Nodular or tumorous changes in the liver are common in older dogs and may be benign or malignant in nature. Besides primary tumors and masses, the liver may also be affected by hematopoietic neoplasias and by hepatic metastases of tumors of other primary locations. According to one study, only 26% of all liver masses are primary liver tumors (Hammer, Sikkema 1995). Surgery is the treatment of choice in primary and solitary masses, but is only very rarely indicated in hepatic manifestations of hematopoietic tumors and in metastases of primary non-hepatic tumors to the liver.
Independent of their histologic subtype, liver tumors can be solitary or multifocal. In the solitary form, only one liver lobe is affected; while in multifocal disease, multiple distinct nodules of different sizes can be found in several liver lobes.
Hepatocellular Carcinoma
Hepatocellular carcinoma originates from the liver cells and is the most common malignant tumor in the canine liver. There are several histologic subtypes; however, this is of little clinical relevance. The macroscopic appearance is of major surgical and, therefore, prognostic importance. The majority of hepatocellular carcinomas are solitary and have a relatively low metastatic potential. In one study, only 2 out of 48 dogs (< 5%) had metastasis at time of diagnosis (Liptak et al. 2004). Solitary hepatocellular carcinomas occur in 2/3 of the cases in the left sided liver lobes, which are easier to resect than the lobes on the right side.
Cholangiocarcinomas
Cholangiocarcinomas originate from the bile ducts and depending on their anatomic location, intrahepatic, extrahepatic, and the rare gall bladder carcinoma can be distinguished. The intrahepatic form is most common and makes up ¾ of the cases. Macroscopically, bile duct carcinomas present as grey-white to yellow-brown solid or cystic masses. If cysts are present, they are filled with yellowish, gelatinous material. In contrast to hepatocellular carcinomas, which are often soft and fragile, cholangiocarcinomas contain more fibrous tissue and are therefore usually quite firm. They can be solitary but more often they are multiple or diffusely distributed in the liver and have a much higher rate of metastasis. In multifocal or disseminated disease surgery is not indicated.
Hemangiosarcomas
Hemangiosarcomas of the liver usually present as large, sponge-like, cavernous blood-filled masses and due to their fragile texture, they tend to rupture and result in hemascos. More frequently, hemangiosarcomas arise in the liver as metastasis from splenic (or other) primary sites. Only in cases with solitary hepatic presentation can surgery be attempted but this usually carries a poor prognosis. Other sarcomas such as leiomyosarcomas, fibrosarcomas, chondrosarcomas, osteosarcomas, and liposarcomas may arise in the liver and surgery is indicated as long as the tumors are solitary and nonmetastasized.
Carcinoids
Carcinoids of the liver are very rare in dogs. Histogenetically, they are of neuroectodermal origin and are part of the APUD-system. The term carcinoid comes from their histologic resemblance with carcinoma cells, but they can be differentiated from carcinomas by special silver stains. Immunohistochemistry is required for diagnosis (positive reaction for neuron-specific enolase (NSE), synaptophysin, and chromogranin-A. Since this tumor usually presents with multiple nodules, or diffuse infiltration of the entire liver and multiple metastases, surgery is rarely indicated.
Lymphomas of the liver are very rarely solitary, far more commonly they are a manifestation of a systemic malignant lymphoma. Other abdominal organs such as spleen, kidneys, and abdominal lymph nodes are usually affected as well. A special form of lymphoma affecting the liver is the extranodal gamma delta T-cell lymphoma of the liver and spleen. Peripheral lymphadenopathy is usually lacking, but the bone marrow is frequently affected. Diagnosis relies on histologic and immunohistologic identification of blastic T-lymphocytes (positive for CD3 and gamma delta T-cell receptor). Concurrent poly or pancytopenia is frequent due to bone marrow infiltration. Lymphomas are not treated surgically. Chemotherapy is possible but carries a poor prognosis.
Hepatocellular Adenomas
Hepatocellular adenomas are also called "hepatomas" in veterinary medicine and differentiation from nodular hyperplasia or regenerative nodules is difficult to impossible macroscopically and even histologically. The masses are well circumscribed and sometimes pedunculated and may be solitary or multiple. Hepatocellular adenomas and regenerative nodules can grow enormous and may lead to clinical symptoms either via compression of other abdominal organs, rupture, or via paraneoplastic hypoglycemia. Rupture with massive bleeding is not uncommon because of their fragile texture. Due to their sometimes massive and/or multiple presentation, adenomas and regenerative nodules can be erroneously regarded as malignant neoplasias, which stresses the importance of histopathologic confirmation of the diagnosis prior to further steps.
Dogs with liver masses are either free of symptoms or may present with nonspecific signs, such as weight loss, anorexia, PU/PD, and vomiting. Rarely, neurologic symptoms due to paraneoplastic hypoglycemia are present. In one study, only 45% of all hepatocellular carcinomas were palpable (Liptak et al. 2004). Ascites or icterus is rare. Rupture of the masses leads to hemoabdomen with subsequent collapse and represents a surgical emergency.
