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

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.

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 bleeding.Conclusions: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

Gut microbiota in women:The secret of psychological and physical well-being

The gut microbiota works in unison with the host,promoting its health.In particular,it has been shown to exert protective,metabolic and structural functions.Recent evidence has revealed the influence of the gut microbiota on other organs such as the central nervous system,cardiovascular and the endocrine-metabolic systems and the digestive system.The study of the gut microbiota is outlining new and broader frontiers every day and holds enormous innovation potential for the medical and pharmaceutical fields.Prevention and treatment of specific women’s diseases involves the need to deepen the function of the gut as a junction organ where certain positive bacteria can be very beneficial to health.The gut microbiota is unique and dynamic at the same time,subject to external factors that can change it,and is capable of modulating itself at different stages of a woman’s life,playing an important role that arises from the intertwining of biological mechanisms between the microbiota and the female genital system.The gut microbiota could play a key role in personalized medicine.

Dynamic contrast enhanced ultrasound in gastrointestinal diseases:A current trend or an indispensable tool?

Contrast enhanced ultrasound(CEUS)has been widely implemented in clinical practice because of the enormous quantity of information it provides,along with its low cost,reproducibility,minimal invasiveness,and safety of the secondgeneration ultrasound contrast agents.To overcome the limitation of CEUS given by the subjective evaluation of the contrast enhancement behaviour,quantitative analysis of contrast kinetics with generation of time-intensity curves has been introduced in recent years.The quantification of perfusion parameters[named as dynamic-CEUS(D-CEUS)]has several applications in gastrointestinal neoplastic and inflammatory disorders.However,the limited availability of large studies and the heterogeneity of the technologies employed have precluded the standardisation of D-CEUS,which potentially represents a valuable tool for clinical practice in management of gastrointestinal diseases.In this article,we reviewed the evidence exploring the application of D-CEUS in gastrointestinal diseases,with a special focus on liver,pancreas,and inflammatory bowel diseases.

Choosing the best endoscopic approach for post-bariatric surgical leaks and fistulas:Basic principles and recommendations

Post-surgical leaks and fistulas are the most feared complication of bariatric surgery.They have become more common in clinical practice given the increasing number of these procedures and can be very difficult to treat.These two related conditions must be distinguished and characterized to guide the appropriate treatment.Leak is defined as a transmural defect with communication between the intra and extraluminal compartments,while fistula is defined as an abnormal communication between two epithelialized surfaces.Traditionally,surgical treatment was the preferred approach for leaks and fistulas and was associated with high morbidity with significant mortality rates.However,with the development of novel devices and techniques,endoscopic therapy plays an increasingly essential role in managing these conditions.Early diagnosis and endoscopic therapy initiation after clinical stabilization are crucial to success since clinical success rates are higher for acute leaks and fistulas when compared to late and chronic leaks and fistulas.Several endoscopic techniques are available with different mechanisms of action,including direct closure,covering/diverting or draining.The treatment should be individualized by considering the characteristics of both the patient and the defect.Although there is a lack of high-quality studies to provide standardized treatment algorithms,this narrative review aims to provide a summary of the current scientific evidence and,based on this data and our extensive experience,make recommendations to help choose the best endoscopic approach for the management of post-bariatric surgical leaks and fistulas.

Gut microbiota role in irritable bowel syndrome:Newtherapeutic strategies

In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome(IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial(Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful(Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.

Serrated colorectal cancer: Molecular classification, prognosis, and response to chemotherapy

Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer(CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of Cp G islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy.

Immunological alterations in hepatitis C virus infection

A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus(HCV)infection,focusing the attention of physicians and researchers on the close association between HCV and immune disorders.HCV lymphotropism represents the most important step in the pathogenesis of virusrelated immunological diseases and experimental,virologic,and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases,such as rheumatoid arthritis,Sj?gren syndrome,hemolytic anemia and severe thrombocytopenia,and in organ-specific autoimmune diseases,such as autoimmune hepatitis,thyroid disorders and diabetes.This review will outline the principal aspects of such HCVinduced immunological alterations,focusing on the prevalence of these less characterized HCV extrahepatic manifestations.

