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BACKGROUND Strategies for integrating artificial intelligence (AI) into thyroid nodule management require additional development and testing. We developed a deep-learning AI model (ThyNet) to differentiate between malignant tumours and benign thyroid nodules and aimed to investigate how ThyNet could help radiologists improve diagnostic performance and avoid unnecessary fine needle aspiration. METHODS ThyNet was developed and trained on 18 049 images of 8339 patients (training set) from two hospitals (the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, and Sun Yat-sen University Cancer Center, Guangzhou, China) and tested on 4305 images of 2775 patients (total test set) from seven hospitals (the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; the Guangzhou Army General Hospital, Guangzhou, China; the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; the First Affiliated Hospital of Sun Yat-sen University; Sun Yat-sen University Cancer Center; and the First Affiliated Hospital of Guangxi Medical University, Nanning, China) in three stages. All nodules in the training and total test set were pathologically confirmed. The diagnostic performance of ThyNet was first compared with 12 radiologists (test set A); a ThyNet-assisted strategy, in which ThyNet assisted diagnoses made by radiologists, was developed to improve diagnostic performance of radiologists using images (test set B); the ThyNet assisted strategy was then tested in a real-world clinical setting (using images and videos; test set C). In a simulated scenario, the number of unnecessary fine needle aspirations avoided by ThyNet-assisted strategy was calculated. FINDINGS The area under the receiver operating characteristic curve (AUROC) for accurate diagnosis of ThyNet (0·922 [95% CI 0·910-0·934]) was significantly higher than that of the radiologists (0·839 [0·834-0·844]; p

Diffuse leptomeningeal glioneuronal tumor with the first symptom of acute rapid blindness in both eyes are rare in adolescents. We present a case of an adolescent female without a history of cancer who developed a dramatic loss of vision and eventually blindness, and was diagnosed as diffuse leptomeningeal glioneuronal tumor by cerebrospinal fluid cytology and enhanced MRI. In order to save vision, under the condition of ineffective dehydration treatment, timely emergency surgery to implant Ommaya sac drainage cerebrospinal fluid. According to the pathophysiological mechanism of cerebral edema, we added Edaravone to scavenge oxygen free radicals, Alprostadil to improve microcirculation, Monosialotetrahexosylganglioside nutrient nerve, Butylphthalide to promote collateral circulation, combined with hyperbaric oxygen and acupoint injection of Anisodine. Finally, the patient's vision returned to normal. Conclusion: when dehydration treatment is ineffective, timely surgery to reduce intracranial pressure, combined with comprehensive treatment, can effectively save vision.

Diffuse leptomeningeal glioneuronal tumor has various clinical manifestations and is easily misdiagnosed. This article aims to describe the clinical features of a patient with diffuse leptomeningeal glioneuronal tumor misdiagnosed as optic neuromyelitis lineage disease (NMOSD), analyze the causes of misdiagnosis, and identify the disease with similar clinical manifestations. Adolescent women with decreased vision and headache, nausea, and vomiting were initially diagnosed as NMOSD. Immunotherapy was ineffective; enhanced MRI and cerebrospinal fluid cytology examination were completed and compared with classic meningeal carcinoma, NMOSD, multiple sclerosis, and Vogt-Koyanagi-Harada (VKH) syndrome. Diffuse leptomeningeal glioneuronal tumor was finally diagnosed in adolescent women with no history of tumor. Compared with NMOSD: no history of infection, no AQP4, MOG antibody, no spinal segmental abnormalities, immunotherapy was ineffective; compared with multiple sclerosis: no history of infection, no plaque, no oligoclonal antibody, immunotherapy was ineffective; compared with VKH syndrome: no history of infection, no fever, no treatment for immunotherapy; and compared with classic meningeal carcinoma: adolescents, no extracranial tumor lesions, super high protein, more different sugar excess. Patients with acute visual impairment should consider not only NMOSD, but also diffuse leptomeningeal glioneuronal tumor (DLGNT) and other diseases. DLGNT could not be excluded when CSF cytology and MRI plain scan were negative. The positive rate of malignant cells can only be increased by repeatedly sending fresh cerebrospinal fluid for examination; DLGNT needs to be differentiated from NMOSD, multiple sclerosis, VKH syndrome, and other diseases. Early diagnosis and molecular targeted therapy can improve the quality of life and prolong life.

The development of micro-cracks during damage to rocks affects the propagation of macroscopic cracks on the surface. To explore the crack evolution among pre-existing flaws in rocks, based on the acoustic emission (AE) source location results, the paper analysed the influences of micro-crack development on failure mode. By analyzing AE characteristic parameters, the main controlling factors affecting the development of micro-fractures are determined. The results show that: (1) the development of micro-cracks in rock samples presents a trend of having a high-energy fracture point, the low-energy and small fracture region, the extensive fracture region, and a macroscopic fracture zone. (2) The difference in rock failure mode arises from the influence of rock bridge on the number, location, and extension direction of high-energy fractures, which results in the difference in the formation of main damage zone in rock samples. (3) The total number of micro-cracks, the proportion of shear cracks, and mixed-mode cracks gradually increase with the increase of the rock bridge inclination angle, leading to the gradual evolution of rock samples from simple tensile failure mode to complex crack penetration mode. The variation of the rock bridge inclination angle affects the stress direction of the rock particles at a microscopic level, while it affects the direction of macroscopic crack propagation at a macroscopic level.

Purpose This trial evaluated the addition of cetuximab to a modified FOLFOXIRI (mFOLFOXIRI: 5-fluorouracil/folinic acid, oxaliplatin, irinotecan) as conversion therapy in a two-group, nonrandomized, multicenter, phase II trial in patients with initially technically unresectable colorectal liver-limited metastases (CLM) and BRAF/RAS wild-type. Patients and Methods Patients were enrolled to receive cetuximab (500 mg/m2) plus mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, folinic acid 400 mg/m2, 5-fluorouracil 2,800 mg/m2 46-hour infusion, every 2 weeks) (the cetuximab group) or the same regimen of mFOLFOXIRI alone (the control group), in a 2:1 ratio allocation. The primary endpoint was the rate of no evidence of disease (NED) achieved. Secondary endpoints included resection rate, objective response rate (ORR), survival, and safety. Results Between February 2014 and July 2019, 117 patients were registered for screening at six centers in China, and 101 of these were enrolled (67 cetuximab group, 34 control group). The rate of NED achieved was 70.1% in the cetuximab group and 41.2% in the control group (difference 29.0%; 95% confidence interval [CI], 9.1%–48.8%; p = .005). Patients in the cetuximab group had improved ORR (95.5% vs. 76.5%; difference 19.1%; 95% CI, 17.4%–36.4%; p = .010) compared with those in control group. Progression-free survival and overall survival showed the trend to favor the cetuximab group. The incidence of grade 3 and 4 adverse events was similar in the two groups. Conclusion Addition of cetuximab to mFOLFOXIRI improved the rate of NED achieved. This combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable CLM. Implications for Practice This trial evaluated the addition of cetuximab to a modified FOLFOXIRI as conversion therapy in a phase II trial in patients with initially technically unresectable colorectal liver-limited metastases and BRAF/RAS wild-type. The rate of no evidence of disease achieved was 70.1% in the cetuximab plus modified FOLFOXIRI group and 41.2% in the modified FOLFOXIRI group. Objective response rates, overall survival, and progression-free survival were improved in the cetuximab group when compared with the modified FOLFOXIRI group. Addition of cetuximab to modified FOLFOXIRI increased the rate of no evidence of disease achieved, and this combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable colorectal liver-limited metastasis.

COVID-19 is currently a pandemic in the world, can invade multiple systems, and has a high morbidity and mortality. So far, no cases of acute cerebrovascular disease have been reported. This article reports the clinical features of a COVID-19 patient whose first symptom was cerebral hemorrhage. More importantly, after the craniotomy, the patient had high fever and it was difficult to retreat. After cerebrospinal fluid testing, it was determined that an intracranial infection had occurred. After anti-infection and plasma infusion of the recovered person, the patient's symptoms gradually improved. This case suggests that COVID-19 may infringe on cerebral blood vessels and cause cerebral hemorrhage. Transfusion of plasma from rehabilitation patients is effective for critically ill patients.

