Prognostic role of neutrophil-to-lymphocyte ratio to laryngeal squamous cell carcinoma: a meta-analysis / Papel prognóstico da relação neutrófilo-linfócito no carcinoma espinocelular da laringe: uma metanálise

Abstract Introduction New evidence suggests that the ratio of neutrophils to lymphocytes is associated with the prognosis of other carcinoma, but the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma remains controversial. Objective The objective of this meta-analysis was to clarify the prognostic effectiveness of the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma. Methods According to the meta-analysis of the free guide, we searched EMBASE, Pubmed, the Cochrane Library databases. The ratio of neutrophils to lymphocytes of laryngeal squamous cell carcinoma patients was evaluated using mean standard vehicle and confidence interval. The overall survival, disease-free survival and progression free survival of patients with laryngeal squamous cell carcinoma were expressed by standard mean carrier method and confidence interval. The risk ratio of 95% confidence interval was used as an evaluation index for patients with laryngeal squamous cell carcinoma. Results Eight studies, including 1780 patients, used a variety of different end values to classify the ratio of neutrophils to lymphocytes (range 1.78-4.0). Among the eight studies that reported risk ratio of the overall survival, the higher median value was 2.72, and 2 of 4 studies reported disease-free survival results. The critical value of ratio of neutrophils to lymphocytes and overall survival deterioration (risk ratio = 1.68, 95% confidence interval 1.43-1.99, p< 0.001), disease-free survival (risk ratio = 2.09, 95% confidence interval 1.62-2.6, p< 0.001) and progression free survival (risk ratio = 1.92, 95% confidence interval 1.75-2.10, p< 0.001) was associated with with laryngeal aquamous cell carcinoma. The ratio of neutrophils to lymphocytes had prognostic value for laryngeal squamous cell carcinoma. Conclusion The results of this meta-analysis showed that the increase of neutrophils to lymphocytes ratio was related to poor prognosis of laryngeal squamous cell carcinoma. The neutrophils to lymphocytes ratio may serve as a cost-effective prognostic biomarker of poor prognosis of laryngeal squamous cell carcinoma. More high-quality prospective trials are needed to assess the practicability of evaluating the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma.

Resumo Introdução Novas evidências sugerem que a relação neutrófilo-linfócito está associada ao prognóstico de vários carcinomas, mas a relação neutrófilo-linfócito no carcinoma espinocelular da laringe ainda permanece controversa. Objetivo Esclarecer a eficácia prognóstica da relação neutrófilo-linfócito no carcinoma espinocelular de laringe. Método De acordo com as diretrizes de metanálise, conduzimos uma busca nas bases de dados Embase, PubMed, e Cochrane Library. A relação neutrófilo-linfócito de pacientes com carcinoma espinocelular de laringe foi avaliado com a diferença de médias padronizadas e intervalo de confiança. A sobrevida global, sobrevida livre de doença e sobrevida livre de progressão de pacientes com carcinomaespinocelular de laringe foram expressas pelo método da diferença de médias padronizadas e intervalo de confiança. A razão de risco do intervalo de confiança 95% foi usada como um índice de avaliação para pacientes com carcinoma espinocelular de laringe. Resultados Oito estudos, que incluíram 1.780 pacientes, usaram uma variedade de valores finais diferentes para classificar a relação neutrófilo-linfócito (intervalo de 1,78-4,0). Entre os oito estudos que relataram a razão de risco de sobrevida global, o maior valor médio foi de 2,72 e 2 de 4 estudos relataram resultados com sobrevida livre de doença. O valor crítico de relação neutrófilo-linfócito e deterioração da sobrevida global (razão de risco = 1,68, intervalo de confiança 95% 1,43-1,99, p ˂ 0,001), sobrevida livre de doença (razão de risco = 2,09, intervalo de confiança 95% 1,62-2,6, p ˂ 0,001) e sobrevida livre de progressão (razão de risco = 1,92, intervalo de confiança 95% 1,75-2,10, p ˂ 0,001) foi associado com carcinoma espinocelular de laringe. A relação neutrófilo-linfócito tem valor prognóstico para carcinoma espinocelular de laringe. Conclusão Os resultados da metanálise mostraram que o aumento da relação neutrófilo-linfócito estava relacionado ao mau prognóstico do carcinoma espinocelular de laringe. A relação neutrófilo-linfócito pode servir como um biomarcador custo-efetivo de prognóstico do carcinoma espinocelular de laringe. Entretanto, mais estudos prospectivos de alta qualidade são necessários para avaliar a sua praticabilidade.

