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Synovial cell sarcoma (SCS) with metastasis to the regional lymph node was diagnosed in two cats. Synovial cell sarcomas are rare in cats and metastatic SCS has not previously been reported. In both cases, treatment consisted of limb amputation and adjuvant doxorubicin. Local tumour recurrence and pulmonary metastases were diagnosed in one cat 316 days postoperatively. This cat died of chronic renal failure 444 days after limb amputation. The second cat died of an acute pulmonary thromboembolism 41 days postoperatively without evidence of local tumour recurrence or metastatic disease.

Objective: To compare use of doxorubicin, surgery, and radiation versus surgery and radiation alone for treatment of cats with vaccine-associated sarcoma., Design: Retrospective study., Animals: 25 cats with vaccine-associated sarcomas., Procedure: Time to first recurrence and survival time were compared between the 2 treatment groups. The number of surgeries (1 or > 1) were compared with respect to time to first recurrence and survival time., Results: Median time to first recurrence was 661 days for the group that received doxorubicin, surgery, and radiation. Median time to first recurrence has not yet been attained for the group treated with surgery and radiation alone. Median survival time was 674 days for the group treated with doxorubicin, surgery, and radiation and 842 days for the group treated with surgery and radiation alone. For time to first recurrence and survival time, significant differences were not detected between cats that had 1 surgery and those that had > 1 surgery., Conclusions and Clinical Relevance: Significant differences between the 2 treatment groups were not detected. The efficacy of doxorubicin in the treatment of vaccine-associated sarcomas is uncertain.

Vaccine adjuvants provide enhanced immune responses to a variety of antigens. Unlike human vaccines that are limited to aluminum-based adjuvants, veterinary vaccines may contain a large number of substances either alone or in combination that act as vaccine adjuvants. Although the use of adjuvants in veterinary vaccines enhances the immunogenicity of vaccines, they have been responsible for a number of side effects. This article explores the rationale of currently used vaccine adjuvants and some of the adverse events associated with their use in veterinary medicine.

Epidemiologic evidence shows a strong association between the administration of inactivated feline vaccines (feline leukemia virus and rabies) and subsequent soft tissue sarcoma development at vaccine sites. Although more research is needed to understand the complete pathogenesis of vaccine-induced tumors in cats, good evidence exists that inflammation plays a role.

Vaccine-induced sarcomas are reported to occur in 1 in 10,000 or less cats vaccinated with feline leukemia virus (FeLV) vaccines. The potential of local vaccine site adjuvant-associated inflammation plays in the pathogenesis of these tumors is probably significant. However, it is believed that the feline leukemia antigens contained within these vaccines also play an important role in malignant transformation.

