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Biomedical subjects

R C Straw

Publications and source records attributed to R C Straw.

At least 19 recordsLinked to original sources

Multilobular osteochondrosarcoma of the hard palate in a dog.

A 14-year-old castrated male Rhodesian Ridgeback was presented with a history of sneezing and epistaxis. Diagnostic procedures included physical examination, regional and thoracic radiography, computed tomography and histological examination of an incisional biopsy. A multilobular osteochondrosarcoma of the hard palate with pulmonary metastases was diagnosed. Surgical resection of the primary tumour was achieved with clean margins and the defect was repaired using bilateral mucosal transposition flaps from the lips. Wound dehiscence and oesophageal stricture were postoperative complications, but these resolved with treatment. A long-term survival time of 14 months resulted, with good quality of life and function during this time.

Animals↗

Matrix metalloproteinase-2 and -9 involvement in canine tumors.

Matrix metalloproteinases (MMPs) are a family of enzymes implicated in the degradation and remodeling of extracellular matrix and in vascularization. They are also involved in pathologic processes such as tumor invasion and metastasis in experimental cancer models and in human malignancies. We used gelatin zymography and immunohistochemistry to determine whether MMP-2 and MMP-9 are present in canine tumors and normal tissues and whether MMP production correlates with clinicopathologic parameters of prognostic importance. High levels of pro-MMP-9, pro-MMP-2, and active MMP-2 were detected in most canine tumors. Significantly higher MMP levels were measured in canine tumors than in nontumors, malignancies had higher MMP levels than benign tumors, and sarcomas had higher active MMP-2 than carcinomas. Cartilaginous tumors produced higher MMP levels than did nonsarcomatous malignancies, benign tumors, and normal tissues, and significantly greater MMP-2 than osteosarcomas and fibrosarcomas. Pro-MMP-9 production correlated with the histologic grade of osteosarcomas. The 62-kd form of active MMP-2 was detected only in high-grade, p53-positive, metastatic malignancies. Zymography proved to be a sensitive and quantitative technique for the assessment of MMP presence but has the limitation of requiring fresh tissue; immunohistochemistry is qualitative and comparatively insensitive but could be of value in archival studies. MMP presence was shown in a range of canine tumors, and their link to tumor type and grade was demonstrated for the first time. This study will allow a substantially improved evaluation of veterinary cancer patients and provides baseline information necessary for the design of clinical trials targeting MMPs.

Animals↗

Use of mandibular symphysiotomy to allow extensive caudal hemimaxillectomy in a dog.

A 5-year-old dog was presented with a large caudal maxillary osteosarcoma, which was causing extreme pain on opening of the mouth. The mass was not resectable through a standard oral approach. This article describes the successful use of mandibular symphysiotomy to allow extensive caudal hemimaxillectomy to remove the mass and provide excellent postoperative quality of life for the dog.

Animals↗

Effects of a controlled-release cisplatin delivery system used after resection of mammary carcinoma in mice.

OBJECTIVE: To evaluate efficacy of a controlled-release cisplatin delivery system, used after marginal resection of mammary carcinoma (ie, resection of grossly evident tumor) in mice, to prevent tumor regrowth and metastasis. ANIMALS: 42 female C3H-HeJ mice. PROCEDURE: Mice were inoculated with mammary carcinoma cells. Between 2 and 6 days later, tumors were marginally resected and mice were assigned to 1 of 3 groups: no treatment (control; n = 14), cisplatin administered intraperitoneally (i.p. cisplatin; 14), and cisplatin delivered by use of an open-cell polylactic acid system placed within the tumor bed (slow-release cisplatin; 14). Tumor regrowth was measured daily. Mice were euthanatized 14 days after surgery, and complete necropsies were performed. RESULTS: Tumor regrowth was not detected in the slow-release cisplatin group; however, tumor regrowth was detected in 7 of 14 mice in the i.p. cisplatin group and 14 of 14 mice in the control group. Median (+/-SD) number of days to tumor regrowth was 13.5+/-0.64 and 7.79+/-0.87 in the i.p. cisplatin and control groups, respectively. Mice in the i.p. cisplatin group had significantly delayed tumor regrowth, compared with control mice. Metastases to lungs were detected in 8 of 14 control mice but were not detected in mice in either cisplatin treatment group. CONCLUSIONS AND CLINICAL RELEVANCE: The open-cell polylactic acid with cisplatin delivery system was successful in delaying local tumor regrowth and metastasis in mice with marginally resected mammary carcinoma. Use of a controlled-release cisplatin delivery system may be an effective adjunct treatment following excision of mammary carcinoma in humans and other animals.

