Fibroblastic Subtype has a Favourable Prognosis in Appendicular Osteosarcoma of Dogs.

Osteosarcoma (OS) is an aggressive malignant bone neoplasm that occurs mostly in the appendicular skeleton of dogs and people. OS is classified based on the presence of malignant stroma and the formation of extracellular matrix into osteoblastic, chondroblastic and fibroblastic forms. This study investigated the correlation between the three histological subtypes of canine OS and clinical outcome. Additionally, we examined whether there was any difference in the immunolabelling of desmin, S100 and neuron-specific enolase (NSE) between the three histological subtypes. Formalin-fixed and paraffin wax-embedded tissues from 87 dogs with primary OS were available for this study. The survival times were correlated with appendicular OS subtypes in dogs that were treated surgically, received adjuvant chemotherapy and had no pulmonary metastasis at the time of diagnosis. Dogs with an appendicular fibroblastic OS had significantly prolonged mean average survival times (546 ± 105 days) in comparison with dogs having appendicular osteoblastic (257 ± 48 days) or appendicular chondroblastic (170 ± 28 days) OS (P = 0.003, Log Rank). The results also revealed that the appendicular chondroblastic subtype is a significant indicator for poor prognosis in dogs compared with the fibroblastic or osteoblastic subtypes (P = 0.006, Cox regression). Moreover, the findings indicated that there was no significant correlation between the localization of desmin, NSE or S100 and histological subtypes. Importantly, dogs with appendicular fibroblastic OS were found to have a better prognosis when compared with dogs with other subtypes. This may suggest that histological subtypes of appendicular OS have diverse behaviour and could be used to categorize patients for risk-based assessment.

Immunohistochemical Validation of Spontaneously Arising Canine Osteosarcoma as a Model for Human Osteosarcoma.

Osteosarcoma (OS) originates from bone-forming mesenchymal cells and represents one of the primary bone tumours. It is the most common primary bone tumour in dogs and man. The characterization of an appropriate natural disease animal model to study human OS is essential to elucidate the pathogenesis of the disease. This study aimed to validate canine OS as a model for the human disease by evaluating immunohistochemically the expression of markers known to be important in human OS. The immunohistochemical panel included vimentin, alkaline phosphatase (ALP), desmin, S100, neuron-specific enolase (NSE), runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 4 (BMP4). Immunohistochemistry was conducted on formalin-fixed, paraffin wax-embedded tissue sections from 59 dogs with confirmed primary OS. Vimentin, ALP, Runx2 and BMP4 were highly expressed by all tumours, while desmin, S100 and NSE were expressed variably. The findings were similar to those described previously for human OS and suggest that canine OS may represent a useful model for the study of the human disease.

Retrieval of ureteral calculus using a new method of endoscopic assistance in a cat.

A 9-year-old female spayed domestic short-haired cat presented with ureteral obstruction due to a ureteral calculus 4 cm distal to the renal pelvis. Preoperative creatinine was 844 mmol/L. A novel approach to this condition was utilised whereby a flexible endoscope was passed through a hole made in the renal capsule into the renal pelvis and ureter. The calculus was visualised, and the endoscope was removed. A 1.4 mm flexible grasping forceps was introduced into the proximal ureter through the same hole in the renal capsule and the calculus was removed. The creatinine dropped to 282 micromol/L within 2 weeks of surgery. The cat died of apparently unrelated causes several months after surgery.

Effect of gas-plasma sterilization on the osteoinductive capacity of demineralized bone matrix.

The current study evaluated the effect of low-temperature hydrogen peroxide gas plasma sterilization on the osteoinductive capability of human demineralized bone matrix using a rat model. Twelve athymic rats received three separate implants consisting of steam-sterilized demineralized bone matrix (negative control), sterile-harvest demineralized bone matrix (positive control), and gas-plasma-sterilized demineralized bone matrix. A demineralized bone matrix pellet from each sterilization group was placed individually into one of three separate soft tissue pockets created in the epaxial musculature of each rat. All 12 rats were euthanized 9 weeks after implantation. Each implantation site was removed along with 0.5-cm normal tissue around the implant. Histologic examination was done on each implant site to determine the presence or absence of new bone, cartilage, or bone marrow elements. All 12 sterile harvest demineralized bone matrix sites histologically contained new bone elements, whereas none of the negative control or gas plasma sterilized demineralized bone matrix sites contained any of these same elements. The results of this study indicate that demineralized bone matrix sterilized with low-temperature, gas-plasma sterilization loses its osteoinductive capacity in a manner similar to that of steam-sterilized demineralized bone matrix, making low-temperature, gas- plasma sterilization unsuitable as a method of secondary sterilization of demineralized bone matrix.

