Endoscopic retrograde cholangiopancreatography training used to be in virtually all district general hospitals, resulting in a large number of trainees with an inadequate case load and achieving poor levels of skill. ...Endoscopic retrograde cholangiopancreatography training used to be in virtually all district general hospitals, resulting in a large number of trainees with an inadequate case load and achieving poor levels of skill. Training is now restricted to a small number of trai nees working in approved units. Continuous audit of outcomes and the appointment of a training lead in the unit are essential. Use of the global rating scale helps clinicians advise hospital administration on the prior it ies for a quality training program.展开更多
AIM:To investigate the prevalence of undernutrition,risk of malnutrition and obesity in the Italian gastroenterological population.METHODS:The Italian Hospital Gastroenterology Association conducted an observational,c...AIM:To investigate the prevalence of undernutrition,risk of malnutrition and obesity in the Italian gastroenterological population.METHODS:The Italian Hospital Gastroenterology Association conducted an observational,cross-sectional multicenter study.Weight,weight loss,and body mass index were evaluated.Undernutrition was defined as unintentional weight loss>10%in the last threesix months.Values of Malnutrition Universal Screening Tool(MUST)>2,NRS-2002>3,and Mini Nutritional Assessment(MNA)from 17 to 25 identified risk of malnutrition in outpatients,inpatients and elderly patients,respectively.A body mass index≥30 indicated obesity.Gastrointestinal pathologies were categorized into acute,chronic and neoplastic diseases.RESULTS:A total of 513 patients participated in the study.The prevalence of undernutrition was 4.6%in outpatients and 19.6%in inpatients.Moreover,undernutrition was present in 4.3%of the gastrointestinal patients with chronic disease,11.0%of those with acute disease,and 17.6%of those with cancer.The risk of malnutrition increased progressively and significantly in chronic,acute and neoplastic gastrointestinal diseases in inpatients and the elderly population.Logistical regression analysis confirmed that cancer was a risk factor for undernutrition(OR=2.7;95%CI:1.2-6.44,P=0.02).Obesity and overweight were more frequent in outpatients.CONCLUSION:More than 63%of outpatients and 80%of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment.展开更多
BACKGROUND Coronavirus disease 2019(COVID-19)significantly affected endoscopy practice,as gastrointestinal endoscopy is considered a risky procedure for transmission of infection to patients and personnel of endoscopy...BACKGROUND Coronavirus disease 2019(COVID-19)significantly affected endoscopy practice,as gastrointestinal endoscopy is considered a risky procedure for transmission of infection to patients and personnel of endoscopy units(PEU).AIM To assess the impact of COVID-19 on endoscopy during the first European lockdown(March-May 2020).METHODS Patients undergoing endoscopy in nine endoscopy units across six European countries during the period of the first European lockdown for COVID-19(March-May 2020)were included.Prior to the endoscopy procedure,participants were stratified as low-or high-risk for potential COVID-19 infection according to the European Society of Gastrointestinal Endoscopy(ESGE)and the European Society of Gastroenterology and Endoscopy Nurses and Associates(ESGENA)joint statement,and contacted 7-14 d later to assess COVID-19 infection status.PEU were questioned regarding COVID-19 symptoms and/or infection via questionnaire,while information regarding hospitalizations,intensive care unitadmissions and COVID-19-related deaths were collected.The number of weekly endoscopies at each center during the lockdown period was also recorded.RESULTS A total of 1267 endoscopies were performed in 1222 individuals across nine European endoscopy departments in six countries.Eighty-seven(7%)were excluded because of initial positive testing.Of the 1135 pre-endoscopy low risk or polymerase chain reaction negative for COVID-19,254(22.4%)were tested post endoscopy and 8 were eventually found positive,resulting in an infection rate of 0.7%[95%CI:0.2-0.12].The majority(6 of the 8 patients,75%)had undergone esophagogastroduodenoscopy.Of the 163 PEU,5[3%;(95%CI:0.4-5.7)]tested positive during the study period.A decrease of 68.7%(95%CI:64.8-72.7)in the number of weekly endoscopies was recorded in all centers after March 2020.All centers implemented appropriate personal protective measures(PPM)from the initial phases of the lockdown.CONCLUSION COVID-19 transmission in endoscopy units is highly unlikely in a lockdown setting,provided endoscopies are restricted to emergency cases and PPM are implemented.展开更多
Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is importan...Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.展开更多
A knowledge of the epidemiology and clinical aspects of non-hepatotropic viruses is becoming increasingly important in lieu of the rising incidence of acute liver injury caused by them in various circumstances.Broadly...A knowledge of the epidemiology and clinical aspects of non-hepatotropic viruses is becoming increasingly important in lieu of the rising incidence of acute liver injury caused by them in various circumstances.Broadly,they include the Herpesviridae group,the hemorrhagic fever viruses and certain respiratory viruses that infect the liver.They can affect both the immunocompetent and the immunocompromised individual,more commonly the latter as part of disseminated systemic infection with symptoms ranging from self-limited transaminitis to acute liver failure Various reasons for their rising importance are increased exposure to these viruses by way of:(1)Overcrowding,climatic and environmental changes,increasing tourism and settlement in hitherto unexplored areas where they are endemic and spread either by direct contact or through local fauna which serve as their reservoir host;and(2)Tampering with the normal protective human immunity by using immunomodulator drugs in scenarios of organ transplants,immune and non-immune related inflammatory disorders and various cancers,all of which are rising in incidence due to the aging world population living longer with many comorbidities.As such infections are relatively rare with non-specific presentation,and self-limited clinical course,they are seldom thought of or investigated for in the early disease stages which lead to the development of complications.This review of the most common non-hepatotropic viruses focusses on their epidemiology,etiopathogenesis,clinical manifestations,and management.They should be listed in the differential diagnosis of acute liver injury in appropriate clinical setting like recent travel to endemic areas,immunocompromised state,or exposure to these viruses.展开更多
