High intensity focused ultrasound: A noninvasive therapy for locally advanced pancreatic cancer

The noninvasive ablation of pancreatic cancer with high intensity focused ultrasound(HIFU) energy is received increasingly widespread interest. With rapidly temperature rise to cytotoxic levels within the focal volume of ultrasound beams, HIFU can selectively ablate a targeted lesion of the pancreas without any damage to surrounding or overlying tissues. Preliminary studies suggest that this approach is technical safe and feasible, and can be used alone or in combination with systemic chemotherapy for the treatment of patients with locally advanced pancreatic cancer. It can effectively alleviate cancer-related abdominal pain, and may confer an additional survival benefit with few significant complications. This review provides a brief overview of HIFU, describes current clinical applications, summarizes characteristics of continuous and pulsed HIFU, and discusses future applications and challenges in the treatment of pancreatic cancer.

Safety trial of high-intensity focused ultrasound therapy for pancreatic cancer

AIM:To evaluate the safety and clinical application of high-intensity focused ultrasound(HIFU)therapy for unresectable pancreatic cancer(PC).METHODS:Thirty PC patients(16 cases in stage III and 14 cases in stage IV)with visualized pancreatic tumors were admitted for HIFU therapy as an optional local therapy in addition to systemic chemotherapy or chemoradiotherapy.Informed consent was obtained.This study began at the end of 2008 and was approved by the ethics committee of our hospital[Institutional Review Board(IRB):890].The HIFU device used was the FEP-BY02(Yuande Bio-Medical Engineering,Beijing,China).RESULTS:The mean tumor size after HIFU therapy changed to 30.9±1.7 mm from 31.7±1.7 mm at pre-therapy.There were no significant changes in tumor size,mean number of treatment sessions(2.7±0.1 mm),or mean total treatment time(2.4±0.1 h).The rate of symptom relief effect was 66.7%.The effectiveness of primary lesion treatment was as follows:complete response,0;partial response,4;stable disease,22;progressive disease,4.Treatment after HIFU therapy included 2 operations,24 chemotherapy treatments,and 4 best supportive care treatments.Adverse events occurred in 10%of cases,namely pseudocyst formation in 2 cases and mild pancreatitis development in 1.However,no severe adverse events occurred in this study.CONCLUSION:We suggest that HIFU therapy is safe and has the potential to be a new method of combination therapy for PC.

High-intensity focused ultrasound treatment for patients with unresectable pancreatic cancer

BACKGROUND: High-intensity focused ultrasound (HIFU) is a non-invasive method of solid tissue ablation therapy. However, only a few studies have reported the effect of HIFU for unresectable pancreatic cancer. This study aimed to evaluate the clinical benefits, survival time and complications associated with the use of HIFU ablation in patients with unresectable pancreatic cancer. METHODS: Twenty-five patients with unresectable pancreatic cancer were enrolled in our study. All patients received HIFU therapy for tumors at least once. The therapeutic effects of HIFU was evaluated in terms of Karnofsky performance status (KPS) scores, pain relief, serum CA19-9, and imaging by B-US and CT before and after the therapy. We also recorded median overall survival time and complications caused by the treatment. RESULTS: In the 25 patients, KPS scores were above 60, and increased KPS was observed in 23 patients after treatment. Pain relief occurred in 23 patients. Serum CA19-9 levels were significantly reduced one month after HIFU treatment and became negative in 5 patients. B-US revealed enhanced tumor echogenicity in 13 patients and decreased tumor blood supply in 9. Tumor necrosis was confirmed by CT in 8 patients one month after HIFU treatment. The median overall survival time was 10 months, and the 1-year survival rate was 42%. No severe complications were observed after HIFU treatment. CONCLUSION: HIFU can effectively relieve pain, increase KPS, decrease tumor growth and prolong the survival time of patients with unresectable pancreatic cancer.

