Endoscopic management of benign biliary strictures: Looking for the best stent to place.

Benign biliary strictures (BBS) might occur due to different pancreaticobiliary conditions. The etiology and location of biliary strictures are responsible of a wide array of clinical manifestations. The endoscopic approach endoscopic retrograde cholangiopancreatography represents the first-line treatment for BBS, considering interventional radiology and surgery when endoscopic treatment fails or it is not suitable. The purpose of this review is to provide an overview of possible endoscopic treatments for the optimal management of this subset of patients.

Endoscopic Biliary Drainage in Surgically Altered Anatomy.

Endoscopic retrograde cholangiopancreatography (ERCP) is considered the preferred method for managing biliary obstructions. However, the prevalence of surgically modified anatomies often poses challenges, making the standard side-viewing duodenoscope unable to reach the papilla in most cases. The increasing instances of surgically altered anatomies (SAAs) result from higher rates of bariatric procedures and surgical interventions for pancreatic malignancies. Conventional ERCP with a side-viewing endoscope remains effective when there is continuity between the stomach and duodenum. Nonetheless, percutaneous transhepatic biliary drainage (PTBD) or surgery has historically been used as an alternative for biliary drainage in malignant or benign conditions. The evolving landscape has seen various endoscopic approaches tailored to anatomical variations. Innovative methodologies such as cap-assisted forward-viewing endoscopy and enteroscopy have enabled the performance of ERCP. Despite their utilization, procedural complexities, prolonged durations, and accessibility challenges have emerged. As a result, there is a growing interest in novel enteroscopy and endoscopic ultrasound (EUS) techniques to ensure the overall success of endoscopic biliary drainage. Notably, EUS has revolutionized this domain, particularly through several techniques detailed in the review. The rendezvous approach has been pivotal in this field. The antegrade approach, involving biliary tree puncturing, allows for the validation and treatment of strictures in an antegrade fashion. The EUS-transmural approach involves connecting a tract of the biliary system with the GI tract lumen. Moreover, the EUS-directed transgastric ERCP (EDGE) procedure, combining EUS and ERCP, presents a promising solution after gastric bypass. These advancements hold promise for expanding the horizons of comprehensive and successful biliary drainage interventions, laying the groundwork for further advancements in endoscopic procedures.

The Evolving Scenario in the Assessment of Radiological Response for Hepatocellular Carcinoma in the Era of Immunotherapy: Strengths and Weaknesses of Surrogate Endpoints.

Hepatocellular carcinoma (HCC) is a challenging malignancy characterised by clinical and biological heterogeneity, independent of the stage. Despite the application of surveillance programs, a substantial proportion of patients are diagnosed at advanced stages when curative treatments are no longer available. The landscape of systemic therapies has been rapidly growing over the last decade, and the advent of immune-checkpoint inhibitors (ICIs) has changed the paradigm of systemic treatments. The coexistence of the tumour with underlying cirrhosis exposes patients with HCC to competing events related to tumour progression and/or hepatic decompensation. Therefore, it is relevant to adopt proper clinical endpoints to assess the extent of treatment benefit. While overall survival (OS) is the most accepted endpoint for phase III randomised controlled trials (RCTs) and drug approval, it is affected by many limitations. To overcome these limits, several clinical and radiological outcomes have been used. For instance, progression-free survival (PFS) is a useful endpoint to evaluate the benefit of sequential treatments, since it is not influenced by post-progression treatments, unlike OS. Moreover, radiological endpoints such as time to progression (TTP) and objective response rate (ORR) are frequently adopted. Nevertheless, the surrogacy between these endpoints and OS in the setting of unresectable HCC (uHCC) remains uncertain. Since most of the surrogate endpoints are radiology-based (e.g., PFS, TTP, ORR), the use of standardised tools is crucial for the evaluation of radiological response. The optimal way to assess the radiological response has been widely debated, and many criteria have been proposed over the years. Furthermore, none of the criteria have been validated for immunotherapy in advanced HCC. The coexistence of the underlying chronic liver disease and the access to several lines of treatments highlight the urgent need to capture early clinical benefit and the need for standardised radiological criteria to assess cancer response when using ICIs in mono- or combination therapies. Here, we review the most commonly used clinical and radiological endpoints for trial design, as well as their surrogacy with OS. We also review the criteria for radiological response to treatments for HCC, analysing the major issues and the potential future perspectives.

Direct-acting antiviral agents and risk of Hepatocellular carcinoma: Critical appraisal of the evidence.

Direct-acting antivirals (DAAs) revolutionized the treatment of chronic HCV-related disease achieving high rates of sustained virological response (SVR), even in advanced cirrhosis, with modest contraindications and a low rate of adverse events. However, the risk of hepatocellular carcinoma (HCC) persists due to the underlying chronic liver disease, both in patients with and without history of HCC. Although some initial studies reported a presumptive high risk of HCC development after DAA therapy, more recent observational studies denied this hypothesis. The residual risk for HCC occurrence after HCV eradication seems being progressively reduced with time after SVR. Data on recurrence of HCC after DAA exposure in patients with previously treated carcinoma initially reported conflicting results too, this being also due to methodological issues in analysis of retrospective multicenter studies. Anyway, current evidence support the use of DAAs in HCV-HCC treated patients, without any higher risk of tumor recurrence linked to antiviral therapy. Less effort has been made to evaluate the efficacy of DAA therapy in patients with untreated active HCC and it has been questioned whether a lower rate of SVR would be obtained among patients with active HCC. Studies conducted in this perspective concluded that HCC status does not influence the likelihood to obtain SVR with DAAs, making DAAs appropriate in HCC-active patients. As far as survival is concerned, recent studies conducted in cirrhotic HCV-related early-stage HCC found that DAAs improved overall survival, a benefit probably due to the reduction of hepatic decompensation.

Real-Life Clinical Data of Lenvatinib versus Sorafenib for Unresectable Hepatocellular Carcinoma in Italy.

BACKGROUND: Lenvatinib has been approved in Italy since October 2019 as a first-line therapy for advanced hepatocellular carcinoma (HCC) and to date data on effectiveness and safety of lenvatinib are not available in our region. To fill this gap, we performed a multicentric analysis of the real-world treatment outcomes with the propensity score matching in a cohort of Italian patients with unresectable HCC who were treated with either sorafenib or lenvatinib. AIMS AND METHODS: To evaluate the effectiveness of sorafenib and lenvatinib as primary treatment of advanced HCC in clinical practice we performed a multicentric analysis of the treatment outcomes of 288 such patients recruited in 11 centers in Italy. A propensity score was used to mitigate confounding due to referral biases in the assessment of mortality and progression-free survival. RESULTS: Over a follow-up period of 11 months the Cox regression model showed 48% reduction of death risk for patients treated with lenvatinib (95% CI: 0.34-0.81; p = 0.0034), compared with those treated with sorafenib. The median PFS was 9.0 and 4.9 months for lenvatinib and sorafenib arm, respectively. Patients treated with lenvatinib showed a higher percentage of response rate (29.4% vs 2.8%; p < 0.00001) compared with patients treated with sorafenib. Sorafenib was shown to be correlated with more HFSR, diarrhea and fatigue, while lenvatinib with more hypertension and fatigue. CONCLUSION: Our study highlighted for the first time the efficacy and safety of lenvatinib in an Italian cohort of patients.