OBJECTIVES Increasing studies have reported focal chemotherapy-induced sinusoidal injury (CSI) mimicking colorectal liver metastasis (CRLM) on imaging studies, resulting in unnecessary lobectomy. This study aimed to investigate the contrast-enhanced ultrasound (CEUS) imaging features of focal CSI. METHODS We retrospectively evaluated 16 patients who had a pathologic diagnosis of focal CSI and underwent CEUS between January 2013 and January 2019. The images were compared with those obtained from 27 patients with CRLM. RESULTS On CEUS, 14 (87.5%) focal CSIs showed heterogeneous isoenhancement, 1 (6.3%) peripheral hyperenhancement, and 1 (6.3%) homogeneous hyperenhancement during the arterial phase. Compared with the adjacent liver parenchyma, the initial enhancement time of focal CSI was earlier in 2 (12.5%), simultaneous in 9 (56.3%), and later in 5 (31.3%) patients. In the portal and late phases, all of the focal CSI cases showed hypoenhancement compared with the adjacent liver parenchyma. Focal CSI had the following CEUS findings, which were different from those of CRLM: (1) heterogeneous isoenhancement in the arterial phase (87.5% versus 0%; P

Purpose: To investigate the clinical effectiveness and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for colorectal liver metastasis (CRLM) and evaluate the influencing factors of local efficacy. Methods: From January 2013 to January 2017, 137 CRLM patients accepting US-guided percutaneous MWA were included. The 2450-MHz microwave ablation system and a cooled-shaft antenna were used. All patients were regularly followed up for at least 6 months. Technical success, complete ablation, local tumor progression (LTP), complications and side effects were assessed. Logistic regression analysis was used to identify the independent prognostic factors for LTP. Results: In total, 411 lesions (mean diameter 15.4 ± 7.2 mm, range 5–67 mm) were treated. Complete ablation was achieved in 99.27% (408/411) of lesions and 97.81% (134/137) of patients. LTP occurred in 5.35% (22/411) of lesions and 16.06% (22/137) of patients. LTP was more likely to occur in lesions larger than 3 cm in diameter (OR: 14.71; p

Imaging-based total bacterial count and type identification of bacteria play crucial roles in clinical diagnostics, public health, biological and medical science, and environmental protection. Herein, we designed and synthesized a series of tetraphenylethenes (TPEs) functionalized with one or two aldehyde, carboxylic acid, and quaternary ammonium groups, which were successfully used as fluorescent materials for rapid and efficient staining of eight kinds of representative bacterial species, including pathogenic bacteria Vibrio cholera, Klebsiella pneumoniae, and Listeria monocytogenes and potential bioterrorism agent Yersinia pestis. By comparing the fluorescence intensity changes of the aggregation-induced-emission (AIE) materials before and after bacteria incubation, the sensing mechanisms (electrostatic versus hydrophobic interactions) were simply discussed. Moreover, the designed AIE materials were successfully used as an efficient artificial tongue for bacteria discrimination, and all of the bacteria tested were identified via linear discriminant analysis. Our current work provided a general method for simultaneous broad-spectrum bacterial imaging and species discrimination, which is helpful for bacteria surveillance in many fields.

Two water-soluble carbohydrate-coated AIE-activate fluorescent organic nanoparticles TPE3G and TPE4G were designed and synthesized for the detection of heparin. Different from the reported strategy, we not only utilized the general detection mechanism of electrostatic interactions, but also introduced the concept of carbohydrate-carbohydrate interactions (CCIs) to enrich the detection mechanism of heparin. TPE3G can serve as an efficient "turn-on" probe with higher selectivity towards heparin than TPE4G. TEM studies revealed that the micro-aggregated TPE3G was encapsulated with the heparin chain to form a complex self-assemblied composite and emits strong fluorescence. It is believed that the results illustrated in this study provide a novel strategy based on CCls to design water-soluble and more efficient bio-probes for various biological and clinical applications.

To assess influencing factors for quantitative analysis of contrast-enhanced ultrasound (CEUS) in Crohn's disease (CD), dynamic CEUS examinations from 77 consecutive CD patients were recorded. Peak intensity (PI) values were calculated using the pre-installed quantification software of the ultrasound scanner. The influence of depth, pressure from the ultrasound probe and intraluminal gas was analyzed. The PI value of the anterior wall was lower than that of the posterior wall when the depth was ≤3.4 cm (17.9 dB vs. 21.3 dB; p 0.05) or evident pressure was exerted (19.1 dB vs. 22.5 dB; p 0.01). In the presence of intraluminal gas, the PI of the anterior wall was higher than that of the posterior wall (20.7 dB vs. 18.8 dB; p 0.05). Nevertheless, no significant difference was found between the PI value of anterior and posterior walls when the depth was3.4 cm (19.8 dB vs. 20.3 dB), moderate pressure was exerted (20.5 dB vs. 21.1 dB) or luminal gas was excluded between the two bowel walls (18.9 dB vs. 21.2 dB; p ≥ 0.05). The factors of depth, pressure from the ultrasound probe and intraluminal gas can affect the quantification results of CEUS. It is preferable to place the region of interest in the posterior wall when luminal gas is absent and in the anterior wall when luminal gas is present. In the latter case, more attention should be paid to reducing pressure by the ultrasound probe.

99 Background: Conversion therapy for unresectable colorectal liver metastases (LM) can downsize tumours and create a situation where the patient has no evidence of disease (NED). We assessed the effectiveness of cetuximab plus mFOLFOXIRI or mFOLFOXIRI in this setting. Methods: FOCULM was a prospective 2:1 controlled, multicenter, phase II trial. Given no free drugs offered and the patients' affordability for cetuximab, the study design has been amended from randomization to non-randomization since September, 2016. Patients with unresectable LM were assigned to receive cetuximab (500mg/m2) plus mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, folinic acid 400 mg/m2, 5-fluorouracil 2800mg/m2 46h infusion, every 2 weeks) (group A) or mFOLFOXIRI (group B). Primary endpoint was the rate of NED achieved, secondary endpoints were ORR, resection rate, the rate of local and ablative treatment (LAT), OS, PFS and DpR. Results: From February 2014 to July 2019, 114 patients were enrolled at 6 centers in China and 101 patients were in the ITT population (67 group A, 34 group B). Treatment groups were generally well balanced, although more patients with ≥5 LM were in group A. The rate of NED achieved was 62.7% in group A and 38.2% in group B (P = 0.020). At a median follow-up of 19.4 months, patients in group A had significantly prolonged the mOS, increased ORR, the rate of LAT and DpR compared with those in group B (Table). Patients with NED achieved yielded a significant survival benefit, whether in group A (Not reached vs. 49.4 months; P = 0.001) or group B (Not reached vs. 25.1 months; P = 0.007). Conclusions: The addition of cetuximab to a mFOLFOXIRI in patients with RAS/BRAF wild-type unresectable LM colorectal cancer significantly improved the rate of NED achieved, ORR and OS. Clinical trial information: NCT02063529. [Table: see text]

We report a turn-on tetravalent sialic acid-coated tetraphenylethene luminogen (TPE4S) with excellent hydrophilicity, good stability, high sensitivity and unique selectivity towards sialidases, and the maximum fluorescence enhancement was ∼40 fold. More importantly, TPE4S was successfully utilized for the screening of sialidase inhibitors and diagnosis of bacterial vaginosis.

