Gland Tumors In Dogs Research Articles

ASSESSMENT OF SENTINEL LYMPH NODE METASTASIS IN CANINE MAMMARY GLAND TUMORS USING COMPUTED TOMOGRAPHIC INDIRECT LYMPHOGRAPHY.

In the staging process of the breast cancer, demonstrating metastasis of the sentinel lymph node (SLN) has an important prognostic value, in both humans and animals. The aim of this prospective case-control study was to determine the diagnostic value of computed tomographic indirect lymphography (CT-LG) for detecting SLN metastasis in dogs with mammary cancer. Thirty-three female dogs with tumors in the abdominal and inguinal mammary glands were prospectively selected and subjected to CT-LG, 1 and 5 min after injection of 1 ml of contrast agent (iopamidol) in the subareolar tissue of the neoplastic and the contralateral normal mammary glands. The pattern of postcontrast opacification, degree of postcontrast enhancement, and size and shape were assessed in 65 SLNs in total and were correlated with histopathological findings. The absence of opacification or heterogeneous opacification 1 min after contrast medium injection showed the highest sensitivity, specificity, and accuracy (93%, 100%, and 98.4%, respectively). In images taken 1 min after injection, an absolute density value lower than 444 Hounsfield units (HU) in the center of the SLN also provided significant sensitivity and specificity (93.8% and 75%, respectively). The size and shape of the SLN (maximum and minimum diameter, maximum/minimum diameter ratio, maximum diameter/height of fifth thoracic vertebral body ratio) showed the lowest sensitivity and specificity. Results of this study support the hypothesis that CT-LG could help in the assessment of SLN metastasis in cases of mammary gland tumors in dogs.

Expression of Ccdc85C, a causative protein for murine hydrocephalus, in the mammary gland tumors of dogs.

Coiled-coil domain containing 85c (Ccdc85c) is a causative gene for hemorrhagic hydrocephalus mouse which shows hydrocephalus with frequent brain hemorrhage and formation of subcortical band heterotopia. A previous study revealed that Ccdc85C protein is expressed in the systemic simple epithelial cells with proliferative activity in rats and suggested that Ccdc85C expression may be related to the cell proliferation of simple epithelial cells. To reveal the roles of Ccdc85C in the proliferative lesion, we examined the expression patterns of Ccdc85C in the mammary gland tumor of dogs, a common representative tumor derived from simple epithelial cells. In canine mammary gland tumors, Ccdc85C was expressed at the apical junctions of the luminal epithelial cells. Ccdc85C was also distributed throughout the entire cytoplasm of the myoepithelial cells. Ccdc85C expression was observed at the epithelial cells with luminal structures, but was not observed at the epithelial cells forming sheet growth pattern without luminal structure. In carcinomas, Ccdc85C expression in mammary tumor tissue tended to be weaker than that in surrounding normal mammary gland tissue. Ccdc85C is known to cause neurological diseases such as hydrocephalus, and subcortical heterotopia, and the present study is the first to demonstrate Ccdc85C expression in canine mammary tumors and a relationship between Ccdc85C expression and tumor malignancy.

Novel aspects in mammary gland tumors in dogs and cats

Novel aspects in mammary gland tumors in dogs and cats

Steroid Receptor Expression in Perianal Gland Tumours in Dogs in the Context of Possible Use of Anti-Hormone Therapy

Steroid Receptor Expression in Perianal Gland Tumours in Dogs in the Context of Possible Use of Anti-Hormone Therapy

Pathology and Epidemiology of Ceruminous Gland Tumors among Endangered Santa Catalina Island Foxes (Urocyon littoralis catalinae) in the Channel Islands, USA.

