slightly elevated at the base of the lesion.EMR was performed without complications.The formalin-fixed lesion size was 6 cm×3.5 cm×3 cm,showing nodular proliferation of non-dysplastic Brunner's glands compartmentalized by fibrous septa,confirming the diagnosis of BGH.Reports of EMR or hot snare polypectomy are rare for duodenal BGH>6 cm.In this case,the choice of EMR was made by obtaining information on the base of the lesion as well as on the internal characteristics through EUS.CONCLUSION Large duodenal lesions with good endoscopic maneuverability and no evident muscular layer involvement on EUS may be resectable via EMR.

Mucosal healing and inflammatory bowel disease:Therapeutic implications and new targets

Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair.However,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IBD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be understood.Consequently,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,persists.With increased understanding of the molecular mechanisms of IBD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing response.In this review,we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.

Multicenter evaluation of recurrence in endoscopic submucosal dissection and endoscopic mucosal resection in the colon:A Western perspective

BACKGROUND While colon endoscopic mucosal resection(EMR)is an effective technique,removal of larger polyps often requires piecemeal resection,which can increase recurrence rates.Endoscopic submucosal dissection(ESD)in the colon offers the ability for en bloc resection and is well-described in Asia,but there are limited studies comparing ESD vs EMR in the West.AIM To evaluate different techniques in endoscopic resection of large polyps in the colon and to identify factors for recurrence.METHODS The study is a retrospective comparison of ESD,EMR and knife-assisted endoscopic resection performed at Stanford University Medical Center and Veterans Affairs Palo Alto Health Care System between 2016 and 2020.Knife-assisted endoscopic resection was defined as use of electrosurgical knife to facilitate snare resection,such as for circumferential incision.Patients≥18 years of age undergoing colonoscopy with removal of polyp(s)≥20 mm were included.The primary outcome was recurrence on follow-up.RESULTS A total of 376 patients and 428 polyps were included.Mean polyp size was greatest in the ESD group(35.8 mm),followed by knife-assisted endoscopic resection(33.3 mm)and EMR(30.5 mm)(P<0.001).ESD achieved highest en bloc resection(90.4%)followed by knife-assisted endoscopic resection(31.1%)and EMR(20.2%)(P<0.001).A total of 287 polyps had follow-up(67.1%).On follow-up analysis,recurrence rate was lowest in knife-assisted endoscopic resection(0.0%)and ESD(1.3%)and highest in EMR(12.9%)(P=0.0017).En bloc polyp resection had significantly lower rate of recurrence(1.9%)compared to non-en bloc(12.0%,P=0.003).On multivariate analysis,ESD(in comparison to EMR)adjusted for polyp size was found to significantly reduce risk of recurrence[adjusted hazard ratio 0.06(95%CI:0.01-0.57,P=0.014)].CONCLUSION In our study,EMR had significantly higher recurrence compared to ESD and knife-assisted endoscopic resection.We found factors including resection by ESD,en bloc removal,and use of circumferential incision were associated with significantly decreased recurrence.While further studies are needed,we have demonstrated the efficacy of ESD in a Western population.

Feasibility and efficacy of endoscopic purse-string suture-assisted closure for mucosal defects induced by endoscopic manipulations

BACKGROUND Large or transmural defects induced by gastrointestinal endoscopic manipulations are difficult to close,although complete closure is recommended for better recovery.Endoscopic purse-string assisted suturing(EPSS)has been used in clinical practice and has proven to be an effective and safe technique for the closure of large mucosal defects.However,details regarding the efficacy of endoscopic pre-purse-string suture(P-EPSS)are unknown,especially that it offers several advantages over conventional EPSS(C-EPSS).AIM To elucidate the outcomes of EPSS-assisted closure in different clinical situations,and evaluate the efficacy of P-EPSS.METHODS This retrospective observational study included a total of 180 patients who underwent closure assisted by P-EPSS(n=63)or C-EPSS(n=117)between July 2014 and June 2020.The P-EPSS and C-EPSS groups were compared and the intergroup differences in aspects such as the lesion size,location,and morphology,incidence of complete closure,intraoperative perforation,and delayed adverse events were evaluated.Data on the features and clinical course of cases with adverse events were collected for further analysis.RESULTS Patients with lesion size larger than 3 cm,lesions located at the fundus of stomach,or submucosal tumors originating from the deep mucosa were more likely to undergo P-EPSS-assisted closure.The P-EPSS group showed a significantly higher proportion of intraoperative perforation(56%vs 17%)and a much shorter procedure time(9.06±6.14 min vs 14.84±7.25 min).Among adverse events,the incidence of delayed perforation(5%vs 4%;P=0.82)and delayed bleeding(3%vs 4%;P=0.96)did not differ significantly between the groups.Multivariate analysis revealed that lesions with incomplete closure[odds ratio(OR)=21.33;95%confidence interval(CI):5.45-83.45;P<0.01]or size greater than 3 cm(OR=3.14;95%CI:1.08-9.18;P=0.039)showed a statistical tendency to result in an increase in delayed adverse events.CONCLUSION The present study revealed that EPSS could achieve secure complete closure of mucosal defect.PEPSS could shorten the procedure and yield complete closure of mucosal defects.Rather than closure-type selection,incomplete closure or lesion size larger than 3 cm were associated with worse outcomes.