Although observational studies have assessed the relationship between parity and thyroid cancer risk, the findings are inconsistent. To quantitatively assess the association, we conducted a systematic review and meta‐analysis. PubMed and Embase were searched up to January 2015. Prospective or case–control studies that evaluated the association between parity and thyroid cancer risk were included. We used the fixed‐effects model to pool risk estimates. After literature search, 10 prospective studies, 12 case‐control studies and 1 pooled analysis of 14 case‐control studies including 8860 patients were identified. The studies had fair methodological quality. Pooled analysis suggested that there was a significant association between parity and risk of thyroid cancer (RR for parous versus nulliparous: 1.09, 95% CI 1.03‐1.15; I2=33.4%). The positive association persisted in almost all strata of subgroup analyses based on study design, location, study quality, type of controls, and confounder adjustment, although in some strata statistical significance was not detected. By evaluating the number of parity, we identified that both parity number of 2 versus nulliparous and parity number of 3 versus nulliparous demonstrated significant positive associations (RR=1.11, 95% CI 1.01‐1.22; I2=31.1% and RR=1.16, 95% CI 1.01‐1.33; I2=19.6% respectively). The dose‐response analysis suggested neither a non‐linear nor linear relationship between the number of parity and thyroid cancer risk. In conclusion, this meta‐analysis suggests a potential association between parity and risk of thyroid cancer in females. However, the lack of detection of a dose‐response relationship suggests that further studies are needed to better understand the relationship.

To prospectively investigate the usefulness of acoustic structure quantification (ASQ) for noninvasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB). Consecutive patients with CHB scheduled for liver biopsy or partial liver resection underwent standardized ASQ examinations. The ASQ parameter, named focal disturbance (FD) ratio, were compared with METAVIR scores. The analysis was based on receiver operating characteristic (ROC) curves and multiple regression analysis. A total of 114 patients were enrolled in the final analysis. The area under the ROC curve for the FD ratio was 0.84 for significant fibrosis (≥ F2), 0.86 for severe fibrosis (≥ F3), and 0.83 for cirrhosis (= F4). The optimal cutoff values for the FD ratio were 0.25, 0.30 and 0.50 for fibrosis stages ≥ F2, ≥ F3 and = F4, respectively. The prevalence of a difference of at least two stages between the FD ratio and the histological stage was 12.3 % (14 of 114). The fibrosis stage (P

The goal of our study was to evaluate the differences between quantitative parameters of hepatocellular carcinoma (HCC) with or without portal vein tumor thrombosis (PVTT) on contrast-enhanced ultrasound (CEUS). Twenty-four patients with HCC with PVTT and 48 without PVTT underwent CEUS using sulfur hexafluoride microbubbles. Dynamic images were analyzed with quantification software. Time-intensity curves were obtained for HCC and surrounding liver parenchyma, and parameters including the intensity maximum (IMAX), rising time (RT), mean transit time and time to peak (TTP) were compared within and between the PVTT and control groups, respectively. RT and TTP of HCC were significantly faster than those of surrounding liver parenchyma in both the PVTT and control groups. IMAX of HCC was significantly stronger than that of surrounding liver in the control group, but not significantly different from that of liver parenchyma in the PVTT group. RT and TTP of HCC and surrounding liver were significantly faster in the PVTT group compared with the control group, whereas IMAX values of HCC in the PVTT group were lower than those in the control group. HCC with PVTT presents different hemodynamic parameters, with faster RT and TTP and lower IMAX than those for HCC without PVTT. Quantitative perfusion analysis of CEUS may be a potential method for predicting PVTT.

Background and Purpose: The aim of this study was to systematically review the efficacy and tolerability of gabapentin in the treatment of sleep disturbance in patients with medical illness. Methods: PubMed was searched for randomized, double-blinded, placebo controlled trials that reported sleep changes during gabapentin treatment up to November 2015. Findings: This review included 26 studies involving 4,684 participants. Except for Composite Endpoint 3 (standardized mean difference (SMD)=0.09, 95% confidence interval (CI): -0.05 to 0.22), compared with the placebo group, the gabapentin group showed superior outcomes on our endpoints: Composite Endpoint 1 (SMD=0.50, 95% CI: 0.28 to 0.71), Composite Endpoint 2 (SMD=-0.53, 95% CI: -0.77 to -0.30), Composite Endpoint 4 (SMD=-0.38, 95% CI: -0.58 to -0.19), Composite Endpoint 5 (Risk Ratio (RR)=1.79, 95% CI: 1.24 to 2.58), and Composite Endpoint 6 (RR=0.48, 95% CI: 0.32 to 0.72). However, the patients in the gabapentin group showed worse tolerance than those in the placebo group (RR=1.38, 95% CI: 1.08 to 1.76). Implications: This study is the first to systematically assess the clinical value of gabapentin for the treatment of sleep disorders. We found that regardless the type of sleep outcomes, gabapentin displayed stable treatment efficacy for sleep disturbance in patients with medical illness. However, when an average dose of approximately 1,800 mg/day was used, the risk of treatment discontinuation or drug withdrawal was relatively high. We recommend that further studies confirm these findings in patients with primary sleep disorders.

The aim of this study was to summarize the imaging features of chronic radiation proctitis (CRP) on endorectal ultrasound (ERUS) and investigate the value of ERUS in the evaluation of disease activity. 40 CRP patients and 30 control patients were investigated by ERUS. Rectal wall thickness and layers, ulcers and rectovaginal fistulas were evaluated by B-mode ultrasound. Power Doppler imaging was used to evaluate the vascularity of the rectal wall using a semiquantitative score. Disease activity was calculated according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (CTCAE 4.0). Imaging findings for patients with mild and severe CRP were compared. For 30 patients in the control group, the average maximum thickness of the rectal wall was 3.07 ± 0.73 mm, with all exhibiting typical wall stratification and level 0 vascularity. For the 40 CRP patients, there was marked thickening of the rectal wall (average thickness = 9.42 ± 1.94 mm), which was significantly thicker than in the control group (p 0.05). The rectal walls of the mild group were significantly thinner than those of the severe group (8.71 ± 1.67 mm vs. 10.00 ± 2.00 mm, p 0.05). Among the 22 severe cases, 19 cases (19/22, 86.4%) exhibited hyper-vascularity (level IV) or blurred wall stratification (including hypo-echoic submucosa, ulcer and fistula); 12 of the 18 mild cases (166.7%) exhibited a vascularity of level III and typical wall stratification. A significant association (p 0.05) was observed between stratification and vascularity of the rectal wall and CRP activity. When ERUS findings of blurred rectal wall stratification or increasing vascularity (level IV) were used to evaluate CRP activity, the sensitivity was 86.4% (95% confidence interval: 64.0-96.4) and the specificity was 66.7% (95% confidence interval: 41.2-85.6). Thickening of the rectal wall, blurred wall stratification and increased vascularity are characteristic ERUS findings of CRP. ERUS is helpful in the comprehensive evaluation of disease activity and may provide objective evidence during treatment planning and follow-up.

To compare the performance of contrast-enhanced ultrasound (CEUS) using high-frequency linear and convex probes in the detection of small colorectal liver metastases (CRLMs). A total of 85 patients with 143 small CRLMs were evaluated. High-frequency ultrasound (US) and CEUS detected significantly more superficial lesions within 60 mm below the skin than a convex probe (p

Objective To investigate the imaging features of focal splenic lesions (FSLs) on contrast-enhanced ultrasound (CEUS). Methods Thirty two patients with FSLs proved by pathology were retrospectively analyzed. CEUS was performed using intravenous bolus injection of 2.4 ml sulfur hexafluoride-filled microbubble contrast agent and real time scanning. There were hemangioma (n = 7), lymphoma (n = 8), true cyst (n = 3), infarction (n = 4), hematolymphangioma (n = 2), metastasis tumor (n = 2), and one for each of the following entities extramedullary hemopoiesis, hamartoma, tuberculosis, Langerhans’ cell histiocytosis, inflammatory pseudotumor and myxofibrosarcoma. Results Among 21 benign lesions, 4 infarctions and 3 cysts presented non-enhancement throughout CEUS scanning, and the other 14 lesions displayed various enhancement levels with 6 (42.9%) hyper-enhancement, 2 (14.3%) iso-enhancement and 6 (42.9%) hypo-enhancement in arterial phase and 11 (78.6%) hypo-enhancement, 1 (7.1%) iso-enhancement and 2 (14.3%) hyper-enhancement in late phase, respectively. The enhancement pattern included 9 (64.3%) homogeneous, 4 (28.6%) heterogeneous and 1 (7.1%) rim-like enhancement. As for the malignant FSLs, all the lesions became completely or extensively hypo-enhancement during the late phase no matter their vascularity during arterial phase. Conclusions The CEUS features reported in this series may enrich the knowledge for CEUS characterization of FSLs.

