Hui Zhu

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.

Feasibility of magnetic resonance imaging-guided high intensity focused ultrasound therapy for ablating uterine fibroids in patients with bowel lies anterior to uterus

PURPOSE To prospectively evaluate the feasibility of magnetic resonance (MR) imaging-guided high intensity focused ultrasound (HIFU) therapeutic ablation of uterine fibroids in patients with bowel lies anterior to uterus. MATERIALS AND METHODS Twenty-one patients with 23 uterine fibroids underwent MR imaging-guided high intensity focused ultrasound treatment, with a mean age of 39.4+/-6.9 (20-49) years, with fibroids average measuring 6.0+/-1.6 (range, 2.9-9.5)cm in diameter. After being compressed with a degassed water balloon on abdominal wall, MR imaging-guided high intensity focused ultrasound treatment was performed under conscious sedation by using fentanyl and midazolam. This procedure was performed by a Haifu JM focused ultrasound tumour therapeutic system (JM2.5C, Chongqing Haifu Technology Co., Ltd., China), in combination with a 1.5-Tesla MRI system (Symphony, Siemens, Germany), which provides real-time guidance and control. Contrast-enhanced MR imaging was performed to evaluate the efficacy of thermal ablation immediately and 3 months after HIFU treatment. The treatment time and adverse events were recorded. RESULTS The mean fibroid volume was 97.0+/-78.3 (range, 12.7-318.3)cm(3). According to the treatment plan, an average 75.0+/-11.4% (range, 37.8-92.4%) of the fibroid volume was treated. The mean fibroid volume immediately after HIFU was 109.7+/-93.1 (range, 11.9-389.6)cm(3), slightly enlarged because of edema. The average non-perfused volume was 83.3+/-71.7 (range, 7.7-282.9)cm(3), the average fractional ablation, which was defined as non-perfused volume divided by the fibroid volume immediately after HIFU treatment, was 76.9+/-18.7% (range, 21.0-97.0%). There were no statistically significant differences between the treatment volume and the non-perfused volume. Follow-up magnetic resonance imaging (MRI) at 3 months obtained in 12 patients, the fibroid volume decreased by 31.4+/-29.3% (range, -1.9 to 60.0%) in average, with paired t-test showing a statistically significant reduction (P=0.002). The mean treatment time for ablating the average 83.3+/-71.7 (range, 7.7-282.9)cm(3) of fibroid volume was 2.5+/-1.4h (range, 27-390min) in this study, which was relatively short and acceptable to patient and therapist. Four patients experienced mild skin burn (two with skin redness, two with blisters), the skin burn subsided within approximately 2 days. No other adverse events were observed. CONCLUSIONS After the bowel was compressed with a degassed water balloon, MR imaging-guided high intensity focused ultrasound treatment is safe and feasible in ablating uterine fibroids in patients with bowel lies anterior to uterus.

Primary Bone Malignancy: Effective Treatment with High-Intensity Focused Ultrasound Ablation

PURPOSE To evaluate the long-term follow-up results of ultrasonographically (US)-guided high-intensity focused ultrasound ablation in patients with primary bone malignancy. MATERIALS AND METHODS The study was approved by the ethics committee. Each patient or parent (if patient was younger than 18 years), signed an informed consent form before being selected and treated. From December 1997 to November 2004, 80 patients with a primary bone malignancy-60 with stage IIb disease and 20 with stage III disease (Enneking staging system)-were treated with US-guided high-intensity focused ultrasound ablation. High-intensity focused ultrasound ablation combined with chemotherapy was performed in 62 patients with osteosarcoma, one patient with periosteal osteosarcoma, and three patients with Ewing sarcoma. The remaining 14 patients had chondrosarcoma, giant cell bone cancer, periosteal sarcoma, or an unknown malignancy and were treated with high-intensity focused ultrasound ablation only. Magnetic resonance (MR) imaging or computed tomography (CT), and single photon emission computed tomography (SPECT) were used to assess tumor response. Cumulative survival rates were calculated by using the Kaplan-Meier method. Adverse effects were recorded. RESULTS High-intensity focused ultrasound ablation guided by real-time US was performed. Follow-up images demonstrated completely ablated malignant bone tumors in 69 patients and greater than 50% tumor ablation in the remaining 11 patients. Overall survival rates at 1, 2, 3, 4, and 5 years were 89.8%, 72.3%, 60.5%, 50.5%, and 50.5%, respectively. Survival rates at 1, 2, 3, 4, and 5 years were 93.3%, 82.4%, 75.0%, 63.7%, and 63.7%, respectively, in the patients with stage IIb cancer and 79.2%, 42.2%, 21.1%, 15.8%, and 15.8%, respectively, in those with stage III disease. Among the patients with stage IIb disease, long-term survival rates were substantially improved in the 30 patients who received the full treatment-that is, complete high-intensity focused ultrasound and full cycles of chemotherapy-compared with the survival rates for the 24 patients who did not finish the chemotherapy cycles and the six patients who underwent partial ablation only. Only five (7%) of the 69 patients who underwent complete ablation had local cancer recurrence during the follow-up period. Forty adverse events were recorded, with 14 patients requiring surgical intervention. CONCLUSION US-guided high-intensity focused ultrasound ablation of malignant bone tumors is feasible and effective and eventually may be a component of limb-sparing techniques for patients with these cancers.

