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Probiotics intervention in colorectal cancer:From traditional approaches to novel strategies

Chinese Medical Journal 2024年第1期137卷 8-20页

作者： Suki Ha Xiang Zhang Jun Yu Institute of digestive disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina

The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological status.These intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis,metabolism,and immune response.The disruption of microbiota,known as dysbiosis,has been implicated in many intestinal diseases,including colorectal cancer(CRC).As the third most common cancer and the second leading cause of cancer-related death worldwide,CRC poses a significant health burden.There is an urgent need for novel interventions to reduce CRC incidence and improve clinical outcomes.Modulating the intestinal microbiota has emerged as a promising approach for CRC prevention and treatment.Current research efforts in CRC probiotics primarily focus on reducing the incidence of CRC,alleviating treatment-related side effects,and potentiating the efficacy of anticancer therapy,which is the key to successful translation to clinical practice.This paper aims to review the traditional probiotics and new interventions,such as next-generation probiotics and postbiotics,in the context of CRC.The underlying mechanisms of probiotic anti-cancer effects are also discussed,including the restoration of microbial composition,reinforcement of gut barrier integrity,induction of cancer cell apoptosis,inactivation of carcinogens,and modulation of host immune response.This paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and immunotherapy.Despite all the promising findings presented in studies,the evaluation of potential risks,optimization of delivery methods,and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.

关键词： colorectal cancer probiotics gut microbiota dysbiosis adjuvant therapy immune modulation gut barrrier

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Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第2期21卷 144-162页

作者： Yang Song Harry CH Lau Xiang Zhang Jun Yu Institute of digestive disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina Department of Gastroenterology Zhongshan Hospital Xiamen UniversityXiamen 361004China

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

关键词： Bile acid gut microbiota hepatocellular carcinoma therapeutics microbiota modulation

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Are we ready to use new endoscopic scores for ulcerative colitis?

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World Journal of Gastroenterology 2024年第10期30卷 1466-1469页

作者： Rodrigo Quera Paulina Núñez F Universidad de los Andes Inflammatory Bowel Disease ProgramClinica Universidad de los AndesDigestive Disease CenterSantiago 7600976RMChile digestive disease Center Inflammatory Bowel Disease ProgramClínica Universidad de los AndesSantiago 7620157Chile Department of Gastroenterology Universidad de Chile-Hospital San Juan de DiosSantiago 770123Chile

For ulcerative colitis(UC),the variability in inflammatory activity along the colon poses a challenge in management.The focus on achieving endoscopic healing in UC is evident,where the UC Endoscopic Index of Severity and Mayo Endoscopic Subscore are commonly used for evaluation.However,these indices primarily consider the most severely affected region.Liu et al recent study validates the Toronto Inflammatory Bowel disease Global Endoscopic Reporting(TIGER)score offering a comprehensive assessment of inflammatory activity across diverse segments of the colon and rectum and a reliable index correlating strongly with UC Endoscopic Index of Severity and moderately with Mayo Endoscopic Subscore(MES).Despite recommendation,certain aspects warrant further invest-igation.Fecal calprotectin,an intermediate target,correlates with TIGER and should be explored.Determining TIGER scores defining endoscopic remission and response,evaluating agreement with histological activity,and assessing inter-endoscopist agreement for TIGER require scrutiny.Exploring the correlation between TIGER and intestinal ultrasound,akin to MES,adds value.

关键词： Ulcerative colitis Sigmoidoscopy Colonoscopy Score index

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Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models

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World Journal of Gastroenterology 2024年第14期30卷 2038-2058页

作者： Pan Zheng Xue-Yang Li Xiao-Yu Yang Huan Wang Ling Ding Cong He Jian-Hua Wan Hua-Jing Ke Nong-Hua Lu Nian-Shuang Li Yin Zhu Department of Gastroenterology Digestive Disease HospitalThe First Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina

BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,whil

关键词： Acute pancreatitis RNA-sequencing Experimental acute pancreatitis models Inflammatory Apoptosis TLR and NOD-like signaling pathways

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Quantitative assessment of self-management in patients with nonalcoholic fatty liver disease: An unmet clinical need

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World Journal of Gastroenterology 2024年第25期30卷 3143-3146页

