Advancements in minimally invasive image-guided liver therapies

This thesis is a contribution to the fight against cancer. It focuses on patients with hepatic malignancies. Interventional oncology (IO) is a rapidly evolving sub-speciality of interventional radiology with an increasing role in the management of cancer patients. Over the past two decades interventional radiologists together with scientists have ridding the tidal wave of technological innovation to introduce multiple novel cancer treatments. IO procedures are minimally invasive, targeted therapies that are associated with low complication rates and short hospital admissions. Such therapies offer clear advantages over surgical procedures and intense chemotherapeutic regimes that put a larger burden on both the health care budget and patients. In this thesis several novel minimally invasive therapies are investigated. PART I focuses on image-guided percutaneous RFA. PART II discusses transarterial liver therapies, such as transarterial chemoembolisation, radioembolisation and percutaneous hepatic perfusion. PART III investigates ways to improve the management of patients that undergo IO procedures.LUMC / Geneeskund

In Vivo Proof of Superselective Transarterial Chemoembolization with 40-mu m Drug-Eluting Beads in a Patient with Hepatocellular Carcinoma

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Gastric Variceal Hemorrhage in a Noncirrhotic Patient Treated with Balloon-Occluded Retrograde Transvenous Obliteration

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Pilot study evaluating catheter-directed contrast-enhanced ultrasound compared to catheter-directed computed tomography arteriography as adjuncts to digital subtraction angiography to guide transarterial chemoembolization

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

In Reply: Neoadjuvant TKI Study in Early- and Intermediate Stage Hepatocellular Carcinoma

This letter to the editor responds to comments from Rizzo et al on recently reported results of a phase II study of dovitinib therapy for hepatocellular carcinoma.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Gadoxetic acid-enhanced magnetic resonance imaging significantly influences the clinical course in patients with colorectal liver metastases

Surgical oncolog

The role of proportionate kinetic growth rate fraction in future remnant liver function over volume determined by Tc-99m-Mebrofenin hepatobiliary scintigraphy including SPELT and computed tomography in the risk prediction of postoperative mortality in ALPPS

Transplant surger

Neoadjuvant treatment with angiogenesis-inhibitor dovitinib prior to local therapy in hepatocellular carcinoma: a phase II study

Background Hepatocellular carcinoma (HCC) recurrence rates following locoregional treatment are high. As multireceptor tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFRs) are effective in advanced HCC, we assessed the efficacy and safety of neoadjuvant systemic treatment with dovitinib in early- and intermediate-stage HCC. Materials and Methods Twenty-four patients with modified Child-Pugh class A early- and intermediate-stage HCC received neoadjuvant oral dovitinib 500 mg daily (5 days on/2 days off) for 4 weeks, followed by locoregional therapy. Primary endpoints were objective response rates and intratumoral blood flow changes. Secondary endpoints were safety, pharmacodynamical plasma markers of VEGFR-blockade, time to progression (TTP), and overall survival (OS). Results Modified RECIST overall response rate was 48%, including 13% complete remission, and despite dose reduction/interruption in 83% of patients, intratumoral perfusion index decreased significantly. Grade 3-4 adverse events, most frequently (on-target) hypertension (54%), fatigue (25%), and thrombocytopenia (21%), occurred in 88% of patients. Plasma VEGF-A, VEGF-D, and placental growth factor increased significantly, whereas sTie-2 decreased, consistent with VEGFR-blockade. Following neoadjuvant dovitinib, all patients could proceed to their original planned locoregional treatment. No delayed toxicity occurred. Seven patients (three early, four intermediate stage) underwent orthotopic liver transplant after median 11.4 months. Censoring at transplantation, median TTP and OS were 16.8 and 34.8 months respectively; median cancer-specific survival was not reached. Conclusion Already after a short 4-week dovitinib treatment period, intratumoral blood flow reduction and modest antitumor responses were observed. Although these results support use of systemic neoadjuvant strategies, the poor tolerability indicates that dovitinib dose adaptations are required in HCC. Implications for Practice Orthotopic liver transplantation may cure early and intermediate-stage hepatocellular carcinoma. Considering the expected waiting time >6 months because of donor liver scarcity, there is an unmet need for effective neoadjuvant downsizing strategies. Angiogenesis inhibition by dovitinib does not negatively affect subsequent invasive procedures, is safe to administer immediately before locoregional therapy, and may provide a novel treatment approach to improve patient outcomes if tolerability in patients with hepatocellular carcinoma can be improved by therapeutic drug monitoring and personalized dosing.MTG4Molecular tumour pathology - and tumour genetic

Prospective Clinical and Pharmacological Evaluation of the Delcath System's Second-Generation (GEN2) Hemofiltration System in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan

Surgical oncolog