In this study, we examined the prevalence, pathology, and epidemiology of tumors in free-ranging island foxes occurring on three islands in the California Channel Islands, USA. We found a remarkably high prevalence of ceruminous gland tumors in endangered foxes (Urocyon littoralis catalinae) occurring on Santa Catalina Island (SCA)—48.9% of the dead foxes examined from 2001–2008 had tumors in their ears, and tumors were found in 52.2% of randomly-selected mature (≥ 4 years) foxes captured in 2007–2008, representing one of the highest prevalences of tumors ever documented in a wildlife population. In contrast, no tumors were detected in foxes from San Nicolas Island or San Clemente Island, although ear mites (Otodectes cynotis), a predisposing factor for ceruminous gland tumors in dogs and cats, were highly prevalent on all three islands. On SCA, otitis externa secondary to ear mite infection was highly correlated with ceruminous gland hyperplasia (CGH), and tumors were significantly associated with the severity of CGH, ceruminous gland dysplasia, and age group (older foxes). We propose a conceptual model for the formation of ceruminous gland tumors in foxes on SCA that is based on persistent, ubiquitous infection with ear mites, and an innate, over exuberant inflammatory and hyperplastic response of SCA foxes to these mites. Foxes on SCA are now opportunistically treated with acaricides in an attempt to reduce mite infections and the morbidity and mortality associated with this highly prevalent tumor.

Use of contrast-enhanced ultrasonography to characterize adrenal gland tumors in dogs.

To describe the contrast-enhanced ultrasonographic characteristics and vascular patterns of adrenal gland tumors in dogs and determine whether those features are indicative of malignancy or histologic type of tumor. 14 dogs with 16 adrenal gland lesions (10 carcinomas [8 dogs], 3 adenomas [3 dogs], and 3 pheochromocytomas [3 dogs]). Unsedated dogs with adrenal gland lesions underwent B-mode ultrasonography and contrast-enhanced ultrasonography ≤ 48 hours before adrenalectomy; contrast-enhanced ultrasonographic examinations were video-recorded. Macroscopic evaluation of the adrenal gland lesions and histologic examination of removed adrenal gland tissues were subsequently performed. Surgical and histopathologic findings and the ultrasonographic and contrast-enhanced ultrasonographic characteristics were recorded for the various tumor types. Time-intensity curves were generated from the contrast-enhanced ultrasonographic recordings and used to calculate regional blood volume (value proportional to area under the curve) and mean transit time (time the lesion began to enhance to the half-peak intensity). In adrenal gland carcinomas, tortuous feeding vessels were noticeable during the arterial and venous phases of contrast enhancement. Heterogeneity of contrast enhancement was evident only in malignant tumors. Compared with adenomas, adrenal gland carcinomas and pheochromocytomas had significantly less regional blood volume. Mean transit times were significantly shorter in adrenal gland carcinomas and pheochromocytomas than in adenomas. For dogs, evaluation of the vascular pattern and contrast-enhancement characteristics of adrenal gland tumors by means of contrast-enhanced ultrasonography may be useful in assessment of malignancy and tumor type.

Diagnostic and prognostic value of cellular proliferation assessment with Ki-67 protein in dogs suffering from benign and malignant perianal tumors.

In the perianal region of carnivores, skin consists of modified sebaceous glands called perianal glands. Tumors originating from perianal glands are the third most frequent type of neoplasm in male dogs after neoplastic diseases of testes and skin. Ki-67 is a nuclear non-histone protein considered a proliferation marker in normal and neoplastic proliferating cells. Previous investigations revealed that Ki-67 expression may be used as a prognostic factor for breast cancer in humans. Thus, the aim of this study was to estimate the diagnostic and prognostic value of Ki-67 evaluation in dogs suffering from benign and malignant perianal tumors. The highest value of the Ki-67 index was obtained in the carcinoma group (18.50% ± 2.68), significantly higher compared to the values obtained in the control tissue (7.63% ± 2.12) and adenoma (7.33% ± 1.06; all P < 0.05). Statistically significant differences in the Ki-67 index were not found between the epithelioma group (11.95% ± 1.96) and all other groups (P < 0.05). This investigation on dogs with perianal gland tumors has shown significantly increased expression of Ki-67 antigen in carcinoma cells, while the expression of this protein was similar in the case of control tissues, adenoma and epithelioma. Thus, it may be postulated that Ki-67 evaluation in perianal gland tumors in dogs may serve as a useful marker possessing high diagnostic and prognostic value and enabling differentiation of malignant and benign tumors.

