Challenges and advancing strategies of endoscopic submucosal dissection for early gastric cancer:The puzzle of eCura C1

In this editorial,we explore the challenges of managing noncurative resections in early gastric cancer after endoscopic submucosal dissection(ESD),starting from the consideration recently made by Zhu et al.Specifically,we evaluate the management of eCura C1 lesions,where decisions regarding further interventions are pivotal yet contentious.Collaboration among endoscopists,surgeons,and pathologists is underscored to refine risk assessment and personalize therapeutic management.Recent advancements in ESD techniques and interdisciplinary collaboration offer opportunities for outcome optimization in managing eCura C1 lesions.Moreover,despite needing further clinical validation,molecular biomarkers have emerged as promising tools for enhancing prognostication.This manuscript highlights the ongoing research attempts to define treatment paradigms effectively and evaluates the potential of emerging options,ultimately aiming to improve patient care and outcomes in this complex clinical scenario.

Chronic functional constipation is strongly linked to vitamin D deficiency

BACKGROUND Few studies have examined intestinal motility disorders, which are disabling conditions associated with chronic functional constipation, whose pathogenesis is actually not well-defined.AIM To investigate the relationship between serum 25-hydroxyvitamin D levels and functional chronic constipation associated to intestinal motility disorders.METHODS We performed a prospective case-control study, from May-June to November2017. Glucose/lactulose breath tests, radiopaque markers(multiple capsule techniques) and wireless motility capsule analysis were used to assess colonicand oro-cecal transit time, after excluding small-intestinal bacterial overgrowth condition. Then, we measured 25-hydroxyvitamin D levels in patients with intestinal motility disorders and we further evaluated the influence of intestinal motility disorders on psychological symptoms/quality of life using validated questionnaires, the Irritable Bowel Syndrome Quality of life(IBS-QOL), the Short Form Health Survey 12, and the Hospital Anxiety and Depression Scale 14(HADS-14 A and HADS-14 D).RESULTS We enrolled 86 patients with chronic functional constipation associated to intestinal motility disorders and 86 matched healthy subjects. Patients with intestinal motility disorders had lower 25-hydroxyvitamin D levels(P < 0.001), and they showed a significant impairment of all health-related quality of life and psychological tests(IBS-QOL, Short Form Health Survey 12-Physical Component Summary, Short Form Health Survey 12-Mental Component Summary, HADS-14 A and HADS-14 D), as compared to the control group(P < 0.001), which significantly correlated with low vitamin D levels(r =-0.57, P < 0.001; r = 0.21, P = 0.01; r =-0.48, P < 0.001; r =-0.57, P < 0.001; r =-0.29, P < 0.001, respectively). At multivariate analysis vitamin D low levels remained a significant independent risk factor for the occurrence of intestinal motility disorder(odds ratio = 1.19; 95% confidence interval: 1.14-1.26, P < 0.001).CONCLUSION Vitamin D deficiency, anxiety and depression symptoms are commonly associated with chronic functional constipation induced by intestinal motility disorders. Vitamin D serum levels should be routinely measured in these patients.

Factors affecting the quality of bowel preparation for colonoscopy in hard-to-prepare patients:Evidence from the literature

Adequate bowel cleansing is critical for a high-quality colonoscopy because it affects diagnostic accuracy and adenoma detection.Nevertheless,almost a quarter of procedures are still carried out with suboptimal preparation,resulting in longer procedure times,higher risk of complications,and higher likelihood of missing lesions.Current guidelines recommend high-volume or low-volume polyethylene glycol(PEG)/non-PEG-based split-dose regimens.In patients who have had insufficient bowel cleansing,the colonoscopy should be repeated the same day or the next day with additional bowel cleansing as a salvage option.A strategy that includes a prolonged low-fiber diet,a split preparation regimen,and a colonoscopy within 5 h of the end of preparation may increase cleansing success rates in the elderly.Furthermore,even though no specific product is specifically recommended in the other cases for difficult-to-prepare patients,clinical evidence suggests that 1-L PEG plus ascorbic acid preparation are associated with higher cleansing success in hospitalized and inflammatory bowel disease patients.Patients with severe renal insufficiency(creatinine clearance<30 mL/min)should be prepared with isotonic high volume PEG solutions.Few data on cirrhotic patients are currently available,and no trials have been conducted in this population.An accurate characterization of procedural and patient variables may lead to a more personalized approach to bowel preparation,especially in patients undergoing resection of left colon lesions,where intestinal preparation has a poor outcome.The purpose of this review was to summarize the evidence on the risk factors influencing the quality of bowel cleansing in difficult-to-prepare patients,as well as strategies to improve colonoscopy preparation in these patients.

