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.

MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis b- and c-related-hepatocellularcarcinoma

Aim of the present review is to summarize the current knowledge about the potential relationship between mi RNAs and hepatitis B virus(HBV)-hepatitis C virus(HCV) related liver diseases. A systematic computerbased search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine mi RNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma(HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "micro RNAs", "mi RNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma mi RNAs, including mi R-21, mi R-122, mi-125a/b, mi R-199a/b, mi R-221, mi R-222, mi R-223, mi R-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of mi RNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of mi RNAs for HCC early detection and prognosis.

Endoscopic ultrasound-guided treatments: Are we getting evidence based- a systematic review

The continued need to develop less invasive alternatives to surgical and radiologic interventions has driven the development of endoscopic ultrasound(EUS)-guided treatments.These include EUS-guided drainage of pancreatic fluid collections,EUS-guided necrosectomy,EUS-guided cholangiography and biliary drainage,EUSguided pancreatography and pancreatic duct drainage,EUS-guided gallbladder drainage,EUS-guided drainage of abdominal and pelvic fluid collections,EUS-guided celiac plexus block and celiac plexus neurolysis,EUSguided pancreatic cyst ablation,EUS-guided vascular interventions,EUS-guided delivery of antitumoral agents and EUS-guided fiducial placement and brachytherapy.However these procedures are technically challenging and require expertise in both EUS and interventional endoscopy,such as endoscopic retrograde cholangiopancreatography and gastrointestinal stenting.We undertook a systematic review to record the entire body of literature accumulated over the past 2decades on EUS-guided interventions with the objective of performing a critical appraisal of published articles,based on the classification of studies according to levels of evidence,in order to assess the scientific progress made in this field.

Long-term alpha interferon and lamivudine combination therapy in non-responder patients with anti-HBe-positive chronic hepatitis B:Results of an open,controlled trial

AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.METHODS: 34 patients received combination treatment (1 month lamivudine, 12 month lamivudine+interferon, 6month lamivudine), 24 received lamivudine (12 months),24 received interferon (12 months). Interferon was administered at 6 MU tiw and lamivudine at 100 mg orally once daily. Patients were followed up for 6 months after treatment.RESULTS: At the end of treatment, HBV DNA negativity rates were 88 % with lamivudine+interferon, 99 % with lamivudine and 55 % with interferon, (P=0.004, combination therapy vs. interferon, and P=0.001 lamivudine vs.interferon), and serum transaminase normalization rates were 84 %, 91% and 53 % (P=0.01 combination therapy vs. interferon, and P=0.012 lamivudine vs. interferon). Six months later, HBV DNA negativity rates were 44 % with lamivudine+interferon, 33 % with lamivudine and 25 % with interferon, and serum transaminase normalization rates were 61%, 42 % and 45 %, respectively, without statistical significance. No YMDD variants were observed with lamivudine+interferon (vs. 12 % with lamivudine). The combination therapy appeared to be safe. CONCLUSION: Although viral clearance and transaminase normalization are slower with long-term lamivudine+interferon than that with lamivudine alone, the combination regimen seems to provide more lasting benefits and to protect against the appearance of YMDD variants. Studies with other regimens regarding sequence and duration are needed.

Endoscopic ultrasound-guided drainage of pancreatic fluid collections

Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid collections include acute fluid collections, acute and chronic pancreatic pseudocysts, pancreatic abscesses and pancreatic necrosis. Before the introduction of linear endoscopic ultrasound (EUS) in the 1990s and the subsequent development of endoscopic ultrasound-guided drainage (EUS-GD) procedures, the available options for drainage in symptomatic PFCs included surgical drainage, percutaneous drainage using radiological guidance and conventional endoscopic transmural drainage. In recent years, it has gradually been recog-nized that, due to its lower morbidity rate compared to the surgical and percutaneous approaches, endoscopic treatment may be the preferred first-line approach for managing symptomatic PFCs. Endoscopic ultrasound-guided drainage has the following advantages, when compared to other alternatives such as surgical, per-cutaneous and non-EUS-guided endoscopic drainage.EUS-GD is less invasive than surgery and therefore does not require general anesthesia. The morbidity rate is lower, recovery is faster and the costs are lower. EUS-GD can avoid local complications related to per-cutaneous drainage. Because the endoscope is placed adjacent to the fluid collection, it can have direct ac-cess to the fluid cavity, unlike percutaneous drainage which traverses the abdominal wall. Complications such as bleeding, inadvertent puncture of adjacent viscera, secondary infection and prolonged periods of drainage with resultant pancreatico-cutaneous fistulae may be avoided. The only difference between EUS and non-EUS drainage is the initial step, namely, gaining access to the pancreatic fluid collection. All the sub-sequent steps are similar, i.e., insertion of guide-wires with fluoroscopic guidance, balloon dilatation of the cystogastrostomy and insertion of transmural stents or nasocystic catheters. With the introduction of the EUS-scope equipped with a large operative channel which permits drainage of the PFCs in 'one step', EUS-GD has been increasingly carried out in many tertiary care centers and has expanded the safety and efficacy of this modality, allowing access to and drainage of overly challenging fluid collections. However, the nature of the PFCs determines the outcome of this procedure. The technique and review of current literature regarding EUS-GD of PFCs will be discussed.