Animals↗

Apparent interaction of dimethyl sulfoxide with cisplatin released from polymer delivery devices injected subcutaneously in dogs.

Local tissue toxicity, systemic toxicity and platinum pharmacokinetics were evaluated in 6 normal healthy beagle dogs injected subcutaneously with two formulations of a polylactide biodegradable polymer (Atrigel) system containing cisplatin. Dogs were injected 4 times at 30 day intervals at platinum dosages of 70, 105 and 157.5 mg/m2 (dose escalation). Once pharmacokinetics were established, 29 dogs with spontaneous stage IIb appendicular osteosarcoma were treated with 4 injections of the same polymer system containing cisplatin at 70 mg/m2 (20 dogs) and 100 mg/m2 (9 dogs) to establish efficacy against micrometastatic disease. Local tissue toxicity was variable. Systemic toxicity, as judged by clinicopathologic evaluation was not noted at any dose level or injection number. Interim (6 month) survival analysis revealed a median disease-free interval of 180 days. Consistent platinum release characteristics were found, however, the lack of toxicity and decreased disease-free-interval raised concerns over the biologic activity of the cisplatin. Prior to completion of the study, it was discovered that dimethyl sulfoxide, the solvent used in the co-polymer system, may be responsible for biologic inactivation of cisplatin. This was subsequently demonstrated in tissue culture assays. The clinical trial was suspended and dogs were treated with traditional chemotherapy.

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Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996).

OBJECTIVE: To determine results of surgery for treatment of soft-tissue sarcomas in dogs and to identify prognostic variables that can be used to predict outcome. DESIGN: Retrospective case series. ANIMALS: Dogs with soft-tissue sarcomas that had surgical treatment only. PROCEDURE: Records were examined for clinically relevant data. Histologic samples were reviewed. Follow-up information was obtained by physical examination or telephone conversations with referring veterinarians or owners. RESULTS: 75 dogs with soft-tissue sarcomas of the trunk and extremities were identified. Median age was 10.6 years. Malignant peripheral nerve sheath tumors were of a significantly lower grade than other tumors. Tumors recurred locally in 11 of 75 (15%) dogs. Evaluation for lack of tumor cells at surgical margins was prognostic for local recurrence. Metastatic disease developed in 13 of 75 (17%) dogs. Tumor mitotic rate was prognostic for development of metastasis. Twenty-five of 75 (33%) dogs died of tumor-related causes. Percentage of tumor necrosis and tumor mitotic rate were prognostic for survival time. Median survival time was 1,416 days. CLINICAL IMPLICATIONS: On the basis of a low local recurrence rate and high median survival time, wide excision of tumor margins or radical surgery appeared to be an effective means for managing soft-tissue sarcomas of the trunk and extremities. Analysis of histologic characteristics for prognosis supported use of preoperative biopsy. Surgical margins should be evaluated, and early use of aggressive surgery is indicated in the management of soft-tissue sarcomas in dogs.

Animals↗

Limb-sparing surgery versus amputation for dogs with bone tumors.

Recently, limb-sparing surgeries have been used in the treatment of dogs with malignant bone tumors. These new techniques are fraught with potential complications. As amputation is a time-honored technique in veterinary medicine for the control of primary bone tumors, the use of newer, more complicated surgeries such as limb sparing may be considered controversial. In this article, amputation and limb sparing are discussed with reference to case selection, outcome, and possible complications.