Background To evaluate the feasibility, accuracy, and utility of sonography (US) and CT fusion imaging guidance for radiofrequency ablation (RFA) of malignant liver tumors not visualized on conventional US. Methods Seventy-seven patients with hepatocellular carcinoma and 15 patients with metastatic liver cancer with a total of 136 lesions underwent RFA with US and CT fusion imaging guidance. The mean number of punctures, success rate of a single ablation session, local tumor progression rates, and long-term outcome were evaluated. Treatment efficacy was evaluated by dynamic CT and contrast-enhanced US 1 month after RFA. Results RFA was technically feasible in all patients, and no major complications occurred. The mean ± SD time needed to synchronize US and CT images was 13.9 ± 11.9 minutes (range, 5–55 minutes). The success rate of a single ablation session was 83.8% (114/136), and tumor residue was present in 7.4% of lesions (10/136). The mean number of treatment sessions was 1.2 ± 0.5 sessions. During follow-up, local tumor progression was observed for 15 (11.9%) lesions. Distant tumor recurrence was found in 51 (55.4%) patients. Conclusions US and CT fusion-assisted RFA is a safe and efficacious treatment for patients with hepatocellular carcinoma and metastatic liver cancer. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:321–330, 2014

This study was aimed to investigate whether the tumor necrosis induced by radiofrequency ablation (RFA) can improve the ratio of tumor-to-normal tissue (T/NT) after intratumoral injection of (131)I-chTNT.Eighteen New Zealand rabbits bearing VX2 tumor on the thigh were randomly divided into two treatment groups (control group: intratumoral injection of (131)I-chTNT alone; RFA group: RFA + intratumoral injection of (131)I-chTNT 3 days after RFA) and each group was further divided into three subgroups I, II, and III (1-2 cm, 2-3 cm, and 3-4 cm in maximum diameter, respectively), by the tumor size. SPECT was performed to evaluate the T/NT on days 1, 8, and 15 after (131)I-chTNT injection.After treatment, all rabbits underwent the SPECT whole-body scan and the T/NT was analyzed. The results showed that T/NT in the RFA group (55.45±41.83) was significantly higher compared with the control group (7.23±5.61) (F=18.89, p=0.001). Meanwhile, a linear ascending trend was found for T/NT in the RFA group along with the follow-up time (r=0.47, p=0.01). The tumor size or the dose of (131)I-TNT injection had no significant effect on the variation of T/NT in both groups (p0.05).RFA before intratumoral injection of (131)I-chTNT can dramatically improve T/NT, demonstrating the potential application of this combination therapy.

Background Radiofrequency ablation (RFA) is a widely applied treatment for hepatocellular carcinoma (HCC), but insufficient RFA can promote rapid progression of the residual tumor through the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) pathway. Although sorafenib has been successfully applied to advanced HCC, the use of sorafenib in residual tumor cells after RFA has rarely been tested. Purpose To evaluate the potential role of sorafenib as an adjunct to RFA to reduce the recurrence rate after insufficient RFA. Material and Methods Xenograft tumors of SMMC 7721 were created by subcutaneously inoculating nude mice with hepatoma cells (5× 106 cells per mouse). Fourteen days after inoculation, all mice were divided into three groups (control group [sham puncture], RFA group, and RFA combined with sorafenib treatment group) with six mice in each group. Each group was given a different treatment procedure. After treatment, the volume of the tumors was calculated from the resected specimens. The mRNA and protein expression of HIF-1a and VEGFA was quantified by real-time PCR and immunohistochemistry analysis. The micro-vessel density (MVD) was determined by CD34 immunohistochemistry. Results Real-time PCR and immunohistochemistry analysis showed that, compared to the RFA group, HIF-1α and VEGFA expression were significantly decreased in the group that received RFA combined with sorafenib treatment ( P < 0.05). By comparing the control group with the RFA group, we found that insufficient RFA promoted HIF-1α and VEGFA expression ( P < 0.05). Similar results were obtained for MVD expression. Additionally, the combination of RFA with sorafenib therapy resulted in a synergistic reduction in tumor growth compared to insufficient RFA and sham puncture ( P < 0.05). Conclusion Sorafenib was able to inhibit the expression of HIF-1α and VEGFA, and sorafenib was able to increase time to recurrence when used as an adjunct to RFA.

This study was to evaluate the role of quantitative perfusion analysis of 3-dimensional (3D) contrast-enhanced ultrasound (CEUS) in detecting microvascular invasion (MVI) of liver tumor in vivo. VX2 tumors were implanted in the livers of sixteen New Zealand rabbits. On day 10, real-time 3D CEUS was performed, and the real-time dynamic images were analyzed using online quantification software. The animals were sacrificed and sent for pathology examinations. According to the gold standard of pathology, the animals were divided into an MVI group and a group without MVI (non-MVI group). Time-intensity curves (TICs) were obtained for the VX2 tumors and the surrounding liver parenchyma, and the parameters peak intensity (PI), mean transit time (MTT), and time to peak (TTP) were compared within and between the MVI and non-MVI groups. The TTP and MTT of the VX2 tumors were significantly faster than those of the surrounding liver parenchyma in both MVI and non-MVI groups. The PI of the VX2 tumors was significantly lower than that of the surrounding liver parenchyma in the non-MVI group but not the MVI group. The TTP and MTT of the VX2 tumors and surrounding liver parenchyma were not significantly different in the MVI group compared with the non-MVI group, whereas the ΔPI (the PI ratio between the VX2 liver tumors and the reference liver parenchyma) of the VX2 tumors in the MVI group was larger than that in the non-MVI group. VX2 tumors with MVI present different hemodynamic parameters, with a larger ΔPI than tumors without MVI. Our data suggest that quantitative perfusion analysis of 3D CEUS might be a promising method for predicting MVI in liver tumors.

To evaluate the diagnostic performance of quantitative analysis as an adjunctive diagnostic tool to contrast-enhanced ultrasound (US) for the differentiation of atypical benign focal liver lesions (FLLs) from malignancies in fatty liver. Twenty-seven benign FLLs and fifty-six malignant FLLs that appeared hyper-enhanced during the arterial phase with washout in the portal or late phase in fatty liver were analyzed. Chi-square tests and logistic regression were applied to identify the specific features. Three sets of criteria were assigned: 1) all FLLs subjected to routine contrast-enhanced US; 2) all FLLs subjected to quantification analysis and contrast-enhanced US; and 3) parts of FLLs that could not be diagnosed using contrast-enhanced US (n = 66, 75.9%) but instead were diagnosed using parametric features. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) of the three sets of criteria were analyzed. The AUCs of the criterion set 2 were significantly higher than those of criterion set 1 (0.904 versus 0.792, P = 0.008). Criterion set 3 showed a relatively high sensitivity (90.2%) with a relatively high AUC (0.845). The quantification analysis offers improved diagnostic performance for the differential identification of atypical benign FLLs from malignancies in fatty liver.