A practical approach to the diagnosis of autoimmune pancreatitis

Autoimmune pancreatitis is a disease characterized by specific pathological features,different from those of other forms of pancreatitis,that responds dramatically to steroid therapy.The pancreatic parenchyma may be diffusely or focally involved with the possibility of a low-density mass being present at imaging,mimicking pancreatic cancer.Clinically,the most relevant problems lie in the diagnosis of autoimmune pancreatitis and in distinguishing autoimmune pancreatitis from pancreatic cancer.Since in the presence of a pancreatic mass the probability of tumour is much higher than that of pancreatitis,the physician should be aware that in focal autoimmune pancreatitis the first step before using steroids is to exclude pancreatic adenocarcinoma.In this review,we briefly analyse the strategies to be followed for a correct diagnosis of autoimmune pancreatitis.

Non-surgical treatment of esophageal achalasia

Esophageal achalasia is an infrequent motility disorder characterized by a progressive stasis and dilation of the oesophagus; with subsequent risk of aspiration, weight loss, and malnutrition. Although the treatment of achalasia has been traditionally based on a surgical approach, especially with the introduction of laparoscopic techniques, there is still some space for a medical approach. The present article reviews the non-surgical therapeutic options for achalasia.

Small bowel capsule endoscopy in 2007:Indications,risks and limitations

囊内视镜检查法有 revoluzionized 由提供一个可靠方法评估的小肠的学习，内视镜的联盟者，全部小肠。在最后六年里，几份报纸被出版了处于不同临床的条件探索这考试的可能的角色。在现在的时间囊，内视镜检查法通常被推荐为第三考试，在否定双向内视镜检查法以后，在有阴暗胃肠的流血的病人。证据的成长身体也处于象 Crohn 的疾病，乳糜泻，小肠息肉病症候群或小肠肿瘤那样的另外的临床的条件为这考试建议一个重要角色。这考试的主要复杂并发症是在以前未知的小肠苛评的地点的设备的保留。然而，也由于这个工具的技术限制主要有一些另外的开的问题(它没从遥控被驾驶，是不能的拿活体检视到 insufflate 空气，正确地缩放并且定位损害到 suck 液体或碎片并且到有时) 。最近发达的双汽球肠脓毒病，尽管侵略、耗时，由于它的能力指向了活体检视探索小肠的大部分并且拿，能克服囊内视镜检查法的一些限制。在现在预定，在临床的条件的多数(即阴暗官方补给的流血)，赢的策略似乎是联合这二种技术探索小肠在一无痛苦，安全、完全的方法(与囊内视镜检查法)并且识别了定义并且对待损害(与两倍汽球肠寄生物)。

Multidrug resistance 1 gene in inflammatory bowel disease: A meta-analysis

MDR1 基因是为煽动性的肠疾病(IBD ) 并且也许的致病的吸引人的候选人基因对治疗的反应，与在功能、基因的层次的证据。它的产品， P-glycoprotein (P-gp ) 作为因此影响许多药的布置和反应的 transmembrane 流出泵工作，一些(即 glucocorticoids ) 对 IBD 中央治疗。另外， P-gp 高度在许多上皮的表面被表示，包括的胃肠道(官方补给) 与在减少的一个通常认为的角色吸收内长或外毒素，并且也许主人细菌相互作用。MDR1 基因的许多基因变化被描述了，在为不同 P-gp 表示的一些例子证据，也，药新陈代谢被提供了。然而，数据经常由于采用的基因异质和不同方法论正在冲突。也许，在官方补给的道的 P-gp 的生理的重要性的证据的最大的片来自对老鼠建模的 mdr1 大美人的描述，它在特定的没有病原体的环境开发自发的大肠炎。学习调查到 IBD 的基因多型性和倾向也显示出冲突结果的 MDR1，由于在复杂疾病的已知的困难，特别当建议基因贡献是弱的时。在这研究，我们承担了在 IBD 与二 SNP 多型性(C3435T 和 G2677T/A ) 获得的可得到的调查结果的元分析；3435T 等位基因和 3435TT 遗传型的一个重要协会与 UC 被发现了(或 = 1.17， P = 0.003 并且或 = 1.36， P = 0.017，分别地) 。在对比，有 CD 和 G2677T/A 多型性的协会都不能被表明。

Budd-Chiari syndrome management:Lights and shadows

Budd-Chiari syndrome (BCS) is a rare disease whose management should follow a step by step strategy.Anticoagulation and medical therapy should be the first line treatment.Revascularization or TIPS are indicated in case of no response to medical therapy.OLT should be indicated as a rescue therapy and anticoagulation be started soon after OLT.However,no clear indica-tion can actually be given about the timing of different treatments.Moreover,there is some concern about treatment of some subgroup of patients,especially regarding the risk of recurrence after liver transplanta-tion.The topic of this paper is to critically review the actual knowledge of BCS management.

