Optimizing Loco Regional Management of Oligometastatic Colorectal Cancer: Technical Aspects and Biomarkers, Two Sides of the Same Coin

Colorectal cancer (CRC) is the third most common cancer worldwide and has a high rate of metastatic disease which is the main cause of CRC-related death. Oligometastatic disease is a clinical condition recently included in ESMO guidelines that can benefit from a more aggressive locoregional approach. This review focuses the attention on colorectal liver metastases (CRLM) and highlights recommendations and therapeutic locoregional strategies drawn from the current literature and consensus conferences. The different percutaneous therapies (radiofrequency ablation, microwave ablation, irreversible electroporation) as well as trans-arterial approaches (chemoembolization and radioembolization) are discussed. Ablation margins, the choice of the imaging guidance as well as characteristics of the different ablation techniques and other technical aspects are analyzed. A specific attention is then paid to the increasing role of biomarkers (in particular molecular profiling) and their role in the selection of the proper treatment for the right patient. In conclusion, in this review an up-to-date state of the art of the application of locoregional treatments on CRLM is provided, highlighting both technical aspects and the role of biomarkers, two sides of the same coin

Combined transarterial chemoembolization and thermal ablation in candidates to liver transplantation with hepatocellular carcinoma: pathological findings and post-transplant outcome

Objectives Evaluating the pathological response and the survival outcomes of combined thermal ablation (TA) and transarterial chemoembolization (TACE) as a bridge or downstaging for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) > 3 cm. Materials and methods A retrospective review encompassed 36 consecutive patients who underwent combined TA-TACE as bridging or downstaging before LT. Primary objectives included necrosis of the target lesion at explant pathology, post-LT overall survival (OS) and post-LT recurrence-free survival (RFS). For OS and RFS, a comparison with 170 patients subjected to TA alone for nodules <3 cm in size was also made. Results Out of the 36 patients, 63.9% underwent TA-TACE as bridging, while 36.1% required downstaging. The average node size was 4.25 cm. All cases were discussed in a multidisciplinary tumor board to assess the best treatment for each patient. Half received radiofrequency (RF), and the other half underwent microwave (MW). All nodes underwent drug-eluting beads (DEB) TACE with epirubicin. The mean necrosis percentage was 65.9% in the RF+TACE group and 83.3% in the MW+TACE group (p-value = 0.099). OS was 100% at 1 year, 100% at 3 years and 94.7% at 5 years. RFS was 97.2% at 1 year, 94.4% at 3 years and 90% at 5 years. Despite the different sizes of the lesions, OS and RFS did not show significant differences with the cohort of patients subjected to TA alone. Conclusions The study highlights the effectiveness of combined TA-TACE for HCC>3 cm, particularly for bridging and downstaging to LT, achieving OS and RFS rates significantly exceeding 80% at 1, 3 and 5 years

Intrahepatic Administration of Human Liver Stem Cells in Infants with Inherited Neonatal-Onset Hyperammonemia: A Phase I Study

Previous studies have shown that human liver stem-like cells (HLSCs) may undergo differentiation in vitro into urea producing hepatocytes and in vivo may sustain liver function in models of experimentally induced acute liver injury. The aim of this study was to assess the safety of HLSCs intrahepatic administration in inherited neonatal-onset hyperammonemia. The study was approved by the Agenzia Italiana del Farmaco on favorable opinion of the Italian Institute of Health as an open-label, prospective, uncontrolled, monocentric Phase I study (HLSC 01-11, EudraCT-No. 2012-002120-33). Three patients affected by argininosuccinic aciduria (patient 1) and methylmalonic acidemia (patients 2 and 3) and included in the liver transplantation list were enrolled. In all patients, HLSCs were administered by percutaneous intrahepatic injections (once a week for two consecutive weeks) within the first months of life. The first patient received 125,000 HLSCs x gram of liver/dose while the other two patients received twice this dose. No immunosuppression was administered since HLSCs possess immunomodulatory activities. None of the patients experienced infections, hyperammonemia decompensation, or other adverse events during the whole observation period. No donor specific antibodies (DSA) against HLSCs were detected. Patients were metabolic stable despite an increase (~30%) in protein intake. Two patients underwent liver transplantation after 19 and 11 months respectively, and after explantation, the native livers showed no histological alterations. In conclusion, percutaneous intrahepatic administration of HLSCs was safe in newborn with inherited neonatal-onset hyperammonemia. These data pave the way for Phase II studies in selected inherited and acquired liver disorders

Radiofrequency ablation for thyroid nodules: which indications? The first Italian opinion statement

Nodular thyroid disease is a very common finding in clinical practice, discovered by ultrasound (US) in about 50 % of the general population, with higher prevalence in women and in the elderly [1–4]. Whereas therapeutic flowchart is quite established and shared for malignant lesions, multiple options are now available for patients presenting with benign thyroid nod- ules, ranging from simple clinical and US follow-up to thyroid surgery. The majority of thyroid nodules, benign by fine-needle aspiration, are asymptomatic, stable, or slow- growing over time and require no treatmen