Is the use of fully covered metal stents effective in the treatment of difficult lithiasis of the common bile duct?

BACKGROUND: The management of difficult lithiasis of common bile duct (CBD) often requires a multimodal approach. Fully Covered Metal Stents (FCSEMS) could fragment the stones, dilate strictures of the CBD and progressively enlarge the papillary orifice. The aim of the study was to evaluate the efficacy of FCSEMS in the treatment of difficult lithiasis of CBD. METHODS: All consecutive cases of difficult lithiasis of CBD after an attempt of clearance with complete sphincterotomy were retrospectively considered from 2009 to 2019. Intrahepatic lithiasis cases were excluded. Multivariable analysis (stepwise logistic regression if p value < 0.1 at univariable analysis) was made to understand factors associated with efficacy of FCSEMS in difficult lithiasis of CBD. RESULTS: 163 cases of difficult lithiasis over 1516 cases of lithiasis of CBD (incidence of 11%) were considered. Among eligible patients, 96 (mean age 78 ± 11.9 years, 43% males) placed a FCSEMS during the first ERCP. Mean diameter of stone was 17.5 ± 5.5 mm. An attempt of dilation during the same procedure was made in 18% cases. After removal of the stent, 52 (54%) patients had complete clearance of CBD at cholangiography. The rest of patients (44), subsequently underwent multimodal treatment (final success of 95%). After logistic regression, variables positively associated with clearance of CBD were sex male (OR 3.5) and stent permanence ≥ 30 days (OR 3.2). Diameter of the stone ≥ 2 cm was associated with failure (OR 0.2). 7 post-ERCP pancreatitis, 6 post-sphincterotomy bleeding and 3 cholangitis occurred. CONCLUSIONS: FCSEMS are useful in the approach of difficult lithiasis of CBD with no significant adverse events associated.

Lack of reduction in serum alpha-fetoprotein during treatment with direct antiviral agents predicts hepatocellular carcinoma development in a large cohort of patients with hepatitis C virus-related cirrhosis.

Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct-acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow-up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan-Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha-fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end-stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan-Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP <6 ng/mL had the lowest risk (P = 0.0002). At logistic regression, platelets (P = 0.009, OR 0.99 CI: 0.99-1.00), previous HCC (P < 0.000 01, OR: 10.76, 95% CI: 5.89-19.34) and no reduction in AFP during treatment (P = 0.0005, OR: 2.98, CI: 1.60-5.54) were independent predictors of HCC. In conclusion, risk of HCC after DAA treatment remains substantial. It is higher among patients with previous HCC, low platelets and without reduction in AFP during treatment.

Modification of splenic stiffness on acoustic radiation force impulse parallels the variation of portal pressure induced by transjugular intrahepatic portosystemic shunt.

BACKGROUND AND AIM: Spleen and liver stiffness (LS) measured by acoustic radiation force impulse (ARFI) imaging has been shown to be useful in identifying patients with portal hypertension. The study aims to establish if the modification of portal pressure induced by a transjugular intrahepatic portosystemic shunt (TIPS) parallels the modification of spleen or LS measured by ARFI in order to understand if ARFI may be used to monitor the modification of portal pressure in patients with cirrhosis. METHODS: Thirty-eight patients with severe portal hypertension underwent LS and spleen stiffness (SS) before TIPS and 1 week after TIPS. Portal atrial gradient (PAG) was measured before and after the shunt opening. RESULTS: Portal atrial gradient decreased significantly from 19.5 to 6 mmHg (P < 0.001). SS decreased significantly after TIPS (pre-TIPS 3.7 m/s vs post-TIPS 3. 1 m/s; P < 0.001), and LS was also significantly modified by TIPS (pre-TIPS 2.8 m/s vs post-TIPS 2.4 m/s; P = 0.003). PAG and SS values measured before and after TIPS were significantly correlated (r = 0.56; P < 0.001); on the other hand, PAG and LS were not (r = 0.19; P = 0.27). Two patients developed a persistent hepatic encephalopathy refractory to medical treatment and were submitted to the reduction of the stent diameter. The modification of SS was parallel to the modification of PAG. CONCLUSION: Spleen stiffness is superior to LS in detecting the modification of portal pressure induced by TIPS. This makes SS a potential non-invasive method to monitor the modification of portal hypertension. Further investigations are needed to establish applicability and clinical utility of this promising tool in the treatment of portal hypertension.

A New Step-Up Dual Endoscopic Approach for Large-Size Infected Pancreatic Necrosis: Percutaneous Endoscopic Necrosectomy Followed by Transluminal Endoscopic Drainage/Necrosectomy.