Primary biliary cholangitis is a chronic cholestatic autoimmune liver disease that progressively damages the bile ducts,leading to cholestasis and,in advanced stages,cirrhosis.While it primarily affects middle-aged wo...Primary biliary cholangitis is a chronic cholestatic autoimmune liver disease that progressively damages the bile ducts,leading to cholestasis and,in advanced stages,cirrhosis.While it primarily affects middle-aged women,recent data indicate a rising incidence in men.The interplay between genetic susceptibility,environmental exposures,and gut microbiome alterations is thought to drive disease onset.Diagnosis relies on persistent cholestatic enzyme elevation,diseasespecific autoantibodies,and,in select cases,liver biopsy.Ursodeoxycholic acid remains the cornerstone of treatment,but many patients show an incomplete response.The recent withdrawal of obeticholic acid from the market,due to insufficient evidence of long-term benefit,has highlighted the urgent need for effective second-line therapies.Agonists of peroxisome proliferator-activated receptors,such as elafibranor and seladelpar,have demonstrated promising biochemical improvements and may reshape the therapeutic landscape.Future research is focused on refining risk assessment,optimizing treatment combinations,and addressing symptoms such as fatigue and pruritus to enhance patient well-being.A shift toward early intervention and personalized treatment strategies may further improve long-term outcomes in primary biliary cholangitis.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)now affects roughly one-quarter of the world’s population,reflecting the global spread of obesity and insulin resistance.Reframing non-alcoholic fatty liver ...Metabolic dysfunction-associated fatty liver disease(MAFLD)now affects roughly one-quarter of the world’s population,reflecting the global spread of obesity and insulin resistance.Reframing non-alcoholic fatty liver disease as MAFLD emphasizes its metabolic roots and spotlights the gut-liver axis,where intestinal dysbiosis acts as a key driver of hepatic injury.Altered microbial com-munities disrupt epithelial integrity,promote bacterial translocation,and trigger endotoxin-mediated inflammation that accelerates steatosis,lipotoxicity,and fibrogenesis.Concurrent shifts in bile acid signaling and short-chain fatty acid profiles further impair glucose and lipid homeostasis,amplifying cardiometabolic risk.Epidemiological studies reveal pervasive dysbiosis in MAFLD cohorts,linked to diet quality,sedentary behavior,adiposity,and host genetics.Newly developed microbiome-derived biomarkers,advanced elastography,and integrated multi-omics panels hold promise for non-invasive diagnosis and stratification,although external validation remains limited.In early trials,interventions that re-engineer the microbiota including tailored pre-/pro-/synbiotics,rational diet patterns,next-generation fecal microbiota transplantation,and bile-acid-modulating drugs show encouraging histological and metabolic gains.Optimal care will likely couple these tools with weight-centered lifestyle programmes in a pre-cision-medicine framework.Key challenges include inter-ethnic variability in microbiome signatures,the absence of consensus treatment algorithms,and regulatory barriers to live biotherapeutics.Rigorous longitudinal studies are required to translate mechanistic insight into durable clinical benefit and improve patient-centered outcome measures.展开更多
Treatment with immune checkpoint inhibitors(ICIs)is an innovative therapy for managing certain types of malignancy and has the potential to improve overall patient survival significantly.The most widely used ICIs sele...Treatment with immune checkpoint inhibitors(ICIs)is an innovative therapy for managing certain types of malignancy and has the potential to improve overall patient survival significantly.The most widely used ICIs selectively target different receptors comprising programmed cell death-1 receptor,programmed cell death-ligand 1 receptor,and cytotoxic T lymphocyte antigen 4 receptor.The widespread utilization of ICIs over the past several years,however,is frequently accompanied by immune-related adverse events(irAEs)that substantially impact the patient’s quality of life,particularly those affecting the digestive system,including both the upper and lower gastrointestinal tract.Based on a literature search covering databases such as PubMed,Web of Science,Embase,and the Cochrane Library,we present an insight into primary gastrointestinal irAEs,with a special focus on endoscopic manifestations.Additionally,we analyze data regarding the pathogenetic mechanisms,diagnostic approaches,histological characteristics,and proposed therapeutic interventions for managing irAEs involving the gastrointestinal tract.展开更多
BACKGROUND Lymphadenectomy of the infrapyloric region remains technically demanding in laparoscopic radical gastrectomy.Traditional vessel-guided approaches often result in incomplete dissection and higher complicatio...BACKGROUND Lymphadenectomy of the infrapyloric region remains technically demanding in laparoscopic radical gastrectomy.Traditional vessel-guided approaches often result in incomplete dissection and higher complication rates,especially at station No.6.AIM To propose a mesentery-based strategy for infrapyloric lymphadenectomy and evaluate its safety,feasibility,and efficacy.METHODS By identifying key anatomical landmarks and defining the inferior mesenteric boundary of the pyloric region(right gastro-omental mesentery),this approach enables full exposure and en bloc resection of anterior and posterior mesenteric planes,with proximal ligation at the root of feeding vessels.A retrospective cohort study was conducted on 330 gastric cancer patients who underwent D2 lymphadenectomy(D2)from January 2020 to December 2021.Outcomes were compared between 165 patients treated with D2 plus complete mesogastric excision(D2+CME)and 165 matched controls receiving conventional D2.RESULTS The D2+CME group demonstrated significantly improved surgical outcomes,including shorter total operative time(279.19±45.50 minutes vs 301.25±52.30 minutes,P<0.001),reduced infrapyloric dissection time(22.24±3.80 minutes vs 27.58±4.20 minutes,P<0.001),and lower blood loss(4.71±1.12 mL vs 24.83±6.35 mL,P<0.001).More lymph nodes were retrieved overall(43.80±10.05 vs 37.25±8.80,P<0.001),particularly at station No.6(5.26±0.87 vs 4.14±0.41,P<0.001).Postoperative recovery indicators and hospital stay were comparable between groups,while the complication rate was significantly lower in the D2+CME group(20%vs 30.3%,P=0.042).CONCLUSION The mesentery-based approach enables safe pyloric lymphadenectomy.Systematic mesogastric excision improves operative efficiency and lymph node yield,especially at station No.6,offering potential oncological benefits in gastric cancer surgery.展开更多
BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease de...BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease detection.AIM To propose a practical cut-off value for identifying patients with hepatocellular carcinoma(HCC)among those with compensated advanced CLD or healthy individuals using the GALAD score,an algorithm based on a formula that incorporates gender,age,serum alpha-fetoprotein(AFP),AFP-L3,and des-gamma-carboxy prothrombin values.METHODS This cross-sectional analysis was conducted using prospectively collected data from five cohorts(n=1431)comprising healthy individuals,cirrhosis,and HCC patients.These subjects were enrolled from an Italian retrospective cohort,including patients from the IRCCS“Saverio de Bellis”,Department of Gastroenterology,the University of Modena and Reggio Emilia Gastroenterology Department,and the Padua University Hospital and the Department of Gastroenterology,Hepatology,Infectious diseases and Endocrinology,Hannover Medical School.RESULTS Using healthy subjects as reference,a GALAD score cut-off of-1.67 identified HCC with a sensitivity of 89.77%and specificity of 97.59%.Individuals with GALAD values>-1.67 exhibited a moderate to very high probability(over 90%)of having HCC.When cirrhotic patients were used as the reference category,a cut-off of-0.77 yielded a sensitivity of 78.17%and a specificity of 89.55%.CONCLUSION We strongly recommend incorporating this GALAD cut-off into clinical guidelines for the screening of patients with a compensated advanced CLD who are at high risk of developing HCC.Given the rapid global rise in metabolic-associated steatotic liver disease(MASLD)-related CLD,future research should prioritize larger MASLD cohorts to establish the most appropriate GALAD cut-off for diagnostic use,compared to healthy controls and to patients with other forms of CLD.展开更多