Helicobacter pylori-induced inflammation masks the underlying presence of low-grade dysplasia on gastric lesions

BACKGROUND Helicobacter pylori(H.pylori)infection has been associated with a long-term risk of precancerous gastric conditions(PGC)even after H.pylori eradication.AIM To investigate the efficacy of High-Resolution White-Light Endoscopy with Narrow-Band Imaging in detecting PGC,before/after H.pylori eradication.METHODS We studied 85 consecutive patients with H.pylori-related gastritis with/without PGC before and 6 mo after proven H.pylori eradication.Kimura-Takemoto modified and endoscopic grading of gastric intestinal metaplasia classifications,were applied to assess the endoscopic extension of atrophy and intestinal metaplasia.The histological result was considered to be the gold standard.The Sydney System,the Operative-Link on Gastritis-Assessment,and the Operative-Link on Gastric-Intestinal Metaplasia were used for defining histological gastritis,atrophy and intestinal metaplasia,whereas dysplasia was graded according to World Health Organization classification.Serum anti-parietal cell antibody and anti-intrinsic factor were measured when autoimmune atrophic gastritis was suspected.RESULTS After H.pylori eradication histological signs of mononuclear/polymorphonuclear cell infiltration and Mucosal Associated Lymphoid Tissue-hyperplasia,disappeared or decreased in 100%and 96.5%of patients respectively,whereas the Operative-Link on Gastritis-Assessment and Operative-Link on Gastric-Intestinal Metaplasia stages did not change.Low-Grade Dysplasia prevalence was similar on random biopsies before and after H.pylori eradication(17.6%vs 10.6%,P=0.19),but increased in patients with visible lesions(0%vs 22.4%,P<0.0001).At a multivariate analysis,the probability for detecting dysplasia after resolution of H.pylori-related active inflammation was higher in patients with regression or reduction of Mucosal Associated Lymphoid Tissue hyperplasia,greater alcohol consumption,and anti-parietal cell antibody and/or anti-intrinsic factor positivity[odds ratio(OR)=3.88,95%confidence interval(CI):1.31-11.49,P=0.01;OR=3.10,95%CI:1.05-9.12,P=0.04 and OR=5.47,95%CI:1.33-22.39,P<0.04,respectively].CONCLUSION High-Resolution White-Light Endoscopy with Narrow-Band Imaging allows an accurate diagnosis of Low-Grade Dysplasia on visible lesions after regression of H.pylori-induced chronic gastritis.Patients with an overlap between autoimmune/H.pylori-induced gastritis may require more extensive gastric mapping.

Surveillance strategies for precancerous gastric conditions after Helicobacter pylori eradication:There is still need for a tailored approach

Prevailing evidence declares that Helicobacter pylori (H. pylori) eradication therapycould shift precancerous gastric conditions (PGC) and positively confines gastriccancer (GC) risk during long-term endoscopic follow-up. Nonetheless, there is ayet unsolved controversy regarding the best-individualized surveillance strategiesfollowing H. pylori eradication, based on malignant risk stratification. This lastdispute is due to the uncertainty of contemporary evidence and the role of H.pylori inflammatory changes in underestimating PGC at the index endoscopy.However, the current state of the art suggests that it is reasonable that highqualityendoscopy with histological assessment for the most accurate diagnosis ofPGC may be delayed in selected high-risk patients without alarm signs formalignancy, following the eradication of H. pylori. Notwithstanding, these aspectsneed to be further examined in the next future to establish and optimize the mostbeneficial and cost-effective strategies for recognizing and managing H. pyloripositivepatients with PGC in the short- and long-term follow-up. Accordingly,additional studies are yet required to sharpen the hazard stratification of patientswith the greatest chance of GC evolution, also recognizing the evolving racial,ethnic, immigration factors and the necessity of novel biomarkers to limit GCdevelopment or accomplish a diagnosis of malignancy at an early stage.

Atezolizumab plus bevacizumab versus sorafenib or atezolizumab alone for unresectable hepatocellular carcinoma:A systematic review

