Radiotherapy of malignant nasal tumors in 67 dogs

The nasal cavity of 67 dogs with malignant nasal neoplasia was treated with radiation. Preirradiation surgical cytoreduction of the tumor was done in 41 dogs. Fifty dogs were irradiated by use of 10 fractions over 22 days, and 17 dogs were given a similar total dose in 5 fractions over 35 days. The range of survival times (0.5 to 42 months), median survival time (8.5 months), and 1- and 2-year survival rates (38% and 30%, respectively) were better than those expected for other methods of treatment. Serious complications were few (4%). Survival times for dogs were determined on the basis of histologic tumor type and on the basis of megavoltage (cobalt or linear accelerator) vs softer deep radiation (cesium or orthovoltage) treatment, with or without cytoreductive surgery. Survival times of 10 dogs given softer radiation without surgery were shorter than those of 14 dogs that were given softer radiation and had cytoreductive surgery. Survival times of dogs that were given softer radiation and had surgery were similar to those of dogs that were given megavoltage radiation only. Cytoreductive surgery did not improve survival times for dogs that were given megavoltage radiation. Median survival time for 38 dogs with adenocarcinoma was 12 months, compared with 6 months for 14 dogs with squamous cell or undifferentiated carcinoma. Median survival time for 16 dogs with a variety of sarcomas was 11.2 months. Survival times of dogs with adenocarcinoma or sarcoma were significantly better (P less than 0.02 or 0.03) than for dogs with squamous cell or undifferentiated carcinoma. Necropsies were performed on 27 of 58 dogs that died or were euthanatized.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic value of histologic stage and proliferative activity in canine malignant mammary tumors.

The aim of this study was to investigate the correlation between the histologic invasiveness (histologic stage) and various cell proliferation activity assays (quantity of argyrophil proteins associated with nucleolar organizer regions [AgNORs], mitotic activity, MIB1 [Ki67] immunohistochemical detection) for predicting the biologic behavior of malignant canine mammary tumors. Sixty specimens from malignant canine mammary tumors with no distant metastases (M0) at surgery were selected, and follow-up data were collected over a 2-year period. The histologic invasiveness was graded by histologic stage (stage 0 = tumors without stromal invasion; stage I = tumors with stromal invasion; stage II = tumors with neoplastic emboli in vessels), and the proliferative indices were expressed as MIB1 index (the percentage of nuclear area immunohistochemically stained by MIB1 antibody), mitotic index (the number of mitoses per 1,000 neoplastic cells), and AgNOR index (the ratio between mean AgNOR area of tumor cells and the mean AgNOR area of fibroblasts/lymphocytes). The measures of proliferative activity were compared among groups with different histologic stages, and the influence of different prognostic variables (histologic stage, AgNOR index, mitotic index, MIB1 index) on survival time was evaluated. A significant difference in the proliferation patterns was recorded between the different histologic stages for the mitotic index (P = 0.0006) and MIB1 index (0.0013). Among the different parameters considered, histologic stage (P < 0.05), AgNOR index (P = 0.0291), and MIB1 index (P = 0.014) revealed a significant association with prognosis in univariate analysis. AgNOR index for 1-year survival and histologic stage for 2-year survival were the most significant parameters influencing survival, as determined by multiple nonlinear logistic regression.     

Cytologic differentiation of benign from malignant canine mammary tumors

Cytologic and histologic examination of 91 canine mammary masses was performed by two cytologists and two histopathologists. Ten important cytologic criteria of malignancy for canine mammary tumors were identified. A cytologic grading system for differentiation of benign from malignant mammary tumors was proposed using these criteria. With this system, approximately one fourth of the malignant mammary tumors were given a concordant cytologic diagnosis. Approximately one-half of the benign masses were given a concordant cytologic diagnosis by the two cytologists. One-half of all the tumors examined were given inconclusive cytologic diagnoses by both cytologists. The cytologic identification of spindle cells did not differentiate complex and mixed mammary tumors from simple tumors. Only five of the animals studied died of mammary cancer, precluding a critical analysis of the cytologic criteria for prediction of cancer mortality.     