Fifteen previously untreated dogs with histologically confirmed, high-grade multicentric lymphoma were entered into a phase I study to evaluate combined doxorubicin and whole-body hyperthermia (DOX/WBH). Groups of three, four, and eight dogs were treated with whole-body hyperthermia and concurrent doxorubicin at 12 mg/m2, 24 mg/m2 and 30 mg/m2, respectively, after one doxorubicin induction dose at 30 mg/m2. Plateau temperature (42 +/- 0.1 degree C) was maintained for 90 minutes using a radiant heating device. A total of five DOX/WBH treatments per dog were planned, and these were given every 21 days. Treatment-related toxicity was not seen in the 12-mg/m2 doxorubicin dose group. Tumor progression prohibited administration of more than three DOX/WBH treatments to any dog in the 12-mg/m2 group. Premature ventricular contractions developed after the fifth treatment in one of the four dogs treated with 24 mg/m2 of doxorubicin. Two dogs (25%) in the 30-mg/m2 dose group had treatment-related toxicity. One dog experienced acute serious myelosuppression 1 week after the third treatment. This dog received all planned DOX/WBH treatments. Asymptomatic cardiac toxicosis consisting of decreased ejection fraction and fractional shortening developed in the second dog. This dog received only two DOX/WBH treatments. The three dogs treated at 12 mg/m2 had partial responses of short duration (60-83 days). Four dogs treated at 24 mg/m2 had complete responses for 150, 164, 186, and 200 days. Eight dogs treated at 30 mg/m2 had complete responses with a mean and median duration of 241 and 190 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred and fifteen dogs with neoplasms of the lower urinary tract (bladder and/or urethra) were retrospectively evaluated at five referral institutions participating in ongoing studies by the Veterinary Cooperative Oncology Group. Most tumors were malignant (97%) and of epithelial origin (97%). Lower urinary tract tumors were more common in older dogs weighing greater than 10 kg. The following significant (P less than 0.05) statistical associations were found using the University of Guelph hospital population as control; there was no sex predisposition although the female:male ratio was 1.95:1. Neutered dogs were predisposed as were Airedale Terriers, Beagles, and Scottish Terriers, whereas German Shepherds were significantly under-represented among dogs with lower urinary tract tumors. These statistical associations should be interpreted cautiously because of possible demographic differences in hospital populations among the University of Guelph and other cooperating institutions. There were no significant correlations between age, gender, weight, breed, response to therapy, and survival time. Clinical signs were indicative of lower urinary tract disease and included hematuria, stranguria, and pollakiuria. The laboratory data were nonspecific except for urinalysis test results. Hematuria and inflammatory urinary sediments were most commonly reported; neoplastic cells were identified in the urine sediment of 30% of dogs with lower urinary tract tumors. Contrast cystography was a useful noninvasive diagnostic method since 96% of the dogs had a mass or filling defect in the lower urinary tract demonstrated by this technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Sixty-one dogs with histologically confirmed, untreated, high-grade lymphoma were evaluated and treated with doxorubicin (DOX, 30 mg/m2) alone. Forty-seven dogs (77%) achieved a complete response. Forty-six of the 47 dogs were randomized to receive five additional treatments with doxorubicin +/- whole-body hyperthermia (WBH). Median disease-free survival for the group treated with DOX alone (n = 22) was 189 days and for the DOX plus WBH (n = 24) was 239 days (p = 0.17). After the analysis was adjusted for stratification variables (i.e. institution, weight, stage), the effect of heat on disease-free survival remained statistically insignificant (p = 0.10), but suggested a tendency towards increased disease-free survival in hyperthermic dogs. Intact male dogs had significantly shorter disease-free survival than neutered males and neutered females (178 days vs 266 days, respectively; p = 0.013). No intact females were treated. Body weight, when evaluated as a continuous variable, was found to be a negative prognostic factor (p = 0.036). Tumour volume, stage and institution were not significant. Clinical incidence of cardiac dysfunction was not increased in dogs receiving DOX and WBH; however, post-mortem histological analysis of cardiac tissue suggested that the combined therapy of DOX and WBH was associated with greater myocyte degeneration (p = 0.012) and a tendency for increased cardiac fibrosis (p = 0.08). We concluded that continued refinement of DOX-WBH protocols is warranted, and may ultimately result in significant therapeutic improvement.

Heartworm antigenemia was evaluated and found to be negative in 1010 dogs in Northeastern Colorado that were examined at the Colorado State University Veterinary Teaching Hospital. The estimated prevalence of canine heartworm for the native Northeastern Colorado population was determined to be 0.3% and is similar to the prevalence reported 10 years ago in the same area. We conclude there has not been an increase in prevalence of heartworm in the last 10 years; because of the low prevalence, there is no need for routine testing or testing and prophylaxis in the study area at this time.

The maximum tolerated dose of melphalan combined with whole body hyperthermia (WBH) in dogs with spontaneous malignant melanoma was lower than in dogs not receiving WBH by a factor of 1.9 +/- 0.71. Thirty-three dogs were treated monthly with escalating doses of melphalan and followed weekly for toxicity and, when possible, tumour response. Toxicity was manifested as myelosuppression with nadir neutrophil and platelet counts occurring at 7-10 days post-treatment. The TD50 (+/- S.E.), defined by logistic regression analysis, was 0.63 (+/- 0.07) mg/kg and 0.33 (+/- 0.10) mg/kg for melphalan alone and combined with WBH, respectively. Objective tumour response in this limited series occurred in three of fourteen evaluable dogs (three of eleven treated with melphalan alone and none of three treated with WBH plus melphalan). It is concluded that melphalan combined with WBH can be safely administered, although a reduction in dose is necessary. A randomized clinical trial is required to investigate the possibility of achieving therapeutic benefit from combined melphalan and WBH.

