John Berg

Prognostic Significance of Serum Alkaline Phosphatase Activity in Canine Appendicular Osteosarcoma

Sixty-one dogs with appendicular osteosarcoma were treated with amputation and chemotherapy of cisplatin and doxorubicin. Serum samples were obtained before and after treatment for determination of total alkaline phosphatase (TALP) activity as well as the activities of the constituent bone (BALP), liver (LALP), and corticosteroid-induced (CALP) isoenzymes. The relationship between alkaline phosphatase activities and survival was examined by Cox proportional hazards regression analysis and Kaplan-Meier log rank analysis. Mean activity of TALP, BALP, and LALP decreased significantly after treatment (P < .001). TALP and LALP activities before treatment were significantly correlated with survival (P = .006 and .001, respectively). The correlation between BALP activity before treatment and survival approached significance (P = .054). CALP activity and TALP, BALP, and LALP activities after treatment were not significantly correlated with survival. Dogs with normal pretreatment TALP and BALP activities survived significantly longer than dogs with increased pretreatment activities (P = .001 and .003, respectively). Median survival times for dogs with normal or increased TALP activities before treatment were 12.5 and 5.5 months, respectively; and median survival times for dogs with normal or increased BALP activities before treatment were 16.6 and 9.5 months, respectively. In the design of future clinical trials involving dogs with osteosarcoma, consideration should be given to stratifying the randomization according to alkaline phosphatase activity. In addition, alkaline phosphatase activity should be a factor considered by clinicians attempting to tailor the aggressiveness of adjuvant chemotherapy to the needs of individual patients or owners.

Association between outcome and organ system dysfunction in dogs with sepsis: 114 cases (2003-2007)

OBJECTIVE To determine whether multiple organ dysfunction syndrome (MODS) could be identified in dogs with sepsis secondary to gastrointestinal tract leakage, and whether the number of affected organ systems was significantly associated with mortality rate. DESIGN Multicenter retrospective case series. ANIMALS 114 dogs. PROCEDURES Medical records for dogs treated surgically because of sepsis secondary to gastrointestinal tract leakage between 2003 and 2007 were reviewed. Sepsis was diagnosed on the basis of results of bacterial culture of peritoneal fluid, gross evidence of gastrointestinal tract leakage at surgery, or both. Renal dysfunction was defined as a > or = 0.5 mg/dL increase in serum creatinine concentration after surgery. Cardiovascular dysfunction was defined as hypotension requiring vasopressor treatment. Respiratory dysfunction was defined as a need for supplemental oxygen administration or mechanical ventilation. Hepatic dysfunction was defined as a serum bilirubin concentration > 0.5 mg/dL. Dysfunction of coagulation was defined as prolonged prothrombin time, prolonged partial thromboplastin time, or platelet count < or = 100,000/microL. RESULTS 89 (78%) dogs had dysfunction of 1 or more organ systems, and 57 (50%) dogs had MODS. Mortality rate increased as the number of dysfunctional organ systems increased. Mortality rate was 70% (40/57) for dogs with MODS and 25% (14/57) for dogs without. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MODS, defined as dysfunction of at least 2 organ systems, can be identified in dogs with sepsis and that organ system dysfunction increased the odds of death.

Association between outcome and changes in plasma lactate concentration during presurgical treatment in dogs with gastric dilatation-volvulus: 64 cases (2002-2008).

