Experimental Studies of Portal Venous Embolization with Iodized Oil in Rats with Experimentally Induced Liver Cancer

Dong, Youhai; Lin, Gui

doi:10.1016/s1051-0443(93)71935-1

Cited by 9 publications

(5 citation statements)

References 11 publications

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“…But, small HCCs in human patients (< 2 cm) are frequently not hypervascular [ 26 ] and can be further divided into two types, namely vaguely nodular, well-differentiated tumor (“early” HCC), and distinctly nodular lesion with similar histological feature to “classic” large HCC (small HCC of distinctly nodular type) [ 27 ]. Likewise, in DENA-induced rat liver cancer, it has been shown that hepatic tumor nodules smaller than 5 mm are fundamentally supplied by the portal vein, which is distinguishing from the large rat HCCs [ 20 ]. Given the diverse HCC vascularity, it would be valuable to analyze the early HCCs as a subgroup of micro-HCCs.…”

Section: Discussionmentioning

confidence: 99%

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Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P

et al. 2017

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We sought to investigate anticancer efficacy of a vascular disrupting agent (VDA) combretastatin A-4 phosphate (CA4P) in relation to tumor size among hepatocellular carcinomas (HCCs) in rats using magnetic resonance imaging (MRI) and postmortem techniques. Nineteen rats with 43 chemically-induced HCCs of 2.8–20.9 mm in size on liver cirrhosis received CA4P intravenously at 10 mg/kg. Tumor-diameter was measured by T2-weighted imaging (T2WI) to define microcancers (< 5 mm) versus larger HCCs. Vascular responses and tissue necrosis were detected by diffusion-weighted imaging (DWI), contrast-enhanced T1-weighted imaging (CE-T1WI) and dynamic contrast enhanced (DCE-) MRI, which were validated by microangiography and histopathology. MRI revealed nearly complete necrosis in 5 out of 7 micro-HCCs, but diverse therapeutic necrosis in larger HCCs with a positive correlation with tumor size. Necrosis in micro-HCCs was 36.9% more than that in larger HCCs. While increased diffusion coefficient (ADCdiff) suggested tumor necrosis, perfusion coefficient (ADCperf) indicated sharply decreased blood perfusion in cirrhotic liver together with a reduction in micro-HCCs. DCE revealed lowered tumor blood flow from intravascular into extravascular extracellular space (EES). Microangiography and histopathology revealed hypo- and hypervascularity in 4 and 3 micro-HCCs, massive, partial and minor degrees of tumoral necrosis in 5, 1 and 1 micro-HCCs respectively, and patchy necrotic foci in cirrhotic liver. CD34-PAS staining implicated that poorly vascularized micro-HCCs growing on liver cirrhosis tended to respond better to CA4P treatment. In this study, more complete CA4P-response occurred unexpectedly in micro-HCCs in rats, along with CA4P-induced necrotic foci in cirrhotic liver. These may help to plan clinical applications of VDAs in patients with HCCs and liver cirrhosis.

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Section: Discussionmentioning

confidence: 99%

“…The inferior effects of VDAs in smaller tumors are likely due to their main portions of blood supply largely rooting from the vessels of the surrounding normal tissues [ 17 , 18 ]. Indeed, tumors smaller than 5 mm in diameter often lack their own vasculature and are nourished by the nutrients diffused from their host organs [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P

et al. 2017

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“…A plausible explanation to the inferior effect of VDAs in smaller tumors is that their blood supply relies, to a large extent, on the normal blood vessels from the surrounding liver, while normal vasculature is not supposed to be targeted by VDAs [69,70]. However, nearly radical effect was paradoxically discovered in hepatic micro-HCCs [24], which is against earlier consensus that normally tumors smaller than 5 mm lack their own vasculature and are nourished by the blood diffused from their host organs [71]. This counterintuitive observation was reproduced in a rodent model with secondary liver malignancy [72].…”