The Efficacy of High-Intensity Focused Ultrasound (HIFU) in Advanced Pancreatic Cancer

OBJECTIVE To observe the efficacy of high-intensity focused ultrasound (HIFU) in the treatment of late-stage pancreatic cancer. METHODS Sixteen patients with advanced pancreatic cancer received HIFU therapy.Evaluation of efficacy was made on the basis of changes in clinical symptoms and variations in the tumor echo and size. RESULTS Clinical symptoms such as pain were significantly alleviated,echo of the tumor was enhanced with B-US and the quality of life such as eating,sleeping and mental status was markedly improved;no serious complications were observed. CONCLUSION The use of HIFU in the treatment of advanced pancreatic cancer is feasible and safe.It is effective in killing the carcinoma cells and alleviating pain.This technique may offer non-invasive therapy for the treatment of patients with late-stage pancreatic cancer.

Analgesic effect of high intensity focused ultrasound in patients with advanced pancreatic cancer

Objective： The aim of this study was to evaluate the analgesic effect of high intensity focused ultrasound （HIFU） in patients with advanced pancreatic cancer. Methods： A total of 106 patients with advanced pancreatic cancer accompanied by abdominal pain were treated by HIFU. Pain intensities and quantities of morphine consumption before and after treatment were observed and compared. Results： The average pain intensities before treatment, and at d3, d7 after treatment were 5.80 ±2.14, 2.73 ± 2.68, 2.45 ± 2.43 respectively （P 〈 0.01）. Fifty-nine cases （55.7%） got to extremely effective, and 29 cases （27.4%） effective. Total efficient rate was 83.0 %. The average quantities of morphine consumption before and after treatment in the patients with grade III pain were 114.9 ± 132.5 rag, 16.8 ± 39.7 mg each person everyday respectively （P 〈 0.01）. Conclusion： HIFU can relieve pain suffered by patients with pancreatic cancer effectively. It is a new adjuvant treatment for pancreatic cancer pain.

Effect of high-intensity focused ultrasound (HIFU) combined with radiotherapy on tumor malignancy in patients with advanced pancreatic cancer and evaluation of side effects

Objective:To study the effect of high-intensity focused ultrasound (HIFU) combined with radiotherapy on tumor malignancy in patients with advanced pancreatic cancer and the corresponding side effects.Methods:A total of 84 patients with advanced pancreatic cancer treated in our hospital between May 2013 and March 2016 were selected and randomly divided into HIFU group and IGRT group, HIFU group accepted high-intensity focused ultrasound combined with radiotherapy and IGRT group received radiotherapy alone. 4 weeks after treatment, the levels of tumor markers, liver and kidney function indexes, perineural invasion-related molecules and cytokines in serum as well as the levels of immune cells in peripheral blood were determined.Results:4 weeks after treatment, serum CA199, CA242, OPN, NGAL, RBP4, NGF, TrkA, p75, BDNF and TrkB levels of HIFU group were significantly lower than those of IGRT group, serum IL-2, TNF-α, IFN-γ and IL-13 levels as well as peripheral blood NKT cell and CD4+T cell levels were significantly higher than those of IGRT group, and serum ALT, AST, Cr and BUN levels were not significantly different from those of IGRT group.Conclusion:HIFU combined with radiotherapy treatment of advanced pancreatic cancer can more effectively kill cancer cells, inhibit pancreatic cancer cell invasion to the peripheral nerve and enhance the antitumor immune response mediated by NKT cells and CD4+T cells.

Lax Facial Skin Treated with High-Intensity Focused Ultrasound Devices: Efficacy and Safety Evaluations

Background: High-intensity focused ultrasound (HIFU) has been introduced to improve skin laxity in recent years. However, very few studies have evaluated the safety and effectiveness of HIFU in Chinese populations. Methods: In the study, 30 Chinese participants underwent HIFU (Bolida, Inc., Changsha, China) rejuvenation between February 1, 2022, and September 30, 2022. There were three different focal depths used depending on the area where shots were captured (4.5 mm, 4 MHz;3 mm, 7 MHz;1.5 mm, 7 MHz). After 3 months and 6 months of treatment, efficacy and safety were assessed by quantitative analysis. Results: Patients were satisfied with the clinical effects of HIFU rejuvenation after one session. In terms of effectiveness, HIFU was most successful in areas around the jawline, cheek, and perioral. In four cases, erythema was observed, in two cases, swollen gums were seen, but all of these effects were transient and mild. Conclusion: Bolida system can be safe and effective for facial tightening, additionally, they are most effective for jawline, cheek, and perioral improvements. In clinical practice, the Bolida system can be recommended as a reliable treatment option. .

