Chemoembolization for Non-resectable Liver Tumors

Initial findings
• Signalment: 7-year-old male spayed American Staffordshire terrier mix (13 kgs)
• Presenting complaint: Slight lethargy, decreased appetite
• Pertinent history: No significant previous medical history until 3 weeks prior when abdominal exploratory surgery performed for liver mass – biopsy consistent with nonresectable, massive, low-grade hepatocellular carcinoma
• Medications: Milk thistle, SaME
• Physical examination findings: Bright, alert, and responsive; body condition score 4/9; Distended abdomen with no fluid wave but palpable firm mass in cranial abdomen

Diagnostic evaluation
• Complete blood count: 16,600 WBCs, 13200 neutrophils, 410 platelets
• Serum chemistry profile: ALT 1134, AST 596, ALP 980
• Bile Acids: Resting 15, Post-prandial 26
• Coagulation Screen: Within normal limits
• Thoracic radiographs: Thorax within normal limits, hepatomegaly
• Abdominal Ultrasonography: Large, cavitated right-sided hepatic mass abutting diaphragm and caudal vena cava.
• Computed Tomography (CT) Angiography (Figure 1): Heterogeneous right-sided massive liver tumor with portal vein and caudal vena cava compression

1Figure 1

Treatment decisions
This patient had previous abdominal surgery in which the nonresectable liver mass was biopsied. The surgery report described the mass as adhered to the portal vein, pancreas and bile duct, originating from the base of the liver and attaching to the body wall, right lateral, quadrate liver lobes and gall bladder. A biopsy at that time was consistent with a well-differentiated hepatocellular carcinoma (HCC). As these tumors do not demonstrate substantial biological responses to systemic chemotherapy and radiation of the liver is not performed, historical standard therapy involves benign neglect and supportive care until these tumors either metastasize or, more commonly, rupture.
Following a CT angiogram (Figure 1), this patient was determined to be a good candidate for drug-eluting bead (DEB) trans-arterial chemoembolization (TACE) which was performed the following day. A combination of 1 ml of DEBs was mixed with Doxorubicin (30mg/m2) in order to allow the beads to absorb the chemotherapy. A 2-3cm surgical incision in the groin permits placement of a vascular sheath within the femoral artery. A catheter is advanced under fluoroscopic guidance into the celiac artery. Super-selective access is gained using a 2.4Fr microcatheter in order to minimize non-target (normal liver parenchyma) embolization and to achieve maximal concentrations of chemotherapy and DEBs within the actual tumor. Figure 2 demonstrates a digital subtraction arteriogram (DSA) of the contributing right hepatic artery illustrating vascularization of the right-sided liver tumor prior to (Figure 2A) and following (Figure 2B) chemoembolization. After delivery of the DEBs, there is less blood supply to the tumor as identified on the subsequent arteriogram. The procedure was repeated six weeks later. Figure 3 demonstrates the same superselection and microcatheter location prior to (Figure 3A) and following (Figure 3B) the second chemoembolization procedure. Notice the smaller, more consolidated, liver mass on this angiogram compared to Figure 2.

2Figure 2

3Figure 3

Outcome
This patient recovered uneventfully and was discharged from the hospital the following day with prednisone, Clavamox, tramadol, ondansetron, and omeprazole. Repeat complete blood counts at 1, 2, and 3 weeks post TACE were unremarkable. A second treatment was performed five weeks later at which point the tumor appeared angiographically more consolidated and smaller. Five weeks following the second treatment a repeat CT angiogram demonstrated approximately 25% tumor size reduction with the animal clinically doing well (Figure 4). These procedures can be repeated as needed.

