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- Author or Editor: Michael D. Lucroy x
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Abstract
Objective—To determine whether transitional cell carcinoma (TCC) cells incubated in media containing 5-aminolevulinic acid (ALA) would produce sufficient protoporphyrin IX (PpIX) to cause lethal phototoxic effects when exposed to 635-nm light.
Sample Population—Canine TCC cells (K9TCC).
Procedure—Cultured K9TCC cells were exposed to graded doses of ALA, and PpIX concentrations were determined. Cells then were exposed to various doses of 635-nm light from a diode laser, and cell viability was assayed.
Results—Production of PpIX was dependent on time and dose of ALA. The K9TCC cells incubated with ALA produced sufficient PpIX to cause lethal phototoxic effects when exposed to 635-nm light. Phototoxic effects were dependent on time and dose of ALA. Increasing laser power density and energy density decreased cell survival.
Conclusions and Clinical Relevance—ALA is an effective photosensitizer for in vitro photodynamic treatment of K9TCC cells. Further studies are warranted to assess the safety and efficacy of ALA as a photosensitizer for use in treating dogs with TCC.
Impact for Human Medicine—On the basis of this study, dogs with TCC may be useful in the development of protocols for ALA-based photodynamic therapy of humans affected with muscle-invasive bladder cancer. (Am J Vet Res 2003;64:131–136)
Abstract
Objective—To determine whether the presence of anemia (Hct ≤ 37%) at the time of diagnosis of lymphoma is a negative prognostic indicator for response to treatment and survival time in dogs that are undergoing chemotherapy.
Design—Retrospective case series.
Animals—96 dogs with lymphoma that were receiving chemotherapy.
Procedures—Information regarding signalment, initial hematologic data, chemotherapy protocol, clinical response, and date of death was retrospectively collected from medical records of dogs with lymphoma. Univariate, multivariate, and survival analyses were performed to determine the effect of anemia on initial response to chemotherapy and on survival time.
Results—Overall, dogs without anemia (n = 56) were 4 times as likely as dogs with anemia (40) to have a complete response following chemotherapy. Anemic dogs had a significantly shorter median survival time (139 days), compared with survival time of nonanemic dogs (315 days). Subset analysis of dogs with multicentric lymphoma (matched for clinical stage and chemotherapy protocol) revealed that the dogs with anemia (n = 24) had a significantly shorter median survival time (101 days), compared with survival time of dogs without anemia (24; 284 days). Other variables were not associated with survival time.
Conclusions and Clinical Relevance—These findings suggested that anemia is a negative prognostic factor for dogs with lymphoma that are undergoing chemotherapy. Further investigation will be necessary to determine the impact of resolution of anemia on clinical outcome in dogs with lymphoma.
Objective
To describe diseases, prognosis, and clinical outcomes associated with leukocytosis and neutrophilia in dogs.
Design
Retrospective study.
Animals
118 dogs with leukocytosis and neutrophilia.
Procedure
Medical records from 1996 to 1998 were examined for dogs with WBC ≥ 50,000 cells/μl and neutrophilia ≥ 50%. Signalment, absolute and differential WBC counts, body temperature, clinical or pathologic diagnosis, duration and cost of hospitalization, and survival time were reviewed.
Results
Mean age was 7.7 years, WBC count was 65,795 cells/μl, and absolute neutrophil count was 53,798 cells/μI. Mean duration of hospitalization was 7.4 days and cost of hospitalization was $2,028.00. Forty (34%) dogs were febrile, and 73 (62%) dogs died. Overall median survival time was 17 days. Dogs with neoplasia or fever were more likely to die than dogs that were hospitalized or had systemic or local infections.
Clinical Implications
Leukocytosis and neutrophilia were associated with high mortality rate and have prognostic value. Given the mean duration and cost of hospitalization, frank discussion with an owner at first recognition of leukocytosis and neutrophilia may be warranted. (J Am Vet Med Assoc 1999;214:805–807)
Abstract
Objective—To describe diseases, prognosis, and clinical outcomes associated with extreme neutrophilic leukocytosis in cats.