Magnetic resonance image-guided versus ultrasound-guided high-intensity focused ultrasound in the treatment of breast cancer

Image-guided high-intensity focused ultrasound (HIFU) has been used for more than ten years, primarily in the treatment of liver and prostate cancers. HIFU has the advantages of precise cancer ablation and excellent protection of healthy tissue. Breast cancer is a common cancer in women. HIFU therapy, in combination with other therapies, has the potential to improve both oncologic and cosmetic outcomes for breast cancer patients by providing a curative therapy that conserves mammary shape. Currently, HIFU therapy is not commonly used in breast cancer treatment, and efforts to promote the application of HIFU is expected. In this article, we compare different image-guided models for HIFU and reviewed the status, drawbacks, and potential of HIFU therapy for breast cancer.

The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound （HIFU） combined with （＋） low-dose external beam radiotherapy （LRT） as supplemental therapy for advanced prostate cancer （PCa） following hormonal therapy （HT）. Our definition of HIFU＋LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy （CRT）. We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU＋LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU ＋LRT treatment. There were significant differences among four groups with regard to overall survival （OS） and disease-specific survival （DSS） curves （P=0.018 and 0.015）. Further comparison between each pair of groups suggested that the long-term DSS of the H IFU ＋ LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU＋LRT group and the CRT group. Multivariable Cox＇s proportional hazard model showed that both HIFU＋LRT and CRT were independently associated with DSS （P=0.001 and 0.035） and had protective effects with regard to the risk of death. Compared with CRT, HIFU ＋LRT significantly decreased incidences of radiation-related late gastrointestinal （GI） and genitourinary （GU） toxicity grade ≥ II. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and reRional lymph node metastases after HT. As an alternative to CRT, HIFU＋LRT showed Rood efficacy and better safety.

Transrectal High-Intensity Focused Ultrasound for the Treatment of Localized Prostate Cancer: Current Role

Over the past 25 years, the average life expectancy for men has increased by 4 years, and the age of prostate cancer detection has decreased an average of 10 years with diagnosis increasingly made at early-stage disease where curative therapy is possible. These changing trends in the age and extent of malignancy at diagnosis have revealed limitations in conventional curative therapies for prostate cancer, including a significant risk of aggressive cancer recurrence, and the risk of long-term genitourinary morbidity and its detrimental impact on patient quality of life (QOL). Greater awareness of the shortcomings in radical prostatectomy, external radiotherapy and brachytherapy have prompted the search for alternative curative therapies that offer comparable rates of cancer control and less treatment-related morbidity to better preserve QOL. High intensity focused ultrasound (HIFU) possesses characteristics that make it an attractive curative therapy option. HIFU is a non-invasive approach that uses precisely-delivered ultrasound energy to achieve tumor cell necrosis without radiation or surgical excision. In current urological oncology, HIFU is used clinically in the treatment of prostate cancer, and is under experimental investigation for therapeutic use in renal and breast malignancies. Clinical research on HIFU therapy for localized prostate cancer began in the 1990s, and there have now been approximately 30,000 prostate cancer patients treated with HIFU, predominantly with the Ablatherm (EDAP TMS, Lyon, France) device. Transurethral resection of the prostate (TURP) has been combined with HIFU since 2000 to reduce prostate size, facilitate tissue destruction, and to minimize side effects. Advances in imaging technologies are expected to further improve the already superior efficacy and morbidity outcomes, and ongoing investigation of HIFU as a focal therapy and in salvage and palliative indications are serving to expand the role of HIFU as a highly versatile non-invasive therapy for prostate cancer.