Radiographs are quite nonspecific in locating abdominal masses, and ultrasonography has become the diagnostic tool of choice for screening for abdominal neoplasias. Size, number, and location of liver masses can be determined by ultrasound, but sensitivity of liver sonography is only satisfactory at best and lesions can be missed. In addition, sonography is very nonspecific and cannot differentiate between benign and malignant disease (Lamb et al. 1991; Stowater et al. 1990). Target lesions (hypoechogenic center surrounded by hyperechoic periphery) are more commonly associated with malignant disease (Cuccovillo, Lamb 2002). Sonographic contrast agents can improve sensitivity and specificity (Nakamura et al. 2010), but as a general rule, sonographic diagnosis of a liver tumor always needs to be verified by histopathologic examination. Computed tomography and MRI are noninvasive methods to examine the liver. In one study, MRI reached a sensitivity and specificity of 100% and 90%, respectively. All cases of hepatocellular carcinomas were correctly diagnosed (Clifford et al. 2004). The author prefers computed tomography for the planning of hepatic surgery.
Laboratory changes in liver tumors such as anemia and neutrophilic leukocytosis are common and may be accompanied by thrombocytopenia or thrombocytosis. Elevation of liver enzymes is also common but a nonspecific finding. Paraneoplastic hypoglycemia can occur and, in severe cases, must be treated prior to surgery. α-Fetoprotein (AFP) is a glycoprotein which is produced physiologically in the fetal liver but can also be found in the serum of dogs with hepatic carcinomas. In healthy dogs, serum AFP values are usually below 70 ng/dl, while carcinomas are usually associated with values > 250 ng/ml. Benign liver disease can also increase AFP, but values rarely exceed 500 ng/dl (Yamada et al. 1999). After complete resection of a carcinoma with elevated AFP, normalisation of AFP values can be expected, and AFP can be utilized as a marker in monitoring for tumor recurrence.
Because radiography, sonography and macroscopic findings cannot be used for differentiating benign from malignant disease, histopathologic and sometimes immunohistologic examination of liver changes are indispensable. Biopsies can be taken percutaneously by Tru-Cut needle under sonographic or CT guidance. Laparoscopic biopsy techniques offer the advantage of direct visualization of the biopsy site and possible postbiopsy bleeding. In addition, other abdominal organs and lymph nodes can be directly visualized.
Partial liver resection (hepatectomy) is the treatment of choice for localized hepatic processes. Both benign and malignant hepatic masses are frequently quite fragile and vascularized. Therefore, intra- or perioperative hemorrhage can occur and blood transfusions should be at hand. Preoperatively, a hemostasis screen should be performed.
The tumor is exposed by median laparotomy and large Balfour retractors, malleable retractors, and abdominal sponges are used to expose the mass and retract the intestines. Especially in large and deep-chested dogs and large liver masses, standard median laparotomy is frequently insufficient for exposition of the mass and the liver hilus. The author recommends performing a small incision into the diaphragm to create a pneumothorax which allows the surgeon to retract the diaphragm and thus the liver caudally into the abdomen which improves visualisation, access and manipulation of the tumor, liver hilus and the large vessels. For some cases, splitting of the caudal sternum and semicircular separation of the diaphragm from the abdominal wall or paracostal incisions into the abdominal wall have been recommended, but in the author's experience this is only very rarely necessary.
In cases of a pedunculated tumor, resection can easily be performed by ligation or stapling of the connecting tissue segment to the otherwise normal liver lobe. More commonly, tumors develop from inside a liver lobe, therefore a partial or complete lobectomy is indicated. Smaller masses at the periphery of a liver lobe can be resected by partial lobe resection; in most of the cases, however, a complete resection of the affected lobe at the hilus is necessary. Partial liver lobe resections can be performed by manual preparation technique or by using a surgical TA-stapler. For the manual technique, a sharp incision is made through the Glisson capsule followed by careful manual blunt compression-dissection of the liver tissue between thumb and index finger. Blood vessels and bile ducts are not injured by this technique and can be isolated, and, depending on the diameter of the vessel, occluded using cautery, suture ligation or surgical hemoclips. If suture ligation is used it is recommended to double ligate larger vessels and bile ducts using surgical silk or slowly absorbable suture. Significant bleeding from the bluntly dissected liver tissue is rare.
Tumor resections on the left side of the liver are much easier to perform than on the right side. It is therefore important to identify the affected liver lobe prior to surgery on CT scans. Resections of large and especially bleeding tumors on the right side of the liver require advanced surgical skills. The caudal vena cava, portal vein and common bile duct are in immediate proximity of the hilus of the right-sided lobes and have to be identified and preserved. Especially difficult to resect is the caudate lobe, which is attached to the right kidney by the hepatorenal ligament and extends with its papillary process dorsal to the vena cava to the left side. Similarly, the right medial lobe is difficult to remove, because it lies next to the gall bladder, the bile duct and has very short veins entering the vena cava. Surgeons approaching large masses on the right side of the liver have to be prepared to perform vascular surgery. In one study, 3 of 5 dogs with tumors on the right side of the liver experienced a vena caval laceration, which resulted in intraoperative death in two cases (Liptak et al. 2004). In case of inadvertent damage to the caudal vena cava with major bleeding, the author recommends incision of the diaphragm and to crossclamp the caudal vena cava and the descending aorta on the thoracic side, which leaves space for manipulations and suturing of the lacerated vein.
The liver has an enormous capacity for regeneration. Up to ¾ of the liver can be removed without problems provided the function of the remaining liver is uncompromised. Within 6–8 weeks hypertrophy and hyperplasia will result in significant enlargement of the remaining parts of the liver.
Benign masses can become quite large, but after successful resection carry a good prognosis. The prognosis for resectable malignant liver tumors is relatively good independent of their size. In Liptak's study with solitary hepatocellular carcinomas, median survival time exceeded 1.460 days. Less than 10% of all patients with lobectomy died from their tumor. Neither size of tumor nor microscopically complete resection were prognostic (Liptak et al. 2004).
References
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