Microscopic anatomy of the horizontal part of the external ear canal was evaluated in 24 dogs. Sixteen dogs were from breeds known to have a predisposition to otitis externa. The remaining 8 dogs were from breeds that do not have a predisposition to otitis externa. Dogs were separated into groups according to predisposition to otitis externa: group 1-predisposed dogs without otic inflammation, group 2-predisposed dogs with otic inflammation, and group 3-nonpredisposed dogs without otic inflammation. Qualitative microscopic evaluation of distribution of hair follicles revealed hair within proximal, middle, and distal regions of the horizontal ear canal in all breeds. The degree of keratinization was directly proportional to the presence of otic inflammation and was excessive in group-2 dogs. Quality of sebaceous glands within the horizontal ear canal was similar among dogs with and without otitis externa, whereas the quantity of apocrine tubular glands was significantly increased (P less than 0.05) in dogs with otitis. Quantity of apocrine tubular glands was also greater in group-1 dogs than in group-3 dogs. Thickness of the soft tissue in the external ear canal increased in direct proportion to the progression of disease and was greatest in the proximal region of the affected ear canal. Soft tissue located caudally between nonopposing ends of the annular cartilage, within the proximal region of the horizontal ear canal, contained few glands and hair follicles in dogs without otitis externa. In dogs with otitis externa, this region was infiltrated by distended apocrine tubular glands.

Feline and human mucopolysaccharidosis VI (MPS VI or Maroteaux-Lamy syndrome) are inherited autosomal recessive deficiencies of lysosomal enzyme arylsulphatase B. Affected cats and children exhibit lesions caused by incompetent degradation, retinal atrophy and excessive urinary excretion of dermatan facial dysmorphia, corneal stromal opacities, leukocyte granulation, retinal atrophy and excessive urinary excretion of dermatan sulphate--and usually die before adulthood. Most attempts to treat humans affected with MPS VI or other mucopolysaccharidoses have been ineffective or logistically prohibitive, but allogeneic bone marrow transplantation (BMT) offers promise for cure of certain inborn errors of metabolism. Engraftment of normal donor marrow may endow the enzyme-deficient recipient with a continuous source of enzyme-competent blood cells and tissue macrophages to facilitate degradation of stored substrate and to prevent genesis of further malformations. To test this hypothesis, we performed allogeneic BMT in a 2-year-old male Siamese cat with advanced MPS VI. Here we describe BMT-induced correction of this hereditary enzyme deficiency.

Whole body hyperthermia to 42 degrees C was induced in five normal beagles, using a humidity- and temperature-controlled chamber. Core temperatures of 41.2-43.0 degrees C were achieved in 50 min and maintained for 60 min. Cardiopulmonary responses included marked tachypnea and tachycardia. Blood gases underwent progressive drops in both PO2 (mean, 117 torr) and PCO2 (mean, 22 torr), suggesting the possibility of the development of a diffusion barrier during heating. Increased anion gaps in the face of respiratory alkalosis indicated that a metabolic acidosis developed in the heated dogs. Transient but significant drops in serum potassium and phosphorus were also observed during hyperthermia. Other physiological data, including serum chemistries, complete blood count, colony-forming units, and urine electrolyte excretion, did not change significantly.

A dog with a lymphoproliferative disease resembling the Sézary syndrome variant of mycosis fungoides in man had large numbers of circulating morphologically abnormal lymphoid cells, multicentric cutaneous nodules and plaques, and extracutaneous involvement of lymph nodes and viscera. The presence of Pautrier's microabscesses, intracutaneous hyperchromatic cells, and leukemic cells with convoluted nuclei distinguished the disease from other types of cutaneous lymphoma.

