Temporal base intradural transpetrosal approach to the petoclival region: an appraisal of anatomy, operative technique and clinical experience.

BACKGROUND: Tumours in the petroclival region have been a challenge to neurosurgeons. We present a cohort of 24 patients with petroclival meningioma (PCM) and trigeminal schwannoma (TS) in the petroclival region with extension to the middle fossa which were removed with the temporal base intradural transpetrosal (TBIT) approach. METHODS: To avoid damage to the important surrounding structures in the petrosal bone, a morphometric analysis in the TBIT approach was performed in 15 cadaveric heads, and the 'safe area of intradural petrosectomy' was identified in the TBIT approach. Subsequently, 14 patients with PCM and 10 patients with TS in the petroclival region were operated on with the TBIT approach. RESULTS: There were no operative deaths in this cohort related to the surgery. Common complications included light hemiparesis in two patients (8.0%), new cranial nerve paresis in nine (37.5%), post-operative pneumonia in one (4.0%) and transient cerebrospinal fluid leak in one (4.0%). Total tumour resection was achieved in 20 patients (83.3%) and subtotal resection in 4 (16.7%). There was no tumour recurrence in all patients at follow-up with a mean duration of 37 months. CONCLUSIONS: Surgical strategy for PCM and TS in the petroclival region should be tailored to individual patients. The TBIT approach may improve the exposure of tumours in the petroclival region. A clear description of the 'safe area of intradural petrosectomy' appears to decrease the risk associated with petrosectomy procedure in the TBIT approach.

[Value of SQLE Expression in Prognostic Evaluation of Patients with Acute Myeloid Leukemia].

OBJECTIVE: To analyze the relationship between the expression level of SQLE and the prognosis of patients with acute myeloid leukemia (AML) through large sample data. METHODS: The data of genome, transcriptome, gene chip expression, and clinical information were statistically analyzed in multiple cohorts of AML patients with large samples. RESULTS: It was found that the expression level of SQLE gene in tumor cells of AML patients was significantly higher than that of healthy controls (P=0.001). In the three AML corhort, the SQLE high expression group showed a worse therapeutic outcome (OS, P=0.009, P=0.0001, P=0.006; EFS, P=0.005, P=0.001). The unvariate and multivariate survival prognosis analysis indicated that the high expression of SQLE suggests lower event-free survival rate (EFS, HR=1.551, P<0.05) and overall survival rate (OS, HR=1.484, P<0.05). At the same time, it was also found that among different risk subgroups, the expression of SQLE in high risk group was higher (P<0.001, P=0.01), while the patients with high SQLE expression, who received allogeneic HSCT, had longer overall survival time (P=0.006). CONCLUSION: The up-regulation SQLE expression suggests a poor prognosis for the patients with AML.

Icariside II ameliorates myocardial ischemia and reperfusion injury by attenuating inflammation and apoptosis through the regulation of the PI3K/AKT signaling pathway.

Icariside II (ICAII) is a bioflavonoid compound which has demonstrated anti­oxidative, anti­inflammatory and anti­apoptotic biological activities. However, to the best of our knowledge, whether ICAII can alleviate myocardial ischemia and reperfusion injury (MIRI) remains unknown. The aim of the present study was to determine whether ICAII exerted a protective effect on MIRI and to investigate the potential underlying mechanism of action. A rat MIRI model was established by ligation of the left anterior descending coronary artery for 30 min, followed by a 24 h reperfusion. Pretreatment with ICAII with or without a PI3K/AKT inhibitor was administered at the beginning of reperfusion. Morphological and histological analyses were detected using hematoxylin and eosin staining; the infarct size was measured using Evans blue and 2,3,5­triphenyltetrazolium chloride staining; and plasma levels of lactate dehydrogenase (LDH) and creatine kinase­myocardial band (CK­MB) were analyzed using commercialized assay kits. In addition, the cardiac function was evaluated by echocardiography and the levels of cardiomyocyte apoptosis were determined using a TUNEL staining. The protein expression levels of Bax, Bcl­2, cleaved caspase­3, interleukin­6, tumor necrosis factor­α, PI3K, phosphorylated (p)­PI3K, AKT and p­AKT were analyzed using western blotting analysis. ICAII significantly reduced the infarct size, decreased the release of LDH and CK­MB and improved the cardiac function induced by IR injury. Moreover, ICAII pretreatment significantly inhibited myocardial apoptosis and the inflammatory response. ICAII also upregulated the expression levels of p­PI3K and p­AKT. However, the protective effects of ICAII were abolished by an inhibitor (LY294002) of the PI3K/AKT signaling pathway. In conclusion, the findings of the present study suggested that ICAII may mitigate MIRI by activating the PI3K/AKT signaling pathway.

