Effects of problem-based learning in Chinese radiology education: A systematic review and meta-analysis.

BACKGROUND: In recent years, the problem-based learning (PBL) teaching method has been extensively applied as an experimental educational method in Chinese radiology education. However, the results of individual studies were inconsistent and inconclusive. A meta-analysis was performed to evaluate the effects of PBL on radiology education in China. METHODS: Databases of Chinese and English languages were searched from inception up to November 2017. The standard mean difference (SMD) with its 95% confidence interval (95% CI) was used to determine the over effects of PBL compared with the traditional teaching method. RESULTS: Seventeen studies involving 1487 participants were included in this meta-analysis. Of them, 16 studies provided sufficient data for the pooled analysis and showed that PBL teaching method had a positive effect on achieving higher theoretical scores compared with the traditional teaching method (SMD = 1.20, 95% CI [0.68, 1.71]). Thirteen studies provided sufficient data on skill scores, and a significant difference in favor of PBL was also observed (SMD = 2.10, 95% CI [1.38, 2.83]). Questionnaire surveys were applied in most of the included studies and indicated positive effects of PBL on students' learning interest, scope of knowledge, team spirit, and oral expression. CONCLUSION: The result shows that PBL appears to be more effective on radiology education than traditional teaching method in China. However, the heterogeneity of the included studies cannot be neglected. Further well-designed studies about this topic are needed to confirm the above findings.

High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer.

BACKGROUND: Lymphatic vessel density and lymphovascular invasion are commonly assessed to identify the clinicopathological outcomes in breast cancer. However, the prognostic values of them on patients' survival are still uncertain. METHODS: Databases of PubMed, Embase, and Web of Science were searched from inception up to 30 June 2016. The hazard ratio with its 95% confidence interval was used to determine the prognostic effects of lymphatic vessel density and lymphovascular invasion on disease-free survival and overall survival in breast cancer. RESULTS: Nineteen studies, involving 4215 participants, were included in this study. With the combination of the results of lymphatic vessel density, the pooled hazard ratios and 95% confidence intervals were 2.02 (1.69-2.40) for disease-free survival and 2.88 (2.07-4.01) for overall survival, respectively. For lymphovascular invasion study, the pooled hazard ratios and 95% confidence intervals were 1.81 (1.57-2.08) for disease-free survival and 1.64 (1.43-1.87) for overall survival, respectively. In addition, 29.56% (827/2798) of participants presented with lymphovascular invasion in total. CONCLUSIONS: Our study demonstrates that lymphatic vessel density and lymphovascular invasion can predict poor prognosis in breast cancer. Standardized assessments of lymphatic vessel density and lymphovascular invasion are needed.

Intratumoral and peritumoral lymphatic vessel density both correlate with lymph node metastasis in breast cancer.

The status of lymph node involvement is an important prognostic factor for breast cancer. However, the presence of intratumoral lymphatic vessels in primary tumor lesions and the relationship between lymphatic vessel density (LVD) and lymph node metastasis (LNM) have not been firmly established. Therefore, we performed a meta-analysis study to investigate these issues. According to the pre-established inclusion and exclusion criteria, 13 studies, involving 1029 breast cancer patients, were included in this study. Using immunohistochemical staining, intratumoral lymphatic vessels were detected in 40.07% of breast cancer patients (240/599), and peritumoral lymphatics were detected in 77.09% (397/515). All studies demonstrated that peritumoral LVD was higher than intratumoral LVD, with a pooled standard mean difference and 95% confidence interval (95% CI) of 1.75 (1.28 to 2.21). Both intratumoral LVD and peritumoral LVD positively correlated with LNM, with correlation coefficients of 0.14 (95% CI 0.05 to 0.23) and 0.31 (95% CI 0.13 to 0.49), respectively. In summary, our study reports the overall detection rate of intratumoral lymphatics and demonstrates the associations between intratumoral LVD, peritumoral LVD, and LNM in breast cancer. Additionally, controlled studies with a larger number of subjects are needed to establish these relationships.

The relationship of lymphatic vessel density, lymphovascular invasion, and lymph node metastasis in breast cancer: a systematic review and meta-analysis.

