Endoscopy at Bedside in Isolated Patients with Severe COVID-19: Our Approach during the Pandemic

The COVID-19 pandemic changed the management of emergency medicine and those complications that needed interventional procedures, such as endoscopy or other radiological procedures. At the beginning of the outbreak, there were no exploitable recommendations regarding the proper policy to apply for limiting the virus spread during endoscopy. Between the first and the second wave, the approach regarding interventional procedures changed, due to higher awareness and newly defined protocols, even if different among the health centers. Patients with severe COVID-19 may develop major gastrointestinal complications or require nutritional support, so interventional procedures are required at bedsid…

Endoscopic Treatment of Iatrogenic Perforation of Sigmoid Diverticulum: A Case Report of Multidisciplinary Management

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-the-scope 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 appr…

Combined endoscopical treatments for tracheo‐esophageal fistula developed during V‐V ECMO for severe COVID‐19: A case series

Optimizing Sequential Systemic Therapies for Advanced Hepatocellular Carcinoma: A Decision Analysis

Background: An optimal sequential systemic therapy for advanced hepatocellular carcinoma (HCC) has not been discovered. We developed a decision model based on available clinical trials to identify an optimal risk/benefit strategy for sequences of novel systemic agents. Methods: A Markov model was built to simulate overall survival (OS) among patients with advanced HCC. Three first-line (single-agent Sorafenib or Lenvatinib, and combination of Atezolizumab plus Bevacizumab) followed by five second-line treatments (Regorafenib, Cabozantinib, Ramucirumab, Nivolumab, Pembrolizumab) were compared in fifteen sequential strategies. The likelihood of transition between states (initial treatment, ca…

First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> A Markov model was built to estimate the overall survival (OS) of sequential first- and second-line systemic treatments. Seque…

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: An individual patient data meta-analysis

ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk fac…

Outcomes of hepatocellular carcinoma patients treated with sorafenib: a meta-analysis of Phase III trials

Aim: To benchmark overall survival (OS) and time to radiological progression (TTP) of patients enrolled in randomized controlled trials (RCTs) assessing sorafenib in advanced hepatocellular carcinoma using individual participant survival data, and to meta-analyze prognostic factors for OS and TTP. Methods: RCTs were identified through literature search until December 2018. Individual participant survival was reconstructed with an algorithm from published Kaplan–Meier curves. Results: Ten RCTs were included. Median OS was 10.0 months (95% CI: 9.6–10.5), and median TTP was 4.1 months (95% CI: 3.8–4.3). Multivariable analyses showed HCV positivity, absence of macrovascular invasion and extra-…

Mirizzi syndrome type V complicated with both cholecystobiliary and cholecystocolic fistula: a case report

Abstract Mirizzi syndrome (MS) is a common bile duct (CBD) obstruction caused by extrinsic compression from an impacted stone in the cystic duct or infundibulum of the gallbladder. Patients affected by MS may present abdominal pain and jaundice. A 37-year-old male with neurologic residuals post-encephalitis arrived at the emergency department reporting abdominal pain, jaundice and fever. An ultrasound of the abdomen identified cholecystolithiasis with a dilated CBD. He did not undergo CT or MRI due to poor compliance and parents’ disagreement. Eventually, they accepted to perform endoscopic retrograde cholangiopancreatography, which diagnosed MS with both cholecystobiliary and cholecystocol…

Mirizzi syndrome in a patient with partial gastrectomy with Billroth II anastomosis: A case report

Highlights • Obstructive jaundice may be a challenge for differential diagnosis. • Mirizzi Syndrome may simulate clinical and radiological presentation of common bile duct stones. • ERCP hardly achieves cannulation of biliary duct in altered anatomy, so gastroscope may be a correct choice in these cases. • Surgical treatment is essential in Mirizzi Syndrome.

Are radiological endpoints surrogate outcomes of overall survival in hepatocellular carcinoma treated with transarterial chemoembolization?