Diagnosis and management of choledocholithiasis in the golden age of imaging, endoscopy and laparoscopy

Biliary lithiasis is an endemic condition in both Western and Eastern countries, in some studies affecting 20% of the general population. In up to 20% of cases, gallbladder stones are associated with common bile duct stones(CBDS), which are asymptomatic in up to one half of cases. Despite the wide variety of examinations and techniques available nowadays, two main open issues remain without a clear answer: how to cost-effectively diagnose CBDS and, when they are finally found, how to deal with them. CBDS diagnosis and management has radically changed over the last 30 years, following the dramatic diffusion of imaging, including endoscopic ultrasound(EUS) and magnetic resonance cholangiography(MRC), endoscopy and laparoscopy. Since accuracy, invasiveness, potential therapeutic use and costeffectiveness of imaging techniques used to identifyCBDS increase together in a parallel way, the concept of "risk of carrying CBDS" has become pivotal to identifying the most appropriate management of a specific patient in order to avoid the risk of "under-studying" by poor diagnostic work up or "over-studying" by excessively invasive examinations. The risk of carrying CBDS is deduced by symptoms, liver/pancreas serology and ultrasound. "Low risk" patients do not require further examination before laparoscopic cholecystectomy. Two main "philosophical approaches" face each other for patients with an "intermediate to high risk" of carrying CBDS: on one hand, the "laparoscopy-first" approach, which mainly relies on intraoperative cholangiography for diagnosis and laparoscopic common bile duct exploration for treatment, and, on the other hand, the "endoscopy-first" attitude, variously referring to MRC, EUS and/or endoscopic retrograde cholangiography for diagnosis and endoscopic sphincterotomy for management. Concerning CBDS diagnosis, intraoperative cholangiography, EUS and MRC are reported to have similar results. Regarding management, the recent literature seems to show better short and long term outcome of surgery in terms of retained stones and need for further procedures. Nevertheless, open surgery is invasive, whereas the laparoscopic common bile duct clearance is time consuming, technically demanding and involves dedicated instruments. Thus, although no consensus has been achieved and CBDS management seems more conditioned by the availability of instrumentation, personnel and skills than cost-effectiveness, endoscopic treatment is largely preferred worldwide.

Prevalence of overweightedness in patients with gastro-esophageal reflux

AIM: To evaluate whether the prevalence of overweight and obese conditions is increased in gastro-esophageal reflux disease (GERD) patients (with 24-h pathological pH recordings) in comparison to general population. METHODS: A total of 196 consecutive patients (103 females, age range 18-83 years) with symptoms of gastro-esophageal reflux (GER) and 24-h pathological esophageal pH-metry. Body mass index (BMI) of the patients was calculated and its distribution (%) was compared with that of the Italian general population as assessed by National Bureau of Census (ISTAT). To evaluate the association of GERD with weight categories, the binomial test was employed. P < 0.05 was considered statistically significant. RESULTS: In males, overweightedness (BMI 25-25.9) was present in 43% of GERD patients vs 41.8% of Italian population (IP) (ns), obesity (BMI ≥ 30) in 10.9% vs 9.1% (ns). In females overweight was present in 34.9% of GERD patients vs 25.7% of IP (P < 0.01), obesity in 13.6% of GERD patients vs 9.1% of IP (P < 0.01). No statistically significant differences were noted in different age classes. CONCLUSION: In comparison to the Italian general population, the prevalence of overweightedness and obesity is increased in female but not in male patients with ascertained gastro-esophageal reflux disease.

Changes in nutritional status after liver transplantation

Chronic liver disease has an important effect on nutritional status, and malnourishment is almost universally present in patients with end-stage liver disease who undergo liver transplantation. During recent decades,a trend has been reported that shows an increase in number of patients with end-stage liver disease and obesity in developed countries. The importance of carefully assessing the nutritional status during the workup of patients who are candidates for liver replacement is widely recognised. Cirrhotic patients with depleted lean body mass(sarcopenia) and fat deposits have an increased surgical risk; malnutrition may further impact morbidity, mortality and costs in the post-transplantation setting. After transplantation and liver function is restored, many metabolic alterations are corrected,dietary intake is progressively normalised, and lifestyle changes may improve physical activity. Few studies have examined the modifications in body composition that occur in liver recipients. During the first 12 mo, the fat mass progressively increases in those patients who had previously depleted body mass, and the muscle mass recovery is subtle and non-significant by the end of the first year. In some patients, unregulated weight gain may lead to obesity and may promote metabolicdisorders in the long term. Careful monitoring of nutritional changes will help identify the patients who are at risk for malnutrition or over-weight after liver transplantation. Physical and nutritional interventions must be investigated to evaluate their potential beneficial effect on body composition and muscle function after liver transplantation.

