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.

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.

High-intensity focused ultrasound ablation as a bridging therapy for hepatocellular carcinoma patients awaiting liver transplantation

The scarcity of liver grafts in Asia leads to a significant dropout of patients from liver transplant waiting lists, particularly patients with hepatocellular carcinoma and a low model for end-stage liver disease score. In order to reduce dropping out, different bridging therapies are employed. We report the use of high-intensity focused ultrasound ablation as a bridging therapy for a patient with hepatocellular carcinoma of stage two and an extremely low platelet count (20×10 9 /L). The ablation was successful. Blood tests showed that his liver function was similar before and after the treatment. No adhesion was encountered in the liver transplantation performed six months later.

Treatable focal region modulated by double excitation signal superimposition to realize platform temperature distribution during transcranial brain tumor therapy with high-intensity focused ultrasound

Recently, the phase compensation technique has allowed the ultrasound to propagate through the skull and focus into the brain. However, the temperature evolution during treatment is hard to control to achieve effective treatment and avoid over-high temperature. Proposed in this paper is a method to modulate the temperature distribution in the focal region. It superimposes two signals which focus on two preset different targets with a certain distance. Then the temperature distribution is modulated by changing triggering time delay and amplitudes of the two signals. The simulation model is established based on an 82-element transducer and computed tomography （CT） data of a volunteer＇s head. A finite- difference time-domain （FDTD） method is used to calculate the temperature distributions. The results show that when the distances between the two targets respectively are 7.5-12.5 mm on the acoustic axis and 2.0-3.0 mm in the direction perpendicular to the acoustic axis, a focal region with a uniform temperature distribution （64-65 ℃） can be created. Moreover, the volume of the focal region formed by one irradiation can be adjusted （26.8-266.7 mm3） along with the uniform temperature distribution. This method may ensure the safety and efficacy of HIFU brain tumor therapy.

Salvage Transrectal High-Intensity Focused Ultrasound Therapy for Patients with Recurrence of Vesico-Urethral Anastomosis after Radical Prostatectomy

Background: Salvage radiotherapy has been used as the treatment for patients with local recurrence after radical prostatectomy. However, the therapy is time-consuming and it experiences adverse effects of some kind. Simple and less invasive treatment is highly anticipated. Objectives: To evaluate the outcomes of salvage transrectal high-intensity focused ultrasound (HIFU) therapy for patients with localized recurrence of a vesicourethral anastomosis (VUA) after radical prostatectomy. Material and methods: Sixteen patients with suspected local recurrence of a VUA after prostatectomy were treated with HIFU. All patients had prostate-specific antigen (PSA) failure (>0.2 ng/ml), positive findings of a VUA with biopsy and/or MRI, TRUS and CT, and no distant metastasis by CT, MRI and bone scintigraphy before HIFU. Recurrence after HIFU was determined by PSA failure (>0.2 ng/ml), histological findings, metastasis and start of systemic therapies. Results: HIFU treatments were performed in 16 patients, and followed-up for 7 - 159 months (median 46.5). The pre-HIFU PSA levels ranged from 0.318 to 3.1 ng/ml. Sonication time ranged from 9 - 42 min. All patients had a decline of PSA after HIFU, and 88% of the PSA nadir was Conclusion: HIFU therapy for local recurrence after prostatectomy may become a feasible salvage therapeutic option because of its ease and simple procedure. For salvage HIFU therapy, further research and additional follow-up are required to evaluate and correct the diagnosis of recurrence areas and to provide the sufficient sonication.

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.

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.

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 MRI 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.

Experimental Study on the Effect of High-intensity Focused Ultrasound (HIFU) Using Sonablate-500 in the Ablation of Canine Prostate

To investigate the safety, feasibility and effectiveness of transrectal high-intensity focused ultrasound （HIFU） in the ablation of canine prostate, 20 dogs were divided randomly into 5 groups. Sixteen canine prostates were treated with the third-generation transrectal HIFU device （Sonablate-500^TM）. Transrectal ultrasound images of the prostate and prostatic urethra were observed preoperatively and postoperatively. Serial study was performed 30 min, 30 days, 60 days and 180 days after the therapy. The rectum, periprostatic tissues, and prostate were excised en bloc and the tissues were fixed for gross and histological analysis. Our results showed that the average maximal diameter of prostatic urethra was 0.59-0.11 cm before the operation and 2.57±0.98 cm 60 days after the operation. The volume of prostate was 6.5±3.12 cm^3 before the treatment while the volume was 4.13±0.23 cm^3 60 days after the treatment and the differences were statistically significant （P〈0.05）. Histologically, there was a clear demarcation between the necrotic area of the treated tissues and the unaffected surrounding tissues. All the necrotic tissues in the targeted zone broke off and the prostatic urethra became cavitary 60 days later. The more frequent complications were urinary retention and frequency and hematuria. No rectal injury occurred during the treatment. It is concluded that the third-generation transrectal HIFU is capable of destroying prostatic tissue, substantially increasing the width of the prostatic urethra without causing injury to the adjacent tissues. The risk of postoperative complications associated with HIFU was low. HIFU may become a safe, effective and minimally invasive alternative for the treatment of prostatic diseases.

