PMC9845258_01
Computed tomography of a dog with combined hepatocellular-cholangiocarcinoma. (A) Sagittal view showing a left medial liver lobe multicystic mass (arrow) with adhesion to diaphragm and caudal vena cava. (B) Plain and (C) postcontrast axial view of the cranial abdominal region showing a hypoattenuated liver mass (arrows) with minimal contrast enhancement.
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Computed tomography (CT) identified a left medial liver lobe multicystic mass measuring 7.4 x 4.8 x 4.9 cm, showing adhesions with the diaphragm, caudal vena cava, right medial lobe, and quadrate lobe (Figure 1).
Gross morphological and histopathological findings of the liver mass in a dog with combined hepatocellular- cholangiocarcinoma. (A) During surgery, these pictures were taken before and after the partial hepatectomy. Complete excision of the liver mass was impossible because of significant adhesion to diaphragm. The mass (arrow) was excised as much as possible but about 10% of the mass (arrow) remained unresected. (B) Histopathology of the hepatic mass revealed that the hepatic parenchyma includes two overlapping proliferations. One section comprised tubules, cysts, and epithelial cell nests in fibrovascular stroma. The neoplastic cells had variably distinct cell borders, moderate amount of eosinophilic cytoplasm, and oval nuclei. Marked anisokaryosis and anisocytosis were observed with two mitotic figures in 10 high-power fields (400x). The second section comprised a hepatocellular neoplasm. Two to four hepatocyte-wide hepatic cords were observed, with loss of lobular architecture. Hepatocytes had abundant cytoplasm with central to peripheralized nuclei. Mild anisokaryosis and anisocytosis were observed with 12 mitotic figures in 10 high power fields (400x). Magnification 400 x; scale bar = 50 mum. H&E, hematoxylin & eosin.
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Therefore, the histopathologic findings were suggestive of cHCC-CC (Figure 2).
Anticancer drug response prediction test. The tumor tissue obtained from the patient was harvested, lysed, and filtered. The tumor sample was dissociated into single cells and cultured in medium. Cells were seeded and incubated in 96-well plates, and the medium was replaced with that containing gradient doses of chemotherapy drugs. After 24 h, cell viability was examined. The result revealed that toceranib had the best cancer cell-killing effect among gemcitabine, carboplatin, toceranib, sorafenib, and imatinib.
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The result revealed that toceranib (Palladia , Zoetis, USA) had the best cancer cell-killing effect among gemcitabine, carboplatin, toceranib, sorafenib, and imatinib (Figure 3).
(A) Dose of toceranib and trilostane administered and hepatic enzyme level following the administration of toceranib. Trilostane was prescribed at initial presentation and dose escalation was conducted according to the ACTH stimulation test results and clinical signs of hyperadrenocorticism. At toceranib day 74, trilostane was escalated to the final dose (5 mg/kg, PO, q12h). Hepatic enzyme levels decreased gradually after the administration of toceranib, and the levels of all four hepatic enzymes appeared within the normal range since toceranib day 434. (B) Change in the remnant hepatic mass size in terms of the sum of its width and height measured on abdominal ultrasonography. The mass size was measured to 2.3 x 2.0 cm on toceranib day 64, 1.7 x 1.4 cm on toceranib day 307, and 1.6 x 1.0 cm on toceranib day 434. ALP, Alkaline Phosphatase. ALT, Alanine Aminotransferase. AST, Aspartate Aminotransferase. GGT, Gamma Glutamyltransferase. W+H length, width plus height length.
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The hepatic enzyme levels decreased gradually and have been within the normal range since toceranib day 434 (Figure 4A). On abdominal ultrasonography, the remnant mass size reduced gradually and was 1.6 x 1.0 cm at toceranib day 434 (Figure 4B).