Current potential pathogenic mechanisms of copper-zinc superoxide dismutase 1 (SOD1) in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease which damages upper and lower motor neurons (UMN and LMN) innervating the muscles of the trunk, extremities, head, neck and face in cerebrum, brain stem and spinal cord, which results in the progressive weakness, atrophy and fasciculation of muscle innervated by the related UMN and LMN, accompanying with the pathological signs leaded by the cortical spinal lateral tract lesion. The pathogenesis about ALS is not fully understood, and no specific drugs are available to cure and prevent the progression of this disease at present. In this review, we reviewed the structure and associated functions of copper-zinc superoxide dismutase 1 (SOD1), discuss why SOD1 is crucial to the pathogenesis of ALS, and outline the pathogenic mechanisms of SOD1 in ALS that have been identified at recent years, including glutamate-related excitotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, axonal transport disruption, prion-like propagation, and the non-cytologic toxicity of glial cells. This review will help us to deeply understand the current progression in this field of SOD1 pathogenic mechanisms in ALS.

5-Hydroxytryptamine: a potential therapeutic target in amyotrophic lateral sclerosis.

Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis (ALS) is closely linked to 5-hydroxytryptamine (5-HT). To investigate this further, we administered 5-HT receptor antagonists to SOD1*G93A transgenic (ALS mouse model) and wide-type mice. This involved intraperitoneal injections of either granisetron, piboserod, or ritanserin, which inhibit the 5-HT3, 5-HT4, and 5-HT2 receptors, respectively. The transgenic mice were found to have fewer 5-HT-positive cells in the spinal cord compared with wide-type mice. We found that the administration of granisetron reduced the body weight of the transgenic mice, while piboserod and ritanserin worsened the motor functioning, as assessed using a hanging wire test. However, none of the 5-HT receptor antagonists affected the disease progression. We analyzed the distribution and/or expression of TAR DNA binding protein 43 (TDP-43) and superoxide dismutase 1 G93A (SOD1-G93A), which form abnormal aggregates in ALS. We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists. In addition, the disease-related mislocalization of TDP-43 to the cytoplasm increased markedly for all three drugs. In certain anatomical regions, the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons. These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells. 5-HT could therefore be a potential therapeutic target for amyotrophic lateral sclerosis.

A candidate protective factor in amyotrophic lateral sclerosis: heterogenous nuclear ribonucleoprotein G.

Heterogenous nuclear ribonucleoprotein G is down-regulated in the spinal cord of the Tg(SOD1*G93A)1Gur (TG) amyotrophic lateral sclerosis mouse model. However, most studies have only examined heterogenous nuclear ribonucleoprotein G expression in the amyotrophic lateral sclerosis model and heterogenous nuclear ribonucleoprotein G effects in amyotrophic lateral sclerosis pathogenesis such as in apoptosis are unknown. In this study, we studied the potential mechanism of heterogenous nuclear ribonucleoprotein G in neuronal death in the spinal cord of TG and wild-type mice and examined the mechanism by which heterogenous nuclear ribonucleoprotein G induces apoptosis. Heterogenous nuclear ribonucleoprotein G in spinal cord was analyzed using immunohistochemistry and western blotting, and cell proliferation and proteins (TAR DNA binding protein 43, superoxide dismutase 1, and Bax) were detected by the Cell Counting Kit-8 and western blot analysis in heterogenous nuclear ribonucleoprotein G siRNA-transfected PC12 cells. We analyzed heterogenous nuclear ribonucleoprotein G distribution in spinal cord in the amyotrophic lateral sclerosis model at various time points and the expressions of apoptosis and proliferation-related proteins. Heterogenous nuclear ribonucleoprotein G was mainly localized in neurons. Amyotrophic lateral sclerosis mice were examined at three stages: preonset (60-70 days), onset (90-100 days) and progression (120-130 days). The number of heterogenous nuclear ribonucleoprotein G-positive cells was significantly higher in the anterior horn of the lumbar spinal cord segment of TG mice at the preonset stage than that of control group but lower than that of the control group at the onset stage. The number of heterogenous nuclear ribonucleoprotein G-positive cells in both central canal and surrounding gray matter of the whole spinal cord of TG mice at the onset stage was significantly lower than that in the control group, whereas that of the lumbar spinal cord segment of TG mice was significantly higher than that in the control group at preonset stage and significantly lower than that in the control group at the progression stage. The numbers of heterogenous nuclear ribonucleoprotein G-positive cells in the posterior horn of cervical and thoracic segments of TG mice at preonset and progression stages were significantly lower than those in the control group. The expression of heterogenous nuclear ribonucleoprotein G in the cervical spinal cord segment of TG mice was significantly higher than that in the control group at the preonset stage but significantly lower at the progression stage. The expression of heterogenous nuclear ribonucleoprotein G in the thoracic spinal cord segment of TG mice was significantly increased at the preonset stage, significantly decreased at the onset stage, and significantly increased at the progression stage compared with the control group. heterogenous nuclear ribonucleoprotein G expression in the lumbar spinal cord segment of TG mice was significantly lower than that of the control group at the progression stage. After heterogenous nuclear ribonucleoprotein G gene silencing, PC12 cell survival was lower than that of control cells. Both TAR DNA binding protein 43 and Bax expressions were significantly increased in heterogenous nuclear ribonucleoprotein G-silenced cells compared with control cells. Our study suggests that abnormal distribution and expression of heterogenous nuclear ribonucleoprotein G might play a protective effect in amyotrophic lateral sclerosis development via preventing neuronal death by reducing abnormal TAR DNA binding protein 43 generation in the spinal cord.

