Introduction to a special issue of the International Journal of Hyperthermia: “the status and prospects of the clinical applications of high intensity focused ultrasound”

We are fortunate to live in a period of accelerated technological advancement and to be able to enjoy the benefits this brings. At the same time, we are fortunate to be directly involved in this technology revolution and to be able to use our work to bring changes to the world we live in.

High intensity focused ultrasound (HIFU) is a revolutionary piece of technology. The principle of HIFU treatment involves using ultrasound’s ability to penetrate human skin and organs without harming these structures in the process. The ultrasound beams are generated outside of the human body and can be converted from mechanical energy to thermal energy, ultimately targeting a specific part of a tumor inside the human body, achieving noninvasive treatment. In the 1940s, Lynn et al. first brought up the concept of HIFU [1]. Then in the 1950s, Fry was the first to experimentally prove the use of HIFU generated outside the body to achieve thermal ablation on a lesion inside the body [2]. However, at the time, real-time monitoring technology was still primitive, so HIFU techniques did not start developing until the 1980s, when radiographic techniques started improving and HIFU gained more attention from the world. After 10 years of basic science research, HIFU was first used in a clinical research setting in 1997, which started a new wave of studies on HIFU [3]. As of now, this technology has been used to successfully treat solid tumors and benign diseases of certain organs. According to the Focused Ultrasound Foundation, HIFU is suitable in the treatment of more than 100 conditions. In order to better elucidate the current breadth of HIFU treatment, 14 well-known experts of ultrasound-guided tumor ablation were invited to contribute their reviews and research for this special issue.

As an experienced obstetrics-gynecologist, Dr. Lee Keen Whye of Singapore, in the article ‘The Asian perspective on HIFU’, recounted his experience from open surgery to minimally invasive surgery to noninvasive virtual surgery [4]. In the article, he stated: ‘in my lifetime, I am lucky to have witnessed the transformation, revolution and subversion of the foundational knowledge related to obstetrics and gynecology surgical treatments.’ He believes that HIFU has allowed us to achieve the fundamental principle of surgery: minimizing pain, side effects, and harm to the diseased organ, and protecting the human body to the best of our ability. He also indicates that his colleagues who are also experienced in minimally invasive surgery share his sentiments.

Uterine fibroids are the most common subject of study for HIFU ablation. Many studies have supported the safety and efficacy of HIFU for treatment of uterine fibroids [5–8]. One important issue that has received a lot of attention is whether HIFU can be a viable treatment option for patients with uterine fibroids who desire to conceive. Because HIFU can accurately ablate tumors while only minimally affecting the surrounding structures around the tumor, a HIFU treatment can, on a large scale, prevent damage to normal uterine smooth muscle. This can help shorten the expected time required to conceive and may reduce the likelihood of complications. Indeed, there are publications showing that post-HIFU patients did not experience complications such as uterine rupture during pregnancy and childbirth [9,10]. However, a study from China found a high rate of Cesarean sections [9]. In comparison, a study by Rodriguez in this special issue showed that after HIFU, patients had an average pregnancy length of 8 months, with a 60% vaginal birth rate [11]. Therefore, China’s high rate of C-sections could be due to social factors.

Wang et al. did a preliminary study and found that broad ligament fibroids can be treated with HIFU [12]. Xu et al. performed a meta-analysis comparing the efficacy of HIFU, UAE and myomectomy on uterine uterine fibroids; they found that all three treatment options can safely treat uterine fibroids. In this study, HIFU was found to have the least complications but required a higher re-intervention rate compared to the other two techniques. In a comparison between MR-guided HIFU (MRgHIFU) and ultrasound-guided HIFU (USgHIFU), MRgHIFU-treated fibroids had a higher re-intervention rate compared to USgHIFU-treated ones [13]. This may have occurred because the MRgHIFU uterine fibroid ablation rate is lower than that of USgHIFU. Dr. Marinova of Germany has also confirmed this finding [14]. HIFU is now in clinical practice in China; more than 10,000 patients per year with uterine fibroids are treated using HIFU.

Another commonly-debated topic around HIFU treatment of uterine fibroids is post-treatment pathological diagnosis. Since HIFU is a noninvasive procedure, a pathological diagnosis cannot be made. It is important to determine how we can prevent mistaking a uterine sarcoma for a uterine fibroid. Does misdiagnosis and treatment of a lesion thought to be a uterine fibroid with HIFU lead to disastrous results? Wang et al. performed a retrospective study with a total of 15,759 patients, taking a decade of HIFU treatments into consideration [15]. The study examined records from 10 hospitals dating from 2008 to 2019 and found that pre-operative MRI plays an important role in distinguishing sarcomas from fibroids. Even if a misdiagnosis occurred, however, treating sarcoma patients with HIFU did not lead to worse outcomes compared to patients who were found to have a sarcoma and underwent open surgery.