BACKGROUND: Acute pancreatitis in 10% to 20% of cases can be associated with necrosis of the pancreatic gland, peripancreatic tissue, or both. We report a case series of a new endoscopic approach to treat infected pancreatic necrosis (IPN). PATIENTS AND METHODS: Consecutive patients with IPN, extending from the perigastric area up to the paracolic gutters or into the pelvis, were prospectively studied from January 2017 to June 2022. The treatment protocol was radiologic percutaneous drainage as the first step, followed by fully covered metal stent placement (FC-SEMS) in the track of the catheter. Percutaneous endoscopic necrosectomy (PEN) was performed 2 to 4 days later using a flexible endoscope through the percutaneous tract. About 2 to 4 weeks later, when a matured sac was visible, EUS-guided endoscopic transluminal drainage (ETD) with lumen-apposing metal stents (LAMS) was performed. Control of sepsis with resolution of collection(s) was the primary outcome measure. RESULTS: We included 18 patients, males in 50% of cases with age 60±12 years old. Most frequent cause of pancreatitis was biliary (7 cases) followed by alcoholic in 6 cases; in 3 cases pancreatitis was caused by hyperlipemia and in 2 cases was idiopathic. Mean size of WON was 18±2 cm. For PEN, SEMSs used were esophageal FC-SEMS. LAMS used for ETD were Hot Axios, Hot Spaxus and Nagistent. Mean time of endoscopic intervention for PEN and ETD was 18±3 and 37±4 days, respectively. In 5 cases adverse events occurred: 3 cases of overinflations resolved with introduction of Verres needles in abdomen. In 2 cases postprocedural GI bleeding required endoscopic intervention. In all cases control of sepsis was reached together with resolution of collections. No cases of deaths were observed. CONCLUSIONS: Step-up percutaneous and transluminal endoscopic necrosectomy therapy is an effective strategy for large-size IPN with combined central and peripheral necrosis.

Acute left-sided malignant colonic obstruction: Is there a role for endoscopic stenting?

The therapy of left-sided malignant colonic obstruction continues to be one of the largest problems in clinical practice. Numerous studies on colonic stenting for neoplastic colonic obstruction have been reported in the last decades. Thereby the role of self-expandable metal stents (SEMS) in the treatment of malignant colonic obstruction has become better defined. However, numerous prospective and retrospective investigations have highlighted serious concerns about a possible worse outcome after endoscopic colorectal stenting as a bridge to surgery, particularly in case of perforation. This review analyzes the most recent evidence in order to highlight pros and cons of SEMS placement in left-sided malignant colonic obstruction.

Dilation assisted stone extraction for complex biliary lithiasis: Technical aspects and practical principles.

Common bile duct stones are frequently diagnosed worldwide and are one of the main indications for endoscopic retrograde cholangio-pancreatography. Endoscopic sphincterotomy (EST) has been used for the removal of bile duct stones for the past 40 years, providing a wide opening to allow extraction. Up to 15% of patients present with complicated choledocholithiasis. In this context, additional therapeutic approaches have been proposed such as endoscopic mechanical lithotripsy, intraductal or extracorporeal lithotripsy, or endoscopic papillary large balloon dilation (EPLBD). EPLBD combined with EST was introduced in 2003 to facilitate the passage of large or multiple bile duct stones using a balloon greater than 12 mm in diameter. EPLBD without EST was introduced as a simplified technique in 2009. Dilation-assisted stone extraction (DASE) is the combination of two techniques: EPLBD and sub-maximal EST. Several studies have reported this technique as safe and effective in patients with large bile duct stones, without any increased risk of adverse events such as pancreatitis, bleeding, or perforation. Nevertheless, it is difficult to analyze the outcomes of DASE because there are no standard techniques and definitions between studies. The purpose of this paper is to provide technical guidance and specific information about the main issues regarding DASE, based on current literature and daily clinical experience in biliary referral centers.

Endoscopic ultrasound-guided biliary drainage for malignant biliary obstruction after failed ERCP in low performance status patients.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with the placement of a biliary stent is the treatment of choice for palliation of malignant obstructive jaundice. In 5-10% of cases ERCP fails. In these cases an effective alternative is endoscopic ultrasonography-guided biliary drainage (EUS-BD). AIM: Evaluation of the principal clinical outcomes of direct transluminal EUS-BD. PATIENTS AND METHODS: This study is a retrospective analysis. All consecutive patients with malignant obstructive jaundice, in whom ERCP had failed, were enrolled. The primary outcome was the technical success of EUS-BD defined as the correct placement of the metal or plastic stent across the stomach or duodenum to the biliary tree. The most important secondary outcomes were early and late clinical success, both linked to the decrease of bilirubin haematic level. RESULTS: Between January 2011 and November 2017 thirty-six patients were included. Technical success was obtained in 91.6%. A clinical success, early or late was obtained in 75.8%. The ECOG performance status of less than 3 was correlated with clinical success. Adverse events occurred in 30.3% of patients. CONCLUSIONS: EUS-BD is an effective and safe procedure.

