Nicole Ehrhart

Use of alternating administration of carboplatin and doxorubicin in dogs with microscopic metastases after amputation for appendicular osteosarcoma: 50 cases (1999–2006)

OBJECTIVE To evaluate the efficacy and toxicity of an alternating carboplatin and doxorubicin chemotherapy protocol in dogs with putative microscopic metastases after amputation for appendicular osteosarcoma and assess patient-, tumor-, and treatment-related factors for associations with prognosis. DESIGN Retrospective case series. ANIMALS 50 client-owned dogs. PROCEDURES Records of dogs that underwent amputation for appendicular osteosarcoma and received an alternating carboplatin and doxorubicin chemotherapy protocol were reviewed. Dogs had full staging and were free of detectable metastases prior to chemotherapy. Data on disease-free interval (DFI), survival time, and toxicoses were retrieved from medical records and owner or referring veterinarian communications. RESULTS Median DFI was 202 days. Median survival time was 258 days. Twenty-nine (58%) dogs completed the protocol as planned, and the rest were withdrawn typically because of metastases or toxicoses. Grade 3 or 4 myelosuppression was reported in 9 of 50 (18%) dogs and grade 3 or 4 gastrointestinal toxicosis in 6 of 50 (12%) dogs. There were no chemotherapy-related fatalities. Univariate factors associated with significant improvement in DFI included tumor location (radius), receiving doxorubicin as the first drug, starting chemotherapy more than 14 days after amputation, and no rib lesions on preamputation bone scans. Multivariate factors associated with a significant improvement in survival time were tumor location (radius) and completing chemotherapy. CONCLUSIONS AND CLINICAL RELEVANCE Alternating administration of carboplatin and doxorubicin resulted in DFI and survival time similar to those reported for single-agent protocols. Clients should be counseled regarding the likelihood of toxicoses. Relevance of sequence and timing of starting chemotherapy should be further evaluated.

Soft-Tissue Sarcomas in Dogs: A Review

Soft-tissue sarcomas are a heterogeneous group of tumors with similar biological behaviors. Wide surgical excision remains the cornerstone of treatment for these tumors. Local recurrence is common following conservative resection, and recurrent tumors are more difficult to treat. Radiation therapy or re-excision with wider margins is indicated if excision is microscopically incomplete. Chemotherapy is often recommended as an adjunctive treatment for high-grade soft-tissue sarcomas because of their higher metastasis rates when compared to low-or intermediate-grade soft-tissue sarcomas. Knowledge of extent of disease and histological grade is helpful in guiding treatment choices.

Cardiopulmonary effects of intrathoracic insufflation in dogs.

This study was designed to quantify the effects of incremental positive insufflation of the intrathoracic space on cardiac output (CO), heart rate (HR), arterial pressure (AP), central venous pressure (CVP), and percent saturation of hemoglobin with oxygen (SPO2) in anesthetized dogs. Seven healthy, adult dogs from terminal teaching laboratories were maintained under anesthesia with isoflurane delivered with a mechanical ventilator. The experimental variables were recorded before introduction of an intrathoracic catheter, at intrathoracic pressures (IP) of 0 mm Hg, 3 mm Hg insufflation, and additional increments of 1 mm Hg insufflation thereafter until the SPO2 remained <85% despite increases in minute volume. Finally the variables were measured again at 0 mm Hg IP. The cardiac output and systolic and diastolic AP significantly (P < 0.05) decreased at 3 mm Hg IP. Significant decreases in SPO2 were seen at 10 mm Hg IP. Significant increase in CVP was noted at 6 mm Hg IP. Heart rate decreased significantly at 5 to 6 mm Hg IP but was not decreased above 6 mm Hg IP. Given the degree of CO decrease at low intrathoracic pressures, insufflation-aided thoracoscopy should be used with caution and at the lowest possible insufflation pressure. Standard anesthetic monitoring variables such as HR and AP measurements may not accurately reflect the animals cardiovascular status.

