Low enhancement on multiphase contrast-enhanced CT images: an independent predictor of the presence of high tumor grade of clear cell renal cell carcinoma.

PubMed

Zhu, Ye-Hua; Wang, Xun; Zhang, Jin; Chen, Yong-Hui; Kong, Wen; Huang, Yi-Ran

2014-09-01

The purpose of this study was to assess the relation between tumor enhancement on multiphase contrast-enhanced CT images and Fuhrman grade of clear cell renal cell carcinoma. A single-institution retrospective review was conducted on the records of 255 patients who underwent radical or partial nephrectomy and received a histologic diagnosis of clear cell renal cell carcinoma. Two radiologists recorded the radiographic features of each patient, including the attenuation value of the lesion, lesion size, calcification within the lesion, cystic versus solid appearance, and margin regularity. Parameters representing the extent of tumor enhancement were defined and calculated. The association between tumor enhancement and Fuhrman grade was analyzed, and multivariate analysis was performed to find independent predictors of high tumor grade. Significant differences existed in tumor enhancement among different Fuhrman grades (p < 0.001). High-grade tumors had significantly lower enhancement (p < 0.001). The enhancement parameter had a sensitivity of 0.84 and specificity of 0.93 in prediction of high tumor grade. In the multivariate analysis, more advanced age, irregular margin, and low tumor enhancement were the three independent predictors of high tumor grade. Tumor enhancement of clear cell renal cell carcinoma on multiphase contrast-enhanced CT images is associated with Fuhrman grade. Low tumor enhancement in the corticomedullary phase is an independent predictor of high tumor grade. This system may be helpful in clinical decision making about the care of patients treated by nonsurgical approaches.

Correlation of 6-18F-fluoro-L-dopa PET uptake with proliferation and tumor grade in newly diagnosed and recurrent gliomas.

PubMed

Fueger, Barbara J; Czernin, Johannes; Cloughesy, Timothy; Silverman, Daniel H; Geist, Cheri L; Walter, Martin A; Schiepers, Christiaan; Nghiemphu, Phioanh; Lai, Albert; Phelps, Michael E; Chen, Wei

2010-10-01

6-(18)F-fluoro-l-dopa ((18)F-FDOPA) measured with PET as a biomarker of amino acid uptake has been investigated in brain tumor imaging. The aims of the current study were to determine whether the degree of (18)F-FDOPA uptake in brain tumors predicted tumor grade and was associated with tumor proliferative activity in newly diagnosed and recurrent gliomas. Fifty-nine patients (40 men, 19 women; mean age ± SD, 44.4 ± 12.3 y) with newly diagnosed (n = 22) or recurrent (n = 37) gliomas underwent (18)F-FDOPA PET perioperatively. Tumor tissue was obtained by resection or biopsy in all patients. The tumor grade and Ki-67 proliferation index were obtained by standard pathology assays. Tumor (18)F-FDOPA uptake was quantified by determining various standardized uptake value (SUV) parameters (mean SUV, maximum SUV [SUVmax], mean values of voxels with top 20% SUVs, and tumor-to-normal-brain tissue ratios) that were then correlated with histopathologic grade and Ki-67 proliferation index. Fifty-nine lesions in 59 patients were analyzed. (18)F-FDOPA uptake was significantly higher in high-grade than in low-grade tumors for newly diagnosed tumors (SUVmax, 4.22 ± 1.30 vs. 2.34 ± 1.35, P = 0.005) but not for recurrent tumors that had gone through treatment previously (SUVmax, 3.36 ± 1.26 vs. 2.67 ± 1.18, P = 0.22). An SUVmax threshold of 2.72 differentiated low-grade from high-grade tumors, with a sensitivity and specificity of 85% and 89%, respectively, using receiver-operating-characteristic curve analysis (area under the curve, 0.86). (18)F-FDOPA PET uptake correlated significantly with Ki-67 tumor proliferation index in newly diagnosed tumors (r = 0.66, P = 0.001) but not in recurrent tumors (r = 0.14, P = 0.41). (18)F-FDOPA uptake is significantly higher in high-grade than in low-grade tumors in newly diagnosed but not recurrent tumors that had been treated previously. A significant correlation between (18)F-FDOPA uptake and tumor proliferation in newly diagnosed tumors

Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study.

PubMed

Thomas, Nancy E; Busam, Klaus J; From, Lynn; Kricker, Anne; Armstrong, Bruce K; Anton-Culver, Hoda; Gruber, Stephen B; Gallagher, Richard P; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A; Groben, Pamela A; Hao, Honglin; Orlow, Irene; Reiner, Anne S; Luo, Li; Paine, Susan; Ollila, David W; Wilcox, Homer; Begg, Colin B; Berwick, Marianne

2013-11-20

Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas. On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined. Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (P(trend) < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage. At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions.

Tumor-Infiltrating Lymphocyte Grade in Primary Melanomas Is Independently Associated With Melanoma-Specific Survival in the Population-Based Genes, Environment and Melanoma Study

PubMed Central

Thomas, Nancy E.; Busam, Klaus J.; From, Lynn; Kricker, Anne; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A.; Groben, Pamela A.; Hao, Honglin; Orlow, Irene; Reiner, Anne S.; Luo, Li; Paine, Susan; Ollila, David W.; Wilcox, Homer; Begg, Colin B.; Berwick, Marianne

2013-01-01

Purpose Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas. Patients and Methods On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined. Results Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (Ptrend < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage. Conclusion At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions. PMID:24127443

Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas.

PubMed

Pyka, Thomas; Gempt, Jens; Hiob, Daniela; Ringel, Florian; Schlegel, Jürgen; Bette, Stefanie; Wester, Hans-Jürgen; Meyer, Bernhard; Förster, Stefan

2016-01-01

Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L-tyrosine (FET) is well established in the diagnostic work-up of malignant brain tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been shown to be highly valuable for the detection of viable hypermetabolic brain tumor tissue; however, it has not proven equally useful for tumor grading. Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a method to quantify the heterogeneity of glucose metabolism in a variety of tumor entities. Herein we evaluate whether textural FET-PET features are of utility for grading and prognostication in patients with high-grade gliomas. One hundred thirteen patients (70 men, 43 women) with histologically proven high-grade gliomas were included in this retrospective study. All patients received static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric parameters and textural parameters based on gray-level neighborhood difference matrices were derived from static FET-PET images. Receiver operating characteristic (ROC) and discriminant function analyses were used to assess the value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox regression were employed for analysis of progression-free and overall survival. All FET-PET textural parameters showed the ability to differentiate between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC 0.775). Further improvement in discriminatory power was possible through a combination of texture and metabolic tumor volume, classifying 85 % of tumors correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with tumor grade, but showed lower AUC values (0.644 and 0.710, respectively). Furthermore, a correlation of FET-PET texture but not TBR was shown with patient PFS and OS, proving significant in multivariate analysis as well. Volumetric parameters were predictive for OS, but this correlation

The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors.

PubMed

Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias; Stummer, Walter

2016-03-01

Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. Age, tumor volume, and F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether

Grading system for blood vessel tumor emboli of invasive ductal carcinoma of the breast.

PubMed

Sugiyama, Michiko; Hasebe, Takahiro; Shimada, Hiroko; Takeuchi, Hideki; Shimizu, Kyoko; Shimizu, Michio; Yasuda, Masanori; Ueda, Shigeto; Shigekawa, Takashi; Osaki, Akihiko; Saeki, Toshiaki

2015-06-01

We previously reported that the number of mitotic and apoptotic figures in tumor cells in blood vessel tumor emboli had the greatest significant power for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. The purpose of the present study was to devise a grading system for blood vessel tumor emboli based on the mitotic and apoptotic figures of tumor cells in blood vessel tumor emboli, enabling accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 263 invasive ductal carcinomas into the following 3 grades according to the numbers of mitotic and apoptotic figures in tumor cells located in blood vessels within 1 high-power field: grade 0, no blood vessel invasion; grade 1, absence of mitotic figures and presence of any number of apoptotic figures, or 1 mitotic figure and 0 to 2 apoptotic figures; and grade 2, 1 mitotic figure and 3 or more apoptotic figures, or 2 or more mitotic figures and 1 or more apoptotic figures. Multivariate analyses with well-known prognostic factors demonstrated that grade 2 blood vessel tumor emboli significantly increased the hazard ratios for tumor recurrence independent of the nodal status, pathological TNM stage, hormone receptor status, or HER2 status. The presently reported grading system for blood vessel tumor emboli is the strongest histologic factor for accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. Copyright © 2015 Elsevier Inc. All rights reserved.

Differentiation of low- and high-grade clear cell renal cell carcinoma: Tumor size versus CT perfusion parameters.

PubMed

Chen, Chao; Kang, Qinqin; Xu, Bing; Guo, Hairuo; Wei, Qiang; Wang, Tiegong; Ye, Hui; Wu, Xinhuai

To compare the utility of tumor size and CT perfusion parameters for differentiation of low- and high-grade clear cell renal cell carcinoma (RCC). Tumor size, Equivalent blood volume (Equiv BV), permeability surface-area product (PS), blood flow (BF), and Fuhrman pathological grading of clear cell RCC were retrospectively analyzed. High-grade clear cell RCC had significantly higher tumor size and lower PS than low grade. Tumor size positively correlated with Fuhrman grade, but PS negatively did. Tumor size and PS were significantly independent indexes for differentiating high-grade from low-grade clear cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Proposal for a new risk stratification classification for meningioma based on patient age, WHO tumor grade, size, localization, and karyotype

PubMed Central

Domingues, Patrícia Henriques; Sousa, Pablo; Otero, Álvaro; Gonçalves, Jesus Maria; Ruiz, Laura; de Oliveira, Catarina; Lopes, Maria Celeste; Orfao, Alberto; Tabernero, Maria Dolores

2014-01-01

Background Tumor recurrence remains the major clinical complication of meningiomas, the majority of recurrences occurring among WHO grade I/benign tumors. In the present study, we propose a new scoring system for the prognostic stratification of meningioma patients based on analysis of a large series of meningiomas followed for a median of >5 years. Methods Tumor cytogenetics were systematically investigated by interphase fluorescence in situ hybridization in 302 meningioma samples, and the proposed classification was further validated in an independent series of cases (n = 132) analyzed by high-density (500K) single-nucleotide polymorphism (SNP) arrays. Results Overall, we found an adverse impact on patient relapse-free survival (RFS) for males, presence of brain edema, younger patients (<55 years), tumor size >50 mm, tumor localization at intraventricular and anterior cranial base areas, WHO grade II/III meningiomas, and complex karyotypes; the latter 5 variables showed an independent predictive value in multivariate analysis. Based on these parameters, a prognostic score was established for each individual case, and patients were stratified into 4 risk categories with significantly different (P < .001) outcomes. These included a good prognosis group, consisting of approximately 20% of cases, that showed a RFS of 100% ± 0% at 10 years and a very poor-prognosis group with a RFS rate of 0% ± 0% at 10 years. The prognostic impact of the scoring system proposed here was also retained when WHO grade I cases were considered separately (P < .001). Conclusions Based on this risk-stratification classification, different strategies may be adopted for follow-up, and eventually also for treatment, of meningioma patients at different risks for relapse. PMID:24536048

Secondary Glioblastoma: Molecular and Clinical Factors That Affect Outcome After Malignant Progression of a Lower Grade Tumor.

PubMed

Gessler, Florian; Zappi, Johannes; Konczalla, Juergen; Bernstock, Joshua D; Forster, Marie-Therese; Wagner, Marlies; Mittelbronn, Michel; Seifert, Volker; Senft, Christian

2017-06-01

There is limited information on prognostic factors and outcomes in patients with secondary glioblastoma (sGBM). Herein we report on the outcomes of patients with sGBM and identify clinically relevant prognostic factors. We retrospectively analyzed our institutional database for patients with histologic evidence of World Health Organization (WHO) grade II-III gliomas that went on to develop WHO grade IV sGBM. The assessment of the isocitrate dehydrogenase-1 (IDH1) R132H mutation was performed by immunohistochemical staining. Forty-five patients with sGBM were included within our analysis (median age, 41 years). Mutated IDH1 (R132H) protein was present within the gliomas of 24 patients and was absent in 17. Immunohistochemistry assessment could not be performed for 4 patients. The median time between first diagnosis of glioma and sGBM was 158.9 weeks. Median overall survival (OS) after a diagnosis of sGBM was 63.6 weeks. When assessing patient-specific (i.e., therapy-independent) factors, mutated IDH1 (R132H) protein (P = 0.01; hazard ratio (HR), 0.54; confidence interval (CI) 0.33-0.87), WHO grade II tumor as precursor lesion (P = 0.05; HR, 0.49; CI 0.25-0.97), and a frontal tumor location (P = 0.04; HR, 0.48; CI 0.23-0.99) were found to be associated with better OS by multivariate analysis. Our data further indicate that complete tumor removal is associated with better patient survival in sGBM patients within certain risk groups (time period to development of sGBM, >104 weeks; initial WHO grade II tumor, IDH1 mutation, and time period to development of sGBM, >104 weeks; initial WHO grade II or III tumor, IDH1 wild type, frontal lobe localization). Our retrospective analysis suggested that the presence of an IDH1 (R132H) mutation, frontal tumor location, and WHO grade of the initial tumor are associated with OS after progression to sGBM. In addition, some patients with sGBM may benefit from complete tumor resection depending on these patient-specific parameters

The relation between Ring Box-1 protein overexpression and tumor grade and stage in bladder urothelial cell carcinoma.

PubMed

Celik, Zeliha Esin; Kaynar, Mehmet; Karabagli, Pinar; Gergerlioglu, Nursadan; Goktas, Serdar

2017-12-06

Ring Box Protein-1 (RBX-1), a component of SCF E3 ubiquitin ligases, has a crucial role in bladder urothelial cell carcinoma (UCC) carcinogenesis and progression. In the present study, it is aimed to determine the expression of RBX-1 protein in bladder UCC and the association between tumor grade, stage and RBX-1 expression. Ninety UCC samples and 20 samples containing foci of normal bladder urothelium were recruited and analyzed immunohistochemically in terms of RBX-1 expression. Immuno-reactivity scoring system (IRS) was used to determine RBX-1 expression levels. RBX-1 overexpression was associated with high tumor grade (p= 0.001) and advanced stage (p= 0.001). pT1 tumors showed higher RBX-1 expression than pTa tumors. pT2 tumors showed not only higher expression than pTa tumors but also higher expression than the total of pTa and pT1 groups combined. There was no statistically significant relation between RBX-1 expression and patient gender (p= 0.116) or age (p= 0.191). In bladder UCC, RBX-1 overexpression is associated with high tumor grade and advanced stage and represents biological potential of invasiveness and aggressive disease. Results of the present study have to be supported with further studies to reveal clinical and therapeutic implications of RBX-1 overexpression in bladder UCC.

Quantitative CT analysis for the preoperative prediction of pathologic grade in pancreatic neuroendocrine tumors

NASA Astrophysics Data System (ADS)

Chakraborty, Jayasree; Pulvirenti, Alessandra; Yamashita, Rikiya; Midya, Abhishek; Gönen, Mithat; Klimstra, David S.; Reidy, Diane L.; Allen, Peter J.; Do, Richard K. G.; Simpson, Amber L.

2018-02-01

Pancreatic neuroendocrine tumors (PanNETs) account for approximately 5% of all pancreatic tumors, affecting one individual per million each year.1 PanNETs are difficult to treat due to biological variability from benign to highly malignant, indolent to very aggressive. The World Health Organization classifies PanNETs into three categories based on cell proliferative rate, usually detected using the Ki67 index and cell morphology: low-grade (G1), intermediate-grade (G2) and high-grade (G3) tumors. Knowledge of grade prior to treatment would select patients for optimal therapy: G1/G2 tumors respond well to somatostatin analogs and targeted or cytotoxic drugs whereas G3 tumors would be targeted with platinum or alkylating agents.2, 3 Grade assessment is based on the pathologic examination of the surgical specimen, biopsy or ne-needle aspiration; however, heterogeneity in the proliferative index can lead to sampling errors.4 Based on studies relating qualitatively assessed shape and enhancement characteristics on CT imaging to tumor grade in PanNET,5 we propose objective classification of PanNET grade with quantitative analysis of CT images. Fifty-five patients were included in our retrospective analysis. A pathologist graded the tumors. Texture and shape-based features were extracted from CT. Random forest and naive Bayes classifiers were compared for the classification of G1/G2 and G3 PanNETs. The best area under the receiver operating characteristic curve (AUC) of 0:74 and accuracy of 71:64% was achieved with texture features. The shape-based features achieved an AUC of 0:70 and accuracy of 78:73%.

The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors

PubMed Central

Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias

2015-01-01

BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased

Vascular endothelial growth factor and soft tissue sarcomas: tumor expression correlates with grade.

PubMed

Chao, C; Al-Saleem, T; Brooks, J J; Rogatko, A; Kraybill, W G; Eisenberg, B

2001-04-01

Vascular endothelial growth factor (VEGF), an endothelial-specific mitogen overexpressed in various epithelial malignancies is thought to be a potent regulator of angiogenesis. We hypothesized that some soft tissue sarcomas, due to their high propensity for hematogenous metastases (1) would overexpress VEGF, (2) that the degree of expression may represent a significant biologic predictor for disease-specific survival, and (3) that recurrent tumor would express as high or higher VEGF compared with the primary tumor. Selected paraffin-embedded tissue of surgical specimens from 79 patients with soft tissue sarcomas, treated between 1989 and 1995 were stained with a rabbit polyclonal anti-VEGF antibody at a concentration of 2 microg/ml. Slides were assessed for VEGF expression as high or low by two investigators blinded to the clinicopathologic data. Twelve patients had VEGF expression of their primary tumors, and their recurrent tumors were compared. The Fishers' exact test assessed for differences in VEGF expression; survival analyses were performed according to the methods of Kaplan and Meier. Seventy-eight percent (29 of 37) of patients who died of disease had high VEGF expression. However, VEGF expression was not an independent predictor of either overall or disease-free survival. Tumor grade correlated with VEGF expression significantly. For the low-grade tumors, 7 of 13 expressed low VEGF, whereas for high-grade tumors, 53 of 66 expressed high VEGF (P = .016). Seven of the 12 paired tumor samples expressed identical VEGF immunostaining. The majority of high-grade soft tissue sarcomas in this study have high intensity VEGF expression. This finding may provide useful information on individual soft tissue sarcomas and offer the basis for therapeutic and biologic targeting in high-risk patients using anti-angiogenesis strategies. However, in our analysis, after accounting for tumor grade, VEGF does not seem to be an independent predictor of clinical outcome.

Oncocytoma-Like Renal Tumor With Transformation Toward High-Grade Oncocytic Carcinoma

PubMed Central

Sirintrapun, Sahussapont J.; Geisinger, Kim R.; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L.; Ghazalpour, Anatole; Bender, Ryan P.; Gatalica, Zoran

2014-01-01

Abstract Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt–Hogg–Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the

Neurosurgical treatment of pediatric low-grade midbrain tumors: a single consecutive institutional series of 15 patients.

PubMed

Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Egge, Arild; Scheie, David; Brandal, Petter; Stensvold, Einar; Due-Tønnessen, Paulina

2014-12-01

The authors delineate the long-term results of surgical treatment for pediatric low-grade midbrain glioma. A series of 15 consecutive patients (age range 0-15 years) who underwent primary tumor resection for a low-grade midbrain glioma during the years 1989-2010 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily living were scored according to the Barthel Index. Of the 15 patients, 10 were in their 1st decade (age 0-9 years) and 5 were in their 2nd decade of life (age 10-15 years) at the time of surgery. The male/female ratio was 0.50 (5:10). No patients were lost to follow-up. One patient died in the postoperative period (32 days posttreatment). Another 2 patients died during follow-up. One patient succumbed to acute bleeding in the resection cavity 8 months after surgery, and the other died of shunt failure 21 years after initial treatment. Twelve patients are alive at the time of this writing, with follow-up periods from 3 to 24 years (median 8 years). Among the 12 survivors, the Barthel Index scores were normal (100) in 11 patients and 80 in 1 patient. A total of 25 tumor resections were performed. In 1 patient, further resection was performed 5 days after initial resection due to MRI-confirmed residual tumor. Another 5 patients underwent repeat tumor resection after MRI-confirmed progressive tumor disease and clinical deterioration ranging from 3 months to 4 years after the initial operation. Three of these 5 patients also underwent a third resection, and 1 of the 3 underwent a fourth operation. Six children received adjuvant therapy: local radiotherapy in 2 patients, chemotherapy in 3 patients, and both in 1 patient. Twelve (80%) of the 15 patients needed treatment for persistent hydrocephalus. Selected cases of low-grade midbrain gliomas may clearly benefit from resection with favorable results, even for prolonged periods. Three

Grade classification of neuroepithelial tumors using high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and pattern recognition.

PubMed

Chen, WenXue; Lou, HaiYan; Zhang, HongPing; Nie, Xiu; Lan, WenXian; Yang, YongXia; Xiang, Yun; Qi, JianPin; Lei, Hao; Tang, HuiRu; Chen, FenEr; Deng, Feng

2011-07-01

Clinical data have shown that survival rates vary considerably among brain tumor patients, according to the type and grade of the tumor. Metabolite profiles of intact tumor tissues measured with high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy (HRMAS (1)H NMRS) can provide important information on tumor biology and metabolism. These metabolic fingerprints can then be used for tumor classification and grading, with great potential value for tumor diagnosis. We studied the metabolic characteristics of 30 neuroepithelial tumor biopsies, including two astrocytomas (grade I), 12 astrocytomas (grade II), eight anaplastic astrocytomas (grade III), three glioblastomas (grade IV) and five medulloblastomas (grade IV) from 30 patients using HRMAS (1)H NMRS. The results were correlated with pathological features using multivariate data analysis, including principal component analysis (PCA). There were significant differences in the levels of N-acetyl-aspartate (NAA), creatine, myo-inositol, glycine and lactate between tumors of different grades (P<0.05). There were also significant differences in the ratios of NAA/creatine, lactate/creatine, myo-inositol/creatine, glycine/creatine, scyllo-inositol/creatine and alanine/creatine (P<0.05). A soft independent modeling of class analogy model produced a predictive accuracy of 87% for high-grade (grade III-IV) brain tumors with a sensitivity of 87% and a specificity of 93%. HRMAS (1)H NMR spectroscopy in conjunction with pattern recognition thus provides a potentially useful tool for the rapid and accurate classification of human brain tumor grades.

An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value.

PubMed

Andriantsoa, Maeva; Hoibian, Solene; Autret, Aurelie; Gilabert, Marine; Sarran, Anthony; Niccoli, Patricia; Raoul, Jean-Luc

2017-01-01

In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.

High-grade adenocarcinoma, (ductal type) arising in unilateral Warthin tumor of the parotid gland.

PubMed

Deodhar, Kedar K; Shah, Milap; Chaturvedi, Pankaj

2011-01-01

Warthin tumor is a well-recognized benign salivary gland neoplasm consisting of an epithelial as well as a lymphoid component. Malignant transformation in Warthin tumor is rare and its reported incidence is up to 1%. The more common types of carcinomas described in Warthin tumor are the squamous and mucoepidermoid types, with high-grade adenocarcinoma being extremely rare. A high-grade adenocarcinoma (ductal type) arising in the Warthin tumor in a 72-year-old man is presented for its rarity and diagnostic difficulties.

High-grade tumor differentiation is an indicator of poor prognosis in African Americans with colonic adenocarcinomas.

PubMed

Alexander, Dominik; Jhala, Nirag; Chatla, Chakrapani; Steinhauer, Jon; Funkhouser, Ellen; Coffey, Christopher S; Grizzle, William E; Manne, Upender

2005-05-15

To identify the factors that contribute to poorer colon carcinoma survival rates for African Americans compared with Caucasians, the authors evaluated survival differences based on the histologic grade (differentiation) of the tumor. All 169 African Americans and 229 randomly selected non-Hispanic Caucasians who underwent surgery during 1981-1993 for first primary sporadic colon carcinoma at the University of Alabama at Birmingham or its affiliated Veterans Affairs hospital were included in the current study. None of these patients received presurgery or postsurgery therapies. Recently, the authors reported an increased risk of colon carcinoma death for African Americans in this patient population, after adjustment for stage and other clinicodemographic features. The authors generated Kaplan-Meier survival probabilities according to race and tumor differentiation and multivariate Cox proportional hazards models to estimate hazard ratios (HR) with 95% confidence intervals (95% CI). There were no differences in the distribution of pathologic tumor stage between racial groups after stratifying by histologic tumor grade. Among patients with high-grade tumors, 54% of African Americans and 21% of Caucasians died within the first year after surgery (P = 0.007). African Americans with high-grade tumors were 3 times (HR = 3.05; 95% CI, 1.32-7.05) more likely to die of colon carcinoma within 5 years postsurgery, compared with Caucasians with high-grade tumors. There were no survival differences by race among patients with low-grade tumors. These findings suggested that poorer survival among African-American patients with adenocarcinomas of the colon may not be attributable to an advanced pathologic stage of disease at diagnosis, but instead may be due to aggressive biologic features like high tumor grades.

Use of a 2-tier histologic grading system for canine cutaneous mast cell tumors on cytology specimens.

PubMed

Hergt, Franziska; von Bomhard, Wolf; Kent, Michael S; Hirschberger, Johannes

2016-09-01

Mast cell tumors (MCT) represent the most common malignant skin tumor in the dog. Diagnosis of an MCT can be achieved through cytologic examination of a fine-needle aspirate. However, the grade of the tumor is an important prognostic marker and currently requires histologic assessment. Recently a 2-tier histologic grading system based on nuclear features including number of mitoses, multinucleated cells, bizarre nuclei, and karyomegaly was proposed. The aim of this study was to assess if the cytomorphologic criteria proposed in the 2-tier histologic grading system are applicable to cytology specimens. A total of 141 MCT specimens reported as grade I, II, or III according to the Patnaik system with both histologic specimens and fine-needle aspirates available were histologically and cytologically reevaluated in a retrospective study. According to the 2-tier grading system, 38 cases were diagnosed histologically as high-grade and 103 as low-grade MCT. Cytologic grading resulted in 36 high-grade and 105 low-grade tumors. Agreement between histologic and cytologic grading based on the 2-tier grading system was achieved in 133 cases (sensitivity 86.8%, specificity 97.1%, kappa value 0.853), but 5 high-grade tumors on histology were classified as low-grade on cytology. Cytologic grading of MCT in the dog is helpful for initial assessment. However, the reliability of cytology using the 2-tier grading system is considered inadequate at this point. Prospective studies including clinical outcome should be pursued to further determine diagnostic accuracy of cytologic mast cell grading. © 2016 American Society for Veterinary Clinical Pathology.

An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value

PubMed Central

Andriantsoa, Maeva; Hoibian, Solene; Autret, Aurelie; Gilabert, Marine; Sarran, Anthony; Niccoli, Patricia

2017-01-01

Background In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). Patients and methods We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Results Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Conclusions Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value. PMID:28562682

Differentiating ictal panic with low-grade temporal lobe tumors from psychogenic panic attacks.

PubMed

Ghods, Ali J; Ruban, Dmitry S; Wallace, David; Byrne, Richard W

2013-11-01

Indolent low-grade temporal lobe tumors may present with ictal panic that may be difficult to differentiate from psychogenic panic attacks. The current study aims to demonstrate the differences between the two disorders and help physicians generate a diagnostic paradigm. This was a retrospective study of 43 patients who underwent a temporal lobectomy between 1981 and 2008 for the treatment of intractable temporal lobe epilepsy secondary to low-grade neoplasms at Rush University Medical Center. A total of 10 patients in this group presented with ictal panic who were previously being treated for psychogenic panic attacks. Medical records were reviewed for age at seizure onset, duration of symptoms, lateralization of the epileptogenic zone, pathological diagnosis, and postsurgical seizure outcome according to the modified Engel classification. Neuropathologic findings of the 10 tumors were pleomorphic xanthoastrocytoma, ganglioglioma, oligodendroglioma, and dysembryoplastic neuroepithelial. The mean age of the patients undergoing surgery was 28 years (range, 15-49). The mean duration of panic symptoms prior to surgery was 9.8 years (range, 3-23). All patients had unprovoked ictal panic. None had symptoms suggestive of a brain tumor, such as signs of increased intracranial pressure or any focal neurologic deficit. In 5 of the patients, other symptoms associated with the ictal panic, including unusual sounds, nausea, automatism, uprising gastric sensation, and déjà vu were identified. Gross total resection of the lesion resulted in improved seizure outcome in all patients undergoing surgery. Patient follow-up was, on average, 7.4 years (range, 2-14) from time of surgery. Although similar, ictal panic from epilepsy and classic panic attacks are clinically distinguishable entities with different modalities of treatment. A careful history may help differentiate patients with ictal panic from those with psychogenic panic attacks and determine for which patients to obtain

PET/CT imaging of the diapeutic alkylphosphocholine analog 124I-CLR1404 in high and low-grade brain tumors

PubMed Central

Hall, Lance T; Titz, Benjamin; Robins, H Ian; Bednarz, Bryan P; Perlman, Scott B; Weichert, Jamey P; Kuo, John S

2017-01-01

CLR1404 is a cancer-selective alkyl phosphocholine (APC) analog that can be radiolabeled with 124I for PET imaging, 131I for targeted radiotherapy and/or SPECT imaging, or 125I for targeted radiotherapy. Studies have demonstrated avid CLR1404 uptake and prolonged retention in a broad spectrum of preclinical tumor models. The purpose of this pilot trial was to demonstrate avidity of 124I-CLR1404 in human brain tumors and develop a framework to evaluate this uptake for use in larger studies. 12 patients (8 men and 4 women; mean age of 43.9 ± 15.1 y; range 23-66 y) with 13 tumors were enrolled. Eleven patients had suspected tumor recurrence and 1 patient had a new diagnosis of high grade tumor. Patients were injected with 185 MBq ± 10% of 124I-CLR1404 followed by PET/CT imaging at 6-, 24-, and 48-hour. 124I-CLR1404 PET uptake was assessed qualitatively and compared with MRI. After PET image segmentation SUV values and tumor to background ratios were calculated. There was no significant uptake of 124I-CLR1404 in normal brain. In tumors, uptake tended to increase to 48 hours. Positive uptake was detected in 9 of 13 lesions: 5/5 high grade tumors, 1/2 low grade tumors, 1/1 meningioma, and 2/4 patients with treatment related changes. 124I-CLR1404 uptake was not detected in 1/2 low grade tumors, 2/4 lesions from treatment related changes, and 1/1 indeterminate lesion. For 6 malignant tumors, the average tumor to background ratios (TBR) were 9.32 ± 4.33 (range 3.46 to 15.42) at 24 hours and 10.04 ± 3.15 (range 5.17 to 13.17) at 48 hours. For 2 lesions from treatment related change, the average TBR were 5.05 ± 0.4 (range 4.76 to 5.33) at 24 hours and 4.88 ± 1.19 (range 4.04 to 5.72) at 48 hours. PET uptake had areas of both concordance and discordance compared with MRI. 124I-CLR1404 PET demonstrated avid tumor uptake in a variety of brain tumors with high tumor-to-background ratios. There were regions of concordance and discordance compared with MRI, which has

Susceptibility Imaging in Glial Tumor Grading; Using 3 Tesla Magnetic Resonance (MR) System and 32 Channel Head Coil.

PubMed

Aydin, Omer; Buyukkaya, Ramazan; Hakyemez, Bahattin

2017-01-01

Susceptibility weighted imaging (SWI) is a velocity compensated, high-resolution three-dimensional (3D) spoiled gradient-echo sequence that uses magnitude and filtered-phase data. SWI seems to be a valuable tool for non-invasive evaluation of central nervous system gliomas. Relative cerebral blood volume (rCBV) ratio is one of the best noninvasive methods for glioma grading. Degree of intratumoral susceptibility signal (ITSS) on SWI correlates with rCBV ratio and histopathological grade. This study investigated the effectiveness of ITSS grading and rCBV ratio in preoperative assessment. Thirty-one patients (17 males and 14 females) with histopathogical diagnosis of glial tumor undergoing routine cranial MRI, SWI, and perfusion MRI examinations between October 2011 and July 2013 were retrospectively enrolled. All examinations were performed using 3T apparatus with 32-channel head coil. We used ITSS number for SWI grading. Correlations between SWI grade, rCBV ratio, and pathological grading were evaluated. ROC analysis was performed to determine the optimal rCBV ratio to distinguish between high-grade and low-grade glial tumors. There was a strong positive correlation between both pathological and SWI grading. We determined the optimal rCBV ratio to discriminate between high-grade and low-grade tumors to be 2.21. In conclusion, perfusion MRI and SWI using 3T MR and 32-channel head coil may provide useful information for preoperative glial tumor grading. SWI can be used as an accessory to perfusion MR technique in preoperative tumor grading.

Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location.

PubMed

Karremann, Michael; Gielen, Gerrit H; Hoffmann, Marion; Wiese, Maria; Colditz, Niclas; Warmuth-Metz, Monika; Bison, Brigitte; Claviez, Alexander; van Vuurden, Dannis G; von Bueren, André O; Gessi, Marco; Kühnle, Ingrid; Hans, Volkmar H; Benesch, Martin; Sturm, Dominik; Kortmann, Rolf-Dieter; Waha, Andreas; Pietsch, Torsten; Kramm, Christof M

2018-01-10

The novel entity of "diffuse midline glioma, H3 K27M-mutant" has been defined in the 2016 revision of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS). Tumors of this entity arise in CNS midline structures of predominantly pediatric patients and are associated with an overall dismal prognosis. They are defined by K27M mutations in H3F3A or HIST1H3B/C, encoding for histone 3 variants H3.3 and H3.1, respectively, which are considered hallmark events driving gliomagenesis. Here, we characterized 85 centrally reviewed diffuse gliomas on midline locations enrolled in the nationwide pediatric German HIT-HGG registry regarding tumor site, histone 3 mutational status, WHO grade, age, sex, and extent of tumor resection. We found 56 H3.3 K27M-mutant tumors (66%), 6 H3.1 K27M-mutant tumors (7%), and 23 H3-wildtype tumors (27%). H3 K27M-mutant gliomas shared an aggressive clinical course independent of their anatomic location. Multivariate regression analysis confirmed the significant impact of the H3 K27M mutation as the only independent parameter predictive of overall survival (P = 0.009). In H3 K27M-mutant tumors, neither anatomic midline location nor histopathological grading nor extent of tumor resection had an influence on survival. These results substantiate the clinical significance of considering diffuse midline glioma, H3 K27M-mutant, as a distinct entity corresponding to WHO grade IV, carrying a universally fatal prognosis. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Age-Grade Distribution, 1984-85. OEA Analytic Report.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn. Office of Educational Assessment.

The 1984-85 age-grade distribution for the New York City Public Schools shows that one-third of the city's approximately 850,000 general education and resource room students were above the standard age for their grade. The proportion of overage students increased in the upper grades; in grades nine, ten, and eleven, over half were above standard…

Glomeruloid Microvascular Proliferation, Desmoplasia, and High Proliferative Index as Potential Indicators of High Grade Canine Choroid Plexus Tumors.

PubMed

Muscatello, Luisa Vera; Avallone, Giancarlo; Serra, Fabienne; Seuberlich, Torsten; Mandara, Maria Teresa; Sisó, Silvia; Brunetti, Barbara; Oevermann, Anna

2018-05-01

Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRβ, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT.

Expression of EphA2 protein is positively associated with age, tumor size and Fuhrman nuclear grade in clear cell renal cell carcinomas.

PubMed

Wang, Longxin; Hu, Haibing; Tian, Feng; Zhou, Wenquan; Zhou, Shuigen; Wang, Jiandong

2015-01-01

The receptor tyrosine kinase of EphA2 has been shown frequently overexpressed in various types of human carcinomas, which implicated that it plays important roles in carcinogenesis. Although EphA2 protein expression has been investigated in many types of human carcinomas, the relationship between the expression of EphA2 protein in clear cell renal cell carcinoma was not well documented. In the present study, using specific anit-EphA2 polyclonal antibody and immunohistochemistry, we evaluated EphA2 protein expression levels in clear cell RCC specimens surgically resected from 90 patients. Our results shows that EphA2 protein was positively expressed in all normal renal tubes of 90 samples (100%, 3+), which was expressed at low levels in renal cortex but high levels in the collecting ducts of the renal medulla and papilla. EphA2 was negatively or weakly expressed in 30 out of 90 samples (33.3%, 0/1+), moderately expressed in 24 samples (26.7%, 2+) and strongly expressed in 36 samples (40%, 3+). Expression of EphA2 was positively associated with age (P=0.029), tumor diameters (P<0.001) and Fuhrman nuclear grade (P<0.001). Our results indicate that EphA2 variably expressed in clear cell renal cell carcinomas. High expression of EphA2 was more often found in big size and high nuclear grade tumors, which indicated EphA2 protein may be used as a new marker for the prognosis of clear cell renal cell carcinoma.

Grade Assignment by Ki-67 Proliferative Index, Mitotic Count, and Phosphohistone H3 Count in Surgically Resected Gastrointestinal and Pancreatic Neuroendocrine Tumors.

PubMed

Murphy, Claire E; McCormick, Kinsey A; Shankaran, Veena; Reddi, Deepti M; Swanson, Paul E; Upton, Melissa P; Papanicolau-Sengos, Antonios; Khor, Sara; Westerhoff, Maria

The aim of this study was to evaluate the concordance in grade assignment for gastroenteropancreatic neuroendocrine tumors using mitotic count (MC), Ki-67 proliferative index (KPI), and phosphohistone H3 count (PHH3C). Resected gastroenteropancreatic neuroendocrine tumors were graded based on MC, KPI, and PHH3C. Concordance was determined using a weighted κ statistic. Median survival across each grade category was determined using Kaplan-Meier methods. Of the 110 patients, the majority had gastrointestinal primaries and grade 1 or 2 tumors. Rates of discordance in grade assignment were 29% of cases for KPI versus MC (κW = 0.26), 32% for PHH3C versus MC (κW = 0.34), and 32% for PHH3C versus KPI (κW = 0.37). There was fair agreement between grading by KPI and MC. Relative to grade by KPI and MC, PHH3C tended to upgrade tumors. The proportion alive at 3 and 5 years was not significantly different for patients with grade 1 versus grade 2 tumors. The concordance between KPI and MC was fair. Phosphohistone H3 count tended to upgrade tumors using the cutoffs established by MC. Grade 1 and grade 2 tumors were associated with similar survival regardless of grading method. The overall relevance of the current cutoff values used in grading neuroendocrine tumors may need to be revisited.

The End of the Reading Age: Grade and Age Effects in Early Schooling

ERIC Educational Resources Information Center

Alexander, James R.M.; Martin, Frances

2004-01-01

During the school years, psychological test norms may be indexed by age or by grade. A number of studies have shown that using age-based norms appears to produce biases associated with grade assignment. Cahan and Cohen [Child Dev. 60 (1989) 1239-1249] showed that the effect of one grade was over twice the effect of 1 year of age for most verbal…

Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials

PubMed Central

Chamberlain, Marc; Schiff, David; Reijneveld, Jaap C.; Armstrong, Terri S.; Ruda, Roberta; Wen, Patrick Y.; Weller, Michael; Koekkoek, Johan A. F.; Mittal, Sandeep; Arakawa, Yoshiki; Choucair, Ali; Gonzalez-Martinez, Jorge; MacDonald, David R.; Nishikawa, Ryo; Shah, Aashit; Vecht, Charles J.; Warren, Paula; van den Bent, Martin J.; DeAngelis, Lisa M.

2017-01-01

Patients with low-grade glioma frequently have brain tumor–related epilepsy, which is more common than in patients with high-grade glioma. Treatment for tumor-associated epilepsy usually comprises a combination of surgery, anti-epileptic drugs (AEDs), chemotherapy, and radiotherapy. Response to tumor-directed treatment is measured primarily by overall survival and progression-free survival. However, seizure frequency has been observed to respond to tumor-directed treatment with chemotherapy or radiotherapy. A review of the current literature regarding seizure assessment for low-grade glioma patients reveals a heterogeneous manner in which seizure response has been reported. There is a need for a systematic approach to seizure assessment and its influence on health-related quality-of-life outcomes in patients enrolled in low-grade glioma therapeutic trials. In view of the need to have an adjunctive metric of tumor response in these patients, a method of seizure assessment as a metric in brain tumor treatment trials is proposed. PMID:27651472

A semi-quantitative World Health Organization grading scheme evaluating worst tumor differentiation predicts disease-free survival in oral squamous carcinoma patients.

PubMed

Jain, Dhruv; Tikku, Gargi; Bhadana, Pallavi; Dravid, Chandrashekhar; Grover, Rajesh Kumar

2017-08-01

We investigated World Health Organization (WHO) grading and pattern of invasion based histological schemes as independent predictors of disease-free survival, in oral squamous carcinoma patients. Tumor resection slides of eighty-seven oral squamous carcinoma patients [pTNM: I&II/III&IV-32/55] were evaluated. Besides examining various patterns of invasion, invasive front grade, predominant and worst (highest) WHO grade were recorded. For worst WHO grading, poor-undifferentiated component was estimated semi-quantitatively at advancing tumor edge (invasive growth front) in histology sections. Tumor recurrence was observed in 31 (35.6%) cases. The 2-year disease-free survival was 47% [Median: 656; follow-up: 14-1450] days. Using receiver operating characteristic curves, we defined poor-undifferentiated component exceeding 5% of tumor as the cutoff to assign an oral squamous carcinoma as grade-3, when following worst WHO grading. Kaplan-Meier curves for disease-free survival revealed prognostic association with nodal involvement, tumor size, worst WHO grading; most common pattern of invasion and invasive pattern grading score (sum of two most predominant patterns of invasion). In further multivariate analysis, tumor size (>2.5cm) and worst WHO grading (grade-3 tumors) independently predicted reduced disease-free survival [HR, 2.85; P=0.028 and HR, 3.37; P=0.031 respectively]. The inter-observer agreement was moderate for observers who semi-quantitatively estimated percentage of poor-undifferentiated morphology in oral squamous carcinomas. Our results support the value of semi-quantitative method to assign tumors as grade-3 with worst WHO grading for predicting reduced disease-free survival. Despite limitations, of the various histological tumor stratification schemes, WHO grading holds adjunctive value for its prognostic role, ease and universal familiarity. Copyright © 2017 Elsevier Inc. All rights reserved.

High-grade endometrial stromal sarcomas: a clinicopathologic study of a group of tumors with heterogenous morphologic and genetic features.

PubMed

Sciallis, Andrew P; Bedroske, Patrick P; Schoolmeester, John K; Sukov, William R; Keeney, Gary L; Hodge, Jennelle C; Bell, Debra A

2014-09-01

The existence of a "high-grade endometrial stromal sarcoma" category of tumors has been a controversial subject owing to, among other things, the difficulty in establishing consistent diagnostic criteria. Currently, the recommended classification for such tumors is undifferentiated uterine/endometrial sarcoma. Interest in this subject has recently increased markedly with the identification of recurrent molecular genetic abnormalities. At Mayo Clinic, a group of neoplasms has been observed that morphologically resemble, either cytologically or architecturally, classic "low-grade" endometrial stromal sarcoma but feature obvious deviations, specifically, 17 tumors with unequivocally high-grade morphology. These high-grade tumors displayed 3 morphologic themes: (1) tumors with a component that is identical to low-grade ESS that transitions abruptly into an obviously higher-grade component; (2) tumors composed exclusively of high-grade cells with uniform nuclear features but with a permeative pattern of infiltration; (3) tumors similar to the second group but with a different, yet characteristic, cytomorphology featuring enlarged round to ovoid cells (larger than those found in low-grade ESS) with smooth nuclear membranes and distinct chromatin clearing but lacking prominent nucleoli. We collected clinicopathologic data, applied immunohistochemical studies, and also tested tumors by fluorescence in situ hybridization for abnormalities in JAZF1, PHF1, YWHAE, and CCND1. Tumors from these 3 groups were found to be immunohistochemically and genetically distinct from one another. Most notable was the fact that category 3 contained all the cases that tested positive for YWHAE rearrangement, did not show any classic translocations for JAZF1, PHF1, or CCND1, often presented at a high stage, and behaved aggressively. This study demonstrates the morphologic, immunophenotypic, and molecular genetic heterogeneity that exists within "undifferentiated endometrial sarcomas" as

Tumor Budding and PDC Grade Are Stage Independent Predictors of Clinical Outcome in Mismatch Repair Deficient Colorectal Cancer.

