Nasal Mucosal Adenocarcinoma in a Pet Rabbit

A 6-year-old male rabbit (Oryctolagus cuniculus) presented with upper respiratory disease that was nonresponsive to antibiotic therapy. Computed tomography revealed a severe space-occupying lesion of the right nasal cavity, deviation of the nasal septum to the left, and narrowing of the left nasal cavity. An exploratory rhinostomy was performed for the purposes of diagnostic sample collection and to improve airflow as clinical signs of dyspnea were becoming more pronounced. The histopathologic disease diagnosis from the biopsy samples was nasal mucosal adenocarcinoma. Palliative rhinostomy provided only temporary improvement in airflow, and the patient was euthanized 3 days later. On necropsy, neoplasia was found to extend into the rhinopharynx. This is the first reported case of nasal mucosal adenocarcinoma in rabbits. This important differential diagnosis should be considered for any rabbit with clinical signs of upper respiratory disease that is nonresponsive to medical therapy.     

Salivary Gland Adenocarcinoma in a Domestic Rabbit (Oryctolagus cuniculus)

A 2.4 kg, 7-year-old, female Rex rabbit was presented with a 4-month history of a left-sided head tilt, difficulty in mastication, lethargy, and chronic wasting. Diagnostic testing of the patient revealed a severe heterophilic leukocytosis and radiographic images of the skull radiographs indicated irregularity of the left tympanic bulla. A computed tomographic scan highlighted a heterogeneously contrast-enhancing mass, ventral and rostral to the left tympanic bulla, with contrast enhancement of the meninges on the left, consistent with an aggressive neoplasm. The patient was euthanized and the mass was identified as a salivary gland adenocarcinoma. The gland of origin is suspected to be the left parotid, owing to its location and close association with normal parotid tissue. To the authors' knowledge, this is the first report of a salivary gland adenocarcinoma in a domestic rabbit. A computed tomography (CT) scan and histopathology examination were useful modalities for identifying the neoplasm in this case.     

Suppurative granulomatous sinorhinitis associated with Nocardia spp. infection in a cat

A 9-year-old spayed female cat was examined for cheek skin drainage. The skin lesion did not respond to medical therapy; thereafter, facial deformity developed. A computed tomography revealed an intranasal mass and maxillary osteolysis. The mass was histopathologically diagnosed as suppurative granulomatous inflammation caused by filamentous bacteria. The lesion responded well to radiation therapy. Although actinomycosis was suspected histopathologically, no actinomycetes were detected in the nasal lesion by a bacterial culture conducted at a commercial laboratory. The submandibular lymph node and subcutaneous tissue exhibited swelling. Microbiological examination and genetic analysis based on 16S rDNA gene sequence revealed that Nocardia spp. were isolated from both lesions.     

Spontaneous Mammary Adenocarcinoma in a Twelve-week-old Female Sprague-Dawley Rat

Spontaneous mammary adenocarcinoma was observed in a 12-week-old female SD rat. A movable mass in the right cervical region was found at 11 weeks of age, and the rat was sacrificed the following week. The mass was located in the vicinity of the right salivary gland and measured 38 mm × 26 mm × 16 mm in gross size. It was a firm whitish mass, with a cut surface that was also whitish in appearance. Histopathologically, neoplastic cells formed glandular structures that contained secreted eosinophilic material. Ultrastructurally, similar secreted material and lipid droplets were in the cytoplasm of the neoplastic cells. Immunohistochemically, the neoplastic cells were positive for cytokeratin 8, cytokeratin 18 and estrogen receptor α. Based on these findings, the tumor was diagnosed as a mammary gland adenocarcinoma, and we therefore conclude that this tumor type can occur spontaneously in female SD rats as young as 12 weeks of age.     