Design—Retrospective study.
Animals—104 cats with extreme neutrophilic leukocytosis.
Procedure—Medical records from 1991 to 1999 were examined to identify cats that had ≥ 50,000 WBC/µl with ≥ 50% neutrophils. Signalment, absolute and differential WBC counts, rectal temperature, clinical or pathologic diagnosis, duration and cost of hospitalization, and survival time were reviewed.
Results—Mean age of cats was 8.3 years, mean WBC count was 73,055 cells/µl, and mean absolute neutrophil count was 59,046 cells/µl. Mean duration of hospitalization was 5.9 days, and mean cost of hospitalization was $2,010. Twenty-nine (28%) cats were febrile, and 63 (61%) cats died. Overall median survival time was 30 days. Cats with neoplasia were nearly 14 times as likely to die unexpectedly as cats with other diseases.
Conclusions and Clinical Relevance—Extreme neutrophilic leukocytosis was associated with a high mortality rate. The prognostic importance of extreme neutrophilic leukocytosis should not be overlooked. Cats and dogs have similar diseases, mortality rates, and treatment costs associated with extreme neutrophilic leukocytosis. (J Am Vet Med Assoc 2001;218:736–739)
Abstract
Objective—To determine the threshold for acute toxicosis of parenterally administered zinc phthalocyanine tetrasulfonate (ZnPcS4), a candidate second-generation photosensitizer, in mice and evaluate the compound's safety in a phase I clinical trial of ZnPcS4-based photodynamic therapy (PDT) in pet dogs with naturally occurring tumors.
Animals—Male Swiss-Webster mice and client-owned dogs with naturally occurring neoplasms.
Procedures—For the study of acute toxicosis, mice were given graded doses of ZnPcS4. To determine safety, a rapid-titration phase I clinical trial of ZnPcS4-based PDT in tumor-bearing dogs was conducted.
Results—In mice, administration of ≥ 100 mg of ZnPcS4/kg resulted in renal tubular necrosis 24 hours after IP injection. In tumor-bearing dogs, ZnPcS4 doses ≤ 4 mg/kg induced no signs of toxicosis and resulted in partial to complete tumor responses in 10 of 12 dogs 4 weeks after PDT. Tumor remission was observed with ZnPcS4 doses as low as 0.25 mg/kg.
Conclusions and Clinical Relevance—A conservative starting dose of ZnPcS4 was arrived at on the basis of mouse toxicosis findings. Zinc phthalocyanine tetrasulfonate–based PDT was tolerated well by all dogs and warrants further study. The identification of the maximum tolerated dose through traditional phase I clinical trials may be unnecessary for evaluating novel PDT protocols.
Objective
To determine clinical and pathologic findings in cats with alimentary malignant lymphoma and results of treatment with a combination of prednisone, l-asparaginase, vincristine, cyclophosphamide, doxorubicin, and methotrexate.
Design
Retrospective study.
Animals
21 cats with alimentary malignant lymphoma.
Procedure
Medical records were reviewed, and information on signalment, clinical history and signs, previous treatments, and results of laboratory tests, thoracic radiography, and abdominal ultrasonography were obtained.
Results
Test results in all cats were negative for FeLV; 3 of 19 were positive for feline immunodeficiency virus. Thirteen tumors were stage III, 7 were stage IV, and 1 was stage V. Diagnosis was confirmed on the basis of microscopic examination of histologic (n = 13) or cytologic (8) specimens. Immunophenotyping was performed on 13 tumors; 10 were T-cell and 3 were B-cell lymphomas. Overall median duration of first remission was 20 weeks. Overall median survival time was 40 weeks. The only factor significantly associated with duration of first remission was whether cats had a complete response following induction chemotherapy; duration of first remission was significantly associated with survival time. Cats tolerated treatment well; only 1 cat had a delay in the treatment schedule because of neutropenia.