[Prognostic Value of SLC25A12 Expression in Patients with Acute Myeloid Leukemia Based on Integrated Analysis of Multi-dimensional Clinical Data].

OBJECTIVE: To investigate the clinical and prognostic value of SLC25A12 in patients with acute myeloid leukemia (AML). METHODS: The expression levels of SLC25A12 in bone marrow or peripheral blood cells of AML patients and healthy people in two independent cohorts (n=46, n=290, respectively) were compared. Then it was assessed that the prognostic value of SLC25A12 expression in two independent AML study cohorts (n=163, n=329, respectively) by mean of integrated analysis of genomic, transcriptome, clinical and prognosis information. RESULTS: The expression of SLC25A12 in AML patients significantly increased as compared with that of healthy people (P=0.0001, P=0.0238, respectively). Univariate and multivariate analyze showed that high SLC25A12 expression was significantly associated with shorter event-free survival (EFS)(HR=1.605, P=0.018) and overall survival (OS)(HR=1.818, P=0.002) of patients. In favorable-risk and intermediate-risk subgroups, patients with high SLC25A12 expression showed shorter EFS and OS than patients with low SLC25A12 expression. CONCLUSION: High SLC25A12 expression significantly associated with poor prognosis of AML patients, which suggests that SLC25A12 aberrant expression can be used as a potential molecular marker for prognosis evaluation of AML patients.

Volume-based histogram analysis of dynamic contrast-enhanced MRI for estimation of gliomas IDH1 mutation status.

PURPOSE: The study aimed to investigate whether isocitrate dehydrogenase 1 (IDH1) mutation status in gliomas can be estimated by volume-based histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: Preoperative DCE-MRI data of 85 pathologically confirmed glioma patients including 33 carrying IDH1 mutant type (IDH1mut) and 52 with IDH1 wildtype (IDH1wt) were reviewed in a retrospective approach. Regions of interest (ROI) covering entire tumor volume were manually delineated using O.K. software (OmniKinetics, GE Healthcare, China). Histogram parameters of volume transfer constant (Ktrans) and volume of extravascular /extracellular space per unit volume of tissue (Ve) derived from DCE-MRI were obtained. Mann-Whitney U tests were made to compare the differences in histogram parameters of Ktrans and Ve between IDH1mut and IDH1wt in all gliomas and high-grade gliomas (HGGs, grade III and IV). Receiver operator characteristic (ROC) analysis were implemented to assess the diagnostic performance. RESULTS: In histogram parameters of Ktrans and Ve, pairwise comparisons demonstrated statistically significant differences in mean, standard deviation (SD), 90th and 95th percentiles (90%, 95%) values between IDH1mut and IDH1wt in all cases of gliomas and HGGs (P < 0.05, respectively). The ROC analysis revealed that the cut-off values of 95% value of Ktrans (0.097 min-1) and mean value of Ve (0.099) provided the best combination of sensitivity and specificity to distinguish all gliomas with IDH1mut from IDH1wt. In HGGs, the cut-off values of mean value of Ktrans and Ve (0.044 min-1, 0.099) played similar role. CONCLUSION: Volume-based histogram analysis of DCE-MRI performs well in identification of IDH1mut gliomas.

Quantitative Assessment of Tumor Cell Proliferation in Brain Gliomas with Dynamic Contrast-Enhanced MRI.