A Characterization Study of the Patients Visiting Hospital due to Laryngopharyngeal Reflux Suspicion: A Prospective Case-Control Study.

BACKGROUND: This study aimed to explore the characteristics of laryngopharyngeal reflux (LPR) and the association between LPR and allergic rhinitis (AR). METHODS: In this prospective case-control study, a total of 102 patients with suspected LPR who visited the Department of Otolaryngology Head and Neck Surgery, Heping Hospital Affiliated to Changzhi Medical College, between June 2019 and June 2021 were consecutively included. They were divided into the LPR-positive group and the LPR-negative group according to 24-h Dx-pH monitoring. The influencing factors of LPR, including the scores for AR (SFAR) and AR prevalence, were compared between the two groups. RESULTS: The total SFAR and scores in items 1, 3, 4, and 5 of the LPR-positive group were significantly higher than those of the LPR-negative group (p < 0.05). The prevalence of AR in the LPR-positive group was 60%, which was significantly higher than that in the LPR-negative group (36.54%) (p < 0.05). After excluding confounding factors, AR was positively correlated with the incidence of LPR, and the incidence of LPR with AR was 2.372 times that of non-AR. Receiver operating characteristic curve results show that AR has the highest predictive value for LPR, and the area of AR under the curve is was 0.617. CONCLUSIONS: The SFAR and incidence of AR are high in patients with positive LPR, and AR may be a risk factor for LPR. The results of this study may deepen our understanding of the occurrence of LPR.

Prognostic role of neutrophil-to-lymphocyte ratio to laryngeal squamous cell carcinoma: a meta-analysis.

INTRODUCTION: New evidence suggests that the ratio of neutrophils to lymphocytes is associated with the prognosis of other carcinoma, but the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma remains controversial. OBJECTIVE: The objective of this meta-analysis was to clarify the prognostic effectiveness of the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma. METHODS: According to the meta-analysis of the free guide, we searched EMBASE, Pubmed, the Cochrane Library databases. The ratio of neutrophils to lymphocytes of laryngeal squamous cell carcinoma patients was evaluated using mean standard vehicle and confidence interval. The overall survival, disease-free survival and progression free survival of patients with laryngeal squamous cell carcinoma were expressed by standard mean carrier method and confidence interval. The risk ratio of 95% confidence interval was used as an evaluation index for patients with laryngeal squamous cell carcinoma. RESULTS: Eight studies, including 1780 patients, used a variety of different end values to classify the ratio of neutrophils to lymphocytes (range 1.78-4.0). Among the eight studies that reported risk ratio of the overall survival, the higher median value was 2.72, and 2 of 4 studies reported disease-free survival results. The critical value of ratio of neutrophils to lymphocytes and overall survival deterioration (risk ratio = 1.68, 95% confidence interval 1.43-1.99, p < 0.001), disease-free survival (risk ratio = 2.09, 95% confidence interval 1.62-2.6, p < 0.001) and progression free survival (risk ratio = 1.92, 95% confidence interval 1.75-2.10, p < 0.001) was associated with with laryngeal aquamous cell carcinoma. The ratio of neutrophils to lymphocytes had prognostic value for laryngeal squamous cell carcinoma. CONCLUSION: The results of this meta-analysis showed that the increase of neutrophils to lymphocytes ratio was related to poor prognosis of laryngeal squamous cell carcinoma. The neutrophils to lymphocytes ratio may serve as a cost-effective prognostic biomarker of poor prognosis of laryngeal squamous cell carcinoma. More high-quality prospective trials are needed to assess the practicability of evaluating the ratio of neutrophils to lymphocytes in laryngeal squamous cell carcinoma.