作者： Raffaele Borriello Giorgio Esposto Irene Mignini Antonio Gasbarrini Maria Assunta Zocco CEMAD digestive disease Center Fondazione Policlinico Universitario A.Gemelli IRCCSCatholic University of RomeRome 00168Italy

In this editorial we comment on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et al published in a recent issue of the World Journal of Gastroenterology.Non-alcoholic fatty liver disease(NAFLD)represents one of the current challenges in hepatology and public health,due to its continuous growing prevalence and the rising incidence of NAFLD-related fibrosis,non-alcoholic steatohepatitis and cirrhosis.The only effective therapeutic strategy for this dis-ease is represented by encouraging patients to improve their lifestyle through the modification of dietary intake and increased physical exercise,but the effective application of such modifications is often limited by various factors such as lack of information,psychological barriers or poor social support.While poor adherence to a healthy lifestyle can be decisive in determining the clinical outcome,in daily practice there is a lack of quantitative instruments aimed at identifying patients with the lowest adherence to lifestyle changes and higher risk of disease progre-ssion in the course of follow-up.In this article,Zeng et al propose a quantitative scale to assess the grade of adherence of patients with NAFLD to hea-lthy lifestyle intervention,called the Exercise and Diet Adherence Scale(EDAS).This scale,consisting of 33 items divided into 6 dimensions which relates to six subjective aspects in the self-management of NAFLD,has shown a good correlation with the identification of the sub-cohort of patients with the highest reduction in caloric intake,increase in physical exercise,probability of a reduction in liver stiffness measurement and alanine aminotransferase levels.The cor-relation among clinical outcomes and specific dimensions of this scale also highlights the pivotal role of a good and confidential doctor-patient relationship and of an effective communication.There is an urgent need for practical and effective instruments to assess the grade of self

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Liver cirrhosis Metabolic associated fatty liver disease Metabolic associated steatohepatitis Insulin resistance Self-management Self-management measurement Patient education

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Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication:A systematic review and meta-analysis

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World Journal of Gastroenterology 2024年第10期30卷 1450-1460页

作者： Giorgio Esposto Paolo Santini Linda Galasso Irene Mignini Maria Elena Ainora Antonio Gasbarrini Maria Assunta Zocco CEMAD digestive disease Center Fondazione Policlinico Universitario“A.Gemelli”IRCCSCatholic University of RomeRome 00168Italy Fondazione Policlinico Universitario Agostino Gemelli IRCCS Fondazione Policlinico Universitario Agostino Gemelli IRCCS-UniversitàCattolica del Sacro CuoreRome 00168Italy Medicina Interna e Gastroenterologia CEMAD Digestive Disease CenterUniversitàCattolica del Sacro CuoreFondazione Policlinico Universitario A Gemelli IRCCSRome 00168Italy

BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

关键词： Shear-wave elastography Hepatocellular carcinoma Hepatitis C virus Sustained virologic response

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New therapeutic strategy with extracorporeal membrane oxygenation for refractory hepatopulmonary syndrome after liver transplant: A case report

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World Journal of Transplantation 2024年第1期14卷 210-214页

作者： Belinda Sánchez Pérez María Pérez Reyes Jose Aranda Narvaez Julio Santoyo Villalba Jose Antonio Perez Daga Claudia Sanchez-Gonzalez Julio Santoyo-Santoyo Hepatobiliary and Trasplantation unit General and Digestive Surgery DepartmentUniversity Regional HospitalMalaga 29010Spain Department of General and digestive Surgery Regional University Hospital of MalagaMalaga 29010Spain