OBJECTIVE To determine whether changes in presurgical plasma lactate concentration (before and after initial fluid resuscitation and gastric decompression) were associated with short-term outcome for dogs with gastric dilatation-volvulus (GDV). DESIGN Retrospective case series. ANIMALS 64 dogs. PROCEDURES Medical records were reviewed, and signalment, history, resuscitative treatments, serial presurgical lactate concentrations, surgical findings, and short-term outcome were obtained for dogs with confirmed GDV. RESULTS 36 of 40 (90%) dogs with an initial lactate concentration <or= 9.0 mmol/L survived, compared with only 13 of 24 (54%) dogs with a high initial lactate (HIL) concentration (> 9.0 mmol/L). Within HIL dogs, there was no difference in mean +/- SD initial lactate concentration between survivors and nonsurvivors (10.6 +/- 2.3 mmol/L vs 11.2 +/- 2.3 mmol/L, respectively); however, there were significant differences in post-treatment lactate concentration, absolute change in lactate concentration, and percentage change in lactate concentration following resuscitative treatment. By use of optimal cutoff values within HIL dogs, survival rates for dogs with final lactate concentration > 6.4 mmol/L (23%), absolute change in lactate concentration <or= 4 mmol/L (10%), or percentage change in lactate concentration <or= 42.5% (15%) were significantly lower than survival rates for dogs with a final lactate concentration <or= 6.4 mmol/L (91%), absolute change in lactate concentration > 4 mmol/L (86%), or percentage change in lactate concentration > 42.5% (100%). CONCLUSIONS AND CLINICAL RELEVANCE Calculating changes in plasma lactate concentration following initial treatment in dogs with GDV may assist in determining prognosis and identifying patients that require more aggressive treatment.

Canine digital tumors : A veterinary cooperative oncology group retrospective study of 64 dogs

We compared clinical characteristics and outcomes for dogs with various digital tumors. Medical records and histology specimens of affected dogs from 9 veterinary institutions were reviewed. Risk factors examined included age, weight, sex, tumor site (hindlimb or forelimb), local tumor (T) stage, metastases, tumor type, and treatment modality. The Kaplan-Meier product limit method was used to determine the effect of postulated risk factors on local disease-free interval (LDFI), metastasis-free interval (MFI), and survival time (ST). Outcomes were thought to differ significantly between groups when P < or = .003. Sixty-four dogs were included. Squamous cell carcinoma (SCC) accounted for 33 (51.6%) of the tumors. Three dogs presented with or developed multiple digital SCC. Other diagnoses included malignant melanoma (MM) (n = 10; 15.6%), osteosarcoma (OSA) (n = 4; 6.3%), hemangiopericytoma (n = 3; 4.7%), benign soft tissue tumors (n = 5; 7.8%), and malignant soft tissue tumors (n = 9; 14%). Fourteen dogs with malignancies had black hair coats, including 5 of the 10 dogs with MM. Surgery was the most common treatment and, regardless of the procedure, had a positive impact on survival. None of the patient variables assessed, including age, sex, tumor type, site, and stage, had a significant impact on ST. Both LDFI and MFI were negatively affected by higher T stage, but not by type of malignancy. Although metastasis at diagnosis correlated with a shorter LDFI, it did not have a significant impact on ST. On the basis of these findings, early surgical intervention is advised for the treatment of dogs with digital tumors, regardless of tumor type or the presence of metastatic disease.

Canine Osteosarcoma: Amputation and Chemotherapy

One of the most important advances in veterinary oncology during the past 10 years has been the use of adjuvant chemotherapy for treatment of the micrometastases of canine osteosarcoma. This article reviews the biologic behavior of osteosarcoma and discusses chemotherapy with the two agents known to be effective: cisplatin and doxorubicin.

Prognosis for dogs with nonlymphomatous, small intestinal tumors treated by surgical excision

Long-term follow-up information was obtained for 39 dogs that had undergone surgical excision of nonlymphomatous, small intestinal tumors. For all dogs evaluated in this study, the median survival time was 10 months, and the one- and two-year survival rates were 40.5% and 33.1%, respectively. There was no difference in survival times between dogs with adenocarcinomas (n=23) and dogs with leiomyosarcomas (n=16). Survival times were significantly (p less than 0.0001) shorter for dogs with histological evidence of metastases at the time of surgery (median, 3.0 months) than for dogs with no histiological evidence of metastases (median, 15.0 months).

