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- Karalli, Amar
(författare)
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Transarterial chemoembolization in primary liver and kidney malignancies
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and the most current treatment for unresectable hepatocellular carcinoma is transarterial chemoembolization using drug-eluting beads (DEB-TACE). The concept of TACE might also technically be applicable to other types of hypervascular cancers such as renal cell carcinoma (RCC). The overall aims of this project were to improve the understanding of DEB-TACE as a treatment of unresectable HCC and to assess its feasibility in treating RCC. By using computerized tomography (CT) imaging before and early after DEB-TACE, in addition to the routine follow-up imaging, it was shown in study I that high arterial and low portal perfusion early after TACE indicated incomplete response with good diagnostic accuracy. Interestingly, it was also shown that portal perfusion of HCC was significantly higher in treated HCC compared to non-treated HCC (p = 0.01). In study II the drug delivery performance, safety, and the grade of necrosis after DEBTACE were compared to those of an alternative treatment, transarterial infusion (TAI) of doxorubicin-in-lipiodol emulsion. TAI is applied by injecting the emulsion in the vessel supplying a liver lobe without performing an embolization. Free doxorubicin and its metabolites were collected locally by placement of a pigtail catheter adjacent to the orifice of the liver veins and peripherally through standard venous blood samples and in urine samples. It was shown that the release of doxorubicin from the drug-eluting embolic agent was more controlled and prolonged. It was also shown that DEB-TACE caused milder adverse effects than TAI. The overall response (complete and partial response combined) for DEB-TACE was 91% compared to 67% for TAI, but this difference was not statistically significant. TAI of the doxorubicin-in-lipiodol emulsion followed by embolization of the HCCs’ feeding artery is known as conventional TACE (cTACE). In our center a switch from cTACE to DEB-TACE was made in 2009. A retrospective comparison between cTACE and DEB-TACE in this tertiary center (study III) showed no significant difference in overall survival between the two treatments. The adverse effects were significantly less common (p < 0.05) after DEB-TACE compared to after cTACE. In study IV, randomizing 12 patients with RCC eligible for surgery to either DEBTACE or transarterial embolization (TAE) using the same embolic agent as in DEBTACE, but unsaturated with doxorubicin, made it possible to evaluate the feasibility of these two techniques in treating RCC and to assess their effect using CT preoperatively and microscopy postoperatively. Both treatments were feasible. DEBDEB- TACE caused significantly more tumor necrosis (p < 0.018 on CT and p < 0.016 on microscopy) than TAE. The results of the evaluation by CT correlated significantly with the results of the evaluation by the microscopy (p < 0.005), suggesting that CT can be used to evaluate the effect of embolization on RCC. The fact that viable cancer cells were seen on microscopy even when CT showed total necrosis of the treated RCC limits DEB-TACE to palliation. In conclusion, DEB-TACE changes HCC perfusion, causes fewer adverse effects compared to TAI and cTACE, and can be used to treat RCC.
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- Lilienberg, Elsa, et al.
(författare)
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In vivo Drug Delivery Performance of Lipiodol-based Emulsion or Drug-eluting Beads in Patients with Hepatocellular Carcinoma
- 2017
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:2, s. 448-458
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Tidskriftsartikel (refereegranskat)abstract
- Doxorubicin (DOX) delivered in a lipiodol-based emulsion (LIPDOX) or in drug-eluting beads (DEBDOX) is used as palliative treatment in patients with intermediate-stage hepatocellular carcinoma (HCC). The primary objective of this study was to evaluate the in vivo delivery performance of DOX from LIPDOX or DEBDOX in HCC patients using the local and systemic pharmacokinetics of DOX and its main metabolite doxorubicinol (DOXol). Urinary excretion of DOX and DOXol, and their short-term safety and anti-tumor effects were also evaluated. In this open, prospective, non-randomized multi-center study, LIPDOX (n=13) or DEBDOX (n=12) were injected into the feeding arteries of the tumor. Local (vena cava/hepatic vein orifice) and systemic (peripheral vein) plasma concentrations of DOX and DOXol were determined in samples obtained up to 6 h and 7 days after treatment. Tumor response was assessed using computed tomography or magnetic resonance imaging. The Cmax and AUC0-24 h for DOX were 5.6-fold and 2.4-fold higher in LIPDOX vs DEBDOX recipients, respectively (p <0.001). After 6 h, the respective mean proportions of the dose remaining in the liver or drug-delivery system (DDS) were 49% for LIPDOX and 88% for DEBDOX. LIPDOX releases DOX faster than DEBDOX in HCC patients and provides more extensive local and systemic exposure (AUC) to DOX and DOXol initially (0-7 days). DEBDOX formulation has a release and distribution of DOX that is more restricted and rate controlled than LIPDOX.
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