Radiofrequency ablation versus surgical resection for multiple HCCs meeting the Milan criteria: propensity score analyses of 10-year therapeutic outcomes.

AIM: To assess the long-term therapeutic outcomes of radiofrequency ablation (RFA) versus surgical resection (SR) as a first-line treatment for patients meeting the Milan criteria with multiple hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. Between January 2004 and December 2009, among 3,441 patients with treatment-naive HCCs, 88 patients meeting the Milan criteria with multiple HCCs (Barcelona Clinic Liver Cancer [BCLC] A stage) who underwent either RFA (n=62) or SR (n=26) were included. Recurrence-free survival (RFS) and overall survival (OS) rates were compared by using propensity score matching. In addition, multivariate analysis was performed for assess the prognostic factor. RESULTS: Matching yielded 20 matched pairs of patients. In the two matched groups, the RFS rates were 30% and 30% at 5- and 10-years, respectively, in the RFA group and 60% and 48.6% in the SR group (p=0.054). The corresponding OS rates were 63.3% and 46.1% in the RFA group and 100% and 73.6% in the SR group, respectively (p=0.061). In multivariate analysis, treatment type was independently associated with RFS (hazard ratio [HR]=0.51; p=0.043) whereas it was not a statistically significant factor for OS (HR=0.50; p=0.088). CONCLUSION: In patients meeting the Milan criteria with multiple HCCs (BCLC A stage), SR may provide better RFS compared to RFA.

Radiofrequency ablation and transarterial chemoembolisation as first-line treatment for recurrent hepatocellular carcinoma or isolated intrahepatic recurrent hepatocellular carcinoma in transplanted livers.

AIM: To evaluate the efficacy of radiofrequency ablation (RFA) and transarterial chemoembolisation (TACE) as a first-line treatment for isolated intrahepatic recurrent hepatocellular carcinoma (IIR-HCC) after liver transplantation (LT). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board. Between January 2005 and January 2015, 588 consecutive patients underwent LT for the treatment of HCC. Among them, 27 patients with IIR-HCCs after LT who were treated with RFA (n=6) or TACE (n=21) as a first-line treatment were retrospectively included in this study. Disease-free and overall survival rates were estimated using the Kaplan-Meier method. Risk factors affecting these outcomes were assessed with Cox regression models. RESULTS: Except for the total number of recurrent tumours and time-to-tumour recurrence after LT, baseline characteristics were not significantly different between the groups. The 2-year disease-free survival rates for RFA and TACE (20% versus 14%, respectively; p=0.180) and 4-year overall survival rates (33% versus 25%, respectively; p=0.065) were not significantly different between groups. In addition, the types of treatment were not associated with disease-free or overall survival in multivariate analyses. CONCLUSION: TACE may be an effective treatment comparable to RFA in patients with IIR-HCC after LT when RFA is not feasible.

Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus.

Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic-pituitary-adrenal axis activity.

Hepatic radiofrequency ablation: in vivo and ex vivo comparisons of 15-gauge (G) and 17-G internally cooled electrodes.

OBJECTIVE: To compare the performance of the 15-G internally cooled electrode with that of the conventional 17-G internally cooled electrode. METHODS: A total of 40 (20 for each electrode) and 20 ablation zones (10 for each electrode) were made in extracted bovine livers and in in vivo porcine livers, respectively. Technical parameters, three dimensions [long-axis diameter (Dl), vertical-axis diameter (Dv) and short-axis diameter (Ds)], volume and the circularity (Ds/Dl) of the ablation zone were compared. RESULTS: The total delivered energy was higher in the 15-G group than in the 17-G group in both ex vivo and in vivo studies (8.78 ± 1.06 vs 7.70 ± 0.98 kcal, p = 0.033; 11.20 ± 1.13 vs 8.49 ± 0.35 kcal, p = 0.001, respectively). The three dimensions of the ablation zone had a tendency to be larger in the 15-G group than in the 17-G group in both studies. The ablation volume was larger in the 15-G group than in the 17-G group in both ex vivo and in vivo studies (29.61 ± 7.10 vs 23.86 ± 3.82 cm(3), p = 0.015; 10.26 ± 2.28 vs 7.79 ± 1.68 cm(3), p = 0.028, respectively). The circularity of ablation zone was not significantly different in both the studies. CONCLUSION: The size of ablation zone was larger in the 15-G internally cooled electrode than in the 17-G electrode in both ex vivo and in vivo studies. ADVANCES IN KNOWLEDGE: Radiofrequency ablation of hepatic tumours using 15-G electrode is useful to create larger ablation zones.

