Impact of Different Embolic Agents for Transarterial Chemoembolization (TACE) Procedures on Systemic Vascular Endothelial Growth Factor (VEGF) Levels

Schicho, Andreas; Hellerbrand, Claus; Krüger, Kristina; Beyer, Lukas Philipp; Wohlgemuth, Walter A.; Niessen, Christoph; Hohenstein, Ernst; Stroszczynski, Christian; Pereira, Philippe L.; Wiggermann, Philipp

doi:10.14218/jcth.2016.00058

Cited by 52 publications

(30 citation statements)

References 36 publications

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“…Serum VEGF levels increase after TACE and remain elevated for at least four weeks, especially after conventional TACE. 23–25 VEGF is associated not only with outcome after TACE 23,26 but is also involved in the pathophysiology of PHT, as it promotes vasodilation and splanchnic vascularization, aggravating hyperdynamic splanchnic circulation and eventually increasing portal pressure. 27,28 Notably, anti–VEGF-targeted treatment has previously been shown to ameliorate portal hypertensive syndrome in rats.…”

Section: Discussionmentioning

confidence: 99%

Short‐ and long‐term effects of transarterial chemoembolization on portal hypertension in patients with hepatocellular carcinoma

et al. 2019

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Background Transarterial chemoembolization (TACE) affects hepatic perfusion, and might have an impact on portal pressure in patients with hepatocellular carcinoma (HCC). Objective The objective of this article is to report the secondary outcome “hepatic hemodynamics” from the AVATACE trial, a prospective randomized, placebo-controlled trial on the efficacy of conventional TACE in combination with bevacizumab or placebo. Methods Hepatic venous pressure gradient (HVPG) was measured at baseline (prior to first TACE), within nine days (“acute effects”), two months (“intermediate effects”) and six months (“long-term effects”) after the first TACE. Results Of 28 patients with early-intermediate stage HCC, n = 20 (71%) had clinically significant portal hypertension (CSPH, HVPG ≥ 10 mmHg) at baseline (median, 12 (interquartile range (IQR): 9–19) mmHg). TACE had neither “acute effects” nor “intermediate effects” on HVPG. However, in 13 patients with available HVPG measurement at month 6, there was a significant increase in HVPG (median, 16 (IQR: 11–19) mmHg) compared with baseline (median, 10 (IQR: 5–12) mmHg; p = 0.007). Portal hypertension-related complications occurred exclusively in patients with CSPH (8 (40%) vs 0). Conclusions Repeated TACE was associated with a significant long-term increase in HVPG. This should be considered when deciding whether to continue with TACE or switch to systemic treatment, since CSPH drives the development of complications.

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Section: Discussionmentioning

confidence: 99%

Short‐ and long‐term effects of transarterial chemoembolization on portal hypertension in patients with hepatocellular carcinoma

et al. 2019

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“…Permanent occlusion of TFV or an incomplete embolization has effects on tumour stromal microenvironment and induces intra-and intercellular signaling processes counteracting and reversing hypoxia (Carmeliet, 2005;Orlacchio et al, 2020), such as the activation of HIFs (hypoxia-inducible factors) and the subsequent release of vascular endothelial growth factor (VEGF), a promoter of neoangiogenesis, tumour proliferation and metastatic growth (Lencioni et al, 2013). To avoid VEGF overexpression and minimize detrimental effects on liver function, both induced by post-embolization ischemia, the idea of the transient occlusion of tumour feeding arteries (a half-life in vitro of 35-50 min) using DSM was born (Pieper et al, 2015;Schicho et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Degradable Starch Microspheres Transcatheter Arterial Chemoembolization as a Bridging Therapy in Patients with Early Stage Hepatocellular Carcinoma and Child-Pugh Stage B Eligible for Liver Transplant

et al. 2021

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In patients with early-stage hepatocellular carcinoma, awaiting liver transplantation, current guidelines by AASLD and ESMO recommend a bridging therapy with a loco-regional treatment to prevent progression outside transplantation criteria. The standard of care in delaying disease progression has been recognized to be the transarterial chemoembolization. Permanent occlusion of tumor feeding vessels has effects on tumour stromal microenvironment by inducing intra- and intercellular signaling processes counteracting hypoxia, such as the release of vascular endothelial growth factor, a promoter of neoangiogenesis, tumour proliferation and metastatic growth. Among chemoembolization interventions, TACE with degradable starch microspheres represents an alternative to conventional cTACE and DEB-TACE and it minimizes detrimental effects on tumour stromal microenvironment, guaranteeing a transient occlusion of tumour feeding arteries and avoiding VEGF overexpression.Between January 2015 and September 2020, 54 consecutive patients with early-stage hepatocellular carcinoma and Child-Pugh stage B, who had undergone DSM-TACE as a bridging therapy while awaiting liver transplantation, were eligible for the study. A total of 154 DSM-TACE was performed, with a mean number of 2.85 procedures per patient. 18 patients (33.3%) succeeded in achieving liver transplantation, with a mean waiting time-to-transplantation of 11.7 months. The cumulative rates of patients still active on the WL at 6 months were about 91 and 93% when considering overall drop-out and tumour-specific drop-out respectively. Overall survival was about 96% at 6 months and 92% at 12 months. 17 patients experienced adverse events after the chemoembolizations. For patients with HCC in the transplant waiting list and within the Child-Pugh B stage, life expectancy may be dominated by the liver dysfunction, rather than by the tumour progression itself. In this population subset, the choice of LRT is critical because LRT itself could become a dangerous tool that is likely to precipitate liver dysfunction to an extent that survival is shortened rather than prolonged. Hence, the current study demonstrates that DSM-TACE is not far from being an ideal LRT, because it has an excellent safety profile, maintaining an efficacy that guarantees a clear advantage on the dropout rate with respect to the non-operative strategy, thus justifying its use.

