Histotripsy ablation for the treatment of feline injection site sarcomas: a first-in-cat in vivo feasibility study.

PURPOSE: Feline soft tissue sarcoma (STS) and injection site sarcoma (fISS) are rapidly growing tumors with low metastatic potential, but locally aggressive behavior. Histotripsy is a non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue. In this study, we investigated the in vivo safety and feasibility of histotripsy to treat fISS using a custom 1 MHz transducer. MATERIALS AND METHODS: Three cats with naturally-occurring STS were treated with histotripsy before surgical removal of the tumor 3 to 6 days later. Gross and histological analyses were used to characterize the ablation efficacy of the treatment, and routine immunohistochemistry and batched cytokine analysis were used to investigate the acute immunological effects of histotripsy. RESULTS: Results showed that histotripsy ablation was achievable and well-tolerated in all three cats. Precise cavitation bubble clouds were generated in all patients, and hematoxylin & eosin stained tissues revealed ablative damage in targeted regions. Immunohistochemical results identified an increase in IBA-1 positive cells in treated tissues, and no significant changes in cytokine concentrations were identified post-treatment. CONCLUSIONS: Overall, the results of this study demonstrate the safety and feasibility of histotripsy to target and ablate superficial feline STS and fISS tumors and guide the clinical development of histotripsy devices for this application.

Mechanical High-Intensity Focused Ultrasound (Histotripsy) in Dogs With Spontaneously Occurring Soft Tissue Sarcomas.

INTRODUCTION: Histotripsy is a non-invasive focused ultrasound therapy that uses controlled acoustic cavitation to mechanically disintegrate tissue. To date, there are no reports investigating histotripsy for the treatment of soft tissue sarcoma (STS). OBJECTIVE: This study aimed to investigate the in vivo feasibility of ablating STS with histotripsy and to characterize the impact of partial histotripsy ablation on the acute immunologic response in canine patients with spontaneous STS. METHODS: A custom 500 kHz histotripsy system was used to treat ten dogs with naturally occurring STS. Four to six days after histotripsy, tumors were surgically resected. Safety was determined by monitoring vital signs during treatment and post-treatment physical examinations, routine lab work, and owners' reports. Ablation was characterized using radiologic and histopathologic analyses. Systemic immunological impact was evaluated by measuring changes in cytokine concentrations, and tumor microenvironment changes were evaluated by characterizing changes in infiltration with tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) using multiplex immunohistochemistry and differential gene expression. RESULTS: Results showed histotripsy ablation was achievable and well-tolerated in all ten dogs. Immunological results showed histotripsy induced pro-inflammatory changes in the tumor microenvironment. Conclusion & Significance: Overall, this study demonstrates histotripsy's potential as a precise, non-invasive treatment for STS.

Use of imaging-guided intensity-modulated stereotactic body radiation therapy to treat a well-differentiated hepatocellular carcinoma in a dog.

CASE DESCRIPTION: A 14-year-old 5.6-kg (12.3-lb) castrated male Toy Poodle was evaluated because of high serum activities of alkaline phosphatase and alanine aminotransferase and the presence of a hepatic mass. CLINICAL FINDINGS: Abdominal CT revealed a large (approx 6.8 × 7.1 × 6.5-cm) soft tissue mass along the midline of the liver. The mass either originated from the papillary process of the caudate lobe or the left medial liver lobe. TREATMENT AND OUTCOME: A partial liver lobectomy was performed, and approximately a third of the mass was successfully removed and submitted for histologic examination. Consultation with the oncology service was advised to determine whether radiation therapy could be used to treat the residual disease. On 5 consecutive days, the dog underwent imaging-guided intensity-modulated radiotherapy-stereotactic body radiation therapy (4 Gy/treatment) with a simultaneous integrated boost to the center of the tumor. The dog received a base dose of 20 Gy that was then boosted to 28 Gy. In the 10-month period after completion of radiation therapy, the hepatocellular mass continued to decrease in size, and overall improvements in the dog's serum liver enzyme abnormalities were evident. CLINICAL RELEVANCE: There are few treatment options for dogs with incompletely excised hepatocellular carcinomas. On the basis of the positive outcome in this case, radiation therapy could be useful following incomplete surgical removal of hepatocellular carcinomas in dogs.

Developing zebrafish models relevant to PTSD and other trauma- and stressor-related disorders.

While post-traumatic stress disorder (PTSD) and other trauma- and stress-related disorders (TSRDs) represent a serious societal and public health concern, their pathogenesis is largely unknown. Given the clinical complexity of TSRD development and susceptibility, greater investigation into candidate biomarkers and specific genetic pathways implicated in both risk and resilience to trauma becomes critical. In line with this, numerous animal models have been extensively used to better understand the pathogenic mechanisms of PTSD and related TSRD. Here, we discuss the rapidly increasing potential of zebrafish as models of these disorders, and how their use may aid researchers in uncovering novel treatments and therapies in this field.

Developing 'integrative' zebrafish models of behavioral and metabolic disorders.

Recently, the pathophysiological overlap between metabolic and mental disorders has received increased recognition. Zebrafish (Danio rerio) are rapidly becoming a popular model organism for translational biomedical research due to their genetic tractability, low cost, quick reproductive cycle, and ease of behavioral, pharmacological or genetic manipulation. High homology to mammalian physiology and the availability of well-developed assays also make the zebrafish an attractive organism for studying human disorders. Zebrafish neurobehavioral and endocrine phenotypes show promise for the use of zebrafish in studies of stress, obesity and related behavioral and metabolic disorders. Here, we discuss the parallels between zebrafish and other model species in stress and obesity physiology, as well as outline the available zebrafish models of weight gain, metabolic deficits, feeding, stress, anxiety and related behavioral disorders. Overall, zebrafish demonstrate a strong potential for modeling human behavioral and metabolic disorders, and their comorbidity.