Diffusion Kurtosis Imaging Reflects GFAP, TopoIIα, and MGMT Expression in Astrocytomas.

OBJECTIVE: Preliminary study of magnetic resonance (MR) diffusion kurtosis imaging (DKI) assessing the pathological glial fibrillary acidic protein (GFAP), TopoIIα, and O 6-methylguanine-DNA methyltransferase (MGMT) expression in astrocytomas. MATERIALS AND METHODS: This study was approved by the local ethics committee, and informed consent was obtained from all participants. Sixty-six cases with pathologically proven astrocytomas were enrolled in this study; of which, 34 were high grade and remaining 32 were low grade. They patients underwent conventional MRI head scan, DKI scan, and enhanced scan under the same conditions. Fractional anisotropy (FA) and mean kurtosis (MK) calculated from DKI, as well as GFAP, TopoIIα, and MGMT expression level were compared prospectively between high and low-grade astrocytomas. Spearman rank correlation analysis was used for comparing values of DKI and GFAP, TopoIIα, and MGMT expression level in the two groups. RESULTS: The MK values were significantly higher in high-grade astrocytomas than those in low-grade astrocytomas (P < 0.05); FA values demonstrated no significant difference between the two groups (P = 0.331). GFAP expression level was significantly lower in high-grade astrocytomas than in low-grade astrocytomas (P < 0.05). Topo-IIα expression level were significantly higher in high-grade astrocytomas than in low-grade astrocytomas (P < 0.05). There was no significant difference in MGMT expression level between the two groups (P = 0.679). MK values were negatively correlated with the expression of GFAP (r = -0.836; P = 0.03), however, they were positively correlated with the expression of Topo-IIα (r = 0.896; P = 0.01). FA values were not correlated with the expression of GFAP (r = 0.366; P = 0.05), Topo-IIα (r = -0.562; P = 0.05), and MGMT (r = -0.153; P = 0.10). CONCLUSION: MK, the DKI parameter values of astrocytomas, was significantly correlated to the expression of GFAP and TopoIIα. To a certain extent, applying DKI may provide the biological behavior of tumor cell differentiation, proliferation activity, invasion and metastasis, and can guide individual treatment.

Family environmental risk factors for developmental speech delay in children in Northern China.

Most reported risk factors for developmental speech delay (DSD) remain controversial, and studies on paternal influencing factors are rare. This study investigated family environmental risk factors for DSD in northern China. The medical records of 276 patients diagnosed with DSD at four centres between October 2018 and October 2019 were retrospectively analysed. A questionnaire was designed that contained items such as maternal age at the child's birth, child sex, child age, birth order, family type and parental personality. Patients whose medical records lacked complete information for this investigation were contacted by e-mail or phone. Additionally, 339 families whose children received routine physical examinations at the four involved centres completed the survey. Data were collected, and potential risk factors were analysed using the t test or chi-square test; the obtained outcomes were subjected to multivariable logistic regression for further analysis. The multivariable regression showed that older maternal age at the child's birth (OR = 1.312 (1.192-1.444), P < 0.001), introverted paternal personality (OR = 0.023 (0.011-0.048), P < 0.001), low average parental education level (OR = 2.771 (1.226-6.263), P = 0.014), low monthly family income (OR = 4.447 (1.934-10.222), P < 0.001), and rare parent-child communication (OR = 6.445 (3.441-12.072), P < 0.001) were independent risk factors for DSD in children in North China. The study results may provide useful data for broadening and deepening the understanding of family risk factors for DSD.

Differentiating high-grade glioma recurrence from pseudoprogression: Comparing diffusion kurtosis imaging and diffusion tensor imaging.