In Vivo Assessment of Absorbable Knotless Barbed Suture for Single Layer Gastrotomy and Enterotomy Closure

OBJECTIVE To compare the performance of an absorbable barbed suture device to absorbable monofilament suture after single layer, appositional gastrotomy and enterotomy closure. STUDY DESIGN Experimental comparative study. ANIMALS Purpose-bred adult mongrel hounds (n = 14). METHODS Bursting strengths up to 250 mmHg of incisional closure with either monofilament or barbed suture in a simple continuous, appositional pattern at sites in the stomach (2), jejunum (4), and colon (4) were compared at postoperative Days 3, 7, and 14. Time for incisional closure was compared between materials. RESULTS Bursting strength was not significantly different between gastrotomies/enterotomies closed with the monofilament suture or the barbed device. Closure time was significantly reduced with the barbed device in jejunal enterotomy closure. CONCLUSION The barbed device compared favorably with monofilament suture for gastrotomy and enterotomy (small intestine, colon) closure. Results demonstrate comparable burst strengths between monofilament suture and the barbed device. Closure time was significantly reduced in jejunum closure using the barbed device.Objective To compare the performance of an absorbable barbed suture device to absorbable monofilament suture after single layer, appositional gastrotomy and enterotomy closure. Study Design Experimental comparative study. Animals Purpose-bred adult mongrel hounds (n = 14). Methods Bursting strengths up to 250 mmHg of incisional closure with either monofilament or barbed suture in a simple continuous, appositional pattern at sites in the stomach (2), jejunum (4), and colon (4) were compared at postoperative Days 3, 7, and 14. Time for incisional closure was compared between materials. Results Bursting strength was not significantly different between gastrotomies/enterotomies closed with the monofilament suture or the barbed device. Closure time was significantly reduced with the barbed device in jejunal enterotomy closure. Conclusion The barbed device compared favorably with monofilament suture for gastrotomy and enterotomy (small intestine, colon) closure. Results demonstrate comparable burst strengths between monofilament suture and the barbed device. Closure time was significantly reduced in jejunum closure using the barbed device.

Chitosan-heparin polyelectrolyte multilayers on cortical bone: Periosteum-mimetic, cytophilic, antibacterial coatings

Cortical bone allografts suffer from high rates of failure due to poor integration with host tissue, leading to non‐union, fracture, and infection following secondary procedures. Here, we report a method for modifying the surfaces of cortical bone with coatings that have biological functions that may help overcome these challenges. These chitosan‐heparin coatings promote mesenchymal stem cell attachment and have significant antibacterial activity against both S. aureus and E. coli. Furthermore, their chemistry is similar to coatings we have reported on previously, which effectively stabilize and deliver heparin‐binding growth factors. These coatings have potential as synthetic periosteum for improving bone allograft outcomes. Biotechnol. Bioeng. 2013; 110: 609–618.

Outcome following curative-intent surgery for oral melanoma in dogs: 70 cases (1998–2011)

OBJECTIVE To evaluate the outcome in terms of progression-free interval (PFI) and overall survival time (ST) after curative-intent resection of oral melanoma in dogs. DESIGN Retrospective case series. ANIMALS 70 client-owned dogs. PROCEDURES An electronic medical record search and review was performed for dogs that underwent curative-intent resection of oral melanoma (May 1, 1998, to December 31, 2011). Information gathered included signalment, oral location of tumor, staging results, type of surgery, type of adjuvant therapy, findings on histologic evaluation, and outcome. RESULTS 36 (51.4%), 16 (22.9%), 13 (18.6%), and 1 (1.4%) of 70 dogs had tumors classified as stage I, II, III, and IV, respectively; tumor stage could not be determined for 4 (5.7%) dogs because of the lack of tumor size information. Fifty-one (72.9%) dogs had tumors completely excised. Twenty-nine (41.4%) dogs received adjuvant therapy. Median PFI and ST were 508 and 723 days, respectively. Thirty-two (45.7%) dogs had disease progression. Significant associations with PFI or ST were found for administration of adjuvant therapy, presence of metastatic disease at the time of diagnosis, higher tumor stage (III or IV), increased tumor size (> 3 cm), and sexually intact female dogs. Administration of adjuvant treatment was associated with a 130% increased hazard (hazard ratio, 2.3; 95% confidence interval [CI], 1.0 to 5.0) of disease progression; the presence of metastases at the time of diagnosis was associated with a 281% increased hazard (hazard ratio, 3.8; 95% CI, 1.5 to 9.6) of death. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dogs with oral melanoma can have a long PFI and ST after resection with wide margins.