Pathology of perianal gland tumours in dogs

Two cases of perianal gland adenoma were recorded in 6–8 years old male dogs. In one case, the growth was located by the side of anal opening, while in other case the growth was seen at the ventral surface of the tail about 4.0 cm. away from the base of the tail. Histomorphological features resembled hepatic lobule (hepatoid appearance) with well differentiated parenchymal cells and intact capsule. Additional features included squamous metaplasia with pearl formation in some of the lobules.

Innovative Approach to Laparoscopic Adrenalectomy for Treatment of Unilateral Adrenal Gland Tumors in Dogs

To report a technique for, and short-term outcome of unilateral laparoscopic adrenalectomy in dogs positioned in sternal recumbency without abdominal support. Experimental and prospective clinical study. Healthy dogs (n = 5) and dogs with unilateral adrenal gland tumor (n = 9). Anesthetized dogs were positioned in sternal recumbency with 2 cushions placed under the dog to elevate the chest and pelvic area so that the abdomen was not in contact with the surgical table allowing gravitational displacement of the abdominal viscera. Three 5-mm portals were located in the paralumbar fossa. Adrenal glands were carefully dissected and surrounding tissues sealed and cut using a vessel-sealing device. A retrieval bag or part of a surgical glove finger was used to remove the adrenal gland from the abdomen. Surgical time and complications were recorded, and short-term outcome assessed. Adrenal glands in normal dogs and unilateral adrenal tumors (8 left, 1 right) not involving the caudal vena cava in affected dogs were successfully removed laparoscopically. There were no major intraoperative complications. Of the dogs with adrenal tumors, 1 dog died within 24 hours of surgery from unrelated causes. Eight dogs recovered within 1 day and were discharged within 72 hours. Surgical times ranged from 42 to 117 minutes and were significantly shorter than those reported previously. Positioning anesthetized dogs in sternal recumbency with the abdomen suspended to facilitate gravitational displacement of the abdominal viscera improves access to, and visibility of, the adrenal gland for laparoscopic removal.

Matrix metalloproteinase-9 expression in mammary gland tumors in dogs and its relationship with prognostic factors and patient outcome

To immunohistochemically evaluate matrix metalloproteinase (MMP)-9 expression in benign and malignant mammary gland tumors (MMTs) in dogs and relate expression to prognostic factors and patient outcome. 118 female dogs with naturally occurring mammary gland tumors and 8 dogs without mammary gland tumors. 24 benign mammary gland tumors and 94 MMTs (1/affected dog) were obtained during surgical treatment; control mammary gland tissue samples were collected from unaffected dogs after euthanasia for reasons unrelated to the study. Tumors were evaluated for proliferation, invasive growth, histologic grade, and metastatic capacity; expression of MMP-9 was determined immunohistochemically, and its relationship with clinical and histologic findings was investigated. For dogs with MMTs, follow-up continued for 2 years; data were used to compute overall survival time and disease-free interval and construct survival curves. MMTs had significantly higher MMP-9 expression in stromal cells and in neo-plastic cells than did the benign neoplasms. Stromal MMP-9 expression was also higher in highly proliferative tumors and in tumors with invasive growth, high histologic grade, and metastatic capacity. Furthermore, tumors from patients with shorter overall survival times and disease-free intervals had higher expression of MMP-9 in stromal cells. In dogs with MMTs, level of MMP-9 expression by stromal cells was related to factors of poor prognosis and shorter overall survival times and disease-free intervals. These results suggested that MMP-9 produced by tumor-adjacent stromal cells contributed to MMT progression in female dogs and that assessment of MMP-9 expression may be a valuable prognostic factor.