Percutaneous ultrasonography-guided radiofrequency ablation of hepatocellular carcinomas: usefulness of image fusion with three-dimensional ultrasonography.

AIM: To evaluate the usefulness of fusion imaging with real-time ultrasonography (US) and three-dimensional (3D) US for the guidance of radiofrequency ablation (RFA) of hepatocellular carcinomas (HCCs) 2-5 cm in diameter. MATERIALS AND METHODS: This study was conducted as a retrospective cohort study. It was approved by the institutional review board and informed consent was waived. During percutaneous RFA of HCCs, targeting was performed under conventional fusion imaging guidance, whereas monitoring and controlling were conducted under fusion with 3D US guidance. Technical success, technique effectiveness, incidence of major complications, and local tumour progression rate were evaluated. According to tumour size (small: <3 cm versus medium: 3-5 cm), the roundness indexes of the ablation zones and local tumour progression rates were compared. RESULTS: There were 29 small-sized HCCs (2.5 ± 0.3 cm) and 17 medium-sized HCCs (3.4 ± 0.5 cm). All RFA procedures were performed in a single RFA session. Both the technical success and technique effectiveness rates were 100%. One patient with medium-sized HCC developed a hepatic abscess (n = 1) as a major complication. The local tumour progression rate was 8.7% (4/46) with a mean follow-up period of 18.2 months. The roundness indexes of the ablation zone were not significantly different between small- and medium-sized HCCs, and the local tumour progression rates were also not significantly different between the two groups [3.4% (1/29) versus 17.6% (3/17); p = 0.135]. CONCLUSION: Image fusion with real-time US and 3D US is useful for the guidance of percutaneous RFA for HCCs 2-5 cm in diameter.

Percutaneous radiofrequency ablation of hepatic tumours: factors affecting technical failure of artificial ascites formation using an angiosheath.

AIM: To evaluate the technical feasibility of artificial ascites formation using an angiosheath before percutaneous radiofrequency ablation (RFA) for hepatic tumours and to determine predictive factors affecting the technical failure of artificial ascites formation. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board. One hundred and thirteen patients underwent percutaneous RFA of hepatic tumours after trying to make artificial ascites using an angiosheath to avoid collateral thermal damage. The technical success rate of making artificial ascites using an angiosheath and conversion rate to other techniques after initial failure of making artificial ascites were evaluated. The technical success rate for RFA was assessed. In addition, potential factors associated with technical failure including previous history of transcatheter arterial chemoembolization (TACE) or RFA, type of abdominal surgery, and adjacent perihepatic structures were reviewed. Predictive factors for the technical failure of artificial ascites formation were analysed using multivariate analysis. RESULTS: The technical success rates of artificial ascites formation by angiosheath and that of RFA were 84.1% (95/113) and 97.3% (110/113), respectively. The conversion rate to other techniques after the failure of artificial ascites formation using an angiosheath was 15.9% (18/113). Previous hepatic resection was the sole independent predictive factor affecting the technical failure of artificial ascites formation (p<0.001, odds ratio = 29.03, 95% confidence interval: 4.56-184.69). CONCLUSION: Making artificial ascites for RFA of hepatic tumours using an angiosheath was technically feasible in most cases. However, history of hepatic resection was a significant predictive factor affecting the technical failure of artificial ascites formation.

Acute postoperative pain relief with immediate-release tapentadol: randomized, double-blind, placebo-controlled study conducted in South Korea.

