The dose of focused ultrasound ablation surgery (FUAS) for unresectable pancreatic cancer is predictable: A multicenter retrospective study.

To analyze the influencing factors of energy efficiency factors (EEF) in focused ultrasound ablation surgery (FUAS) for unresectable pancreatic cancer and build a dosimetry model. The patients with unresectable pancreatic cancer that underwent FUAS were enrolled from 3 clinical centers between June 2015 and June 2022 for retrospective analysis. The significance of the factors with the potential to affect the EEF was assessed, correlations among the factors were analyzed, and the accuracy of the prediction models established by the factors containing different imaging features was compared. From a total of 236 cases, 215 cases were screened for study, EEF was significantly correlated with mode of anesthesia, grayscale change, tumor volume, tumor location, the distance from the tumor center to skin, contrast-enhanced computer tomography enhancement type, T2-weighted imaging fat suppression signal intensity and contrast-enhanced T1-weighted imaging enhancement type on magnetic resonance imaging. The resultant multiple regression models of EEF achieved significance, contains predictors of Tumor volume, the distance from tumor center to skin, T2-weighted imaging fat suppression signal intensity, and contrast-enhanced T1-weighted imaging enhancement type had better goodness of fit. Compared with CT, the EEF prediction model established by adding magnetic resonance imaging features showed better prediction in FUAS treatment of unresectable pancreatic cancer.

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.

Leveraging the genetic basis of Rett syndrome to ascertain pathophysiology.

Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), a progressive X-linked neurological disorder characterized by loss of developmental milestones, intellectual disability and breathing abnormality. Despite being a monogenic disorder, the pathogenic mechanisms by which mutations in MeCP2 impair neuronal function and underlie the RTT symptoms have been challenging to elucidate. The seemingly simple genetic root and the availability of genetic data from RTT patients have led to the generation and characterization of a series of mouse models recapitulating RTT-associated genetic mutations. This review focuses on the studies of RTT mouse models and describe newly obtained pathogenic insights from these studies. We also highlight the potential of studying pathophysiology using genetics-based modeling approaches in rodents and suggest a future direction to tackle the pathophysiology of intellectual disability with known or complex genetic causes.

High-intensity focused ultrasound (HIFU) for adenomyosis: Two-year follow-up results.

OBJECTIVE: To evaluate the long-term improvement of clinical symptoms of adenomyosis after treatment with ultrasound-guided high intensity focused ultrasound (USgHIFU). METHODS: From January 2010 to December 2011, 350 patients with adenomyosis were treated with USgHIFU. Among the 350 patients, 224 of them completed the two years follow-up. The patients were followed up at 3 months, 1 year, and 2 years after HIFU treatment. Adverse effects and complications were recorded. RESULTS: All patients completed HIFU ablation without severe postoperative complications. 203 of the 224 patients who showed varying degrees of dysmenorrhea before treatment had the symptom scores decreased significantly after treatment (P<0.001). The relief rate was 84.7%, 84.7%, and 82.3%, respectively at 3 months, 1 year, and 2 years after treatment. The menstrual volume in 109 patients with menorrhagia was significantly improved after treatment (P<0.001) with a relief rate of 79.8%, 80.7%, and 78.9%, respectively at 3 months, 1 year, and 2 years after HIFU treatment. CONCLUSION: With its ability to sustain long-term clinical improvements, HIFU is a safe and effective treatment for adenomyosis.

Safety of ultrasound-guided ultrasound ablation for uterine fibroids and adenomyosis: A review of 9988 cases.