Factors influencing treatment decisions in HIFU treatment of adenomyosis: A retrospective study.

Objective: To explore the influencing factors of decision-making in patients with adenomyosis, who are receiving high-intensity focused ultrasound (HIFU) treatment. Methods: A total of 776 patients with adenomyosis were enrolled into HIFU group (241 cases) and hysterectomy group (535 cases) according to the treatment methods. The general data, clinical symptoms, marital and childbearing history, and economic status were compared between the two groups, and factors with P < 0.05 were introduced into multivariate logistic regression analysis to determine the determinants of patients choosing HIFU. Results: The average age of the patients in the HIFU group was 39.1 ± 5.2 years, which was lower than that in the hysterectomy group, which was 45.1 ± 3.9 years (P < 0.05). The basic medical insurance for urban workers in the HIFU group was more than the hysterectomy group (P < 0.05). 95.9% of the hysterectomy group had no desire to have children, compared to 60.6% of the HIFU group, the difference was significant (P < 0.05). The treatment costs of HIFU group were significantly lower than that of hysterectomy group (P < 0.05). The main symptoms of the two groups were dysmenorrhea, menorrhagia, and secondary anemia. The results of multivariate logistic regression analysis showed that 31-40 years old, fertility desire, dysmenorrhea, menorrhagia, anemia and dizziness and fatigue were the influencing factors for the decision-making of HIFU for patients with adenomyosis. Conclusion: 31-40 years old, fertility desire, dysmenorrhea, menorrhagia, anemia and dizziness and fatigue were the influencing factors for patients to choose HIFU treatment. HIFU therapy has emerged as a new option for patients with adenomyosis as an alternative to hysterectomy.

Tolerance and efficacy of HIFU ablation for uterine fibroids NPVR ≥ 90%: a nested case-control study.

OBJECTIVE: To investigate the tolerance and efficacy of HIFU ablation for uterine fibroids with a non-perfused volume ratio (NPVR) ≥ 90%. METHODS: A prospective cohort study of 2411 patients from 20 clinical centers was available. Contrast-enhanced MRI was used to assess the non-perfused volume ratio (NPVR). The International Society of Interventional Radiotherapy (SIR) complication grading system was used as the tolerance index. Uterine Fibroids-related Symptoms-Quality of Life (UFS-QoL) was used to evaluate the efficacy. RESULTS: A total of 1352 patients underwent USgHIFU ablation treatment enrolled, NPVR was median 91.9% (IQR, 81.4%,100.0%). There was 761 case (56.3%) in the NPVR ≥ 90% group in which 17.5% case experienced SIR-B abdominal pain, 591 cases (43.7%) in NPVR < 90% group in which 9.3% case had SIR-B abdominal pain. There were statistically differences in the improvement degree of UFS at 12 months among the four subgroups (NPVR < 70%, 70%-80%, 80%-90%, 90%-100%) (all p < 0.05). CONCLUSIONS: Patients with NPVR ≥ 90% had a higher incidence of SIR-B lower abdominal pain. NPVR was positively correlated with the degree of symptom relief at 12 months, and NPVR ≥ 90% was more likely to obtain better clinical symptom relief.

