Minjuan Zheng

Extracorporeal Ablation of Uterine Fibroids With High-Intensity Focused Ultrasound Imaging and Histopathologic Evaluation

The purpose of this study was to evaluate the therapeutic efficacy of high‐intensity focused ultrasound (HIFU) in the treatment of uterine fibroids by using imaging and histopathologic examination.

Enhancement of ultrasound contrast agent in high-intensity focused ultrasound ablation.

High-intensity focused ultrasound (HIFU) is becoming an increasingly attractive modality for ablation. Enhancement of HIFU is an important issue that has been discussed and investigated worldwide. Ultrasound contrast agents are considered to constitute an efficient medium for changing acoustic characteristics and improving energy deposition in the focal region. The role of microbubbles in inducing enhanced heating, cavitation, and other related events in HIFU ablation has been investigated, with the goal of improving coagulation necrosis volume or decreasing acoustic power and exposure duration. Consequently, with the use of ultrasound contrast agents, applications of HIFU are expected to become more efficient, safe, and accurate and to produce fewer adverse effects. This paper reviews studies that have been conducted to investigate the enhancement of ultrasound contrast agents in HIFU ablation through experiments that were carried out in vitro and in vivo; an analysis of results of this enhancement mechanism is provided.

Enhancing Effects of SonoVue, a Microbubble Sonographic Contrast Agent, on High-Intensity Focused Ultrasound Ablation in Rabbit Livers In Vivo

The purpose of this study was to explore the enhancing biological effects of SonoVue (Bracco SpA, Milan, Italy), a sulfur hexafluoride sonographic contrast agent, on high‐intensity focused ultrasound (HIFU) ablation in vivo.

Sonographically guided extracorporeal ablation of uterine fibroids with high-intensity focused ultrasound: midterm results.

To the Editor: In our previous study, we reported the imaging and pathologic results of high-intensity focused ultrasound (HIFU) treatment of uterine fibroids in 119 patients.1 However, we did not mention the follow-up results of these patients. In the following period, we treated another 26 patients. We are very concerned about the follow-up results of these patients, including quality-of-life improvement and symptom recovery. In this study, we mainly focused on the clinical midterm results and complications analysis of these 145 patients. Noninvasive treatment of tumors is highly desirable and provides an alternative to surgery. One such treatment undergoing active research is HIFU.2,3 Although studies have been performed in many different areas, including breast, brain, and liver tumors,4–7 the largest body of work to date has taken place in women with symptomatic uterine fibroids. Most studies in European countries are focused on magnetic resonance imaging–guided HIFU.8–11 In China, however, sonographically guided HIFU is much more popular. In our previous study, we reported our experience using extracorporeal sonographically guided HIFU for the treatment of patients with uterine fibroids and described the imaging and histopathologic evaluation results of the efficacy of HIFU treatment. In this study, we have included more patients and will mainly report the clinical midterm results and complication analysis. Patients with symptomatic fibroids were enrolled in this study at Xijing Hospital of the Fourth Military Medical University, Xi’an, China. Finally, 145 consecutive patients with 220 uterine fibroids underwent HIFU ablation between May 2004 and October 2005. This study was approved by the Institutional Review Board, and written informed consent was obtained from all patients. Table 1 describes the patient data and baseline characteristics of uterine fibroids. An HIFUNIT 9000 tumor therapy system (Shanghai Aishen Technology, Shanghai, China) was used. A schematic diagram of the therapeutic arrangement used in this work is shown in Figure 1. The specific treatment method and treatment parameters are as in the previous study.1 Before treatment, all patients from the study were asked to fill out a questionnaire about fibroid-related symptoms. They were supposed to report the occurrence (yes or no) and intensity (on a scale from 1 to 10, where 1 meant no such symptom and 10 meant maximal severity of the symptom) of the following conditions: (1) menometrorrhagia or hypermenorrhea, (2) dysmenorrheal, (3) dyspareunia, (4) pelvic pain, (5) dysuria, and (6) bulk-related symptoms. Each woman was interviewed 1 week after treatment, and the interest was focused on early complications and the duration until full recovery. Office visits were also planned at 1, 3, 6, and 12 months after HIFU treatment. A telephone interview or office visit also was completed every year thereafter. The women were asked to evalu-

Study of Sequential Histopathologic Changes, Apoptosis, and Cell Proliferation in Rabbit Livers After High-Intensity Focused Ultrasound Ablation

The purpose of this study was to investigate the sequential changes of rabbit liver tissue after high‐intensity focused ultrasound (HIFU) ablation in histopathologic characteristics, apoptosis, and expression of proliferating cell nuclear antigen (PCNA).

Analysis of apoptosis and cell proliferation after high intensity-focused ultrasound ablation combined with microbubbles in rabbit livers.

Objective To analyze apoptosis and expression of proliferating cell nuclear antigen (PCNA) sequentially in the rabbit liver tissue after high-intensity focused ultrasound (HIFU) ablation combined with microbubbles. Methods Fifty rabbits were divided into two groups randomly. Rabbits in group I received injections with ultrasound contrast agent Sonovue, before HIFU ablation, on their livers and those in group II were ablated by a single HIFU exposure without microbubbles. Rabbits were killed on days 0, 1, 3, 7 and 14 after HIFU ablation. The livers were excised for light microscopic examination with hematoxylin and eosin staining, immunohistochemical staining for PCNA expression and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling (TUNEL) staining for apoptosis. Results A fibra tissue band composed of fibrocytes and capillary vessels, which was detected by light microscope in the rim of the targeted area after 3 days in group I, was wider than that in group II. The apoptosis index (the number of apoptotic events divided by the total cell number in the same field) and PCNA-positive index (the number of PCNA-positive cells divided by the total cell number in the same field) in group I on days 0, 1, 3, 7 and14 after HIFU ablation were higher than those in group II. Conclusion Microbubbles can improve the apoptosis and cell proliferation in zones surrounding coagulated necrosis areas after HIFU ablation, which may be explored to benefit enhanced HIFU treatment.