BACKGROUND Due to the lack of published literature about treatment of refractory hepatopulmonary syndrome(HPS)after liver transplant(LT),this case adds information and experience on this issue along with a treatment with positive outcomes.HPS is a complication of end-stage liver disease,with a 10%-30%incidence in cirrhotic patients.LT can reverse the physiopathology of this process and restore normal oxygenation.However,in some cases,refractory hypoxemia persists,and extracorporeal membrane oxygenation(ECMO)can be used as a rescue therapy with good results.CASE SUMMARY A 59-year-old patient with alcohol-related liver cirrhosis and portal hypertension was included in the LT waiting list for HPS.He had good liver function(Model for End-Stage Liver disease score 12,Child-Pugh class B7).He had pulmonary fibrosis and a mild restrictive respiratory pattern with a basal oxygen saturation of 82%.The macroaggregated albumin test result was>30.Spirometry demonstrated a forced expiratory volume in one second(FEV1)of 78%,forced vital capacity(FVC)of 74%,FEV1/FVC ratio of 81%,diffusion capacity for carbon monoxide of 42%,and carbon monoxide transfer coefficient of 57%.He required domiciliary oxygen at 2 L/min(16 h/d).The patient was admitted to the intensive care unit(ICU)and extubated in the first 24 h,needing high-flow therapy and non-invasive ventilation and inhaled nitric oxide afterwards.Reintubation was needed after 72 h.Due to the non-response to supportive therapies,installation of ECMO was decided with progressive recovery after 9 d.Extubation was possible on the tenth day,maintaining a high-flow nasal cannula and de-escalating to conventional oxygen therapy after 48 h.He was discharged from ICU on postoperative day(POD)20 with a 90%-92%oxygen saturation.Steroid recycling was needed twice for acute rejection.The patient was discharged from hospital on POD 27 with no symptoms,with an 89%-90%oxygen saturation.CONCLUSION Due to the favorable results observed,ECMO could become the central axis of treatment of HPS and ref

关键词： Liver transplantation Hepatopulmonary syndrome Refractory hypoxemia Treatment Extracorporeal membrane oxygenation Case report

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Use of endoscopic ultrasound-guided gallbladder drainage as a rescue approach in cases of unsuccessful biliary drainage

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World Journal of Gastroenterology 2024年第1期30卷 70-78页

作者： Alessandro Fugazza Kareem Khalaf Katarzyna M Pawlak Marco Spadaccini Matteo Colombo Marta Andreozzi Marco Giacchetto Silvia Carrara Chiara Ferrari Cecilia Binda Benedetto Mangiavillano Andrea Anderloni Alessandro Repici Division of Gastroenterology and digestive Endoscopy Humanitas Research Hospital-IRCCSRozzano 20089MilanoItaly Division of Gastroenterology St.Michael’s HospitalUniversity of TorontoToronto M5B 1W8ONCanada Department of Anesthesia Humanitas Research Hospital-IRCCSRozzano 20089MilanoItaly Gastroenterology and digestive Endoscopy unit Forlì-Cesena HospitalsRomagna 47121Italy Gastrointestinal Endoscopy unit Humanitas Mater DominiCastellanza 21100Italy Gastroenterology and digestive Endoscopy unit Fondazione IRCCS Policlinico San MatteoPavia 27100Italy

This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.

关键词： Endoscopic ultrasound-guided gallbladder drainage Gallbladder drainage Acute cholecystitis Malignant obstruction Interventional endoscopic ultrasound Lumen-apposing metal stents

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Percutaneous transhepatic cholangioscopy-assisted biliary polypectomy for local palliative treatment of intraductal papillary neoplasm of the bile duct

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1821-1832页

作者： Xu Ren Yong-Ping Qu Chun-Lan Zhu Xiao-Hong Xu Hong Jiang Yi-Xia Lu Hong-Peng Xue digestive disease Hospital of Heilongjiang Provincial Hospital Heilongjiang Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Pancreaticobiliary DiseasesHarbin 150001Heilongjiang ProvinceChina digestive Endoscopy Center of Heilongjiang Provincial Hospital Heilongjiang Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Pancreaticobiliary DiseasesHarbin 150001Heilongjiang ProvinceChina Second Department of Gastroenterology Digestive Disease Hospital of Heilongjiang Provincial Hospitaland Heilongjiang Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Pancreaticobiliary DiseasesHarbin 150001Heilongjiang ProvinceChina Department of Pathology Heilongjiang Provincial HospitalHarbin 150001Heilongjiang ProvinceChina