RATIONALE AND OBJECTIVES: This study aimed to investigate whether volume transfer constant (Ktrans) and volume of extravascular extracellular space per unit volume of tissue (Ve) derived from dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) could quantitatively assess the tumor proliferation index (Ki-67) of gliomas noninvasively. MATERIALS AND METHODS: The preoperative DCE MRI data of 69 patients with pathologically confirmed glioma (28, 8, and 33 cases in grades Ⅱ, Ⅲ, and Ⅳ) were retrospectively reviewed. The maximal Ktrans and Ve were measured in the tumor body. The immunohistochemistry was used to detect the expression of Ki-67 proteins in glioma specimens. The Mann-Whitney U test was applied to analyze the differences in Ktrans, Ve, and Ki-67 index across histologically defined glioma grades. Spearman correlation was performed between Ktrans, Ve, and Ki-67 index. The receiver operating characteristic curve analysis was used to determine the cutoff values of Ktrans and Ve in distinguishing different Ki-67 index expression levels. RESULTS: Ktrans, Ve, and Ki-67 index of grade Ⅱ (0.027 min-1, 0.065, 4.04%) were significantly lower than those of grade Ⅲ (0.093 min-1, 0.297, 25.13%) and Ⅳ (0.100 min-1, 0.299, 25.37%). Both Ktrans and Ve significantly correlated with the Ki-67 index in all tumors and high-grade gliomas (HGGs, grade Ⅲ and Ⅳ). The receiver operating characteristic curve analysis revealed that the cutoff values for Ktrans (0.079 min-1) and Ve (0.249) provided the best combination of sensitivity and specificity to distinguish the gliomas with high Ki-67 index from those with low Ki-67 index. CONCLUSION: The DCE MRI-derived parameters were valuable in assessing the tumor cell proliferation in HGG noninvasively.

Comparison between perfusion computed tomography and dynamic contrast-enhanced magnetic resonance imaging in assessing glioblastoma microvasculature.

PURPOSE: Perfusion computed tomography (PCT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provide independent measurements of biomarkers related to tumor perfusion. The aim of this study was to compare the two techniques in assessing glioblastoma microvasculature. MATERIALS AND METHODS: Twenty-five patients diagnosed with glioblastoma (14 males and 11 females; 51±11years old, ranging from 33 to 70 years) were includede in this prospective study. All patients underwent both PCT and DCE-MRI. Imaging was performed on a 256-slice CT scanner and a 3-T MRI system. PCT yielded permeability surface-area product (PS) using deconvolution physiological models; meanwhile, DCE-MRI determined volume transfer constant (Ktrans) using the Tofts-Kermode compartment model. All cases were submitted to surgical intervention, and CD105-microvascular density (CD105-MVD) was measured in each glioblastoma specimen. Then, Spearman's correlation coefficients and Bland-Altman plots were obtained for PS, Ktrans and CD105-MVD. P<0.05 was considered statistically significant. RESULTS: Tumor PS and Ktrans values were correlated with CD105-MVD (r=0.644, P<0.001; r=0.683, P<0.001). In addition, PS was correlated with Ktrans in glioblastoma (r=0.931, P<0.001). Finally, Bland-Altman plots showed no significant differences between PS and Ktrans (P=0.063). CONCLUSION: PCT and DCE-MRI measurements of glioblastoma perfusion biomarkers have similar results, suggesting that both techniques may have comparable utility. Therefore, PCT may serve as an alternative modality to DCE-MRI for the in vivo evaluation of glioblastoma microvasculature.

Overexpression of ATP1B1 predicts an adverse prognosis in cytogenetically normal acute myeloid leukemia.

ATP1B1 encodes the Na,K-ATPase ß subunit, a key regulator of the Na+ and K+ electrochemical gradients across the plasma membrane and an essential regulator of cellular activity. We used several microarray datasets to test the prognostic efficacy of ATP1B1 expression in cytogenetically normal acute myeloid leukemia (CN-AML). Within the primary cohort (n = 157), high ATP1B1 expression (ATP1B1(high)) was associated with shorter overall survival (OS) and event-free survival (EFS) (P = 0.0068, P = 0.0039, respectively). Similar results were also obtained in the European Leukemia Net (ELN) Intermediate-I genetic category (OS: P = 0.0035, EFS: P = 0.0007). Multivariable analyses confirmed ATP1B1(high) is an independent predictor of shorter OS (P = 0.042) and EFS (P = 0.035). Analysis of another CN-AML cohort confirmed that ATP1B1(high) is associated with shorter OS (P = 0.0046, n = 162). In addition, up-regulation of oncogenes/onco-microRNAs such as MYCN, CCND2, CDK6, KIT and miR-155, among others, was associated with ATP1B1(high), which may be indicative of ATP1B1's leukemogenicity. Our results may improve risk stratification and indicate new therapeutic targets for CN-AML.