Accuracy of radiography, nuclear scintigraphy, and histopathology for determining the proximal extent of distal radius osteosarcoma in dogs.

OBJECTIVE: To compare the accuracy of radiography, nuclear scintigraphy, and histopathology for determining the proximal extent of distal radius osteosarcoma in dogs. STUDY DESIGN: Retrospective clinical study. SAMPLE POPULATION: Twenty client-owned dogs taken to Colorado State University with osteosarcoma of the distal radius. METHODS: Medical records of 20 dogs with confirmed osteosarcoma that underwent a limb-salvage procedure were reviewed. Measurements were performed directly from the lateral view of each radius, from both the scintigram and the radiograph, to determine the length of the radius and the distance from the proximal extent of the tumor to the distal radiographic or scintographic extent of the radius. The ratio of distal radial involvement to total radius length was calculated. A similar ratio was also determined using the macroslide, which included the entire portion of bone that was excised during the limb-salvage procedure. All 3 methods of measurement were compared. RESULTS: Nuclear scintigraphy significantly overestimated tumor length when compared with macroslide specimen measurements. Radiography also overestimated tumor length, but these results were not significantly different from macroslide specimen measurements. CONCLUSIONS: Both radiography and nuclear scintigraphy overestimate the extent of distal radius osteosarcoma in dogs when compared with histopathologic macroslides of the same lesions. Nuclear scintigraphy overestimated tumor extent to a larger degree than did radiography. CLINICAL RELEVANCE: Although radiography is a more accurate method of measurement of the extent of distal radius osteosarcoma, because nuclear scintigraphy overestimates tumor length to a greater degree, scintigraphy may provide a larger margin of safety for determining the site of proximal osteotomy during a limb-salvage procedure. However, caution should be taken when utilizing scintigraphy, because this method may overestimate length of radius involved to such an extent as to cause the surgeon to believe that a patient is not a suitable limb-salvage candidate.

Surgical treatment of adrenocortical tumors: 21 cases (1990-1996).

Twenty-four adrenocortical tumors were surgically removed from 21 dogs. Histopathological examination confirmed 18 carcinomas and six adenomas. Four dogs died in the perioperative period. Fifteen of the 17 dogs that survived the perioperative period had long-term resolution of their clinical signs. Two dogs with incompletely resected tumors were treated with mitotane to control their clinical signs. Overall median Kaplan-Meier life-table survival for dogs with carcinomas was 778 days (range, one to 1,593 days). Median survival for dogs with adenomas was not reached (range, 11 to 730 days). Histopathological diagnosis, histopathological cellular features, age of the dog, and tumor size were not prognostic of outcome.

Limb salvage surgery for osteosarcoma of the proximal humerus: outcome in 17 dogs.

OBJECTIVE: To describe function and identify factors that affect outcome in dogs undergoing limb salvage surgery for osteosarcoma (OS) of the proximal humerus. STUDY DESIGN: A retrospective study of dogs in which OS of the proximal humerus was treated with limb salvage surgery. ANIMALS: 17 client-owned dogs. METHODS: Records were analyzed for functional outcome, recurrence, metastasis, and survival. RESULTS: Outcome was good to excellent in 12% of dogs. Recurrence, metastasis, and survival were significantly affected by completeness of surgical margins. Double plating of the distal allograft-host junction significantly reduced frequency of biomechanical failure. CONCLUSIONS: Limb salvage surgery for OS of the proximal humerus did not result in acceptable function and was fraught with postoperative complications. Outcome was significantly affected by completeness of surgical margins. CLINICAL RELEVANCE: Limb salvage surgery for OS of the proximal humerus in dogs cannot be recommended until improvement in functional outcome and reduction in postoperative complications can be achieved. The dependence of outcome on completeness of surgical margins supports aggressive en bloc resection and marking and evaluating surgical margins.

Thoracic surgical oncology.