Endoglin mRNA Expression and Endothelial cell Proliferation in Benign Mammary Gland Tumours in Dogs

Endoglin mRNA Expression and Endothelial cell Proliferation in Benign Mammary Gland Tumours in Dogs

Evaluation of prognostic factors in the surgical treatment of adrenal gland tumors in dogs: 41 cases (1999–2005)

To identify preoperative predictors of survival and assess intraoperative and postoperative complications and survival rates for dogs undergoing adrenalectomy. Retrospective case series. 41 dogs that underwent adrenalectomy. Records were reviewed to collect data regarding preoperative variables. Intraoperative and postoperative variables were also recorded. Variables were evaluated for association with survival duration via log-rank analysis for categoric variables and by use of Cox proportional hazards. Median survival times were calculated by use of Kaplan-Meier life table analysis. 9 (22.0%) dogs did not survive to discharge. Intraoperative mortality rate was 4.8%. Overall Kaplan-Meier median survival time was 690 days. Variables significantly associated with shorter survival times included preoperative weakness or lethargy, thrombocytopenia, increased BUN concentration, increased partial thromboplastin time (PTT), increased aspartate transaminase (AST) activity, hypokalemia, intraoperative hemorrhage, and concurrent nephrectomy. Postoperative variables significantly associated with shorter survival times included pancreatitis and renal failure. In multivariate analysis, preoperative hypokalemia, preoperative increased BUN concentration, and concurrent nephrectomy were significantly associated with a shorter survival time. A high mortality rate was associated with adrenalectomy in dogs; however, those that survived until discharge from a hospital had long survival times. Preoperative factors associated with a shorter survival time were weakness or lethargy, thrombocytopenia, increased BUN concentration, increased PTT, increased AST activity, and hypokalemia. Studies are needed to evaluate how treatment for these factors may affect or change outcome after adrenalectomy. Dogs with adrenal masses that require concurrent nephrectomy and cause intraoperative hemorrhage have a guarded prognosis.

Effect of the VP3 gene of chicken anemia virus on canine mammary tumor cells

To investigate the antitumor effect of the chicken anemia virus (CAV) VP3 gene in canine mammary tumor (CMT) cells. SAMPLE POPULATIONS: Established primary canine cell lines that originated from epithelial cells of resected CMTs and nonneoplastic mammary gland epithelial (MGE) cells. Expression vectors and lentiviral vectors encoding the VP3 gene from a Taiwan-Ilan isolate of CAV were used to deliver the VP3 gene into CMT cells and nonneoplastic MGE cells. Ectopic gene expression and the pro-apoptotic effect of the VP3 gene on CMT and nonneoplastic MGE cells by either transfection or viral infection were evaluated via immunofluorescence microscopy, western blot analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis. Overexpression of the enhanced green fluorescent protein-VP3 fusion protein was detected predominantly in the nuclei of CMT cells. In contrast, the VP3 protein was localized to the cytoplasm of nonneoplastic MGE cells. Among the fusion protein-expressing CMT cells, most underwent characteristic changes of apoptosis, whereas apoptosis was not detected in fusion protein-expressing, nonneoplastic MGE cells. Induction of apoptosis by VP3 gene overexpression in CMT cells was associated with the caspase-9-, but not the caspase-8-, mediated apoptosis pathway. These data indicate that the VP3 gene of the CAV induces apoptosis in malignant CMT cells, but not in nonneoplastic canine MGE cells. On the basis of such tumor cell-specific killing, the VP3 gene may be a promising agent for the treatment of malignant mammary gland tumors in dogs.

Postoperative Adjuvant Treatment of Invasive Malignant Mammary Gland Tumors in Dogs with Doxorubicin and Docetaxel