Epigenetic Silencing of Eyes Absent 4 Gene by Acute Myeloid Leukemia 1-Eight-twenty-one Oncoprotein Contributes to Leukemogenesis in t(8;21) Acute Myeloid Leukemia.

BACKGROUND: The acute myeloid leukemia 1 (AML1)-eight-twenty-one (ETO) fusion protein generated by the t(8;21)(q22;q22) translocation is considered to display a crucial role in leukemogenesis in AML. By focusing on the anti-leukemia effects of eyes absent 4 (EYA4) gene on AML cells, we investigated the biologic and molecular mechanism associated with AML1-ETO expressed in t(8;21) AML. METHODS: Qualitative polymerase chain reaction (PCR), quantitative reverse transcription PCR (RT-PCR), and Western blotting analysis were used to observe the mRNA and protein expression levels of EYA4 in cell lines. Different plasmids (including mutant plasmids) of dual luciferase reporter vector were built to study the binding status of AML1-ETO to the promoter region of EYA4. Chromatin immunoprecipitation assay was used to study the epigenetic silencing mechanism of EYA4. Bisulfite sequencing was applied to detect the methylation status in EYA4 promoter region. The influence of EYA4 gene in the cell proliferation, apoptosis, and cell clone-forming ability was detected by the technique of Cell Counting Kit-8, flow cytometry, and clonogenic assay. RESULTS: EYA4 gene was hypermethylated in AML1-ETO+ patients and its expression was down-regulated by 6-fold in Kasumi-1 and SKNO-1 cells, compared to HL-60 and SKNO-1-siA/E cells, respectively. We demonstrated that AML1-ETO triggered the epigenetic silencing of EYA4 gene by binding at AML1-binding sites and recruiting histone deacetylase 1 and DNA methyltransferases. Enhanced EYA4 expression levels inhibited cellular proliferation and suppressed cell colony formation in AML1-ETO+ cell lines. We also found EYA4 transfection increased apoptosis of Kasumi-1 and SKNO-1 cells by 1.6-fold and 1.4-fold compared to negative control, respectively. CONCLUSIONS: Our study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene. In addition, we provided evidence that EYA4 gene might be a novel therapeutic target and a potential candidate for treating AML1-ETO+ t (8;21) AML.

High expression of inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) as a novel biomarker for worse prognosis in cytogenetically normal acute myeloid leukemia.

Inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) is a key regulator for the activity of calcium ion transmembrane transportation, which plays a critical role in cell cycle and proliferation. However, the clinical impact of ITPR2 in cytogenetically normal acute myeloid leukemia (CN-AML) remained unknown. Several microarray datasets were used to evaluate the association between ITPR2 expression and clinical and molecular characteristics. ITPR2 showed a higher expression in CN-AML patients than normal persons. In a cohort of 157 CN-AML patients, high ITPR2 expression (ITPR2high) was associated with dramatically shorter overall survival (OS; P = 0.004) and event-free survival (EFS; P = 0.01), which were also shown in the European Leukemia Net (ELN) intermediate-I genetic category (OS: P = 0.0066; EFS: P = 0.009). Multivariable analyses adjusting for known prognostic factors confirmed ITPR2high to be associated with shorter OS (P = 0.0019) and EFS (P = 0.012). The prognostic value of ITPR2 was further validated in another cohort of 162 CN-AML patients (P = 0.007). In addition, first gene/microRNA expression signatures were derived that associated with ITPR2high on the genome-wide scale, which provided many indications to illustrate the possible mechanisms why ITPR2 could function. These results could aid to identify new targets and design novel therapeutic strategies for CN-AML patients.

The assessment of immature microvascular density in brain gliomas with dynamic contrast-enhanced magnetic resonance imaging.

PURPOSE: This study was designed to quantitatively evaluate the immature microvascular density (MVD) of brain gliomas using the volume transfer constant (K(trans)) and volume of extravascular extracellular space per unit volume of tissue (Ve) from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) noninvasively. MATERIALS AND METHODS: Fifty-seven patients (35 males, 22 females; age range, 14-70, mean age 46±12 years old) with brain glioma were included in this study. The maximal values of K(trans) and Ve of all patients with brain glioma (grade II 24, III 7 and IV 26) were obtained. The CD105-microvascular density (CD105-MVD) of each tumor was measured in surgical specimen. The differences of K(trans), Ve and CD105-MVD between the different grades of gliomas were analyzed using the Mann-Whitney U-test. The Pearman correlation coefficient was determined between K(trans), Ve and CD105-MVD. A P-value of less than 0.05 was considered statistically significant. RESULTS: The differences in K(trans), Ve and CD105-MVD were statistically significant between low-grade glioma (LGG) and high-grade glioma (HGG) (P=0.001, P<0.001, P<0.001). The K(trans), Ve and CD105-MVD of grade II were significantly lower than those of grade III and IV. K(trans) and Ve were positively correlated with CD105-MVD in HGG (P<0.001, P<0.001). CONCLUSIONS: Our results suggest DCE-MRI plays an important part in noninvasively evaluating the immature MVD of brain gliomas.