Transcatheter Arterial Chemoembolization in Combination With High-Intensity Focused Ultrasound for Intermediate and Advanced Hepatocellular Carcinoma: A Meta-Analysis.

Background: The study was conducted to explore whether high-intensity focused ultrasound (HIFU) can improve the effect of transcatheter arterial chemoembolization (TACE) in intermediate and advanced hepatocellular carcinoma (HCC). Methods: PubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, CQVIP, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) comparing the effect of TACE in combination with HIFU group (group A) to TACE alone group (group B) in treating intermediate and advanced HCC. The primary outcomes were overall survival (OS) rate and tumor response rate. The odds ratio (OR) and 95% confidence interval (CI) for each study were calculated and then pooled with fixed effects model or random effects model. Sensitivity analyses and subgroup analyses were conducted. A publication bias was also evaluated. Results: After literature selection, eleven RCTs involving 803 patients were included in this meta-analysis. This meta-analysis revealed that group A was associated with an increased 6-month OS rate (OR = 0.20), 12-month OS rate (OR = 0.23), 24-month OS rate (OR = 0.32), and overall response rate (WHO criterion, OR = 0.22; RECIST criterion, OR = 0.30). Furthermore, subgroup analyses showed no bias in the result. Given the limited number of studies that reported major complications, no additional meta-analysis of complication was conducted. Despite no special treatment, any complication following HIFU treatment was found to subside within 3-7 days. Conclusion: TACE in combination with HIFU is associated with increased OS and tumor response in intermediate and advanced HCC. Current evidence supports the use of HIFU after TACE treatment in intermediate and advanced HCC.

Association between inflammatory bowel diseases and Parkinson's disease: systematic review and meta-analysis.

Growing evidence suggests that there are similar pathological mechanisms and closely related pathogenic risk factors for inflammatory bowel disease (IBD) and Parkinson's disease (PD). However, the epidemiological features of these two diseases are different. This review systematically evaluated the relationship between inflammatory bowel diseases and Parkinson's disease risk. We searched PubMed, Embase, and Cochrane databases to retrieve observational studies of IBD and PD published from inception to October 2019. Nine observational studies, involving 12,177,520 patients, were included in the final analysis. None of the studies had Newcastle-Ottawa Scale scores that suggested a high risk of bias. After adjusting for confounders and excluding heterogeneous studies, the overall risk of PD was significantly higher in IBD patients than in the general population (adjusted risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.15-1.34, P < 0.001). A meta-analysis of the temporal relationship revealed that the incidence of IBD was significantly increased before (adjusted hazard ratio [HR] = 1.26, 95% CI: 1.18-1.35, P < 0.001) and after (adjusted RR = 1.40, 95% CI: 1.20-1.80, P < 0.001) PD diagnosis. After excluding a heterogeneous study, the pooled risk of PD development in patients with ulcerative colitis (adjusted HR = 1.25, 95% CI: 1.13-1.38, P < 0.001) or Crohn's disease (adjusted HR = 1.33, 95% CI: 1.21-1.45, P < 0.01) was significantly increased. Subgroup analysis revealed no significant differences in risk between men (adjusted HR = 1.23, 95% CI: 1.10-1.39) and women (adjusted HR = 1.26, 95% CI: 1.10-1.43); however, older (> 65 years old) IBD patients (adjusted HR = 1.32, 95% CI: 1.17-1.48) may have a higher risk than younger (≤ 65 years old) patients (adjusted HR = 1.24, 95% CI: 1.08-1.42). Patients with IBD who were not treated with anti-tumor necrosis factor-α or azathioprine had significantly higher PD risk (adjusted HR = 1.6, 95% CI: 1.2-2.2). Thus, our meta-analysis indicates a certain correlation between IBD and PD, and suggests that IBD may moderately increase PD risk regardless of sex, especially in patients over 65 years of age. Moreover, early anti-inflammatory therapies for IBD might reduce the risk of developing PD. Our findings suggest an urgent need for an individualized screening strategy for patients with IBD. However, most studies included in this paper were observational, and more randomized controlled trials are needed to confirm the precise association between IBD and PD.

Phosphoinositide-3-kinase regulatory subunit 4 participates in the occurrence and development of amyotrophic lateral sclerosis by regulating autophagy.

