The safety and ablation efficacy of ultrasound-guided high-intensity focused ultrasound ablation for desmoid tumors.

OBJECTIVE: To evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for desmoid tumors (DTs). METHOD: A total of 111 patients with histologically proven DTs were included and treated by USgHIFU ablation. Adverse events were continuously evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 until 3 months after treatment. The incidence of non-perfused areas within the treated tumors, non-perfused volume rate (NPVR) and tumor volume reduction were evaluated using contrast-enhanced MRI before and one week and 3 months after the procedure. RESULTS: The enrolled patients (32 male, 79 female, mean age 29.5 ± 1.0 years) with 145 DTs (118 extra-abdominal, 16 abdominal wall, 11 intra-abdominal; median maximum diameter: 9.6 cm, range: 3-34.5 cm) underwent 188 sessions of HIFU ablation, and the mean number of ablations was 1.7 (range, 1-7) per patient. In majority of cases (143/145 cases, 98.6%), no serious adverse events were observed. There was no significant difference in the incidence of adverse events between patients who received a single treatment and those who received multiple treatments. Non-perfused area was observed within every treated tumor, and the median NPVR was 84.9% (range, 1.9-100%). The tumor volume reduction rate was 36.1 ± 4.2% at 3 months after treatment. CONCLUSION: USgHIFU ablation, as a noninvasive and easily repeatable local treatment, is a promising treatment for DTs.

Contrast-enhanced ultrasound for evaluation of high-intensity focused ultrasound treatment of benign uterine diseases: retrospective analysis of contrast safety.

As a noninvasive treatment technique, ultrasound-guided high-intensity focused ultrasound (HIFU) has been considered as a routine treatment for uterine fibroids and adenomyosis in China. Contrast-enhanced ultrasound (CEUS) has been proposed as another option to assess the treatment efficacy during HIFU treatment. The aim of this investigation is to evaluate the adverse effects of HIFU ablation for benign uterine diseases in a group of patients studied with ultrasound contrast agent (UCA), in comparison with a group of patients not exposed to UCA. From November 2010 to December 2013, 2604 patients with benign uterine diseases were treated with HIFU. Among them, 1300 patients were exposed to an UCA, whereas 1304 patients were not.During HIFU procedure, the incidences of leg pain, sacral/buttock pain, groin pain, treatment area pain, and the discomfort "hot" sensation on skin were higher in the patients who were exposed to SonoVue (Bracco, Milan, Italy) than those who were not (20.5% vs 11.7%, 52.5% vs 42.3%, 6.5% vs 4.5%, 68.9% vs 55.4%, and 48.1% vs 42.9%, respectively). Among the postoperative adverse effects, the incidence of lower abdominal pain was significantly higher in patients who were exposed to an UCA than those who were not (51.2% vs 39.9%, P < 0.05). Two patients who were exposed to an UCA had acute renal function failure.In conclusion, UCA may increase the incidences of some common HIFU-related adverse effects during HIFU treatment for benign uterine diseases, but most of which were acceptable and self-limited. After HIFU treatment, renal function should be monitored in patients with a history of hypertension or taking nonsteroidal anti-inflammatory drugs.

Extracorporeal focused ultrasound surgery for treatment of human solid carcinomas: early Chinese clinical experience.

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.

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.

Feasibility of ultrasound-guided high intensity focused ultrasound ablating uterine fibroids with hyperintense on T2-weighted MR imaging.