Canine and human osteogenic sarcomas, like most other malignant tumors, cause or are associated with progressive impairment of host immune reactivity. Adjuvant immunotherapy with live BCG had shown increased survival in one study of canine disease. Experiments with induced fibrosarcomas in mice had suggested that some of the host immune defect might be ameliorated by splenectomy. A prospective clinical trial was conducted with several cooperating veterinary centers. Dogs with osteosarcoma apparently confined to a limb were randomized to be treated by amputation and methanol-extracted residue of BCG (MER), or by the same modalities plus splenectomy. Randomization was discontinued relatively early in the study because of higher mortality in the splenectomy group. Animals treated by amputation and MER could be compared only with historic controls; median and one-year survival rates did not differ significantly from those of prior series. Animals treated by amputation, splenectomy, and MER had significantly poorer survival.

For examination of the influence of antibody on the pathogenesis of feline leukemia virus (FeLV) infection, 12 weanling specific-pathogen-free cats were inoculated with isolates of FeLV and were treated beginning at 7, 19, 21, 24, 34, or 49 days post inoculation (DPI) with feline anti-FeLV hyperimmune serum (10 infusions, 37 mg globulin/kg each at 48-hr intervals). Anti-FeLV serum infusion initiated at 7 DPI prevented the onset of hematopoietic cell infection and viremia. Antibody treatment initiated at 19 or 24 DPI abrogated recently established FeLV viremia and extinguished p27 expression in bone marrow and blood cells. Viremia established for longer periods was refractory to antibody infusion despite establishment of enzyme-linked immunosorbent assay antibody titers of 1:80 to 1:320 in the treated cats. Latent FeLV infection was a sequel to antibody-induced curtailment of viral replication in bone marrow cells and was able to reactivate spontaneously in vivo as well as in vitro.

Serum amylase and lipase were measured in 32 healthy dogs and in 55 dogs with serum urea nitrogen values greater than 40 mg/dl, using a nephelometric analyzer (Coleman analyzer model 91). Mean serum amylase and lipase values in normal dogs were 1,085.48 units and 3.98 units, respectively. In dogs with azotemia, the mean serum amylase and lipase values were 1,822.79 units and 12.57 units, respectively. Serum urea nitrogen values could not be correlated with amylase or lipase values.

Rectal and subcutaneous temperatures were measured during a total of 10 whole body hyperthermia treatments conducted in six dogs. During five of the treatments skin cooling, by means of initiating air flow through the radiant heating device, was necessary during the plateau phase because rectal temperature exceeded the target value. Skin cooling was not necessary in the other five treatments. Although the rectal temperatures were similar in all 10 treatments, extensive and rapid subcutaneous temperature non-uniformity, of approximately 4 degrees C, developed during treatments where skin cooling was necessary. During the treatments where skin cooling was not necessary, the subcutaneous temperature remained approximately equal to the rectal temperature. These data indicate that the environment in the radiant heating device during the plateau phase can have a profound effect on the temperature at superficial sites, which is not reflected by the temperature measured at deeper sites. The temperature at superficial sites should be measured during whole body hyperthermia to assure that the prescribed heat dose is administered to the largest percentage of body mass possible. Active skin cooling during whole body hyperthermia should be avoided if possible.

Thirty-four canine tumor specimens (13 sarcomas and 21 carcinomas) were grown in soft agar gel. Susceptibility after continuous exposure to doxorubicin at concentrations of 1, 5, and 10 micrograms/ml was compared with that of control cultures. Plating efficiency averaged 0.096%. Doxorubicin at a concentration of 1 microgram/ml was found to result in greater than 70% inhibition of colony formation in 3 of 13 sarcomas and 1 of 21 carcinomas tested, and greater than 50%, but less than 70%, inhibition in 3 carcinomas and 1 sarcoma. Twenty-six tumors had less than 50% reduction in colony formation and were considered resistant. Minor differences in responses to drug in primary and metastatic locations were observed and attributed to tumor heterogeneity and test variability.