High intensity focused ultrasound (HIFU) therapy for local treatment of hepatocellular carcinoma: role of partial rib resection.

OBJECTIVE It has long been known that high intensity focused ultrasound (HIFU) can kill tissue through coagulative necrosis. However, it is only in recent years that practical clinical applications are becoming possible. Since the ribs have strong reflections to ultrasonic beams, they may affect the deposition of ultrasound energy, decreasing the efficacy of HIFU treatment and increasing the chance of adverse events when the intra-abdominal tumours concealed by ribs are treated. The aim of this study was to evaluate the influence of partial rib resection on the efficacy and safety of HIFU treatment. METHODS This prospective study was approved by the ethics committee at Chongqing University of Medical Sciences. An informed consent form was obtained from each patient and family member. A total of 16 patients with hepatocellular carcinoma (HCC), consisting of 13 males and 3 females, were studied. All patients had the successful HIFU treatment. To create a better acoustic pathway for HIFU treatment, all of the 16 patients had the ribs that shield the tumour mass to be removed. Magnetic resonance imaging (MRI) was used to evaluate the efficacy of HIFU treatment. RESULTS Sixteen cases had 23 nodules, including 12 cases with a single nodule, 1 case with 2 nodules, 3 cases with 3 nodules. The mean diameter of tumours was 7.0+/-2.1 cm (5-10 cm). According to TNM classification, 9 patients were diagnosed as stage II, 4 patients were stage III, and 3 patients were stage IV. Follow-up imaging showed an absence of tumour blood supply and shrinkage of all treated lesions. The survival rates at 1, 2, 3, 4, and 5 years were 100%, 83.3%, 69.4%, 55.6%, and 55.6%, respectively. No serious complications were observed in the patients treated with HIFU. CONCLUSION Partial rib resection can create a better acoustic pathway of HIFU therapy. Even though it is an invasive treatment, this measure offers patients an improved prospect of complete tumour ablation when no other treatment is available.

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.

High-intensity focused ultrasound combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: Long-term follow-up and clinical analysis

OBJECTIVE High-intensity focused ultrasound (HIFU) combined with transarterial chemoembolization (TACE) has been used to treat unresectable HCC, but its long-term effects and major prognostic factors remain to be determined. The purpose of this study was to assess its long-term effects and find major prognostic factors to help us select eligible patients in the future. METHODS 73 patients with unresectable HCC received follow-up after HIFU+TACE. The variables of sex, age, AFP level, liver function, tumor location, tumor number, tumor size, TNM staging (5th edition), TNM staging (6th edition), portal vein invasion, ultrasonic pathway of HIFU, TACE session and ablation response were evaluated by univariate analysis. Those variables with significant difference were assessed by multivariate analysis. RESULTS The mean follow-up time was 11.7±11.1 months (range, 1-60 months). The median survival time and overall survival rates of 1, 2, 3-year were 12 months, 49.1%, 18.8%, 8.4%, respectively. 45.2% patients achieved complete ablation. At the end of follow-up, 51 patients (69.9%) died from tumor progression (27 patients), liver function failure (18 patients), hemorrhage of upper digestive tract (3 patients) and infection (3 patients). 1 with liver abscess, 2 with serious skin burns and 2 with rib fracture were observed after HIFU. On univariate analysis, age (P=0.017), tumor size (P=0.000), tumor number (P=0.039), the 5th edition of TNM staging (P=0.023), portal vein invasion (P=0.02) and ablation response (P=0.000) had significant difference. On multivariate analysis, ablation response (P=0.001) and tumor size (P=0.013) were major prognostic factors. CONCLUSION HIFU combined with TACE is a safe method with a low rate of severe complications. As major prognostic factors, ablation response and tumor size may help us predict the survival and select eligible patients clinically.

Usefulness of US-CT 3D dual imaging for the planning and monitoring of hepatocellular carcinoma treatment using HIFU

PURPOSE We evaluated the safety and usefulness of high-intensity focused ultrasound (HIFU) assisted by ultrasound-computed tomography three-dimensional (US-CT 3D) dual imaging for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS HIFU ablation was performed in 13 patients with small HCC (≤3 lesions, ≤3 cm in diameter). The HIFU system (Chongqing Haifu Tech) was used under ultrasound guidance. By transferring the sagittal or axial plane of the 3D US and the CT volume data into the ZioM900, multiplanar reconstruction images were displayed in a manner resembling conventional monitor US to assist the HIFU treatment. RESULTS Overall, 69% (9/13) of the patients in whom good visualization using B-mode sonography could not be obtained because of the influence of multi-reflections, rib shadows, and unclear tumor margins were successfully treated under the guidance of US-CT 3D dual imaging. In 5 of the 13 patients, multi-reflections were responsible for the poor visualization. In 2 cases, the tumor was poorly visualized because of a rib shadow. In one case, the margin of the tumor was too unclear to be detected using ultrasography. The 3D US images obtained as part of the US-CT 3D dual imaging had a high resolution and were useful for examining the area of HCC invasion and for determining the extent of the ablation area. The CT images, which are not influenced by bone shadows or multi-reflections, were useful for detecting the tumors and for visualizing the presence of the intestines in the sonication zone. HIFU treatments were successfully performed in all the patients with the assistance of US-CT 3D dual imaging. CONCLUSION US-CT 3D dual imaging is useful for HIFU treatment for HCC, compensating for the occasionally poor visualization provided by US monitor.