Percutaneous ablative therapies (PAT) are valuable modalities for posthepatectomy recurrent hepatocellular carcinoma (RHCC), but its impact on long-term outcome and prognosis prediction have not been well documented. The present study aimed to analyze prognostic factors and to propose a prognosis-predicting model for RHCC treated with PAT. A total of 288 patients with posthepatectomy RHCC treated with percutaneous ethanol ablation, radiofrequency ablation, microwave ablation, or ethanol ablation combined with radiofrequency ablation were included. Survival and prognostic factors were analyzed. A prognosis-predicting model was created by quantifying and integrating all prognostic factors. Three-, 5-, and 7-year postablation survival rates were 37.8, 20.7, and 14.2 %, respectively. Multivariate analysis revealed that interval between recurrence and initial hepatectomy, tumor number, largest diameter of tumor, and Barcelona Clinic Liver Cancer stage at hepatectomy were independent prognostic factors for survival. A scoring system for prognostic factors was proposed, and summation of 4 prognostic factors (prognostic score) was ranged from 4 to 10. Prognostic score was classified into three strata, designated as prognostic classes A (score 4 and 5), B (score 6 and 7), and C (≥8). Three-, 5-, and 7-year postablation survival rates were 62.8, 39.4, and 26.9 % in class A, 36.9, 15.5, and 7.2 % in B, and 5.5, 0, and 0 % in class C, respectively (p = 0.00). Three-, 5-, 7-, and 10-year survival rates after initial hepatectomy were 82.4, 66.3, 52.1, and 36.4 % in class A, 51.6, 34.8, 20.7, and 6.6 % in class B, and 11.9, 7.8, 0, and 0 % in class C, respectively (p = 0.00). The prognostic model developed in the study could clearly predict different long-term outcomes for patients with posthepatectomy RHCC and thus help decide appropriate therapeutic strategy.

To retrospectively determine the accuracy of baseline ultrasound (BUS) and of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of pancreatic solid-cystic lesions.Fifty-four pancreatic solid-cystic lesions in 52 patients were examined with BUS and CEUS, two different seniority radiologists read the images independently, Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic value of BUS and CEUS in the diagnosis of benign or malignant pancreatic solid-cystic lesions, the diagnostic consistency between different seniority radiologists was evaluated by Kappa statistics.Among the 54 lesions, there were pancreatic cyst five cases, pancreatic pseudocyst twenty cases, pancreatic cystadenoma eight cases, pancreatic cystadenocarcinoma seven cases, intraductal papillary mucinous neoplasm of pancreas (IPMN) three cases, pancreatic carcinoma combined liquefied six cases, solid-pseudopallary tumor of pancreas (SPTP) three cases, pancreatic myopericytoma one case, pancreatic lymphangioma one case. After ROC analysis, the areas under the ROC curve (Az) were 0.752 by BUS, 0.928 by CEUS to resident radiologist, and 0.896 by BUS, 0.954 by CEUS to staff radiologist. The correct diagnosis rate of specific disease was 42.6% by BUS, 64.8% by CEUS to staff radiologist (P0.05), and 33.3% by BUS, 53.7% by CEUS to resident radiologist (P0.05). The interobserver agreement in CEUS is higher than that in BUS, the Kappa value was 0.889 ± 0.062 and 0.428 ± 0.126 respectively.Compared with BUS, CEUS can significantly enhance the diagnostic rate of pancreatic solid-cystic lesions.

To prospectively compare microwave (MW) ablation using a modified internal cooled-shaft antenna with radiofrequency (RF) ablation in in vivo porcine liver and in patients with small hepatocellular carcinoma (sHCC).In an animal study, MW and RF ablations using a cooled-shaft antenna or internally cooled electrode were performed in in vivo porcine liver. Coagulation diameters of both ablations were compared. For clinical study, 42 patients with sHCC were treated with MW or RF ablation. Complete ablation (CA) and local tumour progression (LTP) were compared.MW ablation produced significantly larger ablation zones than RF ablation in both porcine liver and sHCC with an ablated volume of 33.3 ± 15.6 cm(3) vs. 18.9 ± 9.1 cm(3) and 109.3 ± 58.3 cm(3) vs. 48.7 ± 30.5 cm(3), respectively. The CA rate was 95.5 % (21/22) for MW ablation and 95.0 % (19/20) for RF ablation. In a 5.1-month follow-up, the LTP rate was 18.2 % (4/22) in the MW ablation group and 15.0 % (3/20) in the RF ablation group.MW ablation using a modified cooled-shaft antenna produces a larger ablation zone than RF ablation, with an efficacy similar to RF ablation in local tumour control. MW ablation is a safe and promising treatment of sHCC.

Background and objectives: Cerebral vasospasm is an important cause of poor outcomes in subarachnoid haemorrhage patients. This study was designed to assess the effectiveness and safety of nimodipine in the prevention of cerebral vasospasm in aneurysmal subarachnoid haemorrhage patients. Methods: We searched Pubmed, OVID, Embase, the Cochrane library, the stroke clinical trial registry, and the National Science and Technology Library database and collected prospective, randomised, controlled clinical trials of the prophylactic use of nimodipine for aneurismal subarachnoid haemorrhage patients. A meta-analysis was performed on the studies that met the criteria for inclusion. Results: Eight studies met the inclusion criteria, and 1514 patients finished trial observation for the different indicators. Compared with the placebo group, fully recovered (all cases) patients increased 64% in the nimodipine group (P = 0.0002, OR = 1.64, 95% CI 1.26 – 2.13, NNT=-1.048), fully recovered or moderately disabled (all cases) patients increased 79% (P = 0.0007, OR = 1.79, 95% CI 1.28 – 2.51, NNT = -5.889), patient death (in cerebral vasospasm cases) decreased 74% (P = 0.008, OR = 0.26, 95% CI 0.09 – 0.71, NNT = 2.298), the incidence of symptomatic cerebral vasospasm decreased 46% (P < 0.00001, OR = 0.54, 95% CI 0.42 – 0.69, NNT = 1.952), the incidence of delayed neurological function deficits (all cases) decreased 38% (P < 0.0001, OR = 0.62, 95% CI 0.50 – 0.78, NNT = 1.078), the occurrence of cerebral infarction (on CT scan) decreased 58% (P = 0.001, OR = 0.58, 95% CI 0.42 – 0.81, NNT = 3.314), the occurrence of cerebral infarction (in cerebral vasospasm cases) decreased 65% (P = 0.003, OR = 0.35, 95% CI 0.17 – 0.69, NNT = 3.688), the occurrence of cerebral infarction (all cases) decreased 48% (P < 0.00001, OR = 0.52, 95% CI 0.41 – 0.66, NNT = 1.196), and the difference in recurrent haemorrhage and adverse reactions between the nimodipine and placebo groups was not statistically significant (nimodipine group versus placebo group, recurrent haemorrhage P = 0.15, OR = 0.75, 95% CI 0.50 – 1.11; adverse reaction P = 0.59, OR = 1.13, 95% CI 0.71 – 1.81). Conclusion: Compared with placebo, nimodipine can significantly improve clinical outcomes, as assessed by self-formulated standards and Glasgow outcome scores, and it can significantly reduce the occurrence of symptomatic cerebral vasospasm and delayed neurological function deficits (all cases), as well as cerebral infarction, although the incidence rate of recurrent haemorrhage and adverse reactions is not significantly reduced by nimodipine.

To detect whether the efficacy of microwave ablation (MWA) could be improved by preinjected fluids in an ex vivo porcine liver model.Ablations were performed for 12 minutes using energy output of impedance-based (power output gradually rose to 200W, maintained until increases in tissue impedance of 20 Ω, reduced to 10W, and switched on again 15 seconds later) in radiofrequency ablation (RFA) or 80 W in MWA. Before ablation, 5 mL of ethanol, distilled water, 0.9% NaCl solution, or 10% NaCl solution (n = 6 each) was injected into the targeted liver tissue. Ablations without fluid injection served as control. The ablation diameter, volume, shape index, and temperature were recorded and compared.Preinjection of 0.9% or 10% NaCl solution resulted in larger coagulation volumes than that of the control group in RFA experiments (28.1 ± 2.9 cm(3), 45.3 ± 6.3 cm(3), 20.0 ± 2.5 cm(3), respectively; P.05). Ethanol and distilled water had no impact on coagulation volumes in RFA. Preinjection of ethanol or 10% NaCl solution created smaller coagulation volumes than that of the control group in MWA experiments (34.3 ± 2.0 cm(3), 33.9 ± 4.1 cm(3), 58.0 ± 6.6 cm(3), respectively; P.001). 0.9% NaCl solution and distilled water had no impact on coagulation volumes in MWA.In an ex vivo porcine liver, preinjected fluids do not benefit microwave ablation as those in radiofrequency ablation.