Clinical Implications
Use of a multidrug chemotherapeutic protocol that includes l-asparaginase and doxorubicin results in minimal adverse effects and prolonged survival times in cats with alimentary malignant lymphoma. (J Am Vet Med Assoc 1998;213:1144-1149)
Abstract
Objective—To determine whether there was a decline in the percentage of dogs undergoing necropsies and whether there was substantial agreement or disagreement between clinical and pathologic diagnoses.
Design—Retrospective study.
Animals—623 dogs.
Procedure—Medical records of hospitalized dogs that died or were euthanatized and necropsied at a veterinary teaching hospital in 1989 and 1999 were reviewed. Clinical and pathologic diagnoses were recorded and compared.
Results—There was a significant decline in the necropsy rate of hospitalized dogs that died or were euthanatized in 1999, compared with 1989. In both 1989 and 1999, there was disagreement between the clinical and pathologic diagnoses in approximately a third of the cases.
Conclusions and Clinical Relevance—Despite improved diagnostic methods, the accuracy of diagnosis did not improve significantly in 1999, compared with 1989. Necropsy is the best method to assess overall diagnostic accuracy. Increased availability of teaching funds may promote efforts to have necropsies performed in veterinary teaching hospitals. ( J Am Vet Med Assoc 2004;224:403–406)
Objective
To compare outcome of surgical versus medical treatment of dogs with beta cell neoplasia.
Design
Retrospective study.
Animals
39 dogs with clinical signs of hypoglycemia and serum glucose and insulin concentrations consistent with a diagnosis of beta cell neoplasia.
Procedure
Information on signalment; clinical history; physical examination findings; results of CBC, serum biochemical analyses, and urinalysis; serum glucose and insulin concentrations; results of thoracic radiography and abdominal ultrasonography; treatment and treatment complications; survival time; and cause of death were obtained from medical records.
Results
26 dogs underwent exploratory celiotomy and partial pancreatectomy; 13 dogs were treated medically (ie, dietary change and prednisone). Median survival time was significantly longer for dogs treated surgically than for dogs treated medically. Significant differences were not found in mean age, body weight, duration of clinical signs prior to diagnosis, serum glucose and insulin concentration, or results of other serum biochemical tests between dogs treated surgically and dogs treated medically; also, there was no significant correlation between any of these parameters and survival time for either group of dogs.
Conclusions and Clinical Relevance
Results suggest that exploratory celiotomy and partial pancreatectomy are indicated once a tentative diagnosis of beta cell neoplasia is established in dogs. (J Am Vet Med Assoc 1999;215:226–230)
Abstract
Objective—To evaluate the antitumor activity and toxic effects of a conservative dose of cisplatin administered in combination with piroxicam to dogs with transitional cell carcinoma (TCC) of the urinary bladder.
Design—Clinical trial (nonrandomized, noncontrolled).
Animals—14 client-owned dogs with histologically confirmed TCC of the urinary bladder.
Procedures—Each dog was treated with cisplatin (50 mg/m2, IV, q 21 d [reduced to 40 mg/m2, IV, q 21 d because of toxic effects]) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h). A CBC, serum biochemical analyses, and urinalysis were performed prior to each cisplatin treatment. Tumor staging (determined from thoracic and abdominal radiographic and urinary bladder ultrasonographic findings) was performed before treatment and at 6-week intervals during treatment.
Results—5 dogs received only 1 dose of cisplatin because of the rapid progression of disease (n = 2) or toxic effects (3). With regard to the neoplastic disease among the other 9 dogs, 1 had partial remission, 5 had stable disease, and 3 had progressive disease after 6 weeks of treatment. Median progression-free interval was 78 days (range, 20 to 112 days). Median survival time was 307 days (range, 29 to 929 days). Moderate to severe renal toxicosis and moderate to severe gastrointestinal toxicosis developed in 5 and 8 dogs, respectively.
Conclusions and Clinical Relevance—Because of minimal efficacy and associated renal and gastrointestinal toxicosis, administration of cisplatin (40 to 50 mg/m2) with piroxicam cannot be recommended for treatment of dogs with TCC of the urinary bladder.