Lymph node status is one of the key parameters used for determining the stage of breast cancer progression. The relationship of lymphatic vessel density (LVD), lymphovascular invasion (LVI), and lymph node metastasis (LNM) has not been clearly demonstrated yet. Databases of PubMed, Embase, and Web of Science were searched from inception up to 25 May 2016. Spearman correlation coefficient (r) and 95% confidence interval (CI) were used to determine the relationship within each group. Based on pre-established inclusion criteria, 28 studies involving 2920 breast cancer patients were included in this study. The r values of LVD-LVI, LVD-LNM, and LVI-LNM were 0.45 (95% CI: 0.31 to 0.57), 0.32 (95% CI: 0.23 to 0.40), and 0.24 (95% CI: 0.19 to 0.28), respectively. Compared with intratumoral LVD, peritumoral LVD showed more robust correlation with LVI (r = 0.53, 95% CI: 0.27 to 0.72) and LNM (r = 0.33, 95% CI: 0.18 to 0.46). The patients in LNM positive group presented with higher LVI detection rate of 45.85%, while in LNM negative group with detection rate of 23.85%. The results describe a triangle relationship between LVD, LVI, and LNM in breast cancer. Both LVD and LVI are indicated to be valuable predictors of LNM occurrence. Compared with intratumoral lymphatic vessels, peritumoral lymphatics might be the main disseminate route for breast tumor cells.

Targeting T1 and T2 dual modality enhanced magnetic resonance imaging of tumor vascular endothelial cells based on peptides-conjugated manganese ferrite nanomicelles.

Tumor angiogenesis plays very important roles for tumorigenesis, tumor development, metastasis, and prognosis. Targeting T1/T2 dual modality magnetic resonance (MR) imaging of the tumor vascular endothelial cells (TVECs) with MR molecular probes can greatly improve diagnostic sensitivity and specificity, as well as helping to make an early diagnosis of tumor at the preclinical stage. In this study, a new T1 and T2 dual modality nanoprobe was successfully fabricated. The prepared nanoprobe comprise peptides CL 1555, poly(ε-caprolactone)-block-poly(ethylene glycol) amphiphilic copolymer shell, and dozens of manganese ferrite (MnFe2O4) nanoparticle core. The results showed that the hydrophobic MnFe2O4 nanoparticles were of uniform spheroidal appearance and narrow size distribution. Due to the self-assembled nanomicelles structure, the prepared probes were of high relaxivity of 281.7 mM(-1) s(-1), which was much higher than that of MnFe2O4 nanoparticles (67.5 mM 1 s(-1)). After being grafted with the targeted CD105 peptide CL 1555, the nanomicelles can combine TVECs specifically and make the labeled TVECs dark in T2-weighted MR imaging. With the passage on, the Mn(2+) ions were released from MnFe2O4 and the size decreased gradually, making the signal intensity of the second and third passage of labeled TVECs increased in T1-weighted MR imaging. Our results demonstrate that CL-poly(ethylene glycol)-MnFe2O4 can conjugate TVECs and induce dark and bright contrast in MR imaging, and act as a novel molecular probe for T1- and T2-enhanced MR imaging of tumor angiogenesis.

Superparamagnetic core/shell GoldMag nanoparticles: size-, concentration- and time-dependent cellular nanotoxicity on human umbilical vein endothelial cells and the suitable conditions for magnetic resonance imaging.

BACKGROUND: GoldMag nanoparticles (GMNPs) possess the properties of colloid gold and superparamagnetic iron oxide nanoparticles, which make them useful for delivery, separation and molecular imaging. However, because of the nanometer effect, GMNPs are highly toxic. Thus, the biosafety of GMNPs should be fully studied prior to their use in biomedicine. The main purpose of this study was to evaluate the nanotoxicity of GMNPs on human umbilical vein endothelial cells (HUVECs) and determine a suitable size, concentration and time for magnetic resonance imaging (MRI). RESULTS: Transmission electron microscopy showed that GMNPs had a typical shell/core structure, and the shell was confirmed to be gold using energy dispersive spectrometer analysis. The average sizes of the 30 and 50 nm GMNPs were 30.65 ± 3.15 and 49.23 ± 5.01 nm, respectively, and the shell thickness were 6.8 ± 0.65 and 8.5 ± 1.36 nm, respectively. Dynamic light scattering showed that the hydrodynamic diameter of the 30 and 50 nm GMNPs were 33.2 ± 2.68 and 53.12 ± 4.56 nm, respectively. The r 2 relaxivity of the 50 nm GMNPs was 98.65 mM(-1) s(-1), whereas it was 80.18 mM(-1) s(-1) for the 30 nm GMNPs. The proliferation, cytoskeleton, migration, tube formation, apoptosis and ROS generation of labeled HUVECs depended on the size and concentration of GMNPs and the time of exposure. Because of the higher labeling rate, the 50 nm GMNPs exhibited a significant increase in nanotoxicity compared with the 30 nm GMNPs at the same concentration and time. At no more than 25 µg/mL and 12 hours, the 50 nm GMNPs exhibited no significant nanotoxicity in HUVECs, whereas no toxicity was observed at 50 µg/mL and 24 hours for the 30 nm GMNPs. CONCLUSIONS: These results demonstrated that the nanotoxicity of GMNPs in HUVECs depended on size, concentration and time. Exposure to larger GMNPs with a higher concentration for a longer period of time resulted in a higher labeling rate and ROS level for HUVECs. Coupled with r 2 relaxivity, it was suggested that the 50 nm GMNPs are more suitable for HUVEC labeling and MRI, and the suitable concentration and time were 25 µg/mL and 12 hours.