Cerebral vasospasm (CVS) is a frequent and unpredictable complication in patients with subarachnoid hemorrhage (SAH) and often leads to poor outcomes. This study was aimed at evaluating the efficacy and safety of fasudil in the treatment of CVS in patients with SAH. A search was conducted using the full-text database of Chinese scientific journals, the Wanfang Database (January 1999 to November 2010), the Chinese Medical Association Digital Journal Database, PubMed, the Cochrane library, OVID, and EMBase (searching through November 2010). A total of 8 studies met the inclusion criteria. The incidence rates of symptomatic CVS and CVS confirmed by angiography among the patients in the fasudil group were only 48% (odds ratio [OR] = 0.48, 95% confidence interval [CI]: 0.32–0.72, P = 0.0005) and 40% (OR = 0.40, 95% CI: 0.24-0–67, P = 0.0004) respectively of that of the control group. The odds ratios of cerebral infarction for all cases and cerebral infarction for CVS cases in the fasudil group were only 50% (OR = 0.50, 95% CI: 0.34–0.76, P = 0.0009) and 43% (OR = 0.43, 95% CI: 0.26–0.70, P = 0.0008) respectively of that of the control group. Fasudil greatly reduces the occurrence of CVS and cerebral infarction in SAH patients, significantly improves the clinical outcomes of the patients (as assessed by the Glasgow Outcome Scale). Because of the limited number of trials and samples available for analysis, the conclusions from the present study still need to be validated with results from large randomized, controlled clinical trials.

Objective: To investigate the potential usefulness of three-dimensional contrast-enhanced ultrasound (3D-CEUS) in evaluating the treatment response for liver cancer after local therapies. Methods: A total of 107 lesions in 95 consecutive patients with liver cancer underwent local therapies and thereafter received low acoustic power 3D-CEUS examination. The LOGIQ 9 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The image quality of 3D-CEUS images was evaluated and the influence of 3D-CEUS to clinical outcome was investigated. Results: The image quality of 3D-CEUS was defined as high in 102 (102/107, 95.3%) lesions and common in 5 (5/107, 4.7%) lesions. 3D-CEUS did not change the diagnosis in any patient compared with 2D-CEUS. However, 3D-CEUS changed the management in 3 (2.8%) of 107 lesions, increased confidence but made no change in diagnosis in 85 (79.5%) lesions, added some information but did not change management or diagnosis in 15 (14.0%), and made no change in 4 (3.7%), respectively, in comparison with 2D-CEUS. Conclusion: 3D-CEUS enhances the diagnostic confidence in the majority of the patients and even changes the management in some patients. 3D-CEUS has potential usefulness in evaluating treatment response for liver cancer after local therapies.

Objective To compare the enhancement pattern of hilar cholangiocarcinoma on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). Methods Thirty-two consecutive patients with pathologically proven hilar cholangiocarcinomas were evaluated by both low mechanical index CEUS and CECT. The enhancement feature of the tumor, portal vein infiltration, and lesion conspicuity on them was investigated. Results In the arterial phase, the numbers of the lesions showing hyperenhancement, isoenhancement, and hypoenhancement, were 14 (43.8%), 14 (43.8%), and 4 (12.6%), on CEUS, and 12 (37.5%), 9 (28.1%), and 11 (34.4%), on CECT ( P = 0.162). In portal phase, the numbers of the lesions showing hypoenhancement, isoenhancement, and hyperenhancement were 30 (93.8%), 1 (3.1%), and 1 (3.1%), on CEUS, and 23 (71.9%), 8 (25.0%), and 1 (3.1%), on CECT ( P = 0.046). The detection rates for portal vein infiltration were 84.2% (16/19) for baseline ultrasound, 89.5% (17/19) for CEUS, and 78.9% (15/19) for CECT (all P > 0.05 between every two groups). CEUS significantly improved the lesion conspicuity in comparison with CECT. CEUS and CECT made correct diagnoses in 30 (93.8%) and 25 (78.1%) lesions prior to pathological examination ( P = 0.125). Conclusion The enhancement pattern of hilar cholangiocarcinoma on CEUS was similar with that on CECT in arterial phase, whereas in portal phase hilar cholangiocarcinoma shows hypoenhancement more likely on CEUS. CEUS and CECT lead to similar results in evaluating portal vein infiltration and diagnosis of this entity.

Purpose The objective of this study was to investigate the contrast-enhanced ultrasound (CEUS) imaging features of focal liver lesions (FLLs) in fatty liver. Method One hundred FLLs in 98 patients with fatty liver were evaluated with real-time CEUS. Results All malignant FLLs showed hyperenhancement in arterial phase and contrast washout in portal and late phases. Among the FLLs, 3.3% of hemangiomas, 12.5% of focal nodular hyperplasias (FNHs), and 2.5% of focal fatty sparing lesions showed contrast washout in the late phase. The sensitivity and specificity for the characterization of hepatocellular carcinoma, metastasis, hemangioma, FNH, and focal fatty sparing lesions were 100% and 95.6%, 60% and 100%, 93.3% and 98.6%, 87.5% and 97.8%, and 92.6% and 100%, respectively. Conclusions Correct characterization of FLLs in fatty liver by CEUS is possible based on their typical enhancement patterns.

Heat shock proteins (HSPs) induced by thermal ablation therapy may help presenting tumor antigen to the host immune system and be a valuable adjuvant in the ablation therapy of liver cancer. This paper described our preliminary study on the expression of HSP70 in rabbit liver after contrast-enhanced ultrasound (CEUS) and radiofrequency (RF) ablation. Twenty-five male New Zealand white rabbits were divided into five groups as: control group (n=5), ultrasound group (n=5), CEUS group (n=5), RF group (n=5) and CEUS+ RF group (n=5). Clinical ultrasound and RF ablation equipment were used in the present experiment. Sonazoid was used as the contrast agent. All the animals were sacrificed 24 h after the procedure, and HSP70 was detected by immunohistochemistry staining and Western blot analysis. In the groups without RF ablation, there was no evidence of HSP70 expression in the liver tissue of the control group and ultrasound group, whereas positive HSP70 expression was detected in the liver tissue of the CEUS group, with a mean optical density of 0.33. In the RF and CEUS+ RF groups, there were cells showing HSP70 expression in the normal liver tissue far from the ablation region. The mean densities of HSP70 expression were 0.31 in the RF group and 0.35 in the CEUS+ RF group, respectively. With regard to the distribution of HSP70 expression of the RF and CEUS+ RF groups, the marginal areas were stronger than liver tissue 1 cm away from the margin, and the ablated tissues showed no evidence of HSP70 expression. The mean density of HSP70 expression in the marginal areas were 0.47 in the RF group and 0.42 in the CEUS+ RF group, respectively. CEUS using Sonazoid may produce HSP70 expression in the normal liver parenchyma after CEUS examination and RF ablation. (E-mail: moriyasu@tokyo-med.ac.jp).

To investigate whether ethanol ablation by using a multipronged needle delivery system (multipronged ethanol ablation) could eradicate hepatocellular carcinoma (HCC) up to 5.0 cm in diameter with a single-session high-dose strategy.The hospital ethics committee approved the prospective study, and each patient provided written informed consent. One hundred forty-one patients (125 men, 16 women; mean age, 53 years; range, 27-76 years) with 164 primary or recurrent HCC ranging from 1.3 to 5.0 cm in diameter (mean, 2.9 cm +/- 0.9) were treated with high-dose multipronged ethanol ablation. Patients were unsuitable for surgery, declined surgery and radiofrequency ablation, or had tumors located at unfavorable sites. Primary technique effectiveness (PTE) (complete ablation within two sessions), local tumor progression (LTP), and complications after the treatment were observed. Twenty risk factors of local effectiveness and complications were analyzed by means of univariate and multivariate analysis.Mean number of treatment sessions was 1.1. The mean volume of ethanol per tumor was 31 mL (range, 8-68 mL). PTE was achieved in 134 (95%) of 141 patients and was significantly associated with tumor pattern (capsulated vs noncapsulated, P = .018). After a mean follow-up period of 25 months, LTP was observed in 16 (12%) of 134 patients, and in nine (56%) patients, LTP occurred in tumors 3.1-5.0 cm in diameter. Alanine aminotransferase level (P = .023) was the independent risk factor for LTP. Three (2%) of 141 patients had major complications.Multipronged ethanol ablation with a high-dose strategy can be used to treat HCC up to 5.0 cm in diameter effectively and safely, often in a single session.