OBJECTIVE: To broaden the ethnic groups in which tapentadol IR is evaluated for treating acute postoperative pain to include Asians. METHODS: In this phase 3, multicenter, double-blind, randomized study, 352 Korean adults with moderate-to-severe pain following hallux valgus surgery received tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours for 72 hours. Patients requesting other (rescue) analgesics during this period were discontinued for lack of efficacy. The primary endpoint, sum of pain intensity difference (SPID) over 48 hours, was evaluated based on the difference between tapentadol IR and placebo in least squares (LS) mean change from baseline using analysis of covariance (ANCOVA). Secondary endpoints included the time to first rescue medication use and the distribution of responder rates. RESULTS: A treatment effect, favoring tapentadol IR, was observed for SPID48 (p < 0.001 for both doses vs. placebo, ANCOVA). The between-group difference (vs. placebo) in LS means of SPID48 was 76.4 (95% CI: 51.0, 101.7) for tapentadol IR 50 mg and 90.6 (95% CI: 65.1, 116.1) for tapentadol IR 75 mg. Time to first rescue medication use was delayed for tapentadol IR (p < 0.001 for both doses vs. placebo; log-rank test). The distribution of responders at 12, 24, 48, and 72 hours favored tapentadol IR (p ≤ 0.001 for both doses vs. placebo; Cochran-Mantel-Haenszel test). Dizziness, nausea, and vomiting were each reported in ≥ 10% tapentadol-treated patients and at an incidence ≥ 2-fold higher vs. placebo. The study findings may be limited by study drug dosing every 4 to 6 hours and frequent monitoring during treatment, neither of which mimic pain treatment in clinical practice. However, any potential bias based on this systematic monitoring of patients would be mitigated by the randomized, double-blind nature of the study, with all treatment groups similarly affected by such biases, if any. CONCLUSIONS: Tapentadol IR reduced acute pain intensity, significantly more than placebo, after orthopedic surgery in Korean patients. CLINICAL TRIAL REGISTRATION: NCT01516008.

Comparison of therapeutic efficacy and safety of radiofrequency ablation of hepatocellular carcinomas between internally cooled 15-G and 17-G single electrodes.

OBJECTIVE: To compare the ablation volume, local tumour progression rate and complication rate of radiofrequency ablation (RFA) for small hepatocellular carcinomas (HCCs) using 15-G and 17-G single electrodes. METHODS: This retrospective study was approved by the institutional review board and informed consent was waived. We reviewed percutaneous RFA cases for HCCs using 15-G or 17-G electrodes without multiple overlapping ablations. A total of 36 pairs of HCCs matched according to tumour size and active tip length were included. We compared ablation volume and complication rate between the two electrode groups. Cumulative local tumour progression rates were estimated using the Kaplan­Meier method and compared using the log-rank test. RESULTS: Tumour size and ablation time were not significantly different between the 15-G and 17-G groups (p50.661 and p50.793, respectively). However, ablation volume in the 15-G electrode group was larger than that in the 17-G group (14.465.4cm3 vs 8.762.5cm3; p,0.001). No statistical difference in complication rates between the two electrode groups was found. The 10- and 20-month local tumour progression rates were not significantly different between the two groups (2.8% and 5.6% vs 11.1% and 19.3%; p50.166). CONCLUSION: Ablation volume by the 15-G electrode was larger than that by the 17-G electrode. However, local tumour progression rate and complication rate were not significantly different between the two electrode groups. ADVANCES IN KNOWLEDGE: RFA of HCC using a 15-G electrode is useful to create larger ablation volumes than a 17-G electrode.

Local tumour progression after loco-regional therapy of hepatocellular carcinomas: value of fusion imaging-guided radiofrequency ablation.