High-energy-density electron beam generation in ultra intense laser-plasma interaction

By using a two-dimensional particle-in-cell simulation,we demonstrate a scheme for highenergy-density electron beam generation by irradiating an ultra intense laser pulse onto an aluminum（Al） target.With the laser having a peak intensity of 4×10^23W cm^-2,a high quality electron beam with a maximum density of 117 nc and a kinetic energy density up to8.79×10^18J m^-3 is generated.The temperature of the electron beam can be 416 Me V,and the beam divergence is only 7.25°.As the laser peak intensity increases（e.g.,1024 W cm^-2）,both the beam energy density（3.56×10^19J m^-3） and the temperature（545 Me V） are increased,and the beam collimation is well controlled.The maximum density of the electron beam can even reach 180 nc.Such beams should have potential applications in the areas of antiparticle generation,laboratory astrophysics,etc.

High-order harmonic generation spectrum of an excited one-dimensional Coulomb atom in an intense laser field

Response of the wave packet of a one-dimensional Coulomb atom to an intense laser field is calculated using the symmetrized split operator fast Fourier method. The high-order harmonic generation （HHG） of the initial state separately being the ground and excited states is presented. When the hardness parameter a in the soft Coulomb potential V（x） =-1√x^2＋α is chosen to be small enough, the so-called hard Coulomb potential V（x）=1/｜x｜ can be obtained. It is well known that the hard one-dimensional Coulomb atom has an unstable ground state with an energy eigenvalue of - 0.5 and it has no states corresponding to physical states in the true atoms, and has the first and second excited states being degenerate. The parity effects on the HHG can be seen from the first and second excited states of the hard one-dimensional Coulomb atom. The HHG spectra of the excited states from both the soft and hard Coulomb atom models are shown to have more complex structures and to be much stronger than the corresponding HHG spectrum of the ground state of the soft Coulomb model with a = 2 in the same laser field. Laser-induced non-resonant one-photon emission is also observed.

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.

Resolving multi-orbital effects on high harmonic generation from aligned N2 molecules in linearly and elliptically polarized intense laser fields

We perform an experimental study of the multi-orbital effect on the high-order harmonic generation(HHG) from aligned N_2 molecules in both linearly and elliptically polarized intense laser fields.Measured by a home-built extreme ultraviolet(XUV) flat grating spectrometer with the pump-probe method, the angular distributions of different orders of HHG are obtained, which show distinctive behaviors for harmonics in the plateau and the cut-off regions.The ellipticity dependence of HHG is investigated by aligning the molecular axis parallel or perpendicular to the laser polarization.Our results indicate that both the highest occupied molecular orbital(HOMO) as well as the lower one(HOMO-1) contribute to the HHG of N2 molecules, in either linearly or elliptically polarized intense laser field.The study paves the way for understanding the ultrafast electron dynamics of molecules exposed to an intense laser field.

Atomic high-order harmonic generation from a circularly polarized laser pulse

We demonstrate theoretically that the high-order harmonic of an atom can be generated by a circularly polarized laser pulse.The harmonic spectrum shows a clear cutoff with an energy Ip ＋ 2Up.In particular,the high-order harmonic generation comes from the multiple recombination of the ionized electron with non-zero initial velocity.These results are verified by the classical model theory and the time-frequency analysis of a harmonic spectrum.

Analysis of electro-optical intensity modulator for bunch arrival-time monitor at SXFEL

A bunch arrival-time monitor(BAM) based on an electro-optical intensity modulation scheme is currently under development at Shanghai Soft X-ray Free-Electron Laser to meet the high-resolution requirements for bunch stability. The BAM uses a radio frequency signal generated by a pickup cavity to modulate the reference laser pulses in an electro-optical intensity modulator(EOM), and the bunch arrival-time information is derived from the amplitude change of the laser pulse after laser pulse modulation.EOM is a key optical component in the BAM system.Through the basic principle analysis of BAM, many parameters of the EOM are observed to affect the measurement resolution of the BAM system. Therefore, a systematic analysis of the EOM is crucial. In this paper, we present two schemes to compare and analyze an EOM and provide a reference for selecting a new version of the EOM.

Absorption of ultrashort intense lasers in laser–solid interactions

With the advent of ultrashort high intensity laser pulses, laser absorption during the laser–solid interactions has received significant attention over the last two decades since it is related to a variety of applications of high intensity lasers,including the hot electron production for fast ignition of fusion targets, table-top bright X-ray and gamma-ray sources,ion acceleration, compact neutron sources, and generally the creation of high energy density matters. Normally, some absorption mechanisms found for nanosecond long laser pulses also appear for ultrashort laser pulses. The peculiar aspects with ultrashort laser pulses are that their absorption depends significantly on the preplasma condition and the initial target structures. Meanwhile, relativistic nonlinearity and ponderomotive force associated with the laser pulses lead to new mechanisms or phenomena, which are usually not found with nanosecond long pulses. In this paper, we present an overview of the recent progress on the major absorption mechanisms in intense laser–solid interactions, where emphasis is paid to our related theory and simulation studies.