Thoracic surgical oncology involves surgical treatment of lesions of the thoracic wall, pulmonary parenchyma, or mediastinum (also including heart, esophagus, or trachea). The most common neoplasms of the thoracic wall are osteosarcoma and chondrosarcoma. Histopathologic type, the use of chemotherapy for osteosarcoma, and completeness of surgical margins are prognostic for survival. Relative to solitary pulmonary masses, carcinomas are most common, with histopathologic type, tumor size, tumor grade, and lymph node status prognostic for survival. Of the aforementioned variables, lymph node status is the most significant. Extensive preoperative workup, including bronchoscopy and transthoracic fine needle aspiration of solitary lung masses, is usually not recommended. Thymomas are the most common surgical mediastinal mass. Patients are frequently affected with paraneoplastic syndromes including myasthenia gravis, polymyositis, and nonthymic neoplasia. Patients without megaesophagus with surgically resectable masses have an excellent prognosis for survival. Provision of analgesia after surgery in thoracotomy patients is extremely important. Carefully selected analgesic agents in thoracotomy patients are far less damaging to cardiovascular status than is tachycardia from excessive pain. Given these and other guidelines, perioperative mortality in thoracotomy patients is minimal, and long-term survival in selected patients is excellent.

Principles of treatment for soft tissue sarcoma.

Soft tissue sarcomas (STS) are mesenchymal tumors arising from connective tissue elements and are grouped together based on a common biologic behavior. The most common histologic types include malignant peripheral nerve sheath tumors (schwannoma and neurofibrosarcoma) "hemangiopericytoma," fibrosarcoma, and malignant fibrous histiocytoma. These tumors are relatively slow growing yet locally invasive with a high rate of recurrence following conservative management. Appropriate preoperative planning and aggressive surgical resection often result in long-term remission or cure. Identification and evaluation of resection margins are paramount in appropriate case management. The addition of radiotherapy after surgical resection can aid in remission for incompletely resected masses. Systemic chemotherapy for STS should be considered for high-grade tumors with a moderate metastatic potential. Potential prognostic factors include grade, resection margins, size, location, histologic type, and previous treatment, with grade and margins being the most important. Tumor types classified as STS that differ slightly in their presentation or treatment, including synovial cell sarcoma, rhabdomyosarcoma, liposarcoma, and vaccine-associated STS in cats, are discussed. Soft tissue sarcomas can be a frustrating disease to treat, but adherence to solid surgical oncology principles can greatly increase the odds of good disease control.

Extraskeletal osteosarcomas in dogs: 14 cases.

Fourteen dogs (11 females, three males) with extraskeletal osteosarcomas (EsOSAs) were identified. The median age was 11.5 years. The median body weight was 18 kg. The primary sites of the EsOSAs were the spleen (n=6), mammary gland (n=3), lung (n=2), and one each in the skin, axilla, and mesenteric root. The overall median survival time was 74 days. The only factor which was found to be prognostic for survival was the use of chemotherapy (p of 0.02). Cases which did not have chemotherapy were 3.62 times as likely to die a tumor-related death than cases which had chemotherapy.

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.

Sub-retinal pigment epithelial deposits in a dominant late-onset retinal degeneration.

PURPOSE: To determine the pathogenesis of an autosomal dominant late-onset retinal degeneration by studies of the retinal histopathology, phenotype of family members, and candidate genes for the disease. METHODS: The retina from an 80-year-old patient donor was prepared for light and electron microscopy, including special stains and immunocytochemistry. Family members were examined clinically and with retinal function tests. Rhodopsin, peripherin/RDS, and TIMP3 genes were screened for mutations, and linkage analysis was performed with short tandem repeat polymorphisms flanking these genes. RESULTS: Affected family members had nyctalopia in the sixth decade of life and severe visual loss developed by the eighth decade. The donor retina showed marked loss of photoreceptors except in the inferior periphery. A thick layer of extracellular deposits was present between the RPE and Bruch's membrane in all retinal regions. A 70-year-old affected family member had a retinopathy resembling retinitis pigmentosa. Her 42-year-old daughter had a patch of punctate yellow-white lesions in one fundus and abnormal dark adaptation. The 50-year-old son of the donor had normal fundi but abnormal dark adaptation and electroretinography. No mutations were detected in the coding sequence of the rhodopsin, peripherin/RDS, and TIMP3 genes. Rhodopsin and TIMP3 were further excluded with linkage analysis. CONCLUSIONS: This novel retinal degeneration shares histopathologic and clinical features with both Sorsby fundus dystrophy and retinitis pigmentosa. The sub-RPE deposits may disrupt the exchange of nutrients and metabolites between the retina and the choriocapillaris, leading to photoreceptor dysfunction and degeneration.

Use of a modified surgical approach to the right atrium for retrieval of heartworms in a dog.