Amputation, Surgical↗

Treatment of thyroid carcinoma in dogs by surgical resection alone: 20 cases (1981-1989).

Of 82 dogs with thyroid carcinoma seen between January 1981 and October 1989, 20 had freely movable tumors without evidence of metastasis and were treated with surgical excision alone. Uncensored mean and median survival times for these 20 dogs were both 20.5 months. Kaplan-Meier survival analysis, which censors for nontumor-related deaths and dogs lost to follow-up, indicated that median survival time was greater than 36 months. Seven dogs died of tumor-related causes: 2 died because of metastasis or local recurrence of the tumor, 5 died of treatment-related complications (eg, laryngeal paralysis, hypocalcemia, tracheostomy complications). Eight dogs died of unrelated causes; 1 dog was lost to follow-up at 26 months after surgery; 3 dogs were alive 19, 24, and 26 months after surgery. Cause of death could not be determined in the remaining dog. Long-term survival is possible following surgical removal of mobile thyroid carcinomas in dogs.

Adenocarcinoma↗

Thymoma in dogs: 23 cases (1980-1991).

Medical records of 23 dogs in which thymoma was diagnosed between Jan 1, 1980 and Dec 31, 1991 were reviewed. All thymomas were located in the cranial mediastinum. Eleven dogs had megaesophagus, and myasthenia gravis was confirmed in 7 of these 11. One dog developed clinical signs of myasthenia gravis after removal of the thymoma. Concurrent, nonthymic neoplasms were found in 5 dogs, and 2 had hypercalcemia. Three dogs developed third-degree atrioventricular heart block, 1 of which had generalized myositis involving the cardiac muscle. None of the dogs had evidence of distant metastasis. Histologically, the predominant tumor types were differentiated epithelial type (9/23) and lymphocyte-rich type (6/23). Clear cells (large cells with nonstaining cytoplasm) comprised > or = 50% of the cell population in tumors from 5 dogs. Mast cells were detected histologically in 85% of the thymomas evaluated. Sixteen dogs were treated, and in 15 of these, surgery was the primary means of treatment. Six of the 9 dogs with megaesophagus that underwent surgery died or were euthanized within 1 week of diagnosis; whereas only 1 of the 4 dogs without megaesophagus that underwent surgery died within 1 week of diagnosis. Two dogs underwent surgery and received adjuvant chemotherapy. One dog died of complications associated with chemotherapy. One dog was treated with chemotherapy alone and survived 14 months. Seven dogs did not undergo treatment; 4 of these were euthanatized immediately after the mass was first discovered.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Infiltrative lipoma in dogs: 16 cases (1981-1992).

Medical records of 15 dogs with infiltrative lipoma, 1 of which had 2 lesions, were reviewed. Median age of affected dogs was 6.0 years, and median weight was 30.5 kg. The ratio of females to males was 4:1. Eight of the dogs were Labrador Retrievers. In 8 dogs, the lesions had previously been excised. There was not any apparent site predilection. Excision was the only treatment in all 15 dogs, and follow-up information was available for all dogs. Two dogs, each of which had 1 tumor, were euthanatized immediately after surgery, because the tumor could not be completely excised. Of the remaining 14 tumors, 5 (36%) recurred. Median time to recurrence for these 5 tumors was 239 days (range, 96 to 487 days). By means of Kaplan-Meier analysis, the percentage of dogs disease free 1 year after surgery was calculated to be 67%.

Animals↗

Impact of heterogeneity in the predictive value of kinetic parameters in canine osteosarcoma.