Long-Term Outcomes and Prognosis of Transrectal High-Intensity Focused Ultrasound Therapy for Patients with Localized Prostate Cancer—Therapy after Recurrence and Predictive Factors

Objectives: To evaluate the outcomes and prognosis of high-intensity focused ultrasound (HIFU) therapy for patients with localized prostate cancer, and identify suitable candidates for this therapy by investigating the predictive factors. Methods: The 224 patients (low 54, intermediate 111 and high-risk patients 59) with T1-2 stage were treated using the Sonablate device and followed for over 12 months after treatment. Recurrence was determined based on histological findings, prostate-specific antigen (PSA) failure and local or distant metastasis. The factors which are predicting variables with potential effects were investigated by Kaplan-Meier and multivariate analysis. Results: A total of 255 treatment sessions (193 with one, 31 with two) were performed. No patients died of prostate cancer, but 15 died of other causes and 14 patients were lost during follow-up. The 7-year recurrence-free survival (RFS) rates in all patients were 75%, and 5-year RFS rates were 98%, 84% and 59% in the low, intermediate and high-risk patients respectively. In the 216 patients who underwent histological examination at 6 months or later after HIFU, 25 (12%) were positive. In 77 patients with recurrence after first-HIFU, the second treatments were hormonal therapy and HIFU. Of the 31 patients who underwent a second HIFU, the 5-year RFS rates were 64%, and 5-year RFS rates were 100%, 74% and 33% in the low, intermediate and high-risk patients. The significant predictor for recurrence was risk-group, T-stage (T1 vs T2), Gleason score (≤3 + 4 and ≥4 + 3), pretreatment PSA (Conclusions: Prognosis of HIFU for Patients with localized prostate cancer was good, and the low and intermediate-risk patients with T1-staging are suitable indications for HIFU. Effective predictors for outcomes were risk-group, T-stage, Gleason score, pretreatment PSA and nadir PSA.

High intensity focused ultrasound in clinical tumor ablation

Recent advances in high intensity focused ultrasound(HIFU),which was developed in the 1940s as a viable thermal tissue ablation approach,have increased its popularity.In clinics,HIFU has been applied to treat a variety of solid malignant tumors in a well-defined volume,including the pancreas,liver,prostate,breast,uterine fibroids,and soft-tissue sarcomas.In comparison to conventional tumor/cancer treatment modalities,such as open surgery,radio-and chemo-therapy,HIFU has the advantages of non-invasion,non-ionization,and fewer complications after treatment.Over 100 000 cases have been treated throughout the world with great success.The fundamental principles of HIFU ablation are coagulative thermal necrosis due to the absorption of ultrasound energy during transmission in tissue and the induced cavitation damage.This paper reviews the clinical outcomes of HIFU ablation for applicable cancers,and then summarizes the recommendations for a satisfactory HIFU treatment according to clinical experience.In addition,the current challenges in HIFU for engineers and physicians are also included.More recent horizons have broadened the application of HIFU in tumor treatment,such as HIFU-mediated drug delivery,vessel occlusion,and soft tissue erosion(“histotripsy”).In summary,HIFU is likely to play a significant role in the future oncology practice.

Complications of high intensity focused ultrasound in patients with recurrent and metastatic abdominal tumors

AIM： To analyze the local and systemic complications of high intensity focused ultrasound （HIFU） for patients with recurrent and metastatic abdominal tumors. METHODS： From Aug 2001 to Aug 2004, 17 patients with recurrent and metastatic abdominal tumors were enrolled in this study. Real-time sonography was taken, and vital signs, liver and kidney function, skin burns, local reactions, and systemic effects were observed and recored before, during, and after HIFU. CT and MR/were also taken before and after HIFU. RESULTS： All 17 patients had skin burns and pain in the treatment region; the next common complication was neurapraxia of the stomach and intestines to variable degrees. The other local and systemic complications were relatively rare. Severe complications were present in two patients; one developed a superior mesenteric artery infarction resulting in necrosis of the entire small intestines, and the other one suffered from a perforation in terminal ileum due to HIFU treatment. CONCLUSION： Although HIFU is a one of noninvasive treatments for the recurrent and metastatic abdominal tumors, there are still some common and severe complications which need serious consideration.