To investigate the findings of renal cell carcinomas (RCCs) on contrast-enhanced ultrasound (CEUS).CEUS features of 84 RCCs confirmed by pathologic examination in 81 patients were retrospectively analyzed. A contrast-specific mode and a sulfur hexafluoride-filled microbubble contrast agent were used for CEUS. The enhancement pattern, extent, and dynamic change in the cortical, corticomedullary, and late phases were evaluated.On CEUS, the emergence of tumor enhancement was earlier in two nodules (2.4%), simultaneous in 71 (84.5%), and later in 11 (13.1%), in comparison with the adjacent renal cortex. Seventy-four RCC nodules (88.1%) showed hyper-enhancement (n = 2) or iso-enhancement (n = 72) during the cortical phase, and the remaining 10 (11.9%) showed hypo-enhancement. Twenty-three nodules (27.4%) showed homogeneous enhancement and 61 (72.6%) inhomogeneous enhancement. In the corticomedullary phase, the nodules showed hypo-enhancement in 68 (81.0%) and iso-enhancement in 16 (19.0%). In the late phase, all RCCs showed the same enhancement pattern as that shown in the corticomedullary phase. Seventy-two (85.7%) nodules showed a clear perilesional rim-like enhancement in late phase.Hyper- or iso-enhancement during the cortical phase, subsequent washout in late phase, inhomogeneous enhancement, and perilesional rim-like enhancement are clues for RCCs, which might be useful for characterization of RCCs.

We assessed the usefulness of contrast-enhanced ultrasound (CEUS) in the differentiation of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC).The CEUS enhancement patterns of 50 ICCs were retrospectively analysed and compared with 50 HCCs. Two readers independently reviewed the baseline ultrasound (BUS) and CEUS images and the diagnostic performances were evaluated by receiver operating characteristic (ROC) analysis. Time-intensity curves (TIC) were plotted for quantification analysis.In the arterial phase, peripheral rim-like hyperenhancement, heterogeneous hyperenhancement, homogeneous hyperenhancement and heterogeneous hypoenhancement were found in 25, 10, 3 and 12 of the ICCs versus 2, 29, 19 and 0 of the HCCs (P0.001), respectively. The diagnostic performance of both readers in terms of the area under the ROC curve (0.745 vs. 0.933 for reader 1, and 0.803 vs. 0.911 for reader 2), sensitivity (28% vs. 90%, and 44% vs. 82%) and accuracy (64% vs. 90%, and 71% vs. 90%) improved significantly after CEUS (all P0.05). The interobserver agreement increased from kappa = 0.575 at BUS to kappa = 0.720 after CEUS. TICs demonstrated that the intensities of the peripheral and central portions of the ICCs were lower than those of HCCs (both P0.05).CEUS improves the diagnostic performance significantly in the differentiation between ICC and HCC.

Purpose To investigate the behavior of perflubutane microbubbles outside and inside Kupffer cells during diagnostic ultrasound (US) examination, and to determine the thresholds of the acoustic pressure of different kinds of behavior. Methods Acoustic behavior of perflubutane microbubbles inside and outside Kupffer cells in an acoustic field induced by a clinical US transducer and equipment was optically observed in vitro. The acoustic pressure was measured simultaneously by a calibrated hydrophone and an oscilloscope. Results The acoustic behavior of microbubbles was optically categorized as stabilization, oscillation, transposition, shrinkage, and destruction. The mechanical index (MI) displayed on the US equipment correlated well with the acoustic pressure at the level of microbubbles measured hydrophonically. At a frame rate of 15 Hz with a frequency of 3.5 MHz and pulse repetition frequency of 3 KHz, the thresholds in term of MI for free microbubbles to begin oscillation, reach best oscillation, transposition, shrinkage, and destruction were 0.21, 0.44, 0.53, 0.75, and 1.03, respectively. Although adherent and phagocytosed microbubbles showed more stability enduring insonation compared with free microbubbles, the thresholds of shrinkage and destruction were MI 1.03 and 1.18 for adherent microbubbles, and 1.18 and 1.37 for phagocytosed microbubbles, respectively. Neither oscillation nor transposition of microbubbles inside Kupffer cells was observed microscopically. No cell damage because of microbubbles destruction was found in the present study. Conclusion Perflubutane microbubbles outside and inside Kupffer cells respond to external US insonation with same parameters of a clinical contrast-enhanced US study according to the acoustic pressure. Free microbubbles behave as stabilization, oscillation, transposition, shrinkage, and destruction under insonation. The adherent and phagocytosed microbubbles are more stable under insonation than free microbubbles, but still respond showing shrinkage and destruction when MI is over 1.03.

The study was aimed at evaluating the diagnostic performance of contrast-enhanced ultrasound (CEUS) in characterizing complex cystic focal liver lesions (FLLs). Sixty-seven complex cystic FLLs in 65 patients were examined with conventional ultrasound (US) and real-time CEUS. The US and CEUS images were reviewed by a resident radiologist and a staff radiologist independently. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance, and the interobserver agreement was analysed. The results showed that complete non-enhancement throughout three phases of CEUS or sustained enhancement in the portal and late phases were exhibited in most benign lesions. Conversely, hypo-enhancement in the late phase was seen in all malignancies. After ROC analysis, the areas (Az) under the ROC curve were 0.774 at US versus 0.922 at CEUS (P = 0.047) by the resident radiologist, and 0.917 versus 0.935 (P = 0.38) by the staff radiologist. A significant difference in Az between the resident and the staff radiologists was found for US (0.774 versus 0.917, P = 0.044), whereas not found for CEUS (0.922 versus 0.935, P = 0.42). Interobserver agreement was improved after CEUS (κ = 0.325 at US versus κ = 0.774 at CEUS). Real-time CEUS improves the capability of discrimination between benign and malignant complex cystic FLLs, especially for the resident radiologist.

Purpose To evaluate the usefulness of contrast-enhanced sonography (CEUS) in the diagnosis of small hepatocellular carcinoma (HCC) measuring ≤2 cm in diameter. Methods We identified 104 focal liver lesions measuring ≤2 cm in 104 consecutive patients who were enrolled for baseline sonography (BUS) and CEUS examination (49 HCCs, 55 non-HCCs). A real-time, contrast-specific mode of contrast pulse sequencing and a sulphur hexafluoride-filled microbubble contrast agent were used for CEUS. The diagnostic performances of BUS and CEUS in differentiating focal liver lesions (HCC or non-HCC) were analyzed and compared. Results On CEUS, 43 (87.8%) of the 49 HCC lesions were hyperenhanced, 5 (10.2%) were isoenhanced, and 1 (2%) was hypoenhanced during the arterial phase when compared with adjacent liver tissue. Thirty-nine (79.6%) HCCs exhibited washout from the portal phase to the late phase. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy before and after contrast agent administration were 28.6% (14/49) versus 79.6% (39/49) (p 0.05), 82.4% (14/17) versus 90.7% (39/43) (p > 0.05), 59.8% (52/87) versus 90.7% (39/43) (p < 0.01), and 63.5% (66/104) versus 86.5% (90/104) (p < 0.001), respectively. No significant difference in diagnostic performance of CEUS was found between lesions measuring ≤1.5 cm and those 1.6–2 cm and between lesions located at a depth of ≤6 cm from the skin and those located deeper. Conclusions CEUS significantly improved the diagnostic performance in characterization of small HCCs ≤2 cm compared with BUS. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008