AIM: To assess the value of fusion imaging of real-time ultrasonography (US) with liver computed tomography (CT)/magnetic resonance imaging (MRI) images for planning US of radiofrequency ablation (RFA) in improving conspicuity of the lesions and reducing false-positive detection of local tumour progression (LTP) found after transcatheter arterial chemoembolization (TACE) or RFA of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was approved by the institutional review board and informed consent was waived. Fifty patients with LTP (mean ± SD, 1.5 ± 0.6 cm; range 0.5-3 cm) detected at follow-up CT or MRI were included. Planning US was performed by two radiologists using conventional US first and fusion imaging later in the same session. False-positive detection rates were assessed using conventional US based on the results of fusion imaging. The number cases of initially invisible tumours on conventional US that became visible after image fusion were also evaluated. The true-positive detection rate and conspicuity scores of the index tumours were compared between conventional US and fusion imaging. RESULTS: On conventional US, 40 (80%) out of 50 HCCs with LTP were identified. However, the false-positive detection rate of conventional US was 12.5% (5/40). Out of 10 initially invisible HCCs with LTP on conventional US, six (60%) became visible after image fusion. The true-positive detection rate on conventional US was 70% (35/50), whereas it was increased to 92% (46/50) after image fusion (p = 0.0026). CONCLUSION: Fusion imaging can improve the conspicuity of lesions and reduce the false-positive detection of LTP after TACE or RFA.

Gadoxetic acid-enhanced MRI for T-staging of gallbladder carcinoma: emphasis on liver invasion.

OBJECTIVE: To evaluate the diagnostic performance of gadoxetic acid-enhanced MRI with an emphasis on the usefulness of the hepatobiliary phase (HBP) in T-staging of gallbladder carcinoma. METHODS: 66 patients with surgically confirmed gallbladder carcinoma underwent MRI. Two radiologists independently reviewed two sets of gadoxetic acid-enhanced MRI without and with the HBP. Local tumour spread was evaluated according to T-staging, and the results were compared with pathological findings. The diagnostic performance of two image sets to differentiate each T-stage was compared. RESULTS: The sensitivities of MRI with the HBP to differentiate T1 vs ≥ T2 lesions, ≤ T2 vs ≥ T3 lesions and ≤ T3 vs T4 lesions were 96.3%, 85.7% and 100% for Observer 1 and 92.6%, 95.2% and 100% for Observer 2, respectively (p<0.0001). By adding the HBP, the sensitivities to differentiate ≤ T2 vs ≥ T3 lesions were increased from 66.7% to 85.7% for Observer 1 and from 81.0% to 95.2% for Observer 2, although there was no significant difference (p>0.05). The overall accuracies for T-staging were increased from 80.3% to 86.4% for Observer 1, a statistically significant degree (p=0.046), and from 83.8% to 87.9% for Observer 2 (p>0.05). The k-value for the two observers indicated excellent agreement. CONCLUSION: Gadoxetic acid-enhanced MRI provided acceptable diagnostic performance for T-staging of gallbladder carcinoma. Addition of the HBP aids in the detection of liver invasion. ADVANCES IN KNOWLEDGE: In the T-staging of gallbladder carcinoma, gadoxetic acid-enhanced MRI with the HBP may enhance detection of liver invasion.

First-line radiofrequency ablation with or without artificial ascites for hepatocellular carcinomas in a subcapsular location: local control rate and risk of peritoneal seeding at long-term follow-up.

AIM: To compare the long-term local control of hepatocellular carcinoma (HCC) and risk of peritoneal seeding via percutaneous radiofrequency ablation (RFA) using artificial ascites with those of RFA without artificial ascites. MATERIALS AND METHODS: The Institutional Review Board approved this retrospective study. From April 2005 to February 2008, 160 patients (121 men, 39 women; age range 36-79 years) with a single subcapsular HCC (mean size 2.19 cm) were treated with ultrasonography-guided percutaneous RFA as a first-line therapy. Forty-four patients were treated with RFA using artificial ascites, whereas the other 116 patients were treated without artificial ascites. The cumulative local tumour progression (LTP) and peritoneal seeding were compared in both groups using follow-up computed tomography (CT). Cumulative LTP rates were analysed using the Kaplan-Meier method and the log-rank test. Risk of peritoneal seeding was investigated by means of multivariate analysis. RESULTS: The overall median follow-up period was 52.5 months (range 13-76 months). The 1, 2, 4, and 6 year cumulative LTP rates were 17.1, 27.6, 35.2, and 35.2%, respectively, in the group with artificial ascites, and 8, 15.2, 26.6, and 34.4% in the group without artificial ascites, without significant difference (p = 0.332). The rates of peritoneal seeding were 6.8% (3/44) in the group with artificial ascites and 2.6% (3/116) in the group without artificial ascites, a non-significant difference (p = 0.347). The biopsy prior to RFA was the independent risk factor of peritoneal seeding regardless of the use of artificial ascites. CONCLUSION: Long-term local tumour control and risk of peritoneal seeding were comparable for RFA with or without artificial ascites when used as a first-line therapy for subcapsular HCC.