Non-thermal ablation of rabbit liver VX2 tumor by pulsed high intensity focused ultrasound with ultrasound contrast agent:Pathological characteristics

AIM： To investigate the pathological characteristics of non-thermal damage induced by pulsed high intensity focused ultrasound （PHIFU） combined with ultrasound contrast agent （UCA）, SonoVue （Bracco SpA, Milan, Italy） in rabbit liver VX2 tumor. METHODS： Liver VX2 tumor models were established in 20 rabbits, which were divided randomly into PHIFU combined with ultrasound contrast agent group （PHIFU ＋ UCA group） and sham group. In the PHIFU ＋ UCA group, 0.2 mL of SonoVue was injected intravenously into the tumor, followed by ultrasound exposure of Isp 5900 W/cm^2. The rabbits were sacrificed one day after ultrasound exposure. Specimens of the exposed tumor tissues were obtained and observed pathologically under light microscope and transmission electron microscope. The remaining tumor tissues were sent for 2,3,5-Triphenyltetrazolium chloride （TTC） staining. RESULTS： Before Trc staining, tumor tissues in both the sham and the PHIFU ＋ UCA groups resembled gray fish meat, After TIC staining, the tumor tissues were uniformly stained red, with a clear boundary between tumor tissue and normal tissue, Histological examination showed signs of tumor cell injury in PHIFU ＋ UCA group, with cytoplasmic vacuoles of various sizes, chromatin margination and karyopyknosis. Electron microscopic examination revealed tumor cell volume reduction, karyopyknosis, chromatin margination, intercellular space widening, the presence of high electro＇n-density apoptotic bodies and vacuoles in cytoplasm. CONCLUSION： The non-thermal effects of PHIFU combined with UCA can be used to ablate rabbit liver VX2 tumors.

Sonablate-500^(TM) Transrectal High-intensity Focused Ultrasound (HIFU) for Benign Prostatic Hyperplasia Patients

To evaluate the safety and efficacy of transrectal high-intensity focused ultrasound （HIFU） in the treatment of benign prostatic hyperplasia （BPH）, serial studies were conducted in 150 BPH patients before and 30 min, 1, 2, 6 and 12 month（s） after Sonablate-500TM HIFU treatment. A silicon-coated indwelling 16F latex catheter was placed during the determination of the therapy zone. Preoperative and postoperative evaluations were made by using the international prostate symptom score （IPSS）, quality of life （QOL）, uroflowmetric findings and transrectal ultrasound, and incidence of complications. The cystourethrography was done in 23 patients within 1 year postoperatively. The results showed that after HIFU treatment, IPSS and QOL scores were significantly decreased at 1, 2, 6 and 12 month（s） （P〈0.01）. Maximum urine flow rate （6.0 to 17.2 mL/s, P〈0.01）, PVR （75.0 to 30.3, P〈0.01） and prostatic volume （65.0 to 38.1 mL, P〈0.05） were significantly improved 12 months after the operation. Recurrent urinary retention （17=2） and urethrorectal fistula （n=1） occurred at the 15th postoperative day. The duration of the HIFU prostate ablation was 25-90 min. The mean time for an indwelling catheter was 3-19 days. These data demonstrate that treatment of BPH with Sonab- late-500TM HIFU is safe and effective.

High-intensity focused ultrasound ablation:An effective bridging therapy for hepatocellular carcinoma patients