BACKGROUND Endoscopic ultrasound(EUS)has evolved from a diagnostic tool to a management technique for various gastroenterological conditions,including biliary strictures.AIM To summarize the current evidence on EUS’s...BACKGROUND Endoscopic ultrasound(EUS)has evolved from a diagnostic tool to a management technique for various gastroenterological conditions,including biliary strictures.AIM To summarize the current evidence on EUS’s role in diagnosing and managing biliary strictures.METHODS Two independent reviewers searched five electronic databases(PubMed,CENTRAL,Science Direct,Google Scholar,and EMBASE)for articles published up to January 2025.Included articles met specific criteria,and statistical software was used to analyze reported outcomes.RESULTS Of 935 articles,19 met the inclusion criteria.Ten articles focused on diagnostic EUS,while nine focused on EUSguided therapeutic interventions.EUS fine-needle aspiration demonstrated superior sensitivity[0.43-1.00;95%confidence interval(CI):0.24-1.00]compared to conventional techniques(0.36-0.96;95%CI:0.19-0.99)for diagnosing malignant biliary strictures.Both EUS-fine-needle aspiration and conventional methods exhibited high specificity,with most achieving 100%specificity.EUS-guided interventions showed significantly higher clinical success rates than control interventions(odds ratio=2.89;95%CI:1.22-6.84;P=0.02).No significant difference was observed in technical success rates(odds ratio=0.97;95%CI:0.30-3.16;P=0.96).CONCLUSION EUS is a promising tool for diagnosing and managing biliary strictures.Combining EUS-guided and conventional interventions improves diagnostic performance.Further research is needed to investigate the feasibility and use of EUS-guided interventions in this field.展开更多
BACKGROUND Tofacitinib is an oral,selective Janus kinase inhibitor that is approved for the treatment of ulcerative colitis(UC).The 8-week induction protocol involves the administration of 10 mg twice daily(bid)with t...BACKGROUND Tofacitinib is an oral,selective Janus kinase inhibitor that is approved for the treatment of ulcerative colitis(UC).The 8-week induction protocol involves the administration of 10 mg twice daily(bid)with the possibility of extending the induction period to 16 weeks.The maintenance dose of tofacitinib is either 5 mg or 10 mg bid.AIM To assess predictors for clinical remission and drug persistence in patients with UC receiving the extended induction tofacitinib protocol.METHODS This was a real-world multicenter retrospective study in patients with moderateto-severe UC.Patients received physician-directed extended induction tofacitinib treatment.We collected clinical and demographic data at baseline and data regarding clinical,laboratory,and endoscopic evaluations,therapeutic modifications,and adverse events at the 52-week follow-up.Possible predictors for clinical remission at week 52 was the primary endpoint.Differences between patients receiving 5 mg bid vs 10 mg bid at week 52 and identification of predictors for treatment persistence were secondary endpoints.RESULTS Thirty-seven consecutive patients from 11 medical centers were included[51.4%males with median age 39(17-64)years].Twenty-eight patients continued treatment until week 52(75.7%)with 67.9%receiving 10 mg tofacitinib;all had prior history of biologic use.We observed that 57.1%of patients achieved clinical remission(66.7%in the 5 mg tofacitinib group and 52.6%in the 10 mg tofacitinib group,P=0.483).De-escalation to 5 mg tofacitinib was attempted in 17 patients with a success rate of 52.9%.Prior biologic use was significantly more frequent in patients treated with 10 mg tofacitinib.Active smoking was significantly associated with treatment discontinuation at week 52.We identified eight adverse events,and only one led to treatment discontinuation.CONCLUSION Our results supported the extended induction strategy with tofacitinib in selected patients with UC.Patients with prior failure of advanced therapies particularly benefitted,highlighting the importance of personalized maintenance regimens.展开更多
Gastric cancer(GC)is both the fifth most common cancer worldwide and the fifth in mortality.Owing to a lack of symptoms in the early stages and unspecific cli-nical presentation in the later stages,GC is usually diagn...Gastric cancer(GC)is both the fifth most common cancer worldwide and the fifth in mortality.Owing to a lack of symptoms in the early stages and unspecific cli-nical presentation in the later stages,GC is usually diagnosed at advanced stages.This means that only approximately 60%of patients are eligible for curative treat-ment,and overall,GC patients have a 5-year survival rate of only 28.3%,under-scoring the importance of developing new treatment strategies.Drug repurposing involves identifying new therapeutic uses for approved drugs and is a promising strategy for cancer treatment because of its lower cost and faster development time.A variety of targetable pathways are involved in GC progression,including the mitogen-activated protein kinase,phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin,p53,Janus kinase 2/signal transducer and activator of transcription 3,hypoxia-inducible factor-1α,wingless-type mouse mammary tumor virus integration site family/beta-catenin(Wnt/β-catenin),nuclear factor kappa B,and Hippo pathways.Therefore,the repurposing of drugs targeting these pathways represents an interesting option in the search for new treatments for GC.In this review,we explore some relevant pathways involved in the development of GC and the possibilities of repurposing drugs that target them.展开更多
AIM:To investigate the predictive value of narrowband imaging with magnifying endoscopy (NBI-ME) for identifying gastric intestinal metaplasia (GIM) in unselected patients. METHODS:We prospectively evaluated consecuti...AIM:To investigate the predictive value of narrowband imaging with magnifying endoscopy (NBI-ME) for identifying gastric intestinal metaplasia (GIM) in unselected patients. METHODS:We prospectively evaluated consecutive patients undergoing upper endoscopy for various indications, such as epigastric discomfort/pain, anaemia, gastro-oesophageal reflux disease, suspicion of peptic ulcer disease, or chronic liver diseases. Patients underwent NBI-ME, which was performed by three blinded, experienced endoscopists. In addition, five biopsies (2 antrum, 1 angulus, and 2 corpus) were taken and examined by two pathologists unaware of the endoscopic findings to determine the presence or absence of GIM. The correlation between light blue crest (LBC) appearance and histology was measured. Moreover, we quantified the degree of LBC appearance as less than 20% (+), 20%-80% (++) and more than 80% (+++) of an image field, and the semiquantitative evaluation of LBC appearance was correlated with IM percentage from the histological findings. RESULTS:We enrolled 100 (58 F/42 M) patients who were mainly referred for gastro-esophageal reflux disease/dyspepsia (46%), cancer screening/anaemia (34%), chronic liver disease (9%), and suspected celiac disease (6%); the remaining patients were referred for other indications. The prevalence of Helicobacter pylori (H. pylori ) infection detected from the biopsies was 31%, while 67% of the patients used proton pump inhibitors. LBCs were found in the antrum of 33 patients (33%); 20 of the cases were classified as LBC+, 9 as LBC++, and 4 as LBC+++. LBCs were found in the gastric body of 6 patients (6%), with 5 of them also having LBCs in the antrum. The correlation between the appearance of LBCs and histological GIM was good, with a sensitivity of 80% (95%CI:67-92), a specificity of 96% (95%CI:93-99), a positive predictive value of 84% (95%CI:73-96), a negative predictive value of 95% (95%CI:92-98), and an accuracy of 93% (95%CI:90-97). The NBI-ME examination overlooked GIM in 8 cases, but the GIM was less than 5% in 7 of the cases. Moreover, in the 6 false positive cases, the histological examination showed the presence of reactive gastropathy (4 cases) or H. pylori active chronic gastritis (2 cases). The semiquantitative correlation between the rate of LBC appearance and the percentage of GIM was 79% (P < 0.01). CONCLUSION:NBI-ME achieved good sensitivity and specificity in recognising GIM in an unselected population. In routine clinical practice, this technique can reliably target gastric biopsies.展开更多
Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms, although their prevalence has increased substantially over the past three decades. Moreover, there has been an increased clinical recogni...Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms, although their prevalence has increased substantially over the past three decades. Moreover, there has been an increased clinical recognition and characterization of these neoplasms. They show extremely variable biological behavior and clinical course. Most NETs have endocrine function and secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome; however, many are clinically silent until late presentation with mass effects. Investigation and management should be individualized for each patient, taking into account the likely natural history of the tumor and general health of the patient. Management strategies include surgery for cure or palliation, and a variety of other cytoreductive techniques, and medical treatment including chemotherapy, and biotherapy to control symptoms due to hormone release and tumor growth, with somatostatin analogues (SSAs) and alphainterferon. New biological agents and somatostatintagged radionuclides are under investigation. Advances in the therapy and development of centers of excellence which coordinate multicenter studies, are needed to improve diagnosis, treatment and therefore survival of patients with GEP NETs.展开更多
Ischemic colitis is the most common form of ischemic injury of the gastrointestinal tract and can present either as an occlusive or a non-occlusive form. It accounts for 1 in 1000 hospitalizations but its incidence is...Ischemic colitis is the most common form of ischemic injury of the gastrointestinal tract and can present either as an occlusive or a non-occlusive form. It accounts for 1 in 1000 hospitalizations but its incidence is underesti- mated because it often has a mild and transient nature. The etiology of ischemic colitis is multifactorial and the clinical presentation variable. The diagnosis is based on a combination of clinical suspicion, radiographic, endo- scopic and histological findings. Therapy and outcome depends on the severity of the disease. Most cases of the non-gangrenous form are transient and resolve spontaneously without complications. On the other hand, high morbidity and mortality and urgent operative intervention are the hallmarks of gangrenous ischemic colitis.展开更多
Transarterial chemoembolization(TACE) represents the current gold standard for hepatocellular carcinoma(HCC) patients in intermediate stage. Conventional TACE(c TACE) is performed with the injection of an emulsion of ...Transarterial chemoembolization(TACE) represents the current gold standard for hepatocellular carcinoma(HCC) patients in intermediate stage. Conventional TACE(c TACE) is performed with the injection of an emulsion of a chemotherapeutic drug with lipiodol into the artery feeding the tumoral nodules, followed by embolization of the same vessel to obtain a synergistic effect of drug cytotoxic activity and ischemia. Aim of this review is to summarize the main characteristics of drug-eluting beads(DEB)-TACE and the clinical results reported so far in the literature. A literature search was conducted using Pub Med until June 2017. In order to overcome the drawbacks of c TACE, namely lack of standardization and unpredictability of outcomes, non-absorbable embolic microspheres charged with cytotoxic agents(DEBs) have been developed. DEBs are able to simultaneously exert both the therapeutic components of TACE, either drug-carrier function and embolization, unlike c TACE in which applying the embolic agent is a second moment after drug injection. This way, risk of systemic drug release is minimal due to both high-affinity carrier activity of DEBs and absence of a time interval between injection and embolization. However, despite promising results of preliminary studies, clear evidence of superiority of DEB-TACE over c TACE is still lacking. A number of novel technical devices are actually in development in the field of loco-regional treatments for HCC, but only a few of them have entered the clinical arena. In absence of well-designed randomized-controlled trials, the decision on whether use DEB-TACE or c TACE is still controversial.展开更多
Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although th...Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells, and consequently alters allogenic antigen presentation. Finally, acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis, and they interfere with methylation, synthesis and repair of DNA, thereby increasing HCC susceptibility.展开更多
Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in s...Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in several different enteropathies, including inflammatory bowel disease. It develops through complex cell, extracellular matrix, cytokine and growth factor interactions. Distinct cell types are involved in intestinal fibrosis, such as resident mesenchymal cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM-producing cells derived from epithelial and endothelial cells (through a process termed epithelialand endothelial-mesenchymal transition), stellate cells, pericytes, local or bone marrow-derived stem cells. The most important soluble factors that regulate the activation of these cells include cytokines, chemokines, growth factors, components of the renin-angiotensin system, angiogenic factors, peroxisome proliferator-activated receptors, mammalian target of rapamycin, and products of oxidative stress. It soon becomes clear that although inflammation is responsible for triggering the onset of the fibrotic proc-ess, it only plays a minor role in the progression of this condition, as fibrosis may advance in a self-perpetuating fashion. Definition of the cellular and molecular mechanisms involved in intestinal fibrosis may provide the key to developing new therapeutic approaches.展开更多
Although thousands of DNA damaging events occur in each cell every day,efficient DNA repair pathways have evolved to counteract them. The DNA repair machinery plays a key role in maintaining genomic stability by avoid...Although thousands of DNA damaging events occur in each cell every day,efficient DNA repair pathways have evolved to counteract them. The DNA repair machinery plays a key role in maintaining genomic stability by avoiding the maintenance of mutations. The DNA repair enzymes continuously monitor the chromosomes to correct any damage that is caused by exogenous and endogenous mutagens. If DNA damage in proliferating cells is not repaired because of an inadequate expression of DNA repair genes,it might increase the risk of cancer. In addition to mutations,which can be either inherited or somatically acquired,epigenetic silencing of DNA repair genes has been associated with carcinogenesis. Gastric cancer represents the second highest cause of cancer mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes during the lifetime. Among the risk factors,Helicobacter pylori(H. pylori) infection is considered the main driving factor to gastric cancer development. Thus,in this review,we summarize the current knowledge of the role of H. pylori infection on the epigenetic regulation of DNA repair machinery in gastric carcinogenesis.展开更多
文摘Endoscopic retrograde cholangiopancreatography training used to be in virtually all district general hospitals, resulting in a large number of trainees with an inadequate case load and achieving poor levels of skill. Training is now restricted to a small number of trai nees working in approved units. Continuous audit of outcomes and the appointment of a training lead in the unit are essential. Use of the global rating scale helps clinicians advise hospital administration on the prior it ies for a quality training program.