[FLT3 gene overexpression and its clinical significance in acute myeloid leukemia with AML1/ETO fusion gene positive].

This study was aimed to investigate the expression levels of FLT3 gene in AML-M2 patients carrying AML1/ETO fusion gene, and analyze its relation with clinical and laboratorial features and prognosis. RQ-PCR method was used to detect the expression level of FLT3 in bone marrow of 21 AML-M2 patients with AML1/ETO(+). The correlation of the expression level of FLT3 with clinical features, other laboratorial examinations and disease prognosis were analyzed. The results showed that gene expression level of FLT3 (FLT3 gene/ reference gene) in patients at initial diagnosis were 1.65%-261.5%. The expression level of FLT3 over 35% was defined as high expression group (12 cases) , while the expression level below 35% was defined as low expression group (9 cases) . The proportion of patients with extramedullary infiltration in high expression group was higher than that in low expression group (25% vs 0%, P = 0.2286). The proportion of patients at initial diagnosis with white blood cell count > 10×10(9)/L in high expression group was higher than that in low expression group (66.67% vs 22.22%), but there was no statistical significance (P = 0.0805). No significant difference was observed at the age (P = 0.1369) and the rate of bone marrow blasts (P = 0.6923) between the above mentioned two groups. The differences in complete remission rate (66.67% vs 88.89%, P = 0.3383), the relapse rate (66.67% vs 22.22%,P = 0.0805) and the mortality rate (50% vs 22.22%, P = 0.3666) between the two group were not significant, but there was a clear trend that the low expression group has a higher CR rate and a lower relapse rate and mortality rate. It is concluded that FLT3 gene high expression in AML-M2 patients with AML1/ETO(+) have a higher rate of relapse and hence poor prognosis. Therefore, detection of FLT3 expression level in routine clinical practice is important for patient's risk stratification, prognostic evaluation and effective treatment selection.

[Splenic embolization combined with double-mirror method in treatment of cirrhosis with hypersplenism of advanced schistosomiasis patients: a report of 38 cases].

A total of 38 patients with schistosomiasis cirrhosis complicated with hypersplenism were cured by endoscopic variceal ligation (EVL), partial splenic embolization (PSE) and laparoscopic splenectomy (LS). After the surgery, the hemogram and liver function of all the patients recovered within two weeks. The average hospitalization time was shorter, the average hospitalization expense was less, and the complications were also less compared with those of the patients who received the routine therapy. In conclusion, the combination therapy of EVL and PSE combined with LS is effective and safe in the treatment of schistosomiasis cirrhosis complicated with hypersplenism.

Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumor specific cytotoxic T lymphocyte responses.

Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+), but not CD4(+) T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.

Microsurgical excision of the craniocervical neurenteric cysts by the far-lateral transcondylar approach: case report and review of the literature.

Neurenteric cysts in the anterior craniocervical junction (CCJ) region can be found in extremely rare cases. We report one case with craniocervical neurenteric cyst that was excised by the far-lateral transcondylar (FLT) approach. A 43-year-old man presented with a history of recurrent episodes of mild neck pain and dysesthesia in his bilateral hands of 2 years' duration with rapid deterioration 3 weeks prior to admission. Magnetic resonance imaging (MRI) of the CCJ region revealed a well-defined intradural cystic lesion located ventral from the pontomedullary junction to C1 vertebra with medulla and C1 cord compression. This patient underwent total excision of the lesion via the FLT approach without any postoperative neurological deficits, and the histopathologic diagnosis was neurenteric cyst. Follow-up MRI has revealed no evidence of recurrence. The clinical features, imaging studies, and surgical approach options involved in resecting craniocervical neurenteric cysts are discussed, along with a review of the literature.