AIM:To analyze whether high-intensity focused ultrasound(HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma(HCC).METHODS:From January 2007 to December 2010,49 consecutive HCC patients were listed for liver transplantation(UCSF criteria).The median waiting time for transplantation was 9.5 mo.Twenty-nine patients received transarterial chemoembolization(TACE) as a bringing therapy and 16 patients received no treatment before transplantation.Five patients received HIFU ablation as a bridging therapy.Another five patients with the same tumor staging(within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for comparison.Patients were comparable in terms of Child-Pugh and model for end-stage liver disease scores,tumor size and number,and cause of cirrhosis.RESULTS:The HIFU group and TACE group showed no difference in terms of tumor size and tumor number.One patient in the HIFU group and no patient in the TACE group had gross ascites.The median hospital stay was 1 d(range,1-21 d) in the TACE group and two days(range,1-9 d) in the HIFU group(P < 0.000).No HIFU-related complication occurred.In the HIFU group,nine patients(90%) had complete response and one patient(10%) had partial response to the treatment.In the TACE group,only one patient(3%) had response to the treatment while 14 patients(48%) had stable disease and 14 patients(48%) had progressive disease(P = 0.00).Seven patients in the TACE group and no patient in the HIFU group dropped out from the transplant waiting list(P = 0.559).CONCLUSION:HIFU ablation is safe and effective in the treatment of HCC for patients with advanced cirrhosis.It may reduce the drop-out rate of liver transplant candidate.

Identification of denatured and normal biological tissues based on compressed sensing and refined composite multi-scale fuzzy entropy during high intensity focused ultrasound treatment

In high intensity focused ultrasound(HIFU)treatment,it is crucial to accurately identify denatured and normal biological tissues.In this paper,a novel method based on compressed sensing(CS)and refined composite multi-scale fuzzy entropy(RCMFE)is proposed.First,CS is used to denoise the HIFU echo signals.Then the multi-scale fuzzy entropy(MFE)and RCMFE of the denoised HIFU echo signals are calculated.This study analyzed 90 cases of HIFU echo signals,including 45 cases in normal status and 45 cases in denatured status,and the results show that although both MFE and RCMFE can be used to identify denatured tissues,the intra-class distance of RCMFE on each scale factor is smaller than MFE,and the inter-class distance is larger than MFE.Compared with MFE,RCMFE can calculate the complexity of the signal more accurately and improve the stability,compactness,and separability.When RCMFE is selected as the characteristic parameter,the RCMFE difference between denatured and normal biological tissues is more evident than that of MFE,which helps doctors evaluate the treatment effect more accurately.When the scale factor is selected as 16,the best distinguishing effect can be obtained.

High intensity focused ultrasound,liver disease and bridging therapy

High-intensity focused ultrasound(HIFU)is a noninvasive modality that uses an extracorporeal source of focused ultrasound energy.This technique was introduced by Lynn et al and is able to induce coagulative necrosis in selected tissues without damaging adjacent structures.Although HIFU has been studied for 50years,recent technological developments now allow its use for tumours of the liver,prostate and other sites.In liver disease,HIFU has been used to treat unresectable,advanced stages of hepatocellular carcinoma(HCC)and liver metastases.Hepatocellular carcinoma is a serious health problem worldwide and is endemic in some areas because of its association with hepatitis B and C viruses(in 20%of cases).Liver transplantation(LT)has become one of the best treatments available because it removes both the tumour and the underlying liver disease such as cirrhosis(which is present in approximately 80%of cases).The prerequisite for longterm transplant success depends on tumour load and strict selection criteria regarding the size and number of tumour nodules.The need to obtain the optimal benefit from the limited number of organs available has prompted strict selection criteria limited to only those patients with early HCC who have a better long-term outcome after LT.The so-called"bridging therapy"has the aim of controlling disease burden for patients who are on the organ transplant waiting list.Amongst various treatment options,transarterial chemoembolisation and radiofrequency ablation are the most popular treatment choices.Recently,Cheung et al demonstrated that HIFU ablation is a safe and effective method for the treatment of HCC patients with advanced cirrhosis as a bridging therapy and that it reduced the dropout rate from the liver transplant waiting list.In this commentary,we discuss the current value of HIFU in the treatment of liver disease,including its value as a bridging therapy,and examine the potential advantages of other therapeutic strategies.