Preferential killing of human lung cancer cell lines with mitochondrial dysfunction by nonthermal dielectric barrier discharge plasma.

The distinctive cellular and mitochondrial dysfunctions of two human lung cancer cell lines (H460 and HCC1588) from two human lung normal cell lines (MRC5 and L132) have been studied by dielectric barrier discharge (DBD) plasma treatment. This cytotoxicity is exposure time-dependent, which is strongly mediated by the large amount of H2O2 and NOx in culture media generated by DBD nonthermal plasma. It is found that the cell number of lung cancer cells has been reduced more than that of the lung normal cells. The mitochondrial vulnerability to reactive species in H460 may induce distinctively selective responses. Differential mitochondrial membrane potential decrease, mitochondrial enzymatic dysfunction, and mitochondrial morphological alteration are exhibited in two cell lines. These results suggest the nonthermal plasma treatment as an efficacious modality in lung cancer therapy.

Molecular mechanisms of large-conductance ca (2+) -activated potassium channel activation by ginseng gintonin.

Gintonin is a unique lysophosphatidic acid (LPA) receptor ligand found in Panax ginseng. Gintonin induces transient [Ca(2+)]i through G protein-coupled LPA receptors. Large-conductance Ca(2+)-activated K(+) (BKCa) channels are expressed in blood vessels and neurons and play important roles in blood vessel relaxation and attenuation of neuronal excitability. BKCa channels are activated by transient [Ca(2+)]i and are regulated by various Ca(2+)-dependent kinases. We investigated the molecular mechanisms of BKCa channel activation by gintonin. BKCa channels are heterologously expressed in Xenopus oocytes. Gintonin treatment induced BKCa channel activation in oocytes expressing the BKCa channel α subunit in a concentration-dependent manner (EC50 = 0.71 ± 0.08 µg/mL). Gintonin-mediated BKCa channel activation was blocked by a PKC inhibitor, calphostin, and by the calmodulin inhibitor, calmidazolium. Site-directed mutations in BKCa channels targeting CaM kinase II or PKC phosphorylation sites but not PKA phosphorylation sites attenuated gintonin action. Mutations in the Ca(2+) bowl and the regulator of K(+) conductance (RCK) site also blocked gintonin action. These results indicate that gintonin-mediated BKCa channel activations are achieved through LPA1 receptor-phospholipase C-IP3-Ca(2+)-PKC-calmodulin-CaM kinase II pathways and calcium binding to the Ca(2+) bowl and RCK domain. Gintonin could be a novel contributor against blood vessel constriction and over-excitation of neurons.

Differentiating mass-forming intrahepatic cholangiocarcinoma from atypical hepatocellular carcinoma using gadoxetic acid-enhanced MRI.

AIM: To examine the differential features of mass-forming intrahepatic cholangiocarcinoma (ICC) from atypical hypovascular hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived informed patient consent. Seventy patients with pathologically proven ICCs (35) and hypovascular atypical HCCs (35) who had undergone preoperative gadoxetic acid-enhanced MRI were enrolled in this study. Images were analysed for the shape of the lesions and presence of hyperintensity on the T1-weighted image (T1WI) and hypo- or hyperintense areas on the T2-weighted image (T2WI). In addition, images were analysed for the presence of linear hyperintensity or multifocal, tiny, hyperintense foci on T2WI and the presence of rim enhancement during early dynamic phases and a central enhancement with a hypointense rim (target appearance) on the 10 and 20 min hepatobiliary phase images. The significance of these findings was determined by the X(2) test. RESULTS: Univariate analysis revealed that the following significant parameters favour ICC or hypovascular HCC; the presence of T2 hypo- and hyperintense areas and target appearance on the 10 min hepatobiliary phase images favour ICC, and the presence of T2 linear hyperintensity and T2 multifocal hyperintense foci favour hypovascular HCC (p < 0.05). Multivariate analysis revealed that only target appearance on the 10 min hepatobiliary phase was predictive of ICC (p = 0.002) as 30 ICCs (85.7%) showed this feature. However, the target appearance was also observed in all six scirrhous HCCs. CONCLUSION: A target appearance on the 10 min hepatobiliary phase images is the best predictor for identifying mass-forming ICC at gadoxetic acid-enhanced MRI.