Evaluation of satraplatin in dogs with spontaneously occurring malignant tumors

Background: Satraplatin is the 1st orally bioavailable platinum anticancer drug. Objective: Our objectives were to evaluate efficacy in vitro against a canine cancer cell line, to determine the maximally tolerated dose (MTD) of satraplatin in tumor‐bearing dogs, to identify the dose‐limiting and other toxicities in dogs, and to record pharmacokinetics (PK). Animals: Dogs with macro‐ or microscopic malignant neoplasia. Methods: D17 canine osteosarcoma cells first were evaluated in a clonogenic survival assay. Then, dogs with a diagnosis of malignant neoplasia were prospectively entered in standard 3 + 3 cohorts. Additional patients were entered at the MTD to assess efficacy. Total and free platinum (by ultrafiltrate) concentrations were determined with inductively coupled plasma mass spectroscopy. Results: Satraplatin inhibited clonogenic survival in vitro at clinically relevant and achievable concentrations. Twenty‐three dogs were treated, 14 with PK evaluation. The MTD was 35 mg/m²/d for 5 days, repeated every 3–4 weeks. Bioavailability was 41%. PK variables (mean ± SD) at the MTD included T_max 1.8 (± 0.7) hours, C_max 72 (± 26) ng/mL, area under concentration (AUC)_{0–24 h} 316 (± 63) h × ng/mL, and MRT 7 (± 1.3) hours. Higher AUC after the 5th versus the 1st dose suggested drug accumulation. Interestingly, platelets consistently reached nadir sooner than did neutrophils (day 14 versus 19). Myelosuppression was dose‐limiting and gastrointestinal toxicity was mild. Conclusions and Clinical Importance: Satraplatin was well tolerated in tumor‐bearing dogs, thus warranting further investigation in a phase II trial.     

Benign and malignant epithelial tumors of the rete testis in mice

Two papillary cystadenomas and one papillary cystadenocarcinoma in the rete testis were found in two of 500 very old male JCL:ICR mice; the hosts had no other tumors. One mouse had bilateral cystic tumors. A 5 x 3 x 3 mm papillary cystadenoma was observed in the rete of the right testis. A 7 x 3 x 3 mm tumor with a mixed pattern of papillary cystadenocarcinoma and papillotubular adenocarcinoma was found in the rete of the left testis; the latter extended from the mediastinum to the ductuli efferents and the caput epididymis. The other mouse had a 9 x 5 x 5 mm papillary cystadenoma of borderline malignancy in the rete of the right testis. The mice had no clinical signs.     

CT features of malignant tubular genital tract tumors in seven goats

Neoplasia of the tubular genital tract in goats, while rarely described, is most commonly reported as uterine adenocarcinoma, leiomyoma, or leiomyosarcoma. In this retrospective, single-center, case series, medical records were searched for goats with a computed tomography (CT) diagnosis of tubular genital mass and a definitive histologic (surgical biopsy or necropsy) diagnosis of malignant neoplasia. Data recorded from CT images were presence of peritoneal/retroperitoneal fluid, urinary tract obstruction, abdominal lymphadenomegaly, additional abdominal nodules/masses, and pulmonary nodules. For masses, maximum cross-sectional area, contrast enhancement, and uterine luminal fluid accumulation were also recorded. Seven goats met the inclusion criteria (leiomyosarcoma n = 5, adenocarcinoma n = 2). Both goats with adenocarcinoma had upper urinary tract obstruction, moderate to severe regional lymphadenopathy, peritoneal fluid, and peritoneal or hepatic nodules/masses; one goat with adenocarcinoma was discharged and subsequently euthanized, and the other had palliative mass debulking and was lost to follow up. Goats with leiomyosarcoma had infrequent, mild peritoneal fluid and mild sublumbar lymphadenopathy. Of the goats with leiomyosarcoma, two were euthanized at or near the time of CT imaging, two were euthanized at the time of surgery due to perceived mass non-resectability, and one had mass regression approximately four months post ovariohysterectomy but was subsequently lost to follow up. Five goats had pulmonary nodules, three of which had pathologic confirmation (pulmonary metastasis in a single patient with adenocarcinoma, and lungworm granulomas in two goats with leiomyosarcoma). Severe sublumbar lymphadenopathy and obstructive uropathy were sequelae in the two caprine patients with genital adenocarcinoma, and in none with leiomyosarcoma.     