PURPOSE: To compare the diagnostic value of DKI and DTI in differentiation of high-grade glioma recurrence and pseudoprogression (PsP). METHOD: Forty patients with high-grade gliomas who exhibited new enhancing lesions (24 high-grade glioma recurrence and 16 PsP) within 6 months after surgery followed by completion of chemoradiation therapy. All patients underwent repeat surgery or biopsy after routine MRI and DKI (including DTI). They were histologically classified into high-grade glioma recurrence and PsP groups. DKI (mean kurtosis [MK], axial kurtosis [Ka], and radial kurtosis [Kr]) and DTI (mean diffusivity [MD] and fractional anisotropy [FA]) parameters in the enhancing lesions and in the perilesional edema were measured. Inter-group differences between high-grade glioma recurrence and PsP were compared using the Mann-Whitney U test The receiver operating characteristic (ROC) curve was used to assess differential diagnostic efficacy of each parameter, and Z-scores were used to compare the value between DKI and DTI. RESULTS: Relative MK (rMK) was significantly higher and relative MD (rMD) was significantly lower in the enhancing lesions of high-grade glioma recurrence compared to PsP (P <  0.001, P = 0.006, respectively). The AUC was 0.914 for rMK and 0.760 for rMD, and this difference was significant (P = 0.030). In the perilesional edema, rMK values were significantly higher and rMD values were significantly lower in high-grade glioma recurrence compared to PsP (P <  0.001, P =  0.005). CONCLUSIONS: DKI had superior performance in differentiating high-grade glioma recurrence from PsP, and rMK appeared to be the best independent predictor.

Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck. LSCC patients have seriously impaired vocal, respiratory, and swallowing functions with poor prognosis. Circular RNA (circRNA) has attracted great attention in cancer research. However, the expression patterns and roles of circRNAs in LSCC remain largely unknown. METHODS: RNA sequencing was performed on 57 pairs of LSCC and matched adjacent normal mucosa tissues to construct circRNA, miRNA, and mRNA expression profiles. RT-PCR, qPCR, Sanger sequencing, and FISH were undertaken to study the expression, localization, and clinical significance of circCORO1C in LSCC tissues and cells. The functions of circCORO1C in LSCC were investigated by RNAi-mediated knockdown, proliferation analysis, EdU staining, colony formation assay, Transwell assay, and apoptosis analysis. The regulatory mechanisms among circCORO1C, let-7c-5p, and PBX3 were investigated by luciferase assay, RNA immunoprecipitation, western blotting, and immunohistochemistry. RESULTS: circCORO1C was highly expressed in LSCC tissues and cells, and this high expression was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circCORO1C inhibited the proliferation, migration, invasion, and in vivo tumorigenesis of LSCC cells. Mechanistic studies revealed that circCORO1C competitively bound to let-7c-5p and prevented it from decreasing the level of PBX3, which promoted the epithelial-mesenchymal transition and finally facilitated the malignant progression of LSCC. CONCLUSIONS: circCORO1C has an oncogenic role in LSCC progression and may serve as a novel target for LSCC therapy. circCORO1C expression has the potential to serve as a novel diagnostic and prognostic biomarker for LSCC detection.

Combination value of diffusion-weighted imaging and dynamic susceptibility contrast-enhanced MRI in astrocytoma grading and correlation with GFAP, Topoisomerase IIα and MGMT.

The present study aimed to investigate the value of diffusion-weighted imaging (DWI) combined with dynamic susceptibility contrast-enhanced (DSC) magnetic resonance imaging (MRI) scans in astrocytoma grading, and correlated MRI scan parameters of values of apparent diffusion coefficient (ADC) and relative cereberal blood volume (rCBV) with the immunohistochemical (IHC) indices of glial fibrillary acidic protein (GFAP), topoisomerase IIα (Topo IIα) and O 6-methylguanine-DNA methyltransferase (MGMT). A total of 123 patients with pathologically confirmed astrocytomas of differing grades underwent DWI and DSC scans. The values of the ADC and relative cerebral blood volume rCBV were compared with the grade II-IV astrocytomas. Receiver operating characteristic curves were used to compare astrocytoma grading efficiency of ADC, rCBV and the combination of the two values. The parameters of ADC and rCBV with GFAP, Topo IIα and MGMT indices were then correlated. The differences in ADC values were significant between the grades II, III and IV astrocytomas, and the rCBV values for grades II, III and IV were also significant. The combination of DWI and DSC demonstrated the highest values for area under curve in identifying grades II and III, and identifying grades III and IV, respectively. GFAP displayed a positive correlation with ADC and a negative correlation with rCBV. Topo IIα exhibited a negative correlation with ADC, and a positive correlation with rCBV. No correlation was observed between MGMT and ADC or rCBV. The combined application of DWI and DSC may increase astrocytoma grading accuracy. Values of ADC and rCBV exhibit certain correlations with IHC indices, and may predict degree of malignancy of astrocytoma.

