Pilot study supporting the existence of novel lymphatic channels within the canine anterior uveal tract using Lyve-1 and CD31.

OBJECTIVE: To demonstrate the existence of lymphatics in the canine anterior uvea using lymphatic-specific markers Lyve-1, Prox-1, and podoplanin, the endothelial cell marker CD31, and basement membrane matrix marker collagen IV. DESIGN: Prospective Study. ANIMALS: Eight normal globes from animals euthanized for unrelated health problems. PROCEDURES: Sagittally cut serial sections of six normal canine eyes were immunofluorescence double-stained with Lyve-1 and CD31 and single-stained with colorimetric Prox-1 and collagen IV. Three serial sections from 2 additional eyes were cut in the coronal plane at the level of the ciliary body and immunofluorescence double-stained with Lyve-1 and CD31 to map lymphatic channel distribution. Lymphatics from normal canine lymph nodes were used for validation of podoplanin. RESULTS: Four of 6 of the sagitally sectioned eyes had Lyve-1-positive lymphatic-like structures that were distinct from CD31-positive blood vessels in the iris base and ciliary body. Both of the coronally sectioned globes had Lyve-1-positive lymphatic-like structures in the ciliary body. The location of these structures was evaluated and found to be diffusely present circumferentially around the ciliary body. CONCLUSION AND CLINICAL RELEVANCE: These results support the existence of lymphatic channels in the anterior uveal tract of the canine eye. This could indicate the presence of a novel uveolymphatic outflow pathway, which may play a role in aqueous humor outflow. Future studies are needed to confirm the existence and elucidate the role of this proposed uveolymphatic outflow pathway and potentially develop novel treatment options for managing glaucoma.

Detection of papillomavirus in equine periocular and penile squamous cell carcinoma.

Squamous cell carcinoma (SCC) is the most common tumor arising in the periocular and penile areas of horses. Both ultraviolet radiation and papillomaviruses have been implicated in the pathogenesis of SCC in various species, including the horse. This retrospective study used polymerase chain reaction (PCR) to detect papillomavirus DNA in archival biopsy samples from equine periocular and penile SCC from 3 different geographic areas (northeast, southeast, and central United States). Forty-two periocular SCCs were tested; none contained papillomavirus DNA. Twenty-two penile SCCs were tested, and papillomavirus DNA was identified in 10 (43%) cases. Sequencing of the PCR products revealed homology with Equus caballus papillomavirus 2 (EcPV-2). No geographic distribution in the detection of papillomavirus was identified. Penile SCCs were significantly more likely to be papillomavirus positive than the periocular SCCs (P < 0.001). The role of papillomavirus in the development of penile SCC requires further investigation. The differing pathogeneses of periocular and penile SCC suggest that the tumors may respond differently to treatment.

Azoospermia in an 8-month-old boar due to bilateral obstruction at the testis/epididymis interface.

An 8-month-old Yorkshire boar was presented for apparent azoospermia. Two semen collections also revealed azoospermia. Ultrasonographic examination of the gonads revealed bilateral caput epididymal dilatation and anechoic fluid within the tubules. Because a testicular biopsy revealed normal spermatogenesis, an outflow tract obstruction was suspected. Multiple sperm granulomas were found within the parenchyma of both testes at necropsy.

Incidence of acute myeloid leukemia and hepatocellular carcinoma in mice irradiated with 1 GeV/nucleon (56)Fe ions.

Abstract Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the leukemogenic efficacy of one such HZE species, 1 GeV (56)Fe ions, a component of space radiation, in a mouse model for radiation-induced acute myeloid leukemia. CBA/CaJ mice were irradiated with 1 GeV/nucleon (56)Fe ions or (137)Cs gamma rays and followed until they were moribund or to 800 days of age. We found that 1 GeV/nucleon (56)Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia (AML). However, (56)Fe-ion-irradiated mice had a much higher incidence of hepatocellular carcinoma (HCC) than gamma-irradiated mice, with an estimated RBE of approximately 50. These data suggest a difference in the effects of HZE iron ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis.

Validation of a rapid parathyroid hormone assay and intraoperative measurement of parathyroid hormone in dogs with benign naturally occurring primary hyperparathyroidism.

OBJECTIVES: To (1) validate a rapid chemiluminescent parathyroid hormone (PTH) assay, (2) determine it's usefulness locating a parathyroid nodule(s), and (3) determine if >50% decrease in PTH corresponds with excision of autonomously functioning parathyroid tissue. STUDY DESIGN: Prospective cohort study. ANIMALS: Dogs (n=12) with naturally occurring primary hyperparathyroidism and 25 healthy dogs. METHODS: The assay was validated with linearity, precision, and intermethod comparison. Preoperative and postoperative systemic plasma PTH concentrations, measured from saphenous venous blood, were compared. Intraoperative local PTH concentrations were measured in right and left jugular venous blood before and after surgical excision of the grossly abnormal parathyroid gland(s). RESULTS: Within run and day-to-day precisions were acceptable (coefficient of variation <15%). Dilutional parallelism was used to demonstrate high correlation between measured and calculated PTH concentrations (R(2)=0.99). The assay methods had good correlation but numerical results of the rapid assay were usually lower than the immunoradiometric assay. Seven of 12 dogs had uniglandular disease and five had multiglandular disease. Systemic and local PTH concentrations decreased >50% in all the dogs after excision of the parathyroid gland(s). Mean preoperative systemic plasma PTH concentrations were significantly higher than mean postoperative systemic concentrations. Local PTH concentrations could not be used reliably to differentiate the side of the autonomously functioning gland(s). Hypercalcemia resolved postoperatively in all the dogs. CONCLUSION: This assay measures PTH in dogs. Rapid PTH measurement provided documentation of decreased PTH concentration after removal of autonomously functioning parathyroid tissue. CLINICAL RELEVANCE: Use of this assay allows documentation of a significant decrease in PTH concentration after excision of autonomously functioning parathyroid tissue.