Toxicoses associated with administration of mitoxantrone to dogs with malignant tumors

One hundred twenty-nine dogs with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of the new dihydroxyquinone derivative of anthracene, mitoxantrone, which was administered IV at 21-day intervals at dosages ranging from 2.5 to 5 mg/m2 body surface area. Each dog was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the dog died, whichever came first. The number of dogs in each evaluation period were as follows: 1 dose (n = 129), 2 doses (n = 82), 3 doses (n = 43), 4 doses (n = 26), 5 doses (n = 19), 6 doses (n = 9), 7 doses (n = 6), 8 doses (n = 5), 9 doses (n = 3), and 10 doses (n = 1). The most common signs of toxicosis were vomiting, diarrhea, anorexia, and sepsis secondary to myelosuppression. None of the dogs died of complications resulting from mitoxantrone treatment. Dogs with signs of toxicosis during the 21-day interval from administration of the first dose of mitoxantrone were 95 times (P = 0.003) more likely to develop signs of toxicosis during the 21-day interval from the second dose of mitoxantrone. Similarly, dogs that developed signs of toxicosis during the 21-day interval from the administration of the second dose were 34 times (P less than 0.001) more likely to develop signs of toxicosis during the 21-day interval from the administration of the third dose. With each 1 mg/m2 increase in mitoxantrone, the odds of developing signs of toxicosis increased by 5.9 fold (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrine tumors.

Because of the diverse nature of endocrine organs, and their vast range of physiologic functions, endocrine tumors encompass a wide range of origination sites and disease entities. The clinical picture of affected individuals is highly dependent on the tissue of origin, and the presence or absence of functional hormone secretions. Identification, localization, and therapeutic strategies, as well as prognosis can vary greatly. Many endocrine tumors have been described in human as well as veterinary patients. This article focuses on endocrine tumors of dogs and cats. Various tumors affecting the pancreas, thyroid, parathyroid, adrenal and pituitary glands are described, including insulinoma, gastrinoma, glucagonoma, and thyroid carcinoma, as well as parathyroid hormone- and growth hormone-secreting tumors. The syndrome of multiple endocrine neoplasia is also described.     

Expression patterns of the slit subfamily mRNA in canine malignant mammary tumors

Slit, a secreted protein, functions as a chemorepellent factor in axon guidance and neuronal migration and as an inhibitor in leukocyte chemotaxis. In humans, slit2 protein attracts endothelial cells and promotes tube formation in the tumor angiogenic mechanism. In this study, we cloned a part of the canine slit subfamily and examined the expression of slit subfamily mRNAs in 3 normal canine mammary glands and 11 mammary tumor samples by RT-PCR. The cloned part of the slit gene sequences showed high similarity to those of the human, mouse, and rat. The mRNAs were expressed at low levels in the normal mammary gland. The expression levels of slit1 mRNA were low in both the normal and tumor tissues. In contrast, the expression of slit2 mRNA increased in most of the malignant mammary tumors, and an increase in slit3 mRNA expression was observed in 2 of the malignant mixed tumors. These results suggest that the expression of slit2 plays an important role in tumor angiogenesis in canine mammary gland tumors and that slit2 can be a putative marker for malignancy diagnosis of these tumors.     

Hematological toxicity of doxorubicin-containing protocols in dogs with spontaneously occurring malignant tumors

The medical records of 49 dogs with spontaneously occurring malignant tumors treated with doxorubicin-based chemotherapy protocols were evaluated for hematological toxicity. Protocols included vincristine, doxorubicin, and cyclophosphamide (VAC); 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC); doxorubicin and cyclophosphamide (AC); and doxorubicin and dacarbazine (ADIC). Prevalence of Grades 1, 2, or 3 toxicities were less than 30%, and the prevalence of Grade 4 toxicity alone was less than 5%. The frequency of sepsis was less than 2.5% in dogs treated with VAC, FAC, or AC, and it was 15% in dogs treated with ADIC. There were no significant differences in the prevalence or severity of hematological toxicity caused by VAC or AC. Five-fluorouracil, doxorubicin, and cyclophosphamide caused significantly more severe neutropenia than VAC or AC. The low prevalence of hematological complications makes these protocols acceptable for use in practice.     