Microbial translocation and T cell activation are modified by direct-acting antiviral therapy in HCV-infected patients.

BACKGROUND: Microbial translocation from the gut lumen has been involved in the pathogenesis of liver damage in hepatitis C virus (HCV) infection. AIM: To investigate the impact of direct-acting antiviral treatment on microbial translocation and T-cell activation, in patients with hepatitis C-related liver disease. METHODS: We enrolled two groups of HCV-infected patients undergoing direct-acting antiviral treatment: patients with fibrosis ≥F3 according to Metavir (Group ≥F3); patients with hepatitis C recurrence after liver transplantation and Metavir ≥F2 (Group Liver Transplantation + ≥F2). All patients were treated with direct-acting antivirals based on ongoing guidelines. Surrogate biomarkers of microbial translocation (plasma concentrations of soluble-CD14, lipopolysaccharide-binding protein and intestinal fatty acid-binding protein) were evaluated at baseline, at first month, at the end of treatment and 3 months later. T-cell activation was measured by expression of CD38+ HLA-DR at the same time points, only in Group ≥F3. RESULTS: There were 32 patients in Group ≥F3 and 13 in Group LT + ≥F2. At baseline, levels of soluble-CD14 and lipopolysaccharide-binding protein were significantly higher in both groups vs healthy controls. Baseline soluble-CD14 correlated with glutamic-oxalacetic transaminase (r = 0.384, P = 0.009) and glutamic-pyruvic transaminase (r = 0.293, P = 0.05). A significant decrease in plasma levels of surrogate microbial translocation biomarkers was observed during and after treatment in the two groups although values were not normalised. In Group ≥F3, CD38+ HLADR+ T-cell expression was significantly decreased by direct-acting antiviral treatment. Relapsers (9%) showed higher soluble-CD14 levels at baseline. CONCLUSION: Surrogate microbial translocation markers and T cell activation are increased in HCV-infected patients with liver fibrosis and decrease during direct-acting antiviral treatment.

Gut Microbiota and Alcoholic Liver Disease.

The gut-liver axis model has often explained liver disease physiopathology. Among the latter we can mention Non-Alcoholic Liver Steatosis (NAFLD), Liver Steatohepatitis (NASH), liver cirrhosis. In this frame an altered Intestinal Permeability (IP) is the gate for antigenic/toxic substances from gut lumen until target organs such as liver in NAFLD. Altered intestinal permeability was discovered almost forty years ago as consequence of acute and chronic alcohol ingestion. Alcohol Liver Disease (ALD) is a systemic pathology whose beginning and end belong to the intestine. Several recent evidences from the literature show how gut microbiota composition can be altered by alcohol, affects IP and can be modulated by several nonpharmacological and pharmacological agents, becoming the target for ALD treatment. In this review we describe the definition of ALD, gut microbiota composition in healthy and ALD, definition and role of IP in ALD physiopathology and emerging evidences on gut microbiota modulation in ALD treatment from preliminary clinical and non-clinical studies.

Hepatocellular carcinoma in cirrhotic patients with transjugular intrahepatic portosystemic shunt: a retrospective case-control study.

BACKGROUND: An association between Transjugular Intrahepatic Porto-Systemic Shunt (TIPS) and the development of hepatocellular carcinoma in patients with cirrhosis has been suggested, but not confirmed. AIM: To evaluate the potential role of TIPS in hepatocellular carcinoma development. METHODS: We performed a retrospective case-control study among patients with cirrhosis; all cases had undergone TIPS placement. Cases and controls were followed as outpatients at a single liver care centre in the same timeframe. RESULTS: Overall, 101 patients with cirrhosis (mean age 58 ± 9 years, 64.3% male) were included in each group. Median duration of follow-up was 56.7 months (range 8.2-174.5) for TIPS patients and 67.8 months (range 8.3-183.1) for controls (p=0.08). In both groups 94% of patients had Child-Pugh Class A or B cirrhosis. The cumulative incidence of hepatocellular carcinoma at 1, 3, 5, and 10 years was 2%, 7%, 18%, and 46% among TIPS patients, and 3%, 10%, 19%, and 39% among controls (log rank test p=0.19). Compared to controls, hepatocellular carcinoma nodules in TIPS patients were more frequently situated in the right lobe (p<0.05). CONCLUSIONS: TIPS does not seem to increase the risk of hepatocellular carcinoma in patients with Child-Pugh Class A or B cirrhosis; for these patients ultrasound surveillance should not be modified.