Role of CARD15,DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases

AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn’s disease (CD), 186 ulcerative colitis (UC) patients, 434 par- ents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more com- mon in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an in- creased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was morefrequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric on- set of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.

Therapeutic and clinical aspects of portal vein thrombosis in patients with cirrhosis

Portal vein thrombosis(PVT) is a frequent complication in cirrhosis, particularly in advanced stages of the disease. As for general venous thromboembolism, risk factors for PVT are slow blood flow, vessel wall damage and hypercoagulability, all features of advanced cirrhosis. Actually, the old dogma of a hemorrhagic tendency in cirrhosis has been challenged by new laboratory tools and the clinical evidence that venous thrombosis also occurs in cirrhosis. The impaired hepatic synthesis of both pro- and anticoagulants leads to a rebalanced hemostasis, more liable to be tipped towards thrombosis or even bleeding. Conventional anticoagulant drugs(low molecular weight heparin or vitamin K antagonists) may be used in cirrhosis patients with PVT, particularly in those eligible for liver transplantation, to prevent thrombosis progression thus permitting/facilitating liver transplant. However, several doubts exist on the level of anticoagulation achieved as estimated by coagulation tests, on the efficacy of treatment monitoring and on the correct timing for discontinuation in non-transplant candidates, while in transplant candidates there is expert consensus on continuing anticoagulation until transplantation. The recent introduction of direct acting oral anticoagulant drugs(DOACs) in other clinical settings generates much interest on their possible application in patients with cirrhosis and PVT. However, DOACs were not evaluated yet in patients with liver disease and cannot be recommended for the present time.

Treatment of active steroid-refractory inflammatory bowel diseases with granulocytapheresis: Our experience with a prospective study

瞄准：与活跃的类固醇倔强的煽动性的肠疾病(IBD ) 在 14 个病人与 granulocytapheresis (GCAP ) 的使用报导我们的经验以便在完成宽恕并且维持一个长持续没有症状的时期评估它的功效。方法：疾病的活动被临床的活动索引(蔡) 和内视镜的索引(EI ) 在 ulcerative (UC ) 评估，当时由 Crohn 在 Crohn 的疾病(CD ) 的疾病活动索引(CDAI ) 。病人用 Adacolumn 系统被对待，有选择地绑在 granulocytes 和单核白血球的吸附列。GCAP 的一个会议 / 星期为 5 wk 被执行。类固醇在词首字母的脱落期间被停止。结果：所有病人完成了不显示出复杂并发症的五星期的功课。在最后会议的结束， 93% 病人显示出为 6 瞬间坚持了的疾病的临床的宽恕。在治疗的结束以后的九个月， 60% 案例维持了宽恕，当 23% 病人仍然在在 12 瞬间以后的临床的宽恕时。结论：就算我们有类固醇倔强的 IBD 的病人的数字不大，我们能断言 GCAP 很好被容忍并且有效特别在在治疗以后的开始的六个月内，在盒子的一个重要百分比。持续反应的率在 12 瞬间以后在 6 瞬间以后并且显著地稍微落下，然而，严重副作用的缺席能是为进一步评估治疗的新时间表的刺激。

Management of hepatocellular carcinoma: Enlightening the gray zones

Management of hepatocellular carcinoma (HCC) has been continuously evolving during recent years. HCC is a worldwide clinical and social issue and typically a complicates cirrhosis. The incidence of HCC is increasing, not only in the general population of patients with cirrhosis, but particularly in some subgroups of patients, like those with human immunodeficiency virus infection or thalassemia. Since a 3% annual HCC incidence has been estimated in cirrhosis, a biannual screening is generally suggested. The diagnostic criteria of HCC has recently had a dramatic evolution during recent years. HCC diagnosis is now made only on radiological criteria in the majority of the cases. In the context of cirrhosis, the universally accepted criteria for HCC diagnosis is contrast enhancement in arterial phase and washout in venous/late phase at imaging, the so called "typical pattern". However, recently up- dated guidelines slightly differ in diagnostic criteria. Apart from liver transplantation, the only cure of both HCC and underlying liver cirrhosis, all the other treatments have to match with higher rate of HCC recurrence. The latter can be classified into curative (resection and percutaneous ablation) and palliative treatments. The aim of this paper was to review the currentknowledge on management of HCC and to enlighten the areas of uncertainty.