Diffusion Kurtosis Imaging Reflects Glial Fibrillary Acidic Protein (GFAP), Topo IIα, and O6-Methylguanine-DNA Methyltransferase (MGMT) Expression in Astrocytomas.

BACKGROUND Astrocytomas are the most common primary brain neoplasms. Biological indicators of astrocytomas can reflect its biological characteristics. The aim of this study was to assess the expression of the pathological glial fibrillary acidic protein (GFAP) Topo IIα and O6-methylguanine-DNA methyltransferase (MGMT) in astrocytomas using magnetic resonance (MR) diffusion kurtosis imaging (DKI) to evaluate the biological characteristics of astrocytomas. MATERIAL AND METHODS Sixty-six patients with pathologically proven astrocytomas were enrolled in this study. All patients underwent conventional MRI head scanning, DKI scanning, and enhanced scanning under the same conditions. Spearman's rank correlation analysis and Bonferroni correction were used to compare the values of DKI and the expression levels of GFAP, Topo IIα, and MGMT between the 2 groups. RESULTS Mean kurtosis (MK) values were negatively correlated with the expression of GFAP (r=-0.836; P=0.03). However, these were positively correlated with the expression of Topo IIα (r=0.896; P=0.01). Moreover, fractional anisotropy (FA) values were not correlated with the expression of GFAP (r=0.366; P=0.05), Topo IIα (r=-0.562; P=0.05), or MGMT (r=-0.153; P=0.10). CONCLUSIONS MK was significantly associated with the expression of GFAP and Topo IIα. To a certain extent, applying DKI may show the biological behavior of tumor cell differentiation, proliferation activity, invasion, and metastasis, and guide individual treatment.

Brainstem Congestion Due to Dural Arteriovenous Fistula at the Craniocervical Junction: Case Report and Review of the Literature.

BACKGROUND: Dural arteriovenous fistulas (DAVFs) at the craniocervical junction are rare. Clinical manifestations range from acute or chronic myelopathy to subarachnoid hemorrhage to brainstem dysfunction. We encountered 4 cases of DAVFs at the craniocervical junction with progressive brainstem dysfunction and investigated the typical magnetic resonance imaging (MRI) features using T2-weighting imaging, susceptibility-weighted imaging, diffusion-weighted imaging, and contrast-enhanced imaging. Literature review revealed 10 case reports of DAVFs at the craniocervical junction manifesting with brainstem dysfunction. CASE DESCRIPTION: Four patients presented with DAVFs at the craniocervical junction with progressive brainstem dysfunction. Two patients underwent midline suboccipital craniotomy and C1 laminectomy, and 1 patient underwent transarterial endovascular embolization with Onyx 18 under general anesthesia. All neurologic deficits gradually improved after the operation. In the fourth case, the patient received conservative treatment and did not undergo any surgical procedure. MRI showed high signal intensity on T2-weighted imaging, magnetic resonance angiography, and magnetic resonance venography. Abnormal dilated vessels and flow-void signs around the lesions were detected on susceptibility-weighted imaging and contrast-enhanced images. Two cases revealed no abnormalities and had improved neurological deficits than those showed on diffusion-weighted imaging. CONCLUSIONS: Susceptibility-weighted imaging, diffusion-weighted imaging, or contrast-enhanced scanning should be used during MRI examination of patients with progressive brainstem dysfunction to differentiate DAVFs at the craniocervical junction from other diseases, such as glioma or infection. Prompt diagnosis using MRI is of great significance in producing good functional outcomes of the patients.

The value of multi ultra high-b-value DWI in grading cerebral astrocytomas and its association with aquaporin-4.