PubMed

Ryan, Éanna; Khaw, Yi Ling; Creavin, Ben; Geraghty, Robert; Ryan, Elizabeth J; Gibbons, David; Hanly, Ann; Martin, Sean T; O'Connell, P Ronan; Winter, Desmond C; Sheahan, Kieran

2018-01-01

Mismatch repair deficient (dMMR) colorectal cancer (CRC) despite its association with poor histologic grade often has improved prognosis compared with MMR proficient CRC. Tumor budding and poorly differentiated clusters (PDCs) may predict metastatic potential of colorectal adenocarcinoma (CRC). In addition, their assessment may be more reproducible than the evaluation of other histopathologic parameters. Therefore, we wished to determine their potential as prognostic indicators in a cohort of dMMR CRC patients relative to histologic grade. We investigated the predictive value of conventional WHO grade, budding, PDC grade and other histopathologic parameters on the presence of lymph node metastasis (LNM) and clinical outcome in 238 dMMR CRCs. MMR status was determined by immunohistochemistry for the mismatch repair proteins hMLH1, hMSH2, hMSH6, and hPMS2. Tumor budding and PDCs were highly correlated (r=0.701; P<0.000). Both budding and PDC grade were associated with WHO grade, perineural invasion, lympho-vascular invasion, and extramural vascular invasion, and the presence of LNM in dMMR CRC (P<0.009). Independent predictors of LNM were PDC grade (odds ratio, 4.12; 95% confidence interval [CI], 1.69-10.04; P=0.011) and EMVI (odds ratio, 3.81; 95% CI, 1.56-9.19; P<0.000). Only pTstage (hazard ratio [HR], 4.11; 95% CI, 1.48-11.36; P=0.007) and tumor budding (HR, 2.99; 95% CI, 1.72-5.19; P<0.000) were independently associated with worse disease-free survival (DFS). If tumor budding was excluded from the model, PDC grade became significant for DFS (HR, 2.34; 95% CI, 1.34-4.09; P=0.003). WHO Grade does not independently correlate with clinical outcome in dMMR CRC. PDC grade and extramural vascular invasion are independent predictors of LNM. Tumor budding and pTstage are the best predictors of DFS. If tumor budding cannot be assessed, PDC grade may be used as a prognostic surrogate.

Low-grade prostate tumors can harbor signs of aggressive cancer | Center for Cancer Research

Cancer.gov

In a new study, Center for Cancer Research investigators found that low-grade and high-grade regions of prostate tumor tissue shared mutations typically linked to aggressive cancer. Testing for mutations to specific genes could help clinicians decide whether a patient with an initial low-grade result should undergo a follow-up biopsy. Learn more...

[Assessment of skin aging grading based on computer vision].

PubMed

Li, Lingyu; Xue, Jinxia; He, Xiangqian; Zhang, Sheng; Fan, Chu

2017-06-01

Skin aging is the most intuitive and obvious sign of the human aging processes. Qualitative and quantitative determination of skin aging is of particular importance for the evaluation of human aging and anti-aging treatment effects. To solve the problem of subjectivity of conventional skin aging grading methods, the self-organizing map (SOM) network was used to explore an automatic method for skin aging grading. First, the ventral forearm skin images were obtained by a portable digital microscope and two texture parameters, i.e. , mean width of skin furrows and the number of intersections were extracted by image processing algorithm. Then, the values of texture parameters were taken as inputs of SOM network to train the network. The experimental results showed that the network achieved an overall accuracy of 80.8%, compared with the aging grading results by human graders. The designed method appeared to be rapid and objective, which can be used for quantitative analysis of skin images, and automatic assessment of skin aging grading.

DWI-associated entire-tumor histogram analysis for the differentiation of low-grade prostate cancer from intermediate-high-grade prostate cancer.

PubMed

Wu, Chen-Jiang; Wang, Qing; Li, Hai; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin; Zhang, Yu-Dong

2015-10-01

To investigate diagnostic efficiency of DWI using entire-tumor histogram analysis in differentiating the low-grade (LG) prostate cancer (PCa) from intermediate-high-grade (HG) PCa in comparison with conventional ROI-based measurement. DW images (b of 0-1400 s/mm(2)) from 126 pathology-confirmed PCa (diameter >0.5 cm) in 110 patients were retrospectively collected and processed by mono-exponential model. The measurement of tumor apparent diffusion coefficients (ADCs) was performed with using histogram-based and ROI-based approach, respectively. The diagnostic ability of ADCs from two methods for differentiating LG-PCa (Gleason score, GS ≤ 6) from HG-PCa (GS > 6) was determined by ROC regression, and compared by McNemar's test. There were 49 LG-tumor and 77 HG-tumor at pathologic findings. Histogram-based ADCs (mean, median, 10th and 90th) and ROI-based ADCs (mean) showed dominant relationships with ordinal GS of Pca (ρ = -0.225 to -0.406, p < 0.05). All above imaging indices reflected significant difference between LG-PCa and HG-PCa (all p values <0.01). Histogram 10th ADCs had dominantly high Az (0.738), Youden index (0.415), and positive likelihood ratio (LR+, 2.45) in stratifying tumor GS against mean, median and 90th ADCs, and ROI-based ADCs. Histogram mean, median, and 10th ADCs showed higher specificity (65.3%-74.1% vs. 44.9%, p < 0.01), but lower sensitivity (57.1%-71.3% vs. 84.4%, p < 0.05) than ROI-based ADCs in differentiating LG-PCa from HG-PCa. DWI-associated histogram analysis had higher specificity, Az, Youden index, and LR+ for differentiation of PCa Gleason grade than ROI-based approach.

Grading the neuroendocrine tumors of the lung: an evidence-based proposal.

PubMed

Rindi, G; Klersy, C; Inzani, F; Fellegara, G; Ampollini, L; Ardizzoni, A; Campanini, N; Carbognani, P; De Pas, T M; Galetta, D; Granone, P L; Righi, L; Rusca, M; Spaggiari, L; Tiseo, M; Viale, G; Volante, M; Papotti, M; Pelosi, G

2014-02-01

Lung neuroendocrine tumors are catalogued in four categories by the World Health Organization (WHO 2004) classification. Its reproducibility and prognostic efficacy was disputed. The WHO 2010 classification of digestive neuroendocrine neoplasms is based on Ki67 proliferation assessment and proved prognostically effective. This study aims at comparing these two classifications and at defining a prognostic grading system for lung neuroendocrine tumors. The study included 399 patients who underwent surgery and with at least 1 year follow-up between 1989 and 2011. Data on 21 variables were collected, and performance of grading systems and their components was compared by Cox regression and multivariable analyses. All statistical tests were two-sided. At Cox analysis, WHO 2004 stratified patients into three major groups with statistically significant survival difference (typical carcinoid vs atypical carcinoid (AC), P=0.021; AC vs large-cell/small-cell lung neuroendocrine carcinomas, P<0.001). Optimal discrimination in three groups was observed by Ki67% (Ki67% cutoffs: G1 <4, G2 4-<25, G3 ≥25; G1 vs G2, P=0.021; and G2 vs G3, P≤0.001), mitotic count (G1 ≤2, G2 >2-47, G3 >47; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001), and presence of necrosis (G1 absent, G2 <10% of sample, G3 >10% of sample; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001) at uni and multivariable analyses. The combination of these three variables resulted in a simple and effective grading system. A three-tiers grading system based on Ki67 index, mitotic count, and necrosis with cutoffs specifically generated for lung neuroendocrine tumors is prognostically effective and accurate.

PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status

PubMed Central

Edqvist, Per-Henrik D.; Hägerstrand, Daniel; Carlson, Joseph; Lysiak, Malgorzata; Henriksson, Roger; Pontén, Fredrik; Rosell, Johan; Söderkvist, Peter; Stupp, Roger; Tchougounova, Elena; Nistér, Monica; Malmström, Annika; Smits, Anja

2016-01-01

PROX1 is a transcription factor with an essential role in embryonic development and determination of cell fate. In addition, PROX1 has been ascribed suppressive as well as oncogenic roles in several human cancers, including brain tumors. In this study we explored the correlation between PROX1 expression and patient survival in high-grade astrocytomas. For this purpose, we analyzed protein expression in tissue microarrays of tumor samples stratified by patient age and IDH mutation status. We initially screened 86 unselected high-grade astrocytomas, followed by 174 IDH1-R132H1 immunonegative glioblastomas derived from patients aged 60 years and older enrolled in the Nordic phase III trial of elderly patients with newly diagnosed glioblastoma. Representing the younger population of glioblastomas, we studied 80 IDH-wildtype glioblastomas from patients aged 18-60 years. There was no correlation between PROX1 protein and survival for patients with primary glioblastomas included in these cohorts. In contrast, high expression of PROX1 protein predicted shorter survival in the group of patients with IDH-mutant anaplastic astrocytomas and secondary glioblastomas. The prognostic impact of PROX1 in IDH-mutant 1p19q non-codeleted high-grade astrocytomas, as well as the negative findings in primary glioblastomas, was corroborated by gene expression data extracted from the Cancer Genome Atlas. We conclude that PROX1 is a new prognostic biomarker for 1p19q non-codeleted high-grade astrocytomas that have progressed from pre-existing low-grade tumors and harbor IDH mutations. PMID:27626492

Pancreatic neuroendocrine tumors containing areas of iso- or hypoattenuation in dynamic contrast-enhanced computed tomography: Spectrum of imaging findings and pathological grading.

PubMed

Hyodo, Ryota; Suzuki, Kojiro; Ogawa, Hiroshi; Komada, Tomohiro; Naganawa, Shinji

2015-11-01

To evaluate dynamic contrast-enhanced computed tomography (CT) features of pancreatic neuroendocrine tumors (PNETs) containing areas of iso- or hypoattenuation and the relationship with pathological grading. Between June 2006 and March 2014, 61 PNETs in 58 consecutive patients (29 male, 29 female; median-age 55 years), which were surgically diagnosed, underwent preoperative dynamic contrast-enhanced CT. PNETs were classified based on contrast enhancement patterns in the pancreatic phase: iso/hypo-PNETs were defined as tumors containing areas of iso- or hypoattenuation except for cystic components, and hyper-PNETs were tumors showing hyperattenuation over the whole area. CT findings and contrast-enhancement patterns of the tumors were evaluated retrospectively by two radiologists and compared with the pathological grading. Iso/hypo-PNETs comprised 26 tumors, and hyper-PNETs comprised 35 tumors. Not only hyper-PNETs but also most iso/hypo-PNETs showed peak enhancement in the pancreatic phase and a washout from the portal venous phase to the delayed phase. Iso/hypo-PNETs showed larger tumor size than the hyper-PNETs (mean, 3.7 cm vs. 1.6 cm; P<0.001), and were significantly correlated with unclear tumor margins (n=4 vs. n=0; P=0.029), the existence of cystic components (n=10 vs. n=3; P=0.006), intratumoral blood vessels in the early arterial phase (n=13 vs. n=3; P<0.001), and a smooth rim enhancement in the delayed phase (n=12 vs. n=6; P=0.019). Iso/hypo-PNETs also showed significantly higher pathological grading (WHO 2010 classification; iso/hypo, G1=14, G2=11, G3=1; hyper, G1=34, G2=1; P<0.001). PNETs containing iso/hypo-areas showed a rapid enhancement pattern as well as hyper-PNETs, various radiological features and higher malignant potential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Preoperative lymphoscintigraphy and tumor histologic grade are associated with surgical detection of the sentinel lymph node.

PubMed

Arias Ortega, M; Torres Sousa, M Y; González García, B; Pardo García, R; González López, A; Delgado Portela, M

2014-01-01

To study which variables involved in the process of selective sentinel node biopsy (SSNB) influence the intraoperative detection of the sentinel lymph node. This was a prospective cross-sectional study in 210 patients (mean age, 54 years) diagnosed with breast cancer who underwent SSNB. We recorded clinical, radiological, radioisotope administration, surgical, and histological data as well as follow-up data. We did a descriptive analysis of the data and an associative analysis using multivariable regression. Deep injection alone was the most common route of radioisotope administration (72.7%). Most lesions were palpable (57.1%), presented as nodules (67.1%), measured less than 2 cm in diameter (64.8%), were located in the upper outer quadrant (49.1%), were ductal carcinomas (85.7%), were accompanied by infiltration (66.2%), and had a histologic grade of differentiation of ii (44.8%). Preoperative scintigraphy detected the sentinel node in 97.6% of cases and 95.7% were detected during the operation. One axillary relapse was observed. In the associative study, the variables "preoperative lymphoscintigraphy" and "histologic grade of differentiation of the tumor" were significantly associated with the detection of the sentinel lymph node during the operation. The probability of not detecting the sentinel lymph node during the surgical intervention is higher in patients with high histologic grade tumors or in patients in whom preoperative lymphoscintigraphy failed to detect the sentinel node. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Quantifying expert diagnosis variability when grading tumor-infiltrating lymphocytes

NASA Astrophysics Data System (ADS)

Toro, Paula; Corredor, Germán.; Wang, Xiangxue; Arias, Viviana; Velcheti, Vamsidhar; Madabhushi, Anant; Romero, Eduardo

2017-11-01

Tumor-infiltrating lymphocytes (TILs) have proved to play an important role in predicting prognosis, survival, and response to treatment in patients with a variety of solid tumors. Unfortunately, currently, there are not a standardized methodology to quantify the infiltration grade. The aim of this work is to evaluate variability among the reports of TILs given by a group of pathologists who examined a set of digitized Non-Small Cell Lung Cancer samples (n=60). 28 pathologists answered a different number of histopathological images. The agreement among pathologists was evaluated by computing the Kappa index coefficient and the standard deviation of their estimations. Furthermore, TILs reports were correlated with patient's prognosis and survival using the Pearson's correlation coefficient. General results show that the agreement among experts grading TILs in the dataset is low since Kappa values remain below 0.4 and the standard deviation values demonstrate that in none of the images there was a full consensus. Finally, the correlation coefficient for each pathologist also reveals a low association between the pathologists' predictions and the prognosis/survival data. Results suggest the need of defining standardized, objective, and effective strategies to evaluate TILs, so they could be used as a biomarker in the daily routine.

Defining the optimal method for reporting prostate cancer grade and tumor extent on magnetic resonance/ultrasound fusion-targeted biopsies.

PubMed

Gordetsky, Jennifer B; Schultz, Luciana; Porter, Kristin K; Nix, Jeffrey W; Thomas, John V; Del Carmen Rodriguez Pena, Maria; Rais-Bahrami, Soroush

2018-06-01

Magnetic resonance (MR)/ultrasound fusion-targeted biopsy (TB) routinely samples multiple cores from each MR lesion of interest. Pathologists can evaluate the extent of cancer involvement and grade using an individual core (IC) or aggregate (AG) method, which could potentially lead to differences in reporting. We reviewed patients who underwent TB followed by radical prostatectomy (RP). TB cores were evaluated for grade and tumor extent by 2 methods. In the IC method, the grade for each TB lesion was based on the core with the highest Gleason score. Tumor extent for each TB was based on the core with the highest percent of tumor involvement. In the AG method, the tumor from all cores within each TB lesion was aggregated to determine the final composite grade and percentage of tumor involvement. Each method was compared with MR lesional volume, MR lesional density (lesion volume/prostate volume), and RP. Fifty-five patients underwent TB followed by RP. Extent of tumor by the AG method showed a better correlation with target lesion volume (r= 0.27,P= .022) and lesional density (r = 0.32, P = .008) than did the IC method (r= 0.19 [P = .103] andr= 0.22 [P = .062]), respectively. Extent of tumor on TB was associated with extraprostatic extension on RP by the AG method (P= .04), but not by the IC method. This association was significantly higher in patients with a grade group (GG) of 3 or higher (P= .03). A change in cancer grade occurred in 3 patients when comparing methods (2 downgraded GG3 to GG2, 1 downgraded GG4 to GG3 by the AG method). For multiple cores obtained via TB, the AG method better correlates with target lesion volume, lesional density, and extraprostatic extension. Copyright © 2018 Elsevier Inc. All rights reserved.

Testing for NRAS Mutations in Serous Borderline Ovarian Tumors and Low-Grade Serous Ovarian Carcinomas

PubMed Central

Grzanka, Dariusz; Grabiec, Marek

2018-01-01

The Idylla NRAS Mutation Test, performed on the Biocartis Idylla system, is an in vitro diagnostic tool for the qualitative assessment of 18 NRAS mutations in codons 12, 13, 59, 61, 117, and 146. Low-grade serous ovarian cancer (LGSC) represents less than 10% of all serous ovarian carcinomas. LGSCs are believed to arise from preexisting cystadenomas or serous borderline tumors (SBOTs) that eventually progress to an invasive carcinoma. The molecular analysis of cancer-causing mutations and the development of targeted biological therapies constitute a milestone in the diagnosis and therapy of ovarian malignancies. According to some authors, NRAS may be an important oncogene for the progression of SBOT to a frankly invasive disease. The primary aim of this study was to verify if a fully integrated, real-time PCR-based Idylla system can be used for the rapid determination of the NRAS mutation status in patients with serous borderline ovarian tumors and low-grade serous ovarian carcinomas. The study included tissue specimens from 12 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz (Poland), between January 2009 and June 2012. The mean age of the study patients was 52.5 years (range 27–80 years). NRAS mutation in codon 13 (G13D, p.Gly13Asp; nucleotide: c.38G>A) was found in one patient, a woman with low-grade serous ovarian carcinoma. To the best of our knowledge, our experiment was the first published study using the novel Idylla NRAS Mutation Test for the evaluation of ovarian tumors in a clinical setting. The Idylla platform is an interesting ancillary first-line rapid and fully automated instrument to detect NRAS mutations in SBOTs and LGSCs. However, the clinical usefulness of this method still needs to be verified in larger groups of cancer patients. PMID:29682098

Infiltration characteristics and influencing factors of retroperitoneal liposarcoma: Novel evidence for extended surgery and a tumor grading system.

PubMed

Wang, Zhen; Wu, Jianhui; Lv, Ang; Li, Chengpeng; Li, Zhongwu; Zhao, Min; Hao, Chunyi

2018-05-13

This study sought to evaluate the infiltration tendency of retroperitoneal liposarcoma (RPLS) from a new pathological angle by exploring the infiltration characteristics, which could provide helpful information to facilitate surgical decision-making and prognosis prediction. Concurrently, we aim to identify significant indicators of infiltration. A total of 61 consecutive patients with RPLS at our institution were retrospectively analyzed. All patients received extended surgery. The tumor infiltration characteristics and influencing factors were studied based on the pathological diagnosis. Univariate and multivariate analyses of organ infiltration (OI) and surrounding fat infiltration (SFI) were performed. OI was found in 95 (28.5%) resected organs from 39 (60.7%) patients, and SFI was found in 119 (35.7%) resected organs from 47 (77%) patients. The tumor infiltrated the serosal layer of 13 organs (13/37, 35.1%), the muscularis layer of 18 organs (18/37, 48.6%) and the submucosa of 6 organs (6/37, 16.2%). The percentage of lipoblasts and the rates of necrosis and mitosis were all significantly higher in high-grade tumors (dedifferentiated, round cell, and pleomorphic). A high lipoblast percentage (≥ 20%) was the only independent risk factor for OI. A recurrent tumor and a high-grade tumor were independent risk factors for SFI. In conclusion, RPLS has a high infiltration tendency, such that it frequently infiltrates organs and surrounding fat tissue. Therefore, extended resection of the tumor and the adjacent organs is recommended. The percentage of lipoblasts was associated with the tumor grade and infiltration characteristics; thus, lipoblast percentage may become a new grading factor for RPLS.

Evaluation of myeloid cells (tumor-associated tissue eosinophils and mast cells) infiltration in different grades of oral squamous cell carcinoma.

PubMed

Debta, Priyanka; Debta, Fakir Mohan; Chaudhary, Minal; Bussari, Smita

2016-01-01

The multifunctional involvement and infiltration of myeloid cells (tumor-associated tissue eosinophils [TATE] and mast cells) can provide a unique opportunity to define relevant effectors functions that may represent novel, therapeutic options for modulation of tumor onset/growth. Our study aimed to evaluate infiltration of myeloid cells (TATE and Mast cells) infiltration in different grades (WHO grading) of oral squamous cell carcinoma (OSCC). Total 30 cases of OSCC were selected for this study. Hematoxylin and eosin stain and toluidine blue special stain, to evaluate TATE and the mast cells infiltration, were used. Three-year follow-up of OSCC cases was done. Among 30 cases, 63.33% cases of OSCC showed TATE-positive and 36.66% cases showed TATE-negative. Regarding mast cells infiltration, 66.66% OSCC cases showed mast cells positive and 33.33% cases did not show significant mast cells infiltration. We found significant association of TATE and mast cells infiltration in OSCC cases. These myeloid cells infiltration significantly associated with age of patients but did not show any significant association with gender, site, and habit of cases. When we compared these cells infiltration with clinical stages and different histological grades of tumor, we found their infiltration is decreasing, from Stages 1 to Stage 3 of tumor and from well to poorly differentiated carcinoma. We have also found the less infiltration of these myeloid in recurrence cases of OSCC. As the infiltration of TATE and mast cells are correlated, along with evaluation of TATE, we should also evaluate the presence of mast cells infiltration in OSCC. The assessment of myeloid cells could become, in the future, useful for therapeutic approaches in this subset of the patient.

Differential somatostatin, CXCR4 chemokine and endothelin A receptor expression in WHO grade I-IV astrocytic brain tumors.

PubMed

Lange, Franziska; Kaemmerer, Daniel; Behnke-Mursch, Julianne; Brück, Wolfgang; Schulz, Stefan; Lupp, Amelie

2018-04-25

Glioblastomas represent the most common primary malignant tumor of the nervous system and the most frequent type of astrocytic tumors. Despite improved therapeutic options, prognosis has remained exceptionally poor over the last two decades. Therefore, new treatment approaches are urgently needed. An overexpression of somatostatin (SST) as well as chemokine CXCR4 and endothelin A (ETA) receptors has been shown for many types of cancer. Respective expression data for astrocytic brain tumors, however, are scarce and contradictory. SST subtype, CXCR4 and ETA expression was comparatively evaluated in a total of 57 grade I-IV astrocytic tumor samples by immunohistochemistry using well-characterized monoclonal antibodies. Overall, receptor expression on the tumor cells was only very low. SST5 was the most prominently expressed receptor, followed by SST3, ETA, SST2 and CXCR4. In contrast, tumor capillaries displayed strong SST2, SST3, SST5, CXCR4 and ETA expression. Presence of SST5, CXCR4 and ETA on tumor cells and of SST3, CXCR4 and ETA on microvessels gradually increased from grade II to grade IV tumors. Ki-67 values correlated significantly with CXCR4 expression on tumor cells and with vascular SST3, CXCR4 or ETA positivity. SST5 or CXCR4 positivity of tumor cells and vascular SST3 or CXCR4 expression negatively correlated with patient outcome. Though having some prognostic value, SST, CXCR4 or ETA expression on astrocytic tumor cells is clearly of no therapeutic relevance. Indirect targeting of these highly vascularized tumors via SST3, SST5, CXCR4 or ETA on the microvessels, in contrast, may represent a promising additional therapeutic strategy.

EGFR expression in circulating tumor cells from high-grade metastatic soft tissue sarcomas.

PubMed

Braun, Alexcia Camila; de Mello, Celso Abdon Lopes; Corassa, Marcelo; Abdallah, Emne Ali; Urvanegia, Ana Cláudia; Alves, Vanessa Silva; Flores, Bianca C T C P; Díaz, Mônica; Nicolau, Ulisses Ribaldo; Silva, Virgilio Souza E; Calsavara, Vinicius; Paterlini-Brechót, Patrizia; Chinen, Ludmilla Thomé Domingos

2018-06-03

Soft tissue Sarcomas (STS) are rare malignances, with high mortality rates. Half of patients develop metastasis. The presence of isolated Circulating Tumor Cells (CTCs) and Circulating Tumor Microemboli (CTM) in the blood may be early markers of tumor invasion. Epidermal Growth Factor (EGF) family receptors can also influence this process. to quantify CTCs and identify CTM as well as the EGF Receptor (EGFR) protein expression in these cells and correlate with clinical outcome in metastatic STS. Approximately 8mL of blood was prospectively collected from patients with different types of high-grade STS, before the beginning of chemotherapy. The samples were processed and filtered by ISET (Rarecells, France) for the isolation and quantification of CTCs and CTMs. EGFR expression was analyzed by immunocytochemistry (ICC) on CTCs/ CTMs. We analyzed 18 patients with median age of 49 years (18-77 y). The positivity for EGFR protein expression in CTCs was observed in 93.75% of the patients. This result shows that targeting EGFR positive CTCs from STS origen can be translated in clinical benefit for some patients. In addition, if target therapy is chosen, the EGFR expression in CTCs can be used in follow-up to measure treatment effectiveness. This is the first study to demonstrate the expression of EGFR protein in CTCs from sarcoma patients. It may open an area for future investigations. The next step is to characterize CTCs in a larger cohort of patients to better understand the role of EGFR in sustaining tumor metastasis in sarcomas.

Diagnostic efficacy of smear cytology and Robinson’s cytological grading of canine mammary tumors with respect to histopathology, cytomorphometry, metastases and overall survival

PubMed Central

Czopowicz, Michał; Gruk-Jurka, Anna; Wojtkowska, Agata; Sapierzyński, Rafał; Jurka, Piotr

2018-01-01

Cytology is a simple, rapid, and inexpensive method used for pre-operative diagnosis of canine mammary tumors (CMTs) in veterinary practice. Studies related to human breast cancer showed the Robinson’s grading system—established for invasive ductal carcinoma, not otherwise specified (IDC, NOS) and used on cytological material—to not only closely correspond to the histopathological grading but also be helpful in assessing prognosis and selecting most suitable treatments before surgery. The objectives of this study were: to evaluate the accuracy of cytological diagnosis and cytological Robinson’s grading system compared to the histopathological examination of CMTs; to compare of cytological features and cytomorphometric parameters with tumor behavior, as well as cytological and histological grading; and to determine an association of the Robinson’s grading system and cytological background details with metastases, and patients’ survival. We report substantial diagnostic accuracy in detecting simple types and high grade tumors. Cytological diagnosis of tumor behavior showed relatively low sensitivity and specificity compared to human studies, and this might be caused by the heterogeneous morphology of CMTs. The presence of mucosecretory material and extracellular matrix was not significantly associated with tumor behavior. We report a positive correlation between both grading systems and cytological features (included in Robinson’s grading), the presence of necrotic debris, inflammation, and red blood cells. A negative correlation was determined only for the presence of extracellular matrix. The univariate and multivariate analyses confirmed a significantly higher risk of developing metastasis and shorter overall survival for dogs with tumors of grade 2 or 3 on cytology. In addition, these tumors were the most common cause of CMT-related deaths in dogs. Taken together, our findings suggest that the Robinson’s method of cytological grading applied for

Correlation Between Ki-67 Index, World Health Organization Grade and Patient Survival in Glial Tumors With Astrocytic Differentiation

PubMed Central

Dzhenkov, Deyan L; Kitanova, Martina; Donev, Ivan S; Ghenev, Peter

2017-01-01

Background Glioblastoma multiforme (GBM) is a class IV astrocytic tumor, the most malignant of the four groups of World Health Organization (WHO) tumors with astrocytic differentiation. Aim The aim of this study was to estab­lish whether a correlation exists between the Ki-67 index of tumors with astrocytic differentiation, WHO grade, and patient survival. Materials and methods A retrospective non-clinical approach to patient selection was chosen for the aim of the study. A total of 47 patients diagnosed and treated for CNS tumors with astrocytic differentiation in the St. Marina University Hospital, Varna, Bulgaria, from September 2012 to July 2016 were retrospectively included into the study cohort. The cases were tested for their immunohistochemistry (IHC) reaction with Ki-67 after their original Hematoxylin and Eosin and IHC slides were reviewed by a single author and blind coded. The Ki-67 positivity index of the nuclei was estimated after digitalization of the slides and calculated by the ImmunoRatio automated count­ing tool. The individual Ki-67 index and patient survival of each case were statistically compared. Results The histopathological groups, after the blind Ki-67 index automated calculation was carried out, revealed no WHO grade I, two WHO grade II samples, four WHO grade III samples and 41 WHO grade IV cases, and these were included in the analysis. The two samples of WHO grade II astrocytic tumors had a mean Ki-67 index of 25%; however, they comprised tumors with an individual index of 43% and 7%, both individual values with a highly unlikely index for this group. The four samples of WHO grade III had a mean Ki-67 index of 4%, standard deviation ±2.16 (p>0.05), with the lowest index being 1% and the highest one being 6%. Both WHO grade II and III did not include enough samples to allow for a proper statistical analysis of patient survival. The 41 GBM cases had a mean Ki-67 index of 17.34%, standard deviation ±10.79 (p>0

Tumor volumetric measurements in surgically inaccessible pediatric low-grade glioma.

PubMed

Kilday, John-Paul; Branson, Helen; Rockel, Conrad; Laughlin, Suzanne; Mabbott, Donald; Bouffet, Eric; Bartels, Ute

2015-01-01

Tumor measurement is important in unresectable pediatric low-grade gliomas (pLGGs) to determine either the need for treatment or assess response. Standard methods measure the product of the largest 2 lengths from transverse, anterior-posterior, and cranio-caudal dimensions (SM, cm). This single-institution study evaluated tumor volume measurements (VM, cm) in such pLGGs. Of 50 patients treated with chemotherapy for surgically inaccessible pLGG, 8 met the inclusion criteria of having 2 or more sequential MRI studies of T1-weighted Fast-Spoiled Gradient Recalled acquisition. SM and VM were performed by 2 independent neuroradiologists. Associations of measurement methods with defined therapeutic response criteria and patient clinical status were assessed. The mean tumor size at the first MRI scan was 20 cm and 398 cm according to SM and VM, respectively. VM results did not differ significantly from SM-derived spherical volume calculations (Pearson correlation, P<0.0001) with a high interrater reliability. Both methods were concordant in defining the tumor response according to the current criteria, although radiologic progressive disease was not associated with clinical status (SM: P=0.491, VM: P=0.208). In this limited experience, volumetric analysis of unresectable pLGGs did not seem superior to the standard linear measurements for defining tumor response.

Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters.

PubMed

Ueno, Hideki; Hase, Kazuo; Hashiguchi, Yojiro; Shimazaki, Hideyuki; Tanaka, Masafumi; Miyake, Ohki; Masaki, Tadahiko; Shimada, Yoshifumi; Kinugasa, Yusuke; Mori, Yoshiyuki; Kishimoto, Mitsuo; Kameoka, Shingo; Sato, Yu; Matsuda, Keiji; Nakadoi, Koichi; Shinto, Eiji; Nakamura, Takahiro; Sugihara, Kenichi

2014-02-01

The study aimed to determine the value of a novel site-specific grading system based on quantifying poorly differentiated clusters (PDC; Grade(PDC)) in colorectal cancer (CRC). A multicenter pathologic review involving 12 institutions was performed on 3243 CRC cases (stage I, 583; II, 1331; III, 1329). Cancer clusters of ≥5 cancer cells and lacking a gland-like structure (PDCs) were counted under a ×20 objective lens in a field containing the maximum clusters. Tumors with <5, 5 to 9, and ≥10 PDCs were classified as grades G1, G2, and G3, respectively. According to Grade(PDC), 1594, 1005, and 644 tumors were classified as G1, G2, and G3 and had 5-year recurrence-free survival rates of 91.6%, 75.4%, and 59.6%, respectively (P<0.0001). Multivariate analysis showed that Grade exerted an influence on prognostic outcome independently of TNM staging; approximately 20% and 46% of stage I and II patients, respectively, were selected by Grade(PDC) as a population whose survival estimate was comparable to or even worse than that of stage III patients. Grade(PDC) surpassed TNM staging in the ability to stratify patients by recurrence-free survival (Akaike information criterion, 2915.6 vs. 2994.0) and had a higher prognostic value than American Joint Committee on Cancer (AJCC) grading (Grade(AJCC)) at all stages. Regarding judgment reproducibility of grading tumors, weighted κ among the 12 institutions was 0.40 for Grade(AJCC) and 0.52 for Grade(PDC). Grade(PDC) has a robust prognostic power and promises to be of sufficient clinical value to merit implementation as a site-specific grading system in CRC.

Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors.

PubMed

Kim, Min Jeong; Kwon, Mi Jung; Kang, Ho Suk; Choi, Kyung Chan; Nam, Eun Sook; Cho, Seong Jin; Park, Hye-Rim; Min, Soo Kee; Seo, Jinwon; Choe, Ji-Young; Park, Hyoung-Chul

2018-01-01

Mitotic counts in the World Health Organization (WHO) grading system have narrow cutoff values. True mitotic figures, however, are not always distinguishable from apoptotic bodies and darkly stained nuclei, complicating the ability of the WHO grading system to diagnose well-differentiated neuroendocrine tumors (NETs). The mitosis-specific marker phosphohistone H3 (PHH3) can identify true mitoses and grade tumors reliably. The aim of this study was to investigate the correspondence of tumor grades, as determined by PHH3 mitotic index (MI) and mitotic counts according to WHO criteria, and to determine the clinically relevant cutoffs of PHH3 MI in rectal and nonrectal gastrointestinal NETs. Mitotic counts correlated with both the Ki-67 labeling index and PHH3 MI, but the correlation with PHH3 MI was slightly higher. The PHH3 MI cutoff ≥4 correlated most closely with original WHO grades for both rectal NETs. A PHH3 MI cutoff ≥4, which could distinguish between G1 and G2 tumors, was associated with disease-free survival in patients with rectal NETs, whereas that cutoff value showed marginal significance for overall survival in patient with rectal NETs. In conclusion, the use of PHH3 ≥4 correlated most closely with original WHO grades.

Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors

PubMed Central

Kim, Min Jeong; Kang, Ho Suk; Choi, Kyung Chan; Nam, Eun Sook; Cho, Seong Jin; Park, Hye-Rim; Seo, Jinwon; Choe, Ji-Young

2018-01-01

Mitotic counts in the World Health Organization (WHO) grading system have narrow cutoff values. True mitotic figures, however, are not always distinguishable from apoptotic bodies and darkly stained nuclei, complicating the ability of the WHO grading system to diagnose well-differentiated neuroendocrine tumors (NETs). The mitosis-specific marker phosphohistone H3 (PHH3) can identify true mitoses and grade tumors reliably. The aim of this study was to investigate the correspondence of tumor grades, as determined by PHH3 mitotic index (MI) and mitotic counts according to WHO criteria, and to determine the clinically relevant cutoffs of PHH3 MI in rectal and nonrectal gastrointestinal NETs. Mitotic counts correlated with both the Ki-67 labeling index and PHH3 MI, but the correlation with PHH3 MI was slightly higher. The PHH3 MI cutoff ≥4 correlated most closely with original WHO grades for both rectal NETs. A PHH3 MI cutoff ≥4, which could distinguish between G1 and G2 tumors, was associated with disease-free survival in patients with rectal NETs, whereas that cutoff value showed marginal significance for overall survival in patient with rectal NETs. In conclusion, the use of PHH3 ≥4 correlated most closely with original WHO grades. PMID:29780816

What Is the Ideal Tumor Regression Grading System in Rectal Cancer Patients after Preoperative Chemoradiotherapy?

PubMed Central

Kim, Soo Hee; Chang, Hee Jin; Kim, Dae Yong; Park, Ji Won; Baek, Ji Yeon; Kim, Sun Young; Park, Sung Chan; Oh, Jae Hwan; Yu, Ami; Nam, Byung-Ho

2016-01-01

Purpose Tumor regression grade (TRG) is predictive of therapeutic response in rectal cancer patients after chemoradiotherapy (CRT) followed by curative resection. However, various TRG systems have been suggested, with subjective categorization, resulting in interobserver variability. This study compared the prognostic validity of four different TRG systems in order to identify the most ideal TRG system. Materials and Methods This study included 933 patients who underwent preoperative CRT and curative resection. Primary tumors alone were graded according to the American Joint Committee on Cancer (AJCC), Dworak, and Ryan TRG systems, and both primary tumors and regional lymph nodes were graded according to a modified Dworak TRG system. The ability of each TRG system to predict recurrence-free survival (RFS) and overall survival (OS) was analyzed using chi-square and C statistics. Results All four TRG systems were significantly predictive of both RFS and OS (p < 0.001 each), however none was a better predictor of prognosis than ypStage. Among the four TRGs, the mDworak TRG system was a better predictor of RFS and OS than the AJCC, Dworak, and Ryan TRG systems, and both the chi-square and C statistics were higher for the former, although the differences were not statistically significant. The combination of ypStage and the modified Dworak TRG better predicted RFS and OS than ypStage alone. Conclusion The modified Dworak TRG system for evaluation of entire tumors including regional lymph nodes is a better predictor of survival than current TRG systems for evaluation of the primary tumor alone. PMID:26511803

Correlation of serum intercellular adhesion molecule 1 and vascular endothelial growth factor with tumor grading and staging in breast cancer patients.

PubMed

Haghi, Alireza Rastgoo; Vahedi, Amir; Shekarchi, Ali Akbar; Kamran, Aziz

2017-01-01

Breast cancer is the most common cancer among women. There are several prognostic factors for this disease. The aim of this article is to explore the correlation of serum level of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM1) with tumor, node, metastasis staging and grading of breast cancer. Serum samples of 51 patients with breast cancer were assessed with enzyme-linked immunosorbent assay for the level of VEGF and ICAM1 preoperatively. After the operation, histopathologic specimens stained with hematoxylin and eosin were evaluated for tumor size, histopathologic subtype, grade, lymph node, vascular and lymphatic involvement. Then, the correlation of tumor stage and grade and serum level of markers was analyzed. There was no significant correlation between serum level of markers with vascular invasions, lymph node involvement, and menstruation. There was a weak correlation between tumor size and serum level of ICAM1 with Pearson score correlation, but there was no significant correlation with VEGF. There was no significant correlation between tumor grading and staging with the level of markers. There was a significant correlation between the level of VEGF and ICAM1 and histologic type of tumors in invasive through in situ tumors. Levels of VEGF and ICAM1 can be used as a predictor of tumor invasion and also for target therapy.

TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanlioglu, Ahter D.; Department of Medical Biology and Genetics, Akdeniz University Faculty of Medicine, Antalya; Korcum, Aylin F.

2007-11-01

Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, thismore » study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.« less

Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development

PubMed Central

Beheshti, Afshin; Wage, Justin; McDonald, J. Tyson; Lamont, Clare; Peluso, Michael; Hahnfeldt, Philip; Hlatky, Lynn

2015-01-01

The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3ε, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease. PMID:26497558

Mucosal Proliferations in Completely Examined Fallopian Tubes Accompanying Ovarian Low-grade Serous Tumors: Neoplastic Precursor Lesions or Normal Variants of Benign Mucosa?

PubMed

Wolsky, Rebecca J; Price, Matt A; Zaloudek, Charles J; Rabban, Joseph T

2018-05-01

cytologically resembled the epithelial component of SBT or LGSC. Mucosal proliferations were identified in subsets of all populations, including the control populations. Overall, type 1 proliferations were in 28% to 61% of all patients and type 2 alterations in 4% to 16%. There was no statistically significant difference in the incidence of type 1 or type 2 proliferations between the class of ovarian serous tumors (benign, SBT, LGSC), between early and advanced stage SBT, or between patients with any ovarian serous tumor and the control population of nonserous diagnoses. Type 3 alterations were only identified in patients with advanced stage SBT/LGSC and not in any early stage SBT or cystadenoma. These findings suggest that type 3 alterations floating in the fallopian tube lumen represent exfoliation of tumor cells from ovarian and/or peritoneal origin. Our study did not identify a mucosal-based proliferation of the fallopian tubes that was specific to ovarian low-grade serous tumors. Cytologically bland mucosal proliferations appear to be common in fallopian tubes from patients of all ages and unrelated to ovarian tumorigenesis. A consensus on diagnostic criteria and terminology for these types of proliferations is needed, as well as further study into their etiology, including possible association with hormonal environment.

Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors.

PubMed

Sharma, Vikas; Purkait, Suvendu; Takkar, Sonam; Malgulwar, Prit Benny; Kumar, Anupam; Pathak, Pankaj; Suri, Vaishali; Sharma, Mehar C; Suri, Ashish; Kale, Shashank Sharad; Kulshreshtha, Ritu; Sarkar, Chitra

2016-04-01

Enhancer of Zeste homologue2 (EZH2) is an epigenetic regulator that functions as oncogene in astrocytic tumors, however, EZH2 regulation remains little studied. In this study, we measured EZH2 levels in low (Gr-II,DA) and high grade (Gr-IV,GBM) astrocytic tumors and found significant increased EZH2 transcript level with grade(median DA-8.5, GBM-28.9).However, a different trend was reflected in protein levels, with GBMs showing high EZH2 LI(median-26.5) compared to DA (median 0.3). This difference in correlation of EZH2 protein and RNA levels suggested post-transcriptional regulation of EZH2, likely mediated by miRNAs. We selected eleven miRNAs that strongly predicted to target EZH2 and measured their expression. Three miRNAs (miR-26a-5p,miR27a-3p and miR-498) showed significant correlation with EZH2 protein, suggesting them as regulators of EZH2, however miR-26a-5p levels decreased with grade. ChIP analyses revealed H3K27me3 modifications in miR-26a promoter suggesting feedback loop between EZH2 and miR26a. We further measured six downstream miRNA targets of EZH2 and found significant downregulation of four (miR-181a/b and 200b/c) in GBM. Interestingly, EZH2 associated miRNAs were predicted to target 25 genes in glioma-pathway, suggesting their role in tumor formation or progression. Collectively, our work suggests EZH2 and its miRNA interactors may serve as promising biomarkers for progression of astrocytic tumors and may offer novel therapeutic strategies.

PTEN loss and chromosome 8 alterations in Gleason grade 3 prostate cancer cores predicts the presence of un-sampled grade 4 tumor: implications for active surveillance.