Transplantation of mesenchymal stem cells overexpressing IL10 attenuates cardiac impairments in rats with myocardial infarction

Mesenchymal stem cell (MSC) has been well known to exert therapeutic potential for patients with myocardial infarction (MI). In addition, interleukin‐10 (IL10) could attenuate MI through suppressing inflammation. Thus, the combination of MSC implantation with IL10 delivery may extend health benefits to ameliorate cardiac injury after MI. Here we established overexpression of IL10 in bone marrow‐derived MSC through adenoviral transduction. Cell viability, apoptosis, and IL10 secretion under ischemic challenge in vitro were examined. In addition, MSC was transplanted into the injured hearts in a rat model of MI. Four weeks after the MI induction, MI, cardiac functions, apoptotic cells, and inflammation cytokines were assessed. In response to in vitro oxygen‐glucose deprivation (OGD), IL10 overexpression in MSC (Ad.IL10‐MSC) enhanced cell viability, decreased apoptosis, and increased IL10 secretion. Consistently, the implantation of Ad.IL10‐MSCs into MI animals resulted in more reductions in myocardial infarct size, cardiac impairment, and cell apoptosis, compared to the individual treatments of either MSC or IL10 administration. Moreover, the attenuation of both systemic and local inflammations was most prominent for Ad.IL10‐MSC treatment. IL10 overexpression and MSC may exert a synergistic anti‐inflammatory effect to alleviate cardiac injury after MI.

Stable H3 peptide was delivered by gold nanorods to inhibit LSD1 activation and induce human mesenchymal stem cells differentiation

Recently, lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, regulates post-translational modifications and has great promise as new targets for cancer and other diseases. Moreover, the ability of LSD1 to induce the differentiation of stem cells has attracted great attention in biological fields. In this study, we designed LSD1 peptide inhibitor based on its substrate H3 peptide. Through introducing a disulfide bond to stabilize the native peptide into alpha helical structure, we get a peptide with higher cell permeability and stability compared to its parent form. Using gold nanorods (AuNRs) as delivery systems to deliver stable peptide into human MSCs, the delivery efficiency has been enhanced significantly by flow cytometry and cell fluorescent imaging. The intracellular delivery of stable peptide by AuNRs-PEI-based nanocarriers could inhibit the activation of LSD1, which together with hepatocyte growth factor (HGF) exhibits obviously synergistic effect to induce human MSCs differentiation. Furthermore, the hepatic marker genes AFP (alpha fetal protein) and ck19 are up-regulated by AuNRs-stable peptide (AuNRs- SP- PEI) with HGF. In conclusion, our study is the first time to use stable H3 peptide to inhibit LSD1 activation, which has been further delivered by AuNRs as nanocarriers into human MSCs.

Effects of radiofrequency ablation versus other ablating techniques on hepatocellular carcinomas: a systematic review and meta-analysis

BackgroundPercutaneous ablation has quickly arisen as one of the important alternative treatments for hepatocellular carcinoma (HCC). We aimed to compare the therapeutic effects of radiofrequency ablation (RFA) and other ablative techniques on HCCs.MethodsDatabases were searched to identify literature on complete tumor ablation (CTA), overall survival (OS), local tumor recurrence (LTR), and complications of RFA in the treatment of HCC, compared with those of microwave ablation (MWA), percutaneous ethanol injection (PEI), PEI plus RFA, cryoablation (CRA), laser ablation (LSA), and high-intensity focused ultrasound. Randomized controlled trials and high-quality cohort studies were included in the assessment.ResultsThe effects of MWA and CRA appeared to be similar to those of RFA, but lower rates of LTR and higher rates of CTA in large tumors compared with RFA were reported (P < 0.05). CTA rates were lower in patients treated with PEI (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.06–0.42), and higher in those treated with PEI plus RFA (OR 2.28, 95% CI 1.19–3.60), with an increased incidence of fever (P < 0.05). LSA resulted in lower CTA rates (OR 0.32, 95% CI 0.13–0.81) and OS (hazard ratio 1.47, 95% CI 1.01–2.15), with a lower incidence of complications.ConclusionsCompared with RFA, identical effects were found in MWA and CRA groups. Fewer complications were observed in PEI and LSA group. PEI plus RFA appeared more effective, with a higher rate of complications. Well-designed randomized controlled trials are further needed to confirm above results.

Percutaneous Radiofrequency Ablation of Obstructive Right Ventricular Giant Myxoma

Surgical resection is the conventional therapeutic action for patients with an obstructive cardiac tumor. However, for patients in poor clinical condition, cardiac operation can be risky. We report on the successful percutaneous radiofrequency (RF) ablation treatment of a right ventricular giant myxoma in a 70-year-old woman with right ventricular outflow tract (RVOT) and pulmonary artery stenosis, who was unable to tolerate operation. The treatment was effective in relieving RVOT stenosis and improving symptoms. We believe the RF ablation may also be used as a supplementary technique for the treatment of obstructive cardiac tumors, when only partial resection is possible.