Intratumoral heterogeneity has been identified as a potential problem in the efficacy of predictive assays. Canine osteosarcoma is an extremely heterogeneous solid tumor that has been shown to be an excellent model for the human disease. Intratumoral heterogeneity of kinetic parameters and the effect of heterogeneity on predicting outcome of treatment (time until metastasis) were studied in dogs with naturally occurring osteosarcoma. Dogs were treated with amputation or tumor excision and limb-sparing followed by chemotherapy with cisplatin. Kinetic parameters evaluated included v, duration of DNA synthesis (Ts), and potential doubling time (Tpot), determined using in vivo labeling with bromodeoxyuridine and flow cytometry. In 30 tumors, multiple samples were obtained and evaluated. There was significantly more variation between tumors from different dogs than intratumoral variation of v, Ts, and Tpo. Variations in v, Ts, and Tpot within a tumor were associated with both sample location and tumor subpopulation. Time to metastasis was determined in 51 dogs with tumors sampled for kinetics. Multiple samples were available from 25 of these tumors. Cox proportional hazard analysis was performed using either the fastest or slowest Tpot from each sample. The fastest available Tpots were highly significant (P < 0.001) for prediction of outcome. The slowest available Tpots were also significant predictors, although the statistical strength was compromised (P = 0.024). Obtaining at least two samples in large tumors known to be heterogeneous is recommended to improve the predictive ability of Tpot. v is a more limited predictor but can useful when Tpot is not available. In canine osteosarcoma, an extremely heterogeneous tumor, kinetic parameters were shown to be predictors of outcome.

Animals↗

Histologically low-grade, yet biologically high-grade, fibrosarcomas of the mandible and maxilla in dogs: 25 cases (1982-1991).

Medical records of 25 dogs with histologically low-grade fibrous masses of the maxilla and mandible were reviewed. Most of the dogs had extensive clinical histories and had had previous biopsies of the affected regions, from which specimens were often interpreted as benign fibrous connective tissue. The most common breed represented was Golden Retriever (13/25 dogs, 52%). Skull radiographs were evaluated for 22 dogs, and 16 dogs (72%) had evidence of bone lysis. At admission, none of the dogs had radiographic evidence of pulmonary metastasis. On subsequent examinations and necropsy, prevalence of pulmonary metastasis was 12% (3/25 dogs) and of regional lymph node metastasis, 20% (5/25 dogs). Histologic appearance of all specimens was similar and was characterized by proliferation of fibrous connective tissue, with moderate to low cellularity, that aggressively infiltrated adjacent normal tissue. Treatment modalities varied considerably. Surgical excision in combination with radiation therapy, surgery alone, radiation therapy alone, and radiation therapy used adjunctly with localized hyperthermia prolonged survival times in some dogs. The clinical signs, tumor behavior, and histologic characteristics of these lesions were distinctive from those in previously described oral fibrosarcomas in dogs. Comparatively, these tumors most closely resembled aggressive fibromatoses in human beings in regard to clinical signs, local invasive behavior, and histologic appearance, but differed in the prevalence of metastasis.

Animals↗

Effects of cis-diamminedichloroplatinum II released from D,L-polylactic acid implanted adjacent to cortical allografts in dogs.

This study was performed to determine the pharmacokinetics and local and systemic effects of cis-diamminedichloroplatinum II (cisplatin) released from an open-cell polylactic acid polymer when the drug delivery device was placed adjacent to a cortical allograft. Bilateral intercalary femoral allografts were implanted in six normal beagles. The polymer containing cisplatin was implanted adjacent to the allograft in one femur, and the polymer without cisplatin was implanted adjacent to the allograft in the contralateral femur. Systemic toxicity was evaluated clinically by hematologic and serum biochemistry tests and urinalysis. Healing of the allograft was monitored radiographically. The femora were evaluated biomechanically, histologically, and histomorphometrically 7.5 months after surgery. Total serum platinum levels were measured by atomic absorption spectrophotometry, and pharmacokinetic parameters were calculated. Healing was impaired slightly by the presence of the polymer with cisplatin, and systemic and local toxicity was mild and transient. After implantation of the polymer with cisplatin, the mean peak total serum platinum concentration was low (1.71 +/- 0.19 micrograms/ml). However, the area under the curve for total serum platinum concentration versus time for the first 21 days was large (27,050 +/- 3,201 micrograms.min/ml). When cisplatin was given as an intravenous bolus at a dose of 70 mg/m2 to six other beagles, the mean peak total platinum concentration was 8.80 +/- 2.1 micrograms/ml and the area under the curve was 940.3 +/- 256.7 micrograms.min/ml. These results indicate that a sustained release of cisplatin can be delivered safely from an open-cell polylactic acid polymer. This device may be useful in the treatment of solid tumors.