Is endoscopic mucosal resection-precutting superior to conventional methods for removing sessile colorectal polyps?

We reviewed a study that reported a comparative analysis of the effects of endoscopic mucosal resection(EMR)precutting and conventional EMR for removing non-pedunculated,10-20 mm sized colorectal polyps.We identified some statistical deficiencies in this study.In addition,we believe that the differences between the treatments failed to achieve significance,and therefore,further analysis is required.

Endoscopic mucosal resection with double band ligation versus endoscopic submucosal dissection for small rectal neuroendocrine tumors

BACKGROUND Endoscopic resection remains an effective method for the treatment of small rectal neuroendocrine tumors(NETs)(≤10 mm).Moreover,endoscopic mucosal resection(EMR)with double band ligation(EMR-dB),a simplified modification of EMR with band ligation,is an alternative strategy to remove small rectal NETs.AIM To evaluate the feasibility and safety of EMR-dB for the treatment of small rectal NETs(≤10 mm).METHODS A total of 50 patients with small rectal NETs,without regional lymph node enlargement or distant metastasis confirmed by endoscopic ultrasound,computerized tomography scan,or magnetic resonance imaging,were enrolled in the study from March 2021 to June 2022.These patients were randomly assigned into the EMR-dB(n=25)group or endoscopic submucosal dissection(ESD)group(n=25).The characteristics of the patients and tumors,procedure time,devices cost,complete resection rate,complications,and recurrence outcomes were analyzed.RESULTS There were 25 patients(13 males,12 females;age range 28-68 years old)in the EMR-dB group,and the ESD group contained 25 patients(15 males,10 females;age range 25-70 years old).Both groups had similar lesion sizes(EMR-dB 4.53±1.02 mm,ESD 5.140±1.74 mm;P=0.141)and resected lesion sizes(1.32±0.52 cm vs 1.58±0.84 cm;P=0.269).Furthermore,the histological complete resection and en bloc resection rates were achieved in all patients(100%for each).In addition,there was no significant difference in the complication rate between the two groups.However,the procedure time was significantly shorter and the devices cost was significantly lower in the EMRdB group.Besides,there was no recurrence in both groups during the follow-up period.CONCLUSION The procedure time of EMR-dB was shorter compared with ESD,and both approaches showed a similar curative effect.Taken together,EMR-dB was a feasible and safe option for the treatment of small rectal NETs.

Expanding endoscopic boundaries:Endoscopic resection of large appendiceal orifice polyps with endoscopic mucosal resection and endoscopic submucosal dissection

BACKGROUND Large appendiceal orifice polyps are traditionally treated surgically.Recently,endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)have been utilized as alternative resection techniques.AIM To evaluate the efficacy and safety of endoscopic resection techniques for the management of large appendiceal orifice polyps.METHODS This was a retrospective observational study conducted to assess the feasibility and safety of EMR and ESD for large appendiceal orifice polyps.This project was approved by the Baylor College of Medicine Institutional Review Board.Patients who underwent endoscopic resection of appendiceal orifice polyps≥1 cm from 2015 to 2022 at a tertiary referral endoscopy center in the United States were enrolled.The main outcomes of this study included en bloc resection,R0 resection,post resection adverse events,and polyp recurrence.RESULTS A total of 19 patients were identified.Most patients were female(53%)and Caucasian(95%).The mean age was 63.3±10.8 years,and the average body mass index was 28.8±6.4.The mean polyp size was 25.5±14.2 mm.74%of polyps were localized to the appendix(at or inside the appendiceal orifice)and the remaining extended into the cecum.68%of polyps occupied≥50%of the appendiceal orifice circumference.The mean procedure duration was 61.6±37.9 minutes.Polyps were resected via endoscopic mucosal resection,endoscopic submucosal dissection,and hybrid procedures in 5,6,and 8 patients,respectively.Final pathology was remarkable for tubular adenoma(n=10)[one with high grade dysplasia],sessile serrated adenoma(n=7),and tubulovillous adenoma(n=2)[two with high grade dysplasia].En bloc resection was achieved in 84%with an 88%R0 resection rate.Despite the large polyp sizes and challenging procedures,89%(n=17)of patients were discharged on the same day as their procedure.Two patients were admitted for post-procedure observation for conservative pain management.Eight patients underwent repeat colonoscopy without evidence of residual or recurrent adenomatous polyps.CONCLUSION Our study highlights how endoscopic mucosal resection,endoscopic submucosal dissection,and hybrid procedures are all appropriate techniques with minimal adverse effects,further validating the utility of endoscopic procedures in the management of large appendiceal polyps.