Sleep Quality for Patients Receiving Noninvasive Positive Pressure Ventilation and Nasal High-Flow Oxygen Therapy in an ICU: Two Case Studies

Aim: The purpose of this case study was to examine the sleep quality of patients receiving noninvasive positive pressure ventilation (NPPV) or nasal high-flow oxygen therapy (NHF) in an intensive care unit and to investigate what types of nursing support are offered to such patients. Methods: We examined one patient each for NPPV and NHF. Polysomnography (PSG), review of the patient charts, and semi-structured interviews were used to collect the data for analysis. Results: Patients treated with NPPV or NHF demonstrated a noticeable reduction in deep sleep, with most of their sleep being shallow. Their sleep patterns varied greatly from those of healthy individuals. These results suggest that, in addition to experiencing extremely fragmented sleep, sleep in these patients was more likely to be interrupted by nursing interventions, such as during auscultation of breath sounds. Furthermore, it was revealed that “anxiety or discomfort that accompanies the mask or air pressure” in patients treated with NPPV and “discomfort that accompanies the nasal cannula or NHF circuit” in patients treated with NHF may be primary causes of disrupted sleep. Our results suggest a need for nursing care aimed at improving sleep quality in patients treated with NPPV or NHF.

Harnessing macrophages in thermal and non-thermal ablative therapies for urologic cancers-Potential for immunotherapy

Prostate and bladder cancers are one of the cancers occurring worldwide.In addition to radical surgery,the past decade has also focused on targeted therapy of overexpressed cancer proteins that are lethal and critical for cancer cell survival.However,targeted therapy cannot adapt for changing of cancer molecular characteristics and,ultimately,a clone that bypasses the targeted therapy emerges.This can be overcome by immunotherapy.New studies on ablative therapy of cancers show presence of immunomodulatory effect in these modalities.Tumor ablation prime the immune system for further destruction of persistent primary tumor in addition to destruction of concurrent metastatic disease and also reduce recurrence.Ablative therapies can achieve a state of increased antigenicity.Its combination with a novel macrophage targeted therapy may enhance immune priming,trafficking,and/or effector phases;thereby improving clinical outcomes.Tumor associated macrophages or M2 phenotype are now known to mediate this immunosuppressive pro-tumorigenic effect.Alteration of macrophage differentiation may enhance tumor destruction of ablative therapy.This breakthrough in immunotherapy opens up arenas for further robust clinical trials on combinatorial therapies.In the present review,we aim to elucidate the major aspects of immune stimulatory minimal invasive approaches by combining with macrophage directed pathways.

前列腺癌局灶治疗的研究进展

前列腺癌是全世界男性中第二常见的肿瘤性疾病,并且其发病率仍呈现逐步上升的趋势。大部分前列腺癌患者都采用根治性前列腺切除术的方式进行治疗,不过随着影像学的发展和理论技术的创新,前列腺癌局灶治疗表现出了更好的应用前景。与根治性前列腺切除术相比,前列腺癌局灶治疗具有良好的疗效和较少的并发症,并且可以避免过度治疗和降低疾病治疗的经济负担。本文通过分析近年来前列腺癌局灶治疗的临床试验,对冷冻消融、高强度聚焦超声、不可逆电穿孔、光动力疗法在内的局灶治疗方法作一综述。

基于真实世界的高强度聚焦超声联合中药二期双联疗法治疗子宫腺肌病的临床研究

目的:评价高强度聚焦超声(high intensity focused ultrasound,HIFU)联合中药二期双联疗法治疗子宫腺肌病(adenomyosis,AM)的临床疗效。方法:收集2017年9月至2022年12月于成都中医药大学附属医院就诊,明确诊断为AM并进行HIFU治疗的194例患者为研究对象,其中试验组102例予以HIFU联合中药二期双联疗法治疗3月,对照组92例单纯行HIFU治疗,两组均随访至术后6月。以中医药干预和预后影响因素为暴露和混杂因素,将真实医疗环境中的临床资料和随访数据采用倾向性评分法控制混杂因素,将两组临床基线资料进行倾向性匹配,得到每组61例患者。比较两组患者治疗后的临床表现(痛经程度、月经量、子宫体积、病灶体积)、生活质量的改善情况(UFS-QOL、EQ-5D量表)、治疗满意度、术后不良反应等。结果:所有患者治疗后在痛经、月经量、子宫及病灶体积等临床表现方面得到有效改善(P<0.05),且试验组较对照组疗效更好(P<0.05)。UFS-QOL、EQ-5D量表及治疗满意度比较显示,试验组在改善AM患者HIFU术后的生活质量和治疗满意度方面优于对照组(P<0.05)。所有不良反应轻微,均不需临床处理。结论:HIFU治疗AM在改善痛经、减少月经量、促进子宫及病灶体积的缩小等方面取得较好临床疗效;HIFU术后联合中医药治疗可进一步增强疗效,可行性高,不良反应少,能有效提高患者生活质量,临床可根据患者病情推荐使用中医药治疗作为术后联合治疗方案。