Section: Distinct Volume-efficacy Relation Between Micro-hccs and Macmentioning

confidence: 93%

Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation

et al. 2020

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Vascular disrupting agents (VDAs) have entered clinical trials for over 15 years. As the leading VDA, combretastatin A4 phosphate (CA4P) has been evaluated in combination with chemotherapy and molecular targeting agents among patients with ovarian cancer, lung cancer and thyroid cancer, but still remains rarely explored in human liver cancers. To overcome tumor residues and regrowth after CA4P monotherapy, a novel dual targeting pan-anticancer theragnostic strategy, i.e., OncoCiDia, has been developed and shown promise previously in secondary liver tumor models. Animal model of primary liver cancer is time consuming to induce, but of value for more closely mimicking human liver cancers in terms of tumor angiogenesis, histopathological heterogeneity, cellular differentiation, tumor components, cancer progression and therapeutic response. Being increasingly adopted in VDA researches, multiparametric magnetic resonance imaging (MRI) provides imaging biomarkers to reflect in vivo tumor responses to drugs. In this article as a chapter of a doctoral thesis, we overview the construction and clinical relevance of primary and secondary liver cancer models in rodents. Target selection for CA4P therapy assisted by enhanced MRI using hepatobiliary contrast agents (CAs), and therapeutic efficacy evaluated by using MRI with a non-specific contrast agent, dynamic contrast enhanced (DCE) imaging, diffusion weighted imaging (DWI) are also described. We then summarize diverse responses among primary hepatocellular carcinomas (HCCs), secondary liver and pancreatic tumors to CA4P, which appeared to be related to tumor size, vascularity, and cellular differentiation. In general, imaging-histopathology correlation studies allow to conclude that CA4P tends to be more effective in secondary liver tumors and in more differentiated HCCs, but less effective in less differentiated HCCs and implanted pancreatic tumor. Notably, cirrhotic liver may be responsive to CA4P as well. All these could be instructive for future clinical trials of VDAs.

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“…HCC tumor blood is mainly supplied by the hepatic artery, while the portal vein is involved in the peripheral part of the liver and extends to the center with a small branch (34). When the tumor size is >5 cm, the hepatic artery and portal vein are intertwined to form a vascular lake around the tumor, whereas the tumor blood supply is partially or completely derived from the portal vein when the tumor size is <5 cm (35–37). The portal venous system has multiple collateral circulations and may exhibit a small blood flow in HCC with ER (37,38).…”

Section: Discussionmentioning

confidence: 99%

Preoperative color Doppler ultrasonography predicts early recurrence in AFP‑positive hepatocellular carcinoma

et al. 2019

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The present study aimed to evaluate the hepatic hemodynamics of patients with α-fetoprotein (AFP)-positive hepatocellular carcinoma (HCC) and early recurrence (ER), as determined by color Doppler ultrasound. Screening with color Doppler ultrasound was performed in 150 patients with AFP-positive HCC, yielding 43 cases with postoperative ER. In addition, 35 healthy controls were enrolled in the study for comparison of the blood flow parameters between the healthy control and the HCC groups. Receiver operating characteristic curve analysis was performed to evaluate the predicted effect of Doppler for the ER of HCC. The average mean flow velocity of portal vein in patients with HCC (14.686±5.873 cm/s) was significantly lower in the HCC group compared with the healthy control group (17.631±3.569 cm/s; P=0.005). Additionally, the preoperative portal vein diameter in the HCC group was significantly higher compared with that in the healthy control group (P=0.001). Regarding the effect of surgery, the portal vein diameter was significantly increased in the patients postoperatively compared with preoperatively (P=0.003), while the pulsation and resistance indexes exhibited a decreasing trend in the postoperative group (P=0.001 and P=0.003, respectively). Notably, patients with HCC and ER presented with a higher resistance index (1.163±0.342) compared with the ER-free group (1.023±0.176; P=0.004). Furthermore, a significant difference in hepatic artery pulsation index was also observed between the ER group (0.673±0.075) and the ER-free group (0.624±0.056; P=0.018), indicating that an increased hepatic artery pulsation index may significantly predict the ER of HCC. In addition, areas under the curve of 0.683 and 0.700, respectively, suggested that the hepatic artery resistance and pulsation indexes may be used to diagnose ER in HCC (P=0.009 and P=0.004, respectively). Taken together, Doppler ultrasound provides a reliable and accurate quantification of hepatic hemodynamics for detecting ER in HCC with a good diagnostic accuracy.

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Experimental Studies of Portal Venous Embolization with Iodized Oil in Rats with Experimentally Induced Liver Cancer

Cited by 9 publications

References 11 publications

Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P

Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P

Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation

Preoperative color Doppler ultrasonography predicts early recurrence in AFP‑positive hepatocellular carcinoma

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