Figure. Porcine kidney after histotripsy immediately post treatment (coronal, A; axial, B), day 7 (coronal, C; axial, D), and day 28 (coronal, E; axial, F) demonstrating immediate hypoenhancement with subsequent treatment involution. Arrows show the ablation zone evolution with time. POD indicates postoperative day.

Introduction

Kidney cancer is the 10th most prevalent cancer in the US with estimates projecting 81,610 cases to be diagnosed in 2024.1 With the increased detection of incidentally discovered small renal masses, there has been greater emphasis on management with minimally invasive treatment and nephron-sparing surgery. Although partial nephrectomy remains the gold standard for the management of small renal tumors, over the past 15 years there has been increased adoption of noninvasive focal ablative therapies, particularly for patients who may not be surgical candidates.^2,3 These focal therapies have their own unique limitations, including the lack of visualization of the ablation effect in real time, influence of heat-sink effect, the degree of invasiveness, and the variability in local recurrence-free survival.^2,4,5 Histotripsy is a novel noninvasive, nonionizing, mechanically based treatment modality with real-time visualization of treatment effect which has shown promise in the management of other solid organ malignancies.⁶ In this case study, we present images from a porcine animal model to highlight the radiographic evidence of initial tissue destruction and involution after treatment with histotripsy.

Case Report

As the current US-based #Hope4kidney trial is ongoing, we present here representative images of porcine renal histotripsy from collaborators Knott et al⁷ to highlight the radiographic changes noted on axial imaging. As part of the #Hope4kidney study protocol, patients with solitary nonmetastatic renal lesions undergo biopsy to confirm diagnosis. Once an acoustically safe window that entirely encompasses the lesion is determined, the patient can undergo therapy.

Here, as stated previously, we present radiographic images after porcine renal histotripsy. The procedure was performed under general anesthesia. Diagnostic ultrasound imaging was used for procedure planning, targeting, and real-time tissue effect feedback to the clinician. A preoperative planning tool was used to simulate subject positioning and energy required for adequate tissue treatment. The porcine renal unit underwent simulated treatment for a 2.5-cm spherical treatment volume. Mean ablation time was approximately 26 minutes and no immediate postoperative complications were reported. The Figure highlights the acute post treatment, day 7, and day 28 CT imaging, with the posttreatment scan highlighting a lack of enhancement at the treatment site. Most notably, there is a marked decrease in the size of the ablation zone by day 28. In addition, there is complete resolution of the injury zone surrounding the targeted treatment volume. While not illustrated here, Knott et al⁷ performed necropsy which additionally demonstrated ablation zone involution and sharply demarcated margin between treated and untreated tissue.

Discussion

Histotripsy involves the delivery of extremely high amplitude, short pulses of ultrasound energy to produce bubbles confined to the targeted focus that result in nonthermal mechanical fractionation of targeted tissues.⁸ This mechanism offers several advantages over existing ablative therapies, including avoidance of thermal energy associated with collateral thermal injury and heat-sink effect, superior precision of ablation with less than 100 microns of transition between treatment to untreated areas, and real-time ultrasound image guidance capability utilizing B-mode ultrasound.⁸ Histotripsy was recently approved by the US Food and Drug Administration for the treatment of solid organ malignancies in the liver.⁹ This report highlights the feasibility of histotripsy in the management of small renal masses and is the basis of the UK-based CAIN trial and an ongoing clinical trial in the US (#Hope4kidney, NCT05820087) looking to provide further evidence for its use in the management of small renal masses.

Inclusion criteria include solitary, nonmetastatic, biopsy-proven, primarily solid renal lesions less than or equal to 3 cm in patients over the age of 22 without prior locoregional therapy for the target lesion.