OBJECTIVE: To investigate the value of multi-ultrahigh-b-value diffusion-weighted imaging (UHBV-DWI) in differentiating high-grade astrocytomas (HGAs) from low-grade astrocytomas (LGAs), analyze its association with aquaporin (AQP) expression. METHODS: 40 astrocytomas divided into LGAs (N = 15) and HGAs (N = 25) were studied. Apparent diffusion coefficient (ADC) and UHBV-ADC values in solid parts and peritumoral edema were compared between LGAs and HGAs groups by the t-test. Using receiver operating characteristic curves to identify the better parameter. Using real time polymerase chain reaction to assess AQP messenger ribonucleic acid (mRNA). Using spearman correlation analysis to assess the correlation of AQP mRNA with each parameter. RESULTS: ADC values in solid parts of HGAs were significantly lower than LGAs (p = 0.02), while UHBV-ADC values of HGAs were significantly higher than LGAs (p < 0.01). Area under the curve (AUC) of UHBV-ADC (0.810) was larger than ADC (0.713), and the area under the curve of UHBV-ADC was significantly higher than that of ADC (p = 0.041). AQP4 mRNA was significantly higher in HGAs than that in LGAs (p < 0.01); there was less AQP9 mRNA and no AQP1 mRNA in LGAs and HGAs groups (p > 0.05); ADC value showed a negative correlation with AQP4 mRNA (r = -0.357; p = 0.024). UHBV-ADC value positively correlated with the AQP4 mRNA (r = 0.646; p < 0.01). CONCLUSION: UHBV-DWI allowed for a more accurate grading of cerebral astrocytoma than DWI, and UHBV-ADC value may be related with the AQP4 mRNA levels. UHBV-DWI could be of value in the assessment of astrocytoma. Advances in knowledge: UHBV-DWI generated by multi UHBV could have particular value for astrocytoma grading, and the level of AQP4 mRNA might be potentially linked to the change of UHBV-DWI parameter, and we might find the exact reason for the difference of UHBV-ADC between the LGAs and HGAs.

Grading of Gliomas by Using Radiomic Features on Multiple Magnetic Resonance Imaging (MRI) Sequences.

BACKGROUND Gliomas are the most common primary brain neoplasms. Misdiagnosis occurs in glioma grading due to an overlap in conventional MRI manifestations. The aim of the present study was to evaluate the power of radiomic features based on multiple MRI sequences - T2-Weighted-Imaging-FLAIR (FLAIR), T1-Weighted-Imaging-Contrast-Enhanced (T1-CE), and Apparent Diffusion Coefficient (ADC) map - in glioma grading, and to improve the power of glioma grading by combining features. MATERIAL AND METHODS Sixty-six patients with histopathologically proven gliomas underwent T2-FLAIR and T1WI-CE sequence scanning with some patients (n=63) also undergoing DWI scanning. A total of 114 radiomic features were derived with radiomic methods by using in-house software. All radiomic features were compared between high-grade gliomas (HGGs) and low-grade gliomas (LGGs). Features with significant statistical differences were selected for receiver operating characteristic (ROC) curve analysis. The relationships between significantly different radiomic features and glial fibrillary acidic protein (GFAP) expression were evaluated. RESULTS A total of 8 radiomic features from 3 MRI sequences displayed significant differences between LGGs and HGGs. FLAIR GLCM Cluster Shade, T1-CE GLCM Entropy, and ADC GLCM Homogeneity were the best features to use in differentiating LGGs and HGGs in each MRI sequence. The combined feature was best able to differentiate LGGs and HGGs, which improved the accuracy of glioma grading compared to the above features in each MRI sequence. A significant correlation was found between GFAP and T1-CE GLCM Entropy, as well as between GFAP and ADC GLCM Homogeneity. CONCLUSIONS The combined radiomic feature had the highest efficacy in distinguishing LGGs from HGGs.

Comparison of the values of MRI diffusion kurtosis imaging and diffusion tensor imaging in cerebral astrocytoma grading and their association with aquaporin-4.