Enhancement of antitumor vaccine in ablated hepatocellular carcinoma by high-intensity focused ultrasound

AIM:To investigate whether tumor debris created by high-intensity focused ultrasound(HIFU)could trigger antitumor immunity in a mouse hepatocellular carcinoma model. METHODS:Twenty C57BL/6J mice bearing H22 hepatocellular carcinoma were used to generate antitumor vaccines.Ten mice underwent HIFU ablation,and the remaining 10 mice received a sham-HIFU procedure with no ultrasound irradiation.Sixty normal mice were randomly divided into HIFU vaccine,tumor vaccine and control groups.These mice were immunized with HIFU-generated vaccine,tumor-generated vaccine,and saline,respectively.In addition,20 mice bearing H22 tumors were successfully treated with HIFU ablation. The protective immunity of the vaccinated mice was investigated before and after a subsequent H22 tumor challenge.Using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay,the cytotoxicity of splenic lymphocytes co-cultured with H22 cells wasdetermined in vitro before the tumor challenge,and tumor volume and survival were measured in vivo after the challenge in each group.The mechanism was also explored by loading the vaccines with bone marrowderived dendritic cells(DCs). RESULTS:Compared to the control,HIFU therapy, tumor-generated and HIFU-generated vaccines significantly increased cytolytic activity against H22 cells in the splenocytes of the vaccinated mice(P<0.001). The tumor volume was significantly smaller in the HIFU vaccine group than in the tumor vaccine group(P <0.05)and control group(P<0.01).However,there was no tumor growth after H22 rechallenge in the HIFU therapy group.Forty-eight-day survival rate was 100%in mice in the HIFU therapy group,30%in both the HIFU vaccine and tumor vaccine groups,and 20% in the control group,indicating that the HIFU-treated mice displayed significantly longer survival than the vaccinated mice in the remaining three groups(P< 0.001).After bone marrow-derived DCs were incubated with HIFU-generated and tumor-generated vaccines, the number of mature DCs expressing MHC-Ⅱ + ,CD80 + and CD86 + molecules was significantly increased,and interleukin-12 and interferon-γlevels were significantly higher in the supernatants when compared with immature DCs incubated with mouse serum(P<0.001). However,no differences of the number of mature DCs and cytokine levels were observed between the HIFU- generated and tumor-generated vaccines(P>0.05). CONCLUSION:Tumor debris remaining after HIFU can improve tumor immunogenicity.This debris releases tumor antigens as an effective vaccine to develop host antitumor immune response after HIFU ablation.

Sequential transcatheter arterial chemoembolization,three-dimensional conformal radiotherapy,and high-intensity focused ultrasound treatment for unresectable hepatocellular carcinoma patients

The purpose of this study was to evaluate the outcome of patients with unresectable hepatocellular carcinoma（HCC） treated by sequential therapy of transcatheter arterial chemoembolization（TACE）,three-dimensional conformal radiotherapy（3-DCRT） and high-intensity focused ultrasound（HIFU）.From October,2005 to September,2010,120 patients with unresectable HCC received the sequential treatments of several courses of TACE followed in 2-4 weeks by 3-DCRT and then a single session of HIFU with a curative intent.The median tumor irradiation dose was 40 Gy.Tumor response,toxicity and overall survival rate were analyzed.Clinicopathologic factors affecting the primary technique effectiveness and overall survival rates were investigated by univariate analysis or multivariate analysis.All 120 HCC patients were followed up by the last follow-up time.Among these patients,hepatic toxicities due to treatment were notable in 9 cases.Gastrointestinal bleeding after the overall treatment occurred in 2 cases,leukopenia of grade III was detected in 1 case,radiation-induced liver disease（RILD） was observed in 2 patients,and first-and second-degree skin burn around the HIFU treatment zone were observed in 2 patients and 1 patient,respectively.Among 120 patients,23,83 and 14 cases achieved partial response,stable disease and progressive disease,respectively.The overall survival rates at 1 year,3 years and 5 years were 70%,35% and 15%,respectively,with a median survival time of 26 months.Both Child-Pugh liver function grading and radiation dose were determined to be independent predictors for overall survival revealed by the multivariate analysis.It is concluded that the sequential therapy of TACE,3-DCRT and HIFU is a promising therapeutic regimen for unresectable HCC.