Characterizing the Ablative Effects of Histotripsy for Osteosarcoma: In Vivo Study in Dogs.

Osteosarcoma (OS) is a malignant bone tumor treated by limb amputation or limb salvage surgeries and chemotherapy. Histotripsy is a non-thermal, non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue. Recent ex vivo and in vivo pilot studies have demonstrated the ability of histotripsy for ablating OS but were limited in scope. This study expands on these initial findings to more fully characterize the effects of histotripsy for bone tumors, particularly in tumors with different compositions. A prototype 500 kHz histotripsy system was used to treat ten dogs with suspected OS at an intermediate treatment dose of 1000 pulses per location. One day after histotripsy, treated tumors were resected via limb amputation, and radiologic and histopathologic analyses were conducted to determine the effects of histotripsy for each patient. The results of this study demonstrated that histotripsy ablation is safe and feasible in canine patients with spontaneous OS, while offering new insights into the characteristics of the achieved ablation zone. More extensive tissue destruction was observed after histotripsy compared to that in previous reports, and radiographic changes in tumor size and contrast uptake following histotripsy were reported for the first time. Overall, this study significantly expands our understanding of histotripsy bone tumor ablation and informs future studies for this application.

Sternohyoideus-sternothyroideus muscle flap to reconstruct oronasal fistulas due to maxillary cancer in four dogs.

OBJECTIVE: To describe the repair of oronasal fistulas in dogs treated for maxillary cancer, with a novel sternohyoideus-sternothyroideus muscle flap, and to report the outcome. ANIMALS: Client-owned dogs (n = 4) with oronasal fistulas related to cancer. STUDY DESIGN: Short case series. METHODS: Maxillary defects were caused by tissue destruction by the tumor and tumor response to radiation therapy in two cases and a complication of caudal maxillectomy in two cases, one of which had neoadjuvant radiation therapy. All tumors were >4 cm at the level of the maxilla. Flaps were harvested by transecting the ipsilateral sternothyroideus and sternohyoideus muscles from their origin at the manubrium and costal cartilage. The muscles were rotated around the base of the cranial thyroid artery and tunneled subcutaneously in the neck and through an incision in the caudodorsal aspect of the oral cavity. The muscle flap was sutured to the edges of the oronasal fistula. RESULTS: The flap reached as far rostral as the level of the first premolar without tension. All dogs had clinical signs that improved postoperatively. All dogs had partial dehiscence of the flap. CONCLUSION: This flap was associated with a high rate of complications; however, all flaps were used in challenging cases. Clinical signs related to oronasal fistula were improved in all dogs in this case series.

Histotripsy Ablation of Spontaneously Occurring Canine Bone Tumors In Vivo.

OBJECTIVE: Osteosarcoma (OS) is a devastating primary bone tumor in dogs and humans with limited non-surgical treatment options. As the first completely non-invasive and non-thermal ablation technique, histotripsy has the potential to significantly improve the standard of care for patients with primary bone tumors. INTRODUCTION: Standard of care treatment for primary appendicular OS involves surgical resection via either limb amputation or limb-salvage surgery for suitable candidates. Biological similarities between canine and human OS make the dog an informative comparative oncology research model to advance treatment options for primary OS. Evaluating histotripsy for ablating spontaneous canine primary OS will build a foundation upon which histotripsy can be translated clinically into a standard of care therapy for canine and human OS. METHODS: Five dogs with suspected spontaneous OS were treated with a 500 kHz histotripsy system guided by real-time ultrasound image guidance. Spherical ablation volumes within each tumor (1.25-3 cm in diameter) were treated with single cycle histotripsy pulses applied at a pulse repetition frequency of 500 Hz and a dose of 500 pulses/point. RESULTS: Tumor ablation was successfully identified grossly and histologically within the targeted treatment regions of all subjects. Histotripsy treatments were well-tolerated amongst all patients with no significant clinical adverse effects. Conclusion & Significance: Histotripsy safely and effectively ablated the targeted treatment volumes in all subjects, demonstrating its potential to serve as a non-invasive treatment modality for primary bone tumors.

Long-term postoperative effects of administration of allogeneic blood products in 104 dogs with hemangiosarcoma.

OBJECTIVE: To determine the influence of administering allogeneic blood products (ABP) on the progression of hemangiosarcoma in dogs. STUDY DESIGN: Multi-institutional, retrospective study. SAMPLE POPULATION: One hundred four dogs with hemangiosarcoma that survived until postoperative discharge from the hospital. METHODS: Medical records of dogs that had been operated on for hemoangiosarcoma were reviewed for signalment, presence of a hemoabdomen, presence of metastatic disease, and whether the dog had received chemotherapy or Yunnan Baiyao. Data that were collected were compared between dogs that received perioperative ABP and those that did not. Disease-free interval was compared between groups. The Kaplan-Meier method was used to obtain univariate descriptive statistics for time to clinical decline. A multivariable Cox regression model was used to analyze association or effect of potential predictor variables. RESULTS: The median disease-free interval (DFI) was shorter in the 67 dogs that received a blood transfusion (76 days; range, 1-836) than in the 37 dogs that did not receive a blood transfusion (120 days; range, 38-916). According to the multivariable Cox regression model, administration of blood products (P = .04) and the presence of gross metastatic disease at the time of surgery (P < .01) shortened the DFI, whereas administration of Yunnan Baiyao (P = .01) prolonged the DFI. CONCLUSION: Allogeneic blood product administration was associated with a shorter disease-free interval in this population. However, we could not demonstrate the association between blood products and shorter DFI because of confounding factors. CLINICAL SIGNIFICANCE: Dogs that receive ABP at the time of surgical therapy for hemangiosarcoma may have accelerated disease progression compared with dogs that do not receive ABP.