First In Vivo Test of Thermoembolization: Turning Tissue Against Itself Using Transcatheter Chemistry in a Porcine Model

Cressman, Erik N.K.; Guo, Cheng

doi:10.1007/s00270-018-2003-3

Cited by 6 publications

(6 citation statements)

References 33 publications

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“…Several studies have used porcine models to establish novel strategies for HCC treatment. For example, Cressman et al [11] attempted thermoembolization with transcatheter chemistry, while Ellebrecht et al [12] reported laparoscopic laser liver resection in normal porcine models. These…”

Section: Discussionmentioning

confidence: 99%

Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model

et al. 2021

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Hepatocellular carcinoma (HCC) is the fifth most common primary tumor and the third leading cause of cancer-related deaths worldwide. Rodent models of HCC have contributed to the advancement of studies investigating liver carcinogenesis, tumor-host interactions, and drug screening. However, their small size renders them unsuitable for surgical or clinical imaging studies, necessitating the development of larger-size HCC models. Here, we developed a xenograft model of human HCC in X-linked interleukin-2 receptor gamma chain gene (Il2rg)-targeted severe combined immunodeficient (SCID) pigs. HepG2 cell suspension in serum-free medium containing 50% membrane matrix was directly injected into the liver parenchyma of eight X-linked Il2rg-targeted SCID pigs (6.6–15.6 kg) via ultrasonography-guided percutaneous puncture. Tumor engraftment was evaluated weekly using ultrasonography, and cone-beam computed tomography was performed during arterial portography (CTAP) and hepatic arteriography (CTHA) to evaluate the hemodynamics of engrafted tumors. The engrafted tumors were histologically analyzed following necropsy and assessed for pathological similarities to human HCCs. Macroscopic tumor formation was observed in seven of the eight pigs (simple nodular tumors in three and multinodular tumors in four). Engrafted tumors were identified as low-echoic upon ultrasonography and as perfusion-defect nodules on the CTAP images. Meanwhile, CTHA showed that the tumors were hyperattenuating. Further, histopathological findings of the engrafted tumors were consistent with those of human HCC. In conclusion, the porcine model of human HCC, successfully generated herein, might help develop more effective therapeutic strategies for HCC.

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Section: Discussionmentioning

confidence: 99%

Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model

et al. 2021

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“…In vivo, delivery via the hepatic artery in a pig model has substantial effects both macroscopically and microscopically [60,61]. Initial results in vivo are encouraging regarding how well the procedure is tolerated [54].…”

Section: Figurementioning

confidence: 96%

“…A more detailed and comprehensive investigation of thermal imaging with exothermic chemistry was recently published [59]. In vivo, delivery via the hepatic artery in a pig model has substantial effects both macroscopically and microscopically [60,61]. Initial results in vivo are encouraging regarding how well the procedure is tolerated [54].…”

Section: Figurementioning

confidence: 99%

Combining Chemistry and Engineering for Hepatocellular Carcinoma: Nano-Scale and Smaller Therapies

et al. 2020

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Primary liver cancer, or hepatocellular carcinoma (HCC), is a major worldwide cause of death from carcinoma. Most patients are not candidates for surgery and medical therapies, including new immunotherapies, have not shown major improvements since the modest benefit seen with the introduction of sorafenib over a decade ago. Locoregional therapies for intermediate stage disease are not curative but provide some benefit. However, upon close scrutiny, there is still residual disease in most cases. We review the current status for treatment of intermediate stage disease, summarize the literature on correlative histopathology, and discuss emerging methods at micro-, nano-, and pico-scales to improve therapy. These include transarterial hyperthermia methods and thermoembolization, along with microfluidics model systems and new applications of mass spectrometry imaging for label-free analysis of pharmacokinetics and pharmacodynamics.

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“…Thermoembolization [19,20] represents a novel treatment approach for patients battling HCC. Thermoembolization is a procedure in which an acid chloride reagent is delivered by an endovascular route.…”

Section: Introductionmentioning

confidence: 99%

“…Current efforts are promising [19,20] and have demonstrated a 40:1 ratio of coagulated tissue volume to injected material and up to a 24.1 C temperature rise. However, from a clinical standpoint, this potential for extensive tissue damage suggests a need for greater understanding of the behavior of these materials when delivered by the endovascular route.…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling of mass and energy transport for thermoembolization

Fuentes

Fahrenholtz

Guo

et al. 2020

International Journal of Hyperthermia

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Background: Thermoembolization presents a unique treatment alternative for patients diagnosed with hepatocellular carcinoma. The approach delivers a reagent that undergoes an exothermic chemical reaction and combines the benefits of embolic as well as thermal-and chemical-ablative therapy modalities. The target tissue and vascular bed are subjected to simultaneous hyperthermia, ischemia, and chemical denaturation in a single procedure. To guide optimal delivery, we developed a mathematical model for understanding the competing diffusive and convective effects observed in thermoembolization delivery protocols. Methods: A mixture theory formulation was used to mathematically model thermoembolization as chemically reacting transport of an electrophile, dichloroacetyl chloride (DCACl), within porous living tissue. Mass and energy transport of each relevant constituent are considered. Specifically, DCACl is injected into the vessels and exothermically reacts with water in the blood or tissue to form dichloroacetic acid and hydrochloric acid. Neutralization reactions are assumed instantaneous in this approach. We validated the mathematical model predictions of temperature using MR thermometry of the thermoembolization procedure performed in ex vivo kidney. Results: Mathematical modeling predictions of tissue death were highly dependent on the vascular geometry, injection pressure, and intrinsic amount of exothermic energy released from the chemical species, and were able to recapitulate the temperature distributions observed in MR thermometry. Conclusion: These efforts present a first step toward formalizing a mathematical model for thermoembolization and are promising for providing insight for delivery protocol optimization. While our approach captured the observed experimental temperature measurements, larger-scale experimental validation is needed to prioritize additional model complexity and fidelity.

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First In Vivo Test of Thermoembolization: Turning Tissue Against Itself Using Transcatheter Chemistry in a Porcine Model

Abstract: Thermoembolization is a new technique for embolization with initial promise. However, results indicate much work must be done to optimize the technique.

Cited by 6 publications

References 33 publications

Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model

Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model

Combining Chemistry and Engineering for Hepatocellular Carcinoma: Nano-Scale and Smaller Therapies

Mathematical modeling of mass and energy transport for thermoembolization

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