The development of amyotrophic lateral sclerosis (ALS) may be related to the abnormal alterations of multiple proteins. Our previous study revealed that the expression of phosphoinositide-3-kinase regulatory subunit 4 (PIK3R4) was decreased in ALS. However, the role of PIK3R4 in ALS pathogenesis remains unknown. This study was the first to find that transfection of PC12 cells with small interfering RNA against the PIK3R4 gene significantly decreased the expression levels of PIK3R4 and the autophagy-related proteins p62 and LC3. Additionally, in vivo experiments revealed that the PIK3R4 protein was extensively expressed in the anterior horn, posterior horn, central canal, and areas surrounding the central canal in cervical, thoracic, and lumbar segments of the spinal cord in adult mice. PIK3R4 protein was mainly expressed in the neurons within the spinal lumbar segments. PIK3R4 and p62 expression levels were significantly decreased at both the pre-onset and onset stages of ALS disease in Tg(SOD1*G93A)1Gur mice compared with control mice, but these proteins were markedly increased at the progression stage. LC3 protein expression did not change during progression of ALS. These findings suggest that PIK3R4 likely participates in the prevention of ALS progression. This study was approved by the Ethics Committee for Animal Care and Use of Jiangxi Provincial People's Hospital, Affiliated People's Hospital of Nanchang University (approval No. 2020025) on March 26, 2020.

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.

A Prediction of NPVR ≥ 80% of Ultrasound-Guided High-Intensity Focused Ultrasound Ablation for Uterine Fibroids.

Objective: To evaluate factors in predicting the treatment outcome of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids with a non-perfused volume ratio (NPVR) of at least 80%. Methods: One thousand patients with uterine fibroids who received USgHIFU were enrolled. Thirty-two independent variables of four dimensions of data set, including general information of patients, clinical symptoms, laboratory tests, and fibroid imaging characteristics, were used to investigate the potential predictors of the NPVR of at least 80% by multivariate logistic regression. NPVR was the gold standard for evaluating the efficiency of HIFU ablation, and a NPVR of at least 80% was considered sufficient ablation, while partial ablation was defined as having an NPVR of <80%. Results: Out of 1,000 fibroids, 758 obtained sufficient ablation and 242 obtained partial ablation, and the median NPVR was 88.3% (interquartile range: 80.3-94.8%). The probability of NPVR reaching 80% fibroids with a signal intensity of T2WI of hypointense, isointense, and hyperintense was 86.4, 76.5, and 62.6%, respectively; fibroids with an enhancement type of T1WI of slight, irregular, and regular was 81.5, 73.6, and 63.7%, respectively; and fibroids with uterine anteroposterior of 30-130 mm was 57.7-78.3%, respectively. In patients with a platelet count of 50 × 109/L-550 × 109/L, the probability of NPVR reaching 80% is from 53.4 to 80.1%, respectively. Conclusions: In predicting NPVR ≥ 80%, the signal intensity on T2WI was the most important factor affecting ablative efficiency, followed by enhancement type on T1WI, uterine anteroposterior, and platelet count.

Comparison of Focused Ultrasound Surgery and Hysteroscopic Resection for Treatment of Submucosal Uterine Fibroids (FIGO Type 2).

The aim of the study described here was to compare the effectiveness of focused ultrasound surgery (FUS), which uses high-intensity focused ultrasound to perform tissue ablation, with that of hysteroscopic transcervical resection of myoma (TCRM) for the treatment of type 2 submucosal fibroids. A prospective cohort study was performed in patients who underwent FUS or TCRM from January 2012 to December 2014. Uterine Fibroid Symptom (UFS) and Quality of Life (QoL) questionnaires were used to measure fibroid-related symptoms and quality of life before and at 3, 6 and 12 mo after treatment. Technical results, adverse events and post-operative recovery times of both groups were also compared. A total of 81 patients with at least one type 2 submucosal fibroid were enrolled. The mean diameter of type 2 submucosal fibroids was 3.8 ± 0.9 cm (range: 2.0-5.0 cm) for 39 patients in the FUS group and 3.5 ± 0.8 cm (range: 2.0-4.8 cm) for the 42 patients enrolled in the TCRM group. No major complication occurred in any patients for either treatment. In both groups, the UFS score decreased significantly and the QoL score increased significantly from baseline successively at 3, 6 and 12 mo post-treatment (p < 0.05). Time spent in hospital post-treatment was significantly shorter (2.56 ± 0.98 d) for the FUS group compared with the TCRM group (3.31 ± 0.60 d) (p < 0.05). Time to return to work after treatment was also significantly shorter for the FUS group (3.14 ± 0.83 d) than for the TCRM group (6.09 ± 0.9 d) (p < 0.05). FUS and TCRM are both tolerable and effective treatments with significant improvement of symptom and quality of life for patients with type 2 submucosal fibroids ≤5 cm in diameter.

