Jian-Zhong Zou

Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound.

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 x cm(-2) to 20,000 W x cm(-2), 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 homogeneous 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.

Extracorporeal High Intensity Focused Ultrasound Ablation in the Treatment of Patients with Large Hepatocellular Carcinoma

AbstractBackground: High intensity focused ultrasound (HIFU) is a noninvasive treatment modality that induces complete coagulative necrosis of a deep tumor through the intact skin. The current study was conducted to determine the safety, efficacy, and feasibility of extracorporeal HIFU in the treatment of patients with hepatocellular carcinoma (HCC). Methods: A total of 55 patients with HCC with cirrhosis were enrolled in this prospective, nonrandomized clinical trial. Among them, 51 patients had unresectable HCC. Tumor size ranged from 4 to 14 cm in diameter with mean diameter of 8.14 cm. According to tumor, node, metastasis (TNM) classification, 15 patients corresponded to stage II, 16 to stage IIIA, and 24 to IIIC. All patients had HIFU, and the median number of HIFU session was 1.69. Safety and efficacy of HIFU were assessed in this trial. Results: No severe side effect was observed in the patients treated with HIFU. Follow-up imaging showed an absence of tumor vascular supply and the shrinkage of treated lesions. Serum α-fetoprotein returned to normal level in 34% of patients. The overall survival rates at 6, 12, and 18 months were 86.1%, 61.5%, and 35.3%, respectively. The survival rates were significantly higher in patients in stage II than those in stage IIIA (P = .0132) and in stage IIIC (P = .0265). Conclusion: As a noninvasive therapy, HIFU appears to be effective, safe, and feasible in the treatment of patients with HCC. It may play an important role in the ablation of large tumors.

Tumor vessel destruction resulting from high-intensity focused ultrasound in patients with solid malignancies

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.

Extracorporeal high intensity focused ultrasound treatment for patients with breast cancer.

Purpose. To investigate the safety, efficacy and feasibility of using high-intensity focused ultrasound (HIFU) as a non-invasive treatment for patients with breast cancer.Patients and Methods. Twenty-two patients with breast cancer were enrolled into this non-randomized prospective trial. Disease TNM stage was classified as stage I in 4 patients, stage IIA in 9 patients, stage IIB in 8 patients, and stage IV in 1 patient. Tumor size ranged from 2 to 4.8 cm in diameter (mean 3.4 cm). All patients received chemotherapy, radiation and tamoxifen, following HIFU for the primary lesions. Outcome measures included radiological and pathologic assessment of the treated tumor, cosmesis, and local recurrence. A cumulative survival rate is calculated by using the Kaplan–Meier method.Results. No severe complications were encountered after HIFU. Post-operative imaging demonstrated positive response and regression of all treated lesions. Follow-up biopsy revealed coagulation necrosis of target tumor and subsequent replacement by fibroblastic tissue. After a median follow-up of 54.8 months, 1 patient died, 1 was lost to follow-up, and 20 were still alive. Two of 22 patients developed local recurrence. Five-year disease-free survival and recurrence-free survival were 95% and 89%, respectively. Cosmetic result was judged as good to excellent in 94% of patients.Conclusions. HIFU treatment is safe, effective, and feasible for patients with breast cancer. But, large-scale, multiple-center clinical trials will be needed to determine the future role of this novel modality.

Changes in biologic characteristics of breast cancer treated with high-intensity focused ultrasound.

Proliferation, invasion, immortalization and metastasis are the main malignant characteristics of cancer. Previous studies have shown that high-intensity focused ultrasound (US), or HIFU, can induce irreversible damage both to breast cancer cells and to tumor blood vessels. However, light microscopy alone may not always show this clearly. In this study, molecular biologic techniques were used to examine any changes in molecular markers associated with malignant behavior after exposure to HIFU. A total of 48 women with breast cancer were randomized to a control group (mastectomy) and a HIFU group (HIFU followed by mastectomy). Immunohistochemical staining, messenger RNA (mRNA) in situ hybridization and telomere-repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP-ELISA) techniques were used to detect tumor expression of proliferating cell nuclear antigen (PCNA), cell adhesion molecule CD44v6, matrix metalloproteinase-9 (MMP-9), erbB2 mRNA, and to measure telomerase activity in both groups. The results demonstrated that there were significant alterations in expression of PCNA, CD44v6, MMP-9, erbB2 mRNA, and a dramatic decrease in telomerase activity in the HIFU group. It is concluded that malignant tumor characteristics are arrested by HIFU, and that biologic factors are potential markers for assessing HIFU efficacy.

Use of high intensity focused ultrasound for treating malignant tumors

ObjectiveTo investigate the efficacy and side effects of high intensity focused ultrasound(HIFU) in the treatment of malignant solid tumors.MethodsThirty patients who refused surgery and/or were refractory to chemotherapy were treated by HIFU alone, with the efficacy and side effects monitored as follows: observation of vital organ signs; functional assay of important organs; imaging examinations including: digital subtraction angiography (DSA), CT, MRI, single photon emission computed tomography (SPECT), large core needle biopsy, complications and metastasis.ResultsAfter HIFU therapy, the vital signs remained stable and the functions of the heart, lung, kidney and liver were also normal. DSA images showed that small or larger arteries were not damaged. After a follow-up of 10–38 months(mean 23.1 months), 26 patients(87%) were alive. The volume of the tumor underwent complete regression in 10 patients. Shrinkage of the tumor volume 3≽50% was observed in 13 patients. Eight of 13 patients were examined by large core needle biopsy, all showing necrosis and /or fibrosis though3patients(10%) had local recurrence. Two of these were retreated again by HIFU and the locally recurrent tumors were controlled. New metastases developed in 5 patients after HIFU. Two patients suffered from peripheral nerve injuriy and they have recovered during the follow-up. One patient developed skin injury.ConclusionHigh intensity focused ultrasound is effective and safe in the treatment of malignant solid tumors.

High-Intensity Focused Ultrasound in the Treatment of Hepatic Metastases from Colorectal Cancer of 18 Patients

ObjectiveTo evaluate the safety and effectiveness of treatment of hepatic metastases from colorectal cancer using high-intensity focused ultrasound (HIFU).MethodsThirty-one lesions in 18 patients with hepatic metastases from colorectal cancer after colectomy were treated with HIFU therapy. The vital signs, function of the vital organs, complications and pathological outcome were studied using imaging examinations such as CT or MRI.ResultsThe vital signs of all patients remained stable and their liver and kidney functions normal. Two of the 18 patients were not followed-up. After a mean follow-up of 16.1 months (6–38 months), 13 survived. The survival rates at the 12th and 18th months were 83.3% and 66.7%, respectively. The median survival rate was 16 months. Among the 25 lesions followed-up, 17 shrank over 50%, 5 grew new metastases and superficial degree II skin injury occurred in 8.ConclusionHIFU is a safe, effective and non-invasive option for the treatment of hepatic metastases from colorectal cancer.