OBJECTIVE: To evaluate the incidence and severity of adverse reactions to ultrasound-guided ultrasound ablation of uterine fibroids through a multicenter, large-scale retrospective study. METHODS: Between July 2006 and June 2007, 9988 patients with uterine fibroids or adenomyosis were enrolled and received ultrasound ablation treatment under conscious sedation. Forty-two doctors administrated the treatment following a standardized clinical protocol. In-treatment and post-treatment side effects and complications were monitored and each patient was followed up for at least 6 months after the treatment. Complications were classified and graded according to the SIR classification system. The technical success and safety of the treatment were evaluated. RESULTS: The mean age of the 9988 patients was 40.4±5.8 years (range, 20-56 years). Among them, 7438 had uterine fibroids and 2549 had adenomyosis. Specifically, 6545 patients had solitary uterine fibroid, 818 had multiple uterine fibroids, and 76 had fibroids complicated with adenomyosis. There were mainly three types of fibroids: submucous myoma in 89 patients (12.0%), intramural myoma in 5059 patients (68.0%) and subserosal myoma in 1478 patients (20.0%). In terms of fibroid location, 3496 fibroids were found in the anterior wall (47.0%), 2306 in the posterior wall (31.0%), 447 in the lateral wall (6.0%), and 1190 in fundus (16.0%). The length of treatment for uterine fibroids and adenomyosis averaged 84.2±38.8 min (range, 30.0-240.0 min) and 93.3±55.4 min (range, 15.0-240.0 min), respectively; and the lengths of sonication were 1243.8±725.2 s (range, 506.0-2658.0 s) and 1169.7±707.7 s (range, 185.0-3600.0 s), respectively. Of the uterine fibroids patients, 98.38% (7319/7439) underwent successful ablation with a mean volume ablation rate of 83.1%±15.6% (range, 25-100%). Of the adenomyosis patients, 94.59% (2411/2549) underwent successful ablation with a mean volume ablation rate of 73.2%±23.6% (range, 21-100%). A total of 1062 patients (10.6%) presented with 1305 events of adverse reactions. According to the SIR classification system, 1228 (94.1%) of these reactions fell under Class A; 45 (3.4%) fell under Class B; 24 (1.8%) fell under Class C; and the rest 8 (0.6%) fell under Class D. Adverse reactions included 874 cases (8.67%) of vaginal secretion, 225 cases (2.23%) of lower abdominal pain 24h after the treatment but requiring no painkillers, 76 cases (0.76%) of melosalgia or buttock pain, 52 cases (0.52%) of odynuria, 20 cases (0.20%) of menstruation-like vaginal bleeding, 2 cases (0.2%) of temporary blurred vision, 26 cases (0.26%) of blisters or tangerine pericarp-like burns in the abdominal skin, 16 cases (0.16%) of urinary retention, 4 cases (0.4%) of fever of 38.5°C, 3 cases (0.3%) of acute renal insufficiency, 2 cases (0.2%) of intestinal perforation, and 1 case (0.01%) of long-term lateral ventral syndrome. No permanent injury or fatal complication occurred. CONCLUSIONS: Based on our observations from 9988 cases, ultrasound ablation treatment for uterine fibroid and adenomyosis is highly effective and safe. Adverse reactions to ultrasound ablation under conscious sedation are slight and temporary for both conditions. Hence, this clinically effective and safe treatment is an alternative treatment for women with uterine fibroids and adenomyosis.

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.

Enhancing ablation effects of a microbubble-enhancing contrast agent ("SonoVue") in the treatment of uterine fibroids with high-intensity focused ultrasound: a randomized controlled trial.

PURPOSE: To evaluate the role of the ultrasound contrast agent SonoVue in enhancing the ablation effects of ultrasound-guided high-intensity focused ultrasound (HIFU) on uterine fibroids. METHODS: Eighty patients with solitary uterine fibroids at a single center were randomly assigned to a control or SonoVue group. Of these, 40 were treated using HIFU alone; 40 who were pretreated with SonoVue received a bolus before the HIFU procedure. All patients underwent magnetic resonance imaging (MRI) scan before and after HIFU treatment. RESULTS: The post-HIFU MRI showed the nonperfused volume (NPV) in all of the treated uterine fibroids; the mean fractional ablation (NPV ratio) was 90.4 ± 8.3 % (range 66.4-100 %) in the SonoVue group and 82.8 ± 13.3 % (range 53.4-100 %) in the control group. The frequency of massive gray-scale changes that occurred during HIFU was greater in the group that received SonoVue than the group that did not. The average sonication time to reach massive gray-scale changes was significantly shorter in the group receiving SonoVue than the group without SonoVue. The acoustic energy for treating 1 mm(3) of uterine fibroid was less in the SonoVue group than the control group. No any major complication occurred in this study. CONCLUSION: Based on the results of this randomized controlled trial, SonoVue could be safely used to enhance the effects of HIFU treatment for uterine fibroids.

Effective ablation therapy of adenomyosis with ultrasound-guided high-intensity focused ultrasound.