PubMed

Trock, Bruce J; Fedor, Helen; Gurel, Bora; Jenkins, Robert B; Knudsen, B S; Fine, Samson W; Said, Jonathan W; Carter, H Ballentine; Lotan, Tamara L; De Marzo, Angelo M

2016-07-01

Men who enter active surveillance because their biopsy exhibits only Gleason grade 3 (G3) frequently have higher grade tumor missed by biopsy. Thus, biomarkers are needed that, when measured on G3 tissue, can predict the presence of higher grade tumor in the whole prostate. We evaluated whether PTEN loss, chromosome 8q gain (MYC) and/or 8p loss (LPL) measured only on G3 cores is associated with un-sampled G4 tumor. A tissue microarray was constructed of prostatectomy tissue from patients whose prostates exhibited only Gleason score 3+3, only 3+4 or only 4+3 tumor (n=50 per group). Cores sampled only from areas of G3 were evaluated for PTEN loss by immunohistochemistry, and PTEN deletion, LPL/8p loss and MYC/8q gain by fluorescence in situ hybridization. Biomarker results were compared between Gleason score 6 vs 7 tumors using conditional logistic regression. PTEN protein loss, odds ratio=4.99, P=0.033; MYC/8q gain, odds ratio=5.36, P=0.010; and LPL/8p loss, odds ratio=3.96, P=0.003 were significantly more common in G3 cores derived from Gleason 7 vs Gleason 6 tumors. PTEN gene deletion was not statistically significant. Associations were stronger comparing Gleason 4+3 vs 6 than for Gleason 3+4 vs 6. MYC/8q gain, LPL/8p loss and PTEN protein loss measured in G3 tissue microarray cores strongly differentiate whether the core comes from a Gleason 6 or Gleason 7 tumor. If validated to predict upgrading from G3 biopsy to prostatectomy these biomarkers could reduce the likelihood of enrolling high-risk men and facilitate safe patient selection for active surveillance.

Access, Age and Grade. Policy Brief Number 2

ERIC Educational Resources Information Center

Online Submission, 2008

2008-01-01

In many low enrolment countries children are over age for their grade. Conventional indicators of enrolment rates conceal this and better indicators are needed. Over age entry and progression disadvantages late starters; generates wide age ranges in classes and results in pedagogic difficulties; and is likely to especially disadvantage older…

Gliomas: Application of Cumulative Histogram Analysis of Normalized Cerebral Blood Volume on 3 T MRI to Tumor Grading

PubMed Central

Kim, Hyungjin; Choi, Seung Hong; Kim, Ji-Hoon; Ryoo, Inseon; Kim, Soo Chin; Yeom, Jeong A.; Shin, Hwaseon; Jung, Seung Chai; Lee, A. Leum; Yun, Tae Jin; Park, Chul-Kee; Sohn, Chul-Ho; Park, Sung-Hye

2013-01-01

Background Glioma grading assumes significant importance in that low- and high-grade gliomas display different prognoses and are treated with dissimilar therapeutic strategies. The objective of our study was to retrospectively assess the usefulness of a cumulative normalized cerebral blood volume (nCBV) histogram for glioma grading based on 3 T MRI. Methods From February 2010 to April 2012, 63 patients with astrocytic tumors underwent 3 T MRI with dynamic susceptibility contrast perfusion-weighted imaging. Regions of interest containing the entire tumor volume were drawn on every section of the co-registered relative CBV (rCBV) maps and T2-weighted images. The percentile values from the cumulative nCBV histograms and the other histogram parameters were correlated with tumor grades. Cochran’s Q test and the McNemar test were used to compare the diagnostic accuracies of the histogram parameters after the receiver operating characteristic curve analysis. Using the parameter offering the highest diagnostic accuracy, a validation process was performed with an independent test set of nine patients. Results The 99th percentile of the cumulative nCBV histogram (nCBV C99), mean and peak height differed significantly between low- and high-grade gliomas (P = <0.001, 0.014 and <0.001, respectively) and between grade III and IV gliomas (P = <0.001, 0.001 and <0.001, respectively). The diagnostic accuracy of nCBV C99 was significantly higher than that of the mean nCBV (P = 0.016) in distinguishing high- from low-grade gliomas and was comparable to that of the peak height (P = 1.000). Validation using the two cutoff values of nCBV C99 achieved a diagnostic accuracy of 66.7% (6/9) for the separation of all three glioma grades. Conclusion Cumulative histogram analysis of nCBV using 3 T MRI can be a useful method for preoperative glioma grading. The nCBV C99 value is helpful in distinguishing high- from low-grade gliomas and grade IV from III gliomas. PMID:23704910

Breed- and age-related differences in canine mammary tumors

PubMed Central

Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

2016-01-01

Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

A neurogenic tumor containing a low-grade malignant peripheral nerve sheath tumor (MPNST) component with loss of p16 expression and homozygous deletion of CDKN2A/p16: a case report showing progression from a neurofibroma to a high-grade MPNST.

PubMed

Tajima, Shogo; Koda, Kenji

2015-01-01

Development of malignant peripheral nerve sheath tumors (MPNSTs) is a stepwise process that involves the alteration of many cell cycle regulators and the double inactivation of the NF1 gene. Inactivation of the TP53 gene and deletion of the CDKN2A/p16 gene are known to play an important role in the process. Herein, we present a 19-year-old man with a familial history of neurofibromatosis type 1, in whom the tumor arose from the intercostal nerve and showed 3 components: a neurofibroma, a low-grade MPNST, and a high-grade MPNST. Loss of p16 expression and homozygous deletion of the CDKN2A/p16 gene were observed in both the low-grade and the high-grade MPNST. In contrast to low-grade MPNSTs, high-grade MPNSTs generally tend to lose expression of p16 and harbor homozygous deletion of the CDKN2A/p16 gene. Loss of p16 expression and homozygous deletion of the CDKN2A/p16 gene in low-grade MPNST in our case might be related to its progression to high-grade MPNST. To the best of our knowledge, this is the first study correlating the p16 expression status and CDKN2A/p16 gene alteration in low-grade MPNSTs.

Serial MR diffusion to predict treatment response in high-grade pediatric brain tumors: a comparison of regional and voxel-based diffusion change metrics

PubMed Central

Rodriguez Gutierrez, Daniel; Manita, Muftah; Jaspan, Tim; Dineen, Robert A.; Grundy, Richard G.; Auer, Dorothee P.

2013-01-01

Background Assessment of treatment response by measuring tumor size is known to be a late and potentially confounded response index. Serial diffusion MRI has shown potential for allowing earlier and possibly more reliable response assessment in adult patients, with limited experience in clinical settings and in pediatric brain cancer. We present a retrospective study of clinical MRI data in children with high-grade brain tumors to assess and compare the values of several diffusion change metrics to predict treatment response. Methods Eighteen patients (age range, 1.9–20.6 years) with high-grade brain tumors and serial diffusion MRI (pre- and posttreatment interval range, 1–16 weeks posttreatment) were identified after obtaining parental consent. The following diffusion change metrics were compared with the clinical response status assessed at 6 months: (1) regional change in absolute and normalized apparent diffusivity coefficient (ADC), (2) voxel-based fractional volume of increased (fiADC) and decreased ADC (fdADC), and (3) a new metric based on the slope of the first principal component of functional diffusion maps (fDM). Results Responders (n = 12) differed significantly from nonresponders (n = 6) in all 3 diffusional change metrics demonstrating higher regional ADC increase, larger fiADC, and steeper slopes (P < .05). The slope method allowed the best response prediction (P < .01, η2 = 0.78) with a classification accuracy of 83% for a slope of 58° using receiver operating characteristic (ROC) analysis. Conclusions We demonstrate that diffusion change metrics are suitable response predictors for high-grade pediatric tumors, even in the presence of variable clinical diffusion imaging protocols. PMID:23585630

Whole-tumor histogram analysis of the cerebral blood volume map: tumor volume defined by 11C-methionine positron emission tomography image improves the diagnostic accuracy of cerebral glioma grading.

PubMed

Wu, Rongli; Watanabe, Yoshiyuki; Arisawa, Atsuko; Takahashi, Hiroto; Tanaka, Hisashi; Fujimoto, Yasunori; Watabe, Tadashi; Isohashi, Kayako; Hatazawa, Jun; Tomiyama, Noriyuki

2017-10-01

This study aimed to compare the tumor volume definition using conventional magnetic resonance (MR) and 11C-methionine positron emission tomography (MET/PET) images in the differentiation of the pre-operative glioma grade by using whole-tumor histogram analysis of normalized cerebral blood volume (nCBV) maps. Thirty-four patients with histopathologically proven primary brain low-grade gliomas (n = 15) and high-grade gliomas (n = 19) underwent pre-operative or pre-biopsy MET/PET, fluid-attenuated inversion recovery, dynamic susceptibility contrast perfusion-weighted magnetic resonance imaging, and contrast-enhanced T1-weighted at 3.0 T. The histogram distribution derived from the nCBV maps was obtained by co-registering the whole tumor volume delineated on conventional MR or MET/PET images, and eight histogram parameters were assessed. The mean nCBV value had the highest AUC value (0.906) based on MET/PET images. Diagnostic accuracy significantly improved when the tumor volume was measured from MET/PET images compared with conventional MR images for the parameters of mean, 50th, and 75th percentile nCBV value (p = 0.0246, 0.0223, and 0.0150, respectively). Whole-tumor histogram analysis of CBV map provides more valuable histogram parameters and increases diagnostic accuracy in the differentiation of pre-operative cerebral gliomas when the tumor volume is derived from MET/PET images.

Resonant Raman spectra of grades of human brain glioma tumors reveal the content of tryptophan by the 1588 cm-1 mode

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Zhou, Lixin; Zhu, Ke; Liu, Yulong; Zhang, Lin; Boydston-White, Susie; Cheng, Gangge; Pu, Yang; Bidyut, Das; Alfano, Robert R.

2015-03-01

RR spectra of brain normal tissue, gliomas in low grade I and II, and malignant glioma tumors in grade III and IV were measured using a confocal micro Raman spectrometer. This report focus on the relative contents of tryptophan (W) in various grades of brain glioma tumors by the intrinsic molecular resonance Raman (RR) spectroscopy method using the 1588cm-1 of tryptophan mode by 532 nm excitation. The RR spectra of key fingerprints of tryptophan, with a main vibrational mode at 1588cm-1 (W8b), were observed. It was found that tryptophan contribution was accumulated in grade I to IV gliomas and the mode of 1588cm-1 in grade III and IV malignant gliomas were enhanced by resonance.

Failing to progress or progressing to fail? Age-for-grade heterogeneity and grade repetition in primary schools in Karonga district, northern Malawi

PubMed Central

Sunny, Bindu S.; Elze, Markus; Chihana, Menard; Gondwe, Levie; Crampin, Amelia C.; Munkhondya, Masoyaona; Kondowe, Scotch; Glynn, Judith R.

2018-01-01

Timely progression through school is an important measure for school performance, completion and the onset of other life transitions for adolescents. This study examines the risk factors for grade repetition and establishes the extent to which age-for-grade heterogeneity contributes to subsequent grade repetition at early and later stages of school. Using data from a demographic surveillance site in Karonga district, northern Malawi, a cohort of 8174 respondents (ages 5–24 years) in primary school was followed in 2010 and subsequent grade repetition observed in 2011. Grade repetition was more common among those at early (grades 1–3) and later (grades 7–8) stages of school, with little variation by sex. Being under-age or over-age in school has different implications on schooling outcomes, depending on the stage of schooling. After adjusting for other risk factors, boys and girls who were under-age at early stages were at least twice as likely to repeat a grade as those at the official age-for-grade (girls: adjusted OR 2.06 p < 0.01; boys: adjusted OR 2.37 p < 0.01); while those over-age at early stages were about 30% less likely to repeat (girls: adjusted OR 0.65 p < 0.01; boys: adjusted OR 0.72 p < 0.01). Being under/over-age at later grades (4–8) was not associated with subsequent repetition but being over-age was associated with dropout. Other risk factors identified that were associated with repetition included both family-level factors (living away from their mother, having young children in the household, lower paternal education) and school-level factors (higher student-teacher ratio, proportion of female teachers and schools without access to water). Reducing direct and indirect costs of schooling for households; and improving school quality and resources at early stages of school may enable timely progression at early stages for greater retention at later stages. PMID:29391662

Failing to progress or progressing to fail? Age-for-grade heterogeneity and grade repetition in primary schools in Karonga district, northern Malawi.

PubMed

Sunny, Bindu S; Elze, Markus; Chihana, Menard; Gondwe, Levie; Crampin, Amelia C; Munkhondya, Masoyaona; Kondowe, Scotch; Glynn, Judith R

2017-01-01

Timely progression through school is an important measure for school performance, completion and the onset of other life transitions for adolescents. This study examines the risk factors for grade repetition and establishes the extent to which age-for-grade heterogeneity contributes to subsequent grade repetition at early and later stages of school. Using data from a demographic surveillance site in Karonga district, northern Malawi, a cohort of 8174 respondents (ages 5-24 years) in primary school was followed in 2010 and subsequent grade repetition observed in 2011. Grade repetition was more common among those at early (grades 1-3) and later (grades 7-8) stages of school, with little variation by sex. Being under-age or over-age in school has different implications on schooling outcomes, depending on the stage of schooling. After adjusting for other risk factors, boys and girls who were under-age at early stages were at least twice as likely to repeat a grade as those at the official age-for-grade (girls: adjusted OR 2.06 p < 0.01; boys: adjusted OR 2.37 p < 0.01); while those over-age at early stages were about 30% less likely to repeat (girls: adjusted OR 0.65 p < 0.01; boys: adjusted OR 0.72 p < 0.01). Being under/over-age at later grades (4-8) was not associated with subsequent repetition but being over-age was associated with dropout. Other risk factors identified that were associated with repetition included both family-level factors (living away from their mother, having young children in the household, lower paternal education) and school-level factors (higher student-teacher ratio, proportion of female teachers and schools without access to water). Reducing direct and indirect costs of schooling for households; and improving school quality and resources at early stages of school may enable timely progression at early stages for greater retention at later stages.

Non-small cell lung cancer: Whole-lesion histogram analysis of the apparent diffusion coefficient for assessment of tumor grade, lymphovascular invasion and pleural invasion.

PubMed

Tsuchiya, Naoko; Doai, Mariko; Usuda, Katsuo; Uramoto, Hidetaka; Tonami, Hisao

2017-01-01

Investigating the diagnostic accuracy of histogram analyses of apparent diffusion coefficient (ADC) values for determining non-small cell lung cancer (NSCLC) tumor grades, lymphovascular invasion, and pleural invasion. We studied 60 surgically diagnosed NSCLC patients. Diffusion-weighted imaging (DWI) was performed in the axial plane using a navigator-triggered single-shot, echo-planar imaging sequence with prospective acquisition correction. The ADC maps were generated, and we placed a volume-of-interest on the tumor to construct the whole-lesion histogram. Using the histogram, we calculated the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC, skewness, and kurtosis. Histogram parameters were correlated with tumor grade, lymphovascular invasion, and pleural invasion. We performed a receiver operating characteristics (ROC) analysis to assess the diagnostic performance of histogram parameters for distinguishing different pathologic features. The ADC mean, 10th, 25th, 50th, 75th, 90th, and 95th percentiles showed significant differences among the tumor grades. The ADC mean, 25th, 50th, 75th, 90th, and 95th percentiles were significant histogram parameters between high- and low-grade tumors. The ROC analysis between high- and low-grade tumors showed that the 95th percentile ADC achieved the highest area under curve (AUC) at 0.74. Lymphovascular invasion was associated with the ADC mean, 50th, 75th, 90th, and 95th percentiles, skewness, and kurtosis. Kurtosis achieved the highest AUC at 0.809. Pleural invasion was only associated with skewness, with the AUC of 0.648. ADC histogram analyses on the basis of the entire tumor volume are able to stratify NSCLCs' tumor grade, lymphovascular invasion and pleural invasion.

Non-small cell lung cancer: Whole-lesion histogram analysis of the apparent diffusion coefficient for assessment of tumor grade, lymphovascular invasion and pleural invasion

PubMed Central

Tsuchiya, Naoko; Doai, Mariko; Usuda, Katsuo; Uramoto, Hidetaka

2017-01-01

Purpose Investigating the diagnostic accuracy of histogram analyses of apparent diffusion coefficient (ADC) values for determining non-small cell lung cancer (NSCLC) tumor grades, lymphovascular invasion, and pleural invasion. Materials and methods We studied 60 surgically diagnosed NSCLC patients. Diffusion-weighted imaging (DWI) was performed in the axial plane using a navigator-triggered single-shot, echo-planar imaging sequence with prospective acquisition correction. The ADC maps were generated, and we placed a volume-of-interest on the tumor to construct the whole-lesion histogram. Using the histogram, we calculated the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC, skewness, and kurtosis. Histogram parameters were correlated with tumor grade, lymphovascular invasion, and pleural invasion. We performed a receiver operating characteristics (ROC) analysis to assess the diagnostic performance of histogram parameters for distinguishing different pathologic features. Results The ADC mean, 10th, 25th, 50th, 75th, 90th, and 95th percentiles showed significant differences among the tumor grades. The ADC mean, 25th, 50th, 75th, 90th, and 95th percentiles were significant histogram parameters between high- and low-grade tumors. The ROC analysis between high- and low-grade tumors showed that the 95th percentile ADC achieved the highest area under curve (AUC) at 0.74. Lymphovascular invasion was associated with the ADC mean, 50th, 75th, 90th, and 95th percentiles, skewness, and kurtosis. Kurtosis achieved the highest AUC at 0.809. Pleural invasion was only associated with skewness, with the AUC of 0.648. Conclusions ADC histogram analyses on the basis of the entire tumor volume are able to stratify NSCLCs' tumor grade, lymphovascular invasion and pleural invasion. PMID:28207858

Factors Influencing Neurocognitive Outcomes in Young Patients With Benign and Low-Grade Brain Tumors Treated With Stereotactic Conformal Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jalali, Rakesh, E-mail: rjalali@tmc.gov.i; Mallick, Indranil; Dutta, Debnarayan

2010-07-15

Purpose: To present the effect of radiotherapy doses to different volumes of normal structures on neurocognitive outcomes in young patients with benign and low-grade brain tumors treated prospectively with stereotactic conformal radiotherapy (SCRT). Methods and Materials: Twenty-eight patients (median age, 13 years) with residual/progressive brain tumors (10 craniopharyngioma, 8 cerebellar astrocytoma, 6 optic pathway glioma and 4 cerebral low-grade glioma) were treated with SCRT to a dose of 54 Gy in 30 fractions over 6 weeks. Prospective neuropsychological assessments were done at baseline before RT and at subsequent follow-up examinations. The change in intelligence quotient (IQ) scores was correlated withmore » various factors, including dose-volume to normal structures. Results: Although the overall mean full-scale IQ (FSIQ) at baseline before RT remained unchanged at 2-year follow-up after SCRT, one third of patients did show a >10% decline in FSIQ as compared with baseline. Logistic regression analysis demonstrated that patients aged <15 years had a significantly higher chance of developing a >10% drop in FSIQ than older patients (53% vs. 10%, p = 0.03). Dosimetric comparison in patients showing a >10% decline vs. patients showing a <10% decline in IQ revealed that patients receiving >43.2 Gy to >13% of volume of the left temporal lobe were the ones to show a significant drop in FSIQ (p = 0.048). Radiotherapy doses to other normal structures, including supratentorial brain, right temporal lobe, and frontal lobes, did not reveal any significant correlation. Conclusion: Our prospectively collected dosimetric data show younger age and radiotherapy doses to left temporal lobe to be predictors of neurocognitive decline, and may well be used as possible dose constraints for high-precision radiotherapy planning.« less

Measurements of diagnostic examination performance and correlation analysis using microvascular leakage, cerebral blood volume, and blood flow derived from 3T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in glial tumor grading.

PubMed

Server, Andrés; Graff, Bjørn A; Orheim, Tone E Døli; Schellhorn, Till; Josefsen, Roger; Gadmar, Øystein B; Nakstad, Per H

2011-06-01

To assess the diagnostic accuracy of microvascular leakage (MVL), cerebral blood volume (CBV) and blood flow (CBF) values derived from dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MR imaging) for grading of cerebral glial tumors, and to estimate the correlation between vascular permeability/perfusion parameters and tumor grades. A prospective study of 79 patients with cerebral glial tumors underwent DSC-MR imaging. Normalized relative CBV (rCBV) and relative CBF (rCBF) from tumoral (rCBVt and rCBFt), peri-enhancing region (rCBVe and rCBFe), and the value in the tumor divided by the value in the peri-enhancing region (rCBVt/e and rCBFt/e), as well as MVL, expressed as the leakage coefficient K(2) were calculated. Hemodynamic variables and tumor grades were analyzed statistically and with Pearson correlations. Receiver operating characteristic (ROC) curve analyses were also performed for each of the variables. The differences in rCBVt and the maximum MVL (MVL(max)) values were statistically significant among all tumor grades. Correlation analysis using Pearson was as follows: rCBVt and tumor grade, r = 0.774; rCBFt and tumor grade, r = 0.417; MVL(max) and tumor grade, r = 0.559; MVL(max) and rCBVt, r = 0.440; MVL(max) and rCBFt, r = 0.192; and rCBVt and rCBFt, r = 0.605. According to ROC analyses for distinguishing tumor grade, rCBVt showed the largest areas under ROC curve (AUC), except for grade III from IV. Both rCBVt and MVL(max) showed good discriminative power in distinguishing all tumor grades. rCBVt correlated strongly with tumor grade; the correlation between MVL(max) and tumor grade was moderate.

Validation of a Proposed Tumor Regression Grading Scheme for Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy as a Prognostic Indicator for Survival.

PubMed

Lee, Sun Mi; Katz, Matthew H G; Liu, Li; Sundar, Manonmani; Wang, Hua; Varadhachary, Gauri R; Wolff, Robert A; Lee, Jeffrey E; Maitra, Anirban; Fleming, Jason B; Rashid, Asif; Wang, Huamin

2016-12-01

Neoadjuvant therapy has been increasingly used to treat patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Although the College of American Pathologists (CAP) grading scheme for tumor response in posttherapy specimens has been used, its clinical significance has not been validated. Previously, we proposed a 3-tier histologic tumor regression grading (HTRG) scheme (HTRG 0, no viable tumor; HTRG 1, <5% viable tumor cells; HTRG 2, ≥5% viable tumor cells) and showed that the 3-tier HTRG scheme correlated with prognosis. In this study, we sought to validate our proposed HTRG scheme in a new cohort of 167 consecutive PDAC patients who completed neoadjuvant therapy and pancreaticoduodenectomy. We found that patients with HTRG 0 or 1 were associated with a lower frequency of lymph node metastasis (P=0.004) and recurrence (P=0.01), lower ypT (P<0.001) and AJCC stage (P<0.001), longer disease-free survival (DFS, P=0.004) and overall survival (OS, P=0.02) than those with HTRG 2. However, there was no difference in either DFS or OS between the groups with CAP grade 2 and those with CAP grade 3 (P>0.05). In multivariate analysis, HTRG grade 0 or 1 was an independent prognostic factor for better DFS (P=0.03), but not OS. Therefore we validated the proposed HTRG scheme from our previous study. The proposed HTRG scheme is simple and easy to apply in practice by pathologists and might be used as a successful surrogate for longer DFS in patients with potentially resectable PDAC who completed neoadjuvant therapy and surgery.

KI-67 heterogeneity in well differentiated gastro-entero-pancreatic neuroendocrine tumors: when is biopsy reliable for grade assessment?

PubMed

Grillo, Federica; Valle, Luca; Ferone, Diego; Albertelli, Manuela; Brisigotti, Maria Pia; Cittadini, Giuseppe; Vanoli, Alessandro; Fiocca, Roberto; Mastracci, Luca

2017-09-01

Ki-67 heterogeneity can impact on gastroenteropancreatic neuroendocrine tumor grade assignment, especially when tissue is scarce. This work is aimed at devising adequacy criteria for grade assessment in biopsy specimens. To analyze the impact of biopsy size on reliability, 360 virtual biopsies of different thickness and lengths were constructed. Furthermore, to estimate the mean amount of non-neoplastic tissue component present in biopsies, 28 real biopsies were collected, the non-neoplastic components (fibrosis and inflammation) quantified and the effective area of neoplastic tissue calculated for each biopsy. Heterogeneity of Ki-67 distribution, G2 tumors and biopsy size all play an important role in reducing the reliability of biopsy samples in Ki-67-based grade assignment. In particular in G2 cases, 59.9% of virtual biopsies downgraded the tumor and the smaller the biopsy, the more frequent downgrading occurs. In real biopsies the presence of non-neoplastic tissue reduced the available total area by a mean of 20%. By coupling the results from these two different approaches we show that both biopsy size and non-neoplastic component must be taken into account for biopsy adequacy. In particular, we can speculate that if the minimum biopsy area, necessary to confidently (80% concordance) grade gastro-entero-pancreatic neuroendocrine tumors on virtual biopsies ranges between 15 and 30 mm 2 , and if real biopsies are on average composed of only 80% of neoplastic tissue, then biopsies with a surface area not <12 mm 2 should be performed; using 18G needles, this corresponds to a minimum total length of 15 mm.

Biologic behavior and prognostic factors for mast cell tumors of the canine muzzle: 24 cases (1990-2001).

PubMed

Gieger, Tracy L; Théon, Alain P; Werner, Jonathan A; McEntee, Margaret C; Rassnick, Kenneth M; DeCock, Hilde E V

2003-01-01

The medical records of 24 dogs with histologically confirmed mast cell tumors (MCT) of the muzzle were retrospectively evaluated to determine their biologic behavior and prognostic factors. Information on signalment, tumor grade and stage, treatment methods, and pattern of and time to failure and death was obtained from the medical record. Twenty-three dogs were treated with combinations of radiotherapy, surgery, and chemotherapy; 1 dog received no treatment. There were 2 Grade 1, 15 Grade 11, and 7 Grade III tumors. Tumors were stage 0 (n = 8), stage 1 (5), stage 2 (6), stage 3 (4), and stage 4 (1). Mean and median survival times of treated dogs were 36 and 30 months, respectively. Prognostic factors affecting survival time included tumor grade and presence of metastasis at diagnosis. Dogs with Grade I and II tumors survived longer than dogs with Grade III tumors. Variables, including sex, age, gross versus microscopic disease, and treatment type were not found to affect survival. Local control rate was 75% at 1 year and 50% at 3 years. Tumor grade was the only variable found to affect local control. Dogs with Grade I tumors had longer disease-free intervals than those with Grade II tumors, and dogs with Grade II tumors had longer disease-free intervals than dogs with Grade III tumors. Eight of 9 dogs dying of MCT had local or regional disease progression. Muzzle MCT a rebiologically aggressive tumors with higher regional metastatic rates than previously reported for MCT in other sites.

Comparison of Tumor- and Bone Marrow-Derived Mesenchymal Stromal/Stem Cells from Patients with High-Grade Osteosarcoma

PubMed Central

Le Nail, Louis-Romée; Brennan, Meadhbh; Rosset, Philippe; Piloquet, Philippe; Pichon, Olivier; Le Caignec, Cédric; Crenn, Vincent; Layrolle, Pierre; Hérault, Olivier; De Pinieux, Gonzague

2018-01-01

Osteosarcoma (OS) is suspected to originate from dysfunctional mesenchymal stromal/stem cells (MSC). We sought to identify OS-derived cells (OSDC) with potential cancer stem cell (CSC) properties by comparing OSDC to MSC derived from bone marrow of patients. This study included in vitro characterization with sphere forming assays, differentiation assays, cytogenetic analysis, and in vivo investigations of their tumorigenicity and tumor supportive capacities. Primary cell lines were isolated from nine high-grade OS samples. All primary cell lines demonstrated stromal cell characteristics. Compared to MSC, OSDC presented a higher ability to form sphere clones, indicating a potential CSC phenotype, and were more efficient at differentiation towards osteoblasts. None of the OSDC displayed the complex chromosome rearrangements typical of high grade OS and none of them induced tumors in immunodeficient mice. However, two OSDC demonstrated focused genomic abnormalities. Three out of seven, and six out of seven OSDC showed a supportive role on local tumor development, and on metastatic progression to the lungs, respectively, when co-injected with OS cells in nude mice. The observation of OS-associated stromal cells with rare genetic abnormalities and with the capacity to sustain tumor progression may have implications for future tumor treatments. PMID:29494553

Oncocytoma-like renal tumor with transformation toward high-grade oncocytic carcinoma: a unique case with morphologic, immunohistochemical, and genomic characterization.

PubMed

Sirintrapun, Sahussapont J; Geisinger, Kim R; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L; Ghazalpour, Anatole; Bender, Ryan P; Gatalica, Zoran

2014-10-01

Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt-Hogg-Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the development of an

Endometrial cancer: correlation of apparent diffusion coefficient with tumor grade, depth of myometrial invasion, and presence of lymph node metastases.

PubMed

Rechichi, Gilda; Galimberti, Stefania; Signorelli, Mauro; Franzesi, Cammillo Talei; Perego, Patrizia; Valsecchi, Maria Grazia; Sironi, Sandro

2011-07-01

The objective of our study was to investigate whether apparent diffusion coefficient (ADC) values of endometrial cancer differ from those of normal endometrium and myometrium and whether they vary according to histologic tumor grade, the depth of myometrial invasion, or lymph node status. Seventy patients with histologically proved endometrial cancer and 36 control subjects with normal endometrium were enrolled in this prospective study. T2-weighted, dynamic T1-weighted, and diffusion-weighted images with b values of 0 and 1000 s/mm(2) were obtained of all patients. The ADC values of endometrial cancer, normal endometrium, and normal myometrium were recorded. Tumor grade, the depth of myometrial invasion, and lymph node status were assessed at postoperative histopathologic analysis. The mean (± SD) ADC value (10(-3) mm(2)/s) of endometrial cancer (0.77 ± 0.12) was significantly lower than that of normal endometrium (1.31 ± 0.11, p < 0.0001) and normal myometrium (1.52 ± 0.21, p < 0.0001), with no overlap between the two former distributions. There was no significant difference between ADC values of endometrial cancer tissue in patients with tumor grade 1 (0.79 ± 0.08, n = 14), grade 2 (0.76 ± 0.14, n = 40), or grade 3 (0.75 ± 0.12, n = 16) (p = 0.67); in patients with deep (0.77 ± 0.13, n = 18) and those with superficial (0.76 ± 0.12, n = 52) myometrial invasion (p = 0.87); and in patients with (0.78 ± 0.10, n = 6) and those without (0.75 ± 0.14, n = 39) lymph node metastases (p = 0.64). ADC values allow normal endometrium to be differentiated from endometrial carcinoma; however, they do not correlate with histologic tumor grade, the depth of myometrial invasion, or whether lymph node metastases are present.

Conditional Deletion of the Pten Gene in the Mouse Prostate Induces Prostatic Intraepithelial Neoplasms at Early Ages but a Slow Progression to Prostate Tumors

PubMed Central

Zhu, Chunfang; Lee, Suk Hyung; Ye, Ding-Wei; Luong, Richard; Sun, Zijie

2013-01-01

The PTEN tumor suppressor gene is frequently inactivated in human prostate cancer. Using Osr1 (odd skipped related 1)-Cre mice, we generated a novel conditional Pten knockout mouse strain, PtenLoxP:Osr1-Cre. Conditional biallelic and monoallelic Pten knockout mice were viable. Deletion of Pten expression was detected in the prostate of PtenLoxP/LoxP:Osr1-Cre mice as early as 2 weeks of age. Intriguingly, PtenLoxP/LoxP:Osr1-Cre mice develop high-grade prostatic intraepithelial neoplasms (PINs) with high penetrance as early as one-month of age, and locally invasive prostatic tumors after 12-months of age. PtenLoxP/+:Osr1-Cre mice show only mild oncogenic changes after 8-weeks of age. Castration of PtenLoxP/LoxP:Osr1-Cre mice shows no significant regression of prostate tumors, although a shift of androgen receptor (AR) staining from the nuclei to cytoplasm is observed in Pten null tumor cells of castrated mice. Enhanced Akt activity is observed in Pten null tumor cells of castrated PtenLoxP/LoxP:Osr1-Cre. This study provides a novel mouse model that can be used to investigate a primary role of Pten in initiating oncogenic transformation in the prostate and to examine other genetic and epigenetic changes that are required for tumor progression in the mouse prostate. PMID:23308230

42 CFR 21.28 - Age requirements, Regular Corps, senior assistant grade and below.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Age requirements, Regular Corps, senior assistant... SERVICES PERSONNEL COMMISSIONED OFFICERS Appointment § 21.28 Age requirements, Regular Corps, senior... permanent assistant grade, or (c) after age 37 to the permanent senior assistant grade: Provided, That the...

Clinicopathological characteristics of duodenal epithelial neoplasms: Focus on tumors with a gastric mucin phenotype (pyloric gland-type tumors).

PubMed

Mitsuishi, Takehiro; Hamatani, Shigeharu; Hirooka, Shinichi; Fukasawa, Nei; Aizawa, Daisuke; Hara, Yuko; Dobashi, Akira; Goda, Kenichi; Fukuda, Takahiro; Saruta, Masayuki; Urashima, Mitsuyoshi; Ikegami, Masahiro

2017-01-01

Epithelial tumors less commonly occur in the duodenum than in the stomach or large intestine. The clinicopathological characteristics of duodenal epithelial tumors remain a matter of debate. We therefore studied resected specimens to investigate the clinicopathological characteristics of duodenal epithelial tumors. Among duodenal epithelial tumors resected endoscopically or surgically in our hospital, we studied the clinicopathological characteristics of 110 adenomas or intramucosal carcinomas. The grade of atypia of all tumors was classified into 3 groups according to the World Health Organization (WHO) 2010 classification. The tumors were immunohistochemically evaluated to determine the frequency of differentiation toward fundic glands. As for patient characteristics, there were 76 men (75.2%) and 25 women (24.8%), with a median age of 65 years (range, 34 to 84). The tumors most commonly arose in the first to second part of the duodenum. Many lesions were flat, and the median tumor diameter was 8.0 mm. The lesions were classified into 2 types according to mucin phenotype: intestinal-type tumors (98 lesions, 89.1%) and gastric-type tumors (12 lesions, 10.9%). Intestinal-type tumors were subdivided into 2 groups: tubular-type tumors (91 lesions, 82.7%) and tubulovillous-type tumors (7 lesions, 6.4%). Gastric-type tumors were classified into 2 types: foveolar type (3 lesions, 2.7%) and pyloric gland-type (PG) tumors (9 lesions, 8.2%). The grade of atypia was significantly higher in gastric-type tumors (p<0.01). PG tumors were gastric-type tumors characterized by pyloric glands and findings suggesting differentiation toward fundic glands. About 10% of the duodenal tumors had a gastric-type mucin phenotype. Gastric-type tumors showed high-grade atypia. In particular, PG tumors showed similarities to PG tumors of the stomach, such as differentiation toward fundic glands.

Collecting and Storing Blood and Brain Tumor Tissue Samples From Children With Brain Tumors

ClinicalTrials.gov

2017-12-11

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Newly Diagnosed Childhood Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma

42 CFR 21.28 - Age requirements, Regular Corps, senior assistant grade and below.

Code of Federal Regulations, 2014 CFR

2014-10-01

... assistant grade and below. No candidate for appointment to the Regular Corps, except in the nurse category, shall be appointed (a) after age 31 to the permanent junior assistant grade, (b) after age 34 to the... 42 Public Health 1 2014-10-01 2014-10-01 false Age requirements, Regular Corps, senior assistant...

42 CFR 21.28 - Age requirements, Regular Corps, senior assistant grade and below.

Code of Federal Regulations, 2013 CFR

2013-10-01

... assistant grade and below. No candidate for appointment to the Regular Corps, except in the nurse category, shall be appointed (a) after age 31 to the permanent junior assistant grade, (b) after age 34 to the... 42 Public Health 1 2013-10-01 2013-10-01 false Age requirements, Regular Corps, senior assistant...

42 CFR 21.28 - Age requirements, Regular Corps, senior assistant grade and below.

Code of Federal Regulations, 2012 CFR

2012-10-01

... assistant grade and below. No candidate for appointment to the Regular Corps, except in the nurse category, shall be appointed (a) after age 31 to the permanent junior assistant grade, (b) after age 34 to the... 42 Public Health 1 2012-10-01 2012-10-01 false Age requirements, Regular Corps, senior assistant...

Advanced age negatively impacts survival in an experimental brain tumor model.

PubMed

Ladomersky, Erik; Zhai, Lijie; Gritsina, Galina; Genet, Matthew; Lauing, Kristen L; Wu, Meijing; James, C David; Wainwright, Derek A

2016-09-06

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.

PubMed

Otto, Benjamin; Gruner, Katharina; Heinlein, Christina; Wegwitz, Florian; Nollau, Peter; Ylstra, Bauke; Pantel, Klaus; Schumacher, Udo; Baumbusch, Lars O; Martin-Subero, José Ignacio; Siebert, Reiner; Wagener, Christoph; Streichert, Thomas; Deppert, Wolfgang; Tolstonog, Genrich V

2013-03-15

Mammary carcinomas developing in SV40 transgenic WAP-T mice arise in two distinct histological phenotypes: as differentiated low-grade and undifferentiated high-grade tumors. We integrated different types of information such as histological grading, analysis of aCGH-based gene copy number and gene expression profiling to provide a comprehensive molecular description of mammary tumors in WAP-T mice. Applying a novel procedure for the correlation of gene copy number with gene expression on a global scale, we observed in tumor samples a global coherence between genotype and transcription. This coherence can be interpreted as a matched transcriptional regulation inherited from the cells of tumor origin and determined by the activity of cancer driver genes. Despite common recurrent genomic aberrations, e.g. gain of chr. 15 in most WAP-T tumors, loss of chr. 19 frequently occurs only in low-grade tumors. These tumors show features of "basal-like" epithelial differentiation, particularly expression of keratin 14. The high-grade tumors are clearly separated from the low-grade tumors by strong expression of the Met gene and by coexpression of epithelial (e.g. keratin 18) and mesenchymal (e.g. vimentin) markers. In high-grade tumors, the expression of the nonmutated Met protein is associated with Met-locus amplification and Met activity. The role of Met as a cancer driver gene is supported by the contribution of active Met signaling to motility and growth of mammary tumor-derived cells. Finally, we discuss the independent origin of low- and high-grade tumors from distinct cells of tumor origin, possibly luminal progenitors, distinguished by Met gene expression and Met signaling. Copyright © 2012 UICC.

TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system

PubMed Central

Klöppel, G.; Alhman, H.; Caplin, M.; Couvelard, A.; de Herder, W. W.; Erikssson, B.; Falchetti, A.; Falconi, M.; Komminoth, P.; Körner, M.; Lopes, J. M.; McNicol, A-M.; Nilsson, O.; Perren, A.; Scarpa, A.; Scoazec, J-Y.; Wiedenmann, B.

2006-01-01

The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor–node–metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients. PMID:16967267

Methylation status as a predictor of intravesical Bacillus Calmette-Guérin (BCG) immunotherapy response of high grade non-muscle invasive bladder tumor.

PubMed

Husek, Petr; Pacovsky, Jaroslav; Chmelarova, Marcela; Podhola, Miroslav; Brodak, Milos

2017-06-01

Genetic and epigenetic alterations play an important role in urothelial cancer pathogenesis. Deeper understanding of these processes could help us achieve better diagnosis and management of this life-threatening disease. The aim of this research was to evaluate the methylation status of selected tumor suppressor genes for predicting BCG response in patients with high grade non-muscle-invasive bladder tumor (NMIBC). We retrospectively evaluated 82 patients with high grade non-muscle-invasive bladder tumor (stage Ta, T1, CIS) who had undergone BCG instillation therapy. We compared epigenetic methylation status in BCG-responsive and BCG-failure groups. We used the MS-MLPA (Methylation-Specific Multiplex Ligation-Dependent Probe Amplification probe sets ME001 and ME004. The control group was 13 specimens of normal urotel (bladder tissue)). Newly identified methylations in high grade NMIBC were found in MUS81a, NTRK1 and PCCA. The methylation status of CDKN2B (P=0.00312 ** ) and MUS81a (P=0.0191 * ) is associated with clinical outcomes of BCG instillation therapy response. CDKN2B and MUS81a unmethylation was found in BCG failure patients. The results show that the methylation status of selected tumor suppressor genes (TSGs) has the potential for predicting BCG response in patients with NMIBC high grade tumors. Tumor suppressor genes such as CDKN2b, MUS81a, PFM-1, MSH6 and THBS1 are very promising for future research.

[The WHO/ISUP grading system for renal carcinoma].

PubMed

Moch, H

2016-07-01

Histological tumor grading is an accepted prognostic parameter of renal cell carcinoma (RCC). In 2012, the International Society of Urologic Pathologists (ISUP) proposed a novel grading system for RCC, mainly based on the evaluation of nucleoli: grade 1 tumors have nucleoli that are inconspicuous and basophilic at ×400 magnification; grade 2 tumors have nucleoli that are clearly visible at ×400 magnification and eosinophilic; grade 3 tumors have clearly visible nucleoli at ×100 magnification; and grade 4 tumors have extreme pleomorphism or rhabdoid and/or sarcomatoid morphology. This grading system was validated for clear cell renal cell carcinoma and papillary renal cell carcinoma. At the same time, the ISUP proposed not grading chromophobe renal cell carcinomas according to this system. At a consensus conference in Zurich the World Health Organization (WHO) recommended the ISUP grading system; thus, the WHO/ISUP grading system is now going to be implemented internationally. The ISUP/WHO grading system has not been validated as a prognostic parameter for other tumor subtypes, but can be used for descriptive purposes.

High-grade soft tissue sarcoma arising in a desmoid tumor: case report and review of the literature.

PubMed

Bertucci, François; Faure, Marjorie; Ghigna, Maria-Rosa; Chetaille, Bruno; Guiramand, Jérôme; Moureau-Zabotto, Laurence; Sarran, Anthony; Perrot, Delphine

2015-01-01

Desmoid tumors are rare benign monoclonal fibroblastic tumors. Their aggressiveness is local with no potential for metastasis or dedifferentiation. Here we report on a 61-year-old patient who presented a locally advanced breast desmoid tumor diagnosed 20 years after post-operative radiotherapy for breast carcinoma. After 2 years of medical treatment, a high-grade undifferentiated pleomorphic soft tissue sarcoma arose within the desmoid tumor. Despite extensive surgery removing both tumors, the patient showed locoregional relapse by the sarcoma, followed by multimetastatic progression, then death 25 months after the surgery. The arising of a soft tissue sarcoma in a desmoid tumor is an exceptional event since our case is the fourth one reported so far in literature. It reinforces the need for timely and accurate diagnosis when a new mass develops in the region of a preexisting desmoid tumor, and more generally when a desmoid tumor modifies its clinical or radiological aspect.

ESR1 methylation in primary tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer.

PubMed

Giannopoulou, Lydia; Mastoraki, Sophia; Buderath, Paul; Strati, Areti; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

2018-05-25

Estrogen receptor, coded by the ESR1 gene, is highly expressed in epithelial ovarian cancer. ESR1 gene is frequently methylated in many types of gynecological malignancies. However, only a few studies attempted to investigate the role of ESR1 methylation and its clinical significance in ovarian cancer so far. The aim of our study was to examine ESR1 methylation status in primary tumors and corresponding circulating tumor DNA of patients with high-grade serous ovarian cancer (HGSC). ESR1 methylation was detected by a highly specific and sensitive real-time methylation-specific PCR assay. Two groups of HGSC samples were analyzed: group A (n = 66 primary tumors) and group B (n = 53 primary tumors and 50 corresponding plasma samples). ESR1 was found methylated in both groups of primary tumors: in 32/66 (48.5%) of group A and in 15/53 (28.3%) of group B. 19/50 (38.0%) corresponding plasma samples of group B were also methylated for ESR1. A significant agreement for ESR1 methylation was observed between primary tumors and paired plasma ctDNA samples (P = 0.004). Interestingly, the presence of ESR1 methylation in primary tumor samples of group B was significantly correlated with a better overall survival (P = 0.027) and progression-free survival (P = 0.041). We report for the first time the presence of ESR1 methylation in plasma ctDNA of patients with HGSC. The agreement between ESR1 methylation in primary tumors and paired ctDNA is statistically significant. Our results indicate a correlation between the presence of ESR1 methylation and a better clinical outcome in HGSC patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Clinical prognostic factors and grading system for rib fracture following stereotactic body radiation therapy (SBRT) in patients with peripheral lung tumors.

