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- Author or Editor: William S. Dernell x
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Abstract
Objective—To identify matrix metalloproteinases (MMP) 2 and 9 in canine tumor tissue and to compare the amount of activity to that in unaffected stromal tissue.
Animals—30 dogs with spontaneously developing, high-grade osteosarcoma.
Procedure—Tumor and nearby stromal tissue (muscle) were obtained at the time of surgery. Specimens were homogenized, and supernatants were assayed, using gelatin zymography. Human derived standards were run concurrently. Densitometry was done to obtain a semiquantitative arbitrary unit value for each specimen. The amount of activity in tumor tissue was compared with the amount in stromal tissue.
Results—Gelatinolytic bands were observed from the analysis of all tumor tissues and in most stromal tissues. These bands migrated in the same molecular weight area as the human MMP 2 and 9 standards. Gelatinolytic activity could be quenched by the addition of 50 mM EDTA and 1 µg of synthetic tissue inhibitor of metalloproteinase (TIMP) 2 per 100 ml. There was significantly more gelatinolytic activity in tumor tissue than in stromal tissue.
Conclusions and Clinical Relevance—MMP 2 and 9 are detectable in canine neoplastic tissue. matrix metalloproteinases activity in tumor tissue is higher than in unaffected stromal tissue, indicating that canine MMP may be involved in the pathogenesis of tumor growth and metastasis. (Am J Vet Res 2000;61:111–114)
Abstract
Objective—To assess survival time in dogs that underwent treatment for stage III osteosarcoma and evaluate factors affecting survival.
Design—Retrospective case series.
Animals—90 dogs with stage III osteosarcoma.
Procedures—Records in the osteosarcoma database at the Animal Cancer Center at Colorado State University from 1985 to 2004 were searched for dogs with metastatic disease at the time of evaluation. Dogs were included in the study if they had metastasis to any site and if treatment was initiated. A Kaplan-Meier survival analysis was performed, and the influences of age, sex, breed, primary tumor site, metastatic sites, and treatment on outcome were analyzed via log-rank analysis.
Results—Median survival time was 76 days, with a range of 0 to 1,583 days. No significant differences in survival times on the basis of age, sex, breed, or primary site were observed. Breeds and primary tumor sites were typical of those usually associated with osteosarcoma in dogs. Dogs treated palliatively with radiation therapy and chemotherapy had a significantly longer survival time (130 days) than dogs in all other treatment groups. Dogs treated with surgery alone had a significantly shorter survival time (3 days) than dogs treated with surgery and chemotherapy (78 days). Dogs with bone metastases had a longer survival time than dogs with soft tissue metastases.
Conclusions and Clinical Relevance—Treatment of dogs with stage III osteosarcoma can result in various survival times. Dogs with metastasis to bone and dogs that were treated palliatively with radiation and chemotherapy had the longest survival times.
Abstract
Objective—To evaluate the efficacy and toxicity of an alternating carboplatin and doxorubicin chemotherapy protocol in dogs with putative microscopic metastases after amputation for appendicular osteosarcoma and assess patient-, tumor-, and treatment-related factors for associations with prognosis.
Design—Retrospective case series.
Animals—50 client-owned dogs.
Procedures—Records of dogs that underwent amputation for appendicular osteosarcoma and received an alternating carboplatin and doxorubicin chemotherapy protocol were reviewed. Dogs had full staging and were free of detectable metastases prior to chemotherapy. Data on disease-free interval (DFI), survival time, and toxicoses were retrieved from medical records and owner or referring veterinarian communications.
Results—Median DFI was 202 days. Median survival time was 258 days. Twenty-nine (58%) dogs completed the protocol as planned, and the rest were withdrawn typically because of metastases or toxicoses. Grade 3 or 4 myelosuppression was reported in 9 of 50 (18%) dogs and grade 3 or 4 gastrointestinal toxicosis in 6 of 50 (12%) dogs. There were no chemotherapy-related fatalities. Univariate factors associated with significant improvement in DFI included tumor location (radius), receiving doxorubicin as the first drug, starting chemotherapy more than 14 days after amputation, and no rib lesions on preamputation bone scans. Multivariate factors associated with a significant improvement in survival time were tumor location (radius) and completing chemotherapy.
Conclusions and Clinical Relevance—Alternating administration of carboplatin and doxorubicin resulted in DFI and survival time similar to those reported for single-agent protocols. Clients should be counseled regarding the likelihood of toxicoses. Relevance of sequence and timing of starting chemotherapy should be further evaluated.
