Association of argyrophilic nucleolar organizing regions, Ki-67, and proliferating cell nuclear antigen scores with histologic grade and survival in dogs with soft tissue sarcomas: 60 cases (1996-2002).

OBJECTIVE: To determine whether argyrophilic nucleolar organizing regions (AgNORs), Ki-67, and proliferating cell nuclear antigen (PCNA) scores were associated with histologic grade and survival in dogs with soft tissue sarcomas (STSs). DESIGN: Retrospective study. ANIMALS: 60 dogs with STSs. PROCEDURE: Medical records were examined and histologic specimens were reviewed. Tissue specimens obtained from archival materials were used to prepare sections for histologic staining for AgNOR and immunohistochemical staining for Ki-67 and PCNA labeling. Follow-up monitoring was obtained by reevaluation or telephone conversations with referring veterinarians or owners. RESULTS: 27 (45%) STSs were grade 1, 23 (38%) were grade 2, and 10 (17%) were grade 3. The mean and median AgNOR, Ki-67, and PCNA scores were determined, and significant positive associations among AgNOR and Ki-67 scores with histologic grade and mitotic score were detected. Fifty-four dogs had adequate follow-up examinations and were included in survival analysis and evaluation of prognostic factors. Overall median survival time was > 1,306 days. Twelve of 54 (22%) dogs died of tumor-related causes. Metastatic disease developed in 8 of 54 (15%) dogs. Results of univariate analysis indicated that increased mitotic score, increased AgNOR score, increased Ki-67 score, incomplete surgical margins, noncurative intent surgery, Ki-67 score greater than the median Ki-67 score, and AgNOR score greater than the median AgNOR score were prognostic factors for decreased survival time. Results of multivariate analysis indicated that increased AgNOR score was the only prognostic factor for decreased survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that AgNORs and possibly Ki-67 should be routinely evaluated with histologic grading for STSs in dogs.

Risk factors for sterile hemorrhagic cystitis in dogs with lymphoma receiving cyclophosphamide with or without concurrent administration of furosemide: 216 cases (1990-1996).

OBJECTIVES: To determine incidence and identify predisposing factors for sterile hemorrhagic cystitis (SHC) in dogs with lymphoma that were treated with cyclophosphamide and to evaluate whether furosemide administered i.v. concurrently with cyclophosphamide decreased the incidence of SHC. DESIGN: Retrospective study. ANIMALS: 216 dogs with lymphoma. PROCEDURE: Medical records of dogs with lymphoma that received cyclophosphamide chemotherapy in accordance with 1 of 2 protocols, with or without concurrent i.v. administration of furosemide, were examined. Data for the 2 groups were analyzed to determine the incidence and predisposing factors (age, breed, sex, weight, previous or preexisting disease, previous or preexisting urinary tract infection, neutropenia, azotemia, dose, and number of cyclophosphamide treatments) for cyclophosphamide-associated SHC. RESULTS: Cyclophosphamide-associated SHC developed in 12 of 133 (9%) dogs that had not received concurrent administration of furosemide and cyclophosphamide treatments; of the 83 dogs that had received furosemide, only 1 (1.2%) developed SHC. Dogs receiving cyclophosphamide and furosemide concurrently were significantly less likely to develop SHC than dogs that did not receive furosemide. Dogs with previous or preexisting immune-mediated disease were significantly more likely to develop cyclophosphamide-associated SHC. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results suggested an association between i.v. administration of furosemide concurrently with cyclophosphamide and decreased incidence of cyclophosphamide-associated SHC. Incidence of cyclophosphamide-associated SHC was similar in treated dogs that did not receive concurrent furosemide to that observed for other studies in which cyclophosphamide was administered orally. Cyclophosphamide-associated SHC appeared to develop early during the course of chemotherapy when furosemide was not administered concurrently with cyclophosphamide.

Principles of chemotherapy.

Chemotherapeutic agents can be used to increase both the length and the quality of the lives of patients with a wide variety of neoplastic diseases. The therapeutic index for many of these agents is very narrow; thus, close attention must be paid to proper dosing and timing of treatment. Proper patient selection is also critical for successful chemotherapy treatment. If the clinician is familiar with the agents being used, then toxicities can often be anticipated and then treated, or in some cases prevented, to ensure continued quality of life. The purpose of this article is to review the basic principles for the safe and effective use of various chemotherapeutic agents in the treatment of neoplastic diseases.