PubMed

Kim, Su Ssan; Song, Si Yeol; Kwak, Jungwon; Ahn, Seung Do; Kim, Jong Hoon; Lee, Jung Shin; Kim, Woo Sung; Kim, Sang-We; Choi, Eun Kyung

2013-02-01

Several studies reported rib fractures following stereotactic body radiation therapy (SBRT) for peripheral lung tumors. We tried to investigate risk factors and grading system for rib fractures after SBRT. Of 375 primary or metastatic lung tumors (296 patients) which were treated with SBRT at the Asan Medical Center (2006-2009), 126 lesions (118 patients) were adjacent to the chest-wall (<1cm) and followed-up with chest computed tomography (CT) for >6 months; these were investigated in the present retrospective study. Three to four fractional doses of 10-20 Gy were delivered to 85-90% iso-dose volume of the isocenter dose. Rib fracture grade was defined from follow-up CT scans as the appearance of a fracture line (Gr1), dislocation of the fractured rib by more than half the rib diameter (Gr2), or the appearance of adjacent soft tissue edema (Gr3). Chest wall pain was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Correlations between dose-volume data and the development of rib fracture were then analyzed. The Kaplan-Meier method, log-rank tests, and chi-square tests were used for statistical analysis. The median age of the patients was 69 years (range: 19-90). Over a median follow-up period of 22 months (range: 7-62), 48 cases of rib fracture were confirmed. Median time to rib fracture was 17 months (range: 4-52). The 2-year actuarial risk of rib fracture was 42.4%. Maximal grade was Gr1 (n=28), Gr2 (n=8), or Gr3 (n=15). The incidence of moderate to severe chest wall pain (CTCAE Gr ≥ 2) increased with maximal fracture grade (17.5% for Gr0-1 and 60.9% for Gr2-3; p<0.001). Multivariate analysis identified female gender, lateral location, and the dose to the 8cc of the chest wall as significant prognostic factors. Female gender and lateral tumor location were clinical risk factors for rib fracture in the present study. Efforts to decrease chest wall dose should be made to reduce the risk of the rib fracture, particularly in

KRAS mutation testing in borderline ovarian tumors and low-grade ovarian carcinomas with a rapid, fully integrated molecular diagnostic system.

PubMed

Sadlecki, Pawel; Antosik, Paulina; Grzanka, Dariusz; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

2017-10-01

Epithelial ovarian neoplasms are a heterogeneous group of tumors, including various malignancies with distinct clinicopathologic and molecular features. Mutations in BRAF and KRAS genes are the most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous and mucinous borderline tumors. Implementation of targeted therapeutic strategies requires access to highly specific and highly sensitive diagnostic tests for rapid determination of mutation status. One candidate for such test is fully integrated, real-time polymerase chain reaction-based Idylla™ system for quick and simple detection of KRAS mutations in formaldehyde fixed-paraffin embedded tumor samples. The primary aim of this study was to verify whether fully integrated real-time polymerase chain reaction-based Idylla system may be useful in determination of KRAS mutation status in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 37 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland) between January 2009 and June 2012. Based on histopathological examination of surgical specimens, 30 lesions were classified as low-grade ovarian carcinomas and 7 as borderline ovarian tumors. Seven patients examined with Idylla KRAS Mutation Test tested positive for KRAS mutation. No statistically significant association was found between the incidence of KRAS mutations and histopathological type of ovarian tumors. Mean survival of the study subjects was 48.51 months (range 3-60 months). Presence of KRAS mutation did not exert a significant effect on the duration of survival in our series. Our findings suggest that Idylla KRAS Mutation Test may be a useful tool for rapid detection of KRAS mutations in ovarian tumor tissue.

Activities for Teaching about Aging: Primary and Intermediate Grades.

ERIC Educational Resources Information Center

Atwood, H. Mason, Ed.

Over 350 activities are suggested for primary and intermediate grade students to learn about aging and older adults. They have been designed for with use with already existing curricula, so that teachers will not feel a need to plan an entire unit on aging. Interdisciplinary in nature, the activities are listed according to the subject areas for…

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA.

PubMed

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

2017-03-28

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA

PubMed Central

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S.

2017-01-01

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients. PMID:28206954

Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

ClinicalTrials.gov

2013-05-01

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Extra-adrenal Paraganglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Ovarian Conservation and Overall Survival in Young Women With Early-Stage Low-Grade Endometrial Cancer.

PubMed

Matsuo, Koji; Machida, Hiroko; Shoupe, Donna; Melamed, Alexander; Muderspach, Laila I; Roman, Lynda D; Wright, Jason D

2016-10-01

To characterize contributing factors for ovarian conservation during surgical treatment for endometrial cancer and to examine the association of ovarian conservation on survival of young women with early-stage, low-grade tumors. This was a population-based study using the Surveillance, Epidemiology, and End Results program to identify surgically treated stage I type I (grade 1-2 endometrioid histology) endometrial cancer cases diagnosed between 1983 and 2012 (N=86,005). Multivariable models were used to identify independent factors for ovarian conservation. Survival outcomes and cause of death were examined for women aged younger than 50 with stage I type I endometrial cancer who underwent ovarian conservation (1,242 among 12,860 women [9.7%]). On multivariable analysis, age younger than 50 years, grade 1 endometrioid histology, and tumor size 2.0 cm or less were noted to be independent factors for ovarian conservation (all, P<.001). For 9,110 women aged younger than 50 years with stage I grade 1 tumors, cause-specific survival was similar between ovarian conservation and oophorectomy cases (20-year rates 98.9% compared with 97.7%, P=.31), whereas overall survival was significantly higher in ovarian conservation cases than oophorectomy cases (88.8% compared with 82.0%, P=.011). On multivariable analysis, ovarian conservation remained an independent prognostic factor for improved overall survival (adjusted hazard ratio 0.73, 95% confidence interval [CI] 0.54-0.98, P=.036) and was independently associated with a lower cumulative risk of death resulting from cardiovascular disease compared with oophorectomy (20-year rates, 2.3% compared with 3.7%, adjusted hazard ratio 0.40, 95% CI 0.17-0.91, P=.029). Contrary, cause-specific survival (20-year rates 94.6% compared with 96.1%, P=.68) and overall survival (81.0% compared with 80.6%, P=.91) were similar between ovarian conservation and oophorectomy among 3,750 women aged younger than 50 years with stage I grade 2 tumors

Diagnostic Accuracy of Centrally Restricted Diffusion in the Differentiation of Treatment-Related Necrosis from Tumor Recurrence in High-Grade Gliomas.

PubMed

Zakhari, N; Taccone, M S; Torres, C; Chakraborty, S; Sinclair, J; Woulfe, J; Jansen, G H; Nguyen, T B

2018-02-01

Centrally restricted diffusion has been demonstrated in recurrent high-grade gliomas treated with bevacizumab. Our purpose was to assess the accuracy of centrally restricted diffusion in the diagnosis of radiation necrosis in high-grade gliomas not treated with bevacizumab. In this prospective study, we enrolled patients with high-grade gliomas who developed a new ring-enhancing necrotic lesion and who underwent re-resection. The presence of a centrally restricted diffusion within the ring-enhancing lesion was assessed visually on diffusion trace images and by ADC measurements on 3T preoperative diffusion tensor examination. The percentage of tumor recurrence and radiation necrosis in each surgical specimen was defined histopathologically. The association between centrally restricted diffusion and radiation necrosis was assessed using the Fisher exact test. Differences in ADC and the ADC ratio between the groups were assessed via the Mann-Whitney U test, and receiver operating characteristic curve analysis was performed. Seventeen patients had re-resected ring-enhancing lesions: 8 cases of radiation necrosis and 9 cases of tumor recurrence. There was significant association between centrally restricted diffusion by visual assessment and radiation necrosis ( P = .015) with a sensitivity of 75% and a specificity of 88.9%, a positive predictive value 85.7%, and a negative predictive value of 80% for the diagnosis of radiation necrosis. There was a statistically significant difference in the ADC and ADC ratio between radiation necrosis and tumor recurrence ( P = .027). The presence of centrally restricted diffusion in a new ring-enhancing lesion might indicate radiation necrosis rather than tumor recurrence in high-grade gliomas previously treated with standard chemoradiation without bevacizumab. © 2018 by American Journal of Neuroradiology.

Immunohistochemical expression of p53 and its clinicopathological correlation with modified Anneroth's histological grading system.

PubMed

Dave, Kajal V; Chalishazar, Monali; Dave, Vishal R; Panja, Pritam; Singh, Manisha; Modi, Tapan G

2016-01-01

Oral squamous cell carcinoma (OSCC) is an epithelial neoplasm generally beginning as focal overgrowth of altered stem cells near the basement membrane, moving upward and laterally, replacing the normal epithelium. Histopathological grading has been used for many decades in an attempt to predict the clinical behavior of oral squamous cell carcinoma. In the present study, Forty biopsies were studied for histological grading and p53 expression. The p53 expression was studied in relation to clinical parameters such as age, sex of patient and site of tumors. Relation between histological grade of malignancy and p53 protein expression was analysed. All cases were classified according to Anneroth's histological malignancy grading system (1987). 40 cases of OSCC were assessed for clinical parameters, Anneroth's histological grading and immunohistochemically stained with p53 protien. The results obtained were analyzed using Spearman's Co-relation. The positive expression of p53 was found in 62% of carcinomas studied. Positivity of p53 showed correlation with histological grade of malignancy and with individual parameters like degree of keratinization, nuclear polymorphism, number of mitoses and lymphoplasmacytic infiltration while showed a negative correlation with pattern of invasion. Our study showed a significant correlation between parameters of tumor cell population, lymphoplasmacytic infiltration and p53 expression. A significant association between high grade of malignancy and p53 overexpression and insignificant correlation of p53 with age, sex of the patient and site of the tumor was found.

Is the two-tier ovarian serous carcinoma grading system potentially useful in stratifying uterine serous carcinoma? A large multi-institutional analysis.

PubMed

Ahmed, Quratulain; Hussein, Yaser; Hayek, Kinda; Bandyopadhyay, Sudeshna; Semaan, Assaad; Abdul-Karim, Fadi; Al-Wahab, Zaid; Munkarah, Adnan R; Elshaikh, Mohamed A; Alosh, Baraa; Nucci, Marisa R; Van de Vijver, Koen K; Morris, Robert T; Oliva, Esther; Ali-Fehmi, Rouba

2014-02-01

A subset of uterine serous carcinoma (USC) may have better clinical behavior bringing up the possibility that there may be morphologic features, which would help in their categorization. The aim of this study is to evaluate the potential use of the MD Anderson Cancer Center 2-tier grading system for ovarian carcinoma in USC. Tumors assigned a combined score included in this analysis were 1) low-grade: tumors without marked atypia and 12 mitoses/10 high power field (HPF) and 2) high grade: tumors with severe nuclear atypia and >12 mitoses/10 HPF. Clinicopathologic parameters evaluated included patients' age, tumor size, myometrial invasion (MI), lymphovascular invasion (LVI), lymph node (LN), FIGO stage, and patient outcome. 140 patients with USC were included, 30 low grade uterine serous carcinoma (LGUSC) and 110 high grade uterine serous carcinoma (HGUSC). Of all parameters only 2 (MI and stage IA) reached statistical significance. 67% of LGUSC cases showed myometrial invasion versus 93.6% HGUSC cases (p = 0.003). A higher percentage of LGUSC (63.3%) versus HGUSC (32.7%) were in stage IA (p = 0.01). However, by multivariate analysis including age, LVI, stage and tumor grade only stage was an independent prognostic factor. The presence of atypia and mitosis across a uterine serous carcinoma is notoriously variable in magnitude and extent, potentially making evaluation of these features difficult and subsequent grading subjective. Our findings thus show that actual prognostic utility of application of MDACC two-tier grading system to uterine serous carcinoma may not be applicable. Copyright © 2013 Elsevier Inc. All rights reserved.

Amide Proton Transfer Imaging Allows Detection of Glioma Grades and Tumor Proliferation: Comparison with Ki-67 Expression and Proton MR Spectroscopy Imaging.

PubMed

Su, C; Liu, C; Zhao, L; Jiang, J; Zhang, J; Li, S; Zhu, W; Wang, J

2017-09-01

Prognosis in glioma depends strongly on tumor grade and proliferation. In this prospective study of patients with untreated primary cerebral gliomas, we investigated whether amide proton transfer-weighted imaging could reveal tumor proliferation and reliably distinguish low-grade from high-grade gliomas compared with Ki-67 expression and proton MR spectroscopy imaging. This study included 42 patients with low-grade ( n = 28) or high-grade ( n = 14) glioma, all of whom underwent conventional MR imaging, proton MR spectroscopy imaging, and amide proton transfer-weighted imaging on the same 3T scanner within 2 weeks before surgery. We assessed metabolites of choline and N -acetylaspartate from proton MR spectroscopy imaging and the asymmetric magnetization transfer ratio at 3.5 ppm from amide proton transfer-weighted imaging and compared them with histopathologic grade and immunohistochemical expression of the proliferation marker Ki-67 in the resected specimens. The asymmetric magnetization transfer ratio at 3.5 ppm values measured by different readers showed good concordance and were significantly higher in high-grade gliomas than in low-grade gliomas (3.61% ± 0.155 versus 2.64% ± 0.185, P = .0016), with sensitivity and specificity values of 92.9% and 71.4%, respectively, at a cutoff value of 2.93%. The asymmetric magnetization transfer ratio at 3.5 ppm values correlated with tumor grade ( r = 0.506, P = .0006) and Ki-67 labeling index ( r = 0.502, P = .002). For all patients, the asymmetric magnetization transfer ratio at 3.5 ppm correlated positively with choline ( r = 0.43, P = .009) and choline/ N -acetylaspartate ratio ( r = 0.42, P = .01) and negatively with N -acetylaspartate ( r = -0.455, P = .005). These correlations held for patients with low-grade gliomas versus those with high-grade gliomas, but the correlation coefficients were higher in high-grade gliomas (choline: r = 0.547, P = .053; N -acetylaspartate: r = -0.644, P = .017; choline/ N

The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging.

PubMed

Panickar, Kiran S; Jewell, Dennis E

2015-08-01

Aging in humans is associated with chronic low-grade inflammation (systemic), and this condition is sometimes referred to as "inflammaging". In general, canines also age similarly to humans, and such aging is associated with a decline in mobility, joint problems, weakened muscles and bones, reduced lean body mass, cancer, increased dermatological problems, decline in cognitive ability, reduced energy, decreased immune function, decreased renal function, and urinary incontinence. Each of these conditions is also associated with an increase in pro-inflammatory cytokines. An inflammatory state characterized by an increase in pro-inflammatory markers including but not restricted to tumor necrosis factor-α, interleukin-6, IL-1β, and C-reactive protein (CRP) is believed to contribute to or worsen a general decline in biological mechanisms responsible for physical function with aging. Nutritional management of inflammation in aging dogs is important in maintaining health. In particular, natural botanicals have bioactive components that appear to have robust anti-inflammatory effects and, when included in the diet, may contribute to a reduction in inflammation. While there are scientific data to support the anti-inflammatory effects and the efficacy of such bioactive molecules from botanicals, the clinical data are limited and more studies are needed to validate the efficacy of these ingredients. This review will summarize the role of dietary ingredients in reducing inflammatory molecules as well as review the evidence available to support the role of diet and nutrition in reducing chronic low-grade systemic inflammation in animal and human studies with a special reference to canines, where possible.

Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence.

PubMed

Fierstra, Jorn; van Niftrik, Bas; Piccirelli, Marco; Burkhardt, Jan Karl; Pangalu, Athina; Kocian, Roman; Valavanis, Antonios; Weller, Michael; Regli, Luca; Bozinov, Oliver

2016-07-01

Current MRI sequences are limited in identifying brain areas at risk for high grade glioma recurrence. We employed intraoperative 3-Tesla functional MRI to assess cerebrovascular reactivity (CVR) after high-grade glioma resection and analyzed regional CVR responses in areas of tumor recurrence on clinical follow-up imaging. Five subjects with high-grade glioma that underwent an intraoperative Blood Oxygen-Level Dependent (BOLD) MRI CVR examination and had a clinical follow-up of at least 18months were selected from a prospective database. For this study, location of tumor recurrence was spatially matched to the intraoperative imaging to assess CVR response in that particular area. CVR is defined as the percent BOLD signal change during repeated cycles of apnea. Of the 5 subjects (mean age 44, 2 females), 4 were diagnosed with a WHO grade III and 1 subject with a WHO grade IV glioma. Three subjects exhibited a tumor recurrence on clinical follow-up MRI (mean: 15months). BOLD CVR measured in the spatially matched area of tumor recurrence was on average 94% increased (range-32% to 183%) as compared to contralateral hemisphere CVR response, 1.50±0.81 versus 1.03±0.46 respectively (p=0.31). For this first analysis in a small cohort, we found altered intraoperative CVR in brain areas exhibiting high grade glioma recurrence on clinical follow-up imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Histological grading of ovarian clear cell adenocarcinoma: proposal for a simple and reproducible grouping system based on tumor growth architecture.

PubMed

Yamamoto, Sohei; Tsuda, Hitoshi; Shimazaki, Hideyuki; Takano, Masashi; Yoshikawa, Tomoyuki; Kuzuya, Kazuo; Tsuda, Hiroshi; Kurachi, Hirohisa; Kigawa, Junzo; Kikuchi, Yoshihiro; Sugiyama, Toru; Matsubara, Osamu

2012-03-01

In this study, we aimed to develop a histological grading system for ovarian clear cell adenocarcinoma (CCA), based on the tumor growth architectures. Cases were defined as Group A if ≥90% of a tumor examined was composed of well-differentiated tubulocystic and/or papillary architectures; Group C if at least 10% of the tumor was composed of very poorly differentiated histology (i.e. solid masses or individual infiltrating tumor cells with no or little glandular/papillary differentiation); and tumors not corresponding to the first 2 descriptions were defined as Group B. The interobserver reproducibility and prognostic value of the assigned groups were analyzed for 159 CCAs from 5 institutions. The level of agreement in assigning the groups between 2 pathologists was 88.7% (=0.82). After consensus was reached, 46 (29%), 79 (50%), and 34 (21%) tumors were classified in Groups A, B, and C, respectively. In early-stage cases [International Federation of Gynecology and Obstetrics (FIGO) stage I-II], Group A tumors had significantly better outcomes (100% 5-yr survival) than Group B tumors (82% 5-yr survival, P=0.024 by log-rank test) or Group C tumors (56% 5-yr survival, P=0.00054 by log-rank test). Moreover, early-stage Group B tumors had significantly better outcomes than Group C tumors (P<0.001 by a generalized Wilcoxon test). In advanced cases (FIGO stage III-IV), Group A tumors had significantly better outcomes than Group C tumors (52% vs. 16% 5-yr survival, respectively, P=0.043). Group A and C tumors defined with our system were identified to have favorable and unfavorable prognostic factors, respectively, independent of the clinical stage of the disease and presence of residual tumors after the initial surgery. The proposed grouping system could divide patients with CCA into 3 subgroups with distinct prognostic indications, providing a 3-tier histological grading system for ovarian CCA.

A case of multicentric low-grade neuroendocrine breast tumor with an unusual histological pattern.

PubMed

D'Antonio, Antonio; Addesso, Maria; Memoli, Domenico; Cascone, Annamaria; Cremone, Luigi

2016-01-01

Neuroendocrine features are detectable in carcinomas of the breast either as scattered cells, that are recognized by their expression of neuroendocrine cell markers. Instead, pure breast carcinomas with neuroendocrine features (NEBC) are very rare and represent <1% of all breast cancer. Usually NEBC may be well or poorly differentiated and more frequent in older woman. These tumors showed variable histological pattern but a common feature is represented by expression of neuroendocrine markers. Here we report a case of a primary multicentric low-grade neuroendocrine carcinoma of the breast presented because of its rarity and for the unusual tubular and cribriform pattern resembling a well-differentiated conventional breast carcinoma. The tumor was treated with left quadrantectomy with concomitant wide excisional biopsy of other two nodules and lymph node sentinel biopsy. No recurrence was observed during 1-year follow-up. Because of its rarity and variability of morphologic features, there exist diagnostic challenges for pathologists to differentiate primary NEBC to some conventional breast carcinomas and to the breast metastasis from neuroendocrine tumor of the lung or gastrointestinal tract. It is important to be able recognize this tumor in order to avoid potential misdiagnosis and improper management of afflicted patients.

Age dependency of primary tumor sites and metastases in patients with Ewing sarcoma.

PubMed

Worch, Jennifer; Ranft, Andreas; DuBois, Steven G; Paulussen, Michael; Juergens, Heribert; Dirksen, Uta

2018-06-01

The median age of patients with Ewing sarcoma (EwS) at diagnosis is around 14-15 years. Older age is associated with a worse outcome. The correlation of age at diagnosis on sites of disease has not been fully described. The goal of this study was to evaluate the differences in sites of primary tumor and metastatic tumor involvement according to age groups. EwS data from the Gesellschaft für Pädiatrische Onkologie und Hämatology (GPOH) database of the Cooperative Ewing Sarcoma Study (CESS) 81/86 and the European Intergroup Cooperative Ewing's Sarcoma Study EICESS 92 and the EUROpean Ewing tumor Working Initiative of National Groups-99-Protocol (EURO-E.W.I.N.G.-99) study were analyzed. Patient and tumor characteristics were evaluated statistically using chi square tests. The study population included 2,635 patients with bone EwS. Sites of primary and metastatic tumors differed according to the age groups of young children (0-9 years), early adolescence (10-14 years), late adolescence (15-19 years), young adults (20-24 years), and adults (more than 24 years). Young children demonstrated the most striking differences in site of disease with a lower proportion of pelvic primary and axial tumors. They presented less often with metastatic disease at diagnosis. Site of primary and metastatic tumor involvement in EwS differs according to patient age. The biological and developmental etiology for these differences requires further investigations. © 2018 Wiley Periodicals, Inc.

The Fuhrman grading system has no prognostic value in patients with nonsarcomatoid chromophobe renal cell carcinoma.

PubMed

Steffens, Sandra; Janssen, Martin; Roos, Frederik C; Becker, Frank; Steinestel, Julie; Abbas, Mahmoud; Steinestel, Konrad; Wegener, Gerd; Siemer, Stefan; Thüroff, Joachim W; Hofmann, Rainer; Stöckle, Michael; Schrader, Mark; Hartmann, Arndt; Hasenfus, Andrea; Kuczyk, Markus A; Junker, Kerstin; Schrader, Andres J

2014-12-01

The prognostic value of the Fuhrman nuclear grading system has been questioned for chromophobe renal cell carcinoma (chRCC) because this subtype frequently displays nuclear and nucleolar pleomorphism. The present study reevaluates this grading system in a series of patients with nonsarcomatoid chRCC. We identified 176 patients (3.6%) with nonsarcomatoid chRCC in a total of 4897 patients who underwent surgery for renal cell carcinoma at 5 centers in Germany between 1990 and 2010. The mean follow-up was 51.1 months. The 3 groups (G1 versus G2 versus G3/4) were comparable in terms of age, sex, tumor diameter, and lymph node metastasis. They only differed significantly in tumor stage (P = .01) and the incidence of synchronous visceral metastasis (P = .04). The 5-year cancer-specific survival rates were 84.4% for G1 (n = 32), 84.3% for G2 (n = 108), and 74.1% for G3/4 tumors (n = 33) (P = .58). Accordingly, multivariate analysis including age, sex, tumor stage, and metastatic disease did not identify Fuhrman grading as an independent predictor of cancer-specific survival in patients with chRCC (P = .4). We were able to demonstrate in a large multicenter cohort that the Fuhrman grading system does not qualify as a prognostic tool in patients with chRCC. Copyright © 2014 Elsevier Inc. All rights reserved.

Determining the relationship between "microvessel density" and different grades of astrocytoma based on immunohistochemistry for "factor VIII-related antigen" (von Willebrand factor) expression in tumor microvessels.

PubMed

Mahzouni, Parvin; Mohammadizadeh, Fereshteh; Mougouei, Kourosh; Moghaddam, Noushin Afshar; Chehrei, Ali; Mesbah, Alireza

2010-01-01

Astrocytic brain tumors are the most common primary central nervous system tumors, which are classified into four grades. One of the most important pathologic criteria for the diagnosis of higher-grade astrocytomas (especially glioblastoma multiforme) is microvessel proliferation, particularly in the form of glomeruloid complex. Because tumor angiogenesis is a necessary factor for growth and invasiveness of malignancies, microvessel density (MVD) and intensity of angiogenesis may be used to determine the grade of astrocytomas and plan therapy accordingly. We have planned this study to evaluate the relationship between vwf expression in microvessels and different grades of astrocytoma. Sixty-four formalin-fixed and paraffin-embedded blocks of surgical specimens with diagnosis of astrocytoma (grades I to IV, each of them 16 blocks) were selected in a simple-nonrandom sampling. Thin sections of tissue blocks underwent immunohistochemical staining for vwf. The stained slides were examined using a light microscope at low (100) and high (400) magnifications. MVD was estimated by calculating the mean number of stained microvessels in three areas of highest vascularization in the high-power field (400). The intensity of staining was determined based on a 3 scale model, in which scores 0, 1, 2, and 3 mean no detectable stain, trace staining, moderate amount of diffuse stain, and strong diffuse staining, respectively. Thirty-six (56%) patients were male and 28 (44%) were female. Scores 0 and 1 of microvessel staining intensity were not observed in any grades studied, but severe staining intensity (score 3) was observed in 18.8%, 37.5%, 56.3%, and 87.5% of grades I, II, III, and IV astrocytomas, respectively. "Vwf vessel index" (MVD staining intensity of microvessels) was 23.84, 25.62, 31.62, and 62.43 in grades I, II, III, and IV astrocytomas, respectively. We found a significant relationship between staining intensity of vwf in microvessels and different grades of

EG-03EXPRESSION OF PRMT5 CORRELATES WITH MALIGNANT GRADE IN GLIOMAS AND PLAYS A PIVOTAL ROLE IN TUMOR GROWTH

PubMed Central

Han, Xiaosi; Li, Rong; Zhang, Wenbin; Yang, Xiuhua; Fathallah-Shaykh, Hassan; Gillespie, Yancey; Nabors, Burt

2014-01-01

Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of ω-NG,N′G-symmetric dimethylarginine residues on histones as well as other proteins. The modification play an important role in cell differentiation and tumor cell growth. However, the role of PRMT5 in human glioma cells has not been characterized. In this study, we assessed protein expression profiles of PRMT5 in control brain, WHO grade II astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme (GBM) by immunohistochemistry. PRMT5 was low in glial cells in control brain tissues and low grade astrocytomas. Its expression increased in parallel with malignant progression, and was highly expressed in GBM. Knockdown of PRMT5 by small hairpin RNA caused alterations of p-ERK1/2 and significantly repressed the clonogenic potential and viability of glioma cells. These findings indicate that PRMT5 is a marker of malignant progression in glioma tumors and plays a pivotal role in tumor growth.

Prognostic value of the expression of tumor suppressor genes p53, p21, p16 and prb, and Ki-67 labelling in high grade astrocytomas treated with radiotherapy.

PubMed

Kirla, R; Salminen, E; Huhtala, S; Nuutinen, J; Talve, L; Haapasalo, H; Kalimo, H

2000-01-01

Cumulative inactivation of tumor suppressor genes and/or amplification of oncogenes lead to progressively more malignant astrocytic tumors. We have analyzed the significance of tumor suppressor genes p53, p21, p16 and retinoblastoma protein (pRb) and proliferative activity for survival in 77 high grade astrocytic tumors. After operation, the patients--25 anaplastic astrocytomas (AA) and 52 glioblastomas (GBs)--were treated with similar radiotherapy. The expression of the suppressor genes and the proliferative activity were analyzed immunohistochemically. p53 immunopositivity was found in 44% of AAs and 46% of GBs. Tumors with aberrant p53 expression had lower proliferation indices than p53 immunonegative tumors. Neither p53 expression nor p21 immunonegativity (52% of AAs and 48% of GBs) correlated with survival. p16 immunostaining was negative in 16% of AAs and in 44% of GBs, and it correlated inversely with survival in both uni- and multivariate analyses. pRb immunostaining was negative only in 8% of both AAs and GBs and the absence of p16 and pRb were mutually exclusive. Ki-67 labelling index (LI) was significantly higher in GBs (26.8%) than in AAs (20.3%), and in multivariate analysis it was an independent prognostic factor for survival. In 48% of AAs Ki-67 LI exceeded 20% and this subset of AAs had similar prognosis as GB. In high grade astrocytic tumors p16 immunonegativity was an independent indicator of poor prognosis in addition to the previously established patient's age, histopathology and Ki-67 LI. Furthermore, there was a subset of AAs with a high proliferation rate (> 20%) in which the histopathological hallmarks of GB were lacking, but which had similarly dismal prognosis as GB.

EURO-B.O.S.S.: A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma.

PubMed

Ferrari, Stefano; Bielack, Stefan S; Smeland, Sigbjørn; Longhi, Alessandra; Egerer, Gerlinde; Sundby Hall, Kirsten; Donati, Davide; Kevric, Matthias; Brosjö, Otte; Comandone, Alessandro; Werner, Mathias; Monge, Odd; Palmerini, Emanuela; Berdel, Wolfgang E; Bjerkehagen, Bodil; Paioli, Anna; Lorenzen, Sylvie; Eriksson, Mikael; Gambarotti, Marco; Tunn, Per-Ulf; Jebsen, Nina L; Cesari, Marilena; von Kalle, Thekla; Ferraresi, Virginia; Schwarz, Rudolf; Bertulli, Rossella; Kasparek, Anne-Katrin; Grignani, Giovanni; Krasniqi, Fatime; Sorg, Benjamin; Hecker-Nolting, Stefanie; Picci, Piero; Reichardt, Peter

2018-01-01

The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators' choice were also eligible for the study. The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity. In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.

Differentiation of Low- and High-Grade Pediatric Brain Tumors with High b-Value Diffusion-weighted MR Imaging and a Fractional Order Calculus Model

PubMed Central

Sui, Yi; Wang, He; Liu, Guanzhong; Damen, Frederick W.; Wanamaker, Christian; Li, Yuhua

2015-01-01

Purpose To demonstrate that a new set of parameters (D, β, and μ) from a fractional order calculus (FROC) diffusion model can be used to improve the accuracy of MR imaging for differentiating among low- and high-grade pediatric brain tumors. Materials and Methods The institutional review board of the performing hospital approved this study, and written informed consent was obtained from the legal guardians of pediatric patients. Multi-b-value diffusion-weighted magnetic resonance (MR) imaging was performed in 67 pediatric patients with brain tumors. Diffusion coefficient D, fractional order parameter β (which correlates with tissue heterogeneity), and a microstructural quantity μ were calculated by fitting the multi-b-value diffusion-weighted images to an FROC model. D, β, and μ values were measured in solid tumor regions, as well as in normal-appearing gray matter as a control. These values were compared between the low- and high-grade tumor groups by using the Mann-Whitney U test. The performance of FROC parameters for differentiating among patient groups was evaluated with receiver operating characteristic (ROC) analysis. Results None of the FROC parameters exhibited significant differences in normal-appearing gray matter (P ≥ .24), but all showed a significant difference (P < .002) between low- (D, 1.53 μm2/msec ± 0.47; β, 0.87 ± 0.06; μ, 8.67 μm ± 0.95) and high-grade (D, 0.86 μm2/msec ± 0.23; β, 0.73 ± 0.06; μ, 7.8 μm ± 0.70) brain tumor groups. The combination of D and β produced the largest area under the ROC curve (0.962) in the ROC analysis compared with individual parameters (β, 0.943; D,0.910; and μ, 0.763), indicating an improved performance for tumor differentiation. Conclusion The FROC parameters can be used to differentiate between low- and high-grade pediatric brain tumor groups. The combination of FROC parameters or individual parameters may serve as in vivo, noninvasive, and quantitative imaging markers for classifying

Anatomic Location of Tumor Predicts the Accuracy of Motor Function Localization in Diffuse Lower-Grade Gliomas Involving the Hand Knob Area.

PubMed

Fang, S; Liang, J; Qian, T; Wang, Y; Liu, X; Fan, X; Li, S; Wang, Y; Jiang, T

2017-10-01

The accuracy of preoperative blood oxygen level-dependent fMRI remains controversial. This study assessed the association between the anatomic location of a tumor and the accuracy of fMRI-based motor function mapping in diffuse lower-grade gliomas. Thirty-five patients with lower-grade gliomas involving motor areas underwent preoperative blood oxygen level-dependent fMRI scans with grasping tasks and received intraoperative direct cortical stimulation. Patients were classified into an overlapping group and a nonoverlapping group, depending on the extent to which blood oxygen level-dependent fMRI and direct cortical stimulation results concurred. Tumor location was quantitatively measured, including the shortest distance from the tumor to the hand knob and the deviation distance of the midpoint of the hand knob in the lesion hemisphere relative to the midline compared with the normal contralateral hemisphere. A 4-mm shortest distance from the tumor to the hand knob value was identified as optimal for differentiating the overlapping and nonoverlapping group with the receiver operating characteristic curve (sensitivity, 84.6%; specificity, 77.8%). The shortest distances from the tumor to the hand knob of ≤4 mm were associated with inaccurate fMRI-based localizations of the hand motor cortex. The shortest distances from the tumor to the hand knob were larger ( P = .002), and the deviation distances for the midpoint of the hand knob in the lesion hemisphere were smaller ( P = .003) in the overlapping group than in the nonoverlapping group. This study suggests that the shortest distance from the tumor to the hand knob and the deviation distance for the midpoint of the hand knob on the lesion hemisphere are predictive of the accuracy of blood oxygen level-dependent fMRI results. Smaller shortest distances from the tumor to the hand knob and larger deviation distances for the midpoint of hand knob on the lesion hemisphere are associated with less accuracy of motor cortex

BMP and TGFbeta pathways in human central chondrosarcoma: enhanced endoglin and Smad 1 signaling in high grade tumors

PubMed Central

2012-01-01

Background As major regulators of normal chondrogenesis, the bone morphogenic protein (BMP) and transforming growth factor β (TGFB) signaling pathways may be involved in the development and progression of central chondrosarcoma. In order to uncover their possible implication, the aim of this study was to perform a systematic quantitative study of the expression of BMPs, TGFBs and their receptors and to assess activity of the corresponding pathways in central chondrosarcoma. Methods Gene expression analysis was performed by quantitative RT-PCR in 26 central chondrosarcoma and 6 healthy articular cartilage samples. Expression of endoglin and nuclear localization of phosphorylated Smad1/5/8 and Smad2 was assessed by immunohistochemical analysis. Results The expression of TGFB3 and of the activin receptor-like kinase ALK2 was found to be significantly higher in grade III compared to grade I chondrosarcoma. Nuclear phosphorylated Smad1/5/8 and Smad2 were found in all tumors analyzed and the activity of both signaling pathways was confirmed by functional reporter assays in 2 chondrosarcoma cell lines. Immunohistochemical analysis furthermore revealed that phosphorylated Smad1/5/8 and endoglin expression were significantly higher in high-grade compared to low-grade chondrosarcoma and correlated to each other. Conclusions The BMP and TGFβ signaling pathways were found to be active in central chondrosarcoma cells. The correlation of Smad1/5/8 activity to endoglin expression suggests that, as described in other cell types, endoglin could enhance Smad1/5/8 signaling in high-grade chondrosarcoma cells. Endoglin expression coupled to Smad1/5/8 activation could thus represent a functionally important signaling axis for the progression of chondrosarcoma and a regulator of the undifferentiated phenotype of high-grade tumor cells. PMID:23088614

Redefining the Ki-67 Index Stratification for Low-Grade Pancreatic Neuroendocrine Tumors: Improving Its Prognostic Value for Recurrence of Disease.

PubMed

Lopez-Aguiar, Alexandra G; Ethun, Cecilia G; Postlewait, Lauren M; Zhelnin, Kristen; Krasinskas, Alyssa; El-Rayes, Bassel F; Russell, Maria C; Sarmiento, Juan M; Kooby, David A; Staley, Charles A; Maithel, Shishir K; Cardona, Kenneth

2018-01-01

The Ki-67 index is an established prognostic marker for recurrence after resection of pancreatic neuroendocrine tumors (PanNETs) that groups tumors into three categories: low grade (< 3%), intermediate grade (3-20%), and high grade (> 20%). Given that the majority of resected PanNETs have a Ki-67 less than 3%, this study aimed to stratify this group further to predict disease recurrence more accurately. The Ki-67 index was pathologically re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables using tissue microarray blocks made in triplicate. All patients who underwent curative-intent resection of non-metastatic PanNETs at a single institution from 2000 to 2013 were included in the study. The primary outcome was recurrence-free survival (RFS). Of 113 patients with well-differentiated PanNETs resected, 83 had tissue available for pathologic re-review. The Ki-67 index was lower than 3% for 72 tumors (87%) and between 3 and 20% for 11 tumors (13%). Considering only Ki-67 less than 3%, the tumors were further stratified by Ki-67 into three groups: group A (< 1%, n = 43), group B (1-1.99%, n = 23), and group C (2-2.99%, n = 6). Compared with group A, groups B and C more frequently had advanced T stage (T3: 44% and 67% vs 12%; p = 0.003) and lymphovascular invasion (50% and 83% vs 23%; p = 0.007). Groups B and C had similar 1- and 3-year RFS, both less than group A. After combining groups B and C, a Ki-67 of 1-2.99% was associated with decreased RFS compared with group A (< 1%). This persisted in the multivariable analysis (hazard ratio [HR] 8.6; 95% confidence interval [CI] 1.0-70.7; p = 0.045), with control used for tumor size, margin-positivity, lymph node involvement, and advanced T stage. PanNETs with a Ki-67 of 1-2.99% exhibit distinct biologic behavior and earlier disease recurrence than those with a Ki-67 lower than 1%. This new stratification scheme, if externally validated, should be incorporated into future

Deferred radiotherapy and upfront procarbazine–ACNU–vincristine administration for 1p19q codeleted oligodendroglial tumors are associated with favorable outcome without compromising patient performance, regardless of WHO grade

PubMed Central

Hata, Nobuhiro; Yoshimoto, Koji; Hatae, Ryusuke; Kuga, Daisuke; Akagi, Yojiro; Suzuki, Satoshi O; Iwaki, Toru; Shono, Tadahisa; Mizoguchi, Masahiro; Iihara, Koji

2016-01-01

Recently updated phase III trials revealed the favorable effect of add-on procarbazine-lomustine-vincristine chemotherapy (CT) to radiotherapy (RT) in treating anaplastic oligodendrogliomas with 1p19q codeletion (codel). However, the underlying rationality of deferring RT and upfront CT administration for these tumors is yet to be elucidated. Here, we retrospectively analyzed the long-term outcome of our case series with oligodendroglial tumors treated with deferred RT and upfront procarbazine+nimustine+vincristine (PAV) in the introduction administration. We enrolled 36 patients with newly diagnosed oligodendroglial tumors (17, grade II and 19, grade III) treated during 1999–2012 and followed up for a median period of 69.0 months. Their clinical and genetic prognostic factors were analyzed, and progression-free survival, overall survival (OS), and deterioration-free survival (DFS) were evaluated. Regardless of the WHO grade, the 25 patients with 1p19q codel tumors never received RT initially, and of these 25, 23 received PAV treatment upfront. The 75% OS of patients with 1p19q codel tumor was 135.3 months (did not reach the median OS), indicating a favorable outcome. Multivariate analysis revealed that IDH mutation and 1p19q, not WHO grade, are independent prognostic factors; furthermore, IDH and 1p19q status stratified the cohort into 3 groups with significantly different OS. The DFS explained the prolonged survival without declining performance in patients with both grade II and III 1p19q codel tumors. Deferred RT and upfront PAV treatment for 1p19q codel oligodendrogliomas were associated with favorable outcomes without compromising performance status, regardless of WHO grade. PMID:27895504

The Minnesota Grading System of eye bank eyes for age-related macular degeneration.

PubMed

Olsen, Timothy W; Feng, Xiao

2004-12-01

The Minnesota Grading System (MGS) is a method to evaluate human eye bank eyes and determine the level of age-related macular degeneration (AMD), by using criteria and definitions from the Age-Related Eye Disease Study (AREDS). Donor eyes (108 pairs) from the Minnesota Lions Eye Bank were cut circumferentially at the pars plana to remove the anterior segment. A 1000 +/- 2.5-microm ruby sphere was placed on the optic nerve as a size reference. A digital, high-resolution, color macular photograph was taken through a dissecting microscope. The neurosensory retina was removed from one globe of the pair. The underlying retinal pigment epithelium was rephotographed, localizing the fovea with a proportional triangle. A grid was superimposed in the macular photographs and images were graded according to AREDS criteria. Twenty pairs were dissected bilaterally and graded for symmetry. Eighty-eight globes were graded into one of four MGS categories. Nineteen (95%) of 20 globes had symmetric grades. The MGS provides a methodology to grade donor tissue from eye bank eyes to correspond to the AREDS classification system. Donor tissue may be used for subsequent molecular analysis, including genomics and proteomics.

A Comparative Study of Survival Rate in High Grade Glioma Tumors Being Treated by Radiotherapy Alone Versus Chemoradiation With Nitrosourea.

PubMed

Houshyari, Mohammad; Hajalikhani, Farzaneh; Rakhsha, Afshin; Hajian, Parastoo

2015-03-25

In adults, malignant glioma (high-grade glioma) is one of the most common brain tumors. In spite of different types of treatment, the outcome is still not likely to be favorable. The aim of this study was to determine the difference between survival rate in adult patients with high grade glioma treated by radiotherapy only and those treated by a combination of radiotherapy and nitrosurea-based chemotherapy. This study was conducted using the records of 48 patients with grade 3 or 4 of glial brain tumor referred to the radiation-oncology ward of Shohada-e-Tajrish Hospital in Tehran, Iran from 2005 to 2012. The patients had undergone radiotherapy alone or adjuvant chemoradiation with nitrosourea. The median survival of patients after receiving the different types of treatment were evaluated using the Kaplan-Meier method and the log -rank exam. Data were analyzed using univariate analysis for median survival regarding to the patients' age, gender, extent of surgery, Karnofsky performance status (KPS) with the Kaplan-Meier method, and the log-rank exam. We used the Cox-model for multivariate analysis. Records of 48 patients were studied (34 men and 14 women). The mean survival were 18 months for men and 15.2 months for women (P=0.05). Around 58% (28 patients) were more than 50 years old, and 42% (20 patients) were less than 50, and mean survival for the two age groups were 13 and 20 months, respectively (P<0.001). Then, the patients were divided into three groups according to the extent of surgery, i.e., excisional biopsy (11 patients), stereotactic biopsy (22 patients), and resection (15 patients), and the mean survival for the three groups were 14.7, 17.3, and 18.8 months, respectively. There was no significant statistical difference for mean survival between the three groups (P=0.23). The KPS was greater than 70% in 23 patients and less than 70% in 21 patients, and the mean survival for the former and latter groups were 17.6 and 16 months, respectively (P=0

Early wound site seeding in a patient with CNS high-grade neuroepithelial tumor with BCOR alteration: A case report.

PubMed

Kirkman, Matthew A; Pickles, Jessica C; Fairchild, Amy R; Avery, Aimee; Pietsch, Torsten; Jacques, Thomas S; Aquilina, Kristian

2018-05-30

Advances in molecular profiling have facilitated the emergence of newly defined entities of central nervous system tumor, including CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR). Relatively little is known about the clinical behaviour of these newly-characterized tumors. We describe a pediatric male patient with CNS HGNET-BCOR who developed seeding of the tumor into the site of the surgical wound within months of surgery for resection of a residual posterior fossa tumor. This case emphasises three important points. First, CNS HGNET-BCOR can be aggressive tumors that necessitate close clinical and radiological surveillance. Second, surveillance imaging in such cases should incorporate the surgical incision site into the field of view, and this should be closely scrutinised to ensure the timely detection of wound site seeding. Third, wound site seeding may still occur despite the use of meticulous surgical techniques. Copyright © 2018. Published by Elsevier Inc.