Animals↗

Toxicoses and efficacy associated with administration of mitoxantrone to cats with malignant tumors.

Eighty-seven cats with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of mitoxantrone, a dihydroxyquinone derivative of anthracene, which was administered at 21-day intervals at dosages ranging from 2.5 to 6.5 mg/m2 of body surface, IV. Eleven of these cats were treated concurrently with radiation but were evaluated separately. Each cat was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the cat developed progressive disease, or until the cat's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. Although the primary purpose of this study was to determine a clinically useful dosage and to characterize the toxicoses associated with mitoxantrone administration, each cat was monitored for response to treatment. Forty-nine cats had been refractory to 1 or more treatment modalities prior to inclusion in this study. The most common signs of toxicosis after treatment with mitoxantrone were vomiting, anorexia, diarrhea, lethargy, sepsis secondary to myelosuppression, and seizures. Two cats died of complications that may have been attributed to mitoxantrone: 1 of cardiomyopathy and the other of pulmonary edema of an undetermined cause. Older cats were more likely to develop signs of toxicosis after the third or fourth mitoxantrone treatment than younger cats (P < or = 0.05). Cats with signs of toxicosis during the 21-day interval after administration of the first dose of mitoxantrone were significantly (P < or = 0.05) more likely to develop signs of toxicosis during the 21-day interval between the second and third doses of mitoxantrone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prevalence of nephrotoxicosis associated with a four-hour saline solution diuresis protocol for the administration of cisplatin to dogs with naturally developing neoplasms.

We evaluated the development of nephrotoxicosis in 64 dogs with malignant neoplasia given cisplatin during 4-hour saline solution diuresis. Cisplatin (70 mg/m2 of body surface area, IV, q 21 d) was given to 8 dogs once, 22 dogs twice, 9 dogs 3 times, and 25 dogs 4 times. For each treatment, cisplatin was given over a 20-minute period after saline (0.9% NaCl) solution was administered IV for 3 hours at a rate of 25 ml/kg/h. After cisplatin infusion, saline solution diuresis was continued at the same rate for 1 hour. Before each treatment with cisplatin, the dogs were evaluated by conducting a physical examination, CBC; and analysis of serum urea nitrogen and creatinine concentrations, and in most cases, serum phosphorus concentration and urine specific gravity were determined. Exogenous creatinine clearance also was evaluated in 8 dogs prior to 1 (n = 8), 2 (n = 8), 3 (n = 6), and 4 (n = 4) treatments. Five (7.8%) of 64 dogs developed clinically evident renal disease after two (n = 3) and three (n = 2) doses of cisplatin. Two of the 5 dogs had preexisting diseases of the urinary tract prior to the start of treatment. Survival time in dogs that developed renal disease (median, 114 days; range, 26 to 273 days) was similar to that of all dogs in this study (median, 145 days; range, 5 to 586 days), with 30 dogs still alive at the conclusion of the study. Three of the 5 dogs that developed renal disease were alive at the conclusion of the study, 1 died of tumor-related causes, and another died as a direct result of nephrotoxicosis. There was a significant (P < 0.05) decrease in median neutrophil counts and a significant (P < 0.05) increase in median creatinine concentrations prior to the third and fourth treatments, compared with pretreatment values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intra-arterial cisplatin with or without radiation in limb-sparing for canine osteosarcoma.