Retinal pigment epithelial damage, breakdown of the blood-retinal barrier, and retinal inflammation in dogs with primary glaucoma.

OBJECTIVE: This paper aims to determine if abnormalities of the retinal pigment epithelium (RPE) and retinal inflammation occur in primary glaucoma. PROCEDURE: Twenty-three canine globes with primary glaucoma, goniodysgenesis, and elevated intraocular pressure were evaluated. Sections from 6 control and 23 glaucomatous canine globes were stained with hematoxylin and eosin, Griffonia simplicifolia isolectin B4, or immunohistochemically stained for CD3 or albumin. The retinal sections were evaluated with light microscopy for morphological and immunohistochemical evidence of pigmentary changes and inflammation. RESULTS: Abnormal pigmented cells including displaced RPE cells and macrophages (identified by lectin binding) were found in the neuroretinas and vitreous bodies of glaucomatous eyes. Other abnormalities included hypertrophy of RPE cells and loss of RPE continuity. Regions of neuroretina with more displaced pigment had fewer remaining neurons. Signs of retinal inflammation found in glaucomatous eyes included infiltration with leukocytes, retinal swelling, and albumin leakage from vessels. Accumulation of perivascular CD3-positive T lymphocytes also occurred in glaucomatous retinas. Chronic glaucomatous retinas had increased pigmentary changes, fewer neutrophils, and less swelling than acute glaucomatous retinas. CONCLUSIONS: Disruption of the RPE, increased permeability of the vascular endothelium, accumulation of inflammatory cells, and retinal swelling or thinning occur in canine primary glaucoma. The displacement of pigment and accumulation of inflammatory cells in the neuroretina suggests that inflammation may be an important contributor to retinal damage.

Intraoperative radiation for limb sparing of the distal aspect of the radius without transcarpal plating in five dogs.

OBJECTIVES: To evaluate intraoperative irradiation (IORT) as a method of limb spare with preservation of the radiocarpal joint. STUDY DESIGN: Prospective case series. ANIMALS: Dogs (n=5) with stage II sarcoma of the distal aspect of the radius. METHODS: A bone segment containing the tumor was isolated surgically, treated by IORT, reimplanted, and secured by internal fixation. In 1 dog, the postradiation tumor bed was curetted and filled with bone cement. Dogs were administered alternating adriamycin and carboplatin starting 2 weeks after IORT and monitored at regular intervals. RESULTS: Four dogs had osteosarcoma and 1 had undifferentiated sarcoma. Implant failure (n=3), deep tissue infection (3), and pathologic fracture (3) resulted in amputation (3) or pancarpal plating (2). The dog with undifferentiated sarcoma was euthanatized because of suspected tumor recurrence 4 months postoperatively. Osteotomy healing was documented by radiography (1), histopathology (2), or by direct observation (2). CONCLUSIONS: A technique for limb-sparing surgery of the distal portion of the radius in dogs using IORT had advantages include healing of the autograft and a source for a perfectly fitting autograft but did not appear to offer any advantage with respect to infection rate. Long-term preservation of the radiocarpal joint was not successful. CLINICAL RELEVANCE: It was not possible to preserve the function of the radiocarpal joint and so this technique cannot be recommended currently. Further study is needed to evaluate whether or not IORT can be considered in combination with pancarpal plating and possibly curettage and cementation of the tumor to prevent subchondral bone collapse.

Evaluation of prognostic factors associated with outcome in dogs with multiple cutaneous mast cell tumors treated with surgery with and without adjuvant treatment: 54 cases (1998-2004).

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.

Pigmented epidermal plaques in three dogs.

Papillomavirus was identified in pigmented epidermal plaques (PEP) from three dogs: a miniature schnauzer with hyperadrenocorticism and hypoglobulinemia, an American Staffordshire terrier with hypoglobulinemia, and a Pomeranian with unconfirmed hypothyroidism. Squamous cell carcinoma (SCC) arose within several plaques in the Pomeranian. Clinical improvement coincided in the first two cases with treatment of the concurrent disease and the administration of low-dose oral interferon-alpha. This is the first report of PEP in an American Staffordshire terrier and a Pomeranian. The potential for malignant transformation of PEP to SCC emphasizes the need for recognition and clinical management of PEP.

Retroperitoneal sarcomas in dogs: 14 cases (1992-2002).

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.