Inflammation, Apoptosis, and Necrosis Induced by Neoadjuvant Fas Ligand Gene Therapy Improves Survival of Dogs With Spontaneous Bone Cancer

Fas ligand (FasL) gene therapy for cancer has shown promise in rodents; however, its efficacy in higher mammals remains unknown. Here, we used intratumoral FasL gene therapy delivered in an adenovirus vector (Ad-FasL) as neoadjuvant to standard of care in 56 dogs with osteosarcoma. Tumors from treated dogs had greater inflammation, necrosis, apoptosis, and fibrosis at day 10 (amputation) compared to pretreatment biopsies or to tumors from dogs that did not receive Ad-FasL. Survival improvement was apparent in dogs with inflammation or lymphocyte-infiltration scores >1 (in a 3-point scale), as well as in dogs that had apoptosis scores in the top 50th percentile (determined by cleaved caspase-3). Survival was no different than that expected from standard of care alone in dogs with inflammation scores ≤1 or apoptosis scores in the bottom 50th percentile. Reduced Fas expression by tumor cells was associated with prognostically advantageous inflammation, and this was seen only in dogs that received Ad-FasL. Together, the data suggest that Ad-FasL gene therapy improves survival in a subset of large animals with naturally occurring tumors, and that at least in some tumor types like osteosarcoma, it is most effective when tumor cells fail to express Fas.Fas ligand (FasL) gene therapy for cancer has shown promise in rodents; however, its efficacy in higher mammals remains unknown. Here, we used intratumoral FasL gene therapy delivered in an adenovirus vector (Ad-FasL) as neoadjuvant to standard of care in 56 dogs with osteosarcoma. Tumors from treated dogs had greater inflammation, necrosis, apoptosis, and fibrosis at day 10 (amputation) compared to pretreatment biopsies or to tumors from dogs that did not receive Ad-FasL. Survival improvement was apparent in dogs with inflammation or lymphocyte-infiltration scores >1 (in a 3-point scale), as well as in dogs that had apoptosis scores in the top 50th percentile (determined by cleaved caspase-3). Survival was no different than that expected from standard of care alone in dogs with inflammation scores ≤1 or apoptosis scores in the bottom 50th percentile. Reduced Fas expression by tumor cells was associated with prognostically advantageous inflammation, and this was seen only in dogs that received Ad-FasL. Together, the data suggest that Ad-FasL gene therapy improves survival in a subset of large animals with naturally occurring tumors, and that at least in some tumor types like osteosarcoma, it is most effective when tumor cells fail to express Fas.

Increased Duration of Heating Boosts Local Drug Deposition during Radiofrequency Ablation in Combination with Thermally Sensitive Liposomes (ThermoDox) in a Porcine Model