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a premalignant biliarytype epithelial neoplasm with intraductal papillary or villous growth.Currently reported local palliative therapeutic modalities,including endoscopic nasobiliary drainage,stenting and biliary curettage,endoscopic biliary polypectomy,percutaneous biliary drainage,laser ablation,argon plasma coagulation,photodynamic therapy,and radiofrequency ablation to relieve mechanical obstruction are limited with weaknesses and disadvantages.We have applied percutaneous transhepatic cholangioscopy(PTCS)-assisted biliary polypectomy(PTCS-BP)technique for the management of IPNB including mucin-hypersecreting cast-like and polypoid type tumors since 2010.AIM To assess the technical feasibility,efficacy,and safety of PTCS-BP for local palliative treatment of IPNB.METHODS Patients with mucin-hypersecreting cast-like or polypoid type IPNB and receiving PTCS-BP between September 2010 and December 2019 were included.PTCS-BP was performed by using a half-moon type snare with a soft stainless-steel wire,and the tumor was snared and resected with electrocautery.The primary outcome was its feasibility,indicated by technical success.The secondary outcomes were efficacy,including therapeutic success,curative resection,and clinical success,and safety.RESULTS Five patients(four with mucin-hypersecreting cast-like type and one with polypoid type IPNB)were included.Low-and high-grade intraepithelial neoplasia(HGIN)and recurrent IPNB with invasive carcinoma were observed in one,two,and two patients,respectively.Repeated cholangitis and/or obstructive jaundice were presented in all four patients with mucin-hypersecreting cast-like type IPNB.All five patients achieved technical success of PTCS-BP.Four patients(three with mucin-hypersecreting cast-like type and one with polypoid type IPNB)obtained therapeutic success;one with mucin-hypersecreting cast-like type tumors in the intrahepatic small bile duct and HGIN had residual tumors.All four patients with mucin-

关键词： Intraductal papillary neoplasm of the bile duct Percutaneous transhepatic cholangioscopy Biliary polypectomy Feasibility Efficacy

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Dynamic contrast enhanced ultrasound in differential diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2804-2815页

作者： Giorgio Esposto Paolo Santini Fabrizio Termite Linda Galasso Irene Mignini Maria Elena Ainora Antonio Gasbarrini Maria Assunta Zocco Department of CEMAD digestive disease Center Fondazione Policlinico Universitario A Gemelli IRCCSCatholic University of RomeRome 00168Italy Department of Fondazione Policlinico Universitario Agostino Gemelli IRCCS UniversitàCattolica del Sacro CuoreRome 00168Italy Department of Medicina Interna e Gastroenterologia CEMAD Digestive Disease CenterFondazione Policlinico Universitario A Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy

BACKGROUND Non-invasive differential diagnosis between hepatocellular carcinoma(HCC)and other liver cancer(i.***.cholangiocarcinoma or metastasis)is highly challenging and definitive diagnosis still relies on histological exam.The patterns of enhancement and wash-out of liver nodules can be used to stratify the risk of malignancy only in cirrhotic patients and HCC frequently shows atypical features.Dynamic contrast-enhanced ultrasound(DCEUS)with standardized software could help to overcome these obstacles,providing functional and quantitative parameters and potentially improving accuracy in the evaluation of tumor perfusion.AIM To explore clinical evidence regarding the application of DCEUS in the differential diagnosis of liver nodules.METHODS A comprehensive literature search of clinical studies was performed to identify the parameters of DCEUS that could relate to histological diagnosis.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS Rise time was significantly higher in HCC patients with a standardized mean difference(SMD)of 0.83(95%CI:0.48-1.18).Similarly,other statistically significant parameters were mean transit time local with a SMD of 0.73(95%CI:0.20-1.27),peak enhancement with a SMD of 0.37(95%CI:0.03-0.70),area wash-in area under the curve with a SMD of 0.47(95%CI:0.13-0.81),wash-out area under the curve with a SMD of 0.55(95%CI:0.21-0.89)and wash-in and wash-out area under the curve with SMD of 0.51(95%CI:0.17-0.85).SMD resulted not significant in fall time and wash-in rate,but the latter presented a trend towards greater values in HCC compared to intrahepatic cholangiocarcinoma.CONCLUSION DCEUS could improve non-invasive diagnosis of HCC,leading to less liver biopsy and early treatment.This quantitative analysis needs to be applied on larger cohorts to confirm these preliminary results.

关键词： Dynamic contrast enhanced ultrasound Hepatocellular carcinoma Intracellular cholangiocarcinoma Quantitative ultrasound Liver cancer Time-intensity curve

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