BERKELEY, CA (UroToday.com) - Ultrasound has been used as a real-time diagnostic modality in healthcare for years because of its non-ionization, non-invasiveness, and low cost.
In the past decade, with the development of modern image guidance, ultrasound transducer and electronic control, as well as the further understanding of ultrasound-induced bio-effects, therapeutic ultrasound has become feasible in clinics and has rapidly gained popularity. High-intensity focused ultrasound (HIFU), one of the “hot” topics in ultrasound therapy, can focus acoustic energy non-invasively in the human body, to a small tissue volume and is able to raise the temperature over 65 °C within seconds. As a result, tissue protein can be denatured, forming irreversible coagulative thermal necrosis. Over 100,000 cases, including the pancreas, liver, prostate, breast, uterine fibroids and soft-tissue sarcomas, have been carried out with great success, mostly in Asia and Europe. In comparison to conventional cancer treatment modalities such as open surgery, radio- and chemo-therapy, fewer complications were observed after HIFU ablation. In this paper, the fundamental principle of HIFU ablation (thermal and mechanical effects), systematic structure of commercial HIFU devices (i.e., extracorporeal and transrectal type), and clinical outcomes for applicable cancers are reviewed. Recommendations for a satisfactory HIFU treatment according to clinical experiences are summarized for the operator, so are current technical and clinical challenges for engineers and physicians.
Specifically, transrectal HIFU treatment of prostate tumors is one of the pilot investigations. Both benign prostate hyperplasia (BPH) and prostate carcinoma have been targeted - mostly at university medical centers in Japan and Europe. Initial clinical trials for BPH treatment were encouraging, with an increase in flow rate and decreases in post-void residual volume. However, the long-term results were disappointing, about half of patients requiring a salvage transurethral resection of the prostate (TURP) within 4 years. Therefore, HIFU has no proved significant benefits over the “gold standard,” TURP, and is not recommended for BPH treatment in EAU guidelines. In contrast, the trial on prostate cancer is more promising, especially for the whole ablated gland. Recently, control rates for the treated tumor can be up to 90%. Mid-term follow-up (2-5 years) has shown that prostate specific antigen (PSA) levels remain low and that the negative biopsy rate remains around 90%. In total, about 60% to 80% of patients can be disease-free at repeated biopsy and show a reduction of serum PSA values to less than 4 ng/mL. Whole-gland treatment also resulted in a reduced incidence of recurrent tumor. Even in patients not found to be disease-free, greater than 90% reduction in tumor volume was found. Complications after prostate HIFU treatment include urinary retention, incontinence, urinary infection, impotence, chronic pain, rectal anal fistulas, and incomplete treatment of disease. Repeat treatment with HIFU is associated with much higher complication rates than single treatments. Prostate HIFU seems most appropriate in men older than 65 years, those who are not candidates for surgery, and those who are obese.
Furthermore, HIFU-related other tumor therapy methods are discussed.
- In clinical trials it is found that HIFU exposure may enhance tumor immunogenicity and subsequently augment the host anti-tumor immune response. Although the mechanisms behind this phenomenon remain unknown, it is conceivable that HIFU ablation may induce massive tumor cell death and/or necrosis, which could lead to the release of tumor antigens to stimulate the immune system. These changes may ultimately enhance the immune function of tumor-bearing patients and improve their prognosis.
- HIFU has also been used to interrupt blood flow to produce infarction and necrosis of the perfusion tissue. The renal artery branches of rabbits (diameter about 0.6 mm) were occluded by HIFU. Complete cessation of blood flow was observed by color Doppler imaging and MRI, and lack of perfusion was also observed in the renal cortex in the contrast-enhanced image.
- Histotripsy was developed to produce fragmentation of tissue to a sub-cellular level surrounded by an almost imperceptibly narrow margin of cellular injury, resulting in a liquefied core with sharply demarcated mechanical fractionation of tissue structure using the effect of bubble-ultrasound interaction. Animal experiments of histotripsy on BPH and kidney are being performed.
The development direction of modern medical treatments and techniques is the minimization of intervention to the patient and reduction in the length of hospital stay. HIFU is the least invasive approach among available thermal ablation therapies and is being increasingly used for limited applications in Asia and Europe. However, further random multi-center studies are necessary before the widespread use of HIFU can be recommended. Long-term medical benefit as well as the economic impact for oncology is of both clinical and social importance.
Another barrier of wide acceptance and application of HIFU technology in the USA is the reimbursement policy of healthcare insurance. Despite that, patients opt to go to Canada and Mexico to undergo HIFU treatment for their prostate cancers despite out-of-pocket cost. Altogether, with the better understanding of HIFU-induced bio-effects, advances in HIFU technology, release of calibration standards for HIFU system from US FDA, and the issue of healthcare reimbursement, the versatility of HIFU will increase and its range of applicability will expand.
Yufeng Zhou, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.