文摘AIM:To investigate the prevalence of undernutrition,risk of malnutrition and obesity in the Italian gastroenterological population.METHODS:The Italian Hospital Gastroenterology Association conducted an observational,cross-sectional multicenter study.Weight,weight loss,and body mass index were evaluated.Undernutrition was defined as unintentional weight loss>10%in the last threesix months.Values of Malnutrition Universal Screening Tool(MUST)>2,NRS-2002>3,and Mini Nutritional Assessment(MNA)from 17 to 25 identified risk of malnutrition in outpatients,inpatients and elderly patients,respectively.A body mass index≥30 indicated obesity.Gastrointestinal pathologies were categorized into acute,chronic and neoplastic diseases.RESULTS:A total of 513 patients participated in the study.The prevalence of undernutrition was 4.6%in outpatients and 19.6%in inpatients.Moreover,undernutrition was present in 4.3%of the gastrointestinal patients with chronic disease,11.0%of those with acute disease,and 17.6%of those with cancer.The risk of malnutrition increased progressively and significantly in chronic,acute and neoplastic gastrointestinal diseases in inpatients and the elderly population.Logistical regression analysis confirmed that cancer was a risk factor for undernutrition(OR=2.7;95%CI:1.2-6.44,P=0.02).Obesity and overweight were more frequent in outpatients.CONCLUSION:More than 63%of outpatients and 80%of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment.
文摘BACKGROUND Coronavirus disease 2019(COVID-19)significantly affected endoscopy practice,as gastrointestinal endoscopy is considered a risky procedure for transmission of infection to patients and personnel of endoscopy units(PEU).AIM To assess the impact of COVID-19 on endoscopy during the first European lockdown(March-May 2020).METHODS Patients undergoing endoscopy in nine endoscopy units across six European countries during the period of the first European lockdown for COVID-19(March-May 2020)were included.Prior to the endoscopy procedure,participants were stratified as low-or high-risk for potential COVID-19 infection according to the European Society of Gastrointestinal Endoscopy(ESGE)and the European Society of Gastroenterology and Endoscopy Nurses and Associates(ESGENA)joint statement,and contacted 7-14 d later to assess COVID-19 infection status.PEU were questioned regarding COVID-19 symptoms and/or infection via questionnaire,while information regarding hospitalizations,intensive care unitadmissions and COVID-19-related deaths were collected.The number of weekly endoscopies at each center during the lockdown period was also recorded.RESULTS A total of 1267 endoscopies were performed in 1222 individuals across nine European endoscopy departments in six countries.Eighty-seven(7%)were excluded because of initial positive testing.Of the 1135 pre-endoscopy low risk or polymerase chain reaction negative for COVID-19,254(22.4%)were tested post endoscopy and 8 were eventually found positive,resulting in an infection rate of 0.7%[95%CI:0.2-0.12].The majority(6 of the 8 patients,75%)had undergone esophagogastroduodenoscopy.Of the 163 PEU,5[3%;(95%CI:0.4-5.7)]tested positive during the study period.A decrease of 68.7%(95%CI:64.8-72.7)in the number of weekly endoscopies was recorded in all centers after March 2020.All centers implemented appropriate personal protective measures(PPM)from the initial phases of the lockdown.CONCLUSION COVID-19 transmission in endoscopy units is highly unlikely in a lockdown setting,provided endoscopies are restricted to emergency cases and PPM are implemented.
文摘Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.
文摘A knowledge of the epidemiology and clinical aspects of non-hepatotropic viruses is becoming increasingly important in lieu of the rising incidence of acute liver injury caused by them in various circumstances.Broadly,they include the Herpesviridae group,the hemorrhagic fever viruses and certain respiratory viruses that infect the liver.They can affect both the immunocompetent and the immunocompromised individual,more commonly the latter as part of disseminated systemic infection with symptoms ranging from self-limited transaminitis to acute liver failure Various reasons for their rising importance are increased exposure to these viruses by way of:(1)Overcrowding,climatic and environmental changes,increasing tourism and settlement in hitherto unexplored areas where they are endemic and spread either by direct contact or through local fauna which serve as their reservoir host;and(2)Tampering with the normal protective human immunity by using immunomodulator drugs in scenarios of organ transplants,immune and non-immune related inflammatory disorders and various cancers,all of which are rising in incidence due to the aging world population living longer with many comorbidities.As such infections are relatively rare with non-specific presentation,and self-limited clinical course,they are seldom thought of or investigated for in the early disease stages which lead to the development of complications.This review of the most common non-hepatotropic viruses focusses on their epidemiology,etiopathogenesis,clinical manifestations,and management.They should be listed in the differential diagnosis of acute liver injury in appropriate clinical setting like recent travel to endemic areas,immunocompromised state,or exposure to these viruses.