Gastric autoimmune disorders in patients with chronic hepatitis C before,during and after interferon-alpha therapy

AIM:To explore the prevalence of autoimmune gastritis in chronic hepatitis C virus (HCV) patients and the influence of α-interferon (IFN) treatment on autoimmune gastritis. METHODS:We performed a prospective study on 189 patients with positive anti-HCV and viral RNA enrolled in a 12-month IFN protocol.We evaluated:a) the baseline prevalence of autoimmune gastritis,b) the impact of IFN treatment on development of biochemical signs of autoimmune gastritis (at 3,6 and 12 months),c) the evolution after IFN withdrawal (12 months) in terms of anti-gastric-parietal-cell antibodies (APCA),gastrin,anti-thyroid,and anti-non-organ- specific antibodies. RESULTS:APCA positivity and 3-fold gastrin levels were detected in 3 (1.6%) and 9 (5%) patients,respectively,at baseline,in 25 (13%) and 31 (16%) patients at the end of treatment (both P<0.001,vs baseline),and in 7 (4%) and 14 (7%) patients 12 months after withdrawal (P=0.002 and P=0.01 respectively,vs baseline;P=not significant vs end of treatment).The development of autoimmune gastritis was strictly associated with the presence of autoimmune thyroiditis (P=0.0001),no relationship was found with other markers of autoimmunity. CONCLUSION:In HCV patients,IFN frequently precipitates latent autoimmune gastritis,particularly in females.Following our 12-month protocol,the phenomenon generally regressed.Since APCA positivity and high gastrin levels are associated with the presence of antithyroid antibodies, development of autoimmune thyroiditis during IFN treatment may provide a surrogate preliminary indicator of possible autoimmune gastritis to limit the need for invasive examinations.

Current status of peroral cholangioscopy in biliary tract diseases

Peroral cholangioscopy(POC) is an important tool for the management of a selected group of biliary diseases. Because of its direct visualization, POC allows targeted diagnostic and therapeutic procedures. POC can be performed using a dedicated cholangioscope that is advanced through the accessory channel of a duodenoscope or via the insertion of a small-diameter endoscope directly into the bile duct. POC was first described in the 1970 s, but the use of earlier generation devices was substantially limited by the cumbersome equipment setup and high repair costs. For nearly ten years, several technical improvements, including the single-operator system, high-quality images, the development of dedicated accessories and the increased size of the working channel, have led to increased diagnostic accuracy, thus assisting in the differentiation of benign and malignant intraductal lesions, targeting biopsies and the precise delineation of intraductal tumor spread before surgery. Furthermore, lithotripsy of difficult bile duct stones, ablative therapies for biliary malignancies and direct biliary drainage can be performed under POC control. Recent developments of new types of conventional POCs allow feasible, safe and effective procedures at reasonable costs. In the current review, we provide an updated overview of POC, focusing our attention on the main current clinical applications and on areas for future research.

Microbiota-gut-brain axis and its affect inflammatory bowel disease:Pathophysiological concepts and insights for clinicians

Despite the bi-directional interaction between gut microbiota and the brain not being fully understood,there is increasing evidence arising from animal and human studies that show how this intricate relationship may facilitate inflammatory bowel disease(IBD)pathogenesis,with consequent important implications on the possibility to improve the clinical outcomes of the diseases themselves,by acting on the different components of this system,mainly by modifying the microbiota.With the emergence of precision medicine,strategies in which patients with IBD might be categorized other than for standard gut symptom complexes could offer the opportunity to tailor therapies to individual patients.The aim of this narrative review is to elaborate on the concept of the gutbrain-microbiota axis and its clinical significance regarding IBD on the basis of recent scientific literature,and finally to focus on pharmacological therapies that could allow us to favorably modify the function of this complex system.