Involvements of Estrogen Receptor,Proliferating Cell Nuclear Antigen and p53 in Endometrial Adenocarcinoma Development in Donryu Rats

Involvements of estrogen receptor (ER)α, proliferating cell nuclear antigen (PCNA) and p53 in the uterine carcinogenesis process in Donryu rats, a high yield strain of the uterine cancer were investigated immunohistochemically. ERα was expressed in atypical endometrial hyperplasia, accepted as a precancerous lesion of the uterine tumors, as well as well- and in moderately-differentiated endometrial adenocarcinomas, and the intensities of expression were similar to those in the luminal epithelial cells of the atrophic uterus at 15 months of age. The expression, however, was negative in the tumor cells of poorly differentiated type. Good growth of implanted grafts of the poorly-differentiated adenocarcinomas in both sexes with or without gonadectomy supported the estrogen independency of tumor progression to malignancy. PCNA labeling indices were increased with tumor development from atypical hyperplasia to adenocarcinoma. The tumor cells in poorly-differentiated adenocarcinomas were positive for p53 positive but negative for p21 expression, suggesting accumulation of mutated p53. These results indicate that the consistent ERα expression is involved in initiation and promotion steps of uterine carcinogenesis, but not progression. In addition, PCNA is related to tumor development and the expression of mutated p53 might be a late event during endometrial carcinogenesis.     

Exocrine Pancreatic Adenocarcinoma and Associated Extrahepatic Biliary Obstruction in a Ferret

A 7-year-old neutered, male, fitch ferret presented for weight loss, decreased appetite, reduced bowel movements, and occasional bruxism. Physical examination confirmed weight loss of 340 g over the preceding 7 months. Abnormal clinicopathologic results included lymphopenia, monocytosis, increased alkaline phosphatase, increased alanine transferase, markedly increased total bilirubin, and hypocalcemia. Plasma glucose was normal. After a discussion of diagnostic and therapeutic options, the owner decided to humanely euthanize the patient and consented to cosmetic necropsy. Microscopic examination of submitted tissues revealed an unencapsulated, infiltrative neoplasm that effaced the pancreatic architecture and metastasized to several other organs, including the lung, liver, and jejunum. Based on the cellular morphology, presence of distinctive rosettes, immunonegativity for insulin, and widespread metastasis, the disease diagnosis was exocrine pancreatic adenocarcinoma.     

A complication probability study for a definitive‐intent,moderately hypofractionated image‐guided intensity‐modulated radiotherapy protocol for anal sac adenocarcinoma in dogs

Previous trials showed the importance of administering radiation therapy (RT) with small doses per fraction in canine pelvic tumours to maintain acceptable toxicity levels. With increased accuracy/precision of RT, namely intensity‐modulated RT (IMRT), this approach might be challenged. Theoretical toxicity calculations for a new definitive‐intent moderately hypofractionated RT protocol for canine anal sac adenocarcinomas (ASAC) were performed, focussing on the risk of toxicity in pelvic organs at risk (OAR). Computed tomography datasets of 18 dogs with stage 3b ASAC were included. Re‐planning with margins for daily image‐guidance/IMRT was performed and a new protocol isoeffective to previously described definitive‐intent protocols was computed. Dose‐volume information were derived from individual plans and used for normal tissue complication probability (NTCP) computations. A 12 × 3.8 Gy protocol was computed for risk estimation. Tumour volumes ranged from 27.9 to 820.4 cm³ (mean 221.3 cm³ ± 188.9). For late rectal toxicity/bleeding ≥grade 2, median risk probability was 2.3% inter quartile range (IQR: 5.9; 95% confidence interval (CI): 1.2, 8.4) (rho = 0.436) and 3.4% (IQR: 0.96; 95%CI: 3.1, 4.0) (rho = 0.565), respectively. Median late toxicities in urinary bladder, kidneys and small bowel were <1%, except in one kidney. Myelopathy/myelonecrosis had a median risk probability of 4.1% (IQR: 23.5; 95%CI: 2.1, 25.2) (rho = 0.366) and 5.6% (IQR: 13.5; 95%CI: 3.1, 14.1) (rho = 0.363), respectively. However, graded risk showed a probability estimate for late spinal cord toxicity of ≥5% in 8/18 patients. The daily‐imaging IMRT 12 × 3.8 Gy protocol for canine ASAC seems tolerable for most cases, even in advanced disease. Theoretical dose computations serve as estimate, but are safe measures before implementing new protocols into clinical use.     