Language Learning Strategies, Course Grades, and Age in EFL Secondary School Learners

ERIC Educational Resources Information Center

Tragant, Elsa; Victori, Mia

2012-01-01

In studies dealing with language learning strategies in the school context, the variables of proficiency and age are often difficult to isolate since students accumulate more hours of foreign language instruction as they move up from grade to grade. This study aimed to deal with these two variables independently by analysing learning strategy use…

Analysis of expression of microRNAs and genes involved in the control of key signaling mechanisms that support or inhibit development of brain tumors of different grades.

PubMed

Koshkin, Philip Alexandrovich; Chistiakov, Dimitry Alexandrovich; Nikitin, Alexey Georgievich; Konovalov, Alexander Nikolaevich; Potapov, Alexander Alexandrovich; Usachev, Dmitry Yrevich; Pitskhelauri, David Ilich; Kobyakov, Gregory Lvovich; Shishkina, Lyudmila Valentinovna; Chekhonin, Vladimir Pavlovich

2014-03-20

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of key biological processes. Different miRNAs with pro-oncogenic and anti-oncogenic properties have been identified in glioblastomas. We decided to analyze expression profiles of 10 mature miRNAs (miR-7-1, miR-10а, miR-17, miR-20а, miR-21, miR-23а, miR-26а, miR-137, and miR-222) in post-surgery glioma specimens of different grades in order to find whether the expression level correlates with tumor grades. We also measured expression of six key genes such as PTEN, p21/CDKN1A, MDR1, ABCG2, BAX, and BCL-2 involved in the regulation of critical glioma signaling pathways to establish the effect of miRNAs on these signaling mechanisms. Using RT-PCR, we performed expression analysis of 25 tumor fresh samples (grades II-IV). We found gradual increase in miR-21 and miR-23a levels in all tumor grades whereas miR-7 and miR-137 were significantly down-regulated depending on the glioma grade. MDR, ABCG2, and p21/CDKN1A levels were significantly up-regulated while expression of PTEN was down-regulated in tumor samples compared to the normal brain tissue. These observations provide new insights into molecular pathogenic mechanisms of glioma progression and suggest about a potential value of miRNAs as a putative diagnostic marker of brain tumors. Copyright © 2014 Elsevier B.V. All rights reserved.

Recurrent high-grade glioma.

PubMed

Quant, Eudocia C; Drappatz, Jan; Wen, Patrick Y; Norden, Andrew D

2010-07-01

Opinions vary on the best treatment options for recurrent high-grade glioma. Some argue that bevacizumab should become standard of care for patients with recurrent glioblastoma, especially in light of recent FDA approval for this indication. However, this opinion is not uniformly accepted. Age, performance status, histology, tumor size and location, O6-methylguanine-DNA methyltransferase (MGMT) methylation status for glioblastoma, 1p/19q status for oligodendroglial tumors, and the number and types of prior therapies are important considerations. In addition, recurrent disease must be distinguished from "pseudoprogression" due to treatment effects. Enrollment in a clinical trial is the optimal choice for most patients with recurrent high-grade glioma after failure of radiation therapy and temozolomide. For patients who are ineligible or do not have access to clinical trials, then either bevacizumab monotherapy or bevacizumab in combination with a second agent such as irinotecan is recommended. Involved-field external beam radiation should be considered for patients with anaplastic gliomas who have not received radiation. For patients with anaplastic astrocytoma who progress after radiotherapy, temozolomide may be used. For patients with anaplastic oligodendroglioma who progress after radiotherapy, PCV chemotherapy and temozolomide are options. Oligodendroglial tumors with 1p/19q deletions are more likely to respond to treatment. In the past, carmustine was commonly used to treat recurrent high-grade glioma, but the utility of carmustine in the modern era is unknown because most studies were performed prior to the widespread use of temozolomide. High-precision re-irradiation such as stereotactic radiosurgery is another option in high-grade glioma, especially for patients with poor bone marrow reserve or inability to tolerate chemotherapy, but there is a paucity of studies with adequate controls. Surgery may be useful as adjuvant treatment for patients with symptoms

CT Features of Ovarian Tumors: Defining Key Differences Between Serous Borderline Tumors and Low-Grade Serous Carcinomas.

PubMed

Nougaret, Stephanie; Lakhman, Yulia; Molinari, Nicolas; Feier, Diana; Scelzo, Chiara; Vargas, Hebert A; Sosa, Ramon E; Hricak, Hedvig; Soslow, Robert A; Grisham, Rachel N; Sala, Evis

2018-04-01

The objective of our study was to investigate whether the CT features of serous borderline tumors (SBTs) differ from those of low-grade serous carcinomas (LGSCs) and to evaluate if mutation status is associated with distinct CT phenotypes. This retrospective study included 59 women, 37 with SBT and 22 with LGSC, who underwent CT before primary surgical resection. Thirty of 59 patients were genetically profiled. Two radiologists (readers 1 and 2) independently and retrospectively reviewed CT examinations for qualitative features and quantified total tumor volumes (TTVs), solid tumor volumes (STVs), and solid proportion of ovarian masses. Univariate and multivariate associations of the CT features with histopathologic diagnoses and mutations were evaluated, and interreader agreement was determined. At multivariate analysis, the presence of bilateral ovarian masses (p = 0.03), the presence of peritoneal disease (PD) (p = 0.002), and higher STV of ovarian masses (p = 0.002) were associated with LGSC. The presence of nodular PD pattern (p < 0.001 each reader) and the presence of PD calcifications (reader 1, p = 0.02; reader 2, p = 0.003) were associated with invasive peritoneal lesions (i.e., LGSC). The presence of bilateral ovarian masses (p = 0.04 each reader), PD (reader 1, p = 0.01; reader 2, p = 0.004), and higher STV (p = 0.03 for each reader) were associated with the absence of BRAF mutation (i.e., wild type [wt]-BRAF). The CT features of LGSCs were distinct from those of SBTs. The CT manifestations of LGSC and the wt-BRAF phenotype were similar.

B-cell lymphoma 2 is associated with advanced tumor grade and clinical stage, and reduced overall survival in young Chinese patients with colorectal carcinoma.

PubMed

Wang, Jiasheng; He, Gan; Yang, Qiang; Bai, Lian; Jian, Bin; Li, Qugang; Li, Zhongfu

2018-06-01

The development of biomarkers that accurately and reliably detect colorectal cancer is a promising approach for colorectal cancer screening. Therefore, the objective of the present study was to evaluate the protein expression of α-methylacyl-CoA racemase (P504S/AMACR), tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2) and Ki-67/mindbomb E3 ubiquitin protein ligase 1 (MIB-1) in a population of Chinese patients with colorectal carcinoma. Colorectal tumors with matched normal tissue margins were collected from 148 surgical patients, and the demographic and clinical characteristics were collected. Immunohistochemical staining and western blot analysis of P504S/AMACR, p53, Bcl-2 and Ki-67/MIB-1 were conducted. Statistical analyses were used to compare protein expression in the colorectal tumors and matched normal tissue margins and to identify any associations between them and various clinicopathological parameters. Survival analyses were performed using the Kaplan-Meier method. In the present study, immunohistochemistry and western blot analysis revealed significantly higher expression of all four proteins in colorectal tumors compared with matched normal tissue margins (P<0.001). Spearman's rank correlation analysis revealed that Bcl-2 expression was negatively correlated with pathological grade and Tumor-Node-Metastasis (TNM) stage (-0.827 and -0.388, respectively; P<0.05). Bcl-2 expression was revealed to be a significant prognostic indicator of colorectal carcinoma [relative risk (95% CI), 0.703 (0.552-0.895); P<0.05]. The log-rank test revealed a significant association between low Bcl-2 expression and reduced overall survival (P=0.039), as well as a significant association between older age (>55 years) and reduced overall survival (P<0.001) in Chinese patients with colorectal carcinoma. In conclusion, low expression of Bcl-2 is significantly correlated with advanced pathological grade and TNM stage and is a prognostic indicator of reduced overall survival in

Shorter telomere length increases age-related tumor risks in von Hippel-Lindau disease patients.

PubMed

Wang, Jiang-Yi; Peng, Shuang-He; Ning, Xiang-Hui; Li, Teng; Liu, Sheng-Jie; Liu, Jia-Yuan; Hong, Bao-An; Qi, Nie-Nie; Peng, Xiang; Zhou, Bo-Wen; Zhang, Jiu-Feng; Cai, Lin; Gong, Kan

2017-09-01

Von Hippel-Lindau (VHL) disease is a rare autosomal dominant cancer syndrome caused by alterations of VHL gene. Patients are predisposed to develop pheochromocytomas and solid or cystic tumors of the central nervous system, kidney, pancreas, and retina. Remarkable phenotypic heterogeneity exits in organ involvement and tumor onset age between and within VHL families. However, no reliable markers have been found to predict the age-related tumor risks in VHL patients. A large Chinese cohort composed of 300 VHL patients and 92 healthy family controls was enrolled in our study. Blood relative telomere length was measured in 184 patients and all the controls available for genomic DNA samples. Age-related risks for the five major VHL-associated tumors were evaluated using Kaplan-Meier plots and Cox regression analysis. Differences in clinical phenotype were observed between Chinese cohort and the United Kingdom cohort. VHL patients showed significantly shorter telomere length than healthy family controls(P = 0.0183), and a positive correlation was found between telomere length and onset age of the five major tumors, respectively. Moreover, patients in the shorter telomere group (age-adjusted telomere length ≤ 0.44) suffered higher age-related risks for VHL-associated central nervous system hemangioblastomas (HR: 1.879, P = 0.004), renal cell carcinoma (HR: 2.126, P = 0.002) and pancreatic cyst and neuroendocrine tumors (HR: 2.093, P = 0.001). These results indicate that blood shorter telomere length is a new biomarker for age-related tumor risks in VHL patients, which will be crucial to genetic counseling and future research about the role of telomere shortening in the pathogenesis of VHL-associated tumors. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Semiautomatic segmentation and follow-up of multicomponent low-grade tumors in longitudinal brain MRI studies

PubMed Central

Weizman, Lior; Sira, Liat Ben; Joskowicz, Leo; Rubin, Daniel L.; Yeom, Kristen W.; Constantini, Shlomi; Shofty, Ben; Bashat, Dafna Ben

2014-01-01

Purpose: Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans. Methods: The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a “gold standard” was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution. Results: Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard. Conclusions: The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior. PMID:24784396

Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

ClinicalTrials.gov

2013-10-07

Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Cilengitide in Treating Children With Refractory Primary Brain Tumors

ClinicalTrials.gov

2013-09-27

Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Incidence of right-sided colonic tumors (non-appendiceal) in patient's ≥40 years of age presenting with features of acute appendicitis.

PubMed

Khan, Suhail Aslam; Khokhar, Haseeb Anwar; Nasr, A R H; Carton, Eleanor

2013-01-01

Non-appendiceal tumors can mimic and present with clinical features of acute appendicitis in patients of age 40 years or above. The aim of this prospective study is to investigate the incidence of right-sided (non-appendiceal) colonic tumors in patients presenting with clinical features of acute appendicitis. A prospective data analysis of 1662 patients using appendectomy database was performed from 2005 to 2011. Patients above age 40 years or older were included. Patients were compared for demographic data, clinical presentation, radiological findings, operative technique & findings, histo-pathological findings and postoperative complications. The primary outcome was incidence of right-sided colonic (non-appendiceal) tumors presenting with features of acute appendicitis. Secondary outcomes measured were, role of diagnostic radiology, negative appendectomy rate, length of stay and changing trends in operative techniques. From 1662 patients initially reviewed, only 179 patients (10.77%) age 40 years or above mean (56 ± 11.75), median 54 (40-89), with clinical features of acute appendicitis were included in the final analysis. F:M ratio was (1:1.06). CT scan showed in only 1 patient (1.25%, OR = 0.806, p = 0.695), suspicion of cecal tumor and underwent right hemicolectomy. Histological examination of specimen showed, 2 patients (1.11%, OR = 1.10, p = 0.47) had primary appendiceal tumors, in which one patient was histologically reported as appendiceal mucocele (mucinous cystadenoma with low-grade dysplasia), while the other one had appendeceal carcinoid (Goblet cell carcinoid). In the other tumor group one patient had metastatic involvement of appendix from ovarian tumor. The time to appendectomy in radiological group was delayed by (9.2 ± 3.7 h). 131 (73.1%) had laparoscopic while 48 (26.81%) underwent open appendectomy. The negative appendectomy rate was (1.12%) and 30 days complication rate was (11.73%, p = 0.27). Mean length of stay was 3.54�

Transcriptional Analysis of Aggressiveness and Heterogeneity across Grades of Astrocytomas

PubMed Central

Wang, Chunjing; Funk, Cory C.; Eddy, James A.; Price, Nathan D.

2013-01-01

Astrocytoma is the most common glioma, accounting for half of all primary brain and spinal cord tumors. Late detection and the aggressive nature of high-grade astrocytomas contribute to high mortality rates. Though many studies identify candidate biomarkers using high-throughput transcriptomic profiling to stratify grades and subtypes, few have resulted in clinically actionable results. This shortcoming can be attributed, in part, to pronounced lab effects that reduce signature robustness and varied individual gene expression among patients with the same tumor. We addressed these issues by uniformly preprocessing publicly available transcriptomic data, comprising 306 tumor samples from three astrocytoma grades (Grade 2, 3, and 4) and 30 non-tumor samples (normal brain as control tissues). Utilizing Differential Rank Conservation (DIRAC), a network-based classification approach, we examined the global and individual patterns of network regulation across tumor grades. Additionally, we applied gene-based approaches to identify genes whose expression changed consistently with increasing tumor grade and evaluated their robustness across multiple studies using statistical sampling. Applying DIRAC, we observed a global trend of greater network dysregulation with increasing tumor aggressiveness. Individual networks displaying greater differences in regulation between adjacent grades play well-known roles in calcium/PKC, EGF, and transcription signaling. Interestingly, many of the 90 individual genes found to monotonically increase or decrease with astrocytoma grade are implicated in cancer-affected processes such as calcium signaling, mitochondrial metabolism, and apoptosis. The fact that specific genes monotonically increase or decrease with increasing astrocytoma grade may reflect shared oncogenic mechanisms among phenotypically similar tumors. This work presents statistically significant results that enable better characterization of different human astrocytoma grades

Transcriptional analysis of aggressiveness and heterogeneity across grades of astrocytomas.

PubMed

Wang, Chunjing; Funk, Cory C; Eddy, James A; Price, Nathan D

2013-01-01

Astrocytoma is the most common glioma, accounting for half of all primary brain and spinal cord tumors. Late detection and the aggressive nature of high-grade astrocytomas contribute to high mortality rates. Though many studies identify candidate biomarkers using high-throughput transcriptomic profiling to stratify grades and subtypes, few have resulted in clinically actionable results. This shortcoming can be attributed, in part, to pronounced lab effects that reduce signature robustness and varied individual gene expression among patients with the same tumor. We addressed these issues by uniformly preprocessing publicly available transcriptomic data, comprising 306 tumor samples from three astrocytoma grades (Grade 2, 3, and 4) and 30 non-tumor samples (normal brain as control tissues). Utilizing Differential Rank Conservation (DIRAC), a network-based classification approach, we examined the global and individual patterns of network regulation across tumor grades. Additionally, we applied gene-based approaches to identify genes whose expression changed consistently with increasing tumor grade and evaluated their robustness across multiple studies using statistical sampling. Applying DIRAC, we observed a global trend of greater network dysregulation with increasing tumor aggressiveness. Individual networks displaying greater differences in regulation between adjacent grades play well-known roles in calcium/PKC, EGF, and transcription signaling. Interestingly, many of the 90 individual genes found to monotonically increase or decrease with astrocytoma grade are implicated in cancer-affected processes such as calcium signaling, mitochondrial metabolism, and apoptosis. The fact that specific genes monotonically increase or decrease with increasing astrocytoma grade may reflect shared oncogenic mechanisms among phenotypically similar tumors. This work presents statistically significant results that enable better characterization of different human astrocytoma grades

Terahertz reflectometry imaging for low and high grade gliomas

NASA Astrophysics Data System (ADS)

Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

2016-10-01

Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.

Pattern of Tumor Shrinkage during Neoadjuvant Chemotherapy Is Associated with Prognosis in Low-Grade Luminal Early Breast Cancer.

PubMed

Fukada, Ippei; Araki, Kazuhiro; Kobayashi, Kokoro; Shibayama, Tomoko; Takahashi, Shunji; Gomi, Naoya; Kokubu, Yumi; Oikado, Katsunori; Horii, Rie; Akiyama, Futoshi; Iwase, Takuji; Ohno, Shinji; Hatake, Kiyohiko; Sata, Naohiro; Ito, Yoshinori

2018-01-01

Purpose To evaluate the association between tumor shrinkage patterns shown with magnetic resonance (MR) imaging during neoadjuvant chemotherapy (NAC) and prognosis in patients with low-grade luminal breast cancer. Materials and Methods This retrospective study was approved by the institutional review board and informed consent was obtained from all subjects. The low-grade luminal breast cancer was defined as hormone receptor-positive and human epidermal growth factor receptor 2-negative with nuclear grades 1 or 2. The patterns of tumor shrinkage as revealed at MR imaging were categorized into two types: concentric shrinkage (CS) and non-CS. Among 854 patients who had received NAC in a single institution from January 2000 to December 2009, 183 patients with low-grade luminal breast cancer were retrospectively evaluated for the development set. Another data set from 292 patients who had received NAC in the same institution between January 2010 and December 2012 was used for the validation set. Among these 292 patients, 121 patients with low-grade luminal breast cancer were retrospectively evaluated. Results In the development set, the median observation period was 67.9 months. Recurrence was observed in 31 patients, and 16 deaths were related to breast cancer. There were statistically significant differences in both the disease-free survival (DFS) and overall survival (OS) rates between patterns of tumor shrinkage (P < .001 and P < .001, respectively). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .001) and OS (P = .009) rate. In the validation set, the median follow-up period was 56.9 months. Recurrence was observed in 20 patients (16.5%) and eight (6.6%) deaths were related to breast cancer. DFS rate was significantly longer in patients with the CS pattern (72.8 months; 95% confidence interval [CI]: 69.9, 75.6 months) than in those with the non-CS pattern (56.0 months; 95% CI: 49.1, 62.9 months

EMMPRIN expression positively correlates with WHO grades of astrocytomas and meningiomas.

PubMed

Tsai, Wen-Chiuan; Chen, Ying; Huang, Li-Chun; Lee, Herng-Sheng; Ma, Hsin-I; Huang, Shih-Ming; Sytwu, Huey-Kang; Hueng, Dueng-Yuan

2013-09-01

High-grade primary brain tumors possessed poor outcome due to invasiveness. Extracellular matrix metalloproteinase inducer (EMMPRIN) stimulates peri-tumoral fibroblasts to secrete matrix metalloproteinase and promote invasiveness. This study hypothesized that high-grade brain tumors overexpress EMMPRIN. Analyzing the public delinked database from the Gene Expression Omnibus profile, the results showed that the EMMPRIN mRNA level was higher in WHO grade IV (n = 81) than in grade III (n = 19, p < 0.0005) astrocytomas and non-tumor brain tissue controls (n = 23, p < 0.00001). The results of tissue microarray-based immunohistochemical (IHC) staining revealed that EMMPRIN levels positively correlated with WHO grades for astrocytomas (p = 0.008) and meningiomas (p = 0.048). EMMPRIN mRNA levels in conventional glioma cell lines (n = 36) was not less than those in glioma primary culture cells (n = 27) and glioblastoma stem-like cells (n = 12). The GBM8401, U87MG, and LN229 human glioma cell lines also overexpressed EMMPRIN. Hematoxylin and eosin, IHC, and immunofluorescence staining of xenografts confirmed that high-grade brain tumors overexpressed EMMPRIN. Lastly, Kaplan-Meier analysis revealed poorer survival in WHO grade IV (n = 56) than in grade III astrocytomas (n = 21, by log-rank test; p = 0.0001, 95 % CI: 1.842-3.053). However, in high-grade astrocytomas, there was no difference in survival between high and low EMMPRIN mRNA levels. Thus, this study identified that high-grade brain tumors overexpress EMMPRIN, which positively correlates with WHO grades in human astrocytomas and meningiomas, and suggests that EMMPRIN may be a therapeutic target of brain tumor.

Pediatric Brain Tumors: Genomics and Epigenomics Pave the Way.

PubMed

Fontebasso, Adam M; Jabado, Nada

2015-01-01

Primary malignant brain tumors remain a disproportionate cause of morbidity and mortality in humans. A number of studies exploring the cancer genome of brain tumors across ages using integrated genetics and epigenetics and next-generation sequencing technologies have recently emerged. This has led to considerable advances in the understanding of the basic biology and pathogenesis of brain tumors, including the most malignant and common variants in children: gliomas and medulloblastoma. Notably, studies of pediatric brain tumors have identified unexpected oncogenic pathways implicated in tumorigenesis. These range from a single pathway/molecule defect such as abnormalities of the mitogen-activated protein kinase pathway, considered to be a hallmark of pilocytic astrocytomas, to alterations in the epigenome as a critical component altered in many subgroups of high-grade brain tumors. Importantly, the type, timing, and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain tumor they target and critical markers for therapy that will help refine pathological grading. We summarize these novel findings in pediatric brain tumors, which also are put in the context of the evolving notion of molecular pathology, now a mandated tool for proper classification and therapy assignment in the clinical setting.

Differentiation between benign and malignant palatal tumors using conventional MRI: a retrospective analysis of 130 cases.

PubMed

Zheng, Yingyan; Xiao, Zebin; Zhang, Hua; She, Dejun; Lin, Xuehua; Lin, Yu; Cao, Dairong

2018-04-01

To evaluate the discriminative value of conventional magnetic resonance imaging between benign and malignant palatal tumors. Conventional magnetic resonance imaging features of 130 patients with palatal tumors confirmed by histopathologic examination were retrospectively reviewed. Clinical data and imaging findings were assessed between benign and malignant tumors and between benign and low-grade malignant salivary gland tumors. The variables that were significant in differentiating benign from malignant lesions were further identified using logistic regression analysis. Moreover, imaging features of each common palatal histologic entity were statistically analyzed with the rest of the tumors to define their typical imaging features. Older age, partially defined and ill-defined margins, and absence of a capsule were highly suggestive of malignant palatal tumors, especially ill-defined margins (β = 6.400). The precision in determining malignant palatal tumors achieved a sensitivity of 92.8% and a specificity of 85.6%. In addition, irregular shape, ill-defined margins, lack of a capsule, perineural spread, and invasion of surrounding structures were more often associated with low-grade malignant salivary gland tumors. Conventional magnetic resonance imaging is useful for differentiating benign from malignant palatal tumors as well as benign salivary gland tumors from low-grade salivary gland malignancies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Cranial Chordoma: A New Preoperative Grading System.

PubMed

Brito da Silva, Harley; Straus, David; Barber, Jason K; Rostomily, Robert C; Ferreira, Manuel; Sekhar, Laligam N

2017-11-03

Chordomas are rare but challenging neoplasms involving the skull base. A preoperative grading system will be useful to identify both areas for treatment and risk factors, and correlate to the degree of resection, complications, and recurrence. To propose a new grading system for cranial chordomas designed by the senior author. Its purpose is to enable comparison of different tumors with a similar pathology to clivus chordoma, and statistically correlate with postoperative outcomes. The numerical grading system included tumor size, site of the tumor, vascular encasement, intradural extension, brainstem invasion, and recurrence of the tumor either after surgery or radiotherapy with a range of 2 to 25 points; it was used in 42 patients with cranial chordoma. The grading system was correlated with number of operations for resection, degree of resection, number and type of complications, recurrence, and survival. We found 3 groups: low-risk 0 to 7 points, intermediate-risk 8 to 12 points, and high-risk ≥13 points in the grading system. The 3 groups were correlated with the following: extent of resection (partial, subtotal, or complete; P < .002); number of operative stages to achieve removal (P < .014); tumor recurrence (P = .03); postoperative Karnofsky Performance Status (P < .001); and with successful outcome (P = .005). The grading system itself correlated with the outcome (P = .005). The proposed chordoma grading system can help surgeons to predict the difficulty of the case and know which areas of the skull base will need attention to plan further therapy. © Congress of Neurological Surgeons 2017.

Neuropsychological status in children and young adults with benign and low-grade brain tumors treated prospectively with focal stereotactic conformal radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jalali, Rakesh; Goswami, Savita; Sarin, Rajiv

2006-11-15

Purpose: To present prospective neuropsychological data at baseline and follow-up in children and young adults with benign and low-grade gliomas treated with focal stereotactic conformal radiotherapy (SCRT). Methods and Materials: A total of 22 patients (age 4-25 years) with residual/progressive benign and low-grade brain tumors considered suitable for SCRT underwent detailed and in-depth neuropsychological and cognitive testing at baseline before SCRT. The test battery included measurement of age-adjusted intelligence quotients (IQs) and cognitive parameters of visual, spatial, visuomotor, and attention concentrations. Anxiety was measured using the State-Trait Anxiety Inventory for Children and Hamilton Anxiety Rating Scale for patients >16 yearsmore » old. Patients were treated with high-precision conformal radiotherapy under stereotactic guidance to a dose of 54 Gy in 30 fractions. All neuropsychological assessments were repeated at 6 and 24 months after SCRT completion and compared with the baseline values. Results: The baseline mean full-scale IQ before starting RT for patients <16 years was 82 (range, 33-105). For those >16 years, the corresponding value was 72 (range, 64-129). Of 20 evaluable patients, 14 (70%) had less than average IQs at baseline, even before starting radiotherapy. The verbal IQ, performance IQ, and full-scale IQ, as well as other cognitive scores, did not change significantly at the 6- and 24-month follow-up assessments for all patients. The memory quotient in older children and young adults was maintained at 6 and 24 months after SCRT, with a mean value of 93 and 100, respectively, compared with a mean baseline value of 81 before RT. The mean anxiety score in children measured by the C1 and C2 components of the State-Trait Anxiety Inventory for Children (STAIC) was 48 and 40, respectively, which improved significantly to mean values of 30 and 26, respectively, at the 24-month follow-up assessment (p = 0.005). The mean depression score

Nonlinear ghost waves accelerate the progression of high-grade brain tumors

NASA Astrophysics Data System (ADS)

Pardo, Rosa; Martínez-González, Alicia; Pérez-García, Víctor M.

2016-10-01

We study a reduced continuous model describing the evolution of high grade gliomas in response to hypoxic events through the interplay of different cellular phenotypes. We show that hypoxic events, even when sporadic and/or limited in space, may have a crucial role on the acceleration of high grade gliomas growth. Our modeling approach is based on two cellular phenotypes. One of them is more migratory and a second one is more proliferative. Transitions between both phenotypes are driven by the local oxygen values, assumed in this simple model to be uniform. Surprisingly, even very localized in time hypoxia events leading to transient migratory populations have the potential to accelerate the tumor's invasion speed up to speeds close to those of the migratory phenotype. The high invasion speed persists for times much longer than the lifetime of the hypoxic event. Moreover, the phenomenon is observed both when the migratory cells form a persistent wave of cells located on the invasion front and when they form a evanescent "ghost" wave disappearing after a short time by decay to the more proliferative phenotype. Our findings are obtained through numerical simulations of the model equations both in 1D and higher dimensional scenarios. We also provide a deeper mathematical analysis of some aspects of the problem such as the conditions for the existence of persistent waves of cells with a more migratory phenotype.

Novel strategies of Raman imaging for brain tumor research.

PubMed

Anna, Imiela; Bartosz, Polis; Lech, Polis; Halina, Abramczyk

2017-10-17

Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma, low grade astrocytoma and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational features and Raman images we provide a real-time feedback method that is label-free to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, proteins, DNA and RNA. Our results indicate marked metabolic differences between low and high grade brain tumors. We discuss molecular mechanisms causing these metabolic changes, particularly lipid alterations in malignant medulloblastoma and low grade gliomas that may shed light on the mechanisms driving tumor recurrence thereby revealing new approaches for the treatment of malignant glioma. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have found that almost all tumors studied in the paper have increased Raman signals of nucleic acids. This increase can be interpreted as increased DNA/RNA turnover in brain tumors. We have shown that the ratio of Raman intensities I 2930 /I 2845 at 2930 and 2845 cm -1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the different lipid and protein contents of cancerous brain tissue compared to the non-tumor tissue. We found that

Novel strategies of Raman imaging for brain tumor research

PubMed Central

Anna, Imiela; Bartosz, Polis; Lech, Polis; Halina, Abramczyk

2017-01-01

Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma, low grade astrocytoma and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational features and Raman images we provide a real–time feedback method that is label-free to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, proteins, DNA and RNA. Our results indicate marked metabolic differences between low and high grade brain tumors. We discuss molecular mechanisms causing these metabolic changes, particularly lipid alterations in malignant medulloblastoma and low grade gliomas that may shed light on the mechanisms driving tumor recurrence thereby revealing new approaches for the treatment of malignant glioma. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have found that almost all tumors studied in the paper have increased Raman signals of nucleic acids. This increase can be interpreted as increased DNA/RNA turnover in brain tumors. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm-1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the different lipid and protein contents of cancerous brain tissue compared to the non-tumor tissue. We found that

A Probabilistic Atlas of Diffuse WHO Grade II Glioma Locations in the Brain

PubMed Central

Baumann, Cédric; Zouaoui, Sonia; Yordanova, Yordanka; Blonski, Marie; Rigau, Valérie; Chemouny, Stéphane; Taillandier, Luc; Bauchet, Luc; Duffau, Hugues; Paragios, Nikos

2016-01-01

Diffuse WHO grade II gliomas are diffusively infiltrative brain tumors characterized by an unavoidable anaplastic transformation. Their management is strongly dependent on their location in the brain due to interactions with functional regions and potential differences in molecular biology. In this paper, we present the construction of a probabilistic atlas mapping the preferential locations of diffuse WHO grade II gliomas in the brain. This is carried out through a sparse graph whose nodes correspond to clusters of tumors clustered together based on their spatial proximity. The interest of such an atlas is illustrated via two applications. The first one correlates tumor location with the patient’s age via a statistical analysis, highlighting the interest of the atlas for studying the origins and behavior of the tumors. The second exploits the fact that the tumors have preferential locations for automatic segmentation. Through a coupled decomposed Markov Random Field model, the atlas guides the segmentation process, and characterizes which preferential location the tumor belongs to and consequently which behavior it could be associated to. Leave-one-out cross validation experiments on a large database highlight the robustness of the graph, and yield promising segmentation results. PMID:26751577

Inhibition of nuclear factor-kappa B enhances the tumor growth of ovarian cancer cell line derived from a low-grade papillary serous carcinoma in p53-independent pathway.

PubMed

Xiao, Xue; Yang, Gong; Bai, Peng; Gui, Shunping; Nyuyen, Tri M Bui; Mercado-Uribe, Imelda; Yang, Mei; Zou, Juan; Li, Qintong; Xiao, Jianguo; Chang, Bin; Liu, Guangzhi; Wang, He; Liu, Jinsong

2016-08-02

NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer. The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells. Western blot analysis indicated increased expression of the anti-apoptotic proteins Bcl-xL and reduced expression of the pro-apoptotic proteins Bax, Bad, and Bid in HOC-7/IĸBαM cell. Further investigations validate this conclusion in KRAS wildtype cell line SKOV3. Interesting, NF-kB can exert its pro-apoptotic effect by activating mitogen-activated protein kinase (MAPK) phosphorylation in SKOV3 ovarian cancer cell, whereas opposite changes detected in p-MEK in HOC-7 ovarian cancer cell, the same as some chemoresistant ovarian cancer cell lines. In vivo animal assay performed on BALB/athymic mice showed that injection of HOC-7 induced subcutaneous tumor growth, which was completely regressed within 7 weeks. In comparison, HOC-7/IĸBαM cells caused sustained tumor growth and abrogated tumor regression, suggesting that knock-down of NF-kB by IĸBαM promoted sustained tumor growth and delayed tumor regression in HOC-7 cells. Our results demonstrated that NF-kB may function as a tumor suppressor by facilitating regression of low grade ovarian serous carcinoma through activating pro-apoptotic pathways.

Contribution of an alveolar cell of origin to the high-grade malignant phenotype of pregnancy-associated breast cancer.

PubMed

Haricharan, S; Hein, S M; Dong, J; Toneff, M J; Aina, O H; Rao, P H; Cardiff, R D; Li, Y

2014-12-11

Pregnancy-associated breast cancers (PABCs) are tumors diagnosed during pregnancy or up to 5 years following parturition, and are usually high-grade, connective tissue-rich, and estrogen receptor (ER)/progesterone receptor-negative. Little is known about the cellular origin of PABCs or the mechanisms by which PABCs are initiated. Using the RCAS retrovirus to deliver the ErbB2 oncogene into the mammary epithelium of our previously reported MMTV-tva transgenic mice, we detected high-grade, poorly differentiated, stroma-rich and ER-negative tumors during pregnancy and lactation. These high-grade and stroma-rich tumors were less frequent in involuted mice or in age-matched nulliparous mice. More importantly, by generating a WAP-tva transgenic line for expression of ErbB2 selectively in WAP(+) mammary alveolar cells, we found that tumors had similar morphological phenotypes (high grade, poorly differentiated, stroma-rich and ER-negative), irrespective of the time since pregnancy and even in the absence of pregnancy. These data suggest that PABCs arise preferentially from an alveolar cell population that expands during pregnancy and lactation. This somatic mouse model may also be useful for preclinical testing of new prophylactic and therapeutic strategies against PABC.

[Neuroendocrine neoplasm of digestive system with different grades: a clinicopathologic and prognostic study].

PubMed

Zhang, Ming-hui; Liu, Yan-hui; Luo, Xin-lan; Lin, Xing-tao; Zhuang, Heng-guo

2012-07-01

To study the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. The clinicopathologic features of 139 cases of neuroendocrine neoplasm occurring in digestive system were retrospectively reviewed and graded according to the 2010 World Health Organization classification of tumours of the digestive system. Immunohistochemical study for synaptophysin, chromogranin A and Ki-67 was carried out. The follow-up and survival data were analysed using Kaplan-Meier method. Prognostic factors were tested by Log-rank testing and independent risk factors were analysed using Cox regression model. Amongst the 139 cases studied, there were 88 cases (63.3%) of grade 1 tumors, 9 cases (6.5%) of grade 2 tumors and 42 cases (30.2%) of grade 3 tumors. There was diffusely positive staining for synaptophysin and chromogranin A in most of the grade 1 and grade 2 tumors. The staining in grade 3 tumors however was focal (P < 0.05). The differences in tumor size, depth of invasion, presence of tumor emboli, perineural permeation, nodal involvement, distant metastasis and survival rate amongst the three groups was statistically significant (P < 0.05). There is significant difference in the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. It is considered as an independent prognostic factor and represents a useful tool for prognostic evaluation of such tumors, both in clinical practice and research.

Radiation associated tumors following therapeutic cranial radiation

PubMed Central

Chowdhary, Abhineet; Spence, Alex M.; Sales, Lindsay; Rostomily, Robert C.; Rockhill, Jason K.; Silbergeld, Daniel L.

2012-01-01

Background: A serious, albeit rare, sequel of therapeutic ionizing radiotherapy is delayed development of a new, histologically distinct neoplasm within the radiation field. Methods: We identified 27 cases, from a 10-year period, of intracranial tumors arising after cranial irradiation. The original lesions for which cranial radiation was used for treatment included: tinea capitis (1), acute lymphoblastic leukemia (ALL; 5), sarcoma (1), scalp hemangioma (1), cranial nerve schwannoma (1) and primary (13) and metastatic (1) brain tumors, pituitary tumor (1), germinoma (1), pinealoma (1), and unknown histology (1). Dose of cranial irradiation ranged from 1800 to 6500 cGy, with a mean of 4596 cGy. Age at cranial irradiation ranged from 1 month to 43 years, with a mean of 13.4 years. Results: Latency between radiotherapy and diagnosis of a radiation-induced neoplasm ranged from 4 to 47 years (mean 18.8 years). Radiation-induced tumors included: meningiomas (14), sarcomas (7), malignant astrocytomas (4), and medulloblastomas (2). Data were analyzed to evaluate possible correlations between gender, age at irradiation, dose of irradiation, latency, use of chemotherapy, and radiation-induced neoplasm histology. Significant correlations existed between age at cranial irradiation and development of either a benign neoplasm (mean age 8.5 years) versus a malignant neoplasm (mean age 20.3; P = 0.012), and development of either a meningioma (mean age 7.0 years) or a sarcoma (mean age 27.4 years; P = 0.0001). There was also a significant positive correlation between latency and development of either a meningioma (mean latency 21.8 years) or a sarcoma (mean latency 7.7 years; P = 0.001). The correlation between dose of cranial irradiation and development of either a meningioma (mean dose 4128 cGy) or a sarcoma (mean dose 5631 cGy) approached significance (P = 0.059). Conclusions: Our study is the first to show that younger patients had a longer latency period and were more likely

Challenges for the functional diffusion map in pediatric brain tumors

PubMed Central

Grech-Sollars, Matthew; Saunders, Dawn E.; Phipps, Kim P.; Kaur, Ramneek; Paine, Simon M.L.; Jacques, Thomas S.; Clayden, Jonathan D.; Clark, Chris A.

2014-01-01

Background The functional diffusion map (fDM) has been suggested as a tool for early detection of tumor treatment efficacy. We aim to study 3 factors that could act as potential confounders in the fDM: areas of necrosis, tumor grade, and change in tumor size. Methods Thirty-four pediatric patients with brain tumors were enrolled in a retrospective study, approved by the local ethics committee, to examine the fDM. Tumors were selected to encompass a range of types and grades. A qualitative analysis was carried out to compare how fDM findings may be affected by each of the 3 confounders by comparing fDM findings to clinical image reports. Results Results show that the fDM in areas of necrosis do not discriminate between treatment response and tumor progression. Furthermore, tumor grade alters the behavior of the fDM: a decrease in apparent diffusion coefficient (ADC) is a sign of tumor progression in high-grade tumors and treatment response in low-grade tumors. Our results also suggest using only tumor area overlap between the 2 time points analyzed for the fDM in tumors of varying size. Conclusions Interpretation of fDM results needs to take into account the underlying biology of both tumor and healthy tissue. Careful interpretation of the results is required with due consideration to areas of necrosis, tumor grade, and change in tumor size. PMID:24305721

Lenalidomide in Treating Young Patients With Recurrent, Progressive, or Refractory CNS Tumors

ClinicalTrials.gov

2013-09-27

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Outcomes of Pediatric Low-grade Gliomas Treated With Radiation Therapy: A Single-institution Study

PubMed Central

Raikar, Sunil S.; Halloran, Donna R.; Elliot, Michael; McHugh, Michele; Patel, Shaun; Gauvain, Karen M.

2014-01-01

Summary Radiation therapy is often considered the treatment of choice for low-grade gliomas. However, given the long-term effects of radiation on the developing brain, the appropriate use of radiation therapy in pediatric patients remains controversial. The purpose of this study was to evaluate progression-free survival (PFS) of pediatric low-grade glioma patients treated with radiation therapy. Data were obtained through a retrospective chart review of patients treated between 1991 and 2008 from a single tertiary care center in the midwest. The study population consisted of 17 patients, of whom 8 (47%) had tumor recurrence after radiation therapy. The median follow-up time was 8.2 years, with a range of 2.3 to 17.2 years. The median age at diagnosis was 5.4 years, and the median age at radiation therapy was 9.4 years. The 3- and the 10-year PFS were 69% ± 11.7% and 46% ± 13.3%, respectively. A significant difference in PFS was seen when comparing brainstem tumors with hypothalamic/optic pathway tumors (P = 0.019). Differences in PFS based on the age at diagnosis, the extent of initial surgery, and indication for radiation therapy were not significant. A larger multicenter study is needed to better assess PFS in these patients. PMID:24714505

The two glycolytic markers GLUT1 and MCT1 correlate with tumor grade and survival in clear-cell renal cell carcinoma

PubMed Central

Dadone, Bérengère; Durand, Matthieu; Borchiellini, Delphine; Amiel, Jean; Pouyssegur, Jacques; Rioux-Leclercq, Nathalie; Pages, Gilles; Burel-Vandenbos, Fanny; Mazure, Nathalie M.

2018-01-01

Background Clear-cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Although ccRCC is characterized by common recurrent genetic abnormalities, including inactivation of the von Hippel-Lindau (vhl) tumor suppressor gene resulting in stabilization of hypoxia-inducible factors (HIFs), the tumor aggressiveness and outcome of ccRCC is variable. New biomarkers are thus required to improve ccRCC diagnosis, prognosis and therapeutic options. This work aims to investigate the expression of HIF and proteins involved in metabolism and pH regulation. Their correlation to histoprognostic parameters and survival was analyzed. Methods ccRCC of 45 patients were analyzed. HIF-1α, HIF-2α, HAF, GLUT1, MCT1, MCT4, CAIX and CAXII expression was assessed by immunohistochemistry in a semi-quantitative and qualitative manner. The GLUT1, MCT1, MCT4, CAIX and CAXII mRNA levels were analyzed in an independent cohort of 43 patients. Results A significant correlation was observed between increased GLUT1, MCT1, CAXII protein expression and a high Fuhrman grade in ccRCC patients. Moreover, while HIF-1α, HIF-2α and HAF expression was heterogenous within tumors, we observed and confirmed that HIF-2α co-localized with HAF. We confirmed, in an independent cohort, that GLUT1, MCT1 and CAXII mRNA levels correlated with the Fuhrman grade. Moreover, we demonstrated that the high mRNA level of both MCT1 and GLUT1 correlated with poor prognosis. Conclusions This study demonstrates for the first time a link between the aggressiveness of high- Fuhrman grade ccRCC and metabolic reprogramming. It also confirms the role of HIF-2α and HAF in tumor invasiveness. Finally, these results demonstrate that MCT1 and GLUT1 are strong prognostic markers and promising therapeutic targets. PMID:29481555

The two glycolytic markers GLUT1 and MCT1 correlate with tumor grade and survival in clear-cell renal cell carcinoma.

PubMed

Ambrosetti, Damien; Dufies, Maeva; Dadone, Bérengère; Durand, Matthieu; Borchiellini, Delphine; Amiel, Jean; Pouyssegur, Jacques; Rioux-Leclercq, Nathalie; Pages, Gilles; Burel-Vandenbos, Fanny; Mazure, Nathalie M

2018-01-01

Clear-cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Although ccRCC is characterized by common recurrent genetic abnormalities, including inactivation of the von Hippel-Lindau (vhl) tumor suppressor gene resulting in stabilization of hypoxia-inducible factors (HIFs), the tumor aggressiveness and outcome of ccRCC is variable. New biomarkers are thus required to improve ccRCC diagnosis, prognosis and therapeutic options. This work aims to investigate the expression of HIF and proteins involved in metabolism and pH regulation. Their correlation to histoprognostic parameters and survival was analyzed. ccRCC of 45 patients were analyzed. HIF-1α, HIF-2α, HAF, GLUT1, MCT1, MCT4, CAIX and CAXII expression was assessed by immunohistochemistry in a semi-quantitative and qualitative manner. The GLUT1, MCT1, MCT4, CAIX and CAXII mRNA levels were analyzed in an independent cohort of 43 patients. A significant correlation was observed between increased GLUT1, MCT1, CAXII protein expression and a high Fuhrman grade in ccRCC patients. Moreover, while HIF-1α, HIF-2α and HAF expression was heterogenous within tumors, we observed and confirmed that HIF-2α co-localized with HAF. We confirmed, in an independent cohort, that GLUT1, MCT1 and CAXII mRNA levels correlated with the Fuhrman grade. Moreover, we demonstrated that the high mRNA level of both MCT1 and GLUT1 correlated with poor prognosis. This study demonstrates for the first time a link between the aggressiveness of high- Fuhrman grade ccRCC and metabolic reprogramming. It also confirms the role of HIF-2α and HAF in tumor invasiveness. Finally, these results demonstrate that MCT1 and GLUT1 are strong prognostic markers and promising therapeutic targets.