Value of diffusion-weighted imaging in the detection of viable tumour after neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer: comparison with T2 weighted and PET/CT imaging.

OBJECTIVES: To evaluate the added value of diffusion-weighted imaging (DWI) in combination with T(2) weighted imaging (T2WI) compared with T2WI alone or positron emission tomography (PET)/CT for detecting viable tumour after neoadjuvant chemoradiation therapy (CRT) in patients with locally advanced rectal cancer. METHODS: 50 consecutive patients with locally advanced rectal cancer (≥T3 or lymph node positive) who underwent neoadjuvant CRT and subsequent surgery were enrolled in this retrospective study. All patients underwent 3.0 T rectal MRI and PET/CT after completing CRT. For qualitative analysis, two radiologists independently reviewed T2WI alone and DWI with T2WI over a 1-month interval. One nuclear medicine physician reviewed PET/CT images using a five-point scale. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting viable tumour were assessed. For quantitative analysis, the apparent diffusion coefficients (ADCs) of the lesions were measured and compared between the viable tumour group and non-viable tumour groups. RESULTS: For detecting viable tumours, DWI with T2WI improved diagnostic accuracies (Reviewer 1 detected 90%; Reviewer 2, 86%) over T2WI alone (Reviewer 1 detected 76%, p=0.5; Reviewer 2, 64%, p=0.013) or PET/CT (48%, p<0.001). The sensitivity of DWI with T2WI (Reviewer 1 detected 98%; Reviewer 2, 91%) was significantly higher than those of T2WI alone (Reviewer 1 detected 77%; Reviewer 2, 64%) or PET-CT (43%, p<0.05). Only for Reviewer 2 was the NPV of DWI with T2WI (43%) significantly different from that of PET/CT (17%, p<0.05). The specificities and PPVs of DWI with T2WI were not improved over those of T2WI alone or of PET/CT (both p>0.05). The mean ADC of the viable tumour group (0.93 × 10(-3) mm(2) sc(-1)) was significantly lower than that of the non-viable tumour group (1.55 × 10(-3) mm(2) sc(-1), p<0.0001). CONCLUSION: Adding DWI to T2WI is helpful for detecting viable tumours after neoadjuvant CRT compared with T2WI alone or PET/CT in patients with locally advanced rectal cancer.

Volumetric feedback ablation of uterine fibroids using magnetic resonance-guided high intensity focused ultrasound therapy.

OBJECTIVE: The purpose of this prospective multicenter study was to assess the safety and technical feasibility of volumetric Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) ablation for treatment of patients with symptomatic uterine fibroids. METHODS: Thirty-three patients with 36 fibroids were treated with volumetric MR-HIFU ablation. Treatment capability and technical feasibility were assessed by comparison of the Non-Perfused Volumes (NPVs) with MR thermal dose predicted treatment volumes. Safety was determined by evaluation of complications or adverse events and unintended lesions. Secondary endpoints were pain and discomfort scores, recovery time and length of hospital stay. RESULTS: The mean NPV calculated as a percentage of the total fibroid volume was 21.7%. Correlation between the predicted treatment volumes and NPVs was found to be very strong, with a correlation coefficient r of 0.87. All patients tolerated the treatment well and were treated on an outpatient basis. No serious adverse events were reported and recovery time to normal activities was 2.3 ± 1.8 days. CONCLUSION: This prospective multicenter study proved that volumetric MR-HIFU is safe and technically feasible for the treatment of symptomatic uterine fibroids. KEY POINTS: • Magnetic-resonance-guided high intensity focused ultrasound allows non-invasive treatment of uterine fibroids. • Volumetric feedback ablation is a novel technology that allows larger treatment volumes • MR-guided ultrasound ablation of uterine fibroids appears safe using volumetric feedback.