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“…In HCC, a temporary overproduction of vascular endothelial growth factor (VEGF) is caused by a single session of TACE. And an increase in serum VEGF is related to tumor growth via neoangiogenesis, metastatic seeding, and cancer cell migration and survival[32]. Lipiodol emulsion, used in cTACE, causes unstable ischemia with reperfusion injury in the targeted tissue[32].…”

Section: Discussionmentioning

confidence: 99%

“…And an increase in serum VEGF is related to tumor growth via neoangiogenesis, metastatic seeding, and cancer cell migration and survival[32]. Lipiodol emulsion, used in cTACE, causes unstable ischemia with reperfusion injury in the targeted tissue[32]. On the other hand, the beads used in DEB-TACE lead to irreversible permanent embolization and ischemia[33].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the beads used in DEB-TACE lead to irreversible permanent embolization and ischemia[33]. Schicho et al[32], compared cTACE with DEB-TACE, finding that VEGF plasma levels were significantly higher in cTACE patients as soon as 24 h after treatment ( P = 0.01) and remained at high levels 28 d after cTACE ( P = 0.03), compared to DEB-TACE patients. Thus, perhaps DEB-TACE should be preferentially used when TACE is the LRT option that is considered.…”

Section: Discussionmentioning

confidence: 99%

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Long-term outcomes of hepatocellular carcinoma that underwent chemoembolization for bridging or downstaging

Affonso

Galastri

Motta-Leal-Filho

et al. 2019

WJG

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BACKGROUNDProspective study of 200 patients with hepatocellular carcinoma (HCC) that underwent liver transplant (LT) after drug-eluting beads transarterial chemoembolization (DEB-TACE) for downstaging versus bridging. Overall survival and tumor recurrence rates were calculated, eligibility for LT, time on the waiting list and radiological response were compared. After TACE, only patients within Milan Criteria (MC) were transplanted. More patients underwent LT in bridging group. Five-year post-transplant overall survival, recurrence-free survival has no difference between the groups. Complete response was observed more frequently in bridging group. Patients in DS group can achieve post-transplant survival and HCC recurrence-free probability, at five years, just like patients within MC in patients undergoing DEB-TACE.AIMTo determine long-term outcomes of patients with HCC that underwent LT after DEB-TACE for downstaging vs bridging.METHODSProspective cohort study of 200 patients included from April 2011 through June 2014. Bridging group included patients within MC. Downstaging group (out of MC) was divided in 5 subgroups (G1 to G5). Total tumor diameter was ≤ 8 cm for G1, 2, 3, 4 (n = 42) and was > 8 cm for G5 (n = 22). Downstaging (n = 64) and bridging (n = 136) populations were not significantly different. Overall survival and tumor recurrence rates were calculated by the Kaplan-Meier method. Additionally, eligibility for LT, time on the waiting list until LT and radiological response were compared.RESULTSAfter TACE, only patients within MC were transplanted. More patients underwent LT in bridging group 65.9% (P = 0.001). Downstaging population presented: higher number of nodules 2.81 (P = 0.001); larger total tumor diameter 8.09 (P = 0.001); multifocal HCC 78% (P = 0.001); more post-transplantation recurrence 25% (P = 0.02). Patients with maximal tumor diameter up to 7.05 cm were more likely to receive LT (P = 0.005). Median time on the waiting list was significantly longer in downstaging group 10.6 mo (P = 0.028). Five-year post-transplant overall survival was 73.5% in downstaging and 72.3% bridging groups (P = 0.31), and recurrence-free survival was 62.1% in downstaging and 74.8% bridging groups (P = 0.93). Radiological response: complete response was observed more frequently in bridging group (P = 0.004).CONCLUSIONTumors initially exceeding the MC down-staged after DEB-TACE, can achieve post-transplant survival and HCC recurrence-free probability, at five years, just like patients within MC in patients undergoing DEB-TACE.

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Impact of Different Embolic Agents for Transarterial Chemoembolization (TACE) Procedures on Systemic Vascular Endothelial Growth Factor (VEGF) Levels

Cited by 52 publications

References 36 publications

Short‐ and long‐term effects of transarterial chemoembolization on portal hypertension in patients with hepatocellular carcinoma

Short‐ and long‐term effects of transarterial chemoembolization on portal hypertension in patients with hepatocellular carcinoma

Safety and Efficacy of Degradable Starch Microspheres Transcatheter Arterial Chemoembolization as a Bridging Therapy in Patients with Early Stage Hepatocellular Carcinoma and Child-Pugh Stage B Eligible for Liver Transplant

Long-term outcomes of hepatocellular carcinoma that underwent chemoembolization for bridging or downstaging

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