Search

Pancreatic fluid collections (PFCs), including pancreatic pseudocysts (PPs) and walled-off pancreatic necrosis (WON), are common complications of pancreatitis and pancreatic surgery. Historically, the treatment of these conditions has relied on surgical and radiological approaches. The treatment of patients with PFCs has already focused toward an endoscopy-based approach, and with the development of dedicated lumen-apposing metal stents (LAMS), it has almost totally shifted towards interventional Endoscopic Ultrasound (EUS)-guided procedures. However, there is still limited consensus on several aspects of PFCs treatment within the multidisciplinary management. The interventional endoscopy and ultrasound (i-EUS) group is an Italian network of clinicians and scientists with special interest in biliopancreatic interventional endoscopy, especially interventional EUS. This manuscript focuses on the second part of the results of a consensus conference organized by i-EUS, with the aim of providing evidence-based guidance on several intra- and post-procedural aspects of PFCs drainage, such as clinical management and follow-up. [ABSTRACT FROM AUTHOR]

Pancreatic fluid collections (PFCs), including pancreatic pseudocysts (PPs) and walled-off pancreatic necrosis (WON), are common complications of pancreatitis and pancreatic surgery. Historically, the treatment of these conditions has relied on surgical and radiological approaches; however, it has later shifted toward an endoscopy-based approach. With the development of dedicated lumen-apposing metal stents (LAMS), interventional Endoscopic Ultrasound (EUS)-guided procedures have become the standard approach for PFC drainage. However, there is still limited consensus on several aspects of the multidisciplinary management of PFCs. The interventional endoscopy and ultrasound (i-EUS) group is an Italian network of clinicians and scientists with special interest in biliopancreatic interventional endoscopy, especially interventional EUS. This manuscript describes the first part of the results of a consensus conference organized by i-EUS with the aim of providing evidence-based guidance on aspects such as indications for treating PFCs, the timing of intervention, and different technical strategies for managing patients with PFCs. [ABSTRACT FROM AUTHOR]

Despite the introduction of serological neoplastic biomarkers and typical radiological characteristics in clinical practice, liver biopsy (LB) is often still necessary to establish a histological diagnosis, especially in ambiguous cases. Nowadays, LB via the percutaneous approach (PC-LB), under computed tomography (CT) scan or ultrasonography (US) guidance, is the route of choice. However, certain focal liver lesions can be challenging to access percutaneously. In such cases, endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) may represent an attractive, minimally invasive alternative. This retrospective observational study aimed to evaluate the efficacy, diagnostic performance, and safety of EUS-FNB conducted on 58 focal liver lesions located in both liver lobes. The adequacy of FNB samples for focal liver lesions located in the left and right lobes was 100% and 81.2%, respectively, and the difference was statistically significant (p = 0.001). Technical success was 100% for both liver lobes. The overall sensitivity and specificity were 95% and 100%, respectively. EUS-FNB is effective in making an accurate diagnosis with an excellent safety profile for focal liver lesions located in both liver lobes. [ABSTRACT FROM AUTHOR]

Mirizzi syndrome (MS) is a challenging diagnosis due to its similar presentation with other biliary diseases; thus, the role of endoscopy is sometimes unclear, especially in altered anatomy. Radiological examinations may usually suspect it, but deeper examinations could be necessary to confirm it. Endoscopic retrograde cholangiopancreatography (ERCP) certainly has a therapeutic role in cases of jaundice, cholangitis or concurrent choledocolithiasis, although surgery is without doubt the definitive treatment in most of the cases. Therefore, surgeons may have a clearer picture of the condition of the biliary tree with respect to fistulas thanks to ERCP, particularly in patients with a higher grade of MS (type higher than 2 in the Csendes classification). Therefore, a complete removal of biliary stones is sometimes not possible due to size and location, so biliary stenting becomes the only option, even if transitory. Our brief report is a further demonstration of the fundamental role of ERCP in managing MS, even when it has no long-term therapeutic aim but is performed as bridge-to-surgery, especially in cases with a more difficult biliary anatomy due to the type of fistula. Moreover, we truly suggest discussing patients affected with MS in a multidisciplinary board, preferably in tertiary hepatobiliary centers. [ABSTRACT FROM AUTHOR]

