**3. Global state-of-the-art treatment**

#### **3.1 Hepatectomy**

*Canine Genetics, Health and Medicine*

**Figure 7.**

**Figure 7** shows the time-dependent curves of the Ga-67 concentration among

*The time-dependent curves of the Ga-67 concentration among various compartments for a liver carcinoma dog.*

**Liver and GI Tract:** In contrast to the I-131 thyroid model or GI Tract model for human patients, the model of Ga-67 for liver carcinoma dog was elaborated by the simplification of the general-purpose biokinetic model, according to the ICRP-30 report. As seen in **Figure 5**, a complicated correlation among compartments allows one to use a MATLAB program to optimize the estimation via the empirical data [27]. The feedback path exists between compartments 2–6 and compartment 1. Each compartment has its biological half-life to transfer the Ga-67 radionuclides among compartments, which also confounds the theoretical estimation. Specifically, the liver provides a 22%-contribution of the body fluid (I12, 0.22), which is the secondlargest share, whereas the GI Tract has the largest share (I13, 0.33 ~ 0.43) after the Ga-67 administration. However, 60% (I21, 0.60) of the Ga-67 radionuclides returns as feedback to the body fluid with a biological half-life of 15 ~ 40 h. Meanwhile, the remaining nuclides of Ga-67 in GI Tract are transferred to the body fluid (I31), liver (I32), or directly to excretion (I38) with a biological half-life of 20 ~ 600 h. Noteworthy is that the effective half-life is defined as the reciprocal of the sum of reciprocal radiological and biological half-lives (1/T1/2(eff) = 1/T1/2(R) + 1/T1/2(bio)). Thus, in practice, either 600 or 20 h of biological half-life still perform as 69 or 16 h of the effective half-life from the continuous gamma camera scanning. Some of Ga-67 radionuclides were found to migrate from the GI Tract to the liver (I32, 0.2 ~ 0.7). Since portal vein circulation provides the blood flow from gastrointestinal section to the liver, the excessive blood pressure will slow the liver's feedback path. **Kidney and bladder.** Nearly 20% of Ga-67 nuclides were transferred to the kidney (I14, 0.2), exhibiting nearly no feedback to body fluid (I41, 0.07), in contrast to the bladder (I47, 0.93), and then were fully transferred to excretion (I78, 1.0).

**Heart.** Only 5–15% of Ga-67 nuclides were transferred to the heart (I15, 0.05–0.15), whereas most of them exhibited an instant feedback to body fluid (I51, 0.99) with a short biological half-time T1/2 of 18–20 h. The derived biological half-life of the heart can be treated as a group of cardiac muscles, which provide the blood circulation loop

A long biological half-life of liver for the liver carcinoma dog (40 h vs. 35 h or 15 h) reveals a potential risk of hepatic disorder, whereas the remaining data are

in the whole body, with no apparent Ga-67 nuclides' repository effect.

various compartments for the dog with liver carcinoma.

**166**

The liver surface is convex and it slightly touches the diaphragm. The liver is located on the left side of the caudoventral tract, contacting the stomach, duodenum, pancreas, and right kidney. There are six hepatic lobes: right medial and lateral, left medial and lateral, and quadrate and caudate lobes. The gallbladder is located between the right medial and quadrate lobes. The liver has two so-called afferent (ingoing) blood supplies: the portal system and the arterial system, while the efferent (outgoing) blood flow of the liver circulation is through the hepatic veins. The hepatic lobules, which are the basic functional units of the liver, are cross-sectioned in a hexagonal shape and the portal triads in the periphery. Portal triads consist of the hepatic artery, portal vein, and bile duct. From the anatomic and histologic views, the liver is complicated, and hepatic tissue is friable. Partial lobectomy is difficult and may injure blood vessels and bile ducts in canine patients with bleeding disorders. Many techniques for partial and complete liver lobe resection have been introduced, and numerous stapling instruments have been adopted for both lobectomies. The survey of Liptak et al. [1], which covered 48 dogs with large massive hepatocellular carcinomas during a decade, revealed that their median survival time exceeded 1,460 days after the hepatectomy procedure. However, numerous complications, including ongoing anemia, hepatopathy, ileus, and lack of appetite, are frequently after liver surgery. Therefore, a proper intensive care is recommended to mitigate these complications and minimize the related risks.

#### **3.2 Chemotherapy**

The most commonly chemotherapy is administered intravenously. According to clinical chemotherapeutic management of neoplastic cases, a significant advance in veterinary practice is observed. However, a large share of HCC canine patients cannot be cured by chemotherapy and require a further integration of conventional treatment modalities, such as surgery, radiation therapy, and innovative chemotherapy methods. Chemotherapeutic agents are generally administered at the maximum tolerated dose and at the highest dose intensity that is usually used in combination. Four advantages of combination chemotherapy include an increased log-kill, prevention of cancer drug resistance, targeting both dividing and resting cells, and allowing for lower doses with less toxicity [6]. Chemotherapeutic agents damage activated pathogenic cells but also affect normal tissues that divide rapidly and are sensitive to anti-mitotic drugs, such as cells in the bone marrow, digestive tract, and hair follicles. The most common side-effects of chemotherapy are myelosuppression, mucositis, and alopecia. In general, malignant tumors cannot be wholly removed surgically and imply a poor prognosis for canine patients. Palliative chemotherapy and other treatments may be gradually applied to delay the tumor progression. Any further health care should involve close monitoring and minimization of side effects.

#### **3.3 Radiotherapy**

As a general rule, surgical resection is considered the best treatment option if a primary tumor can be completely excised. If the region of extensive involvement, normal tissue, or volume of liver tumor make its complete removal problematic, then radiotherapy may be recommended by veterinarians as a palliative treatment of liver tumors. Its effectiveness against the canine liver tumor is limited by the fact that canine patients cannot tolerate cumulative doses exceeding 30 Gy [29]. A share of radiotherapy treatment in US veterinary facilities in 2001 study did not exceed 20% [30], while 92% of facilities in 2010 used the 3D computerized radiotherapy, and 20–100% (with median of 50%) of facilities implemented computer simulation treatment plans [31]. It should be noted the abdominal movement caused by breathing during radiotherapy of liver tumors strongly deteriorates the therapeutic effect, which issue can be resolved for human patients but is hard to control with canine ones.