Factors influencing thermal injury to skin and abdominal wall structures in HIFU ablation of uterine fibroids.

OBJECTIVE: To investigate the factors which may cause thermal injury of abdominal wall structures in ultrasound-guided high-intensity focussed ultrasound (USgHIFU) ablation of uterine fibroids. METHOD: A total of 892 patients with uterine fibroids diagnosed on contrast-enhanced magnetic resonance imaging (MRI) scans received HIFU ablation and follow-up MRI scanning. After therapy, thermal injury to the skin was assessed via measurement of skin redness, blisters, subcutaneous nodules and to the abdominal wall structures via measurement of signal intensity on T2-weighted MRI images. A total of 151 patients were assigned to the injury group, 741 patients were assigned to the non-injury group. The relationship between patient and treatment parameters and injury were analysed using univariate and multiple logistic regression analyses. RESULTS: Univariate logistic regression revealed that sonication time, sonication time per hour, total energy deposited, distance from uterine fibroid ventral side to skin, volume of uterine fibroids, abdominal wall scar, abdominal wall thickness and body mass index (BMI) all affected whether thermal injury occurred (p < 0.05). Subsequently, multiple logistic regression analysis revealed that total energy (p = 0.000, OR = 2.228, 95% CI 1.831-2.712), abdominal wall scar (p = 0.019, OR = 1.639, 95% CI 1.085-2.477) and abdominal wall thickness (p = 0.000, OR = 1.562, 95% CI 1.313-1.857) were significantly correlated with thermal injury. CONCLUSION: Multiple logistic regression analysis revealed that abdominal wall thickness, total energy and abdominal wall scar were the most significant influencing factors that influenced minimal thermal injury of abdominal wall structures in USgHIFU ablation of uterine fibroids.

Pregnancy outcomes in nulliparous women after ultrasound ablation of uterine fibroids: A single-central retrospective study.

To explore the impact of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids in nulliparous women on subsequent pregnancy and delivery. A retrospective analysis was conducted of nulliparous women who received HIFU treatment at Chongqing Medical University, Chongqing,China, from January 1, 2010, to January 1, 2015. A total of 189 cases were enrolled, the median follow-up time was three years. Among them,there were 131 cases pregnancy with a total of 133 times,the pregnancy rate was 69.3% (131/189),and the spontaneous conception rate was 95.4% (125/131). Of 131 pregnant women, 19 were on-going pregnancy, terminated pregnancy 114 times,which include 93 times successfully delivery with a 76.3% (87/114) full-term birth rate,and the cesarean section rate was 72.0% (67/93). Of 94 newborns,the average birth weight was (3.3 ± 0.4)kg (range:1.5-4.8 kg), and a pair of them were identical twins. The incidence of complications during pregnancy and delivery were 10.8% (10/93) and 7.5% (7/93),respectively,except one woman failed on-going pregnancy and one woman suffered hysterectomy due to the complications,others all successful pregnant and delivered. Multiple-factor regression analysis found that age and infertility history were the important factors that may affect pregnancy after HIFU (P < 0.01). Nulliparous women who undergo HIFU treatment for uterine fibroids can subsequently have successful pregnancy and delivery safely.

[Establishment of New Zealand rabbit models of aplastic anemia].