Background& Aims: Time to progression (TTP) and progression-free survival (PFS) are commonly used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of TTP and PFS with overall survival (OS) in studies of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (u-HCC) by innovative methods. Methods: A search of databases for studies of TACE for u-HCC reporting both OS and TTP or PFS was performed. Individual patient data were extracted from TTP/PFS and OS Kaplan-Meier curves of TACE arms. Pooled median TTP and OS were obtained from random-effect model. The surrogate relationships of hazard ratios (HRs) and median TTP for OS …

Biliopancreatic Endoscopy in Altered Anatomy

Background and Objectives: Anatomical post-surgical alterations of the upper gastrointestinal (GI) tract have always been challenging for performing diagnostic and therapeutic endoscopy, especially when biliopancreatic diseases are involved. Esophagectomy, gastrectomy with various reconstructions and pancreaticoduodenectomy are among the most common surgeries causing upper GI tract alterations. Technological improvements and new methods have increased the endoscopic success rate in these patients, and the literature has been rapidly increasing over the past few years. The aim of this systematic review is to identify evidence on the available biliopancreatic endoscopic techniques performed i…

Modeling sequential systemic therapy for unresectable hepatocellular carcinoma in the era of immunotherapy: What comes next?

324 Background: Atezolizumab plus Bevacizumab represents the new best performing first-line approach for unresectable hepatocellular carcinoma (u-HCC). However, the best sequential strategy after every first-line failure (for progression or intolerance) remains elusive, and options for retreating patients failing Atezolizumab plus Bevacizumab with multi-kinase inhibitors (MKI) or immune checkpoint inhibitor (ICI) are yet undefined. Methods: We developed a Markov model to analyze simulated-Overall Survival (s-OS) of second-line ICIs or MKIs after first-line Atezolizumab plus Bevacizumab over a lifetime horizon. For first-line therapy, PFS of Atezolizumab plus Bevacizumab was extracted from …

Recalibrating survival prediction among patients receiving trans‐arterial chemoembolization for hepatocellular carcinoma

Background & Aims The Pre-TACE-Predict model was devised to assess prognosis of patients treated with trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). However, before entering clinical practice, a model should demonstrate that it performs a useful role. Methods We performed an independent external validation of the Pre-TACE model in a cohort that differs in setting and time period from the one that generated the original model. Data from 826 patients treated with TACE for naïve HCC (2008-2018) were used to assess calibration and discrimination of the Pre-TACE-Predict model. Results The four risk-categories identified by the Pre-TACE-Predict model had gradient …

SARS-CoV-2 infection in patients with a normal or abnormal liver.

Abstract 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 …

Monofocal hepatocellular carcinoma: How much does size matter?

Background & Aims: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (>5 cm) monofocal (HCC). Methods: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5 cm; SEM-HCC), 163 patients with larger tumours (>5 cm; LEM-HCC) and 1048 intermediate stage patients (BCLC B). Results: LEM-HCC patients had a worse overall survival (OS) than SEM-HCC (31.0 vs 49.0 months; P…

Material deprivation affects the management and clinical outcome of hepatocellular carcinoma in a high-resource environment

Abstract Aim This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. Methods 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material deprivation (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. Results In more deprived regions, HCC was more frequently diagnosed during surveillan…

Surveillance for hepatocellular carcinoma with a 3-months interval in “extremely high-risk” patients does not further improve survival

Abstract Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveil…

Hepatitis B Virus-Associated Hepatocellular Carcinoma

Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mecha…

An evaluation score of the difficulty of thyroidectomy considering operating time and preservation of recurrent laryngeal nerve.

The purpose of this study was to edit a renovated thyroidectomy difficulty scale (rTDS) in order to identify underlying thyroid diseases with a longer operative time and higher technical difficulty, also considering preservation of recurrent laryngeal nerve. We developed a renovated scale with a maximum score of 20 points by creating a form in which five variables were considered: vascularity, friability, mobility/fibrosis, gland size and difficulty in preservation of the recurrent laryngeal nerve. Two surgeons separately evaluated each of these. Through a simple linear regression analysis, we have analyzed the relationship between rTDS score and operative times, and between rTDS score and …

Progression-Free Survival Early Assessment Is a Robust Surrogate Endpoint of Overall Survival in Immunotherapy Trials of Hepatocellular Carcinoma

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&nd…