4Figure 4

Discussion
Currently there are no effective treatments for veterinary patients with non-resectable liver cancer. Due to poor responses or complications with systemic chemotherapy and radiation therapy, veterinary oncologists typically treat these patients with supportive care. Similar treatment difficulties for nonresectable human HCCs have led to investigation into regional, or liver-directed, therapies including intra-arterial chemotherapy delivery, trans-arterial embolization (TAE), transarterial chemoembolization (TACE), and ablation therapies (typically chemical or thermal). TACE involves a small catheter placed in the femoral artery. Under fluoroscopic guidance, the catheter is advanced up the aorta, into the hepatic artery feeding the tumor, and a full dose of systemic chemotherapy and embolic particles or microspheres are injected to obstruct bloodflow to the tumor. More recently, the development of drug-eluting beads (DEBs) has enabled 100-400 times the concentration of chemotherapy to be achieved within the tumor compared to the same dose given intravenously (systemically). The DEBs slowly elute the doxorubicin over weeks to months within the tumor resulting in less toxicity to the patient, most of whom show no side effects from the chemotherapy (such as immunocompromise or GI toxicities associated with systemic delivery). TACE has been shown in a number of human randomized clinical trials to be associated with prolonged survival times when compared to systemic therapies. Post-embolization syndrome (PES) is characterized in humans by general malaise, fever, nausea, abdominal discomfort. It occurs in many people following TACE but it is generally self-limiting and well managed with supportive care such as anit-inflammatories, anti-nausea medications, antibiotics, pain medications, and gastroprotectants. In addition, DEB TACE has been shown to result in fewer side effects (like post-embolization syndrome) and better results (for large tumors) than standard chemoembolization. It is unclear if animals experience PES however we currently treat them empirically with the same medications just in case.

A video of the procedure can be viewed below.

 
For more case studies and to see how interventional radiology and interventional endoscopy can benefit patients, visit http://amcny.org/interventional-radiology-endoscopy/.

Submitted By Dr. Chick Weisse VMD, DACVS
Animal Medical Center
References/Suggested Reading
Dyet J, Ettles D, Nicholson A, eds., et al. Textbook of Endovascular Procedures. 1st ed. Philadelphia:
Churchill Livingstone, 2000:357-367.

Weisse C, Clifford CA, Holt D, Solomon JA. Percutaneous arterial embolization and
chemoembolization for treatment of benign and malignant tumors in three dogs and a goat. JAVMA 2002
221(10):1430-1436.

Soulen MC: Multimodality image-guided therapy for liver tumors. SIR Annual Meeting 2003
14(2):P211-P217.

Hemingway AP, Allison DJ. Complications of embolization: Analysis of 410 procedures. Radiology 1988;166(3):669-672.
Geschwind JH. Therapy for liver cancer by targeting energy metabolism. SIR Annual Meeting 2003 14(2):P207-P211.

FIGURES

Figure 1: Pre-chemoembolization CT angiogram. A. Sagittal reconstruction of the abdomen with dashed black line outlining the massive hepatocellular carcinoma compressing the caudal vena cava. B. Coronal reconstruction of the abdomen with dashed black line outlining the massive hepatocellular carcinoma compressing the portal vein.

Figure 2: Pre- and Post-chemoembolization hepatic arteriograms during the first TACE procedure. A. Hepatic arteriogram prior to chemoembolization demonstrating considerable vascularization of the tumor outlined by a dashed black line. B. Repeat hepatic arteriogram post-TACE demonstrating reduced vascularity following the TACE procedure.

Figure 3: Pre- and Post-chemoembolization hepatic arteriograms during the second TACE procedure. A. Hepatic arteriogram prior to chemoembolization demonstrating considerable vascularization of the now diminished tumor outlined by a dashed black line. B. Repeat hepatic arteriogram post-TACE demonstrating reduced vascularity following the TACE procedure. Note the smaller mass compared to the prior arteriogram (Figure 2).

Figure 4: Pre-chemoembolization abdominal CT (non-contrast enhanced). A. Sagittal reconstruction of the abdomen with dashed black line outlining the smaller hepatocellular carcinoma when compared to Figure 1A. B. Coronal reconstruction of the abdomen with dashed black line outlining the smaller hepatocellular carcinoma when compared to Figure 1B.

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