OBJECTIVE: To evaluate the effects of ultrasound-guided high-intensity focused ultrasound (HIFU) on adenomyosis. METHODS: In a retrospective analysis, data were reviewed from 202 patients with adenomyosis who underwent ultrasound-guided HIFU between November 2010 and June 2012 at Suining Central Hospital, Sichuan, China. Among these patients, 120 and 82 were classified as having focal adenomyosis and diffuse adenomyosis, respectively. All patients underwent pre-treatment and post-treatment magnetic resonance imaging by a standardized protocol to evaluate the treatment. All adverse effects were recorded. RESULTS: All patients completed the ultrasound-guided HIFU treatment in 1 session. A non-perfused volume ratio of 71.6%±19.1% was achieved. Compared with baseline data, the average menorrhagia severity score and the average dysmenorrhea severity pain score decreased significantly after ultrasound-guided HIFU (both P<0.001). The proportion of women with complete relief of dysmenorrhea at the 3-month follow-up was significantly higher among women with focal adenomyosis than among those with diffuse adenomyosis (P=0.02). No other significant differences were observed between the 2 patient groups. CONCLUSION: Ultrasound-guided HIFU was found to be an effective technique for treating both focal and diffuse adenomyotic lesions to alleviate the symptoms of menorrhagia or dysmenorrhea.

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.

Clinical utility of a microbubble-enhancing contrast ("SonoVue") in treatment of uterine fibroids with high intensity focused ultrasound: a retrospective study.

PURPOSE: To evaluate the clinical value of the contrast agent SonoVue in the treatment of uterine fibroids with ultrasound-guided high intensity focused ultrasound (HIFU) therapeutic ablation. MATERIALS AND METHODS: A total of 291 patients with solitary uterine fibroid from three centers were treated with ultrasound-guided HIFU. Among them, 129 patients from Suining Central Hospital of Sichuan were treated without using SonoVue. 162 patients from the First Hospital of Chongqing Medical University and Chongqing Haifu Hospital were treated with using SonoVue before, during and after HIFU procedure to assess the extent of HIFU. RESULTS: The non-perfused volume (indicative of successful ablation) was observed in all treated uterine fibroids immediately after HIFU ablation; median fractional ablation, defined as non-perfused volume divided by the fibroid volume immediately after HIFU treatment, was 86.0% (range, 28.8-100.0%) in the group with using SonoVue, and 83.0% (8.7-100.0%) without SonoVue. The rate of massive gray scale changes was higher with SonoVue than without the agent. The sonication time to achieve massive gray scale changes was shorter with SonoVue than without. The sonication time for ablating 1cm(3) of fibroid volume was significantly shorter with using SonoVue than without. No major complications were observed in any patients. CONCLUSIONS: Based on our results, SonoVue may enhance the outcome of HIFU ablation and can be used to assess the extent of treatment.

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.

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.

High-intensity focused ultrasound (HIFU): effective and safe therapy for hepatocellular carcinoma adjacent to major hepatic veins.

Hepatocellular carcinoma (HCC) is an especially frequent malignancy in China. Radiofrequency ablation, percutaneous ethanol injection, transarterial chemoembolization, cryoablation, microwave coagulation, and laser-induced interstitial thermotherapy all offer potential local tumor control and occasionally achieve long-term disease-free survival. High-intensity focused ultrasound (HIFU), as a noninvasive therapy, can be applied to treat tumors that are difficult to treat with other techniques. The preliminary results of HIFU in clinical studies are encouraging. The aims of this investigation were to assess the efficacy of the system in obtaining necrosis of the target tissue and to determine whether HIFU ablation is hazardous to adjacent major blood vessels. Over 7 years, thirty-nine patients with HCC were enrolled in this investigation. The inferior vena cava (IVC), main hepatic vein branches, and the portal vein and its main branches were evaluated. The distance between tumor and main blood vessel was less than 1 cm in all these enrolled patients. Contrast-enhanced MRI was used to evaluate the perfusion of tumors and major blood vessels. We conducted HIFU ablation for the treatment of 39 patients with 42 tumors, with each tumor measuring 7.4+/-4.3 (1.5-22) cm in its greatest dimension. Among the 39 patients, 23 were males and 16 females. The average age was 53.2 years (range 25-77 years). Thirty-seven patients had a solitary lesion, one had two lesions, and the remaining one had three lesions. Nineteen lesions were located in the right lobe of liver, 18 in the left lobe, and 5 in both right and left lobes. Among the 42 tumors, 25 were adjacent to 1 blood vessel, 12 adjacent to 2 main vessels, 2 adjacent to 3 main vessels, and 1 adjacent to 4 main vessels. Twenty-one of the 42 tumors were completely ablated, while the rest of the tumors were ablated by more than 50% of lesion volume after one session of HIFU. No major blood vessel injury was observed in any subject after 23.8+/-17.2 months follow-up. HIFU can achieve complete tumor necrosis even when the lesion is located adjacent to the major hepatic blood vessels. Short-term and long-term follow-up results show that HIFU can be safely used to ablate the tumors adjacent to major vessels.

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 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.

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 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.

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.