Bone tumors were an early topic for HIFU treatment. Previous studies showed that the effect of HIFU treatment on primary bone tumors in the limbs is the same as that of limb salvage surgery [16–18]. Also, for painful metastatic bone cancer, especially in patients who failed radiotherapy, chemotherapy and biotherapy, HIFU has been shown to have a significant palliative effect [18]. In recent years, investigators around the world have examined the use of HIFU for the treatment of osteoarthritis [19,20]. This topic is worth a read and can be further explored.

Liver cancer was also one of HIFU’s earliest subjects of study. Of note is the fact that HIFU has a special role in the treatment of liver cancer, in that it can effectively ablate liver cancer lesions anatomically close to structures such as large blood vessels, the gallbladder, and the diaphragm without damaging these structures [21,22]. An article from Hong Kong in this special issue discusses the advantages of using HIFU in treating liver pathology in anatomically challenging locations [23].

Since the pancreas is a retroperitoneal organ, pancreatic cancer can have an insidious onset. By the time of diagnosis, 80% of patients are non-operable with a poor prognosis. HIFU treatment of pancreatic cancer has a 20-year history already. Previous studies showed that in 85 % of HIFU treated patients with late-stage pancreatic cancer, long-lasting pain relief was achieved. The median overall survival and progression-free survival were 16.2 and 16.9 months from diagnosis and 8.3 and 6.8 months from intervention [24,25]. HIFU can prolong patient survival and improve quality of life. For borderline pancreatic cancers, HIFU can lower tumor grade, which can give the patients an opportunity to participate in radical surgery. Articles from Germany and Bulgaria in this special issue present recent findings in regards to HIFU treatment of pancreatic cancer [26,27].

Clinical investigators at the University of Oxford in England started clinical research with HIFU in 2002. They are especially experienced in treating kidney cancer [28]. Prachee et al. share Oxford’s experience in using HIFU in treatment of different solid tumors [29].

In recent years, different teams have been expanding HIFU’s range of treatment indications. Zhang et al. from Chongqing reported a study with the largest sample size to date for HIFU treatment of desmoid tumors [30]. Since desmoid tumors cannot be fully excised with surgery, they can easily relapse. However, this type of lesion is sensitive to HIFU, so there is great potential in using HIFU to treat desmoid tumors.

Likewise, Lei et al. are studying HIFU for treatment of ovarian cancer recurrence. They showed that HIFU has potential in treating recurrent ovarian cancer and is worth further study [31]. They discuss whether combining HIFU with other treatments can benefit patients with this cancer. Focused ultrasound can also be used to treat cervical and vulvar diseases [32,33]. Wang et al. used a combination of focused ultrasound treatment and Interferon to treat HPV infections [34]. They discovered that focused ultrasound significantly increases HPV clearance, which deserves further studies.

In the past year, the whole world has been going through a difficult time period. During this time, three of our invited authors contracted COVID-19. Thus, it is with great sadness that we announce the passing of Professor Suindyk Imankulov of Kazakhstan from complications of COVID-19. He was unable to complete his paper. Professor Imankulov pioneered work in the clinical applications of HIFU, such as his impressive work in HIFU treatment of hepatic hydatid disease [35]. Hydatid disease, also known as alveococcosis, is caused by parasitic infection of the liver by the helminth Alveococcus multilocaris [36]. The primary infected node in the liver can spread regionally or to other distant organs such as the lung and brain. Surgical resection is the only therapeutic option and this can only be done in 25% of cases. The use of HIFU in treating this disease prevented a series of problems that could have otherwise occurred in open surgery. Six months after HIFU treatment, MRI showed that the hepatic hydatid disease lesion shrunk significantly. It is regrettable that we will not be able to see his continued work in this realm, but the work that he has done has created a solid foundation that can be further explored in the future.

Because of the limited amount of articles, there are many other indications that could not be included in this issue. However we hope that with this special issue, we can give readers an insight into the unique clinical applications of HIFU. HIFU is an emerging technology that can continue to benefit patients as technology continues to improve. As can be seen, people engaged in the research and development and application of HIFU technology have already changed the world through hard work. We think we should be proud of the work being done in this emerging field.

Lastly, we would like thank the International Society of Minimally Invasive and Virtual Surgery (ISMIVS) for partially supporting this Special Issue. ISMIVS was founded in 2013 and envisions accelerating progress in minimally invasive and noninvasive medicine. With the help of the ISMIVS, we were able to include more articles in this special issue and show the readers more clinical applications of this technique. We hope to continue cooperating with ISMIVS in the future to promote the development of minimally invasive and noninvasive medicine through research, education, and international collaboration.

Wendy Zhang
Department of Radiology, Zucker School of Medicine at Hofstra Northwell, Staten Island University Hospital, Staten Island, NY, USA

Lian Zhang
Chongqing Haifu Hospital, Chongqing, China
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China

Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, China
[email protected]

Disclosure statement

No potential conflict of interest was reported by the author(s).