Background:Treatment outcome after surgery alone is unsatisfactory in dogs with invasive malignant mammary gland tumors.Hypothesis:Adjuvant doxorubicin or docetaxel will improve the treatment outcome in dogs with high‐risk malignant mammary gland tumors, and the use of docetaxel will be feasible in affected dogs.Animals:Thirty‐one dogs with malignant mammary gland tumors of histologic stages II and III (vascular or lymphatic invasion, regional lymph node metastasis, or distant metastasis) were used.Methods:A prospective clinical trial in which dogs were treated with surgery alone (n = 19) or also received adjuvant chemotherapy (n = 12) with doxorubicin or docetaxel was conducted. Docetaxel was given as an IV infusion at a dose of 30 mg/m2 preceded by dexamethasone and diphenhydramine administration.Results:The recurrence‐free interval ranged from 13 to 2,585 days (median not reached); the median metastasis‐free interval and overall survival were 294 days and 370 days, respectively. Dogs treated with chemotherapy had a tendency toward higher long‐term local control and survival rates, but there was no significant difference in the recurrence‐free interval (P= .17), time to metastasis (P= .71), and overall survival (P= .12). Factors found to influence the time to metastasis and overall survival included lymph node metastasis (P= .009) and tumor fixation to underlying structures (P= .043, time to metastasis), as well as age (P= .018) and histologic stage (P &lt; .001, survival). Mild allergic skin reactions were the most frequently observed complications of docetaxel treatment.Conclusions and Clinical Importance: Chemotherapy did not lead to an improved outcome in this population. Docetaxel treatment was well tolerated. Additional investigations of adjuvant chemotherapy in dogs with high‐risk mammary cancer are warranted.

Expression of the PTEN tumor suppressor gene in malignant mammary gland tumors of dogs

To determine whether changes in expression level of the phosphatase and tensin homolog deleted on the chromosome 10 (PTEN) gene are associated with malignant transformation in mammary gland tumors in dogs. Specimens of 5 benign and 8 malignant mammary gland tumors and 2 unaffected mammary glands from dogs. The open reading frame (ORF) sequence of PTEN gene in each specimen was analyzed via a direct-sequencing method; expression levels of PTEN gene were quantified via a competitive reverse transcription (RT)-PCR method. Compared with findings in clinically normal samples, amounts of PTEN mRNA were increased 2- to 4-fold in 4 of the 5 benign mammary gland tumor samples. In contrast, PTEN expression was remarkably low in 4 of the 8 malignant tumor samples (approx 12% to 37% of the level in unaffected mammary gland specimens). Gene amplification via the RT-PCR method with total RNA prepared from malignant tumor samples as a template yielded 3 bands that were smaller than the full-length ORF product of PTEN gene; in 2 of those 3 RT-PCR products, exons 6 and 7 or exons 3 to 8 were absent. No mutation was detected in the full-length ORF product of PTEN gene. Results suggested that a decreased level of PTEN gene expression (compared with unaffected mammary gland tissue) is associated with malignancy in canine mammary tumors. Analysis of PTENgene expression level in dogs with mammary gland tumors may provide useful prognostic information.

Surgical management of adrenal gland tumors with and without associated tumor thrombi in dogs: 40 cases (1994-2001).

To compare pathologic findings and results of adrenalectomy for adrenal gland tumors in dogs with and without vena caval tumor thrombi. Retrospective study. 40 dogs with adrenal gland tumors. Medical records were examined. An exact logistic regression analysis was used to evaluate associations between tumor type or right-sided versus left-sided tumor involvement and development of caval tumor thrombi and associations between tumor thrombi, tumor type, or right- versus left-sided location and perioperative complications and mortality rate. Survival was compared between dogs with and without tumor thrombi. Caval thrombi were detected in 25% of dogs, including 3 of 28 (11%) dogs with an adrenocortical tumor and 6 of 11 dogs with a pheochromocytoma. A caval tumor thrombus was detected in 6 of 17 right-sided and 4 of 20 left-sided tumors. Sensitivity and specificity of abdominal ultrasonography for detection of caval thrombi were 80 and 90%, respectively. Intraoperative and postoperative complications developed in 15 and 51% of dogs, respectively. The mortality rate was 22%. There were no significant differences in perioperative morbidity and mortality rates between dogs with and without tumor thrombi. Caval thrombi associated with adrenal gland tumors are amenable to adrenalectomy and thrombectomy without significantly increased perioperative morbidity and mortality rates, assuming the surgeon is experienced in appropriate techniques.

Canine mammary gland tumors.