Thiol-PEG-carboxyl-stabilized Fe2O 3/Au nanoparticles targeted to CD105: synthesis, characterization and application in MR imaging of tumor angiogenesis.

OBJECTIVE: To detect tumor angiogenesis in tumor-bearing mice using thiol-PEG-carboxyl-stabilized Fe2O3/Au nanoparticles targeted to CD105 on magnetic resonance imaging (MRI). METHODS: Fe2O3/Au nanoparticles (hybrids) were prepared by reducing Au(3+) on the surface of Fe2O3 nanoparticles. Hybrids were stabilized with thiol-PEG-carboxyl via the Au-S covalent bond, and further conjugated with anti-CD105 antibodies through amide linkages. Characteristics of the hybrid-PEG-CD105 nanoparticles were evaluated. Using these nanoparticles, the labeling specificity of human umbilical vein endothelial cells (HUVECs) was evaluated in vitro. MRI T2-weighted images were obtained at different time points after intravenous administration of the hybrid-PEG-CD105 nanoparticles in the tumor-bearing mice. After MR imaging, the breast cancer xenografts were immediately resected for immunohistochemistry staining and Prussian blue staining to measure the tumor microvessel density (MVD) and evaluate the labeling of blood microvessels by the hybrid-PEG-CD105 nanoparticles in vivo. RESULTS: The mean diameter of the hybrid-PEG-CD105 nanoparticles was 56.6 ± 8.0 nm, as measured by transmission electron microscopy (TEM). Immune activity of the hybrid-PEG-CD105 nanoparticles was 53% of that of the anti-CD105 antibody, as detected by enzyme-linked immunosorbent assay (ELISA). The specific binding of HUVECs with the hybrid-PEG-CD105 nanoparticles was proved by immunostaining and Prussian blue staining in vitro. For breast cancer xenografts, the combination of the hybrid-PEG-CD105 nanoparticles with blood microvessels was detectable by MRI after 60 min administration of the contrast agent. The T2* relative signal intensity (SIR) was positively correlated with the tumor MVD (R(2)=0.8972). CONCLUSION: Anti-CD105 antibody-coupled, thiol-PEG-carboxyl-stabilized core-shell Fe2O3/Au nanoparticles can efficiently target CD105 expressed by HUVECs. Furthermore, the hybrid-PEG-CD105 nanoparticles can be used to detect tumor angiogenesis in vivo.

MRI findings of primary CNS lymphoma in 26 immunocompetent patients.

OBJECTIVE: To record the MR imaging features of primary central nervous system lymphoma (PCNSL) and compare these features in monofocal and multifocal disease. MATERIALS AND METHODS: Twenty-one cases of monofocal disease were compared to five cases of multifocal disease. All patients were examined by non-enhanced and contrast-enhanced MRI. Tumor location, tumor size, signal intensity, enhancement characteristics, age distribution, peritumoral edema, cystic changes, and the presence of calcifications were assessed. The MRI features were compared between the monofocal and multifocal disease cases. RESULTS: The 26 cases, including both the monofocal and multifocal cases, exhibited 37 lesions. Contrast-enhanced images showed variable enhancement patterns: homogeneous enhancement (33 lesions), ring-like enhancement (2), and 'open-ring-like' enhancement (2). The 'notch sign' was noted in four of 33 homogeneously enhancing lesions. One case of hemorrhage and three cases of cystic formation were observed. Intra-tumoral calcification was not found. The frontal lobe, the corpus callosum and the basal ganglia were commonly affected in both the monofocal and multifocal groups. Tumor size differed significantly between the two groups (t = 3.129, p < 0.01) and mildly or moderately enhanced lesions were more frequently found in the monofocal group (p < 0.05). There was no statistical difference between perifocal edema (p > 0.05) and the signal characteristics (p > 0.05) between the two groups. CONCLUSION: Our data show that PCNSL has a variable enhancement pattern on MR images. We first reported two lesions with an 'open-ring' enhancement as well as four cases with a 'notch sign'. Monofocal PCNSL cases typically have larger sized tumors with mild or moderate enhancement.