Introduction Radiofrequency ablation (RFA) is used for the local treatment of liver cancer. RFA is effective for small (<3cm) tumors, but for tumors > 3 cm, there is a tendency to leave viable tumor cells in the margins or clefts of overlapping ablation zones. This increases the possibility of incomplete ablation or local recurrence. Lyso-Thermosensitive Liposomal Doxorubicin (LTLD), is a thermally sensitive liposomal doxorubicin formulation for intravenous administration, that rapidly releases its drug content when exposed to temperatures >40°C. When used with RFA, LTLD releases its doxorubicin in the vasculature around the zone of ablation-induced tumor cell necrosis, killing micrometastases in the ablation margin. This may reduce recurrence and be more effective than thermal ablation alone. Purpose The purpose of this study was to optimize the RFA procedure used in combination with LTLD to maximize the local deposition of doxorubicin in a swine liver model. Pigs were anaesthetized and the liver was surgically exposed. Each pig received a single, 50 mg/m2 dose of the clinical LTLD formulation (ThermoDox®). Subsequently, ablations were performed with either 1, 3 or 6 sequential, overlapping needle insertions in the left medial lobe with total ablation time of 15, 45 or 90 minutes respectively. Two different RFA generators and probes were evaluated. After the final ablation, the ablation zone (plus 3 cm margin) was dissected out and examined for doxorubicin concentration by LC/MS and fluorescence. Conclusion The mean Cmax of plasma total doxorubicin was 26.5 μg/ml at the end of the infusion. Overall, increased heat time from 15 to 45 to 90 minutes shows an increase in both the amount of doxorubicin deposited (up to ~100 μg/g) and the width of the ablation target margin to which doxorubicin is delivered as determined by tissue homogenization and LC/MS detection of doxorubicin and by fluorescent imaging of tissues.

Oesophageal leiomyosarcoma in dogs: surgical management and clinical outcome of four cases

Oesophageal leiomyosarcoma has yet to be reported in dogs. This retrospective case series describes the case management and clinical outcome of four dogs with oesophageal leiomyosarcoma treated by marginal excision alone. Histological features used to determine tumour grade included capsular invasion, percent necrosis, pleomorphism and mitotic rate. All tumours were designated grade 1 leiomyosarcoma. Excision of all grossly evident tumour tissue was achieved in two of the four cases; however, histopathologic evaluation showed tumour cells at the surgical margins in one of these two cases. Two dogs had grossly incomplete excision. Two dogs died from unrelated conditions, one 3 years and 5.5 months after surgery, the other at 65 days. One dog had persistent mega-oesophagus and was lost to follow-up 388 days after surgery and one dog is still alive (last follow-up 405 days after surgery). Despite large tumour size and incomplete excision, surgical removal of low-grade leiomyosarcomas can result in long-term resolution of clinical signs.

Results of surgical excision and evaluation of factors associated with survival time in dogs with lingual neoplasia: 97 cases (1995-2008)

OBJECTIVE To describe the clinical characteristics, treatments, outcomes, and factors associated with survival time in a cohort of dogs with lingual neoplasia that underwent surgical excision. DESIGN Retrospective case series. Animals-97 client-owned dogs. PROCEDURES Medical records of dogs with a lingual tumor examined between 1995 and 2008 were reviewed. Records were included if a lingual tumor was confirmed by histologic examination and surgical excision of the mass was attempted. Data were recorded and analyzed to identify prognostic factors. RESULTS Clinical signs were mostly related to the oral cavity. For 93 dogs, marginal excision, subtotal glossectomy, and near-total glossectomy were performed in 35 (38%), 55 (59%), and 3 (3%), respectively. Surgery-related complications were rare, but 27 (28%) dogs had tumor recurrence. The most common histopathologic diagnoses for the 97 dogs were squamous cell carcinoma (31 [32%]) and malignant melanoma (29 [30%]). Eighteen (19%) dogs developed metastatic disease, and the overall median survival time was 483 days. Median survival time was 216 days for dogs with squamous cell carcinoma and 241 days for dogs with malignant melanoma. Dogs with lingual tumors ≥ 2 cm in diameter at diagnosis had a significantly shorter survival time than did dogs with tumors < 2 cm. CONCLUSIONS AND CLINICAL RELEVANCE Similar to previous studies, results indicated that lingual tumors are most commonly malignant, and squamous cell carcinoma and malignant melanoma predominate. A thorough physical examination to identify lingual tumors at an early stage and surgical treatment after tumor identification are recommended because tumor size significantly affected survival time.