Irinotecan in Treating Children With Refractory Solid Tumors

ClinicalTrials.gov

2013-06-13

Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Miscellaneous rare paratesticular tumors.

PubMed

Henley, J D; Ferry, J; Ulbright, T M

2000-11-01

A few uncommon but distinctive tumors may preferentially involve the paratestis. The 3 unusual tumors that represent the focus of this discussion are the ovarian-type epithelial tumors (OTET), the desmoplastic small round cell tumor (DSRCT), and the melanotic neuroectodermal tumor of infancy (MNTI). The OTETs are testicular homologues of their more common namesake counterparts that arise in the ovary. Most frequent of these are serous tumors of borderline malignancy, with fewer cases of serous carcinomas or other forms of mullerian differentiation. DSRCT is an increasingly recognized, aggressive, "small blue cell" neoplasm with distinctive clinical and pathologic features. These polyphenotypic tumors characteristically, but not invariably, arise in intimate association with the serosal membrane of the peritoneal cavity and harbor a signature translocation-t(11;22)(p13,q12). In the paratestis they often involve the surface of the epididymis. The MNTI is an enigmatic, histologically distinctive, low-grade neoplasm occasionally encountered in the epididymis. Recognition of its features is essential to avoid misdiagnosis as a more aggressive "small blue cell" neoplasm and consequent therapeutic mismanagement. Primary hematopoietic tumors of the paratesticular structures are rare. There appears to be a tendency for young men to have low-grade lymphomas with an indolent course and older patients to develop higher-grade tumors. Plasmacytoma and granulocytic sarcoma of the paratestis are even more rare and are often susceptible to misinterpretation. Finally, metastatic tumors and a variety of other very rare neoplasms are discussed.

Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene-induced lung tumors in aged mice

USDA-ARS?s Scientific Manuscript database

Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic KrasG12D was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activati...

Effect of aged garlic extract on immune responses to experimental fibrosarcoma tumor in BALB/c mice.

PubMed

Tabari, M Abouhosseini; Ebrahimpour, S

2014-01-01

Aged garlic extract (AGE) has many biological activities including radical scavenging, antioxidative and immunomodulative effects. In this research work, the antitumor and immunomodulatory effects of AGE against fibrosarcoma implanted tumor were studied. WEHI-164 fibrosarcoma cells were implanted subcutaneously on day 0 into the right flank of 40 BALB/c mice at age of 8 weeks. Mice were randomly categorized in two separate groups: First received AGE (100 mg/kg, IP), second group as the control group received phosphate buffered saline. Treatments were carried out 3 times/week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flow cytometry. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of interferon gamma (IFN-γ) and interleukin-4 cytokines were measured. The mice received AGE had significantly longer survival time compared with the control mice. The inhibitory effect on tumor growth was seen in AGE treated mice. The CD4+/CD8+ ratio and in vitro IFN-γ production of splenocytes were significantly increased in AGE group. WEHI-164 specific cytotoxicity of splenocytes from AGE mice was also significantly increased at 25:1 E: T ratio. Administration of AGE resulted in improved immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice. AGE showed significant effects on inhibition of tumor growth and longevity of survival times.

Radiogenomic analysis of lower grade glioma: a pilot multi-institutional study shows an association between quantitative image features and tumor genomics

NASA Astrophysics Data System (ADS)

Mazurowski, Maciej A.; Clark, Kal; Czarnek, Nicholas M.; Shamsesfandabadi, Parisa; Peters, Katherine B.; Saha, Ashirbani

2017-03-01

Recent studies showed that genomic analysis of lower grade gliomas can be very effective for stratification of patients into groups with different prognosis and proposed specific genomic classifications. In this study, we explore the association of one of those genomic classifications with imaging parameters to determine whether imaging could serve a similar role to genomics in cancer patient treatment. Specifically, we analyzed imaging and genomics data for 110 patients from 5 institutions from The Cancer Genome Atlas and The Cancer Imaging Archive datasets. The analyzed imaging data contained preoperative FLAIR sequence for each patient. The images were analyzed using the in-house algorithms which quantify 2D and 3D aspects of the tumor shape. Genomic data consisted of a cluster of clusters classification proposed in a very recent and leading publication in the field of lower grade glioma genomics. Our statistical analysis showed that there is a strong association between the tumor cluster-of-clusters subtype and two imaging features: bounding ellipsoid volume ratio and angular standard deviation. This result shows high promise for the potential use of imaging as a surrogate measure for genomics in the decision process regarding treatment of lower grade glioma patients.

Intracranial solitary fibrous tumors/hemangiopericytomas: first report of malignant progression.

PubMed

Apra, Caroline; Mokhtari, Karima; Cornu, Philippe; Peyre, Matthieu; Kalamarides, Michel

2018-06-01

OBJECTIVE Meningeal solitary fibrous tumors/hemangiopericytomas (MSFTs/HPCs) are rare intracranial tumors resembling meningiomas. Their classification was redefined in 2016 by the World Health Organization (WHO) as benign Grade I fibrohyaline type, intermediate Grade II hypercellular type, and malignant highly mitotic Grade III. This grouping is based on common histological features and identification of a common NAB2-STAT6 fusion. METHODS The authors retrospectively identified 49 cases of MSFT/HPC. Clinical data were obtained from the medical records, and all cases were analyzed according to this new 2016 WHO grading classification in order to identify malignant transformations. RESULTS Recurrent surgery was performed in 18 (37%) of 49 patients. Malignant progression was identified in 5 (28%) of these 18 cases, with 3 Grade I and 2 Grade II tumors progressing to Grade III, 3-13 years after the initial surgery. Of 31 Grade III tumors treated in this case series, 16% (5/31) were proved to be malignant progressions from lower-grade tumors. CONCLUSIONS Low-grade MSFTs/HPCs can transform into higher grades as shown in this first report of such progression. This is a decisive argument in favor of a common identity for MSFT and meningeal HPC. High-grade MSFTs/HPCs tend to recur more often and be associated with reduced overall survival. Malignant progression could be one mechanism explaining some recurrences or metastases, and justifying long-term follow-up, even for patients with Grade I tumors.

Isotopic mapping of age provinces in Precambrian high-grade terrains: Sri Lanka

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milisenda, C.C.; Liew, T.C.; Hofmann, A.W.

1988-09-01

Nd model ages of amphibolite- and granulite-grade rocks in Sri Lanka form a simple region pattern that broadly correlates with mappable geological units, and is in effect an isotopic map of the island's basement. The granulite-grade units of the Highland Group and Southwest Group have model ages of 2.2-3.0 Ga indicating derivation mainly from late Archean sources. They are bounded to the east and west by late Proterozoic gneisses of the Vijayan Complex with model ages of 1.1-2.0 Ga. The isotopic data identify three distinct crustal provinces and are not consistent with earlier suggestions that the Vijayan gneisses are retrogrademore » equivalents of the Highland granulites. Sri Lanka is not a direct continuation of the Archean Dharwar Craton of southern India. Identification of Vijayan-type juvenile crustal terrains in other Gondwana fragments may play a key role in determining the precise attachment of southern India-Sri Lanka in eastern Gondwana.« less

Gamma Knife treatment of low-grade gliomas in children.

PubMed

Ekşi, Murat Şakir; Yılmaz, Baran; Akakın, Akın; Toktaş, Zafer Orkun; Kaur, Ahmet Cemil; Demir, Mustafa Kemal; Kılıç, Türker

2015-11-01

Low-grade gliomas have good overall survival rates in pediatric patients compared to adults. There are some case series that reported the effectiveness and safety of Gamma Knife radiosurgery, yet they are limited in number of patients. We aimed to review the relevant literature for pediatric low-grade glial tumors treated with stereotactic radiosurgery, specifically Gamma Knife radiosurgery, and to present an exemplary case. A 6-year-old boy was admitted to clinic due to head trauma. He was alert, cooperative, and had no obvious motor or sensorial deficit. A head CT scan depicted a hypodense zone at the right caudate nucleus. The brain magnetic resonance imaging (MRI) depicted a mass lesion at the same location. A stereotactic biopsy was performed. Histopathological diagnosis was low-grade astrocytoma (grade II, World Health Organization (WHO) classification, 2007). Gamma Knife radiosurgery was applied to the tumor bed. Tumor volume was 21.85 cm(3). Fourteen gray was given to 50% isodose segment of the lesion (maximal dose of 28 Gy). The tumor has disappeared totally in 4 months, and the patient was tumor-free 21 months after the initial treatment. The presented literature review represents mostly single-center experiences with different patient and treatment characteristics. Accordingly, a mean/median margin dose of 11.3-15 Gy with Gamma Knife radiosurgery (GKRS) is successful in treatment of pediatric and adult low-grade glial tumor patients. However, prospective studies with a large cohort of pediatric patients should be conducted to make a more comprehensive conclusion for effectiveness and safety of GKRS in pediatric low-grade glial tumors.

Asphalt pavement aging and temperature dependent properties using functionally graded viscoelastic model

NASA Astrophysics Data System (ADS)

Dave, Eshan V.

Asphalt concrete pavements are inherently graded viscoelastic structures. Oxidative aging of asphalt binder and temperature cycling due to climatic conditions being the major cause of non-homogeneity. Current pavement analysis and simulation procedures dwell on the use of layered approach to account for these non-homogeneities. The conventional finite-element modeling (FEM) technique discretizes the problem domain into smaller elements, each with a unique constitutive property. However the assignment of unique material property description to an element in the FEM approach makes it an unattractive choice for simulation of problems with material non-homogeneities. Specialized elements such as "graded elements" allow for non-homogenous material property definitions within an element. This dissertation describes the development of graded viscoelastic finite element analysis method and its application for analysis of asphalt concrete pavements. Results show that the present research improves efficiency and accuracy of simulations for asphalt pavement systems. Some of the practical implications of this work include the new technique's capability for accurate analysis and design of asphalt pavements and overlay systems and for the determination of pavement performance with varying climatic conditions and amount of in-service age. Other application areas include simulation of functionally graded fiber-reinforced concrete, geotechnical materials, metal and metal composites at high temperatures, polymers, and several other naturally existing and engineered materials.

EG-07CELL CYCLE SIGNATURE AND TUMOR PHYLOGENY ARE ENCODED IN THE EVOLUTIONARY DYNAMICS OF DNA METHYLATION IN GLIOMA

PubMed Central

Mazor, Tali; Pankov, Aleksandr; Johnson, Brett E.; Hong, Chibo; Bell, Robert J.A.; Smirnov, Ivan V.; Reis, Gerald F.; Phillips, Joanna J.; Barnes, Michael; Bollen, Andrew W.; Taylor, Barry S.; Molinaro, Annette M.; Olshen, Adam B.; Song, Jun S.; Berger, Mitchel S.; Chang, Susan M.; Costello, Joseph F.

2014-01-01

The clonal evolution of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast, tumor epigenetic states, including DNA methylation, are reversible and sensitive to the tumor microenvironment, presumably precluding the use of epigenetics to discover tumor phylogeny. Here we examined the spatial and temporal dynamics of DNA methylation in a clinically and genetically characterized cohort of IDH1-mutant low-grade gliomas and their patient-matched recurrences. WHO grade II gliomas are diffuse, infiltrative tumors that frequently recur and may undergo malignant progression to a higher grade with a worse prognosis. The extent to which epigenetic alterations contribute to the evolution of low-grade gliomas, including malignant progression, is unknown. While all gliomas in the cohort exhibited the hypermethylation signature associated with IDH1 mutation, low-grade gliomas that underwent malignant progression to high-grade glioblastoma (GBM) had a unique signature of DNA hypomethylation enriched for active enhancers, as well as sites of age-related hypermethylation in the brain. Genes with promoter hypomethylation and concordant transcriptional upregulation during evolution to GBM were enriched in cell cycle function, evolving in concert with genetic alterations that deregulate the G1/S cell cycle checkpoint. Despite the plasticity of tumor epigenetic states, phyloepigenetic trees robustly recapitulated phylogenetic trees derived from somatic mutations in the same patients. These findings highlight widespread co-dependency of genetic and epigenetic events throughout the clonal evolution of initial and recurrent glioma.

Cervical range of motion, cervical and shoulder strength in senior versus age-grade Rugby Union International front-row forwards.

PubMed

Davies, Mark; Moore, Isabel S; Moran, Patrick; Mathema, Prabhat; Ranson, Craig A

2016-05-01

To provide normative values for cervical range of motion (CROM), isometric cervical and shoulder strength for; International Senior professional, and International Age-grade Rugby Union front-row forwards. Cross-sectional population study. All international level front-row players within a Rugby Union Tier 1 Nation. Nineteen Senior and 21 Age-grade front-row forwards underwent CROM, cervical and shoulder strength testing. CROM was measured using the CROM device and the Gatherer System was used to measure multi-directional isometric cervical and shoulder strength. The Age-grade players had significantly lower; cervical strength (26-57% deficits), cervical flexion to extension strength ratios (0.5 vs. 0.6), and shoulder strength (2-36% deficits) than the Senior players. However, there were no differences between front-row positions within each age group. Additionally, there were no differences between age groups or front-row positions in the CROM measurements. Senior Rugby Union front-row forwards have greater cervical and shoulder strength than Age-grade players, with the biggest differences being in cervical strength, highlighting the need for age specific normative values. Importantly, Age-grade players should be evaluated to ensure they have developed sufficient cervical strength prior to entering professional level Rugby Union. Copyright © 2015 Elsevier Ltd. All rights reserved.

The influence of different classification standards of age groups on prognosis in high-grade hemispheric glioma patients.

PubMed

Chen, Jian-Wu; Zhou, Chang-Fu; Lin, Zhi-Xiong

2015-09-15

Although age is thought to correlate with the prognosis of glioma patients, the most appropriate age-group classification standard to evaluate prognosis had not been fully studied. This study aimed to investigate the influence of age-group classification standards on the prognosis of patients with high-grade hemispheric glioma (HGG). This retrospective study of 125 HGG patients used three different classification standards of age-groups (≤ 50 and >50 years old, ≤ 60 and >60 years old, ≤ 45 and 45-65 and ≥ 65 years old) to evaluate the impact of age on prognosis. The primary end-point was overall survival (OS). The Kaplan-Meier method was applied for univariate analysis and Cox proportional hazards model for multivariate analysis. Univariate analysis showed a significant correlation between OS and all three classification standards of age-groups as well as between OS and pathological grade, gender, location of glioma, and regular chemotherapy and radiotherapy treatment. Multivariate analysis showed that the only independent predictors of OS were classification standard of age-groups ≤ 50 and > 50 years old, pathological grade and regular chemotherapy. In summary, the most appropriate classification standard of age-groups as an independent prognostic factor was ≤ 50 and > 50 years old. Pathological grade and chemotherapy were also independent predictors of OS in post-operative HGG patients. Copyright © 2015. Published by Elsevier B.V.

Expression of ARs in triple negative breast cancer tumors: a potential prognostic factor?

PubMed

Giannos, Aris; Filipits, Martin; Zagouri, Flora; Brandstetter, Anita; Tsigginou, Alexandra; Sotiropoulou, Maria; Papaspyrou, Irene; Sergentanis, Theodoros N; Psaltopoulou, Theodora; Rodolakis, Alexandros; Antsaklis, Aris; Dimopoulos, Meletios-Athanasios; Dimitrakakis, Constantine

2015-01-01

In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC). Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated. AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26-1.70, P=0.393). AR expression does not seem to play a prognostic role in TNBC.

[Influence of molecular-genetic factors on prognosis in patients with oligodendroglial tumors].

PubMed

Absaliamova, O V; Korshunov, A G; Loshakov, V A; Kobiakov, G L; Golanov, A V; Urakov, S V; Amanov, R D; Lichinitser, M R

2009-01-01

Previous studies demonstrated that patients with oligodendroglial tumors (OT) have longer overall and recurrence free survival than patients with other glial tumors of the same grade. Recent investigations showed high influence of genetic alterations on patients' outcome: overall and recurrence free survival increased in the case of presence 1p19q deletion and decreased in the presence of 9p or 10q deletion and/or EGFR amplification. In the series of 241 cases (107 male, 134 female patients, median age -- 38 years, (16-73)) we analyzed the impact of histology, tumor grade and genetic alterations on time to tumor progression (TTP). All patients underwent surgical resection of tumor or biopsy from 2000 to 2005. 70 patterns (oligodendroglioma (O) -- 13 cases, oligoastrocytoma (OA) -- 13, anaplastic oligodendroglioma (AO) -- 30, anaplastic oligoastrocytoma (AOA) -- 14) were assessed by fluorescent in situ hybridization. Median follow up was 24 months. The type of tumor (pure or mixed) didn't influence survival. TTP of patients with grade II and grade III tumors was 37.7 and 48.2 months, respectively (p = 0.035). Deletion 1p19q was noted in 34 (49%) cases. In pure O codeletion 1p19q was detected more frequently (in O -- 75%, in AO -- 56%) than in mixed tumors (in OA -- 31%, in AOA -- 35%). Deletions 9p, 10q and EGFR amplification were noted in 5, 6 and 4 cases, respectively. None of the tumors with 1pl9q deletion had other genetic alterations. Thus, we generated three prognostic groups: A -- deletion 1p19q; B -- balanced chromosomal profile; C -- deletion 9p. Median TTP in groups A, B and C was 46.6, 25.3 and 6.4 months, respectively (p < 0.001). The percentage of OT with 1p19q codeletion was lower than in previous studies. Pure O more frequently had 1p19q deletion than mixed tumors. Genetic alterations predict outcome stronger than histological criteria.

Brain Tumor Statistics

MedlinePlus

... Scientific Advisory Council & Reviewers The International Low Grade Glioma Registry Get Involved Advocacy Breakthrough for Brain Tumors ... an estimated 29,320 new cases in 2018. Gliomas , a broad term which includes all tumors arising ...

Mechanical phenotyping of cells and extracellular matrix as grade and stage markers of lung tumor tissues.

PubMed

Panzetta, Valeria; Musella, Ida; Rapa, Ida; Volante, Marco; Netti, Paolo A; Fusco, Sabato

2017-07-15

The mechanical cross-talk between cells and the extra-cellular matrix (ECM) regulates the properties, functions and healthiness of the tissues. When this is disturbed it changes the mechanical state of the tissue components, singularly or together, and cancer, along with other diseases, may start and progress. However, the bi-univocal mechanical interplay between cells and the ECM is still not properly understood. In this study we show how a microrheology technique gives us the opportunity to evaluate the mechanics of cells and the ECM at the same time. The mechanical phenotyping was performed on the surgically removed tissues of 10 patients affected by adenocarcinoma of the lung. A correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Our findings suggest a sort of asymmetric modification of the mechanical properties of the cells and the extra-cellular matrix in the tumor, being the more compliant cell even though it resides in a stiffer matrix. Overall, the simultaneous mechanical characterization of the tissues constituents (cells and ECM) provided new support for diagnosis and offered alternative points of analysis for cancer mechanobiology. When the integrity of the mechanical cross-talk between cells and the extra-cellular matrix is disturbed cancer, along with other diseases, may initiate and progress. Here, we show how a new technique gives the opportunity to evaluate the mechanics of cells and the ECM at the same time. It was applied on surgically removed tissues of 10 patients affected by adenocarcinoma of the lung and a correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

CD 10 expression intensity in various grades and stages of urothelial carcinoma of urinary bladder.

PubMed

Atique, Muhammad; Abbasi, Muhammad Sajjad; Jamal, Shahid; Khadim, Muhammad Tahir; Akhtar, Farhan; Jamal, Nighat

2014-05-01

To evaluate CD10 expression in urothelial carcinoma of the urinary bladder and the association of immunohistochemical (IHC) CD10 expression intensity with grade and stage. Descriptive cross-sectional analytical study. Armed Forces Institute of Pathology, Rawalpindi, from January to December 2011. Fifty consecutive cases of urothelial bladder carcinomas, obtained through transurethral resections, were included in this study. Hematoxylin-eosin (HE) stained sections from each case were re-evaluated histopathologically according to WHO 2004 grading system. The TNM system was used for pathologic staging. On selected slides IHC CD10 marker was applied and a semiquantitative scoring for its expression based on the percentage of positive cells and intensity was performed. Data was entered and analysed on SPSS version 17. Fisher's exact test was used to compare grades, stages of urothelial carcinoma with CD 10 expression and age groups. P < 0.05 was taken as level of significance. Urothelial carcinoma was more common in males. The male to female ratio was 9:1. The older patients > 50 years had higher grade and stage as compared to the younger patients. All cases of high grade urothelial carcinoma showed higher positivity for CD 10. Twenty cases (86.95%) of high grade urothelial carcinoma were positive with +2 immunostaining while 3 cases (13.04 %) were positive with +1 staining. None of the tumors of stage pTa was positive for CD 10 expression. Of all patients with stage pT 1 tumor, 1 case (5.3%) was CD 10 negative and 17 cases (89.9%) were CD 10 positive having +1 staining with 5 - 50% staining and 1 case (5.3%) had +2 staining with more then 50% expression. Out of all patients with stage pT 2, no tumor was CD 10 negative, 3 (13.6%) patients were CD 10 positive with +1 staining and 19 (86.4%) with stage pT 2 tumor had stained positive with +2 staining. CD 10 expression was greater in high grade and invasive urothelial carcinomas; it may be associated with tumor progression

Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: differences by age, race, and tumor characteristics.

PubMed

Sweeney, Carol; Bernard, Philip S; Factor, Rachel E; Kwan, Marilyn L; Habel, Laurel A; Quesenberry, Charles P; Shakespear, Kaylynn; Weltzien, Erin K; Stijleman, Inge J; Davis, Carole A; Ebbert, Mark T W; Castillo, Adrienne; Kushi, Lawrence H; Caan, Bette J

2014-05-01

Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. We studied a diverse cohort of women with breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1 mm punches from fixed tumor tissue. Quantitative reverse-transcriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. In a subcohort of 1,319 women, the overall subtype distribution based on PAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrine-positive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores from PAM50 were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, P Trend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3-8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR = 0.5 (95% CI, 0.3-0.9). Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes. Subtyping in a population-based cohort revealed distinct profiles by age and race. ©2014 AACR.

Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: Differences by age, race, and tumor characteristics

PubMed Central

Sweeney, Carol; Bernard, Philip S.; Factor, Rachel E.; Kwan, Marilyn L.; Habel, Laurel A.; Quesenberry, Charles P.; Shakespear, Kaylynn; Weltzien, Erin K.; Stijleman, Inge J.; Davis, Carole A.; Ebbert, Mark T.W.; Castillo, Adrienne; Kushi, Lawrence H.; Caan, Bette J.

2014-01-01

Background Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. Methods We studied a diverse cohort of women with breast cancer from the Life After Cancer Epidemiology (LACE) and Pathways studies. RNA was extracted from 1 mm punches from fixed tumor tissue. Quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. Results In a subcohort of 1,319 women, the overall subtype distribution based on PAM50 was 53.1% Luminal A, 20.5% Luminal B, 13.0% HER2-enriched, 9.8% Basal-like, and 3.6% Normal-like. Among low-risk endocrine positive tumors (i.e. estrogen and progesterone receptor positive by immunohistochemistry, Her2 negative, and low histologic grade), only 76.5% were categorized as Luminal A by PAM50. Continuous-scale Luminal A, Luminal B, HER2-enriched, and Normal-like scores from PAM50 were mutually positively correlated; Basal-like score was inversely correlated with other subtypes. The proportion with non-Luminal A subtype decreased with older age at diagnosis, p trend < 0.0001. Compared with non-Hispanic whites, African-American women were more likely to have Basal-like tumors, age-adjusted odds ratio (OR) 4.4 (95% CI 2.3,8.4), whereas Asian and Pacific Islander women had reduced odds of Basal-like subtype, OR 0.5 (95% CI 0.3,0.9). Conclusions Our data indicate that over 50% of breast cancers treated in the community have Luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathological criteria to higher-risk subtypes. Impact Subtyping in a population-based cohort revealed distinct profiles by age and race. PMID:24521995

18F-Fluorocholine PET/CT, Brain MRI, and 5-Aminolevulinic Acid for the Assessment of Tumor Resection in High-Grade Glioma.

PubMed

García Vicente, Ana María; Jiménez Aragón, Fátima; Villena Martín, Maikal; Jiménez Londoño, German Andrés; Borrás Moreno, Jose María

2017-06-01

High-grade glioma is a very aggressive and infiltrative tumor in which complete resection is a chance for a better outcome. We present the case of a 57-year-old man with a brain lesion suggestive of high-grade glioma. Brain MRI and F-fluorocholine PET/CT were performed previously to plan the surgery. Surgery was microscope assisted after the administration of 5-aminolevulinic acid. Postsurgery brain MRI and PET were blind evaluated to the surgery results and reported as probably gross total resection.

Incidence of CNS tumors in Appalachian children

PubMed Central

Huang, Bin; Luo, Alice; Durbin, Eric B.; Lycan, Ellen; Tucker, Thomas; Chen, Quan; Horbinski, Craig; Villano, John L.

2017-01-01

Objective Determine whether the risk of astrocytomas in Appalachian children is higher than the national average. Methods We compared the incidence of pediatric brain tumors in Appalachia versus non-Appalachia regions, covering years 2000–2011. The North American Association of Central Cancer Registries (NAACCR) collects population-based data from 55 cancer registries throughout United States and Canada. All invasive primary (i.e. non-metastatic tumors), with age at diagnosis 0–19 years old, were included. Nearly 27,000 and 2,200 central nervous system (CNS) tumors from non-Appalachia and Appalachia, respectively comprise the cohorts. Age-adjusted incidence rates of each main brain tumor subtype were compared. Results The incidence rate of pediatric CNS tumors was 8% higher in Appalachia, 3.31 [95% CI, 3.17–3.45] versus non–Appalachia, 3.06, [95% CI, 3.02–3.09] for the years 2001–2011, all rates are per 100,000 population. Astrocytomas accounted for the majority of this difference, with the rate being 16% higher in Appalachian children, 1.77, [95% CI, 1.67–1.87] versus non-Appalachian children, 1.52, [95% CI, 1.50–1.55]. Among astrocytomas, World Health Organization (WHO) grade I astrocytomas were 41% higher in Appalachia, 0.63 [95% CI, 0.56–0.70] versus non-Appalachia 0.44 [95% CI, 0.43–0.46] for the years 2004–2011. Conclusions and Relevance This is the first study to demonstrate that Appalachian children are at greater risk of CNS neoplasms, and that much of this difference is in WHO grade I astrocytomas, 41% more common. The cause of this increased incidence is unknown and we discuss the importance of this in relation to genetic and environmental findings in Appalachia. PMID:28285334

Canonical Nlrp3 inflammasome links systemic low grade inflammation to functional decline in aging

PubMed Central

Youm, Yun-Hee; Grant, Ryan W.; McCabe, Laura R.; Albarado, Diana C.; Nguyen, Kim Yen; Ravussin, Anthony; Pistell, Paul; Newman, Susan; Carter, Renee; Laque, Amanda; Münzberg, Heike; Rosen, Clifford J.; Ingram, Donald K.; Salbaum, J. Michael; Dixit, Vishwa Deep

2014-01-01

SUMMARY Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism that the Nlrp3 inflammasome controls systemic low grade age-related ‘sterile’ inflammation in both periphery and brain independently of the non-canonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome and astrogliosis. Consistent with the hypothesis that systemic low grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases. PMID:24093676

Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.

2012-07-15

Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation ofmore » the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold

Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.

2013-02-01

Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation ofmore » the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold

A pragmatic clinicopathobiological grouping/staging system for gliomas: proposal of the Indian TNM subcommittee on brain tumors.

PubMed

Gupta, Tejpal; Sarin, Rajiv; Jalali, Rakesh; Sharma, Suash; Kurkure, Purna; Goel, Atul

2009-01-01

There is no universally accepted staging system for primary brain tumors wherein prognostication is mainly based on complex composite indices. To develop a simple, pragmatic, and widely applicable grouping/staging system for gliomas, the most common primary brain tumor. An expert neurooncology panel with representation from radiation oncology, neurosurgery, pathology, radiology, and medical oncology had several rounds of discussion on issues pertinent to brain tumor staging. The trade off was between the accuracy of prognostic categorization and a pragmatic, widely applicable approach. The Tumor-Node-Metastasis staging was considered irrelevant for gliomas that seldom metastasize to lymphatics or outside the neuraxis. Instead, a 4-point staging/grouping system is proposed, using histological grade as the main prognostic variable and at least one stage migration based on other unfavorable features such as tumor location (brainstem); age (<5 years for all grades, >50 years for high-grade, and >40 years for low-grade gliomas); poor neurological performance status (NPS 2-4); multicentricity and/or gliomatosis; and adverse biological parameters (proliferative index, angiogenesis markers, apoptotic index, cytogenetic abnormalities, and molecular markers). In absence of a grouping/staging system for primary brain tumors, prognostification is mostly based on complex composite indices. The proposed clinicopathobiological grouping/staging system for gliomas is a simple, pragmatic, and user-friendly tool with a potential to fulfill the objectives of staging classification.

Novel, improved grading system(s) for IDH-mutant astrocytic gliomas.

PubMed

Shirahata, Mitsuaki; Ono, Takahiro; Stichel, Damian; Schrimpf, Daniel; Reuss, David E; Sahm, Felix; Koelsche, Christian; Wefers, Annika; Reinhardt, Annekathrin; Huang, Kristin; Sievers, Philipp; Shimizu, Hiroaki; Nanjo, Hiroshi; Kobayashi, Yusuke; Miyake, Yohei; Suzuki, Tomonari; Adachi, Jun-Ichi; Mishima, Kazuhiko; Sasaki, Atsushi; Nishikawa, Ryo; Bewerunge-Hudler, Melanie; Ryzhova, Marina; Absalyamova, Oksana; Golanov, Andrey; Sinn, Peter; Platten, Michael; Jungk, Christine; Winkler, Frank; Wick, Antje; Hänggi, Daniel; Unterberg, Andreas; Pfister, Stefan M; Jones, David T W; van den Bent, Martin; Hegi, Monika; French, Pim; Baumert, Brigitta G; Stupp, Roger; Gorlia, Thierry; Weller, Michael; Capper, David; Korshunov, Andrey; Herold-Mende, Christel; Wick, Wolfgang; Louis, David N; von Deimling, Andreas

2018-04-23

According to the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO), IDH-mutant astrocytic gliomas comprised WHO grade II diffuse astrocytoma, IDH-mutant (AII IDHmut ), WHO grade III anaplastic astrocytoma, IDH-mutant (AAIII IDHmut ), and WHO grade IV glioblastoma, IDH-mutant (GBM IDHmut ). Notably, IDH gene status has been made the major criterion for classification while the manner of grading has remained unchanged: it is based on histological criteria that arose from studies which antedated knowledge of the importance of IDH status in diffuse astrocytic tumor prognostic assessment. Several studies have now demonstrated that the anticipated differences in survival between the newly defined AII IDHmut and AAIII IDHmut have lost their significance. In contrast, GBM IDHmut still exhibits a significantly worse outcome than its lower grade IDH-mutant counterparts. To address the problem of establishing prognostically significant grading for IDH-mutant astrocytic gliomas in the IDH era, we undertook a comprehensive study that included assessment of histological and genetic approaches to prognosis in these tumors. A discovery cohort of 211 IDH-mutant astrocytic gliomas with an extended observation was subjected to histological review, image analysis, and DNA methylation studies. Tumor group-specific methylation profiles and copy number variation (CNV) profiles were established for all gliomas. Algorithms for automated CNV analysis were developed. All tumors exhibiting 1p/19q codeletion were excluded from the series. We developed algorithms for grading, based on molecular, morphological and clinical data. Performance of these algorithms was compared with that of WHO grading. Three independent cohorts of 108, 154 and 224 IDH-mutant astrocytic gliomas were used to validate this approach. In the discovery cohort several molecular and clinical parameters were of prognostic relevance. Most relevant for overall survival (OS

Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide.

PubMed

Kaloshi, Gentian; Sierra del Rio, Monica; Ducray, François; Psimaras, Dimitri; Idbaih, Ahmed; Laigle-Donadey, Florence; Taillibert, Sophie; Houillier, Caroline; Dehais, Caroline; Omuro, Antonio; Sanson, Marc; Delattre, Jean-Yves; Hoang-Xuan, Khe

2010-12-01

There is a growing evidence of using Temozolomide as upfront therapy for progressive low grade gliomas. No data exist on the efficacy of nitrosoureas as an alternative to radiotherapy in those patients who progress after Temozolomide. We retrospectively reviewed 30 patients with median age of 46 years. Twenty-one patients had pure oligodendrogliomas. Thirteen patients had a non-enhancing tumor at progression after Temozolomide. The chromosomes 1p/19q were co-deleted in 5 cases and retained in 10 cases. Response rate was 10% (3 minor responses achieved in non-enhancing tumors). Tolerance was acceptable (17% grade III and IV myelosupression). Median PFS was 6.5 months. Median OS from start of salvage treatment was 23.4 months. Tumors without contrast enhancement demonstrated a better prognosis than those with contrast enhancement both in term of PFS (P = 0.0003) and OS (P = 0.0006). Chromosomes 1p/19q codeletion was not predictive for objective response to salvage treatment but correlated with a better PFS (P = 0.02). In conclusion, salvage NU chemotherapy provide disappointing results in TMZ-pretreated low grade gliomas (LGG), which should be treated in priority by conventional radiotherapy especially in LGG that display contrast enhancement at progression.

Neuroendocrine tumors of colon and rectum: validation of clinical and prognostic values of the World Health Organization 2010 grading classifications and European Neuroendocrine Tumor Society staging systems.

PubMed

Shen, Chaoyong; Yin, Yuan; Chen, Huijiao; Tang, Sumin; Yin, Xiaonan; Zhou, Zongguang; Zhang, Bo; Chen, Zhixin

2017-03-28

This study evaluated and compared the clinical and prognostic values of the grading criteria used by the World Health Organization (WHO) and the European Neuroendocrine Tumors Society (ENETS). Moreover, this work assessed the current best prognostic model for colorectal neuroendocrine tumors (CRNETs). The 2010 WHO classifications and the ENETS systems can both stratify the patients into prognostic groups, although the 2010 WHO criteria is more applicable to CRNET patients. Along with tumor location, the 2010 WHO criteria are important independent prognostic parameters for CRNETs in both univariate and multivariate analyses through Cox regression (P<0.05). Data from 192 consecutive patients histopathologically diagnosed with CRNETs and had undergone surgical resection from January 2009 to May 2016 in a single center were retrospectively analyzed. Findings suggest that the WHO classifications are superior over the ENETS classification system in predicting the prognosis of CRNETs. Additionally, the WHO classifications can be widely used in clinical practice.

Ependymal tumors with oligodendroglioma like clear cells: Experience from a tertiary care hospital in Pakistan

PubMed Central

Hashmi, Fauzan Alam; Khan, Muhammad Faheem; Khan, Saad Akhtar; Waqas, Muhammad; Bari, Muhammad Ehsan; Ahmed, Arsalan

2015-01-01

Background: Ependymal tumors with oligodendroglioma like clear cells have never been reported from Pakistan. We aimed to see the features and outcomes of this rare entity. Methods: It was retrospective cohort conducted at the Department of Neurosurgery, Aga Khan University from 2003 to 2013. The medical records and radiology of patients with proven histopathology were reviewed. Analysis was done on SPSS 20. Results: Eleven cases of ependymal tumors with clear cells were found, which equated to 1.5% of the total tumor burden in 11 years. The median age was 49 years. Most common presenting symptom was headache 54.5%. Out of 11 patients, 9 patients had a supratentorial tumor. Magnetic resonance imaging showed hypointense signals on T1 and hyperintense signals on T2-weighted images in all cases. Contrast enhancement was found in 9 patients (77.8%), necrosis and hemorrhage was found in 4 (36%) and 3 (27%) patients, respectively. Immunohistochemistry showed glial fibrillary acidic protein and epithelial membrane antigen positivity in all cases. Ki-67 showed high proliferative index in 6 patients. According to the World Health Organization grading of ependymal tumors, 2 patients had Grade II tumors, and 9 patients had Grade III tumors with clear cells. Gross total resection was achieved in 6 (54.5%) and subtotal resection in 5 patients (45.4%). Recurrence was observed in 9 patients. Six patients died of the disease. Median progression-free survival and overall survival was 8 months and 10 months, respectively. Conclusion: Ependymal tumors with clear cells presented more commonly in Grade III lesions and were more aggressive in behavior with poorer outcome compared to similar studies. PMID:26664928

PET AND SPECT STUDIES IN CHILDREN WITH HEMISPHERIC LOW-GRADE GLIOMAS

PubMed Central

Juhász, Csaba; Bosnyák, Edit

2016-01-01

Molecular imaging is playing an increasing role in the pre-treatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting and improved detection of tumor recurrence. This review provides a brief overview of single photon emission computed tomography (SPECT) studies followed by a more detailed review of clinical applications of glucose and amino acid PET imaging in low-grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pre- and post-treatment evaluation of pediatric brain tumors. PMID:27659825

PET and SPECT studies in children with hemispheric low-grade gliomas.

PubMed

Juhász, Csaba; Bosnyák, Edit

2016-10-01

Molecular imaging is playing an increasing role in the pretreatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting, and improved detection of tumor recurrence. This review provides a brief overview of single-photon emission computed tomography (SPECT) studies followed by a more detailed review of the clinical applications of glucose and amino acid PET imaging in low-grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity, and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pretreatment and post-treatment evaluation of pediatric brain tumors.

Ispinesib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Lymphoma

ClinicalTrials.gov

2013-01-15

Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Unspecified Childhood Solid Tumor, Protocol Specific

Evaluation of anatomic and morphologic nomogram to predict malignant and high-grade disease in a cohort of patients with small renal masses.

PubMed

Bagrodia, Aditya; Harrow, Brian; Liu, Zhuo-Wei; Olweny, Ephrem O; Faddegon, Stephen; Yin, Gang; Tan, Yung Khan; Han, Woong Kyu; Lotan, Yair; Margulis, Vitaly; Cadeddu, Jeffrey A

2014-01-01

To evaluate a nomogram using the RENAL Nephrometry Score (RENAL-NS) that was developed to characterize masses as benign vs. malignant and high vs. low grade in our patients with small renal masses treated with partial nephrectomy (PN). The nomogram was previously developed and validated in patients with widely variable tumor sizes. Retrospective review of PN performed between 1/2003 and 7/2011. Imaging was reviewed by a urologic surgeon for RENAL-NS. Final pathology was used to classify tumors as benign or malignant and low (I/II) or high (III/IV) Fuhrman grade. Patient age, gender, and RENAL score were entered into the nomogram described by Kutikov et al. to determine probabilities of cancer and high-grade disease. Area under the curve was determined to assess agreement between observed and expected outcomes for prediction of benign vs. malignant disease and for prediction of high- vs. low-grade or benign disease. A total of 250 patients with 252 masses underwent PN during the study period; 179/250 (71.6%) had preoperative imaging available. RENAL-NS was assigned to 181 masses. Twenty-two percent of tumors were benign. Eighteen percent of tumors were high grade. Area under the curve was 0.648 for predicting benign vs. malignant disease and 0.955 for predicting low-grade or benign vs. high-grade disease. The RENAL-NS score nomogram by Kutikov does not discriminate well between benign and malignant disease for small renal masses. The nomogram may potentially be useful in identifying high-grade tumors. Further validation is required where the nomogram probability and final pathologic specimen are available. Copyright © 2014 Elsevier Inc. All rights reserved.

Outcomes After Surgical Resection of Primary Non-Myxoma Cardiac Tumors

PubMed Central

Boyacıoğlu, Kamil; Ak, Adnan; Dönmez, Arzu Antal; Çayhan, Burçin; Aksüt, Mehmet; Tunçer, Mehmet Altuğ

2018-01-01

Objective Primary cardiac tumors are rare lesions with different histological type. We reviewed our 17 years of experience in the surgical treatment and clinical results of primary non-myxoma cardiac tumors. Methods Between July 2000 and February 2017, 21 patients with primary cardiac tumor were surgically treated in our institution. The tumors were categorized as benign non-myxomas and malignants. Data including the demographic characteristics, details of the tumor histology and grading, cardiac medical and surgical history, surgical procedure of the patients were obtained from the hospital database. Results Eleven patients were diagnosed with benign non-myxoma tumor (male/female:7/4), ranging in age from 10 days to 74 years (mean age 30.9±26.5 years). Papillary fibroelastoma was the most frequent type (63.6%). There were two early deaths in benign group (all were rhabdomyoma), and mortality rate was 18%. The mean follow-up period was 69.3±58.7 months (range, 3 to 178 months). All survivals in benign group were free of tumor-related symptoms and tumor relapses. Ten patients were diagnosed with malignant tumor (sarcoma/lymphoma:8/2, male/female:3/7), ranging in age from 14 years to 73 years (mean age 44.7±18.9 years). Total resection could be done in only three (30%) patients. The mean follow-up period was 18.7±24.8 months (range, 0-78 months). Six patients died in the first 10 months. Conclusion Complete resection of the cardiac tumors, whenever possible, is the main goal of surgery. Surgical resection of benign cardiac tumors is safe, usually curative and provides excellent long-term prognosis. On the contrary, malignant cardiac tumors still remain highly lethal. PMID:29898146

Birth weight and order as risk factors for childhood central nervous system tumors.

PubMed

MacLean, Jane; Partap, Sonia; Reynolds, Peggy; Von Behren, Julie; Fisher, Paul Graham

2010-09-01

To determine whether birth characteristics related to maternal-fetal health in utero are associated with the development of childhood central nervous system tumors. We identified, from the California Cancer Registry, 3733 children under age 15 diagnosed with childhood central nervous system tumors between 1988 and 2006 and linked these cases to their California birth certificates. Four controls per case, matched on birth date and sex, were randomly selected from the same birth files. We evaluated associations of multiple childhood CNS tumor subtypes with birth weight and birth order. Low birth weight was associated with a reduced risk of low-grade gliomas (OR=0.67; 95% CI, 0.46 to 0.97) and high birth weight was associated with increased risk of high-grade gliomas (OR=1.57; 95% CI, 1.16 to 2.12). High birth order (fourth or higher) was associated with decreased risk of low-grade gliomas (OR=0.75; 95% CI, 0.56 to 0.99) and increased risk of high-grade gliomas (OR=1.32; 95% CI, 1.01 to 1.72 for second order). Factors that drive growth in utero may increase the risk of low-grade gliomas. There may be a similar relationship in high-grade gliomas, although other factors, such as early infection, may modify this association. Additional investigation is warranted to validate and further define these findings. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Neurodevelopmental Outcomes of Children with Low-Grade Gliomas

ERIC Educational Resources Information Center

Ris, M. Douglas; Beebe, Dean W.