文摘Primary biliary cholangitis is a chronic cholestatic autoimmune liver disease that progressively damages the bile ducts,leading to cholestasis and,in advanced stages,cirrhosis.While it primarily affects middle-aged women,recent data indicate a rising incidence in men.The interplay between genetic susceptibility,environmental exposures,and gut microbiome alterations is thought to drive disease onset.Diagnosis relies on persistent cholestatic enzyme elevation,diseasespecific autoantibodies,and,in select cases,liver biopsy.Ursodeoxycholic acid remains the cornerstone of treatment,but many patients show an incomplete response.The recent withdrawal of obeticholic acid from the market,due to insufficient evidence of long-term benefit,has highlighted the urgent need for effective second-line therapies.Agonists of peroxisome proliferator-activated receptors,such as elafibranor and seladelpar,have demonstrated promising biochemical improvements and may reshape the therapeutic landscape.Future research is focused on refining risk assessment,optimizing treatment combinations,and addressing symptoms such as fatigue and pruritus to enhance patient well-being.A shift toward early intervention and personalized treatment strategies may further improve long-term outcomes in primary biliary cholangitis.
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)now affects roughly one-quarter of the world’s population,reflecting the global spread of obesity and insulin resistance.Reframing non-alcoholic fatty liver disease as MAFLD emphasizes its metabolic roots and spotlights the gut-liver axis,where intestinal dysbiosis acts as a key driver of hepatic injury.Altered microbial com-munities disrupt epithelial integrity,promote bacterial translocation,and trigger endotoxin-mediated inflammation that accelerates steatosis,lipotoxicity,and fibrogenesis.Concurrent shifts in bile acid signaling and short-chain fatty acid profiles further impair glucose and lipid homeostasis,amplifying cardiometabolic risk.Epidemiological studies reveal pervasive dysbiosis in MAFLD cohorts,linked to diet quality,sedentary behavior,adiposity,and host genetics.Newly developed microbiome-derived biomarkers,advanced elastography,and integrated multi-omics panels hold promise for non-invasive diagnosis and stratification,although external validation remains limited.In early trials,interventions that re-engineer the microbiota including tailored pre-/pro-/synbiotics,rational diet patterns,next-generation fecal microbiota transplantation,and bile-acid-modulating drugs show encouraging histological and metabolic gains.Optimal care will likely couple these tools with weight-centered lifestyle programmes in a pre-cision-medicine framework.Key challenges include inter-ethnic variability in microbiome signatures,the absence of consensus treatment algorithms,and regulatory barriers to live biotherapeutics.Rigorous longitudinal studies are required to translate mechanistic insight into durable clinical benefit and improve patient-centered outcome measures.
文摘Treatment with immune checkpoint inhibitors(ICIs)is an innovative therapy for managing certain types of malignancy and has the potential to improve overall patient survival significantly.The most widely used ICIs selectively target different receptors comprising programmed cell death-1 receptor,programmed cell death-ligand 1 receptor,and cytotoxic T lymphocyte antigen 4 receptor.The widespread utilization of ICIs over the past several years,however,is frequently accompanied by immune-related adverse events(irAEs)that substantially impact the patient’s quality of life,particularly those affecting the digestive system,including both the upper and lower gastrointestinal tract.Based on a literature search covering databases such as PubMed,Web of Science,Embase,and the Cochrane Library,we present an insight into primary gastrointestinal irAEs,with a special focus on endoscopic manifestations.Additionally,we analyze data regarding the pathogenetic mechanisms,diagnostic approaches,histological characteristics,and proposed therapeutic interventions for managing irAEs involving the gastrointestinal tract.
基金Supported by the Natural Science Foundation Program in Fujian Province of China,No.2023J011726.
文摘BACKGROUND Lymphadenectomy of the infrapyloric region remains technically demanding in laparoscopic radical gastrectomy.Traditional vessel-guided approaches often result in incomplete dissection and higher complication rates,especially at station No.6.AIM To propose a mesentery-based strategy for infrapyloric lymphadenectomy and evaluate its safety,feasibility,and efficacy.METHODS By identifying key anatomical landmarks and defining the inferior mesenteric boundary of the pyloric region(right gastro-omental mesentery),this approach enables full exposure and en bloc resection of anterior and posterior mesenteric planes,with proximal ligation at the root of feeding vessels.A retrospective cohort study was conducted on 330 gastric cancer patients who underwent D2 lymphadenectomy(D2)from January 2020 to December 2021.Outcomes were compared between 165 patients treated with D2 plus complete mesogastric excision(D2+CME)and 165 matched controls receiving conventional D2.RESULTS The D2+CME group demonstrated significantly improved surgical outcomes,including shorter total operative time(279.19±45.50 minutes vs 301.25±52.30 minutes,P<0.001),reduced infrapyloric dissection time(22.24±3.80 minutes vs 27.58±4.20 minutes,P<0.001),and lower blood loss(4.71±1.12 mL vs 24.83±6.35 mL,P<0.001).More lymph nodes were retrieved overall(43.80±10.05 vs 37.25±8.80,P<0.001),particularly at station No.6(5.26±0.87 vs 4.14±0.41,P<0.001).Postoperative recovery indicators and hospital stay were comparable between groups,while the complication rate was significantly lower in the D2+CME group(20%vs 30.3%,P=0.042).CONCLUSION The mesentery-based approach enables safe pyloric lymphadenectomy.Systematic mesogastric excision improves operative efficiency and lymph node yield,especially at station No.6,offering potential oncological benefits in gastric cancer surgery.
文摘BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease detection.AIM To propose a practical cut-off value for identifying patients with hepatocellular carcinoma(HCC)among those with compensated advanced CLD or healthy individuals using the GALAD score,an algorithm based on a formula that incorporates gender,age,serum alpha-fetoprotein(AFP),AFP-L3,and des-gamma-carboxy prothrombin values.METHODS This cross-sectional analysis was conducted using prospectively collected data from five cohorts(n=1431)comprising healthy individuals,cirrhosis,and HCC patients.These subjects were enrolled from an Italian retrospective cohort,including patients from the IRCCS“Saverio de Bellis”,Department of Gastroenterology,the University of Modena and Reggio Emilia Gastroenterology Department,and the Padua University Hospital and the Department of Gastroenterology,Hepatology,Infectious diseases and Endocrinology,Hannover Medical School.RESULTS Using healthy subjects as reference,a GALAD score cut-off of-1.67 identified HCC with a sensitivity of 89.77%and specificity of 97.59%.Individuals with GALAD values>-1.67 exhibited a moderate to very high probability(over 90%)of having HCC.When cirrhotic patients were used as the reference category,a cut-off of-0.77 yielded a sensitivity of 78.17%and a specificity of 89.55%.CONCLUSION We strongly recommend incorporating this GALAD cut-off into clinical guidelines for the screening of patients with a compensated advanced CLD who are at high risk of developing HCC.Given the rapid global rise in metabolic-associated steatotic liver disease(MASLD)-related CLD,future research should prioritize larger MASLD cohorts to establish the most appropriate GALAD cut-off for diagnostic use,compared to healthy controls and to patients with other forms of CLD.