MR imaging of tumor angiogenesis using sterically stabilized Gd-DTPA liposomes targeted to CD105.

AIM: To depict tumor angiogenesis via the expression of CD105 in tumor-bearing rats using Gd-DTPA liposomes targeted to CD105 (CD105-Gd-SLs) on MR imaging. MATERIALS AND METHODS: Three Gd-DTPA liposomal nanoparticles were prepared in our trial: liposomes entrapping Gd-DTPA (Gd-SLs), Gd-SLs conjugated to immunoglobulins (IgG-Gd-SLs) and CD105-Gd-SLs. Forty glioma-bearing rats were randomized into four groups: (a) Gd-DTPA; (b) Gd-SLs; (c) IgG-Gd-SLs; (d) CD105-Gd-SLs. Axial T1WI MRI images were collected at baseline and repeated at 5, 30, 60 and 120 min post-intravenous injection of Gd-DTPA or liposome. Enhancement features and contrast-to-noise ratio of each group were analyzed. After imaging, tumors were resected for immunohistochemistry and immunofluorescence staining to assess vascularity and angiogenesis. RESULTS: The four groups showed different enhancement features. The enhancement area was restricted for group CD105-Gd-SLs, while diffused for the other three. The degree of enhancement over time varied: group Gd-DTPA showed an early contrast enhancement at instant after injection with a peak at 30 min and a decline to baseline values at 60 min. In group CD105-Gd-SLs, the signal intensity (SI) continuously increased over 120 min. In groups IgG-Gd-SLs and Gd-SLs the SI peaked at 60 min, followed by a minor decrease for IgG-Gd-SLs and a rapid decrease for Gd-SLs almost to baseline. Immunohistochemistry and immunofluorescence showed that the enhancement in the CD105-Gd-SLs group resulted mainly from new microvessels. While in the other three groups, mature microvessels and new microvasculature resulted in the enhancement of the tumor. CONCLUSION: CD105-Gd-SLs can be used to detect early tumor angiogenesis on MR images. This might provide a means to non-invasively reveal a malignant phenotype of extracerebral F98 tumor and evaluate its progression.

[Imaging diagnosis of the vertebral injury in earthquake].

OBJECTIVE: To explore the clinical value of imaging diagnosis of the vertebral injury in earthquake. METHODS: Twenty-two cases of the vertebral injury in earthquake with clinical and imaging data were analyzed retrospectively. All of the cases were performed X-ray plain film examination, CT in 20 cases and MRI in 15 cases. RESULTS: Imaging examination can establish definitive diagnosis in all cases. In the 22 cases, the vertebral compression fracture was found in 20 cases, and vertebral bursting fracture in 2 cases,single-level vertebral fracture in 12 case,and multiple-level vertebral fracture in 10 case. Among the 31 vertebral bodies of fracture, the fracture of cervical vertebra, thoracic vertebra, lumbar vertebra and sacral vertebra was found in 3, 12, 14, 2 vertebral bodies, respectively. CONCLUSION: Imaging examination is the most valuable examination method in diagnosis of the vertebral injury in earthquake. It can not only make definitive diagnosis, but also play an important role in selection of therapeutic method.

Establishing models of portal vein occlusion and evaluating value of multi-slice CT in hepatic VX2 tumor in rabbits.