A multiinstitutional Phase I study using i.v. melphalan was conducted in dogs with spontaneously occurring neoplasia. Melphalan was administered at 7.5, 10, 11.25, 12.5, and 20 mg/m2 of body surface area. Disproportionately greater toxicity was observed in small dogs. Seven of the eight dogs (88%) weighing less than 14 kg experienced severe myelosuppression (neutropenia, less than 1500/mm3; and/or thrombocytopenia, less than 80,000/mm3), whereas only three of 13 dogs (23%) weighing greater than 14 kg developed severe myelosuppression (P = 0.016). We concluded that small dogs are at greater risk of developing bone marrow toxicity from i.v. melphalan than large dogs if body surface area is used to calculate the dose. Although both body surface area and weight were found to be significantly correlated with severity of toxicity, melphalan-induced toxicity in dogs can be more accurately estimated by body weight than by surface area, P = 0.008 versus P = 0.022, respectively. It may be necessary to prescribe antineoplastic agents that are eliminated by processes not primarily under metabolic influence or that produce side effects on tissue not correlated to basal metabolic rate on a parameter other than body surface area. In dogs, melphalan should be dosed on a weight basis, and treatment groups should be stratified by weight in randomized clinical studies, particularly when the weight range of treated subjects is great.

Iatrogenic hypothalamic-hypophysis-adrenal axis suppression occurred in 5 small dogs as a result of ophthalmic instillation of 1% prednisolone acetate. An ophthalmic suspension was applied 4 times a day to each eye, such that 4 mg/day was delivered for 2 weeks followed by 2.67 mg/day for 2 weeks. After treatment week 2, serum cortisol decreased from base-line mean values of 17.66 ng/ml (before ACTH) and 139.16 ng/ml (60 minutes after ACTH) to 3.22 ng/ml (before ACTH) and 13.58 ng/ml (60 minutes after ACTH). After treatment week 4, serum cortisol values decreased to a mean of 1.76 ng/ml (before ACTH) and 4.82 ng/ml (60 minutes after ACTH). Before ACTH cortisol values returned to base line 2 weeks after discontinuing treatment. Values after ACTH administration remained 26% lower than base line (P = 0.0132), although within a normal response range. Hepatic carbohydrate metabolism was altered, allowing marked glycogen accumulation. Marked increases in the blood glucose values after glucagon stimulation testing occurred at 3, 5, 15, 30, and 60 minutes after glucagon administration. The greatest increase corresponded to the 30-minute sample with a mean glucose increase of 112.40 mg/dl from base-line values (P = 0.0022) as a result of the ophthalmic corticosteroid applied. Seemingly, topical ophthalmic corticosteroids have the potential for causing adrenocortical suppression and hepatic metabolic changes. The dosage level of treatment was low enough to avoid major hematologic changes. The exaggerated response to the glucagon tolerance test indicates that this test can be used in detecting hyperglucocorticism.

Despite the fact that the mast cell tumor is a common neoplasm of the dog, we still have only a meager understanding of its etiology and biologic behavior. Many of the published recommendations for treatment are based on opinion rather than facts derived from careful studies and should be viewed with some skepticism. Because of the infrequent occurrence of this tumor in man, only a limited amount of help can be expected from human oncologists; therefore, burden of responsibility for progress in predicting behavior and developing treatment effective for canine mast cell tumors must fall on the shoulders of the veterinary profession.

Our understanding of the etiology, behavior, and most effective form of mast cell tumor treatment is rudimentary. I have tried to indicate specific areas that need further study in order to resolve some of the present controversies. Clinicians should recognize that many of the published recommendations for treatment of mast cell tumors are based on opinion and should be viewed with skepticism. Because of the infrequence of this tumor in man, limited help can be expected from human oncologists, and thus the burden of responsibility for progress in predicting behavior and developing effective treatment for canine mast cell tumors falls on the shoulders of veterinarians.