Colorectal endoscopic submucosal dissection from a Westernperspective:Today's promises and future challenges

Over the last few years, endoscopic submucosal dissection(ESD) has shown to be effective in the management of early colorectal neoplasms, particularly in Asian countries where the technique was born. In the Western world, its implementation has been slow and laborious. In this paper, the indications for ESD, its learning model, the available methods to predict the presence of deep submucosal invasion before the procedure and the published outcomes from Asia and Europe will be reviewed. Since ESD has several limitations in terms of learning achievement in the West, and completion of the procedure for the first cases is difficult in our part of the world, a short review on colorectal assisted ESD has been included. Finally, other endoscopic and surgical treatment modalities that are in competition with colorectal ESD will be summarized.

Dietary supplementation of bilberry anthocyanin on growth performance,intestinal mucosal barrier and cecal microbes of chickens challenged with Salmonella Typhimurium

Background Anthocyanins(AC)showed positive effects on improving the intestinal health and alleviating intestinal pathogen infections,therefore,an experiment was conducted to explore the protective effects of supplemented AC on Salmonella-infected chickens.Methods A total of 240 hatchling chickens were randomly allocated to 4 treatments,each with 6 replicates.Birds were fed a basal diet supplemented with 0(CON,and ST),100(ACL)and 400(ACH)mg/kg of AC for d 60,and orally challenged with PBS(CON)or 10^(9) CFU/bird(ST,ACL,ACH)Salmonella Typhimurium at d 14 and 16.Results(1)Compared with birds in ST,AC supplementation increased the body weight(BW)at d 18 and the average daily gain(ADG)from d 1 to 18 of the Salmonella-infected chickens(P<0.05);(2)AC decreased the number of Salmonella cells in the liver and spleen,the contents of NO in plasma and inflammatory cytokines in ileal mucosa of Salmonella-infected chickens(P<0.05);(3)Salmonella infection decreased the ileal villi height,villi height to crypt depth(V/C),and the expression of zonulaoccludins-1(ZO-1),claudin-1,occludin,and mucin 2(MUC2)in ileal mucosa.AC supplementation relieved these adverse effects,and decreased ileal crypt depth(P<0.05);(4)In cecal microbiota of Salmonella-infected chickens,AC increased(P<0.05)the alpha-diversity(Chao1,Pd,Shannon and Sobs indexes)and the relative abundance of Firmicutes,and decreased(P<0.05)the relative abundance of Proteobacteria and Bacteroidota and the enrichment of drug antimicrobial resistance,infectious bacterial disease,and immune disease pathways.Conclusions Dietary AC protected chicken against Salmonella infection via inhibiting the Salmonella colonization in liver and spleen,suppressing secretion of inflammatory cytokines,up-regulating the expression of ileal barrier-related genes,and ameliorating the composition and function of cecal microbes.Under conditions here used,100 mg/kg bilberry anthocyanin was recommended.

Molecular regulation mechanism of intestinal stem cells in mucosal injury and repair in ulcerative colitis

Ulcerative colitis(UC)is a chronic nonspecific inflammatory disease with complex causes.The main pathological changes were intestinal mucosal injury.Leucinerich repeat-containing G protein coupled receptor 5(LGR5)-labeled small intestine stem cells(ISCs)were located at the bottom of the small intestine recess and inlaid among Paneth cells.LGR5+small ISCs are active proliferative adult stem cells,and their self-renewal,proliferation and differentiation disorders are closely related to the occurrence of intestinal inflammatory diseases.The Notch signaling pathway and Wnt/β-catenin signaling pathway are important regulators of LGR5-positive ISCs and together maintain the function of LGR5-positive ISCs.More importantly,the surviving stem cells after intestinal mucosal injury accelerate division,restore the number of stem cells,multiply and differentiate into mature intestinal epithelial cells,and repair the damaged intestinal mucosa.Therefore,in-depth study of multiple pathways and transplantation of LGR5-positive ISCs may become a new target for the treatment of UC.

