Abdominal CT evaluation of the liver and spleen for staging mast cell tumors in dogs yields nonspecific results

Canine mast cell tumor staging is commonly performed using abdominal ultrasonography and fine‐needle aspiration cytology of masses, lymph nodes, and hepatic and splenic parenchyma. Computed tomography is used for abdominal, thoracic, or whole body imaging in staging mast cell tumors in the authors’ institution enabling evaluation of multiple body areas in one examination. The aim of this study was to compare the CT examinations acquired for staging of mast cell disease to their subsequent liver and spleen cytology findings. Medical records of dogs with primary mast cell tumors that underwent abdominal CT and concurrent liver and spleen aspirates were reviewed. The CT examinations were evaluated for attenuation, size, and margination of the liver and spleen. The relationship between CT findings and cytology results was analyzed. Forty‐nine dogs matched the inclusion criteria: five of forty‐nine dogs with cutaneous mast cell tumors were positive for metastasis from liver and/or spleen aspirates. Of the five dogs with cytological evidence of liver or spleen metastasis, four had normal CT liver attenuation and size, one dog had concurrent primary hepatocellular neoplasia, four dogs had abnormal splenic parenchyma (two nodular and two diffuse heterogeneity), and one dog had a normal attenuation of the spleen. In four dogs, the spleen was subjectively enlarged. Computed tomographic evaluation of the liver showed no consistent pattern associated with mast cell metastasis and did not predict cytology results. Multifocal splenic hypoattenuating lesions more commonly coincided with mast cell metastasis. Sampling of the liver and spleen remains to be considered in the absence of abnormal CT findings for full staging.     

A carcinoid tumor in the gallbladder of a dog

A cholecystectomy was performed on a 10-year-old spayed female mixed-breed dog with chronic weight loss, persistently increased liver enzyme activities, and cholecystomegaly identified by ultrasonographic examination. A subsequent diagnosis of a biliary carcinoid was made based on a neuroendocrine-type histologic pattern, cytoplasmic argyrophilia by Grimelius staining, immunopositivity for chromogranin A, and the ultrastructural finding of cytoplasmic secretory granules in neoplastic cells. Extrahepatic biliary carcinoid tumors are rare tumors of humans and have not been documented in domestic animals.     

Long-term survival in a dog with primary hepatic neuroendocrine tumor treated with toceranib phosphate

Primary hepatic neuroendocrine tumors (PHNETs) are rare in dogs, and limited information exists about the treatment of these tumors. A 12-year-old castrated male French bulldog was presented to our clinic with gastrointestinal signs. Diagnostic tests revealed increased hepatic enzyme levels, a mass in the hepatic quadrate lobe, multiple intrahepatic nodules, and enlarged hepatic hilar lymph nodes. The liver mass was diagnosed cytologically as a malignant epithelial tumor suspected to be of neuroendocrine origin. The dog was treated with single-agent toceranib phosphate (TOC) and survived 25.1 months after the initial presentation. On necropsy, a liver mass was found and was subsequently diagnosed as a PHNET on histopathology. To the best of our knowledge, this is the first report of long-term survival in a dog with PHNET treated with TOC.     

Evaluation of Liposomal Radiochemotherapy for Treatment of Cancer

Introduction: Pegylated liposomes target solid tumors by exploiting the capillary leakage properties of tumor neovasculature. The goal of the study was to investigate distribution and tumor targeting properties of the alpha‐particle emitter ²²³Ra, encapsulated in doxorubicin‐containing‐liposomes (Caelyx^®/Doxil^®). Methods: Caelyx^® was given before the injection of liposomal ²²³Ra to reduce the reticulo‐endothelial‐system uptake. A pilot study was conducted to determine the optimal time interval between the pre‐treatment/treatment. Subsequently a more extensive distribution study was performed in normal BalbC mice. In addition, distribution and tumor uptake was evaluated in a human osteosarcoma xenograft mice model and in a dog with spontaneous osteosarcoma. Results: Optimal blood‐to‐liver and blood‐to‐spleen ratios of liposomal radium was achieved in animals that received pre‐treatment with Caelyx^® 4 days in advance. Blood clearance was relatively slow, in mice t_1/2 was ～28 h (BalbC mice) and in the dog t_1/2 was ～ 39 h. In mice the liver uptake appeared to be relatively low in contrast to the spleen, where there was a significant uptake. In the dog the uptake in both liver and spleen was moderate. In the xenograft model there was generally a higher retention of activity in the tumor vs. soft tissue. In the dog the 24 h uptake was considerably higher in both calcified and non‐calcified tumor metastases of different organs, than in normal tissue. Conclusions: Liposomal ²²³Ra has a relevant biodistribution and blood clearance for tumor targeting. More extensive future studies are supported by the favourable tumor/normal‐tissue ratio in a dog with spontaneous osteosarcoma.     