Abstract
Objective—To determine the efficacy of primary re-excision alone for treatment of soft tissue sarcomas after recent incomplete resection, the frequency and clinical importance of detecting residual tumor in resected scars, and prognostic factors associated with the procedure.
Design—Retrospective case series.
Animals—41 dogs.
Procedures—Medical records of dogs that had undergone recent incomplete excision of a soft tissue sarcoma at a referring veterinary practice and subsequent re-excision of the scar at the Colorado State University Veterinary Medical Center were reviewed.Owners and referring veterinarians were contacted for follow-up information.Slides from re-excised specimens were reviewed.Dogs that underwent radiation therapy after the re-excision procedure were excluded.
Results—41 dogs met the inclusion criteria, and long-term follow-up information was available for 39 dogs.Median follow-up time was 816 days.Local recurrence of tumor developed in 6 of 39 (15%) dogs, and distant metastasis occurred in 4 of 39 (10%) dogs.Healthy tis sue margins of 0.5 to 3.5 cm were achieved at re-excision. Residual tumor was identified in 9 of 41 (22%) resected scars.No tumor-, patient-, or treatment-related variables were associated with local recurrence except for the presence of liposarcoma or fibrosarcoma or whether fine-needle aspiration had been performed prior to surgery.
Conclusions and Clinical Relevance—After incomplete resection of soft tissue sarcomas, resection of local tissue should be performed, even if excisable tissue margins appear narrow.A long-term favorable prognosis is achievable without radiation therapy or amputation. The presence of residual tumor in resected scar tissue should not be used to predict local recurrence.
Abstract
Objective–To describe the clinical features, surgical and histologic findings, biological behavior, and outcome of dogs with retroperitoneal sarcomas.
Design–Retrospective study.
Animals–14 dogs.
Procedures–Medical and pathology records from 1992 to 2002 of dogs with tumors originating in the retroperitoneal space were reviewed. Dogs with retroperitoneal tumors originating from the adrenal glands, kidneys, or ureters were excluded. Inclusion criteria included observation of a tumor arising from the retroperitoneal space during exploratory surgery or necropsy and histologic confirmation of tumor type. Details of clinical signs, diagnostic findings, surgical management, and outcome were determined from medical records and telephone interviews with veterinarians and owners.
Results–Retroperitoneal sarcoma was diagnosed in 14 dogs, 2 at necropsy and 12 during exploratory surgery. Hemangiosarcoma was the most common histologic diagnosis. Seven dogs had regional extension of the sarcoma into adjacent organs, and 4 dogs had metastatic disease. Grossly complete resection was possible in 6 dogs. Cytoreductive surgery or incisional biopsy was performed in the remaining dogs. Two dogs were treated with palliative radiation therapy (1 intraoperatively and 1 postoperatively). Three dogs received adjunctive chemotherapy, although none completed the targeted course because of development of local recurrence or metastatic disease. Local recurrence was reported in 2 of 12 dogs and metastasis in 10 of 14 dogs. Thirteen dogs died or were euthanatized as a result of the retroperitoneal sarcoma; 1 dog was alive and disease-free 410 days after surgery. Median survival time was 37.5 days.
Conclusions and Clinical Relevance–In dogs, retroperitoneal sarcomas are aggressive tumors with a high rate of local recurrence and metastasis, and a poor survival time. (J Am Vet Med Assoc 2004;224: 1471–1477)
Abstract
Objective—To determine the incidence of regional lymph node metastasis in dogs with appendicular osteosarcoma and determine whether regional lymph node metastasis was associated with shortened disease-free interval or survival time.
Design—Retrospective study.
Animals—228 dogs with appendicular osteosarcoma in which regional lymph nodes were examined histologically at the time of limb amputation.
Procedure—Information collected from the medical records included signalment; affected site; initial serum alkaline phosphatase activity; whether treatment involved adjuvant chemotherapy and, if so, chemotherapeutic agents administered and number of treatments; disease-free interval; and survival time.
Results—10 (4.4%) dogs had histologic evidence of regional lymph node metastasis at the time of amputation. Median disease-free interval for dogs without regional lymph node metastasis (238 days; range, 0 to 1,067 days) was significantly longer than median disease-free interval for dogs with regional lymph node metastasis (48 days; range, 2 to 269 days). Median survival time for dogs without lymph node metastasis (318 days; range, 20 to 1,711 days) was significantly longer than median survival time for dogs with lymph node metastasis (59 days; range, 19 to 365 days).