AIM: To establish models of portal vein occlusion of hepatic VX2 tumor in rabbits and to evaluate the value of multi-slice CT. METHODS: Forty New Zealand rabbits were divided into 4 groups according to digital table: Immediate group (group A; transplantation of tumor immediately after the portal vein occlusion), 3-wk group (group B; transplantation of tumor at 3 wk after the portal vein occlusion), negative control group (group C) and positive control group (group D), 10 rabbits in each group. Hepatic VX2 tumor was transplanted with abdominal-embedding inoculation immediately after the portal vein occlusion and at 3 wk after the portal vein occlusion. Meanwhile, they were divided into negative control group (Left external branch of portal vein was occluded by sham-operation, and left exite was embedded and inoculated pseudoly) and positive control group (Transplanted tumor did not suffer from the portal vein occlusion). All rabbits were scanned with multi-slice CT. RESULTS: All 40 animals were employed in the final analysis without death. Tumor did not grow in both immediate group and 3-wk group. In 3-wk group, left endite was atrophied and growth of tumor was inhibited. The maximal diameter of tumor was significantly smaller than that in positive control group (2.55 +/- 0.46 vs 3.59 +/- 0.37 cm, t = 5.57, P < 0.001). Incidences of metastasis in the liver and lung were lower in 3-wk group than those in positive control group (10% vs 40%, and 90% vs 100%, respectively). The expression intensities of the vascular endothelium growth factor (VEGF) in groups A, B, C and D were 0.10 +/- 0.06, 0.66 +/- 0.21, 0.28 +/- 0.09 and 1.48 +/- 0.32, respectively. VEGF expression level in the test group A was significantly lower than that in the negative control group C (t = 5.07; P < 0.001). In addition, VEGF expression in the test group B was significantly lower than that in the positive control group D (t = 6.38; P < 0.001). Scanning with multi-slice CT showed that displaying rate of hepatic artery branches was obviously lower in grade III (40%) than that in grade I (70%) and II (100%) (P < 0.05); but there was no significant difference in displaying rate of the portal vein at various grades. Values of blood flow (BF) of the liver, blood volume (BV), mean transit time (MTT) and permeability of vascular surface (PS) were lower in the immediate group and 3-wk group than those in control groups, but values of hepatic arterial fraction (HAF) were increased. Significant positive correlations were existed between BF and BV (r = 0.905, P < 0.01), and between BF and PS (r = 0.967, P < 0.01), between BV and PS (r = 0.889, P < 0.01). A significant negative correlation existed between PV and HAF (r = -0.768, P < 0.01), between PS and HAF (r = -0.557, P < 0.01). The values of BF, BV and PS had a positive correlation with VEGF (r(BF) = 0.842, r(BV) = 0.579, r(PS) = 0.811, P < 0.01) . However, there was no significant correlation between the values of MTT and HAF and the VEGF expression (r(MTT) = 0.066, r(HAF) = -0.027). CONCLUSION: Ligating the left external branch of portal vein is an ideal way to establish models of portal vein occlusion in rabbits with hepatic VX2 tumor. Multi-slice CT plays a key role in evaluating effect of portal vein occlusion.

[Analysis of the causes of misdiagnosis on CT films of 45 patients with lung cancer].

BACKGROUND: To analyze the causes of computed tomographic misdiagnosis of pulmonary carcinoma. METHODS: From September 1991 to January 2002, 45 cases of pulmonary carcinoma misdiagnosed by CT were analyzed retrospectively. Twenty-six cases of pulmonary tuberculosis and 15 cases of pulmonary pneumonia misdiagnosed as pulmonary carcinoma by CT were studied as control subjects. All of these cases were confirmed by surgery and clinical course. The CT appearances of these cases were independently reviewed in a double blind method by three experienced radiologists. Then they discussed together in order to search for the factors of CT misdiagnosis and formed a consensus interpretation. RESULTS: Forty-five cases of pulmonary carcinoma were misdiagnosed as pulmonary tuberculosis in 19 cases, pneumonia in 14 cases, abscess in 4 cases, pleural mesothelioma in 2 cases, normal in 2 cases, and others in 4 cases. The fundamental manifestations of misdiagnosed cases were lobar or segmental shadows (26 cases), solitary mass or nodule (19 cases).The reasons of CT misdiagnosis were very confusing. The main factors were:(i) Missed diagnosis (2 cases, 4.5%). One case had an endobronchial mass and another had the erosion of rib. (ii) Twenty-four cases (53.3%) due to mis interpretation and lack of experience. (iii) The manifestations in CT were atypical (19 cases,42.2%). CONCLUSIONS: Not identifying accurately the CT appearances and excessively emphasizing the specificity of some signs are the main causes of the misdiagnosis. A reasonable and careful CT examination, summarizing analysis combined with clinical findings, and the accumulation of diagnostic experience will help to reduce the CT misdiagnostic rate of pulmonary carcinomas.