Characteristics of glucose and lipid metabolism and the interaction between gut microbiota and colonic mucosal immunity in pigs during cold exposure

Background Cold regions have long autumn and winter seasons and low ambient temperatures.When pigs are unable to adjust to the cold,oxidative damage and inflammation may develop.However,the differences between cold and non-cold adaptation regarding glucose and lipid metabolism,gut microbiota and colonic mucosal immunological features in pigs are unknown.This study revealed the glucose and lipid metabolic responses and the dual role of gut microbiota in pigs during cold and non-cold adaptation.Moreover,the regulatory effects of dietary glucose supplements on glucose and lipid metabolism and the colonic mucosal barrier were evaluated in cold-exposed pigs.Results Cold and non-cold-adapted models were established by Min and Yorkshire pigs.Our results exhibited that cold exposure induced glucose overconsumption in non-cold-adapted pig models(Yorkshire pigs),decreasing plasma glucose concentrations.In this case,cold exposure enhanced the ATGL and CPT-1αexpression to promote liver lipolysis and fatty acid oxidation.Meanwhile,the two probiotics(Collinsella and Bifidobacterium)depletion and the enrichment of two pathogens(Sutterella and Escherichia-Shigella)in colonic microbiota are not conducive to colonic mucosal immunity.However,glucagon-mediated hepatic glycogenolysis in cold-adapted pig models(Min pigs)maintained the stability of glucose homeostasis during cold exposure.It contributed to the gut microbiota(including the enrichment of the Rikenellaceae RC9 gut group,[Eubacterium]coprostanoligenes group and WCHB1-41)that favored cold-adapted metabolism.Conclusions The results of both models indicate that the gut microbiota during cold adaptation contributes to the protection of the colonic mucosa.During non-cold adaptation,cold-induced glucose overconsumption promotes thermogenesis through lipolysis,but interferes with the gut microbiome and colonic mucosal immunity.Furthermore,glucagon-mediated hepatic glycogenolysis contributes to glucose homeostasis during cold exposure.

Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells

BACKGROUND Gastric precancerous lesions(GPL)precede the development of gastric cancer(GC).They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation,bacterial infection,and injury.Abnormalities in autophagy and glycolysis affect GPL progression,and their effective regulation can aid in GPL treatment and GC prevention.Xiaojianzhong decoction(XJZ)is a classic compound for the treatment of digestive system diseases in ancient China which can inhibit the progression of GPL.However,its specific mechanism of action is still unclear.AIM To investigate the therapeutic effects of XJZ decoction on a rat GPL model and the mechanisms underlying its effects on autophagy and glycolysis regulation in GPLs.METHODS Wistar rats were randomly divided into six groups of five rats each and all groups except the control group were subjected to GPL model construction for 18 wk.The rats’body weight was monitored every 2 wk starting from the beginning of modeling.Gastric histopathology was examined using hematoxylin-eosin staining and Alcian blue-periodic acid-Schiff staining.Autophagy was observed using transmission electron microscopy.The expressions of autophagy,hypoxia,and glycolysis related proteins in gastric mucosa were detected using immunohistochemistry and immunofluorescence.The expressions of the following proteins in gastric tissues:B cell lymphoma/Leukemia-2 and adenovirus E1B19000 interacting protein 3(Bnip-3),microtubule associated protein 1 light chain 3(LC-3),moesin-like BCL2-interacting protein 1(Beclin-1),phosphatidylinositol 3-kimase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),p53,AMP-activated protein kinase(AMPK),and Unc-51 like kinase 1(ULK1)were detected using western blot.The relative expressions of autophagy,hypoxia,and glycolysis related mRNA in gastric tissues was detected using reverse transcription-polymerase chain reaction.RESULTS Treatment with XJZ increased the rats’body weight and improved GPL-related histopathological manifestations.It also decreased autophagosome and autolysosome formation in gastric tissues and reduced Bnip-3,Beclin-1,and LC-3II expressions,resulting in inhibition of autophagy.Moreover,XJZ down-regulated glycolysis-related monocarboxylate transporter(MCT1),MCT4,and CD147 expressions.XJZ prevented the increase of autophagy level by decreasing gastric mucosal hypoxia,activating the PI3K/AKT/mTOR pathway,inhibiting the p53/AMPK pathway activation and ULK1 Ser-317 and Ser-555 phosphorylation.In addition,XJZ improved abnormal gastric mucosal glucose metabolism by ameliorating gastric mucosal hypoxia and inhibiting ULK1 expression.CONCLUSION This study demonstrates that XJZ may inhibit autophagy and glycolysis in GPL gastric mucosal cells by improving gastric mucosal hypoxia and regulating PI3K/AKT/mTOR and p53/AMPK/ULK1 signaling pathways,providing a feasible strategy for the GPL treatment.