文摘BACKGROUND Endoscopic ultrasound(EUS)has evolved from a diagnostic tool to a management technique for various gastroenterological conditions,including biliary strictures.AIM To summarize the current evidence on EUS’s role in diagnosing and managing biliary strictures.METHODS Two independent reviewers searched five electronic databases(PubMed,CENTRAL,Science Direct,Google Scholar,and EMBASE)for articles published up to January 2025.Included articles met specific criteria,and statistical software was used to analyze reported outcomes.RESULTS Of 935 articles,19 met the inclusion criteria.Ten articles focused on diagnostic EUS,while nine focused on EUSguided therapeutic interventions.EUS fine-needle aspiration demonstrated superior sensitivity[0.43-1.00;95%confidence interval(CI):0.24-1.00]compared to conventional techniques(0.36-0.96;95%CI:0.19-0.99)for diagnosing malignant biliary strictures.Both EUS-fine-needle aspiration and conventional methods exhibited high specificity,with most achieving 100%specificity.EUS-guided interventions showed significantly higher clinical success rates than control interventions(odds ratio=2.89;95%CI:1.22-6.84;P=0.02).No significant difference was observed in technical success rates(odds ratio=0.97;95%CI:0.30-3.16;P=0.96).CONCLUSION EUS is a promising tool for diagnosing and managing biliary strictures.Combining EUS-guided and conventional interventions improves diagnostic performance.Further research is needed to investigate the feasibility and use of EUS-guided interventions in this field.
文摘BACKGROUND Tofacitinib is an oral,selective Janus kinase inhibitor that is approved for the treatment of ulcerative colitis(UC).The 8-week induction protocol involves the administration of 10 mg twice daily(bid)with the possibility of extending the induction period to 16 weeks.The maintenance dose of tofacitinib is either 5 mg or 10 mg bid.AIM To assess predictors for clinical remission and drug persistence in patients with UC receiving the extended induction tofacitinib protocol.METHODS This was a real-world multicenter retrospective study in patients with moderateto-severe UC.Patients received physician-directed extended induction tofacitinib treatment.We collected clinical and demographic data at baseline and data regarding clinical,laboratory,and endoscopic evaluations,therapeutic modifications,and adverse events at the 52-week follow-up.Possible predictors for clinical remission at week 52 was the primary endpoint.Differences between patients receiving 5 mg bid vs 10 mg bid at week 52 and identification of predictors for treatment persistence were secondary endpoints.RESULTS Thirty-seven consecutive patients from 11 medical centers were included[51.4%males with median age 39(17-64)years].Twenty-eight patients continued treatment until week 52(75.7%)with 67.9%receiving 10 mg tofacitinib;all had prior history of biologic use.We observed that 57.1%of patients achieved clinical remission(66.7%in the 5 mg tofacitinib group and 52.6%in the 10 mg tofacitinib group,P=0.483).De-escalation to 5 mg tofacitinib was attempted in 17 patients with a success rate of 52.9%.Prior biologic use was significantly more frequent in patients treated with 10 mg tofacitinib.Active smoking was significantly associated with treatment discontinuation at week 52.We identified eight adverse events,and only one led to treatment discontinuation.CONCLUSION Our results supported the extended induction strategy with tofacitinib in selected patients with UC.Patients with prior failure of advanced therapies particularly benefitted,highlighting the importance of personalized maintenance regimens.
基金Supported by the Instituto de Salud Carlos III,No.PI24/00784,No.PI24/00737,No.PI21/01181,No.PI21/00333 and No.INT22/00112Departamento de Universidad,Innovación y Transformación Digital Gobierno de Navarra,No.0011-1408-2024-000011,No.0011-1408-2022-000010.
文摘Gastric cancer(GC)is both the fifth most common cancer worldwide and the fifth in mortality.Owing to a lack of symptoms in the early stages and unspecific cli-nical presentation in the later stages,GC is usually diagnosed at advanced stages.This means that only approximately 60%of patients are eligible for curative treat-ment,and overall,GC patients have a 5-year survival rate of only 28.3%,under-scoring the importance of developing new treatment strategies.Drug repurposing involves identifying new therapeutic uses for approved drugs and is a promising strategy for cancer treatment because of its lower cost and faster development time.A variety of targetable pathways are involved in GC progression,including the mitogen-activated protein kinase,phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin,p53,Janus kinase 2/signal transducer and activator of transcription 3,hypoxia-inducible factor-1α,wingless-type mouse mammary tumor virus integration site family/beta-catenin(Wnt/β-catenin),nuclear factor kappa B,and Hippo pathways.Therefore,the repurposing of drugs targeting these pathways represents an interesting option in the search for new treatments for GC.In this review,we explore some relevant pathways involved in the development of GC and the possibilities of repurposing drugs that target them.