QUANTITATIVE HEPATOBILIARY SCINTIGRAPHY WITH DECONVOLUTIONAL ANALYSIS FOR THE MEASUREMETN OF HEPATIC FUNCTION IN DOGS

A nuclear medicine procedure that has been used for quantification of hepatocyte function in man is applied and validated in the dog. This procedure employs deconvolutional analysis of liver and heart time activity curves obtained following peripheral intravenous injection of hepatobiliary radiopharmaceutical. The deconvolutional analysis simulates a bolus injection of the radiopharmaceutical into the afferent blood supple of the liver which permits the calculation of the hepatic extraction fraction. Hepatic extraction fraction is a measure of hepatocyte function. In this report, the deconvolutional analysis via fast Fourier transformations and subsequent calculation of hepatic extraction fraction is validated by direct afferent intravascular ijection of ^99mTc-mebrofenin. The hepatic extraction fraction determined via deconvolutional analysis was found to be the same as the first pass hepatic extraction fraction determined via deconvolutional analysis was found to be the same as the first pass hepatic extraction fraction determined by direct mesenteric (portal) vein injection. The same results can be obtained in a sedated animal, making the technique clinically applicable. Thus hepatic extraction fraction, obtained from a perlpheral intravenous injection of ^99mTc-mebrofenin, can provide a quatitative measure of hepatocyte function from a non-invasive procedure. The quantitative ability to measure hepatocyte function has potential in many clinical and research situations.     

Canine serum thermostable alkaline phosphatase isoenzyme from a dog with hepatocellular carcinoma

A dog histopathologically diagnosed with hepatocellular carcinoma (HCC) showed very high serum alkaline phosphatase (ALP) activity. A supernatant of ascitic fluid and tumor tissue extracted from the dog also showed much higher ALP activity than normal. ALP isoenzyme analysis of samples was performed using polyacrylamide gel disk electrophoresis, and a wide, broad abnormal band was observed. By various treatments, the abnormal band showed thermostability, which is a characteristic of tumor-associated ALP that has only been reported in humans. The thermostable ALP isoenzyme was not found in sera from 39 dogs with several types of tumor that originated from the liver, except for HCC, nor was it found in 10 dogs with hepatic diseases that did not include hepatic tumors. The thermostable ALP isoenzyme seemed to be associated with canine HCC.     

RADIATION INDUCED VERTEBRAL OSTEOSARCOMA FOLLOWING TREATMENT OF AN INTRADURAL EXTRAMEDULLARY SPINAL CORD TUMOR IN A DOG

A 2-year-old neutered female Rottweiler diagnosed with an intradural extramedullary spinal cord tumor at T12-T13 was successfully treated with cytoreductive surgery followed by Cobalt 60 teletherapy. The dog was euthanised 5-and-a-half years later following diagnosis of an osteosarcoma involving the L1 and L2 vertebrae. Evidence of the initial tumor was not present at necropsy. The vertebral neoplasm fulfilled all of the accepted criteria for a radiation induced tumor. It was concluded that adjunctive irradiation should be considered for treatment of intradural extramedullary tumors of young dogs when total surgical resection is not possible. Although tumor induction is a rare late effect of radiation therapy, the risk of this occurrence should be considered when irradiating young animals. Radiation induced tumors in dogs have been associated with coarse fractionation schemes, or when large intraoperative doses have been administered. A lower dose per fraction, e.g., 3 Gy/fraction or less, is advisable when irradiating young dogs or any dog in which the life expectancy is 3-5 or more years after irradiation.     