2008-01-01

As a group, children with low-grade gliomas (LGGs) enjoy a high rate of long-term survival and do not require the intensity of neurotoxic treatments used with higher risk pediatric brain tumors. Because they are generally considered to have favorable neurobehavioral outcomes, they have not been studied as thoroughly as higher-grade brain tumors by…

Age, Gender and Grade Effect on Foreign Language Anxiety among Children

ERIC Educational Resources Information Center

Aydin, Selami; Harputlu, Leyla; Çelik, Seyda Savran; Ustuk, Özgehan; Güzel, Serhat

2017-01-01

The number of studies on the relationship between certain demographic variables, age, gender and grade, and the levels of foreign language anxiety (FLA) in the English as a foreign language (EFL) context regarding adult and young learners is fairly limited, whereas the findings obtained from prior studies did not reach a consensus on the…

ABT-888 and Temozolomide in Treating Young Patients With Recurrent or Refractory CNS Tumors

ClinicalTrials.gov

2014-07-07

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Lymphovascular infiltration in the tumor bed is a useful marker of biological behavior in breast cancer.

PubMed

Panagiotopoulos, Nikolaos; Lagoudianakis, Emmanouil; Pappas, Apostolos; Filis, Konstantinos; Salemis, Nikolaos; Manouras, Andreas; Kontzoglou, Konstantinos; Zografos, George

2016-01-01

Tumor cells can metastasize by entering existing vessels or new vessels actively recruited into the primary tumor. Invasion of the lymphatics and blood vessels in the periphery of the tumor seems to be a prerequisite step in the metastatic process. The aim of this study was to correlate peripheral lymphatic vessel infiltration (PLI) and peripheral blood vessel infiltration (PVI) in a cohort of patients with invasive ductal carcinoma of the breast with various other prognostic parameters and outcome. The study population consisted of 236 female patients with invasive ductal breast carcinomas, who had been operated between 2011 and 2013. The registered data included age at diagnosis, histological subtype, tumor size, TNM stage, histological grade, estrogen (ER) and progesterone receptors (PR), HER-2, p53, and PLI and PVI. Pathological examination revealed that 22.5% of the patients had PVI and 37.3% had PLI at the tumor front. PVI correlated with younger age (p<0.05), higher histologic grade (p<0.05), advanced TNM stage (p<0.05), higher T stage (p<0.05), higher N stage (p<0.05) and positive Ki67 expression (p<0.05). Similarly, PLI correlated with higher histologic grade (p<0.05), advanced TNM stage (p<0.05), higher T stage (p<0.05) and higher N stage (p<0.05). Statistical analysis did not reveal significant correlation between the presence of tumor blood and lymphatic vessels with infiltration in overall (OS) and disease-free survival (DFS). PLI and PVI are important markers of worse clinical outcome as shown by their association with other established factors, but no association with recurrence and survival could be proven.

Signal transduction molecules in gliomas of all grades.

PubMed

Ermoian, Ralph P; Kaprealian, Tania; Lamborn, Kathleen R; Yang, Xiaodong; Jelluma, Nannette; Arvold, Nils D; Zeidman, Ruth; Berger, Mitchel S; Stokoe, David; Haas-Kogan, Daphne A

2009-01-01

To interrogate grade II, III, and IV gliomas and characterize the critical effectors within the PI3-kinase pathway upstream and downstream of mTOR. Experimental design Tissues from 87 patients who were treated at UCSF between 1990 and 2004 were analyzed. Twenty-eight grade II, 17 grade III glioma, 26 grade IV gliomas, and 16 non-tumor brain specimens were analyzed. Protein levels were assessed by immunoblots; RNA levels were determined by polymerase chain reaction amplification. To address the multiple comparisons, first an overall analysis was done comparing the four groups using Spearman's Correlation Coefficient. Only if this analysis was statistically significant were individual pairwise comparisons done. Multiple comparison analyses revealed a significant correlation with grade for all variables examined, except phosphorylated-S6. Expression of phosphorylated-4E-BP1, phosphorylated-PKB/Akt, PTEN, TSC1, and TSC2 correlated with grade (P < 0.01 for all). We extended our analyses to ask whether decreases in TSC proteins levels were due to changes in mRNA levels, or due to changes in post-transcriptional alterations. We found significantly lower levels of TSC1 and TSC2 mRNA in GBMs than in grade II gliomas or non-tumor brain (P < 0.01). Expression levels of critical signaling molecules upstream and downstream of mTOR differ between non-tumor brain and gliomas of any grade. The single variable whose expression did not differ between non-tumor brain and gliomas was phosphorylated-S6, suggesting that other protein kinases, in addition to mTOR, contribute significantly to S6 phosphorylation. mTOR provides a rational therapeutic target in gliomas of all grades, and clinical benefit may emerge as mTOR inhibitors are combined with additional agents.

The effects of graded levels of calorie restriction: VII. Topological rearrangement of hypothalamic aging networks.

PubMed

Derous, Davina; Mitchell, Sharon E; Green, Cara L; Wang, Yingchun; Han, Jing Dong J; Chen, Luonan; Promislow, Daniel E L; Lusseau, David; Speakman, John R; Douglas, Alex

2016-05-01

Connectivity in a gene-gene network declines with age, typically within gene clusters. We explored the effect of short-term (3 months) graded calorie restriction (CR) (up to 40 %) on network structure of aging-associated genes in the murine hypothalamus by using conditional mutual information. The networks showed a topological rearrangement when exposed to graded CR with a higher relative within cluster connectivity at 40CR. We observed changes in gene centrality concordant with changes in CR level, with Ppargc1a, and Ppt1 having increased centrality and Etfdh, Traf3 and Abcc1 decreased centrality as CR increased. This change in gene centrality in a graded manner with CR, occurred in the absence of parallel changes in gene expression levels. This study emphasizes the importance of augmenting traditional differential gene expression analyses to better understand structural changes in the transcriptome. Overall our results suggested that CR induced changes in centrality of biological relevant genes that play an important role in preventing the age-associated loss of network integrity irrespective of their gene expression levels.

The effects of graded levels of calorie restriction: VII. Topological rearrangement of hypothalamic aging networks

PubMed Central

Derous, Davina; Mitchell, Sharon E.; Green, Cara L.; Wang, Yingchun; Han, Jing Dong J.; Chen, Luonan; Promislow, Daniel E.L.; Lusseau, David; Speakman, John R.; Douglas, Alex

2016-01-01

Connectivity in a gene-gene network declines with age, typically within gene clusters. We explored the effect of short-term (3 months) graded calorie restriction (CR) (up to 40 %) on network structure of aging-associated genes in the murine hypothalamus by using conditional mutual information. The networks showed a topological rearrangement when exposed to graded CR with a higher relative within cluster connectivity at 40CR. We observed changes in gene centrality concordant with changes in CR level, with Ppargc1a, and Ppt1 having increased centrality and Etfdh, Traf3 and Abcc1 decreased centrality as CR increased. This change in gene centrality in a graded manner with CR, occurred in the absence of parallel changes in gene expression levels. This study emphasizes the importance of augmenting traditional differential gene expression analyses to better understand structural changes in the transcriptome. Overall our results suggested that CR induced changes in centrality of biological relevant genes that play an important role in preventing the age-associated loss of network integrity irrespective of their gene expression levels. PMID:27115072

Plasma Levels of Glucose and Insulin in Patients with Brain Tumors

PubMed Central

ALEXANDRU, OANA; ENE, L.; PURCARU, OANA STEFANA; TACHE, DANIELA ELISE; POPESCU, ALISA; NEAMTU, OANA MARIA; TATARANU, LIGIA GABRIELA; GEORGESCU, ADA MARIA; TUDORICA, VALERICA; ZAHARIA, CORNELIA; DRICU, ANICA

2014-01-01

In the last years there were many authors that suggest the existence of an association between different components of metabolic syndrome and various cancers. Two important components of metabolic syndrome are hyperglycemia and hyperinsulinemia. Both of them had already been linked with the increased risk of pancreatic, breast, endometrial or prostate cancer. However the correlation of the level of the glucose and insulin with various types and grades of brain tumors remains unclear. In this article we have analysed the values of plasma glucose and insulin in 267 patients, consecutively diagnosed with various types of brain tumors. Our results showed no correlation between the glycemia and brain tumor types or grades. High plasma levels of insulin were found in brain metastasis and astrocytomas while the other types of brain tumors (meningiomas and glioblastomas) had lower levels of the peptide. The levels of insulin were also higher in brain metastasis and grade 3 brain tumors when compared with grade 1, grade 2 and grade 4 brain tumors. PMID:24791202

Expression of pigment epithelium-derived factor and tumor necrosis factor-α is correlated in bladder tumor and is related to tumor angiogenesis.

PubMed

Feng, Chen-Chen; Wang, Pao-Hsun; Ding, Qiang; Guan, Ming; Zhang, Yuan-Fang; Jiang, Hao-Wen; Wen, Hui; Wu, Zhong

2013-02-01

Angiogenesis is a pivotal process on which solid tumor growth is substantially dependent. Pigment epithelium-derived factor (PEDF) is the most potent natural anti-angiogenic factor, which has seldom been studied in bladder tumor, and whose functioning pathway remains unclear. We have thus investigated PEDF expression in relation to tumor necrosis factor-α (TNF-α) and microvessel density (MVD) with immunohistochemistry. Antibodies of PEDF and TNF-α were examined by Western blotting before immunohistochemistry. Sixty-four urothelial tumor sections and 23 normal controls were stained and expression of PEDF, TNF-α, and MVD were studied. Decreased PEDF expression and increased TNF-α expression was noticed in tumorous tissue compared with healthy urothelium. Lower PEDF expression was related to higher tumor grade but stage. Increased TNF-α expression was noticed in recurrent, larger tumors as well as in tumors with progression in grade and stage. Expression of PEDF and TNF-α was correlated in bladder tumor. PEDF or TNF-α was correlated with MVD negatively or positively, respectively, in cancerous tissue and tumorous grouping without correlation in papillary urothelial neoplasm of low malignant potential. Expressional change of PEDF and TNF-α is in relation to angiogenesis of bladder tumor, especially in bladder cancer development. Copyright © 2013 Elsevier Inc. All rights reserved.

Assessment of mediastinal tumors with diffusion-weighted single-shot echo-planar MRI.

PubMed

Razek, Ahmed Abdel; Elmorsy, Ahmed; Elshafey, Mohsen; Elhadedy, Tamer; Hamza, Osama

2009-09-01

To assess the role of diffusion-weighted single-shot echo-planar magnetic resonance imaging (MRI) in patients with mediastinal tumors. Prospective study was conducted on 45 consecutive patients (29 male, 16 female, age 22-66 years, mean 41 years) with mediastinal tumor. They underwent diffusion-weighted single-shot echo-planar MRI of the mediastinum with a b-factor of 0, 300, and 600 sec/mm(2). The apparent diffusion coefficient (ADC) value of the mediastinal tumor was correlated with the histopathological findings. The mean ADC value of malignant mediastinal tumors was 1.09 +/- 0.25 x 10(-3) mm(2)/sec, and of benign tumors was 2.38 +/- 0.56 x 10(-3) mm(2)/sec. There was a significant difference in the mean ADC value between malignant and benign tumors (P = 0.001) and within different grades of malignancy (0.001). When an ADC value of 1.56 x 10(-3) mm(2)/sec was used as a threshold value for differentiating malignant from benign tumor, the best results were obtained with an accuracy of 95%, sensitivity of 96%, specificity of 94%, positive predictive value of 94%, negative predictive value of 96%, and area under the curve of 0.938. The ADC value is a noninvasive parameter that can be used for differentiation of malignant from benign mediastinal tumors and grading of mediastinal malignancy.

Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors

ClinicalTrials.gov

2013-09-27

Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

21. Increased FDG uptake in Childhood CNS Tumors is Associated with Tumor Malignancy.

PubMed

Borgwardt; Carstensen; Schmiegelow; Højgaard

2000-07-01

Background: In adults PET scanning of CNS tumors with the tracer FDG (18F-flourodeoxyglucose) can provide information about the degree of malignancy, tumor extent, and dissemination. FDG PET can also be able to assess tumor response to therapy and to differentiate recurrence from necrosis. Although CNS tumors are the most common solid tumor in childhood, so far only few PET-studies have been reported. Pre-operative assessment of malignancy would facilitate surgical planning and the use of pre-operative chemotherapy.Materials and Methods: 21 children with CNS tumors were referred to clinical FDG PET prior to therapy (M/F = 12/9, median age: 9 (range 0-16)), (4 PNET/medulloblastomas; 1 gr. III ependymoma, 16 benign tumors)). Image processing included co-registration with MRI and image fusion. The FDG uptake in the tumors was ranked 0-5 by a hotspot/cortex-ratio by two observers independently. The FDG uptake in grey and white matter was used as reference for the grading system with FDG uptakes defined as 4 and 2 respectively.Results: 15 of 16 patients with tumors WHO gr. I-II had FDG-uptake of 1-2, and all 5 patients with tumors WHO gr. III-IV had FDG-uptake of 3-4. A WHO gr. I papilloma, known to have a high metabolism caused by high mitochondrial activity, had FDG uptake of 5. Except for this tumor, the FDG uptake was positively correlated with tumor malignancy. MRI/PET co-registration and image fusion increased the specificity of tumor location, as well as of tumor extent, and of heterogeneity (e.g., areas of necrosis).Conclusion: FDG PET with MRI/PET co-registration and image fusion could be an important adjunct in the diagnostic work up of pediatric CNS tumors, and could help define patients eligible for pre-operative chemotherapy.

Grading of meningeal solitary fibrous tumors/hemangiopericytomas: analysis of the prognostic value of the Marseille Grading System in a cohort of 132 patients.

PubMed

Macagno, Nicolas; Vogels, Rob; Appay, Romain; Colin, Carole; Mokhtari, Karima; Küsters, Benno; Wesseling, Pieter; Figarella-Branger, Dominique; Flucke, Uta; Bouvier, Corinne

2018-03-30

The finding that meningeal solitary fibrous tumors (SFTs) and meningeal hemangiopericytomas (HPCs) are both characterized by NAB2-STAT6 gene fusion has pushed their inclusion in the WHO 2016 Classification of tumors of the central nervous system (CNS) as different manifestations of the same entity. Given that the clinical behavior of the CNS SFT/HPC spectrum ranges from benign to malignant, it is presently unclear whether the grading criteria are still adequate. Here, we present the results of a study that analyzed the prognostic value of an updated version of the Marseille Grading System (MGS) in a retrospectively assembled cohort of 132 primary meningeal SFTs/HPCs with nuclear overexpression of STAT6. The median patient follow-up was 64 months (range 4-274 months); 73 cases (55%) were MGS I, 50 cases (38%) MGS II and 9 cases (7%) were MGS III. Progression-free survival (PFS) and disease-specific survival (DSS) were investigated using univariate analysis: the prognostic factors for PFS included MGS, extent of surgery, radiotherapy, chemotherapy and mitotic activity ≥5/10 high-power field (HPF). Moreover, MGS, radiotherapy, mitotic activity ≥5/10 HPF, and necrosis were the prognostic factors measured for DSS. In multivariate analysis, extent of surgery, mitotic activity ≥5/10 HPF, MGS I and MGS III were the independent prognostic factors measured for PFS while necrosis, MGS III and radiotherapy were the independent prognostic factors for DSS. In conclusion, our results show that assessing the malignancy risk of SFT/HPC should not rely on one single criterion like mitotic activity. Therefore, MGS is useful as it combines the value of different criteria. In particular, the combination of a high mitotic activity and necrosis (MGS III) indicates a particularly poor prognosis. © 2018 International Society of Neuropathology.

MR Fingerprinting of Adult Brain Tumors: Initial Experience.

PubMed

Badve, C; Yu, A; Dastmalchian, S; Rogers, M; Ma, D; Jiang, Y; Margevicius, S; Pahwa, S; Lu, Z; Schluchter, M; Sunshine, J; Griswold, M; Sloan, A; Gulani, V

2017-03-01

MR fingerprinting allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assessed the utility of MR fingerprinting in differentiating common types of adult intra-axial brain tumors. MR fingerprinting acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 World Health Organization grade II lower grade gliomas, and 8 metastases. T1, T2 of the solid tumor, immediate peritumoral white matter, and contralateral white matter were summarized within each ROI. Statistical comparisons on mean, SD, skewness, and kurtosis were performed by using the univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple-comparison testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases, and area under the receiver operator curve was calculated. Mean T2 values could differentiate solid tumor regions of lower grade gliomas from metastases (mean, 172 ± 53 ms, and 105 ± 27 ms, respectively; P = .004, significant after Bonferroni correction). The mean T1 of peritumoral white matter surrounding lower grade gliomas differed from peritumoral white matter around glioblastomas (mean, 1066 ± 218 ms, and 1578 ± 331 ms, respectively; P = .004, significant after Bonferroni correction). Logistic regression analysis revealed that the mean T2 of solid tumor offered the best separation between glioblastomas and metastases with an area under the curve of 0.86 (95% CI, 0.69-1.00; P < .0001). MR fingerprinting allows rapid simultaneous T1 and T2 measurement in brain tumors and surrounding tissues. MR fingerprinting-based relaxometry can identify quantitative differences between solid tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. © 2017 by American Journal of Neuroradiology.

Radiofrequency ablation of pulmonary tumors near the diaphragm.

PubMed

Iguchi, T; Hiraki, T; Gobara, H; Fujiwara, H; Sakurai, J; Matsui, Y; Mitsuhashi, T; Toyooka, S; Kanazawa, S

To retrospectively evaluate the feasibility, safety, and efficacy of radiofrequency ablation (RFA) of lung tumors located near the diaphragm. A total of 26 patients (15 men, 11 women; mean age, 61.5 years±13.0 [SD]) with a total of 29 lung tumors near the diaphragm (i.e., distance<10mm) were included. Mean tumor diameter was 11.0mm±5.3 (SD) (range, 2-23mm). Efficacy of RFA, number of adverse events and number of adverse events with a grade≥3, based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0, were compared between patients with lung tumors near the diaphragm and a control group of patients with more distally located lung tumors (i.e., distance≥10mm). RFA was technically feasible for all tumors near the diaphragm. Four grade 3 adverse events (1 pneumothorax requiring pleurodesis and 3 phrenic nerve injuries) were observed. No grade≥4 adverse events were reported. The median follow-up period for tumors near the diaphragm was 18.3 months. Local progression was observed 3.3 months after RFA in 1 tumor. The technique efficacy rates were 96.2% at 1 year and 96.2% at 2 years and were not different, from those observed in control subjects (186 tumors; P=0.839). Shoulder pain (P<0.001) and grade 1 pleural effusion (P<0.001) were more frequently observed in patients with lung tumor near the diaphragm. The rates of grade≥3 adverse events did not significantly differ between tumors near the diaphragm (4/26 sessions) and the controls (7/133 sessions) (P=0.083). RFA is a feasible and effective therapeutic option for lung tumors located near the diaphragm. However, it conveys a higher rate of shoulder pain and asymptomatic pleural effusion by comparison with more distant lung tumors. Copyright © 2017 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Reduced glucocorticoid receptor expression predicts bladder tumor recurrence and progression.

PubMed

Ishiguro, Hitoshi; Kawahara, Takashi; Zheng, Yichun; Netto, George J; Miyamoto, Hiroshi

2014-08-01

To assess the levels of glucocorticoid receptor (GR) expression in bladder tumors because the status and its prognostic value remain largely unknown. We immunohistochemically stained for GR in bladder tumor and matched non-neoplastic bladder tissue specimens. Overall, GR was positive in 129 (87%) of 149 urothelial tumors, which was significantly (P=.026) lower than in non-neoplastic urothelium (90 [96%] of 94). Forty-two (79%) of 53 low-grade tumors vs 45 (47%) of 96 high-grade carcinomas (P<.001) and 61 (73%) of 84 non-muscle-invasive (NMI) tumors vs 26 (40%) of 65 muscle-invasive (MI) carcinomas (P<.001) were moderately to strongly immunoreactive for GR. Kaplan-Meier and log-rank tests revealed that loss or weak positivity of GR significantly or marginally correlated with recurrence of NMI tumors (P=.025), progression of MI tumors (P=.082), and cancer-specific survival of MI tumors (P=.067). Multivariate analysis identified low GR expression as a strong predictor for recurrence of NMI tumors (P=.034). GR expression was downregulated in bladder tumors compared with nonneoplastic bladder tumors and in high-grade/MI tumors compared with low-grade/NMI tumors. Decreased expression of GR, as an independent prognosticator, predicted recurrence of NMI tumors. These results support experimental evidence suggesting an inhibitory role of GR signals in bladder cancer outgrowth. Copyright© by the American Society for Clinical Pathology.

Correlation of DNA content and nucleomorphometric features with World Health Organization grading of meningiomas.

PubMed

Grunewald, J P; Röhl, F W; Kirches, E; Dietzmann, K

1998-02-01

Many studies dealing with extracranial cancer showed a strong correlation of DNA ploidy to a poor clinical outcome, recurrence, or malignancy. In brain tumors, analysis of DNA content did not always provided significant diagnostic information. In this study, DNA density and karyometric parameters of 50 meningiomas (26 Grade I, 10 Grade II, 14 Grade III) were quantitatively evaluated by digital cell image analyses of Feulgen-stained nuclei. In particular, the densitometric parameter SEXT, which describes nuclear DNA content, as well as the morphometric values LENG (a computer-assisted measurement of nuclear circumference), AREA (a computer-assisted measurement of nuclear area), FCON (a parameter that describes nuclear roundness), and CONC (a describing nuclear contour), evaluated with the software IMAGE C, were correlated to World Health Organization (WHO) grading using univariate and multivariate methods. AREA and LENG values showed significant differences between tumors of Grades I and III. FCON values were unable to distinguish WHO Grade III from Grade I/II but were useful in clearly separating Grade II from Grade I tumors. CONC values detected differences between WHO Grades II and I/III tumors but not between the latter. SEXT values clearly distinguished Grade III from Grade I/II tumors. The 1c, 2c, 2.5c, and 5c exceeding rates showed no predictive values. Only the 6c exceeding rate showed a significant difference between Grades I and III. These results outline the characteristic features of the atypical (Grade II) meningiomas, which make them a recognizable tumor entity distinct from benign and anaplastic meningiomas. The combination of DNA densitometric and morphometric findings seems to be a powerful addition to the histopathologic classification of meningiomas, as suggested by the WHO.

Low-Grade Astrocytoma within a Mature Cystic Teratoma in an Adolescent Patient.

PubMed

Yoder, Nicole; Marks, Asher; Hui, Pei; Litkouhi, Babak; Cron, Julia

2018-06-01

Mature cystic teratomas are the most common ovarian neoplasm in adolescents. They are typically benign, however, malignant transformation rarely occurs. We report a low-grade astrocytoma arising from a mature cystic teratoma in an adolescent patient. The patient was a 12-year-old girl with an asymptomatic ovarian cyst and subsequent cystectomy. Final pathology identified a solid tumor with glial tissue within the cyst, reported as low-grade astrocytoma arising in a mature cystic teratoma. There are few data on astrocytomas in the gynecologic tract. Risk factors for malignant transformation in a mature cystic teratoma include increased age, postmenopausal status, elevated carcinoma antigen 125, and large tumor size. Interestingly, this patient had a history of partial trisomy 20, which has been associated with teratoma formation in a mouse model. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Molecular Subtypes of Indonesian Breast Carcinomas - Lack of Association with Patient Age and Tumor Size

PubMed Central

Rahmawati, Yeni; Setyawati, Yunita; Widodo, Irianiwati; Ghozali, Ahmad; Purnomosari, Dewajani

2018-01-01

Objective: Breast carcinoma (BC) is a heterogeneous disease that exhibits variation in biological behaviour, prognosis and response to therapy. Molecular classification is generally into Luminal A, Luminal B, HER2+ and triple negative/basal-like, depending on receptor characteristics. Clinical factors that determined the BC prognosis are age and tumor size. Since information on molecular subtypes of Indonesian BCs is limited, the present study was conducted, with attention to subtypes in relation to age and tumor size. Methods: A retrospective cross-sectional study of 247 paraffin-embedded samples of invasive BC from Dr. Sardjito General Hospital Yogyakarta in the year 2012- 2015 was performed. Immunohistochemical staining using anti- ER, PR, HER2, Ki-67 and CK 5/6 antibodies was applied to classify molecular subtypes. Associations with age and tumor size were analyzed using the Chi Square Test. Results: The Luminal A was the most common subtype of Indonesian BC (41.3%), followed by triple negative (25.5%), HER2 (19.4%) and luminal B (13.8%). Among the triple negative lesions, the basal-like subtype was more frequent than the non basal-like (58.8 % vs 41.2%). Luminal B accounted for the highest percentage of younger age cases (< 40 years old) while HER2+ was most common in older age (> 50 years old) patients. Triple negative/basal-like were commonly large in size. Age (p = 0.080) and tumor size (p = 0.462) were not significantly associated with molecular subtypes of BC. Conclusion: The most common molecular subtype of Indonesian BC is luminal A, followed by triple-negative, HER2+ and luminal B. The majority of triple-negative lesions are basal-like. There are no association between age and tumor size with molecular subtypes of Indonesian BCs. PMID:29373908

Molecular Subtypes of Indonesian Breast Carcinomas - Lack of Association with Patient Age and Tumor Size

PubMed

Rahmawati, Yeni; Setyawati, Yunita; Widodo, Irianiwati; Ghozali, Ahmad; Purnomosari, Dewajani

2018-01-27

Objective: Breast carcinoma (BC) is a heterogeneous disease that exhibits variation in biological behaviour, prognosis and response to therapy. Molecular classification is generally into Luminal A, Luminal B, HER2+ and triple negative/basal-like, depending on receptor characteristics. Clinical factors that determined the BC prognosis are age and tumor size. Since information on molecular subtypes of Indonesian BCs is limited, the present study was conducted, with attention to subtypes in relation to age and tumor size. Methods: A retrospective cross-sectional study of 247 paraffin-embedded samples of invasive BC from Dr. Sardjito General Hospital Yogyakarta in the year 2012- 2015 was performed. Immunohistochemical staining using anti- ER, PR, HER2, Ki-67 and CK 5/6 antibodies was applied to classify molecular subtypes. Associations with age and tumor size were analyzed using the Chi Square Test. Results: The Luminal A was the most common subtype of Indonesian BC (41.3%), followed by triple negative (25.5%), HER2 (19.4%) and luminal B (13.8%). Among the triple negative lesions, the basal-like subtype was more frequent than the non basal-like (58.8 % vs 41.2%). Luminal B accounted for the highest percentage of younger age cases (< 40 years old) while HER2+ was most common in older age (> 50 years old) patients. Triple negative/basal-like were commonly large in size. Age (p = 0.080) and tumor size (p = 0.462) were not significantly associated with molecular subtypes of BC. Conclusion: The most common molecular subtype of Indonesian BC is luminal A, followed by triple-negative, HER2+ and luminal B. The majority of triple-negative lesions are basal-like. There are no association between age and tumor size with molecular subtypes of Indonesian BCs. Creative Commons Attribution License

Histogram analysis of T2*-based pharmacokinetic imaging in cerebral glioma grading.

PubMed

Liu, Hua-Shan; Chiang, Shih-Wei; Chung, Hsiao-Wen; Tsai, Ping-Huei; Hsu, Fei-Ting; Cho, Nai-Yu; Wang, Chao-Ying; Chou, Ming-Chung; Chen, Cheng-Yu

2018-03-01

To investigate the feasibility of histogram analysis of the T2*-based permeability parameter volume transfer constant (K trans ) for glioma grading and to explore the diagnostic performance of the histogram analysis of K trans and blood plasma volume (v p ). We recruited 31 and 11 patients with high- and low-grade gliomas, respectively. The histogram parameters of K trans and v p , derived from the first-pass pharmacokinetic modeling based on the T2* dynamic susceptibility-weighted contrast-enhanced perfusion-weighted magnetic resonance imaging (T2* DSC-PW-MRI) from the entire tumor volume, were evaluated for differentiating glioma grades. Histogram parameters of K trans and v p showed significant differences between high- and low-grade gliomas and exhibited significant correlations with tumor grades. The mean K trans derived from the T2* DSC-PW-MRI had the highest sensitivity and specificity for differentiating high-grade gliomas from low-grade gliomas compared with other histogram parameters of K trans and v p . Histogram analysis of T2*-based pharmacokinetic imaging is useful for cerebral glioma grading. The histogram parameters of the entire tumor K trans measurement can provide increased accuracy with additional information regarding microvascular permeability changes for identifying high-grade brain tumors. Copyright © 2017 Elsevier B.V. All rights reserved.

Epilepsy and brain tumors

PubMed Central

ENGLOT, DARIO J.; CHANG, EDWARD F.; VECHT, CHARLES J.

2016-01-01

Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70–80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60–75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20–50% of patients with meningioma and 20–35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60–90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life. PMID:26948360

C2 root nerve sheath tumors management.

PubMed

El-Sissy, Mohamed H; Mahmoud, Mostafa

2013-05-01

Upper cervical nerve sheath tumors (NST) arising mainly from C2 root and to lesser extent from C1 root are not uncommon, they constitute approximately 5-12% of spinal nerve sheath tumors and 18-30% of all cervical nerve sheath tumors, unique in presentation and their relationship to neighbouring structures owing to the discrete anatomy at the upper cervical-craniovertebral region, and have atendency for growth reaching large-sized tumors before manifesting clinically due to the capacious spinal canal at this region; accordingly the surgical approaches to such tumors are modified. The aim of this paper is to discuss the surgical strategies for upper cervical nerve sheath tumors. Eleven patients (8 male and 3 females), age range 28-63 years, with C2 root nerve sheath tumors were operated upon based on their anatomical relations to the spinal cord. The magnetic resonance imaging findings were utilized to determine the surgical approach. The tumors had extra- and intradural components in 10 patients, while in one the tumor was purely intradural. The operative approaches included varied from extreme lateral transcondylar approach(n = 1) to laminectomy, whether complete(n = 3) a or hemilaminectomy(n = 7), with partial facetectomy(n = 7), and with suboccipital craniectomy(n = 2). The clinical picture ranged from spasticity (n = 8, 72,72 %), tingling and numbness below neck (n = 6, 54,54 %), weakness (n = 6, 54,54 %), posterior column involvement (n = 4, 26,36 %), and neck pain (n = 4, 36,36 %). The duration of symptoms ranged from 1 to 54 months, total excision was performed in 7 patients; while in 3 patients an extraspinal component, and in 1 patient a small intradural component, were left in situ. Eight patients showed improvement of myelopathy; 2 patients maintained their grades. One poor-grade patient was deteriorated. The surgical approaches for the C2 root nerve sheath tumors should be tailored according to the relationship to the spinal cord, determined by magnetic

Asphalt Pavement Aging and Temperature Dependent Properties Using Functionally Graded Viscoelastic Model

ERIC Educational Resources Information Center

Dave, Eshan V.

2009-01-01

Asphalt concrete pavements are inherently graded viscoelastic structures. Oxidative aging of asphalt binder and temperature cycling due to climatic conditions being the major cause of non-homogeneity. Current pavement analysis and simulation procedures dwell on the use of layered approach to account for these non-homogeneities. The conventional…

Does Relative Age Influence Motor Test Performance of Fourth Grade Pupils?

ERIC Educational Resources Information Center

Wattie, Nick; Tietjens, Maike; Schorer, Jörg; Ghanbari, Marie-Christine; Strauss, Bernd; Seidel, Ilka; Baker, Joseph

2014-01-01

The aim of the current study was to explore relative age's influence on physical and motor tests among fourth grade children (9 to 10 years) from Germany. Data from 1218 children (49% female) who had performed the German Motor Ability Test (Bös et al., 2009) were analysed. The test battery, which was comprised of physical and motor tests, included…

Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

ClinicalTrials.gov

2014-11-04

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

Characterization of Aging Behavior in M250 Grade Maraging Steel Using Ultrasonic Measurements

NASA Astrophysics Data System (ADS)

Rajkumar, K. V.; Kumar, Anish; Jayakumar, T.; Raj, Baldev; Ray, K. K.

2007-02-01

Ultrasonic measurements have been carried out in M250 grade maraging steel specimens subjected to solution annealing at 1093 K for 1 hour followed by aging at 755 K for various durations in the range of 0.25 to 100 hours. The influence of aging on microstructure, room temperature hardness, and ultrasonic parameters (longitudinal and shear wave velocities and Poisson’s ratio) has been studied in order to derive correlations among these parameters in aged M250 maraging steel. Both hardness and ultrasonic velocities exhibit almost similar behaviors with aging time. They increase with the precipitation of intermetallic phases, Ni3Ti and Fe2Mo, and decrease with the reversion of martensite to austenite. Ultrasonic shear wave velocity is found to be more influenced by the precipitation of intermetallic phases, whereas longitudinal wave velocity is influenced more by the reversion of martensite to austenite. Unlike hardness and ultrasonic velocities, the Poisson’s ratio exhibits a monotonous decrease with aging time and, hence, can be used for unambiguous monitoring of the aging process in M250 maraging steel. Further, none of the parameters, i.e., hardness, ultrasonic velocity, or Poisson’s ratio, alone could identify the initiation of the reversion of austenite at early stage; however, the same could be identified from the correlation between ultrasonic velocity and Poisson’s ratio, indicating the advantage of using the multiparametric approach for comprehensive characterization of complex aging behavior in M250 grade maraging steel.

[Tumor markers for bladder cancer: up-to-date study by the Kiel Tumor Bank].

PubMed

Hautmann, S; Eggers, J; Meyhoff, H; Melchior, D; Munk, A; Hamann, M; Naumann, M; Braun, P M; Jünemann, K P

2007-11-01

The number of noninvasive diagnostic tests for bladder cancer has increased tremendously over the last years with a large number of experimental and commercial tests. Comparative analyses of tests for diagnosis, follow-up, and recurrence detection of bladder cancer were performed retrospectively as well as prospectively, unicentrically, and multicentrically. An analysis of multicentric studies with large patient numbers compared with our own Kiel Tumor Bank data is presented. The Kiel Tumor Bank data looked prospectively at 106 consecutive bladder tumor patients from the year 2006. Special focus was put on urine cytology as a reference test, as well as the commercial NMP 22 Bladder Chek. The analysis of the NMP 22 Bladder Chek showed an overall sensitivity of 69% for all tumor grades and stages, with a specificity of 76%. Comparison to multicentric data with an overall sensitivity of 75% for all tumor grades and stages, with a specificity of 73%, showed results similar to those in the literature. Urine cytology showed a comparable overall sensitivity of 73% for all tumor grades and stages, with a specificity of 80%. A large number of noninvasive tests for bladder cancer follow-up with reasonable sensitivity and specificity can currently be used. Because of limited numbers of prospective randomized multicentric studies, no single particular marker for bladder cancer screening can be recommended at this point in time.

[A rare primary tumor of the mediastinum: pleomorphic liposarcoma].

PubMed

Msaad, S; Yangui, I; Ayedi, L; Ketata, W; Sellami, T; Ayoub, A; Jlidi, R

2007-12-01

Liposarcoma of the mediastinum is a rare tumor with various histologic features. We report a case of mediatinal pleomorphic liposarcoma in a 37-year-old man who complained of chest pain. Computed tomography showed an anterior expansive process within the mediastinum. Histological diagnosis was established by a trans-thoracic computed tomography guided core-needle biopsy. Despite a first cure of chemotherapy with gemcitabin/cisplatin, disease progression led to death 3 months after diagnosis. Mediastinal pleomorphic liposarcoma is an exceptional invading tumor affecting the middle-aged adult. This tumor, usually giant, becomes symptomatic by compression of mediastinal structures. Surgery is the best treatment when possible. The role of radiotherapy and chemotherapy are discussed. Prognosis depends both on the quality of resection and the grade malignancy.

Statistical Report of Central Nervous System Tumors Histologically Diagnosed in the Sichuan Province of China from 2008 to 2013: A West China Glioma Center Report.

PubMed

Wang, Xiang; Chen, Jin-Xiu; Zhou, Qiao; Liu, Yan-Hui; Mao, Qing; You, Chao; Chen, Ni; Xiong, Li; Duan, Jie; Liu, Liang

2016-12-01

Sichuan is a province in the west of China with a population of 81.4 million. This is the first statistical report of central nervous system (CNS) tumors surgically treated and histologically diagnosed in a large Chinese population. All the patient data were obtained from 86 medical facilities, which covered the Sichuan province population. Data from patients who underwent surgery between 2008 and 2013 and corresponding histology samples were re-reviewed in the major pathology centers. All the CNS tumors were categorized according to International Classification of Diseases (ICD)-10 and ICD-O-3 classifications and reviewed manually. The tumor distribution was analyzed and stratified by gender, age, race, and tumor sites. Tumors in some ethnic minorities, such as the Tibetan people, also were analyzed. The final analytic dataset included 35,496 records. The top four histologic tumors were meningioma (28.51 %), pituitary adenoma (15.00 %), nerve sheath (13.77 %), and glioblastoma (11.82 %). There was a dramatically high incidence of malignant tumor in males. The median age at diagnosis ranged from 13 years (pineal region tumors) to 56 years (metastatic brain tumors). Most of the tumors in the insular lobe or cerebellum were low grade, whereas those in the thalamus or basal ganglia were likely to be high grade. The incidence of malignant tumors or high-grade gliomas in the Tibetans was significantly lower than in the Chinese Han population. This report is a preliminary statistical analysis of brain and spinal tumors in a large Chinese population and may serve as a useful resource for clinicians, researchers, and patients' families.

IDH mutant and 1p/19q co-deleted oligodendrogliomas: tumor grade stratification using diffusion-, susceptibility-, and perfusion-weighted MRI.

PubMed

Lin, Yu; Xing, Zhen; She, Dejun; Yang, Xiefeng; Zheng, Yingyan; Xiao, Zebin; Wang, Xingfu; Cao, Dairong

2017-06-01

Currently, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion are proven diagnostic biomarkers for both grade II and III oligodendrogliomas (ODs). Non-invasive diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) are widely used to provide physiological information (cellularity, hemorrhage, calcifications, and angiogenesis) of neoplastic histology and tumor grade. However, it is unclear whether DWI, SWI, and DSC-PWI are able to stratify grades of IDH-mutant and 1p/19q co-deleted ODs. We retrospectively reviewed the conventional MRI (cMRI), DWI, SWI, and DSC-PWI obtained on 33 patients with IDH-mutated and 1p/19q co-deleted ODs. Features of cMRI, normalized ADC (nADC), intratumoral susceptibility signals (ITSSs), normalized maxim CBV (nCBV), and normalized maximum CBF (nCBF) were compared between low-grade ODs (LGOs) and high-grade ODs (HGOs). Receiver operating characteristic curve and logistic regression were applied to determine diagnostic performances. HGOs tended to present with prominent edema and enhancement. nADC, ITSSs, nCBV, and nCBF were significantly different between groups (all P < 0.05). The combination of SWI and DSC-PWI for grading resulted in sensitivity and specificity of 100.00 and 93.33%, respectively. IDH-mutant and 1p/19q co-deleted ODs can be stratified by grades using cMRI and advanced magnetic resonance imaging techniques including DWI, SWI, and DSC-PWI. Combined ITSSs with nCBV appear to be a promising option for grading molecularly defined ODs in clinical practice.

Relationships of nuclear, architectural and International Federation of Gynecology and Obstetrics grading systems in endometrial cancer.

PubMed

Toptaş, Tayfun; Peştereli, Elif; Bozkurt, Selen; Erdoğan, Gülgün; Şimşek, Tayup

2018-03-01

To examine correlations among nuclear, architectural, and International Federation of Gynecology and Obstetrics (FIGO) grading systems, and their relationships with lymph node (LN) involvement in endometrioid endometrial cancer. Histopathology slides of 135 consecutive patients were reviewed with respect to tumor grade and LN metastasis. Notable nuclear atypia was defined as grade 3 nuclei. FIGO grade was established by raising the architectural grade (AG) by one grade when the tumor was composed of cells with nuclear grade (NG) 3. Correlations between the grading systems were analyzed using Spearman's rank correlation coefficients, and relationships of grading systems with LN involvement were assessed using logistic regression analysis. Correlation analysis revealed a significant and strongly positive relationship between FIGO and architectural grading systems (r=0.885, p=0.001); however, correlations of nuclear grading with the architectural (r=0.535, p=0.165) and FIGO grading systems (r=0.589, p=0.082) were moderate and statistically non-significant. Twenty-five (18.5%) patients had LN metastasis. LN involvement rates differed significantly between tumors with AG 1 and those with AG 2, and tumors with FIGO grade 1 and those with FIGO grade 2. In contrast, although the difference in LN involvement rates failed to reach statistical significance between tumors with NG 1 and those with NG 2, it was significant between NG 2 and NG 3 (p=0.042). Although all three grading systems were associated with LN involvement in univariate analyses, an independent relationship could not be established after adjustment for other confounders in multivariate analysis. Nuclear grading is significantly correlated with neither architectural nor FIGO grading systems. The differences in LN involvement rates in the nuclear grading system reach significance only in the setting of tumor cells with NG 3; however, none of the grading systems was an independent predictor of LN involvement.

Compliance and safety of a novel home exercise program for patients with high-grade brain tumors, a prospective observational study.

PubMed

Baima, Jennifer; Omer, Zehra B; Varlotto, John; Yunus, Shakeeb

2017-09-01

The purpose of this study is to evaluate compliance with and safety of a novel independent home exercise program for patients with high-grade brain tumors. We designed this program around the preferences and individual capabilities of this population as well as the potential barriers to exercise in cancer patients. Demographics were collected to better understand those that persisted with exercise. Subjects with high-grade brain tumor received one-time training that included watching an exercise video and live demonstration of resistance band exercises, a balance exercise, and recommendations for walking. Subjects were instructed to do the exercises every day for 1 month. Main outcome measures were percentage of subjects who exercised throughout the month, frequency of exercising, demographic factors, quality of life scores (assessed by FACT-BR), and self report of adverse events. Fourteen of the 15 (93%) subjects started the exercises during the course of the month. Nine of the fifteen (60%) continued the exercises throughout the month. Three additional subjects would have continued to exercise if formal or supervised rehabilitation had been offered. Among the subjects who continued the exercises regularly, higher frequency of exercising was significantly associated with living as married (p = 0.033), annual income >$50,000 (p = 0.047), scores of physical well-being (p = 0.047), and brain cancer specific well-being (p = 0.054) subscales. Among those who exercised frequently, there was also a trend towards increase in total FACT-BR scores (p = 0.059). The subjects who scored higher on the social well-being subscale of the FACT-BR at baseline self-reported a higher likelihood to continue the exercises after 1 month of participation in the study (p = 0.018). No adverse events were reported. Our small group of subjects with high-grade brain tumors demonstrated compliance with and safety of a novel independent strength and balance exercise program in the

Time interval between endometrial biopsy and surgical staging for type I endometrial cancer: association between tumor characteristics and survival outcome.