Background: Atezolizumab + bevacizumab represent the current standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, direct comparison with other combination treatments including immune checkpoint inhibitors (ICI) + tyrosine kinase inhibitors (TKIs) are lacking. Objectives: This network meta-analysis (NMA) aims to indirectly compare the efficacy and the safety of first-line systemic therapies for unresectable advanced HCC. Method: A literature search of MEDLINE, Embase, and SCOPUS databases was conducted up to October 31, 2022. Phase 3 randomized controlled trials (RCTs) testing TKIs, including sorafenib and lenvatinib, or ICIs reporting overall survival (OS) and progression-free survival (PFS) were included. Individual survival data were extracted from OS and PFS curves to calculate restricted mean survival time. A Bayesian NMA was performed to compare treatments in terms of efficacy (15- and 30-month OS, 6-month PFS) and safety, represented by grade ≥3 (severe) adverse events (SAEs). The incremental safety-effectiveness ratio as measure of net health benefit was calculated as the difference in SAE probability divided by survival difference between the 2 most effective treatments. Results: Nine RCTs enrolling 6,600 patients were included. Atezolizumab plus bevacizumab showed the highest probability (88%) of achieving the 30-month OS landmark. Lenvatinib showed a probability of 86% of achieving best PFS outcomes. ICI monotherapies ranked as most tolerable. Atezolizumab plus bevacizumab showed the best net health benefit for OS, compared to durvalumab plus tremelimumab. When evaluating the net health benefit for PFS, at a willingness-to-risk threshold of 10% of SAEs for life-month gained, atezolizumab plus bevacizumab was favoured in 78% of cases, while at threshold of 30% of SAEs for life-month gained, lenvatinib was favoured in 76% of cases. Conclusions: Atezolizumab plus bevacizumab is the best treatment in terms of net benefit and therefore it should be recommended as standard of care. Compared to atezolizumab plus bevacizumab, lenvatinib monotherapy had the best net benefit for PFS when physicians and patients are available to accept a higher risk of toxicity. [ABSTRACT FROM AUTHOR]

Iatrogenic perforations are severe complications of gastrointestinal endoscopy; therefore, their management should be adequately planned. A 77-year-old man with a history of diverticulosis underwent a colonoscopy for anemia. During the procedure, an iatrogenic perforation occurred suddenly in the sigmoid colon, near a severe angle among the numerous diverticula. Through-thescope clips were immediately applied to treat it and close mucosal edges. Laboratory tests showed increased levels of inflammation and infection, and although there were no complaints of abdominal pain, the patient had an extremely distended abdomen. A multidisciplinary board began management based on a conservative approach. Pneumoperitoneum was treated with computed tomography-assisted drainage. After 72 hours, his intestinal canalization and laboratory tests were normal. Though this adverse event is rare, a multidisciplinary board should be promptly gathered upon occurrence, even if the patient appears clinically stable, to consider a conservative approach and avoid surgical treatment. [ABSTRACT FROM AUTHOR]

Introduction: Atezolizumab (ATEZO) plus bevacizumab (BEVA) represents the new standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the second-line treatment after the failure of immunotherapy-based first-line remains elusive. Taking into account the weaknesses of the available evidence, we developed a simulation model based on available phase III randomized clinical trials (RCTs) to identify optimal risk/benefit sequential strategies. Methods: A Markov model was built to estimate the overall survival (OS) of sequential first- and second-line systemic treatments. Sequences starting with first-line ATEZO plus BEVA followed by 5 second-line treatments (sorafenib [SORA], lenvatinib [LENVA], regorafenib, cabozantinib, and ramucirumab) were compared. The probability of transition between states (initial treatment, cancer progression, and death) was derived from RCTs. Life-year gained (LYG) was the main outcome. Rates of severe adverse events (SAEs) (≥ grade 3) were calculated. The incremental safety-effectiveness ratio (ISER) was calculated as the difference in probability of SAEs divided by LYG between the 2 most effective sequences. Results: ATEZO plus BEVA followed by LENVA (median OS, 24 months) or SORA (median OS, 23 months) was the most effective sequence, producing a LYG of 0.50 and 0.42 year, respectively. ATEZO plus BEVA followed by SORA was the safest sequence (SAEs 63%). At a willingness-to-risk threshold of 10% of SAEs for LYG, ATEZO plus BEVA followed by second-line SORA was favored in 72% of cases, while at a threshold of 30% of SAEs for LYG, ATEZO plus BEVA followed by second-line LENVA was favored in 69% of cases. Conclusion: Our simulation model provides a strong rationale to support ongoing trials evaluating second-line tyrosine-kinase inhibitors after first-line ATEZO plus BEVA. Future evidence from ongoing RCTs and prospective real-world studies are needed to prove the net health benefit of sequential treatment options for advanced HCC. [ABSTRACT FROM AUTHOR]