Ultrasonographic assessment of liver size in the dog

A simple ultrasonographic method of estimating liver size in the dog was evaluated in this study. A single linear measurement from the tip of the ventral liver lobes to the diaphragm was made, using both transverse and longitudinal planes of section, Assuming careful technique, this measurement proved to be highly reproducible. There was good correlation between the measurements taken on the two planes of section. This measurement was shown to provide a good indicator of liver mass, irrespective of the size or breed of dog. It was concluded that ultrasound provides a simple, quantitative method of assessing liver size in the dog.     

Immunocytological confirmation of bone marrow metastases in a dog with cholangiocarcinoma

The case history of a four-year-old, male Bernese mountain dog is presented. Carcinoma cells were detected in the liver by ultrasound-guided fine-needle aspiration. Bone marrow aspirated from the iliac crest and the left femur showed a distinct infiltration by carcinoma cells. Immunocytological examination of the liver and bone marrow metastases showed a negative staining result for large spectrum cytokeratin (CK) KL1, a strong positive result for CK7 and a focal weak positive result for CK20. The dog was euthanased due to the grave prognosis. Histopathological examination revealed metastatic cholangiocarcinoma. The authors conclude that cytological and immunocytological examination of bone marrow aspirates should be used more frequently for the detection of distant metastases of carcinomas in small animal medicine.     

Vitamin A concentrations in commercial foods for dogs and cats

The vitamin A concentration was determined in 89 Australian brands of commercial foods for dogs and cats. It was found that 8% of the dog foods and 14% of the cat foods had concentrations of vitamin A below the minimum recommended 1.1 mg/kg dry matter (dm) for dogs and 1.8 mg/kg dm for pregnant or lactating cats. Canned and fish-labelled cat foods were the only varieties with less than the minimum recommended concentration of Vitamin A, of which 71% were the same brand. The minimum recommended concentration of vitamin A was exceeded in all canned dog food tested. Concentrations of vitamin A in dry (ca. 6% moisture) dog and cat foods and semi-moist dog foods (ca. 23% moisture) never exceeded 10 mg vitamin A/kg dm. In contrast, canned pet foods stated to contain liver or kidney showed vitamin A concentrations from 13 to 284 mg/kg dm.     

Hilar Liver Resection in Dogs

Objective— To describe hepatic vasculobiliary anatomy important to hilar liver lobe resection in the dog.
Study Design— Experimental study.
Animals— Canine cadavers (n=7).
Methods— The vasculobiliary system of 7 fresh canine livers was injected with a polymer. The parenchyma was dissected at the level of the hilus to determine the vascular and biliary supply to each liver lobe, and then macerated with a corrosion preparation. The information gathered was used to describe a surgical approach for hilar liver lobe resection.
Results— Each liver lobe had a single hepatic artery and biliary duct. The location of these structures was consistent, although minor variations existed (dorsal versus ventral to the lobar portal vein) in the left lateral lobe and papillary process in 2 specimens. Most liver lobes (34/49) were supplied by 1 lobar portal vein and drained by 1 lobar hepatic vein (39/49). The location of the portal and hepatic veins was consistent among specimens.
Conclusions— The left division is the most mobile of the liver lobes and each lobe can be removed separately or en bloc. Because of the location of the hepatic veins, the central division is best removed as a single unit. The right lateral lobe can be removed individually or together with the caudate process. The papillary process is removed by itself.
Clinical Relevance— A hilar liver lobectomy technique can provide an alternative approach to conventional procedures for tumors that encroach upon the hilus of the liver.     

Neuroendocrine carcinoma of the gallbladder in a dog

A 9-year-old Bullmastiff with hematemesis was determined to have primary neuroendocrine carcinoma of the gallbladder. Despite the dismal prognosis when these unusual tumors are located in the liver, the hematemesis resolved, and there was no obvious tumor regrowth in this dog 10 months after cholecystectomy.     

