Abstract
Histotripsy is a noninvasive, nonionizing, and nonthermal focused ultrasound ablation method that is currently being developed for the treatment of liver cancer. Promisingly, histotripsy has been shown for ablating primary [hepatocellular carcinoma (HCC)] and metastatic [colorectal liver metastasis (CLM)] liver tumors in preclinical and early clinical studies. The feasibility of treating cholangiocarcinoma (CC), a less common primary liver tumor that arises from the bile ducts, has not been explored previously. Given that prior work has established that histotripsy susceptibility is based on tissue mechanical properties, there is a need to explore histotripsy as a treatment for CC due to its dense fibrotic stromal components. In this work, we first investigated the feasibility of histotripsy for ablating CC tumors in vivo in a patient-derived xenograft mouse model. The results showed that histotripsy could generate CC tumor ablation using a 1-MHz small animal histotripsy system with treatment doses of 250, 500, and 1000 pulses/point. The second set of experiments compared the histotripsy doses required to ablate CC tumors to HCC and CLM tumors ex vivo. For this, human tumor samples were harvested after surgery and treated ex vivo with a 700-kHz clinical histotripsy transducer. Results demonstrated that significantly higher treatment doses were required to ablate CC and CLM tumors compared to HCC, with the highest treatment dose required for CC tumors. Overall, the results of this study suggest that histotripsy has the potential to be used for the ablation of CC tumors while also highlighting the need for tumor-specific treatment strategies.
Highlights
M ORE than 800 000 people are diagnosed with a malignancy originating from or metastatic to the liver every year
We investigate the in vivo feasibility of histotripsy CC ablation in a subcutaneous patient-derived xenograft (PDX) CC tumor model
Since colorectal liver metastasis (CLM) tumors are stiffer than hepatocellular carcinoma (HCC) tumors [30], [24], we hypothesized that higher treatment doses would be required for generating ablation in these samples
Summary
M ORE than 800 000 people are diagnosed with a malignancy originating from or metastatic to the liver every year. 42 810 cases are projected for the U.S in 2020 [1]. These malignant liver tumors include hepatocellular carcinoma (HCC), liver metastasis (LM), and cholangiocarcinoma (CC). Surgical resection remains the mainstay of liver tumor intervention, less than 25% of patients are candidates for resection due to tumor burden, location, or comorbid disease [2], [3]. Invasive ablation methods have shown some success in treating liver tumors but have limitations due to the thermal mechanism, including lack of precision and high complication rates when treating near critical structures [5]–[14]. Histotripsy is a noninvasive, nonthermal, and image-guided focused ultrasound ablation method that ablates tissue through the generation of acoustic cavitation at the
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