Maximum volume of nasal administration using a mucosal atomization device without aspiration in Japanese White rabbits

Recently, a mucosal atomization device (MAD) has been applied in veterinary medicine. In the present study, the maximum volume of nasal atomization without aspiration using MAD was examined in eight healthy female Japanese White (JW) rabbits. Each rabbit had their head and neck examined by computed tomography before and after nasal atomization with four different doses (0.15, 0.3, 0.45, and 0.6 ml per nostril) of diluted contrast medium (1:2 mixture of iohexol and saline). This was done under general anesthesia by an intramuscular administration of alfaxalone 2.5 mg/kg, medetomidine 40 μg/kg, and butorphanol 0.4 mg/kg, with a 7-day washout period between each treatment. The diluted contrast medium was distributed in the nasal cavity, external nares, and/or oral cavity in all rabbits receiving each treatment. The intranasal distribution volumes of the contrast medium were 287 (250–333) mm³ [median (interquartile range)] for 0.15 ml, 433 (243–555) mm³ for 0.3 ml, 552 (356–797) mm³ for 0.45 ml, and 529 (356–722) mm³ for 0.6 ml of treatment. The intranasal distribution volume for 0.15 ml treatment tended to be lower than that for 0.6 ml treatment (P=0.083). The contrast medium was deposited in the trachea in one rabbit (12.5%) and four rabbits (50%) receiving treatments of 0.45 and 0.6 ml per nostril, respectively. The maximum volume of nasal atomization without aspiration into the trachea was 0.3 ml per nostril for the JW rabbits.     

High-dose-rate brachytherapy for intranasal tumours in dogs: results of a pilot study

This prospective study describes the feasibility and toxicity of ¹⁹²Iridium high‐dose‐rate (HDR) brachytherapy as an alternative strategy for the treatment of canine intranasal tumours. Fifteen dogs with malignant intranasal tumours were treated twice weekly using a hypofractionated protocol with eight fractions, 5 Gy per fraction, resulting in a total dose of 40 Gy. Acute and chronic adverse side‐effects appeared to be rare. Only 7% of the acute side‐effects and 5% of the chronic were classified as severe (grade 3). Eight dogs showed clinical complete remission, and five dogs had partial remission, with a resolution of tumour‐related symptoms. Magnetic resonance imaging showed a reduced tumour mass in 12 cases. Median survival time was 17 months (range 4–48 months), with four dogs (three without disease) still alive. Median time to recurrence of these dogs was 14 months. In nine dogs, progression or recurrence of the tumour was the cause of death. This study suggests that HDR brachytherapy is feasible and well tolerated.     

Comparison of immune responses to intranasal and intrapulmonary vaccinations with the attenuated Mycoplasma hyopneumoniae 168 strain in pigs

The aim of this study was to evaluate the immune responses to intranasal and intrapulmonary vaccinations with the attenuated Mycoplasma hyopneumoniae (Mhp) 168 strain in the local respiratory tract in pigs. Twenty-four pigs were randomly divided into 4 groups: an intranasal immunization group, an intrapulmonary immunization group, an intramuscular immunization group and a control group. The levels of local respiratory tract cellular and humoral immune responses were investigated. The levels of interleukin (IL)-6 in the early stage of immunization (P<0.01), local specific secretory IgA (sIgA) in nasal swab samples (P<0.01); and IgA- and IgG-secreting cells in the nasal mucosa and trachea were higher after intranasal vaccination (P<0.01) than in the control group. Interestingly, intrapulmonary immunization induced much stronger immune responses than intranasal immunization. Intrapulmonary immunization also significantly increased the secretion of IL-6 and local specific sIgA and the numbers of IgA- and IgG-secreting cells. The levels of IL-10 and interferon-γ in the nasal swab samples and the numbers of CD4⁺ and CD8⁺ T lymphocytes in the lung and hilar lymph nodes were significantly increased by intrapulmonary immunization compared with those in the control group (P<0.01). These data suggest that intrapulmonary immunization with attenuated Mhp is effective in evoking local cellular and humoral immune responses in the respiratory tract. Intrapulmonary immunization with Mhp may be a promising route for defense against Mhp in pigs.     

