A review discussing the use of polyethylene glycol microspheres in the treatment of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is indicated in unresectable hepatocellular carcinoma and allows the delivery of embolics inside tumor vascularization to reduce blood supply and release gradually the drug. This lowers the systemic exposure to chemotherapeutics, while increasing their local concentration and tissue necrosis that is higher than conventional TACE. The technology of TACE has seen the introduction of several types of embolics that are made of different materials. Available embolics for TACE include: drug-eluting beads (DC beads), acrylic copolymer, tris-acrylic microspheres and polyethylene glycol (PEG) microspheres. Few studies are available on PEG embolics and their use for TACE. This review focuses on the efficacy and safety of TACE performed with PEG microspheres for the treatment of hepatocellular carcinoma and discusses future therapeutic advantages.

Management of spontaneous soft-tissue hemorrhage secondary to anticoagulant therapy: A cohort study.

STUDY OBJECTIVE: The optimal management of patients receiving heparin, warfarin or direct anti-coagulant therapy who experience spontaneous, severe, life-threatening soft-tissue hemorrhage (SSTH) is unclear. The purpose of this study is to investigate efficacy and safety of the interventional protocol implemented in our department. METHODS: In this retrospective cohort study, we analyzed data from 80 consecutive patients with SSTH secondary to anticoagulation therapy diagnosed by the appropriate computed tomography scan. All patients received a structured clinical pathway, including aggressive resuscitation, reversal of coagulopathy when indicated, Interventional Radiology procedures by transcatheter embolization (TE), clinical observation and repeated laboratory controls. RESULTS: We enrolled 80 patients from 2013 to 2017. Angiography was performed in 60 patients (75%). It revealed the bleeding site in 46 cases, and a TE was performed in all. The rates of technical success of TE, primary clinical success and bleeding control were 98% (45/46), 91% (73/80) and 89% (71/80) respectively. In 5 patients (6%) the control of the bleeding was obtained with a second TE. Short-term and 30-day mortality was 5% (4 patients) and 11% (9 patients), respectively. No adverse events were observed. CONCLUSION: A structured clinical pathway, including TE seems to be an effective and safe method to manage the patients with SSTH due to anticoagulant treatment.

Radiological response and inflammation scores predict tumour recurrence in patients treated with transarterial chemoembolization before liver transplantation.

AIM: To investigate the prognostic value of the radiological response after transarterial chemoembolization (TACE) and inflammatory markers in patients affected by hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). METHODS: We retrospectively evaluated the preoperative predictors of HCC recurrence in 70 patients treated with conventional (n = 16) or doxorubicin-eluting bead TACE (n = 54) before LT. The patient and tumour characteristics, including the static and dynamic alpha-fetoprotein, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (PLR) measurements, were recorded. Treatment response was classified according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and the European Association for the Study of the Liver (EASL) criteria as complete response (CR), partial response (PR), stable disease or progressive disease. After examination of the explanted livers, histological necrosis was classified as complete (100% of the cumulative tumour area), partial (50%-99%) or minimal (< 50%) and was correlated with the preoperative radiological findings. RESULTS: According to the pre-TACE radiological evaluation, 22/70 (31.4%) and 12/70 (17.1%) patients were beyond Milan and University of San Francisco (UCSF) criteria, respectively. After TACE procedures, the objective response (CR + PR) rates were 71.4% and 70.0% according to mRECIST and EASL criteria, respectively. The agreement between the two guidelines in defining the radiological response was rated as very good both for the overall and target lesion response (weighted k-value: 0.98 and 0.93, respectively). Complete and partial histological necrosis were achieved in 14/70 (20.0%) and 28/70 (40.0%) patients, respectively. Using histopathology as the reference standard, mRECIST criteria correctly classified necrosis in 72.9% (51/70) of patients and EASL criteria in 68.6% (48/70) of cases. The mRECIST non-response to TACE [Exp(b) = 9.2, p = 0.012], exceeding UCSF criteria before TACE [Exp(b) = 4.7, p = 0.033] and a preoperative PLR > 150 [Exp(b) = 5.9, p = 0.046] were independent predictors of tumour recurrence. CONCLUSION: The radiological response and inflammatory markers are predictive of tumour recurrence and allow the proper selection of TACE-treated candidates for LT.

Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation.

AIM: To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization (TACE) on recurrence-free survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and to analyze the effects of TACE on tumor histology. METHODS: We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation. Patients who received any other type of treatment such as radiofrequency tumor ablation, percutaneous ethanol ablation or who were not treated at all were excluded. All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation. Doxorubicin-eluting bead TACE (DEB-TACE) was performed in 22 patients (38 nodules), and conventional TACE (c-TACE) in 16 (25 nodules). Patients' and tumors' characteristics were retrospectively reviewed. We performed a per-nodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE (conventional or DEB) and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area, including 21 nodules not reached by TACE. Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent, moderate and enhanced reaction. Uni- and multivariate analysis of risk factors for HCC-recurrence were performed. RESULTS: The number and diameter of the nodules, the time spent on the waiting list and the number of treatments were similar in the two groups. A trend towards higher appropriate response rates (necrosis ≥ 90%) was observed in the DEB-TACE group (44.7% vs 32.0%, P = 0.2834). The mean percentage of necrosis in the cumulative tumor area was 58.8% ± 36.6% in the DEB-TACE group and 50.2% ± 38.1% in the c-TACE group (P = 0.4856). Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group (P < 0.0001, for both the parameters). The three-year recurrence-free survival was higher in DEB-TACE-treated patients than in conventionally treated patients (87.4% vs 61.5%, P = 0.0493). Other factors affecting recurrence-free survival included viable tumor beyond Milan Criteria on histopathological examination, the percentage of necrosis on CTA ≤ 50% and a pre-transplant serum α-fetoprotein level greater than 70 ng/mL. On multivariate analysis, the lack of treatment with DEB-TACE, high levels of α-fetoprotein and viable tumor beyond Milan Criteria at histology examination were identified as independent predictors of tumor recurrence. CONCLUSION: DEB-TACE can effectively promote tumor necrosis and improves recurrence-free survival after LT in HCC.

Trans-arterial chemo-embolization (TACE), with either lipiodol (traditional TACE) or drug-eluting microspheres (precision TACE, pTACE) in the treatment of hepatocellular carcinoma: efficacy and safety results from a large mono-institutional analysis.

More data about TACE and pTACE seem necessary to better define the global treatment strategy for HCC. Aim of our analysis was to evaluate the role of TACE, either with lipiodol (traditional) or drug-eluting microspheres in terms of response rate (RR), time to progression (TTP), overall survival (OS) and toxicity in HCC.Patients with HCC undergoing traditional TACE or pTACE (either alone or in combination with other treatment options) were eligibleOne hundred and fifty patients were analyzed. In the global patient population median OS was 46 months for lipiodol TACE and 19 months for pTACE (p < 0.0001), TTP was 30 months versus 16 months for patients receiving TACE or pTACE respectively (p = 0.003). These results were confirmed also among the group of patients who received exclusive TACE or pTACE. Neither RR nor toxicity was different between TACE or pTACE.At multivariate analysis, age, the Okuda stage, type of TACE and number of TACE proved to be independent prognostic factors influencing overall survival.In our experience, lipiodol TACE showed a better OS and TTP over pTACE, without difference in toxicity profile and RR. Among the staging systems analyzed only the Okuda stage seemed able to reliably predict patients outcome.