METHODS: Forty-nine dogs with spontaneously occurring osteosarcoma underwent limb-sparing surgery after preoperative therapy consisting of intra-arterial cisplatin alone or intra-arterial cisplatin in combination with doses of radiation from 20-40 Gy in 10 fractions. All resections were marginal, and the defect was repaired with a cortical allograft. RESULTS: Local tumor control was strongly influenced by the percent necrosis in the excised specimen. Overall, the estimated 1-year local recurrence rate was approximately 32% (by life-table estimate). Dogs with less than 75% necrosis had an estimated 1-year recurrence rate of 65%; those with greater than 75% necrosis had an estimated 1-year recurrence rate of 15% (P = 0.004, by log-rank test). Local recurrence was influenced by the radiation dose. Dogs receiving 28 Gy or less had an estimated 50% 1-year recurrence rate, and those receiving 32 Gy or more had an estimated 8% 1-year recurrence rate (P = 0.03, by log-rank test). Normal host bone more frequently became necrotic at doses of 36 Gy or more. CONCLUSIONS: Intra-arterial cisplatin in combination with moderate doses of radiation (32 Gy) can achieve a high percent tumor necrosis while maintaining host bone viability. Survival was limited by distant metastasis but was lengthened by treatment compared with some earlier findings.

Amputation, Surgical↗

Evaluation of single-agent chemotherapy for treatment of clinically evident osteosarcoma metastases in dogs: 45 cases (1987-1991).

A study was undertaken to determine the effect chemotherapy had when used to treat 45 dogs with measurable metastatic osteosarcoma. The primary tumor was histologically confirmed as an osteosarcoma in each case. Thirty-nine dogs had the primary tumor surgically removed. Twenty-four of these dogs were treated adjunctively with cisplatin (70 mg/m2 of body surface, IV, q 3 weeks; median 2 doses, range 1 to 6 doses) prior to the onset of metastasis. The remaining 6 dogs from which the primary tumor was not surgically removed were diagnosed as having metastatic osteosarcoma in addition to the primary tumor on initial examination. The median time from initial examination until the development of metastatic disease was 115 days (range, 27 to 1,199 days). The location of the metastatic disease was lungs (31 dogs), bone (3 dogs), soft tissue (1 dog), and multiple sites including lungs, bone, and soft tissue sites (10 dogs). The metastatic lesions were confirmed by pretreatment biopsy (n = 8) or cytologic evaluation (n = 2) in 10 cases and at necropsy in 27 cases. The remaining 8 cases were diagnosed radiographically as multiple metastatic lesions in the lungs consistent with metastatic osteosarcoma. The metastatic disease was treated with cisplatin in 31 dogs (70 mg/m2, IV, q 3 weeks; median 2 doses, range 1 to 4 doses), doxorubicin in 11 dogs (30 mg/m2, IV, q 3 weeks; median 2 doses, range 1 to 3 doses), and mitoxantrone in 3 dogs (5 mg/m2, IV, q 3 weeks; median 2 doses, range 1 to 3 doses).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of intramedullary polymethylmethacrylate on healing of intercalary cortical allografts in a canine model.

The purpose of this study was to evaluate the effect of intramedullary polymethylmethacrylate (PMMA) bone cement on the healing of intercalary allografts. Thirteen adult beagles had bilateral intercalary femoral allografts implanted. The medullary canal of one randomly assigned allograft in each dog was filled with PMMA. Healing was followed clinically and femora were evaluated radiographically, biomechanically, histologically, and histomorphometrically 9 months after surgery. There was an increased percent of eroded surface at the endosteal area of the center region of grafts containing PMMA and there was an increased percent osteoblast surface in this area in grafts not containing PMMA. There was an increased percent eroded surface at the periosteal area in the center region in grafts not containing PMMA and there was an increased percent osteoblast surface at the periosteal area in the graft adjacent to the host junction in grafts containing PMMA. There was no significant difference between PMMA-treated and untreated allografts in any other parameters measured. The results from this study suggest that, although the pattern of incorporation is altered, intramedullary PMMA does not appear to effect allograft healing adversely.

Animals↗