QUANTITATIVE HEPATIC SCINTIGRAPHY IN THE DOG

Quantitative hepatic scintigraphy is a noninvasive test for measurement of relative arterial and portal blood flow to the liver. This technique has been used to evaluate human patients with known or suspected liver tumors or diffuse hepatocellular disease. A computer program to assess the hepatic perfusion index (HPI) in the normal dog is described. Factors affecting study quality and accuracy include injection technique, cardiac function, patient position, respiration, gross patient motion, and user intervention during data processing. HPI for a group of 12 normal dogs was 0.9±0.4 (X±SD). Quantitative scintigraphy could be used to evaluate dogs with primary or secondary liver tumors, portacaval shunts, or chronic liver disease     

Cholestasis Associated With Extrahepatic Bacterial Infection in Five Dogs

Intrahepatic cholestasis associated with severe extrahepatic bacterial infection is well recognized in humans. A similar syndrome is not well characterized in veterinary medicine. Five dogs with severe extrahepatic bacterial infection that developed histologically confirmed intrahepatic cholestasis were selected from the authors' case files. The types of infections included pneumonia, peritonitis secondary to a rectal tear, urinary tract infection, bite wounds, and vegetative endocarditis. Escherichia coli was involved in two of the dogs, mixed infection in one dog, and a gram-positive cocci in the other two dogs. Total bilirubin concentrations ranged from 3.5 to 33.5 mg/dl. Serum liver enzyme activities showed only mild to moderate increases: alkaline phosphatase (ALP, 41-750 IU/l), alanine aminotransferase (ALT, 25-235 IU/l), and aspartate aminotransferase (AST, 99-255 IU/l). Fasting serum bile acids concentration was markedly elevated in the one dog in which it was measured (259 mumol/l). Histologically, the cholestasis was characterized by bile pigment accumulation in hepatocytes, canaliculi, and/or Kupffer's cells. Inflammatory parenchymal changes, when present, were minimal. The findings of hyperbilirubinemia, only a slight increase in the liver enzyme activities, and minimal inflammatory changes in liver tissue specimens in the five dogs with extrahepatic bacterial infections are similar to the findings in intrahepatic cholestasis associated with extrahepatic bacterial infection in humans.     

Transient proximal renal tubular acidosis and Fanconi syndrome in a dog

A 9-year-old spayed female Labrador Retriever was evaluated for anorexia, lethargy, and vomiting of 5 days' duration. Laboratory abnormalities included azotemia, high liver enzyme activities, hyperchloremic metabolic acidosis, glucosuria, ketonuria, proteinuria, and aminoaciduria. These laboratory abnormalities were diagnostic of proximal renal tubular acidosis and Fanconi syndrome. Results of initial and convalescent serologic tests for leptospirosis were negative. The dog was treated with amoxicillin, sodium bicarbonate, and potassium citrate at discharge. Repeated evaluations revealed resolution of the acidosis, azotemia, proteinuria, glucosuria, ketonuria, and high liver enzyme activities. Alkali administration was gradually discontinued, and the dog was clinically normal 8 months after discharge. The dog's clinical condition appeared to have been transient in nature, a phenomenon that is rarely seen in human or veterinary medicine.     

Evaluation of tizanidine as a marker of canine CYP1A2 activity

The dog CYP1A2 enzyme is likely an important contributor to the metabolism of veterinary drugs. Dog CYP1A2 is expressed in liver, plus it is inducible and polymorphic, creating the potential for intersubject differences in pharmacokinetics. Hence, the ability to probe dog CYP1A2 activity and inhibition is relevant toward veterinary drug development and drug–drug interaction assessment. Previous studies have relied on human probes with questionable specificity for CYP1A2, so it was hypothesized that recombinant CYP1A2 could be used to find a specific CYP1A2 substrate. Intrinsic clearance experiments demonstrated that tizanidine was a substrate of CYP1A2. Profiling of tizanidine metabolites generated by CYP1A2 identified the imidazole metabolite that was detectable in dog plasma. The imidazole metabolite was subsequently used to evaluate tizanidine as a CYP1A2 probe. Co‐administration of the CYP1A inhibitor enrofloxacin with tizanidine significantly decreased (30%; n = 3) the formation of the imidazole metabolite vs. control experiments. As enrofloxacin is a weak inhibitor, further studies are required to confirm the sensitivity of tizanidine as an in vivo probe. However, tizanidine may be a more selective CYP1A2 probe than phenacetin when conducting in vitro studies due to the presence of other phenacetin‐metabolizing enzymes in dog liver microsomes.     