Spontaneous Extraskeletal Osteosarcoma in a Rabbit (Oryctolagus cuniculus): Histopathological and Immunohistochemical Findings

A spontaneously occurring subcutaneous mass in the left forelimb of a nine-year-old rabbit (Oryctolagus cuniculus) was examined histopathologically and immunohistochemically. Clinically, edema and hemorrhage were seen around the mass. No connection of the tumor mass to the appendicular skeleton was found. The tumor was arranged in a solid growth pattern and irregular bundles, and neoplastic cells were polygonal to spindle-shape. Osteoid (positive for osteocalcin) and multinucleated giant cells were diffusely or focally seen. Neoplastic cells were positive for vimentin, osterix and Ki-67, indicating the nature of osteoblasts with proliferating activity, but negative for α-smooth muscle actin, desmin or CD204. Based on these findings, a diagnosis of extraskeletal osteosarcoma was made, a very rare tumor both in laboratory and pet rabbits.     

去卵巢及雌激素替代治疗后家兔海马nNOS阳性神经元的形态结构及分布变化

用SABC免疫组织化学技术,观察家兔海马各区nNOS阳性神经元在去卵巢及雌激素替代治疗后的形态结构及分布变化,为雌激素类药物防治绝经后老年性痴呆症提供理论依据。结果表明,家兔海马各区都有nNOS阳性神经元分布;去卵巢后海马nNOS阳性神经元的形态结构及分布变化有区域差异性:与假手术对照组相比,在海马CA1区、CA3区、齿状回(DG)阳性神经元数量明显减少(P0.05),而在CA2区数量明显增多(P0.05)。CA1、CA3区和DG的阳性神经元胞体截面积明显变小,最长突起长度明显变短,第一级突起数变少,与假手术组有显著差异(P0.05)。CA2区阳性神经元胞体截面积明显变小(P0.05),最长突起长度、第一级突起数增多,但差异不显著(P0.05);nNOS阳性神经元的4种指标在雌激素替代治疗组与假手术组之间无显著差异(P0.05)。结果提示:雌激素可能通过影响海马nNOS的表达来影响脑的学习和记忆功能。     

Three‐dimensional conformal versus non‐graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002–2007)

Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non‐graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under‐dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures.     

The Elekta Fraxion™ system is not suitable for maxillary fixation in canine conformal radiation therapy techniques

In this prospective, exploratory study, we evaluated the positioning accuracy in a group of 15 dogs undergoing fractionated stereotactic radiotherapy for tumors affecting the head, using a modified human maxillary fixation device (Elekta Fraxion? system). Positioning was assessed using on‐board volumetric imaging, with a six‐degrees‐of‐freedom image registration technique. Prior to treatment delivery, CBCT images were obtained and patient alignment was corrected, in both translational and rotational planes, using a six‐degrees‐of‐freedom robotic patient positioning system (HexaPOD Evo RT System). The maximum angular inter‐fraction motions observed were 6.1° (yaw), 10.9° (pitch), and 4.5° (roll). The mean systematic translational errors were 4.7, 2.6, and 2.3 mm, mean random translational errors were 3.0, 2.2, and 2.5 mm, and mean overall translational errors were 2.4, 0.7, and 2.3 mm in the cranial‐caudal, lateral, and dorsal‐ventral directions, respectively. The mean systematic rotational errors were 1.17°, 0.77°, and 1.43°, the mean rotational random errors were 1.65°, 1.46°, and 1.34° and the mean overall rotational errors were 0.56°, 0.22°, and 0.29° in the yaw, pitch, and roll directions, respectively. The mean error of the three‐dimensional vector was 6.9 mm with a standard deviation of 3.8 mm. Ninety‐five percent of the three‐dimensional vectors were <14.8 mm. This study demonstrates that this maxillary fixation device relies on six‐degrees‐of‐freedom registration and an ability to apply corrections using a six‐degrees‐of‐freedom couch for accurate patient positioning and tumor targeting. Its use in conformal radiation therapy in dogs is not recommended.