Combined endoscopical treatments for tracheo-esophageal fistula developed during V-V ECMO for severe COVID-19: A case series Keywords: Covid-19; ECMO; endoscopy; SARS-CoV 2; tracheo-esophageal fistula EN Covid-19 ECMO endoscopy SARS-CoV 2 tracheo-esophageal fistula 506 508 3 03/02/22 20220301 NES 220301 INTRODUCTION Patients affected with acute respiratory distress syndrome due to Covid-19 may require veno-venous extracorporeal membrane oxygenation (V-V ECMO), often undergoing tracheostomy.1,2 Tracheo-esophageal fistula (TEF) can develop as an immediate or late complication of tracheostomy, and can be enhanced by several conditions coexisting in severe Covid-19, such as malnutrition, soft tissue hypo-perfusion, need for high-dose vasopressors, mechanical damage during prone position, long hospitalization and ventilation, and long presence of nasogastric tubes.3 Furthermore, TEF can be dramatic in these patients since it may potentially progress to a mediastinitis, worsening the outcomes. CASE SERIES We experienced four cases of TEF among our first 36 tracheostomized patients on V-V ECMO during the COVID-19 second wave, between October, 2020 and May, 2021 (Table 1). [Extracted from the article]

Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), a novel coronavirus causing coronavirus disease 19 (COVID‐19), with an estimated 22 million people infected worldwide so far although involving primarily the respiratory tract, has a remarkable tropism for the liver and the biliary tract. Patients with SARS‐CoV‐2 infection and no antecedent liver disease may display evidence of cytolytic liver damage, proportional to the severity of COVID‐19 but rarely of clinical significance. The mechanism of hepatocellular injury is unclear and possibly multifactorial. The clinical impact of SARS‐CoV‐2 infection in patients with underlying chronic liver disease, a cohort whose global size is difficult to estimate, has been assessed appropriately only recently and data are still evolving. Patients with cirrhosis are at higher risk of developing severe COVID‐19 and worse liver‐related outcomes as compared to those with non‐cirrhotic liver disease. OLT patients have an intermediate risk. Specific interventions in order to reduce the risk of transmission of infection among this high‐risk population have been outlined by international societies, together with recommendations for modified treatment and follow‐up regimens during the COVID‐19 pandemic. When a vaccine against SARS‐CoV‐2 becomes available, patients with fibrotic liver disease and those with OLT should be considered as prime targets for prophylaxis of COVID‐19, as all other highly susceptible subjects. [ABSTRACT FROM AUTHOR]

Simple Summary: Surrogate radiology-based endpoints such as progression-free survival (PFS) and objective response rate (ORR) are commonly used in oncology. However, their surrogacy with overall survival (OS) has not been evaluated in immunotherapy trials for hepatocellular carcinoma (HCC). We found that the surrogacy of PFS with OS is highly variable depending on treatment class (immune-checkpoint inhibitors or multikinase inhibitors) and evaluation time-point. Early PFS is a robust surrogate endpoint for OS in immunotherapy trials, while the surrogacy relationship between ORR and OS is weak. Early assessment of PFS could be useful for allowing analyses with small sample sizes and short accrual times, enhancing the interpretability of immunotherapy trials in HCC. Background: Radiology-based outcomes, such as progression-free survival (PFS) and objective response rate (ORR), are used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of PFS with overall survival (OS) in clinical trials of systemic therapies targeting advanced hepatocellular carcinoma (HCC) by novel meta-regression methods. Methods: A search of databases (PubMed, American Society of Clinical Oncology (ASCO), and European Society for Medical Oncology (ESMO) Meeting Libraries, Clinicaltrials.gov) for trials of systemic therapies for advanced HCC reporting both OS and PFS was performed. Individual patient data were extracted from PFS and OS Kaplan–Meier curves. Summary median PFS and OS data were obtained from random-effect model. The surrogate relationships of median PFS, first quartile (Q1), third quartile (Q3), and restricted mean survival time (RMST) for OS were evaluated by the coefficient of determination R2. Heterogeneity was explored by meta-regression. Results: We identified 49 trials, 11 assessing immune-checkpoint inhibitors (ICIs) and 38 multikinase inhibitors (MKIs). Overall, the correlation between median PFS and median OS was weak (R2 = 0.20. 95% Confidence Intervals [CI]-0.02;0.42). Surrogacy robustness varied between treatment classes and PFS endpoints. In ICI trials only, the correlations between Q1-PFS and Q1-OS and between 12-month PFS-RMST and 12-month OS-RMST were high (R2 = 0.89, 95%CI 0.78–0.98, and 0.80, 95% CI 0.63–0.96, respectively). Interaction p-values obtained by meta-regression confirmed the robustness of results. Conclusions: In trials of systemic therapies for advanced HCC, the surrogate relationship of PFS with OS is highly variable depending on treatment class (ICI or MKI) and evaluation time-point. In ICI trials, Q1-PFS and 12-month PFS-RMST are robust surrogate endpoints for OS. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare that they have no conflict of interest.