PURPOSE: To retrospectively investigate whether uterine fibroids with hyperintense on pretreatment T2-weighted magnetic resonance imaging (MRI) could be treated with ultrasound-guided high intensity focused ultrasound (USgHIFU). MATERIALS AND METHODS: 282 patients with 282 symptomatic uterine fibroids who underwent USgHIFU treatment were retrospectively analyzed. Based on the signal intensity of T2-weighted MRI, uterine fibroids were classified as hypointense, isointense and hyperintense. Hyperintense fibroids were subjectively further subdivided into heterogeneous hyperintense, slightly homogeneous hyperintense and markedly homogeneous hyperintense based on the signal intensity of fibroid relative to myometrium and endometrium on T2-weighted MRI. Enhanced MRI was performed within one month after HIFU treatment. Non-perfused volume (NPV, indicative of successful ablation) ratio, treatment time, treatment efficiency, energy effect ratio and adverse events were recorded. RESULTS: The median volume of uterine fibroids was 70.3 cm(3) (interquartile range, 41.1-132.5 cm(3)). The average NPV ratio, defined as non-perfused volume divided by the fibroid volume after HIFU treatment, was 76.8 ± 19.0% (range, 0-100%) in the 282 patients. It was 86.3 ± 11.9% (range, 40.9-100.0%) in the group with hypointense fibroids, 77.1 ± 16.5% (range, 32.2-100.0%) in isointense fibroids, and 67.6 ± 23.9% (range, 0-100.0%) in hyperintense fibroids. The lowest NPV ratio, lowest treatment efficiency, more treatment time, more sonication energy and pain scores were observed in the slightly homogeneous hyperintense fibroids, and the NPV ratio was 55.8 ± 26.7% (range, 0-83.9%) in this subgroup. CONCLUSION: Based on our results, the heterogeneous and markedly homogeneous hyperintense fibroids were suitable for USgHIFU, and only the slightly homogeneous hyperintense fibroids should be excluded.

Advanced hepatocellular carcinoma: treatment with high-intensity focused ultrasound ablation combined with transcatheter arterial embolization.

PURPOSE: To evaluate ultrasonographically (US)-guided high-intensity focused ultrasound ablation combined with transcatheter arterial chemoembolization (TACE) in the treatment of stage IVA hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. From November 1998 to May 2000, 50 consecutive patients with stage IVA HCC (TNM classification, T4N0-1M0) were alternately enrolled in one of two treatment groups: group 1 (n = 26), in which TACE was performed alone, and group 2 (n = 24), in which transcutaneous ablation of HCC with high-intensity focused ultrasound was performed 2-4 weeks after TACE. The tumors were 4-14 cm in diameter (mean, 10.5 cm). Immediate therapeutic effects were assessed at follow-up with Doppler US and computed tomography or magnetic resonance imaging. All patients were followed up for 3-24 months (mean, 8 months) to observe long-term therapeutic effects and complications in both groups. Tumor reduction rates, median survival time, and cumulative survival rates in both groups were calculated by using the unpaired Student t test and Kaplan-Meier method. RESULTS: No severe complication was observed after focused ultrasound ablation, and no unexpected side effects were noted after TACE. Follow-up images showed absence or reduction of blood supply in the lesions after focused ultrasound ablation when compared with blood supply after TACE alone. The median survival time was 11.3 months in group 2 and 4.0 months in group 1 (P = .004). The 6-month survival rate was 80.4%-85.4% in group 2 and 13.2% in group 1 (P = .002), and the 1-year survival rate was 42.9% and 0%, respectively. Median reductions in tumor size as a percentage of initial tumor volume at 1, 3, 6, and 12 months after treatment, respectively, were 28.6%, 35.0%, 50.0%, and 50.0% in group 2 and 4.8%, 7.7%, 10.0%, and 0% in group 1 (P < .01). CONCLUSION: The combination of high-intensity focused ultrasound ablation and TACE is a promising approach in patients with advanced-stage HCC, but large-scale randomized clinical trials are necessary for confirmation.

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 II(A) in 9 patients, stage II(B) 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 US-guided high-intensity focused ultrasound treatment in patients with advanced pancreatic cancer: initial experience.

The study was approved by the university ethics committee, and informed consent was obtained from all patients. The purpose of this study was to prospectively evaluate ultrasonographically guided high-intensity focused ultrasound in the treatment of patients with advanced-stage pancreatic cancer. Eight patients underwent high-intensity focused ultrasound ablation, and laboratory and radiologic examinations were performed after intervention. Changes in symptoms and survival time were noted at follow-up. No complications were observed, and preexisting severe back pain disappeared after intervention. Follow-up images revealed an absence of tumor blood supply and shrinkage of the ablated tumor. Four patients died, and four patients were alive at the time of this writing, with a median survival time of 11.25 months. The authors conclude that high-intensity focused ultrasound ablation is safe and feasible in the treatment of advanced pancreatic cancer.

Extracorporeal high intensity focused ultrasound ablation in the treatment of patients with large hepatocellular carcinoma.

BACKGROUND: 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 alpha-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.