A 2-year-old 2-kg female Maltese dog was referred for treatment of dirofilariosis and mild caval syndrome characterized by hemolysis and lethargy. Ultrasonography revealed worms within the caudal vena cava, right auricle, right ventricle, and pulmonary artery. Because of the mild clinical signs and small size of the dog, jugular venotomy was not performed, and treatment with sodium caparsolate was instituted. A markedly adverse reaction was noticed on initial injection, characterized by cardiac and respiratory arrest. Further treatment with sodium caparsolate was discontinued. Because of progression of the dog's condition surgical removal of heartworms was elected. A modified surgical approach to the right atrium was performed, using a cannula introduced through a pursestring placed in the wall of the right auricle. This technique allowed almost complete removal of heartworms with minimal blood loss. Postoperative ultrasonography revealed a single heart-worm remaining in the distal portion of the left pulmonary artery, but it was subsequently absorbed.

Controlled cross circulation in dogs: effects on donor hemodynamics.

Controlled cross circulation (CCC) was performed in six pairs of dogs for 45 minutes with aortic cross clamping and cardioplegia. Data were collected in donor dogs at 10 minute intervals three times before, three times during, and three times after CCC and included arterial blood pressure, pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac index (CI), heart rate (HR), blood gas analysis, temperature, maximum rate of rise of left ventricular pressure dP/dt max/End diastolic volume (EDV), blood volume (BV), complete blood count (CBC) and activated clotting times (ACT). Pulse pressure (PP), systemic vascular resistance (SVR), oxygen delivery (DO2), and left ventricular cardiac work (LVCW) were calculated. Arterial blood pressure, CVP, blood gas analysis, temperature, BV, CBC, and ACT were measured in recipient dogs. During CCC, donor hemodynamic changes resembled those observed in models of acute onset arteriovenous fistulas. Insidious BV shifts can occur despite the use of occlusive roller pumps. After CCC, donor hemodynamics resembled acute blood loss, characterized by decreases in mean arterial pressure (MAP), CVP, PCWP, and CI, and increases in SVR and dP/dt max/EDV. These changes were probably caused by pump imbalance and BV shift to the recipient dog.

Sacral fractures in dogs: a review of 32 cases.

Sacral fractures have not been described well in dogs. The records of 32 dogs diagnosed with sacral fractures were evaluated for neurologic deficits at presentation and discharge. Follow-up was in the form of telephone survey or physical examination at recheck. A score was assigned for each dog at presentation, discharge, and follow-up (0 for normal, 1 for minor deficits, and 2 for major deficits). Fractures located lateral to the sacral foramina were called abaxial, and those medial to the sacral foramina were called axial. Axial fractures had significantly more severe deficits at presentation (p = 0.00017) and discharge (p = 0.03063), but not at follow-up. Neurologic status did not improve significantly during hospitalization in either fracture group, but had improved significantly at follow-up.

Modification by cyclic adenosine monophosphate of basolateral membrane chloride conductance in chick retinal pigment epithelium.

PURPOSE: We investigated the hypothesis that cyclic adenosine monophosphate (cAMP) modifies the basolateral membrane chloride conductance of chick retinal pigment epithelium (RPE). METHODS: Placing freshly dissected chick retina-RPE-choroid tissues in a perfusion chamber that allows separate perfusion of its retinal and choroidal sides, the authors examined the effect of choroidal perfusion of forskolin (50 mM), an adenylate cyclase activator, on extracellular and intracellular RPE potentials, resistances, light-evoked responses, and chloride diffusion potentials. RESULTS: Forskolin hyperpolarized the RPE basolateral membrane, decreased the apical/basal membrane resistance ratio, increased the amplitude of the RPE membrane c-wave hyperpolarizations, decreased the amplitude of the transepithelial c-wave, and suppressed the light peak. In addition, forskolin decreased the basolateral membrane chloride diffusion potential by 31%. The effects of forskolin were diminished by pretreatment of the basolateral membrane with DIDS, a chloride channel blocker, or by pretreatment of the apical membrane with bumetanide, a blocker of NaK2Cl cotransport. Transepithelial potential, resistance, and c-wave amplitude were not changed by 1,9-dideoxyforskolin, which does not elevate cAMP levels. CONCLUSIONS: Elevation of cAMP results in diminished basolateral membrane chloride conductance in chick RPE. This could be due to a direct effect on the chloride channel or due to a decrease in intracellular chloride concentration secondary to inhibition of apical membrane NaK2Cl cotransport.