OBJECTIVE: To screen for the optimal dose of benzene and cyclophosphamide using an orthogonal design for establishment of New Zealand rabbit models of aplastic anemia. METHODS: Following an orthogonal experimental design, the effects of 3 levels of 4 factors, namely the dose of benzene (A), the dose of cyclophosphamide (B), the number of benzene injections (C), and the number of cyclophosphamide injections (D) were tested in the establishment of New Zealand rabbit models of aplastic anemia using a L9 (34) orthogonal table, and the optimal protocol for the model establishment was selected from the 9 experimental groups. Each rabbit received subcutaneous injection of benzene on the back every other day, followed by daily cyclophosphamide injection via the ear vein for prescribed times. The blood routine was examined every 6 days, and before modeling and at 36 days after modeling, a small sample of the femoral bone was collected for bone marrow histopathological examination. RESULTS: Comparison of the white blood cell, erythrocyte and platelet counts among the 9 groups showed successful modeling in Groups 4-9, and daily mean reduction rates of the cell counts in Groups 7, 8, and 9 differed significantly from those in the other groups (P<0.05). In Group 7, bone marrow sections showed low myelodysplasia, reduced hematopoietic tissue, reduced or even absence of megakaryocytes, and increased fat cells. Further observation found that the rabbits in Group 7 had sustained bone marrow suppression, consistent with the clinical characteristics of the disease. CONCLUSION: Stable models of aplastic anemia can be established efficiently in New Zealand rabbits by a combination of 8 subcutaneous injections of benzene at 1.5 mL/kg and 4 intravenous injections of cyclophosphamide at 10 mg/kg.

Dynamic contrast-enhanced MRI serves as a predictor of HIFU treatment outcome for uterine fibroids with hyperintensity in T2-weighted images.

The aim of the present study was to investigate the efficacy of dynamic contrast-enhanced magnetic resonance imaging (MRI) in predicting the outcome of using ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for the treatment of uterine fibroids with T2 hyperintensity under MRI. A total of 131 uterine fibroids from 131 patients that appeared hyperintense under T2-weighted MRI were analyzed. The uterine fibroids were subjectively categorized into slight, irregular or regular enhancement groups, according to pretreatment dynamic contrast-enhanced MRI in the arterial phase within 60 sec after the injection of gadolinium. The non-perfused volume (NPV), which is indicative of successful ablation, was represented as the non-perfused area inside the uterine fibroids on enhanced MRI scans following treatment. Additionally, the treatment duration, treatment efficiency, sonication duration, energy efficiency ratio and any adverse events were recorded. The results indicated that the average NPV ratio for all the treated fibroids was 68.5%, while the average NPV ratios for fibroids with slight, irregular or regular enhancement were 84.7, 70.6 and 57.1%, respectively. Fibroids with regular enhancement were associated with the lowest NPV ratio and the lowest treatment efficiency, but exhibited the highest energy effect ratio and an elevated risk of severe adverse effects. The results of the present study indicate that hyperintense uterine fibroids with slight and irregular enhancement in the arterial phase of dynamic contrast-enhanced MRI are suitable for USgHIFU treatment. By contrast, uterine fibroids with regular enhancement were associated with the lowest treatment efficacy and safety.

Feasibility, Safety, and Efficacy of Accurate Uterine Fibroid Ablation Using Magnetic Resonance Imaging-Guided High-Intensity Focused Ultrasound With Shot Sonication.

The aim of this study was to investigate the feasibility, safety, and efficacy of uterine fibroid treatment using magnetic resonance imaging (MRI)-guided high-intensity focused ultrasound (US) with shot sonication for accurate ablation. Forty-three patients with 51 symptomatic uterine fibroids were treated with MRI-guided high-intensity focused US with shot sonication, which was a small acoustic focus of higher intensity with a shorter time (2 seconds) of US exposure and a shorter cooling time (2-3 seconds). The treatment efficacy and adverse events were analyzed, and the changes in the severity of symptoms and the reduction in fibroid volume were assessed 3 and 6 months after the procedure. All patients were successfully treated in a single session, without major complications, and the mean nonperfused volume ratio ± SD was 84.3% ± 15.7% (range, 33.8%-100%).Complete ablation was achieved in 13 T2-hypointense fibroids from 10 patients, and partial ablation was achieved in 38 fibroids from 33 patients. The overall mean treatment time was 135.0 ± 50.9 minutes (2.2 ± 0.8 hours). The transformed symptom severity scores and mean fibroid volumes decreased significantly after treatment (P < .05). In conclusion, MRI-guided high-intensity focused US with shot sonication is a feasible, safe, and effective technique for ablation of uterine fibroids and complete ablation of T2-hypointense fibroids.

Effect of biological characteristics of different types of uterine fibroids, as assessed with T2-weighted magnetic resonance imaging, on ultrasound-guided high-intensity focused ultrasound ablation.

