Ke-Quan Li

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.

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.

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.

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.