"Hepatocellular Carcinoma" TUMOR TIDBITS, A BIWEEKLY VETERINARY ONCOLOGY E-LETTER Volume 3; Number 22; June 21, 2002. Editor: Kevin A. Hahn, DVM, PhD, Dipl - ACVIM (Oncology) & Overall Nice Guy! ANNOUNCEMENTS 1 - Gulf Coast Veterinary Oncology expands to 2 days a week in Sugar Land and San Antonio beginning July 9th! 2 - We're beginning a Phase 2 clinical trial to prevent weakness and anemia in cancer patients and 'geriatric' patients in July - check the web for details. 3 - We're still enrolling dogs with lymphoma into a clinical trial using a novel antiangiogenic agent. It is for dogs with relapsed lymphoma and the criteria for entry are strict. Call or email us for additional details. THIS WEEK'S TUMOR TIDBIT: Hepatocellular Carcinoma OVERVIEW IN THE TEXTBOOKS * Primary hepatic neoplasms are rare in dogs and cats, representing approximately 1.2% and 1.7% of all tumors in these species, respectively. * Hepatocellular carcinoma is the most common hepatic malignancy in dogs, although bile duct carcinoma is more common in cats. SIGNALMENT * Dogs--mean age 10-11 years * Cats--usually older than 10 years * A male predisposition reported in dogs * No breed predilection in dogs or cats SIGNS * Highly variable; patients may have nonspecific signs for several months before diagnosis * Anorexia * Weight loss * Vomiting and/or diarrhea * Lethargy * Abdominal swelling * Signs associated with advanced disease--icterus, ascites, and CNS abnormalities (e.g., seizures and behavioral changes) * Hepatomegaly * Ascites * Abdominal pain * Abdominal distension * Icterus * Palpable abdominal mass more readily detected in patients with hepatocellular carcinoma than with bile duct carcinoma. DIFFERENTIAL DIAGNOSES * Hepatocellular adenoma * Bile duct carcinoma * Nodular hyperplasia * Cirrhosis * Chronic active hepatitis * Use histologic features to differentiate. The histologic distinction between well-differentiated hepatocellular carcinoma and hepatocellular adenoma can be difficult. DIAGNOSTIC TEST RESULTS * Changes in hematologic and biochemical values are common but are nonspecific for liver cancer. High serum enzyme (i.e., ALP, ALT, and AST) activities, hypoalbuminemia, hypergammaglobulinemia, hypoglycemia, and high direct and indirect bilirubin support a diagnosis of liver disease. * Hematologically, nonregenerative anemia and leukocytosis are common. * A coagulogram should be performed before biopsy or surgical procedure. * Abdominocentesis and cytologic examination * Abdominal radiography to help localize the abdominal mass to the liver * Thoracic radiography to identify pulmonary metastases * Abdominal ultrasonography to assess parenchymal integrity, confirm the organ of origin, and guide fine-needle aspiration or biopsy of the tumor GROSS AND HISTOPATHOLOGIC FINDINGS * Vary from small, round, discrete lesions to large, diffuse masses > 10 cm in diameter * Hepatocellular carcinoma is usually soft and friable, unlike bile duct carcinoma which has a firm consistency. * Found in any lobe of the dog's liver, although the left lateral lobe most commonly affected * Neoplasms found in more than one liver lobe because of multiple primary lesions or intrahepatic metastases of a single neoplasm * Histologically, well-differentiated carcinoma may closely resemble normal hepatocytes or hepatocellular adenoma; the undifferentiated neoplasm has highly pleomorphic cells that are not readily recognized as hepatocyte in origin. TREATMENT * Surgical excision the treatment of choice for massive hepatic tumors; palliative for nodular hepatic disease; poor for diffuse hepatic disease. * Up to 75% of the liver can be resected without marked hepatic dysfunction. * No successful chemotherapy has been reported in dogs or cats. * Medications requiring metabolism by the liver should be used with caution in dogs and cats with hepatopathies. * Hepatotoxicity from anticancer drugs appears to be of little or no clinical importance in small animals. FOLLOW-UP * Prognosis poor * Survival times of < 80 days after surgery reported in animals despite lack of evidence of metastases * The degree of invasiveness, presence of metastases, and tumor resectability are the most reliable indicators of survival. * The metastatic rate for hepatocellular carcinoma is 61%. Metastases occurs most commonly to the lungs and hepatic lymph nodes, although metastases to the heart, spleen, kidneys, intestines, brain, and ovary via the vascular system occasionally occurs. The neoplasm also spreads by direct extension to the omentum and peritoneum. WHAT DO WE DO AT GULF COAST? * There are 3 morphological types of liver cancer in dogs - diffuse, nodular, and massive. * In dogs with massive (large, confined to one lobe) hepatocellular carcinoma, surgical lobectomy is the treatment of choice and median survival times of >18 months have been reported. * Surgical cure is not possible in massive hepatocellular carcinoma and recurrence is expected. * Low dose usage of chlorambucil (Luekeran) 4 mg/m2 orally every 2 to 3 days is well-tolerated and decreases the rate of nodular regrowth and metastasis in dogs (unreported, personal experience). * Quality of life is markedly improved with the use of antioxidants and vitamins that abrogate hepatopathies. We recommend the use of silymarin, or milk thistle, found in many drug stores. Our source is through RxVitamins.com. * The prognosis is grave in dogs and cats with diffuse hepatic disease. I hope this info helps. Don't hesitate to call or email us at Gulf Coast Veterinary Oncology! Kevin Kevin A. Hahn, DVM, PhD Diplomate American College of Veterinary Internal Medicine (Oncology) & Overall Nice Guy Gulf Coast Veterinary Diagnostic Imaging & Oncology 1111 West Loop South, Suite 150, Houston, TX 77027 P: 713.693.1166 F: 713.693.1167 W: http://www.gcvs.com Email: mailto:drhahn@gcvs.com