Conclusions and Clinical Relevance—Results suggest that regional lymph node metastasis is rare in dogs with appendicular osteosarcoma but that dogs with lymph node metastasis have a poorer prognosis than do dogs without. (J Am Vet Med Assoc 2005;226:1364–1367)
Abstract
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. (J Am Vet Med Assoc 2001;218:547–550)
Abstract
Objective—To evaluate prognostic factors associated with outcome of dogs with multiple cutaneous mast cell tumors (MCTs) treated with surgery with or without adjuvant treatment.
Design—Retrospective case series.
Animals—54 dogs with a minimum of 2 simultaneous, histologically confirmed cutaneous MCTs that had been excised and had adequate staging and follow-up data.
Procedure—Medical records from 1998 to 2004 were examined. Outcome was assessed with the Kaplan-Meier product-limit method and log-rank analysis. Prognostic factors evaluated included signalment; number, histologic grade, location, size, local recurrence, and de novo development of MCTs; quality of surgical margins; clinical signs at the time of diagnosis; and use of adjuvant treatment.
Results—Medical records of 54 dogs with 153 tumors were included. Median follow-up time was 658 days. Median disease-free interval (1,917 days; range, 11 to 1,917 days) and median survival time (1,917 days; range, 14 to 1,917 days) were not yet reached. The 1- year and 2- to 5-year survival rates were 87% and 85%, respectively. The overall rate of metastasis was 15%. Factors that negatively influenced survival time in the univariate analysis included incomplete excision, local recurrence, size > 3 cm, clinical signs at the time of diagnosis, and use of adjuvant treatment. Presence of clinical signs at the time of diagnosis was the only negative prognostic factor for disease-free interval detected in the multivariate analysis.
Conclusions and Clinical Relevance—Results suggested that multiple cutaneous MCTs in dogs are associated with a low rate of metastasis and a good prognosis for long-term survival with adequate excision of all MCTs.
Abstract
Objective—To determine clinical signs, diagnostic findings, outcome, and prognostic factors in dogs treated surgically for massive hepatocellular carcinoma (HCC) and compare survival times of surgically and conservatively treated dogs.
Design—Retrospective study.
Animals—48 dogs.
Procedure—Medical records were examined for clinical signs, diagnostic and surgical findings, and postoperative outcome. Dogs were allocated into surgery and nonsurgery groups depending on whether curative- intent liver lobectomy was performed. Data from the surgical and nonsurgical groups were analyzed to identify prognostic factors and determine and compare rates of tumor control and survival time.
Results—42 dogs were treated surgically, and 6 were managed conservatively. In the surgery group, intraoperative mortality rate was 4.8% with no local recurrence, metastatic rate was 4.8%, and median survival time was > 1,460 days (range, 1 to 1,460 days). High alanine aminotransferase and aspartate aminotransferase activities were associated with poor prognosis. Median survival time for the nonsurgery group was 270 days (range, 0 to 415 days), which was significantly less than that of surgically treated dogs.
Conclusions and Clinical Relevance—Liver lobectomy is recommended for dogs with massive HCC because tumor-related mortality rate was 15.4 times higher in dogs in the nonsurgery group, compared with the surgery group. Tumor control was excellent after surgical resection with no local recurrence and a low metastatic rate. Prognostic factors were identified, but their clinical relevance was uncertain because only 9.5% of dogs in the surgery group died as a result of their disease. (J Am Vet Med Assoc 2004;225:1225–1230)
Abstract
Objective—To determine outcome for dogs with grade-II mast cell tumors treated with surgery alone.
Design—Retrospective study.
Animals—55 dogs.
Procedures—Medical records were examined, and signalment; location and size of tumor; staging status; dates of local recurrence, metastasis, death, or last follow-up examination; status of surgical margins; previous surgery; postoperative complications; and cause of death were recorded. Follow-up information was obtained via reexamination or telephone conversations with owners or referring veterinarians. Univariate analysis was performed to identify prognostic factors.
Results—60 tumors in 55 dogs were included. Median follow-up time was 540 days. Three (5%) mast cell tumors recurred locally; median time to local recurrence was 62 days. Six (11%) dogs developed another mast cell tumor at a different cutaneous location; median time to a different location was 240 days. Three (5%) dogs developed metastases; median time to metastasis was 158 days. Fourteen dogs died; 3 deaths were related to mast cell tumor, and 7 were unrelated. The relationship with mast cell tumor was not known for 4. Median survival times were 151, 841, and 827 days, respectively, for these 3 groups. Forty-six (84%) dogs were free of mast cell tumors during the study period. A reliable prognostic factor could not be identified.
Conclusions and Clinical Relevance—Results suggest that additional local treatment may not be required after complete excision of grade-II mast cell tumors and that most dogs do not require systemic treatment. (J Am Vet Med Assoc 2001;218:1120–1123)