The aims of this study were to assess the effects of the biological characteristics of different types of uterine fibroids, as assessed with T2-weighted magnetic resonance imaging (MRI), on ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation. Thirty-five patients with 39 symptomatic uterine fibroids who underwent myomectomy or hysterectomy were enrolled. Before surgery, the uterine fibroids were subdivided into hypo-intense, iso-intense, heterogeneous hyper-intense and homogeneous hyper-intense categories based on signal intensity on T2-weighted MRI. Tissue density and moisture content were determined in post-operative samples and normal uterine tissue, the isolated uterine fibroids were subjected to USgHIFU, and the extent of ablation was measured using triphenyltetrazolium chloride. Hematoxylin and eosin staining and sirius red staining were undertaken to investigate the organizational structure of the uterine fibroids. Estrogen and progesterone receptor expression was assayed via immunohistochemical staining. The mean diameter of uterine fibroids was 6.9 ± 2.8 cm. For all uterine fibroids, the average density and moisture content were 10.7 ± 0.7 mg/mL and 75.7 ± 2.4%, respectively; and for the homogeneous hyper-intense fibroids, 10.3 ± 0.5 mg/mL and 76.6 ± 2.3%. The latter subgroup had lower density and higher moisture content compared with the other subgroups. After USgHIFU treatment, the extent of ablation of the hyper-intense fibroids was 102.7 ± 42.1 mm(2), which was significantly less than those of the hypo-intense and heterogeneous hyper-intense fibroids. Hematoxylin and eosin staining and sirius red staining revealed that the homogeneous hyper-intense fibroids had sparse collagen fibers and abundant cells. Immunohistochemistry results revealed that estrogen and progesterone receptors were highly expressed in the homogeneous hyper-intense fibroids. This study revealed that lower density, higher moisture content, sparse collagen fibers, abundant cells and overexpression of estrogen and progesterone receptors are important biological characteristics that resulted in poor efficacy in the treatment of homogeneous hyper-intense fibroids.

Effect of abdominal liposuction on sonographically guided high-intensity focused ultrasound ablation.

OBJECTIVES: The aim of this study was to evaluate the effect of abdominal liposuction on sonographically guided high-intensity focused ultrasound (HIFU) ablation. METHODS: A total of 10 women with uterine fibroids or adenomyosis who had received abdominal liposuction were analyzed after sonographically guided HIFU ablation. Of the 10 women, 6 had a diagnosis of uterine fibroids, and 4 had a diagnosis of uterine adenomyosis. All of them had a history of a horizontal-margin split-cesarean delivery. In addition, 26 women with a history of a single horizontal-margin split-cesarean delivery who had a diagnosis of uterine fibroids or adenomyosis but had not received liposuction were analyzed together as a control group. RESULTS: Of the 10 women, 1 woman with uterine fibroids developed local skin erythema after treatment; 1 women with uterine adenomyosis developed a skin burn after treatment; and the remaining women had obvious skin-burning pain during treatment. All women who had not received liposuction finished the treatment with no serious adverse events during or after treatment. The pain scores and incidence of skin-burning pain were significantly higher in the liposuction group than the control group (P= .021 and .038, respectively). CONCLUSIONS: Abdominal liposuction may increase the risk of skin burns during sonographically guided HIFU ablation.

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.

Outcome of unintended pregnancy after ultrasound-guided high-intensity focused ultrasound ablation of uterine fibroids.

OBJECTIVE: To evaluate the safety of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation of uterine fibroids among women with unintentional pregnancy within 1 year of therapy. METHODS: A retrospective analysis was conducted of 435 women who underwent USgHIFU therapy at Chongqing Medical University, China, between October 1, 2006, and October 1, 2009. RESULTS: Unplanned pregnancy was reported by 24 women within 1 year of USgHIFU ablation; 8 of these women had desired pregnancy before undergoing treatment. A total of 27 fibroids were detected, 24 of which were treated (mean volume 65.9±58.8 cm(3)). Pregnancy was continued by 7 women without any complications. One pregnant woman who had desired pregnancy before therapy underwent an induced abortion owing to concerns about the effects of USgHIFU on the fetus. Fourteen women without pregnancy intention before USgHIFU therapy chose to undergo induced abortion; 2 women experienced spontaneous abortion. No adhesion occurred after USgHIFU therapy. Furthermore, USgHIFU, labor, and abortion had no effect on subsequent menstruation or sexual activities. CONCLUSION: Pregnancy within 1 year after USgHIFU ablation of uterine fibroids appears safe; however, large scale studies are required to confirm these data.