OBJECTIVE: To compare the value of MRI diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in grading cerebral astrocytomas and to analyze the correlation of respective parameters with aquaporin-4 (AQP4) expression. METHODS: Sixty patients with cerebral astrocytoma, including low-grade astrocytomas (LGA, n = 25) and high-grade astrocytomas (HGA, n = 35), were studied. The values of DKI parameters (mean kurtosis [MK], radial kurtosis [Kr], and axial kurtosis [Ka]) and DTI parameters (fractional anisotropy, mean diffusivity [MD]) corrected by contralateral normal-appearing white matter in the solid parts of the tumors and peritumoral edema were compared. Receiver operating characteristic curves were used to identify the best parameters. Spearman correlation analysis was conducted to assess the correlation of AQP4 expression with each parameter value. RESULTS: MK, Ka, and Krvalues were significantly higher whereas MD values were significantly lower in the solid parts of HGA, as compared to those of LGA. MK value in peritumoral edematous tissue was significantly higher in HGA as compared to that in LGA. Ka (0.889) had the largest area under the curve (AUC), followed by MK (0.840), Kr (0.750), and MD (0.764). The AUC of Kaand MK was significantly higher than that of MD. Optimal thresholds for MK, Ka, Kr, and MD for differentiating the two groups were 0.490, 0.525, 0.432, and 1.493, respectively. The AQP4 expression in the solid parts of the tumors was significantly higher in HGAs. MK, Kr, Kavalues positively correlated with the AQP4 expression, whereas MD showed a slight negative correlation with AQP4. CONCLUSION: Use of DKI improved grading of cerebral astrocytomas when compared with DTI. DKI parameters appeared to reflect the level of AQP4 expression in astrocytomas.

Differentiation of high-grade-astrocytomas from solitary-brain-metastases: Comparing diffusion kurtosis imaging and diffusion tensor imaging.

OBJECTIVE: To compare the value of MRI diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in differentiating high-grade-astrocytomas from solitary-brain-metastases. METHODS: Thirty-one high-grade-astrocytomas and twenty solitary-brain-metastases were retrospectively identified. DKI parameters [mean kurtosis (MK), radial kurtosis (Kr), and axial kurtosis (Ka)] and DTI parameters [fractional anisotropy (FA) and mean diffusivity (MD)] values with and without correction by contralateral normal-appearing white matter (NAWM) in the tumoral solid part and peritumoral edema, were compared using the t-test. Receiver operating characteristic (ROC) curves were used to test for the best parameters. RESULTS: The DKI values (MK, Kr, and Ka) and DTI values (FA and MD) in tumoral solid parts did not show significant differences between the two groups. Corrected and uncorrected MK, Kr, and Ka values in peritumoral edema were significantly higher in high-grade-astrocytomas than solitary-brain-metastases, and MD values without correction were lower in high-grade astrocytomas than solitary-brain-metastases. The areas under curve (AUC) of corrected Ka (1.000), MK (0.889), and Kr (0.880) values were significantly higher than those of MD (0.793) and FA (0.472) values. The optimal thresholds for corrected MK, Kr, Ka, and MD were 0.369, 0.405, 0.483, and 2.067, respectively. CONCLUSION: DKI and directional analysis could lead to improved differentiation with better sensitivity and directional specificity than DTI.

Association between the MTHFR C677T polymorphism and risk of cancer: evidence from 446 case-control studies.

Many molecular epidemiological studies have been performed to explore the association between MTHFR C677T polymorphism and cancer risk in diverse populations. However, the results were inconsistent. Hence, we performed a meta-analysis to investigate the association between cancer risk and MTHFR C677T (150,086 cases and 200,699 controls from 446 studies) polymorphism. Overall, significantly increased cancer risk was found when all eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significantly increased breast cancer risk was found in Asians and Indians, significantly decreased colon cancer risk was found, significantly decreased colorectal cancer risk was found in male population, significantly increased gastric cancer risk was found in Caucasians and Asians, significantly increased hepatocellular cancer risk was found in Asians, significantly decreased adult acute lymphoblastic leukemia (AALL) risk was found in Caucasians, significantly decreased childhood acute lymphoblastic leukemia (CALL) risk was found in Asians, and significantly increased multiple myeloma and NHL risk was found in Caucasians. In summary, this meta-analysis suggests that MTHFR C677T polymorphism is associated with increased breast cancer, gastric cancer, and hepatocellular cancer risk in Asians, is associated with increased gastric cancer, multiple myeloma, and NHL risk in Caucasians, is associated with decreased AALL risk in Caucasians, is associated with decreased CALL risk in Asians, is associated with increased breast cancer risk in Asians, is associated with decreased colon cancer risk, and is associated with decreased colorectal cancer risk in male population. Moreover, this meta-analysis also points out the importance of new studies, such as Asians of HNC, Asians of lung cancer, and Indians of breast cancer, because they had high heterogeneity in this meta-analysis (I(2) > 75%).