Endoscopic ultrasound guided biliary drainage

Endoscopic retrograde cholangio-pancreatography is the most appropriate technique for treating common bile duct and pancreatic duct stenosis secondary to benign and malignant diseases. Even if the procedure is performed by skillful endoscopist, there are patients in whom endoscopic stent placement is not possible. Common causes of failure include complex peripapillary diverticula, prior surgery procedures, tumor involvement of the papilla, biliary sphincter stenosis, and impacted stones. Percutaneous trans-hepatic biliary drainage (PTBD) and surgical intervention carry morbidity and mortality. Recently endoscopic ultrasonography-guided biliary drainage has been reported as an alternative technique. Endoscopic ultrasonography- guided biliary drainage using either direct access or a rendezvous technique has attracted attention as an alternative procedure to PTBD, with a technical success between 75%-100% and with low complication rate. We have reviewed published data on EUS guided biliary drainage procedures with the aim of summarizing the efficacy and safety of this promising method.

Feasibility and safety of self-expandable metal stent in nonmalignant disease of the lower gastrointestinal tract

In recent years,self-expandable metal stents(SEMSs)have been employed to treat benign gastrointestinal strictures secondary to several conditions:Acute diverticulitis,radiation colitis,inflammatory bowel disease(IBD),and postanastomotic leakages and stenosis.Other applications include endometriosis and fistulas of the lower gastrointestinal tract.Although it may be technically feasible to proceed to stenting in the aforementioned benign diseases of the lower gastrointestinal tract,the outcome has been reported to be poor.In fact,in some settings(such as complicated diverticulitis and postsurgical anastomotic strictures),stenting seems to have a limited evidence-based benefit as a bridge to surgery,while in other settings(such as endometriosis,IBD,radiation colitis,etc.),even society guidelines are not able to guide the endoscopist through decisional algorithms for SEMS placement.The aim of this narrative paper is to review the scientific evidence regarding the use of SEMSs in nonmalignant diseases of the lower gastrointestinal tract,both in adult and pediatric settings.

Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma:A systematic review

AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus(HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis(PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews:(1) HCV and haematopoietic malignancies;(2) HCV and cholangiocarcinoma;(3) HCV and pancreatic cancer;(4) HCV and breast cancer;(5) HCV and kidney cancer;(6) HCV and skin or oral cancer; and(7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with:(1) a higher incidence of some B-cell Non-HodgkinLymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%;(2) an increased risk of intra-hepatic cholangiocarcinoma; and(3) a correlation between HCV prevalence and pancreatic cancer(PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are requiredto confirm or deny this association.

Endoscopic ultrasound fine-needle biopsy vs fine-needle aspiration for lymph nodes tissue acquisition:a systematic review and meta-analysis

Background:Endoscopic ultrasound(EUS)-guided tissue acquisition represents the choice of methods for suspected lymph nodes(LNs)located next to the gastrointestinal tract.This study aimed to compare the pooled diagnostic performance of EUS-guided fine-needle biopsy(EUS-FNB)and fine-needle aspiration(EUS-FNA)for LNs sampling.Methods:We searched PubMed/MedLine and Embase databases through August 2021.Primary outcome was diagnostic accuracy;secondary outcomes were sensitivity,specificity,sample adequacy,optimal histological core procurement,number of passes,and adverse events.We performed a pairwise meta-analysis using a random-effects model.The results are presented as odds ratio(OR)or mean difference along with 95%confidence interval(CI).Results:We identified nine studies(1,276 patients)in this meta-analysis.Among these patients,66.4%were male;the median age was 67 years.Diagnostic accuracy was not significantly different between the two approaches(OR,1.31;95%CI,0.81–2.10;P=0.270).The accuracy of EUS-FNB was significantly higher when being performed with newer end-cutting needles(OR,1.87;95%CI,1.17–3.00;P=0.009)and in abdominal LNs(OR,2.48;95%CI,1.52–4.05;P<0.001)than that of EUSFNA.No difference in terms of sample adequacy was observed between the two approaches(OR,1.40;95%CI,0.46–4.26;P=0.550);however,histological core procurement and diagnostic sensitivity with EUS-FNB were significantly higher than those with EUS-FNA(OR,6.15;95%CI,1.51–25.07;P=0.010 and OR,1.87;95%CI,1.27–2.74,P=0.001).The number of needle passes needed was significantly lower in the EUS-FNB group than in the EUS-FNA group(mean difference,-0.54;95%CI,-0.97 to -0.12;P=0.010).Conclusions EUS-FNA and EUS-FNB perform similarly in LN sampling;however,FNB performed with end-cutting needles outperformed FNA in terms of diagnostic accuracy.