Cytomorphologic differentiation of benign and malignant mammary tumors in fine needle aspirate specimens from irradiated female Sprague-Dawley rats.

BACKGROUND: Fine needle aspiration (FNA) offers a rapid and minimally invasive means to distinguish malignant from benign neoplasms. However, few studies have been published regarding the cytopathology of mammary tumors in rats despite widespread use of the rat model for breast cancer formation and inhibition. OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of FNA cytology and to develop distinguishing cytologic criteria for the diagnosis of radiation-induced benign and malignant mammary tumors in rats. METHODS: In a study of radiation-induced mammary carcinogenesis, 100 Sprague-Dawley rats with cutaneous masses were randomly chosen for FNA. The aspirates were smeared, fixed, and stained with a modified Papanicolaou procedure for diagnostic evaluation. Cytologic and histologic diagnoses (benign vs malignant) were compared, and diagnostic accuracy was calculated using the histologic diagnosis as the criterion standard. FNA smears were scored semiquantitatively on a scale of 1-4 for cellularity, atypia, nuclear size, chromatin pattern, nuclear membrane thickness, nucleoli, and mitoses. The background was evaluated for necrosis, hemorrhage, inflammation, and mucosecretory material. Cytomorphologic features were compared statistically between benign and malignant tumors, based on the histologic diagnosis. RESULTS: The sensitivity of FNA was 92.3% and specificity was 89.4% for the detection of malignancy. However, 14% of specimens, all fibroadenomas by histology, had insufficient cells for cytologic evaluation, for an overall accuracy rate of 78.0%. Malignant tumors had significantly higher scores for all cytomorphologic features, and were significantly more likely to contain cell clusters and necrotic debris. CONCLUSIONS: FNA is an accurate method for differentiating benign and malignant rat mammary tumors.     

Bilateral intraocular malignant neuroectodermal tumors in a telescope goldfish (Carassius auratus)

A 5‐year‐old male telescope goldfish (Carassius auratus) developed buphthalmia of the left eye. An enucleation was performed and a diagnosis of a neuroectodermal tumor was made on histological examination. Although the fish initially recovered, it was killed 49 days postsurgery due to a severe decline in its condition. On histological evaluation of postmortem tissue samples, it was determined that the fish also had a neuroectodermal tumor of the right eye with local invasion of the brain. On immunohistochemistry, the neoplastic cells were positive for S‐100. To the authors’ knowledge, this is the first published case of naturally occurring bilateral intraocular neuroectodermal tumors in a fish.     

Influence of host factors on survival in dogs with malignant mammary gland tumors

The purpose of our study was to determine if specific host factors, such as age at diagnosis, obesity, and hormone status, influence the prognosis of canine mammary gland carcinomas and to confirm if previously reported risk factors (ie, histologic subtype, tumor size, and World Health Organization [WHO] stage) were important in a large series of affected dogs. Ninety-nine female dogs with mammary gland carcinomas, no previous therapy, an excisional biopsy, and known cause of death were studied. No significant association with survival was noted for age at diagnosis (chronologic or physiologic), obesity, or hormone status (ie, spayed versus intact, regardless of time of being spayed). Of the tumor factors analyzed, the histologic subtype anaplastic carcinoma (P = .02), WHO stage I (P = .01), evidence of metastasis at the time of diagnosis (P = .004), and tumor size of 3 cm or smaller (P = .005) all significantly influenced survival. Dogs that were classified as having tumor-related mortality had a shorter postoperative survival compared to dogs that died of other causes (14 months versus 23 months; P = .03). In conclusion, histologic subtype, WHO stage, and tumor size remain important prognostic factors in canine mammary gland tumors. Further study of other prognostic factors is needed to determine which tumors are adequately addressed with local therapy only and which dogs may require adjuvant treatment with chemotherapy.     

Routine hematology and clinical chemistry in female dogs with benign and malignant mammary tumors

Routine hematological and serum biochemical screening was done in 61 female dogs with benign mammary tumors and 51 female dogs with malignant mammary tumors. Most parameters were not significantly different from age-matched female controls; moreover, no significant difference could be observed between animals with benign and malignant tumors. It is concluded that routine hematology and biochemistry offer little diagnostic or prognostic benefit in female dogs with mammary tumors.