The National Consensus Group recommends that all women with tumors larger than 1 cm be offered chemotherapy regardless of tumor histology of lymph node status. This recommendation is to ensure that everyone at risk for failing, even though the risk may be low in women with relatively small tumors and favorable histology, has a choice and receives the benefit of adjuvant chemotherapy. This type of treatment recommendation may also be made in dogs based on recognized, well-accepted prognostic factors such as tumor size, stage, type, and histologic differentiation. Based on the limited clinical information available in veterinary medicine, the drugs that are effective in human breast cancer, such as cyclophosphamide, 5-fluorouracil, and doxorubicin, may also have a role in the treatment of malignant mammary gland tumors in dogs. Randomized prospective studies are needed, however, to evaluate the efficacy of chemotherapy in dogs with high-risk mammary gland tumors and to determine which drugs and protocols are the most efficacious. Until such studies are performed, the treatment of canine mammary gland tumors will be based on the individual oncologist's understanding of tumor biology, experience, interpretation of the available studies, and a little bit of gut-feeling. Table 2 is a proposal for treatment guidelines for malignant canine mammary gland tumors according to established prognostic factors, results from published veterinary studies, and current recommendations for breast cancer treatment in women.

Occurrence and Frequency of Mammary Gland Tumours in Dogs

Occurrence and Frequency of Mammary Gland Tumours in Dogs

Effect of Spaying and Timing of Spaying on Survival of Dogs with Mammary Carcinoma

The risk of developing mammary gland tumors in dogs is significantly decreased by ovariohysterectomy at an early age. However, previous studies have not found a benefit to ovariohysterectomy concurrent with tumor removal in dogs with established mammary gland tumors, suggesting that the progression of these tumors is independent of continued estrogen stimulation. The purpose of this study was to evaluate the effect of spaying and of the timing of spaying on survival in dogs with mammary gland carcinoma. Signalment, spay status and spay age, tumor characteristics, treatment, survival, and cause of death of 137 dogs with mammary gland carcinoma were analyzed. The dogs were classified into 3 groups according to spay status and spay time: intact dogs, dogs spayed less than 2 years before tumor surgery (SPAY 1), and dogs spayed more than 2 years before their tumor surgery (SPAY 2). Dogs in the SPAY 1 group lived significantly longer than dogs in SPAY 2 and intact dogs (median survival of 755 days, versus 301 and 286 days, respectively,P= .02 and .03). After adjusting for differences between the spay groups with regard to age, histologic differentiation, and vascular invasion, SPAY 1 dogs survived 45% longer compared to dogs that were either intact or in the SPAY 2 group (RR = .55; 95% CI .32–93;P= .03). This study reveals ovariohysterectomy to be an effective adjunct to tumor removal in dogs with mammary gland carcinoma and that the timing of ovariohysterectomy is important in influencing survival.

Effect of spaying and timing of spaying on survival of dogs with mammary carcinoma.

The risk of developing mammary gland tumors in dogs is significantly decreased by ovariohysterectomy at an early age. However, previous studies have not found a benefit to ovariohysterectomy concurrent with tumor removal in dogs with established mammary gland tumors, suggesting that the progression of these tumors is independent of continued estrogen stimulation. The purpose of this study was to evaluate the effect of spaying and of the timing of spaying on survival in dogs with mammary gland carcinoma. Signalment, spay status and spay age, tumor characteristics, treatment. survival, and cause of death of 137 dogs with mammary gland carcinoma were analyzed. The dogs were classified into 3 groups according to spay status and spay time: intact dogs, dogs spayed less than 2 years before tumor surgery (SPAY 1), and dogs spayed more than 2 years before their tumor surgery (SPAY 2). Dogs in the SPAY 1 group lived significantly longer than dogs in SPAY 2 and intact dogs (median survival of 755 days, versus 301 and 286 days, respectively, P = .02 and .03). After adjusting for differences between the spay groups with regard to age, histologic differentiation, and vascular invasion, SPAY 1 dogs survived 45% longer compared to dogs that were either intact or in the SPAY 2 group (RR = .55; 95% CI .32-.93; P = .03). This study reveals ovariohysterectomy to be an effective adjunct to tumor removal in dogs with mammary gland carcinoma and that the timing of ovariohysterectomy is important in influencing survival.