General Clinical Reviews

British Journal of Cancer (2005); 93 890-895.

High-intensity focused ultrasound (HIFU) provides a potential noninvasive alternative to conventional therapies. We report our preliminary experience from clinical trials designed to evaluate the safety and feasibility of a novel, extracorporeal HIFU device for the treatment of liver and kidney tumours in a Western population. The extracorporeal, ultrasound-guided Model-JC Tumor Therapy System (HAIFUÔ Technology Company, China) has been used to treat 30 patients according to four trial protocols. Patients with hepatic or renal tumours underwent a single therapeutic HIFU session under general anaesthesia. Magnetic resonance imaging 12 days after treatment provided assessment of response. The patients were subdivided into those followed up with further imaging alone or those undergoing surgical resection of their tumours, which enabled both radiological and histological assessment. HIFU exposure resulted in discrete zones of ablation in 25 of 27 evaluable patients (93%). Ablation of liver tumours was achieved more consistently than for kidney tumours (100 vs 67%, assessed radiologically). The adverse event profile was favourable when compared to more invasive techniques. HIFU treatment of liver and kidney tumours in a Western population is both safe and feasible. These findings have significant implications for future noninvasive image-guided tumour ablation.

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Ultrasound Med Biol; 30(9):1217-22.

T cell-mediated immune responses represent the main cellular antitumor immunity in cancer patients. Recent studies have shown that that both surgical procedure and radiation therapy could cause the functional suppression of lymphocyte-mediated cellular immunity. The purpose of current study is to evaluate whether high intensity focused ultrasound (HIFU) might change a systemic antitumor immunity, particularly T lymphocyte-mediated immunity in cancer patients. A total of 16 patients with solid malignancies were treated with HIFU. Among them, six patients had osteosarcoma (Enneking stage, II(B)4, III(B) 2), five had hepatocellular carcinoma (TNM stage, III 3, IV 2), and five had renal cell carcinoma (TNM stage, III 2, IV 3). Using flow cytometry technique, T lymphocyte and subset, B lymphocyte and natural killer cell (NK) in the peripheral blood were measured in these patients on the day before HIFU and 7 to 10 d after HIFU. The statistical significance of any observed difference is evaluated by Student's t-test. The results showed a significance increase in the population of CD4(+) lymphocytes (p < 0.01) and the ratio of CD4(+) /CD8(+) (p < 0.05) in the circulation of cancer patients after HIFU treatment. The abnormal levels of CD3(+) lymphocytes returned toward the normal range in two patients, CD4(+)/CD8(+) ratio in 3, CD19(+) lymphocytes in one and cytotoxic NK in one, respectively, in comparison to control values. It is concluded that HIFU could enhance a systemic antitumor cellular immunity in addition to local tumor destruction in patients with solid malignancies.

Ultrasound Med Biol; 30(4): 511 517.

Abstract The theoretical possibility that exposure of a solid malignancy to high-intensity focused ultrasound (US), or HIFU, could lead to an increased rate of metastasis still remains. Using reverse transcriptase polymerase chain reaction (RT-PCR), the potential risk of hematogenous dissemination was assessed in HIFU-treated patients with solid malignancy. RT-PCR can demonstrate the presence or absence of specific RNA fragments. On the day before HIFU ablation, 5-mL peripheral blood samples were collected, and again 5 to 7 days after HIFU, from 26 enrolled patients (hepatocellular carcinoma, HCC: 10; osteosarcoma: 16). Total RNA was isolated and RT-PCR was performed to analyze the mRNA expression of (_-fetoprotein (AFP) and bone-specific alkaline phosphatase (BALP) genes. Positive AFP mRNA expression was preoperatively detected in 8 of 10 patients with HCC. In the postoperative specimens, positive expression was also detected in 8 of 10 patients. In 2 patients, circulating tumor cells were found preoperatively, but not postoperatively. Conversely, 2 patients with no circulating tumor cells preoperatively were found to have circulating tumor cells after HIFU. Of 16 osteosarcoma patients, 12 patients had circulating tumor cells and 4 had none. After HIFU treatment, 2 of the 12 patients had converted from presence to absence of circulating cells and the remaining 4 patients remained negative. It is concluded that patients undergoing complete HIFU ablation may demonstrate conversion from presence to absence of circulating tumor-specific marker mRNA, and that HIFU would not enhance the potential risk of metastasis in patients with malignant diseases.

Ultrasound Med Biol 30(2): 245-60

The objective of this article is to introduce the early Chinese clinical experience of using extracorporeal focused ultrasound (US) surgery (FUS) for the treatment of solid tumors. From December 1997 to October 2001, a total of 1038 patients with solid tumors underwent FUS ablation in 10 Chinese hospitals. The tumors included primary and metastatic liver cancer, malignant bone tumors, breast cancer, soft tissue sarcomas, kidney cancer, pancreatic cancer, abdominal and pelvic malignant tumors, uterine myoma, benign breast tumors, hepatic hemangioma and other solid tumors. In this article, pathologic changes in tumors treated with FUS, real-time diagnostic imaging for targeting, monitoring and assessment of results by follow-up images are presented. Early clinical results and complications of the technique are also reported.

Ultrasound Med Biol; 28(4):535 542.

Abstract The purpose of this study was to explore the sequential imaging and histologic alterations of tumor blood vessels in the patient with solid malignancies after extracorporeal treatment of high-intensity focused ultrasound (HIFU). A total of 164 patients underwent extracorporeal HIFU ablation of malignant solid tumors. After HIFU treatment, enhanced magnetic resonance imaging (MRI), color Doppler ultrasound (US) imaging, dynamic radionuclide scanning, digital subtraction angiography, and histologic study were performed to monitor the response of tumor vessels to HIFU ablation. Compared with tumor images in the patients before HIFU, clinical images showed an abrupt interruption, followed by the cessation of blood flow within the tumor vessels after HIFU treatment. The histologic examination indicated that not only the treated tumor cells showed coagulative necrosis, but also small tumor vessels were severely damaged by the HIFU treatment. The results strongly imply that the damaged tumor vessels might play a critical role in secondary tumor cell death, and then indirectly strengthen the destructive force of focused US beams on tumor tissue. It is concluded that tumor vessel damage can be induced by HIFU, which may be a promising strategy in the treatment of patients with solid malignancies.

Ultrasound Med Biol; 27(8):1099 1106.

Abstract The purpose of this study was to investigate the pathologic changes of extracorporeal ablation of human malignant tumors with high-intensity focused ultrasound (HIFU). HIFU treatment was performed in the 164 patients with liver cancer, breast cancer, malignant bone tumor, soft tissue sarcoma and other malignant tumors at focal peak intensities from 5000 W cm22 to 20,000 W cm22, with operating frequencies of 0.8 to 3.2 MHz. To explore the pathologic impact of extracorporeal HIFU, 30 patients with malignant carcinoma underwent surgical removal after HIFU treatment. Pathologic findings showed that the treated tissues demonstrated homogenous coagulative necrosis with an irreversible tumor cell death and severe damage to tumor blood vessels at the level of microsvasculature within the HIFU-targeted region. Thermolesions to intervening tissue were never observed. The treated region had a sharp border comprising only several cell layers between the treated and untreated areas. The repair of lesions had the processes of necrotic tissue absorption and granulation tissue replacement. It is concluded that extracorporeal treatment of human solid malignancies with HIFU could be safe, effective and feasible. As a noninvasive therapy, HIFU would be used clinically to treat patients with solid malignancies.