BACKGROUND Despite the use of current standard therapy,the prognosis of patients with unresectable hepatocellular carcinoma(HCC)is poor,with median survival times of 40 mo for intermediate HCC(Barcelona Clinic Liver Cancer[BCLC]stage B)and 6-8 mo for advanced HCC(BCLC stage C).Although patients with earlystage HCC are usually suitable for therapies with curative intention,up to 70% of patients experience relapse within 5 years.In the past decade,the United States Food and Drug Administration has approved different immunogenic treatment options for advanced HCC,the most common type of liver cancer among adults.Nevertheless,no treatment is useful in the adjuvant setting.Since 2007,the multikinase inhibitor sorafenib has been used as a first-line targeted drug to address the increased mortality and incidence rates of HCC.However,in 2020,the IMbrave150 trial demonstrated that combination therapy of atezolizumab(antiprogrammed death-ligand 1[PD-L1])and bevacizumab(anti-vascular endothelial growth factor[VEGF])is superior to sorafenib,a single anti-programmed death 1/PD-L1 antibody inhibitor used as an anti-cancer monotherapy for HCC treatment.AIM To conduct a systematic literature review to evaluate the evidence supporting the efficacy and safety of atezolizumab/bevacizumab as preferred first-line drug therapy over the conventional sorafenib or atezolizumab monotherapies,which are used to improve survival outcomes and reduce disease progression in patients with unresectable HCC and non-decompensated liver disease.METHODS A comprehensive literature review was conducted using the PubMed,Scopus,ScienceDirect,clinicaltrials.gov,PubMed Central,Embase,EuropePMC,and CINAHL databases to identify studies that met the inclusion criteria using relevant MeSH terms.This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and risk of bias(RoB)were assessed using the Cochrane RoB 2 tool and Sevis.RESULTS In the atezolizumab/bevacizumab group,an improvement in overall tumor response,reduction of disease progression,and longer progression-free survival were observed compared to monotherapy with either sorafenib or atezolizumab.Hypertension and proteinuria were the most common adverse events,and the rates of adverse events were comparable to those with the monotherapy.Of the studies,there were two completed trials and two ongoing trials analyzed using high quality and low bias.A more thorough analysis was only performed on the completed trials.CONCLUSION Treatment of HCC with atezolizumab/bevacizumab combination therapy was confirmed to be an effective first-line treatment to improve survival in patients with unresectable HCC and non-decompensated liver disease compared to monotherapy with either sorafenib or atezolizumab.

Indications and outcomes of endoscopic resection for nonpedunculated colorectal lesions:A narrative review

In the last years,endoscopic techniques gained a crucial role in the treatment of colorectal flat lesions.At the same time,the importance of a reliable assessment of such lesions to predict the malignancy and the depth of invasion of the colonic wall emerged.The current unsolved dilemma about the endoscopic excision techniques concerns the necessity of a reliable submucosal invasive cancer assessment system that can stratify the risk of the post-procedural need for surgery.Accordingly,this narrative literature review aims to compare the available diagnostic strategies in predicting malignancy and to give a guide about the best techniques to employ.We performed a literature search using electronic databases(MEDLINE/PubMed,EMBASE,and Cochrane Library).We collected all articles about endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)registering the outcomes.Moreover,we analyzed all meta-analyses comparing EMR vs ESD outcomes for colorectal sessile or nonpolypoid lesions of any size,preoperatively estimated as non-invasive.Seven meta-analysis studies,mainly Eastern,were included in the analysis comparing 124 studies and overall 22954 patients who underwent EMR and ESD procedures.Of these,eighty-two were retrospective,twenty-four perspective,nine casecontrol,and six cohorts,while three were randomized clinical trials.A total of 18118 EMR and 10379 ESD were completed for a whole of 28497 colorectal sessile or non-polypoid lesions>5-10 mm in size.In conclusion,it is crucial to enhance the preoperative diagnostic workup,especially in deciding the most suitable endoscopic method for radical resection of flat colorectal lesions at risk of underlying malignancy.Additionally,the ESD necessitates further improvement because of the excessively time-consuming as well as the intraprocedural technical hindrances and related complications.We found a higher rate of en bloc resections and R0 for ESD than EMR for non-pedunculated colorectal lesions.Nevertheless,despite the lower local recurrence rates,ESD had greater perforation rates and needed lengthier procedural times.The prevailing risk for additional surgery in ESD rather than EMR for complications or oncologic reasons is still uncertain.

Emerging artificial intelligence applications in gastroenterology: A review of the literature

Artificial intelligence(AI)allows machines to provide disruptive value in several industries and applications.Applications of AI techniques,specifically machine learning and more recently deep learning,are arising in gastroenterology.Computer-aided diagnosis for upper gastrointestinal endoscopy has growing attention for automated and accurate identification of dysplasia in Barrett’s esophagus,as well as for the detection of early gastric cancers(GCs),therefore preventing esophageal and gastric malignancies.Besides,convoluted neural network technology can accurately assess Helicobacter pylori(H.pylori)infection during standard endoscopy without the need for biopsies,thus,reducing gastric cancer risk.AI can potentially be applied during colonoscopy to automatically discover colorectal polyps and differentiate between neoplastic and nonneoplastic ones,with the possible ability to improve adenoma detection rate,which changes broadly among endoscopists performing screening colonoscopies.In addition,AI permits to establish the feasibility of curative endoscopic resection of large colonic lesions based on the pit pattern characteristics.The aim of this review is to analyze current evidence from the literature,supporting recent technologies of AI both in upper and lower gastrointestinal diseases,including Barrett's esophagus,GC,H.pylori infection,colonic polyps and colon cancer.

The power of prevention:how tenofovir and entecavir are changing the game in hepatocellular carcinoma

Introduction Individual patient data(IPD)meta-analysis by Choi et al.(1)compared hepatocellular carcinoma(HCC)risk between the entecavir(ETV)and tenofovir(TDF)in treatment-naïve chronic hepatitis B(CHB)patients using a multivariable Cox proportional hazards model from 11 Asian studies,totaling 42,939 patients receiving nucles(t)tide analogues(NAs)for more than one year.