Electro-acupuncture and Chinese herbs for treatment of cervical intervertebral disk disease in a dog

A non-ambulatory dog with tetraparesis following a pain episode that had evolved over 2 months was submitted for medical treatment and diagnosed with intervertebral disk disease at C3-C4 and dorsal extradural compression at C1-C2 and C3-C4 using myelography and computed tomography. The dog experienced ambulation recovery after 15 days of treatment with only electroacupuncture and Chinese herbal medicine, with marked improvement occurring after only 10 treatments. Six months of follow-up demonstrated that the dog was stable and had no recurrence of symptoms. Therefore, it was concluded that the combination of electroacupuncture and Chinese herbal medicine was responsible for motor rehabilitation.     

B‐cell lymphoma with Mott cell differentiation in two young adult dogs

Abstract: Two young adult dogs with gastrointestinal signs were each found to have an intra‐abdominal mass based on physical examination and diagnostic imaging. On exploratory laparotomy, small intestinal masses and mesenteric lymphadenopathy were found in both dogs; a liver mass was also found in dog 1. Cytologic and histologic examination of intestinal and liver masses and mesenteric lymph nodes revealed 2 distinct lymphoid cell populations: lymphoblasts and atypical Mott cells. With Romanowsky stains, the atypical Mott cells contained many discrete, clear to pale blue cytoplasmic inclusions consistent with Russell bodies that were positive by immunohistochemistry for IgM and CD79a in both dogs and for IgG in dog 2. The Mott cells and occasional lymphoblasts stained strongly positive with periodic acid‐Schiff. Using flow cytometric immunophenotyping in dog 1, 60% of peripheral blood mononuclear cells and 85% of cells in an affected lymph node were positive for CD21, CD79a, IgM, and MCH II, indicative of B‐cells. With electron microscopy, disorganized and dilated endoplasmic reticulum was seen in Mott cells in tumors from both dogs. Antigen receptor gene rearrangement analysis of lymph node and intestinal masses indicated a clonal B‐cell population. Based on cell morphology, tissue involvement, and evidence for clonal B‐cell proliferation, we diagnosed neoplasms involving Mott cells. To the authors' knowledge, this is the second report of Mott cell tumors or, more appropriately, B‐cell lymphoma with Mott cell differentiation, in dogs. More complete characterization of this neoplasm requires further investigation of additional cases. This lymphoproliferative disease should be considered as a differential diagnosis for canine gastrointestinal tumors.     

Mitotane (o, DDD) resistance in a dog with pituitary-dependent hyperadrenocorticism and phaeochromocytoma

A dog was presented with a 2 year history of polyuria and polydipsia due to pituitary-dependent hyperadrenocorticism. A low-dose dexamethasone suppression test and measurement of plasma ACTH concentration confirmed the diagnosis. Treatment was instituted with mitotane at 44 mg/kg/day and then 88 mg/kg/d without complete resolution of signs. The dog collapsed with signs consistent with liver disease and was euthanased. Necropsy revealed a phaeochromocytoma of the left adrenal medulla with extensive metastases to the liver. A chromophobe adenoma of the pars intermedia of the pituitary was found.     

A case of alveolar hydatid disease in a dog: domestic animals as rare incidental intermediate hosts for Echinococcus multilocularis

A 2-years old male Labrador retriever dog was presented with intermittent therapy-resistant diarrhoea, accompanied by vomiting, inappetence, apathy, and mild fever. The blood analysis showed an anaemia, neutrophilia, eosinophilia, and increased liver enzymes. Abdominal palpation was slightly painful. X-rays and echography revealed a severely enlarged liver with multiple cavernous structures. Histopathologic examination of liver biopsies showed a severe chronic granulomatous hepatitis with numerous parasitic cysts. Morphology of the cysts was compatible with the metacestode stage of Echinococcus multilocularis. The dog was only 2-years old at the time of diagnosis. Although alveolar hydatid disease of the liver is rare in dogs, it should be envisaged as a possible differential diagnosis in cases of space-occupying processes in the liver, even in young animals, as the incubation period of this disease in the dog can be considerably shorter than in humans.