文摘AIM:To investigate the predictive value of narrowband imaging with magnifying endoscopy (NBI-ME) for identifying gastric intestinal metaplasia (GIM) in unselected patients. METHODS:We prospectively evaluated consecutive patients undergoing upper endoscopy for various indications, such as epigastric discomfort/pain, anaemia, gastro-oesophageal reflux disease, suspicion of peptic ulcer disease, or chronic liver diseases. Patients underwent NBI-ME, which was performed by three blinded, experienced endoscopists. In addition, five biopsies (2 antrum, 1 angulus, and 2 corpus) were taken and examined by two pathologists unaware of the endoscopic findings to determine the presence or absence of GIM. The correlation between light blue crest (LBC) appearance and histology was measured. Moreover, we quantified the degree of LBC appearance as less than 20% (+), 20%-80% (++) and more than 80% (+++) of an image field, and the semiquantitative evaluation of LBC appearance was correlated with IM percentage from the histological findings. RESULTS:We enrolled 100 (58 F/42 M) patients who were mainly referred for gastro-esophageal reflux disease/dyspepsia (46%), cancer screening/anaemia (34%), chronic liver disease (9%), and suspected celiac disease (6%); the remaining patients were referred for other indications. The prevalence of Helicobacter pylori (H. pylori ) infection detected from the biopsies was 31%, while 67% of the patients used proton pump inhibitors. LBCs were found in the antrum of 33 patients (33%); 20 of the cases were classified as LBC+, 9 as LBC++, and 4 as LBC+++. LBCs were found in the gastric body of 6 patients (6%), with 5 of them also having LBCs in the antrum. The correlation between the appearance of LBCs and histological GIM was good, with a sensitivity of 80% (95%CI:67-92), a specificity of 96% (95%CI:93-99), a positive predictive value of 84% (95%CI:73-96), a negative predictive value of 95% (95%CI:92-98), and an accuracy of 93% (95%CI:90-97). The NBI-ME examination overlooked GIM in 8 cases, but the GIM was less than 5% in 7 of the cases. Moreover, in the 6 false positive cases, the histological examination showed the presence of reactive gastropathy (4 cases) or H. pylori active chronic gastritis (2 cases). The semiquantitative correlation between the rate of LBC appearance and the percentage of GIM was 79% (P < 0.01). CONCLUSION:NBI-ME achieved good sensitivity and specificity in recognising GIM in an unselected population. In routine clinical practice, this technique can reliably target gastric biopsies.
文摘Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms, although their prevalence has increased substantially over the past three decades. Moreover, there has been an increased clinical recognition and characterization of these neoplasms. They show extremely variable biological behavior and clinical course. Most NETs have endocrine function and secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome; however, many are clinically silent until late presentation with mass effects. Investigation and management should be individualized for each patient, taking into account the likely natural history of the tumor and general health of the patient. Management strategies include surgery for cure or palliation, and a variety of other cytoreductive techniques, and medical treatment including chemotherapy, and biotherapy to control symptoms due to hormone release and tumor growth, with somatostatin analogues (SSAs) and alphainterferon. New biological agents and somatostatintagged radionuclides are under investigation. Advances in the therapy and development of centers of excellence which coordinate multicenter studies, are needed to improve diagnosis, treatment and therefore survival of patients with GEP NETs.
文摘Ischemic colitis is the most common form of ischemic injury of the gastrointestinal tract and can present either as an occlusive or a non-occlusive form. It accounts for 1 in 1000 hospitalizations but its incidence is underesti- mated because it often has a mild and transient nature. The etiology of ischemic colitis is multifactorial and the clinical presentation variable. The diagnosis is based on a combination of clinical suspicion, radiographic, endo- scopic and histological findings. Therapy and outcome depends on the severity of the disease. Most cases of the non-gangrenous form are transient and resolve spontaneously without complications. On the other hand, high morbidity and mortality and urgent operative intervention are the hallmarks of gangrenous ischemic colitis.
文摘Transarterial chemoembolization(TACE) represents the current gold standard for hepatocellular carcinoma(HCC) patients in intermediate stage. Conventional TACE(c TACE) is performed with the injection of an emulsion of a chemotherapeutic drug with lipiodol into the artery feeding the tumoral nodules, followed by embolization of the same vessel to obtain a synergistic effect of drug cytotoxic activity and ischemia. Aim of this review is to summarize the main characteristics of drug-eluting beads(DEB)-TACE and the clinical results reported so far in the literature. A literature search was conducted using Pub Med until June 2017. In order to overcome the drawbacks of c TACE, namely lack of standardization and unpredictability of outcomes, non-absorbable embolic microspheres charged with cytotoxic agents(DEBs) have been developed. DEBs are able to simultaneously exert both the therapeutic components of TACE, either drug-carrier function and embolization, unlike c TACE in which applying the embolic agent is a second moment after drug injection. This way, risk of systemic drug release is minimal due to both high-affinity carrier activity of DEBs and absence of a time interval between injection and embolization. However, despite promising results of preliminary studies, clear evidence of superiority of DEB-TACE over c TACE is still lacking. A number of novel technical devices are actually in development in the field of loco-regional treatments for HCC, but only a few of them have entered the clinical arena. In absence of well-designed randomized-controlled trials, the decision on whether use DEB-TACE or c TACE is still controversial.
文摘Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells, and consequently alters allogenic antigen presentation. Finally, acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis, and they interfere with methylation, synthesis and repair of DNA, thereby increasing HCC susceptibility.
文摘Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in several different enteropathies, including inflammatory bowel disease. It develops through complex cell, extracellular matrix, cytokine and growth factor interactions. Distinct cell types are involved in intestinal fibrosis, such as resident mesenchymal cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM-producing cells derived from epithelial and endothelial cells (through a process termed epithelialand endothelial-mesenchymal transition), stellate cells, pericytes, local or bone marrow-derived stem cells. The most important soluble factors that regulate the activation of these cells include cytokines, chemokines, growth factors, components of the renin-angiotensin system, angiogenic factors, peroxisome proliferator-activated receptors, mammalian target of rapamycin, and products of oxidative stress. It soon becomes clear that although inflammation is responsible for triggering the onset of the fibrotic proc-ess, it only plays a minor role in the progression of this condition, as fibrosis may advance in a self-perpetuating fashion. Definition of the cellular and molecular mechanisms involved in intestinal fibrosis may provide the key to developing new therapeutic approaches.
文摘Although thousands of DNA damaging events occur in each cell every day,efficient DNA repair pathways have evolved to counteract them. The DNA repair machinery plays a key role in maintaining genomic stability by avoiding the maintenance of mutations. The DNA repair enzymes continuously monitor the chromosomes to correct any damage that is caused by exogenous and endogenous mutagens. If DNA damage in proliferating cells is not repaired because of an inadequate expression of DNA repair genes,it might increase the risk of cancer. In addition to mutations,which can be either inherited or somatically acquired,epigenetic silencing of DNA repair genes has been associated with carcinogenesis. Gastric cancer represents the second highest cause of cancer mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes during the lifetime. Among the risk factors,Helicobacter pylori(H. pylori) infection is considered the main driving factor to gastric cancer development. Thus,in this review,we summarize the current knowledge of the role of H. pylori infection on the epigenetic regulation of DNA repair machinery in gastric carcinogenesis.