Pitfalls in the radiological and pathological correlation of tumour response rates of hepatocellular carcinoma following radiofrequency ablation.

According to the American Association for the Study of Liver Diseases (AASLD) guidelines, radiofrequency ablation (RFA) is a safe and effective treatment for patients with unresectable hepatocellular carcinoma (HCC). In most studies, the initial complete tumour response rates of small HCCs < or =3 cm following RFA have been reported as more than 90% or 95%, and local tumour progression rates have been reported as approximately 10% or 20%. Notwithstanding these promising clinical outcomes, the complete tumour response rates for HCC following RFA as determined by conventional histopathological diagnostic criteria have been reported to be less than 50% in many recent reports. While considering that most cases of local tumour progression of HCC are known to occur within two years following RFA, it may not be reasonable to assume that clinical and radiological examinations have significantly overestimated the tumour response rates. On the contrary, it is likely that the conventional histopathological examination techniques may have underestimated the tumour response rates. The apparent discrepancy between the histopathological and the radiological tumour response of radiofrequency ablation for hepatocellular carcinomas can be attributed to several histological features, such as thermal fixation or apoptosis, that were not included in the conventional histopathological diagnostic criteria. However, a robust conclusion cannot be derived because of lack of adequate controlled studies, and further well designed prospective multicentre trials will be helpful to solve this issue.

Impaired long-term memory and long-term potentiation in N-type Ca2+ channel-deficient mice.

Voltage-dependent N-type Ca(2+) channels, along with the P/Q-type, have a crucial role in controlling the release of neurotransmitters or neuromodulators at presynaptic terminals. However, their role in hippocampus-dependent learning and memory has never been examined. Here, we investigated hippocampus-dependent learning and memory and synaptic plasticity at hippocampal CA3-CA1 synapses in mice deficient for the alpha(1B) subunit of N-type Ca(2+) channels. The mutant mice exhibited impaired learning and memory in the Morris water maze and the social transmission of food preference tasks. In particular, long-term memory was impaired in the mutant mice. Interestingly, among activity-dependent long-lasting synaptic changes, theta burst- or 200-Hz-stimulation-induced long-term potentiation (LTP) was decreased in the mutant, compared with the wild-type mice. This type of LTP is known to require brain-derived neurotrophic factor (BDNF). It was found that both BDNF-induced potentiation of field excitatory postsynaptic potentials and facilitation of the frequency of miniature excitatory postsynaptic currents (mEPSCs) were reduced in the mutant. Taken together, these results demonstrate that N-type Ca(2+) channels are required for hippocampus-dependent learning and memory, and certain forms of LTP.

The JAK2 V617F mutation in de novo acute myelogenous leukemias.

A missense somatic mutation in JAK2 gene (JAK2 V617F) has recently been reported in chronic myeloproliferative disorders, including polycythemia vera, essential thrombocythemia and myelofibrosis with myeloid metaplasia, strongly suggesting its role in the pathogenesis of myeloid disorders. As activation of JAK2 signaling is occurred in other malignancies as well, we have analysed 558 tissues from common human cancers, including colon, breast and lung carcinomas, and 143 acute adulthood leukemias by polymerase chain reaction -- single strand conformation polymorphism analysis. We found three JAK2 mutations in the 113 acute myelogenous leukemias (AMLs) (2.7%), but none in other cancers. The mutations consisted of two V617F mutations and one K607N mutation. None of the AML patients with the JAK2 V617F mutation had a history of previous hematologic disorders. This is the first report on the JAK2 gene mutation in AML, and the data indicated that the JAK2 gene mutation may not only contribute to the development of chronic myeloid disorders, but also to some AMLs.