Amplification of chromosome 8q21-qter associated with the acquired paclitaxel resistance of nasopharyngeal carcinoma cells.

OBJECTIVE: to observe relationship between chromosome imbalance and taxol resistance in nasopharyngeal carcinoma (NPC). METHODS: three taxol-resistant sub-lines were established through repeated exposure of escalating doses of paclitaxel to NPC cell lines (CNE-1, HNE-2 and 5-8F). The change of copy number of chromosomes was investigated by the genome-wide analyses of comparative genomic hybridization (CGH). Gene profiles of both parental and resistant cell lines were determined by cDNA microarray. Cell viability was assayed by colony formation assay. RESULTS: The taxol resistant sub-lines (CNE1/Taxol, HNE2/Taxol and 5-8F/Taxol) developed displayed an average 5~8-fold higher IC50 value than their parental cells. The common losses of chromosome 18, 10q11-qter and gains of chromosome 12, 3q21-qter, 5p13-pter and 20q11-qter were observed by CGH in all of 6 NPC cell lines. A common gain region of chromosome 8q21-qter was identified in taxol resistant sub-lines. 15 genes of 762 transcripts on this chromosome region were consistently up-regulated detected by cDNA microarray in three taxol resistant sub-lines, and functionally clustered into various groups, including genes related to vascular formation vascular formation (ANGPT1), apoptosis (MYC, TOP1MT), cell adhesion and cell cycle (PPP1R16A, SDC2, CA2, ANKRD46), gene regulation (HRSP12, ZNF696, SLC39A4, POP1), metabolism (PYCRL). Inhibition of ANGPT1 expression significantly increased the sensitivity of CNE-1/taxol to paclitaxol. CONCLUSION: The common gain of chromosome 8q21-qter in taxol resistant sublines predicates that potential candidate genes on this region may contribute to taxol resistant phenotype. ANGPT1 may be associated with taxol resistance of NPC cells.

Combined value of susceptibility-weighted and perfusion-weighted imaging in assessing who grade for brain astrocytomas.

PURPOSE: To assess the value of combining susceptibility-weighted imaging (SWI) and dynamic susceptibility weighted contrast-enhanced (DSC) perfusion-weighted MRI (PWI) in assessing World Health Organization (WHO)grade for brain astrocytoma . MATERIALS AND METHODS: A total of 94 patients with pathologically confirmed astrocytomas underwent SWI and DSC scans. The evaluation included intratumoral susceptibility signal intensity (ITSS) and relative cerebral blood volume (rCBV) max. The receiver operating characteristic curve (ROC) was used to assess the efficacy of combining two sequences in astrocytoma grading. RESULTS: ITSS within astrocytomas showed significant correlations with rCBV max (r » 0.72; P < 0.01) and with tumor grades (r » 0.92; P < 0.01), and there was also a significant correlation between rCBV and tumor grade (r= 0.77; P < 0.001). The area under the ROC, SWI, PWI,SWI, and PWI, in differentiation of the grades II and III astrocytomas were 0.995, 0.942, and 1.000, respectively;identifying grades III and IV were 0.773, 0.919, and 0.978, respectively; and identifying high and low-grade astrocytomas were 0.999, 0.992, 1.000, respectively. CONCLUSION: ITSS was useful for assessing the WHO tumor grade in this cohort of patients with astrocytoma.The combination of SWI and PWI may improve the diagnostic accuracy of astrocytoma grading.