Survival time of dogs with splenic hemangiosarcoma treated by splenectomy with or without adjuvant chemotherapy: 208 cases (2001–2012)

OBJECTIVE To determine survival time for dogs with splenic hemangiosarcoma treated with splenectomy alone, identify potential prognostic factors, and evaluate the efficacy of adjuvant chemotherapy. DESIGN Retrospective case series. ANIMALS 208 dogs. PROCEDURES Medical records were reviewed, long-term follow-up information was obtained, and survival data were analyzed statistically. RESULTS 154 dogs were treated with surgery alone, and 54 were treated with surgery and chemotherapy. Twenty-eight dogs received conventional chemotherapy, 13 received cyclophosphamide-based metronomic chemotherapy, and 13 received both conventional and metronomic chemotherapy. Median survival time of dogs treated with splenectomy alone was 1.6 months. Clinical stage was the only prognostic factor significantly associated with survival time. When the entire follow-up period was considered, there was no significant difference in survival time between dogs treated with surgery alone and dogs treated with surgery and chemotherapy. However, during the first 4 months of follow-up, after adjusting for the effects of clinical stage, survival time was significantly prolonged among dogs receiving any type of chemotherapy (hazard ratio, 0.6) and among dogs receiving both conventional and metronomic chemotherapy (hazard ratio, 0.4). CONCLUSIONS AND CLINICAL RELEVANCE Clinical stage was strongly associated with prognosis for dogs with splenic hemangiosarcoma. Chemotherapy was effective in prolonging survival time during the early portion of the follow-up period. Combinations of doxorubicin-based conventional protocols and cyclophosphamide-based metronomic protocols appeared to be more effective than either type of chemotherapy alone, but prolongations in survival time resulting from current protocols were modest.

Principles of oncologic orofacial surgery.

The most common orofacial tumors of dogs are malignant melanoma, squamous cell carcinoma, fibrosarcoma, osteosarcoma, and acanthomatous epulis. These tumors vary significantly in their metastatic potential, but are consistently locally invasive. Bone involvement is common, and complete excision often requires partial mandibulectomy or partial maxillectomy. Survival times after surgery are most strongly influenced by tumor type (or metastatic rate) and tumor location. Recent large retrospective studies have reported median survival times ranging from 4.6 to 26 months. The most common oral tumor of cats is squamous cell carcinoma. This is a highly invasive tumor that occasionally can be effectively treated with surgery alone, but that often requires a combination of surgery and radiation therapy.

Risk factors for perioperative death in dogs undergoing splenectomy for splenic masses: 539 cases (2001–2012)

OBJECTIVE To determine the perioperative mortality rate, causes of death, and risk factors for perioperative death in dogs undergoing splenectomy for splenic mass lesions. DESIGN Retrospective case series. ANIMALS 539 dogs. PROCEDURES Medical records of dogs that underwent splenectomy for known splenic masses were reviewed. Perioperative mortality rate and causes of death were determined. Associations between potential prognostic factors and perioperative death were evaluated by multivariable logistic regression analysis. RESULTS 41 of 539 (7.6%) dogs died during the perioperative period. Thrombotic and coagulopathic syndromes and uncontrolled bleeding from metastatic lesions were the most common causes of death. Of the variables selected for multivariable analysis, platelet count at admission, whether PCV at admission was < 30%, and development of ventricular arrhythmias during surgery were significantly associated with outcome. For each decrease in platelet count of 10,000 platelets/μL, odds of death increased by approximately 6%. For dogs with PCV < 30%, odds of death were approximately twice those for dogs with PCV ≥ 30%, and for dogs that developed intraoperative arrhythmias, odds of death were approximately twice those for dogs that did not. CONCLUSIONS AND CLINICAL RELEVANCE Marked preoperative thrombocytopenia or anemia and development of intraoperative ventricular arrhythmias were identified as risk factors for perioperative death in dogs with splenic masses. The risk of death may be limited by efforts to prevent thrombotic and coagulopathic syndromes and to control all sources of intra-abdominal hemorrhage.

Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast Agent in Companion Dogs with Naturally Occurring Cancer.

Objectives Companion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography (CT) imaging of solid tumors in companion dogs with naturally occurring cancer. Materials and Methods The institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years) with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study. Results Liposomal-I resulted in significant (p < 0.05) enhancement and uniform opacification of the vascular compartment. Non-renal, reticulo-endothelial systemic clearance of the contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan. Conclusions The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small and large tumors in companion dogs with naturally occurring cancer. The study warrants future work to assess the sensitivity and specificity of the Liposomal-I agent in various types of naturally occurring canine tumors.