Summary Background & aims The association between breastfeeding and thyroid cancer risk is not consistent from epidemiological studies. To better clarify the association including assessing a potential dose–response relationship, we conducted a comprehensive meta-analysis. Methods We searched PubMed (MEDLINE) up to November 2015 for prospective studies or case-control studies that evaluated the association between breastfeeding and risk of thyroid cancer. Effect estimates were pooled using a fixed-effects model. Results Nine reports (2 prospective studies, 6 case-control studies and 1 pooled analysis of 14 case-control studies) involving 2423 cases and 350,081 non-cases were identified. After pooling relevant studies, there was a significant inverse association between ever breastfeeding and risk of thyroid cancer (RR = 0.91, 95% CI 0.83–0.99), with minor heterogeneity (I2 = 10.1%). The dose-response analysis revealed a significant linear relationship between the duration of breastfeeding and risk of thyroid cancer. The summary RR for an increment of 1 month of breastfeeding with risk of thyroid cancer was 0.983 (95% CI 0.98–0.99). When focusing on cohort studies, a more prominent linear dose–response relationship was detected, with the combined RR for every increment of 1 month of breastfeeding to be 0.965 (95% CI 0.96–0.97). Conclusions This meta-analysis suggests that breastfeeding is potentially inversely associated with thyroid cancer risk. Also longer duration of breastfeeding may further decreases thyroid cancer risk. If validated in large-scale prospective studies, our findings may have implications for impacting women's decision in breastfeeding.

Purpose The objective of this meta-analysis was to systematically evaluate the efficacy of pramipexole for the treatment of primary moderate-to-severe restless leg syndrome (RLS). Methods Databases of PubMed, OVID, ScienceDirect, SpringerLink, Thomson Reuters Web of Science, the Cochrane Library, the Wiley Online Library, ArticleFirst, CALIS, Study, CNKI, and WanFang were searched to identify randomized controlled trials (RCTs) investigating pramipexole for the treatment of primary moderate-to-severe RLS. A meta-analysis was then conducted to pool results. Findings Twelve RCTs involving 3286 participants were included in this study. The mean (SD) treatment duration was 11.12 (5.72) weeks/person. The meta-analysis found that the post-treatment change in the International Restless Leg Syndrome Study Group Rating Scale (IRLS) score of the pramipexole group was significantly superior to that of the placebo group (weighted mean difference [WMD] = –4.64; 95% CI, –5.95 to –3.33; n = 8). More patients in the pramipexole group reported at least a 50% reduction in the IRLS score after treatment (risk ratio [RR] = 1.57; 95% CI, 1.43 to 1.73; n = 8). In terms of the scores for the Clinical Global Impression of Improvement scale (RR = 1.48; 95% CI, 1.31 to 1.66; n = 11) and the Patient Global Impression scale (RR = 1.54; 95% CI, 1.31 to 1.81; n = 9), treatment outcomes of the pramipexole group were significantly superior to those of the placebo group. In terms of the change in quality of life (WMD = 5.39; 95% CI, 2.28 to 8.50; n = 4), the change in daytime tiredness (WMD = –0.61; 95% CI, –1.21 to –0.01; n = 4), the change in the number of periodic limb movements per hour of sleep (WMD = –35.95; 95% CI, –56.42 to –15.48; n = 3), and the change in the quality of sleep (WMD = 3.60; 95% CI, 1.69 to 5.50; n = 6), the treatment outcomes of the pramipexole group were significantly superior to those of the placebo group. Implications This meta-analysis study indicated that pramipexole could effectively improve the symptoms of patients with primary moderate-to-severe RLS, although the quality of evidence was relatively low. Future clinical trials focusing on the medium-term and long-term treatment outcomes and using mainly objective indicators for evaluation are warranted. It is also necessary to pay close attention to augmentation during medication.

To evaluate diagnostic performance of contrast-enhanced (CE) ultrasonography (US) and microflow (MF) imaging in differentiation of atypical hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH).Institutional review board approval was obtained, and informed consent was waived. A total of 103 patients (mean age, 43.9 years; age range, 17-75 years) were included; 38 patients with HCC and 65 with FNH underwent CE US, and vascular architecture pattern (VAP) and arrival time parametric (ATP) images were analyzed. Resident and staff radiologists independently and retrospectively reviewed CE US, VAP, and ATP images. χ(2) test and logistic regression analysis were applied to identify specific features of FNH or HCC on CE US and MF images. To compare diagnostic performance of CE US with or without MF imaging, four sets of criteria were assigned: (a) routine CE US alone, (b) VAP and CE US, (c) ATP imaging and CE US, and (d) all three methods in combination. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of resident and staff radiologists were analyzed. Cohen κ statistic was used to assess agreement of CE US and MF imaging features between staff and resident radiologists.MF imaging offered significant improvements over most detection rates achieved with routine CE US signs in both groups. For staff radiologists, AUCs from criteria sets 3 (AUC = 0.873, P.05) and 4 (AUC = 0.887, P.05) were significantly higher than AUC from criteria set 1 (AUC = 0.835). For resident radiologists, specificity (71% and 69% vs 25%, P.01) and accuracy (78% and 79% vs 50%, P.01) of criteria sets 3 and 4 were significantly higher than those of criteria set 1. Moreover, AUCs for criteria sets 2 (AUC = 0.728, P.05), 3 (AUC = 0.823, P.01), and 4 (AUC = 0.857, P.01) were significantly higher than those for criteria set 1 (AUC = 0.667).When compared with routine CE US, MF imaging can more effectively depict specific features and offers improved diagnostic performance in the differentiation of atypical HCC from FNH, especially when used by resident radiologists. Online supplemental material is available for this article.

We compared the enhancement pattern of 98 hepatocellular carcinoma nodules in 92 patients on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT). Contrast-enhanced ultrasound was performed with SonoVue and a low mechanical index method. In arterial phase, 98 nodules were hyperenhancing on CEUS and 94 on CECT. In portal phase, 82 nodules were hypoenhancing on CEUS and 83 on CECT. Peripheral thin-rim-like enhancement was exhibited in 30 nodules on CEUS and 31 on CECT. Intratumoral vessels were visualized in 94 nodules on CEUS and 36 on CECT.

OBJECTIVE The purpose of this study was to assess the diagnostic performance of real-time contrast-enhanced sonography in characterization of small focal liver lesions (FLLs; < or = 3.0 cm in diameter). METHODS Two hundred small FLLs in 200 patients were examined by contrast-enhanced sonography using a contrast-specific mode of contrast pulse sequencing and a sulfur hexafluoride-filled microbubble contrast agent. The sonographic images were reviewed by 2 independent readers. A 5-point confidence level was used to discriminate malignant from benign FLLs, and specific diagnoses were recorded. The diagnostic performances were evaluated by receiver operating characteristic (ROC) analysis, and the interobserver agreement was analyzed by weighted kappa statistics. RESULTS After review of contrast-enhanced sonography, ROC analysis revealed significant improvement in differentiating between malignant and benign small FLLs that the areas under the ROC curve were 0.856 at baseline sonography versus 0.954 at contrast-enhanced sonography for reader 1 (P < .001) and 0.857 versus 0.954 for reader 2 (P = .003). The sensitivity, negative predictive value, and accuracy for both readers also improved significantly after contrast agent administration (all P < .001). A better result of specific diagnosis was obtained (38.5% [77/200] at baseline sonography versus 80.5% [161/200] at contrast-enhanced sonography for reader 1 and 34.5% [69/200] versus 80.5% [161/200] for reader 2; both P < .001) after contrast agent administration, and a better interobserver agreement was achieved (kappa = 0.425 at baseline sonography versus 0.716 at contrast-enhanced sonography). CONCLUSIONS Real-time contrast-enhanced sonography improves the diagnostic performance in small FLLs compared with baseline sonography.