PubMed

Matsuo, Koji; Opper, Neisha R; Ciccone, Marcia A; Garcia, Jocelyn; Tierney, Katherine E; Baba, Tsukasa; Muderspach, Laila I; Roman, Lynda D

2015-02-01

To examine whether wait time between endometrial biopsy and surgical staging correlates with tumor characteristics and affects survival outcomes in patients with type I endometrial cancer. A retrospective study was conducted to examine patients with grade 1 and 2 endometrioid adenocarcinoma diagnosed by preoperative endometrial biopsy who subsequently underwent hysterectomy-based surgical staging between 2000 and 2013. Patients who received neoadjuvant chemotherapy or hormonal treatment were excluded. Time interval and grade change between endometrial biopsy and hysterectomy were correlated to demographics and survival outcomes. Median wait time was 57 days (range 1-177 days) among 435 patients. Upgrading of the tumor to grade 3 in the hysterectomy specimen was seen in 4.7% of 321 tumors classified as grade 1 and 18.4% of 114 tumors classified as grade 2 on the endometrial biopsy, respectively. Wait time was not associated with grade change (P>.05). Controlling for age, ethnicity, body habitus, medical comorbidities, CA 125 level, and stage, multivariable analysis revealed that wait time was not associated with survival outcomes (5-year overall survival rates, wait time 1-14, 15-42, 43-84, and 85 days or more; 62.5%, 93.6%, 95.2%, and 100%, respectively, P>.05); however, grade 1 to 3 on the hysterectomy specimen remained as an independent prognosticator associated with decreased survival (5-year overall survival rates, grade 1 to 3 compared with grade change 1 to 1, 82.1% compared with 98.5%, P=.01). Among grade 1 preoperative biopsies, grade 1 to 3 was significantly associated with nonobesity (P=.039) and advanced stage (P=.019). Wait time for surgical staging was not associated with decreased survival outcome in patients with type I endometrial cancer.

FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia

ClinicalTrials.gov

2013-01-15

Blastic Phase Chronic Myelogenous Leukemia; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Chronic Myelogenous Leukemia; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

Selumetinib Sulfate in Treating Woman With Recurrent Low-Grade Ovarian Cancer or Peritoneum Cancer

ClinicalTrials.gov

2018-03-30

Borderline Ovarian Epithelial Tumor; Low Grade Ovarian Serous Adenocarcinoma; Primary Peritoneal Carcinoma; Primary Peritoneal Low Grade Serous Adenocarcinoma; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor

Increased expression of placental growth factor in high-grade endometrial carcinoma.

PubMed

Coenegrachts, Lieve; Schrauwen, Stefanie; Van Bree, Rita; Despierre, Evelyn; Luyten, Catherine; Jonckx, Bart; Stassen, Jean Marie; Vergote, Ignace; Amant, Frédéric

2013-02-01

Placental growth factor (PlGF), a homolog of vascular endothelial growth factor (VEGF), exerts pleiotropic functions in cancer by affecting tumor cells as well as endothelial and inflammatory cells. Moreover, PlGF expression correlates with tumor stage, recurrence, metastasis and patient outcome in different types of cancer. Recently, administration of anti-PlGF therapy reduced tumor growth and metastasis in preclinical tumor models. In the present study, we evaluated the diagnostic and prognostic value of systemic and local expression of PlGF in primary endometrial carcinomas. PlGF levels in tumor lysates (n=128) and serum (n=88) of patients with primary endometrial cancer were determined using ELISA. PlGF mRNA expression in endometrial carcinoma tissues was quantified by quantitative qRT-PCR. Results were compared to endometrial cancer stage and grade. Systemic PlGF levels were not altered in patients with endometrial cancer (FIGO stage I-II-III) as compared to healthy controls. Only in FIGO stage IV patients, serum PlGF levels were slightly increased. Local PlGF mRNA and protein expression in endometrial tumors progressively increased with tumor grade. In endometrioid carcinomas, PlGF mRNA expression was significantly increased in endometrioid grade 3 tumors as compared to normal endometrial tissue. PlGF protein expression was significantly increased in endometrioid grade 2 and 3 carcinomas and in serous carcinomas as compared to normal endometrial tissue. Our study showed that systemic/serum PlGF levels cannot be used as a diagnostic or prognostic marker in endometrial cancer. However, the increased local expression of PlGF, primarily in high-grade carcinomas, underscores the possibility for preclinical assessment of anti-PlGF therapy in endometrial cancer.

Genomic characterization of recurrent high-grade astroblastoma.

PubMed

Bale, Tejus A; Abedalthagafi, Malak; Bi, Wenya Linda; Kang, Yun Jee; Merrill, Parker; Dunn, Ian F; Dubuc, Adrian; Charbonneau, Sarah K; Brown, Loreal; Ligon, Azra H; Ramkissoon, Shakti H; Ligon, Keith L

2016-01-01

Astroblastomas are rare primary brain tumors, diagnosed based on histologic features. Not currently assigned a WHO grade, they typically display indolent behavior, with occasional variants taking a more aggressive course. We characterized the immunohistochemical characteristics, copy number (high-resolution array comparative genomic hybridization, OncoCopy) and mutational profile (targeted next-generation exome sequencing, OncoPanel) of a cohort of seven biopsies from four patients to identify recurrent genomic events that may help distinguish astroblastomas from other more common high-grade gliomas. We found that tumor histology was variable across patients and between primary and recurrent tumor samples. No common molecular features were identified among the four tumors. Mutations commonly observed in astrocytic tumors (IDH1/2, TP53, ATRX, and PTEN) or ependymoma were not identified. However one case with rapid clinical progression displayed mutations more commonly associated with GBM (NF1(N1054H/K63)*, PIK3CA(R38H) and ERG(A403T)). Conversely, another case, originally classified as glioblastoma with nine-year survival before recurrence, lacked a GBM mutational profile. Other mutations frequently seen in lower grade gliomas (BCOR, BCORL1, ERBB3, MYB, ATM) were also present in several tumors. Copy number changes were variable across tumors. Our findings indicate that astroblastomas have variable growth patterns and morphologic features, posing significant challenges to accurate classification in the absence of diagnostically specific copy number alterations and molecular features. Their histopathologic overlap with glioblastoma will likely confound the observation of long-term GBM "survivors". Further genomic profiling is needed to determine whether these tumors represent a distinct entity and to guide management strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

Aging and insulin signaling differentially control normal and tumorous germline stem cells.

PubMed

Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

2015-02-01

Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Label-free pathological evaluation of grade 3 cancer using Stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Sordillo, Laura A.; Sordillo, Peter P.; Alfano, R. R.

2016-03-01

In this study, Stokes shift spectroscopy (S3) is used for measuring the aggressiveness of malignant tumors. S3 is an optical tool which utilizes the difference between the emission wavelength (λem) and the absorption wavelength (λabs) (the Stokes shift) to give a fixed wavelength shift (Δλs).Our analysis of tumor samples using S3 shows grade 3 (high grade) cancers consistently have increased relative tryptophan content compared to grade 1 or 2 tumors. This technique may be a useful tool in the evaluation of a patient's cancer.

[Diagnostic imaging of high-grade astrocytoma: heterogeneity of clinical manifestation, image characteristics, and histopathological findings].

PubMed

Okajima, Kaoru; Ohta, Yoshio

2012-10-01

Recent developments in diagnostic radiology, which have enabled accurate differential diagnoses of brain tumors, have been well described in the last three decades. MR and PET imaging can also provide information to predict histological grades and prognoses that might influence treatment strategies. However, high-grade astrocytomas consist of many different subtypes that are associated with different imaging and histological characteristics. Hemorrhage and necrosis results in a variety of imaging features, and infiltrative tumor growth entrapping normal neurons may cause different clinical manifestations. We reviewed patients with high-grade astrocytomas that showed various imaging characteristics, with special emphasis on initial symptoms and histological features. Clinicopathological characteristics of astrocytomas were also compared with other malignant tumors. Neurological deficits were not notable in patients with grade 3-4 astrocytomas when they showed infiltrative tumor growth, while brain metastases with compact cellular proliferation caused more neurological symptoms. Infiltrative tumors did not show any enhancing masses on MR imaging, but these tumors may show intratumor heterogeneity. Seizures were reported to be more frequent in low-grade glioma and in secondary glioblastoma. Tumor heterogeneity was also reported in molecular genetic profile, and investigators identified some subsets of astrocytomas. They investigated IHD1/2 mutation, EGFR amplification, TP53 mutation, Ki-67 index, etc. In summary, high-grade astrocytomas are not homogenous groups of tumors, and this is associated with the heterogeneity of clinical manifestation, image characteristics, and histopathological findings. Molecular studies may explain the tumor heterogeneity in the near future.

MDM2 copy numbers in well-differentiated and dedifferentiated liposarcoma: characterizing progression to high-grade tumors.

PubMed

Ware, Patrick L; Snow, Anthony N; Gvalani, Maya; Pettenati, Mark J; Qasem, Shadi A

2014-03-01

MDM2 gene amplification is associated with well-differentiated (WDL) and dedifferentiated liposarcomas (DDL). Using fluorescent in situ hybridization (FISH), we sought to characterize various patterns of MDM2 amplification among the morphologic spectrum of liposarcoma. Forty-six cases of liposarcoma in various sites were examined and included 22 WDLs, 14 DLLs, and 10 negative control subjects. The MDM2 amplification ratio (MDM2/CEP12) was lower in WDL (10.2) compared with DDL (18.3) cases (P = .0000002). An amplification ratio of 16 showed optimal sensitivity (0.86) and specificity (0.96) as a cutoff point for progression to DDL. Borderline areas, defined as tumors with increased cellularity and atypia but with preserved lipomatous differentiation, showed a significantly higher MDM2 ratio (17.5; P = .0007) compared with WDL. Central (retroperitoneal and intra-abdominal) tumors also showed a significantly higher MDM2 ratio than peripheral ones (P = .02). Differences in MDM2 amplification profiles among liposarcomas could help further define and predict progression to high-grade neoplasia.

Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade.

PubMed

Gupta, Kanika; Kumaresan, Meenakshisundaram; Venkatesan, Bhuvaneswari; Chandra, Tushar; Patil, Aruna; Menon, Maya

2018-01-01

Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Chi square test, ordinal regression, and Goodman and Kruskal tau test. Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor ( β 1.566, P 0.0001 ). The masses with abrupt interface boundary are more likely grade 3 ( β 1.524, P 0.001 ) in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs) with complex solid and cystic echotexture are more likely to be of high histological grade ( β 1.146, P 0.04 ) as compared to masses with hypoechoic echotexture. Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited.

Age is not a prognostic factor in children with Wilms tumor beyond stage I in Africa.

PubMed

Aronson, D C; Hadley, G P

2014-06-01

Patients under age 4 with stage I favorable histology (FH) Wilms tumor have a reported survival advantage. Among children above 10 years, a poorer prognosis has been associated with a higher prevalence of diffuse anaplasia. To determine if, in our practice, patients with Wilms tumors >8 years of age (stage II-V) have a poorer prognosis than those aged <8 years or <4 years. Case-control study of 19 patients >8 years with Wilms tumor stages II-V who were identified from a cohort of 192 new patients (2002-2012). For each patient two controls were chosen matched for stage and histology, one 0-3 years and one 4-7 years. Neo-adjuvant chemotherapy was offered to all, combined with intensive supportive care. Postoperative treatment was determined by local stage and histology. OS and EFS at 5 years for the different age groups were compared. Each age group contained 19 patients, of whom 6 had stage II tumors, 3 stage III, 8 stage IV, and 2 stage V. Histology was intermediate risk (IR) in 17 and high risk (HR) in 2. OS at 5 years was 80.8% and EFS was 79.2% for the whole group. No significant difference in outcome could be shown between age groups. Loss to follow up was 6/57 (11%). The survival advantage of young age (<4 years) associated with stage I FH could not be demonstrated in higher stages. Age had no significant impact on prognosis although a trend to better outcome was seen in children <4 years. © 2014 Wiley Periodicals, Inc.

The Minnesota Grading System using fundus autofluorescence of eye bank eyes: a correlation to age-related macular degeneration (an AOS thesis).

PubMed

Olsen, Timothy W

2008-01-01

To establish a grading system of eye bank eyes using fundus autofluorescence (FAF) and identify a methodology that correlates FAF to age-related macular degeneration (AMD) with clinical correlation to the Age-Related Eye Disease Study (AREDS). Two hundred sixty-two eye bank eyes were evaluated using a standardized analysis of FAF. Measurements were taken with the confocal scanning laser ophthalmoscope (cSLO). First, high-resolution, digital, stereoscopic, color images were obtained and graded according to AREDS criteria. With the neurosensory retina removed, mean FAF values were obtained from cSLO images using software analysis that excludes areas of atrophy and other artifact, generating an FAF value from a grading template. Age and AMD grade were compared to FAF values. An internal fluorescence reference standard was tested. Standardization of the cSLO machine demonstrated that reliable data could be acquired after a 1-hour warm-up. Images obtained prior to 1 hour had falsely elevated levels of FAF. In this initial analysis, there was no statistical correlation of age to mean FAF. There was a statistically significant decrease in FAF from AREDS grade 1, 2 to 3, 4 (P < .0001). An internal fluorescent standard may serve as a quantitative reference. The Minnesota Grading System (MGS) of FAF (MGS-FAF) establishes a standardized methodology for grading eye bank tissue to quantify FAF compounds in the retinal pigment epithelium and correlate these findings to the AREDS. Future studies could then correlate specific FAF to the aging process, histopathology AMD phenotypes, and other maculopathies, as well as to analyze the biochemistry of autofluorescent fluorophores.

Preoperative Embolization of Extra-axial Hypervascular Tumors with Onyx.

PubMed

Fusco, Matthew R; Salem, Mohamed M; Gross, Bradley A; Reddy, Arra S; Ogilvy, Christopher S; Kasper, Ekkehard M; Thomas, Ajith J

2016-03-01

Preoperative endovascular embolization of intracranial tumors is performed to mitigate anticipated intraoperative blood loss. Although the usage of a wide array of embolic agents, particularly polyvinyl alcohol (PVA), has been described for a variety of tumors, literature detailing the efficacy, safety and complication rates for the usage of Onyx is relatively sparse. We reviewed our single institutional experience with pre-surgical Onyx embolization of extra-axial tumors to evaluate its efficacy and safety and highlight nuances of individualized cases. Five patients underwent pre-surgical Onyx embolization of large or giant extra-axial tumors within 24 hours of surgical resection. Four patients harbored falcine or convexity meningiomas (grade I in 2 patients, grade II in 1 patient and grade III in one patient), and one patient had a grade II hemangiopericytoma. Embolization proceeded uneventfully in all cases and there were no complications. This series augments the expanding literature confirming the safety and efficacy of Onyx in the preoperative embolization of extra-axial tumors, underscoring its advantage of being able to attain extensive devascularization via only one supplying pedicle.

Diffuse low-grade glioma: a review on the new molecular classification, natural history and current management strategies.

PubMed

Delgado-López, P D; Corrales-García, E M; Martino, J; Lastra-Aras, E; Dueñas-Polo, M T

2017-08-01

The management of diffuse supratentorial WHO grade II glioma remains a challenge because of the infiltrative nature of the tumor, which precludes curative therapy after total or even supratotal resection. When possible, functional-guided resection is the preferred initial treatment. Total and subtotal resections correlate with increased overall survival. High-risk patients (age >40, partial resection), especially IDH-mutated and 1p19q-codeleted oligodendroglial lesions, benefit from surgery plus adjuvant chemoradiation. Under the new 2016 WHO brain tumor classification, which now incorporates molecular parameters, all diffusely infiltrating gliomas are grouped together since they share specific genetic mutations and prognostic factors. Although low-grade gliomas cannot be regarded as benign tumors, large observational studies have shown that median survival can actually be doubled if an early, aggressive, multi-stage and personalized therapy is applied, as compared to prior wait-and-see policy series. Patients need an honest long-term therapeutic strategy that should ideally anticipate neurological, cognitive and histopathologic worsening.

Glial tumors with neuronal differentiation.

PubMed

Park, Chul-Kee; Phi, Ji Hoon; Park, Sung-Hye

2015-01-01

Immunohistochemical studies for neuronal differentiation in glial tumors revealed subsets of tumors having both characteristics of glial and neuronal lineages. Glial tumors with neuronal differentiation can be observed with diverse phenotypes and histologic grades. The rosette-forming glioneuronal tumor of the fourth ventricle and papillary glioneuronal tumor have been newly classified as distinct disease entities. There are other candidates for classification, such as the glioneuronal tumor without pseudopapillary architecture, glioneuronal tumor with neuropil-like islands, and the malignant glioneuronal tumor. The clinical significance of these previously unclassified tumors should be confirmed. Copyright © 2015 Elsevier Inc. All rights reserved.

Multi-fractal detrended texture feature for brain tumor classification

NASA Astrophysics Data System (ADS)

Reza, Syed M. S.; Mays, Randall; Iftekharuddin, Khan M.

2015-03-01

We propose a novel non-invasive brain tumor type classification using Multi-fractal Detrended Fluctuation Analysis (MFDFA) [1] in structural magnetic resonance (MR) images. This preliminary work investigates the efficacy of the MFDFA features along with our novel texture feature known as multifractional Brownian motion (mBm) [2] in classifying (grading) brain tumors as High Grade (HG) and Low Grade (LG). Based on prior performance, Random Forest (RF) [3] is employed for tumor grading using two different datasets such as BRATS-2013 [4] and BRATS-2014 [5]. Quantitative scores such as precision, recall, accuracy are obtained using the confusion matrix. On an average 90% precision and 85% recall from the inter-dataset cross-validation confirm the efficacy of the proposed method.

Effect of gibberellic Acid on crown gall tumor induction in aging primary pinto bean leaves.

PubMed

Anand, V K; Bauer, C; Heberlein, G T

1975-06-01

Gibberellic acid was tested for its effect on tumor induction by Agrobacterium tumefaciens in primary pinto bean (Phaseolus vulgaris) leaves in various stages of development. The hormone was found to promote tumor induction in partially aged leaves but did not effect tumor induction in very young leaves or in fully matured leaves. It is suggested that the natural loss of susceptibility to tumor induction in maturing pinto bean leaves is associated with a concomitant loss of endogenous gibberellins and/or a sensitivity to gibberellins.

Outcome of primary childhood central nervous system tumors: results from a single center in Iran.

PubMed

Rafsanjani, Kh Arjmandi; Bahoush, Gr; Nikpoor, F; Vossough, P

2012-10-01

Childhood primary central nervous system (CNS) malignancies are one of the most important concerns in pediatric oncology. In this historical cohort, 82 patients treated in Ali-Asghar Children's Hospital between 1996 and 2005 were evaluated for age, gender, type of treatment, tumor pathology, and survival. The records of 38 female (46.3%) and 44 male (53.7%) patients were included. The mean age was 6.8 ± 3.39 years (6 months to 14 years); the frequency of medulloblastoma was significantly more than others (p = 0.012). Complete resection, radiotherapy, and chemotherapy were done in 47.5, 82.9, and 97.56%, respectively. Estimated 5 years overall and event-free survivals (EFSs) were approximately 68.5 and 35%, respectively. The patients with complete resected tumors had significantly better outcome (p = 0.013). Also, low-grade versus high-grade astrocytoma was significantly a better outcome (p = 0.01). The poor EFS with consideration of high number of progressive disease among our patients (50% unresectable tumor) suggests that children in Iran with CNS tumors had high quality of care but availability of advanced treatment protocol and sharing of cooperative trial study is essential for survival improvement. In addition to use more advanced methods and equipments of radiotherapy and chemotherapeutic drugs, we should seriously consider development of better surgical techniques to increase the rate of complete resection of malignant CNS tumors. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Increased expression of placental growth factor in high-grade endometrial carcinoma

PubMed Central

COENEGRACHTS, LIEVE; SCHRAUWEN, STEFANIE; VAN BREE, RITA; DESPIERRE, EVELYN; LUYTEN, CATHERINE; JONCKX, BART; STASSEN, JEAN MARIE; VERGOTE, IGNACE; AMANT, FRÉDÉRIC

2013-01-01

Placental growth factor (PlGF), a homolog of vascular endothelial growth factor (VEGF), exerts pleiotropic functions in cancer by affecting tumor cells as well as endothelial and inflammatory cells. Moreover, PlGF expression correlates with tumor stage, recurrence, metastasis and patient outcome in different types of cancer. Recently, administration of anti-PlGF therapy reduced tumor growth and metastasis in preclinical tumor models. In the present study, we evaluated the diagnostic and prognostic value of systemic and local expression of PlGF in primary endometrial carcinomas. PlGF levels in tumor lysates (n=128) and serum (n=88) of patients with primary endometrial cancer were determined using ELISA. PlGF mRNA expression in endometrial carcinoma tissues was quantified by quantitative qRT-PCR. Results were compared to endometrial cancer stage and grade. Systemic PlGF levels were not altered in patients with endometrial cancer (FIGO stage I-II-III) as compared to healthy controls. Only in FIGO stage IV patients, serum PlGF levels were slightly increased. Local PlGF mRNA and protein expression in endometrial tumors progressively increased with tumor grade. In endometrioid carcinomas, PlGF mRNA expression was significantly increased in endometrioid grade 3 tumors as compared to normal endometrial tissue. PlGF protein expression was significantly increased in endometrioid grade 2 and 3 carcinomas and in serous carcinomas as compared to normal endometrial tissue. Our study showed that systemic/serum PlGF levels cannot be used as a diagnostic or prognostic marker in endometrial cancer. However, the increased local expression of PlGF, primarily in high-grade carcinomas, underscores the possibility for preclinical assessment of anti-PlGF therapy in endometrial cancer. PMID:23232836

Metabolic brain imaging correlated with clinical features of brain tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alavi, J.; Alavi, A.; Dann, R.

1985-05-01

Nineteen adults with brain tumors have been studied with positron emission tomography utilizing FDG. Fourteen had biopsy proven cerebral malignant glioma, one each had meningioma, hemangiopericytoma, primitive neuroectodermal tumor (PNET), two had unbiopsied lesions, and one patient had an area of biopsy proven radiation necrosis. Three different patterns of glucose metabolism are observed: marked increase in metabolism at the site of the known tumor in (10 high grade gliomas and the PNET), lower than normal metabolism at the tumor (in 1 grade II glioma, 3 grade III gliomas, 2 unbiopsied low density nonenhancing lesions, and the meningioma), no abnormality (1more » enhancing glioma, the hemangiopericytoma and the radiation necrosis.) The metabolic rate of the tumor or the surrounding brain did not appear to be correlated with the history of previous irradiation or chemotherapy. Decreased metabolism was frequently observed in the rest of the affected hemisphere and in the contralateral cerebellum. Tumors of high grade or with enhancing CT characteristics were more likely to show increased metabolism. Among the patients with proven gliomas, survival after PETT scan tended to be longer for those with low metabolic activity tumors than for those with highly active tumors. The authors conclude that PETT may help to predict the malignant potential of tumors, and may add useful clinical information to the CT scan.« less

Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups.

PubMed

Bosse, Tjalling; Nout, Remi A; McAlpine, Jessica N; McConechy, Melissa K; Britton, Heidi; Hussein, Yaser R; Gonzalez, Carlene; Ganesan, Raji; Steele, Jane C; Harrison, Beth T; Oliva, Esther; Vidal, August; Matias-Guiu, Xavier; Abu-Rustum, Nadeem R; Levine, Douglas A; Gilks, C Blake; Soslow, Robert A

2018-05-01

Our aim was to investigate whether molecular classification can be used to refine prognosis in grade 3 endometrial endometrioid carcinomas (EECs). Grade 3 EECs were classified into 4 subgroups: p53 abnormal, based on mutant-like immunostaining (p53abn); MMR deficient, based on loss of mismatch repair protein expression (MMRd); presence of POLE exonuclease domain hotspot mutation (POLE); no specific molecular profile (NSMP), in which none of these aberrations were present. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method (Log-rank test) and univariable and multivariable Cox proportional hazard models. In total, 381 patients were included. The median age was 66 years (range, 33 to 96 y). Federation Internationale de Gynecologie et d'Obstetrique stages (2009) were as follows: IA, 171 (44.9%); IB, 120 (31.5%); II, 24 (6.3%); III, 50 (13.1%); IV, 11 (2.9%). There were 49 (12.9%) POLE, 79 (20.7%) p53abn, 115 (30.2%) NSMP, and 138 (36.2%) MMRd tumors. Median follow-up of patients was 6.1 years (range, 0.2 to 17.0 y). Compared to patients with NSMP, patients with POLE mutant grade 3 EEC (OS: hazard ratio [HR], 0.36 [95% confidence interval, 0.18-0.70]; P=0.003; RFS: HR, 0.17 [0.05-0.54]; P=0.003) had a significantly better prognosis; patients with p53abn tumors had a significantly worse RFS (HR, 1.73 [1.09-2.74]; P=0.021); patients with MMRd tumors showed a trend toward better RFS. Estimated 5-year OS rates were as follows: POLE 89%, MMRd 75%, NSMP 69%, p53abn 55% (Log rank P=0.001). Five-year RFS rates were as follows: POLE 96%, MMRd 77%, NSMP 64%, p53abn 47% (P=0.000001), respectively. In a multivariable Cox model that included age and Federation Internationale de Gynecologie et d'Obstetrique stage, POLE and MMRd status remained independent prognostic factors for better RFS; p53 status was an independent prognostic factor for worse RFS. Molecular classification of grade 3 EECs reveals that these tumors are a

Evidence That Selenium Binding Protein 1 Is a Tumor Suppressor in Prostate Cancer

PubMed Central

Ansong, Emmanuel; Ying, Qi; Ekoue, Dede N.; Deaton, Ryan; Hall, Andrew R.; Kajdacsy-Balla, Andre; Yang, Wancai; Gann, Peter H.; Diamond, Alan M.

2015-01-01

Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56) is a selenium-associated protein shown to be at lower levels in tumors, and its lower levels are frequently predictive of a poor clinical outcome. Distinguishing indolent from aggressive prostate cancer is a major challenge in disease management. Associations between SBP1 levels, tumor grade, and disease recurrence following prostatectomy were investigated by duplex immunofluorescence imaging using a tissue microarray containing tissue from 202 prostate cancer patients who experienced biochemical (PSA) recurrence after prostatectomy and 202 matched control patients whose cancer did not recur. Samples were matched by age, ethnicity, pathological stage and Gleason grade, and images were quantified using the Vectra multispectral imaging system. Fluorescent labels were targeted for SBP1 and cytokeratins 8/18 to restrict scoring to tumor cells, and cell-by-cell quantification of SBP1 in the nucleus and cytoplasm was performed. Nuclear SBP1 levels and the nuclear to cytoplasm ratio were inversely associated with tumor grade using linear regression analysis. Following classification of samples into quartiles based on the SBP1 levels among controls, tumors in the lowest quartile were more than twice as likely to recur compared to those in any other quartile. Inducible ectopic SBP1 expression reduced the ability of HCT-116 human tumor cells to grow in soft agar, a measure of transformation, without affecting proliferation. Cells expressing SBP1 also demonstrated a robust induction in the phosphorylation of the p53 tumor suppressor at serine 15. These data indicate that loss of SBP1 may play an independent contributing role in prostate cancer progression and its levels might be useful in distinguishing indolent from aggressive disease. PMID:25993660

Magnetic Resonance Fingerprinting of Adult Brain Tumors: Initial Experience

PubMed Central

Badve, Chaitra; Yu, Alice; Dastmalchian, Sara; Rogers, Matthew; Ma, Dan; Jiang, Yun; Margevicius, Seunghee; Pahwa, Shivani; Lu, Ziang; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Sloan, Andrew; Gulani, Vikas

2016-01-01

Background Magnetic resonance fingerprinting (MRF) allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assesses the utility of MRF in differentiating between common types of adult intra-axial brain tumors. Methods MRF acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 WHO grade II lower-grade gliomas and 8 metastases. T1, T2 of the solid tumor (ST), immediate peritumoral white matter (PW), and contralateral white matter (CW) were summarized within each region of interest. Statistical comparisons on mean, standard deviation, skewness and kurtosis were performed using univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple comparisons testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases and area under the receiver operator curve (AUC) was calculated. Results Mean T2 values could differentiate solid tumor regions of lower-grade gliomas from metastases (mean±sd: 172±53ms and 105±27ms respectively, p =0.004, significant after Bonferroni correction). Mean T1 of PW surrounding lower-grade gliomas differed from PW around glioblastomas (mean±sd: 1066±218ms and 1578±331ms respectively, p=0.004, significant after Bonferroni correction). Logistic regression analysis revealed that mean T2 of ST offered best separation between glioblastomas and metastases with AUC of 0.86 (95% CI 0.69–1.00, p<0.0001). Conclusion MRF allows rapid simultaneous T1, T2 measurement in brain tumors and surrounding tissues. MRF based relaxometry can identify quantitative differences between solid-tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. PMID:28034994

Vasovagal reactions in 'at risk' donors: a univariate analysis of effect of age and weight on the grade of donor reactions.

PubMed

Tondon, Rashmi; Pandey, Prashant; Chaudhary, Rajendra

2008-10-01

It is well known that young age, low weight, and first time donation status increase the probability of having a reaction but the effect of these 'risk' factors on the grade of reaction has not been well studied. To evaluate the prevalence of these factors in blood donation setup, to identify 'at risk' donors with age less than 30 years and weight less than 60 kg and to assess whether there is any contributory role of these risk factors in predicting the grade of reaction. A retrospective analysis of 30370 donations was done during 15 month study period. Donor reaction rate of 1.6% was observed in this study of which 7% experienced reaction of moderate and severe grade. Reaction rate among male and female donors were 1.5% and 3.7% respectively. Female gender was found to be an independent predictor for donor reaction even after nullifying the effect of the blood volume drawn. Incidence of vasovagal reaction in 'at risk' donors was 2.0% in contrast to 0.96% in 'general' donor population. Age had a significant affect on reaction rate (p = .035) and all grades of reaction decreased with the age of the donor. Age was found to be a significant predictor of the grade of reaction (p = .008). The effect of weight on the reaction rate as well as on the grade was found to be insignificant (1.5% in 'at risk' donors vs. 1.6% in 'general' donors with p > 0.05). 1. Age is a significant factor that can predict the rate as well as the grade of reaction; 2. Weight does not predict the grade of reaction, 3. Gender is an independent predictor of donor reaction, with females having 2.5 fold higher chances of reaction. These factors are important for blood collection staff to recognize such 'at risk' donors, and to give more attention to them to reduce donor reaction.

Preoperative Magnetic Resonance Volumetry in Predicting Myometrial Invasion, Lymphovascular Space Invasion, and Tumor Grade: Is It Valuable in International Federation of Gynecology and Obstetrics Stage I Endometrial Cancer?

PubMed

Sahin, Hilal; Sarioglu, Fatma Ceren; Bagci, Mustafa; Karadeniz, Tugba; Uluer, Hatice; Sanci, Muzaffer

2018-05-01

The aim of this retrospective single-center study was to evaluate the relationship between maximum tumor size, tumor volume, tumor volume ratio (TVR) based on preoperative magnetic resonance (MR) volumetry, and negative histological prognostic parameters (deep myometrial invasion [MI], lymphovascular space invasion, tumor histological grade, and subtype) in International Federation of Gynecology and Obstetrics stage I endometrial cancer. Preoperative pelvic MR imaging studies of 68 women with surgical-pathologic diagnosis of International Federation of Gynecology and Obstetrics stage I endometrial cancer were reviewed for assessment of MR volumetry and qualitative assessment of MI. Volume of the tumor and uterus was measured with manual tracing of each section on sagittal T2-weighted images. Tumor volume ratio was calculated according to the following formula: TVR = (total tumor volume/total uterine volume) × 100. Receiver operating characteristics curve was performed to investigate a threshold for TVR associated with MI. The Mann-Whitney U test, Kruskal-Wallis test, and linear regression analysis were applied to evaluate possible differences between tumor size, tumor volume, TVR, and negative prognostic parameters. Receiver operating characteristics curve analysis of TVR for prediction of deep MI was statistically significant (P = 0.013). An optimal TVR threshold of 7.3% predicted deep myometrial invasion with 85.7% sensitivity, 46.8% specificity, 41.9% positive predictive value, and 88.0% negative predictive value. Receiver operating characteristics curve analyses of TVR, tumor size, and tumor volume for prediction of tumor histological grade or lymphovascular space invasion were not significant. The concordance between radiologic and pathologic assessment for MI was almost excellent (κ value, 0.799; P < 0.001). Addition of TVR to standard radiologic assessment of deep MI increased the sensitivity from 90.5% to 95.2%. Tumor volume ratio, based on preoperative

Age-related variation and predictors of long-term quality of life in germ cell tumor survivors.

PubMed

Hartung, Tim J; Mehnert, Anja; Friedrich, Michael; Hartmann, Michael; Vehling, Sigrun; Bokemeyer, Carsten; Oechsle, Karin

2016-02-01

To compare long-term health-related quality of life (QoL) in germ cell tumor survivors (GCTS) and age-adjusted men and to identify predictors of variation in long-term QoL in GCTS. We used the Short-Form Health Survey to measure QoL in a cross-sectional sample of 164 survivors of germ cell tumors from Hamburg, Germany. QoL was compared with age-adjusted German norm data. Sociodemographic and medical data from questionnaires and medical records were used to find predictors of QoL. On average, patients were 44.4 years old (standard deviation = 9.6 y) and average time since first germ cell tumor diagnosis was 11.6 years (standard deviation = 7.3 y). We found significantly lower mental component scores in GCTS when compared with norm data (Hedges g =-0.44, P<0.001). An exploratory analysis by age group showed the largest difference in mental QoL in survivors aged 31 to 40 years (Hedges g =-0.67). Linear regression analysis revealed age (β =-0.46, P<0.001), marital status (β = 0.20, P = 0.024), advanced secondary qualifications (β =-0.25, P = 0.001), time since diagnosis (β = 0.17, P = 0.031), and tumor stage (β = 0.17, P = 0.024) as statistically significant predictors of the physical component score, accounting for 22% of the variance. Statistically significant predictors of the mental component score were higher secondary qualifications (β = 0.17, P = 0.033) and unemployment (β =-0.21, P = 0.009), accounting for 6% of the variance. Survivors of germ cell tumors can expect an overall long-term QoL similar to that of other men of their age. Copyright © 2016 Elsevier Inc. All rights reserved.

The Minnesota Grading System Using Fundus Autofluorescence of Eye Bank Eyes: A Correlation To Age-Related Macular Degeneration (An AOS Thesis)

PubMed Central

Olsen, Timothy W.

2008-01-01

Purpose To establish a grading system of eye bank eyes using fundus autofluorescence (FAF) and identify a methodology that correlates FAF to age-related macular degeneration (AMD) with clinical correlation to the Age-Related Eye Disease Study (AREDS). Methods Two hundred sixty-two eye bank eyes were evaluated using a standardized analysis of FAF. Measurements were taken with the confocal scanning laser ophthalmoscope (cSLO). First, high-resolution, digital, stereoscopic, color images were obtained and graded according to AREDS criteria. With the neurosensory retina removed, mean FAF values were obtained from cSLO images using software analysis that excludes areas of atrophy and other artifact, generating an FAF value from a grading template. Age and AMD grade were compared to FAF values. An internal fluorescence reference standard was tested. Results Standardization of the cSLO machine demonstrated that reliable data could be acquired after a 1-hour warm-up. Images obtained prior to 1 hour had falsely elevated levels of FAF. In this initial analysis, there was no statistical correlation of age to mean FAF. There was a statistically significant decrease in FAF from AREDS grade 1, 2 to 3, 4 (P < .0001). An internal fluorescent standard may serve as a quantitative reference. Conclusions The Minnesota Grading System (MGS) of FAF (MGS-FAF) establishes a standardized methodology for grading eye bank tissue to quantify FAF compounds in the retinal pigment epithelium and correlate these findings to the AREDS. Future studies could then correlate specific FAF to the aging process, histopathology AMD phenotypes, and other maculopathies, as well as to analyze the biochemistry of autofluorescent fluorophores. PMID:19277247

Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade

PubMed Central

Gupta, Kanika; Kumaresan, Meenakshisundaram; Venkatesan, Bhuvaneswari; Chandra, Tushar; Patil, Aruna; Menon, Maya

2018-01-01

Context: Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Aims: Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. Settings and Design: A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Materials and Methods: Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Statistical Analysis Used: Chi square test, ordinal regression, and Goodman and Kruskal tau test. Results: Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor (β 1.566, P 0.0001). The masses with abrupt interface boundary are more likely grade 3 (β 1.524, P 0.001) in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs) with complex solid and cystic echotexture are more likely to be of high histological grade (β 1.146, P 0.04) as compared to masses with hypoechoic echotexture. Conclusions: Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited. PMID:29692540

Under the Radar: The Impact of Relatively Young Age for Grade Level on Academic Achievement

ERIC Educational Resources Information Center

Ryken, Klazina

2012-01-01

The purpose of this study was to determine whether age differences affect students' academic achievement, and whether age differences affect students in low-income areas differently than those in mixed or higher-income areas. Student achievement data for grades 3, 7, and 11 in language arts and math were obtained from a variety of schools located…

Sleep efficiency (but not sleep duration) of healthy school-age children is associated with grades in math and languages.

PubMed

Gruber, Reut; Somerville, Gail; Enros, Paul; Paquin, Soukaina; Kestler, Myra; Gillies-Poitras, Elizabeth

2014-12-01

The objective of this study was to examine the associations between objective measures of sleep duration and sleep efficiency with the grades obtained by healthy typically developing children in math, language, science, and art while controlling for the potential confounding effects of socioeconomic status (SES), age, and gender. We studied healthy typically developing children between 7 and 11 years of age. Sleep was assessed for five week nights using actigraphy, and parents provided their child's most recent report card. Higher sleep efficiency (but not sleep duration) was associated with better grades in math, English language, and French as a second language, above and beyond the contributions of age, gender, and SES. Sleep efficiency, but not sleep duration, is associated with academic performance as measured by report-card grades in typically developing school-aged children. The integration of strategies to improve sleep efficiency might represent a successful approach for improving children's readiness and/or performance in math and languages. Copyright © 2014 Elsevier B.V. All rights reserved.

Classification of pulmonary neuroendocrine tumors: new insights.

PubMed

Pelosi, Giuseppe; Sonzogni, Angelica; Harari, Sergio; Albini, Adriana; Bresaola, Enrica; Marchiò, Caterina; Massa, Federica; Righi, Luisella; Gatti, Gaia; Papanikolaou, Nikolaos; Vijayvergia, Namrata; Calabrese, Fiorella; Papotti, Mauro

2017-10-01

Neuroendocrine tumors of the lung (Lu-NETs) embrace a heterogeneous family of neoplasms classified into four histological variants, namely typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). Defining criteria on resection specimens include mitotic count in 2 mm 2 and the presence or absence of necrosis, alongside a constellation of cytological and histological traits including cell size and shape, nuclear features and overall architecture. Clinically, TC are low-grade malignant tumors, AC intermediate-grade malignant tumors and SCLC/LCNEC high-grade malignant full-blown carcinomas with no significant differences in survival between them. Homologous tumors arise in the thymus that occasionally have some difficulties in differentiating from the lung counterparts when presented with large unresectable or metastatic lesions. Immunohistochemistry (IHC) helps refine NE diagnosis at various anatomical sites, particularly on small-sized tissue material, in which only TC and small cell carcinoma categories can be recognized easily on hematoxylin & eosin stain, while AC and LCNEC can only be suggested on such material. The Ki-67 labeling index effectively separates carcinoids from small cell carcinoma and may prove useful for the clinical management of a metastatic disease to help the therapeutic decision-making process. Although carcinoids and high-grade neuroendocrine carcinomas in the lung and elsewhere make up separate tumor categories on molecular grounds, emerging data supports the concept of secondary high-grade NETs arising in the preexisting carcinoids, whose clinical and biological relevance will have to be placed into the proper context for the optimal management of these patients. In this review, we will discuss the selected, recent literature with a focus on current issues regarding Lu-NET nosology, i.e., classification, derivation and tumor evolution.

Glioma-associated stem cells: a novel class of tumor-supporting cells able to predict prognosis of human low-grade gliomas.

PubMed

Bourkoula, Evgenia; Mangoni, Damiano; Ius, Tamara; Pucer, Anja; Isola, Miriam; Musiello, Daniela; Marzinotto, Stefania; Toffoletto, Barbara; Sorrentino, Marisa; Palma, Anita; Caponnetto, Federica; Gregoraci, Giorgia; Vindigni, Marco; Pizzolitto, Stefano; Falconieri, Giovanni; De Maglio, Giovanna; Pecile, Vanna; Ruaro, Maria Elisabetta; Gri, Giorgia; Parisse, Pietro; Casalis, Loredana; Scoles, Giacinto; Skrap, Miran; Beltrami, Carlo Alberto; Beltrami, Antonio Paolo; Cesselli, Daniela

2014-05-01

Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-the-art markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. We isolated glioma-associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage-independent growth, and supported the malignant properties of both A172 cells and human glioma-stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG-patients. At the multivariate Cox analysis, the GASC-based score was the only independent predictor of overall survival and malignant progression free-survival. The microenvironment of both LGG and HGG hosts non-tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma-initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient-based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma. © 2013 AlphaMed Press.

Dynamic perfusion CT in brain tumors.

PubMed

Yeung, Timothy Pok Chi; Bauman, Glenn; Yartsev, Slav; Fainardi, Enrico; Macdonald, David; Lee, Ting-Yim

2015-12-01

Dynamic perfusion CT (PCT) is an imaging technique for assessing the vascular supply and hemodynamics of brain tumors by measuring blood flow, blood volume, and permeability-surface area product. These PCT parameters provide information complementary to histopathologic assessments and have been used for grading brain tumors, distinguishing high-grade gliomas from other brain lesions, differentiating true progression from post-treatment effects, and predicting prognosis after treatments. In this review, the basic principles of PCT are described, and applications of PCT of brain tumors are discussed. The advantages and current challenges, along with possible solutions, of PCT are presented. Copyright © 2015. Published by Elsevier Ireland Ltd.

SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

PubMed

Hsieh, Min-Shu; Lee, Yi-Hsuan; Chang, Yih-Leong

2016-10-01

Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of postmortem aging and USDA quality grade on Warner-Bratzler shear force values of seventeen individual beef muscles.

PubMed

Gruber, S L; Tatum, J D; Scanga, J A; Chapman, P L; Smith, G C; Belk, K E

2006-12-01

Forty USDA Select and 40 upper two-thirds USDA Choice beef carcasses were used to determine the effects of postmortem aging on tenderness of 17 individual beef muscles. Biceps femoris-long head, complexus, gluteus medius, infraspinatus, longissimus dorsi, psoas major, rectus femoris, semimembranosus, semitendinosus, serratus ventralis, spinalis dorsi, supraspinatus, tensor fasciae latae, teres major, triceps brachii-long head, vastus lateralis, and vastus medialis muscles were removed from each carcass. Seven steaks (2.54-cm thick) were cut from every muscle, and each steak was assigned to one of the following postmortem aging periods: 2, 4, 6, 10, 14, 21, or 28 d postmortem. After completion of the designated aging period, steaks were removed from storage (2 degrees C, never frozen), cooked to a peak internal temperature of 71 degrees C, and evaluated using Warner-Bratzler shear force (WBSF). Analysis of WBSF revealed a 3-way interaction (P = 0.004) among individual muscle, USDA quality grade, and postmortem aging period. With the exception of the Select teres major, WBSF of all muscles (both quality grades) decreased with increasing time of postmortem storage. Nonlinear regression was used to characterize the extent (aging response) and rate of decrease in WBSF from 2 through 28 d postmortem for each muscle within each quality grade. In general, WBSF of upper two-thirds Choice muscles decreased more rapidly from 2 to 10 d postmortem than did corresponding Select muscles. Muscles that had greater aging responses generally had greater 2-d WBSF values. The upper two-thirds Choice psoas major, serratus ventralis, and vastus lateralis muscles required similar aging times to complete a majority of the aging response (< or =0.1 kg of aging response remaining) compared with analogous Select muscles. The upper two-thirds Choice complexus, gluteus medius, semitendinosus, triceps brachii-long head, and vastus medialis muscles required 4 to 6 d less time to complete a

Pediatric low-grade gliomas and the need for new options for therapy: why and how?

PubMed Central

Qaddoumi, Ibrahim; Sultan, Iyad; Broniscer, Alberto

2009-01-01

Pediatric low-grade gliomas are the most common tumors of the central nervous system in children, accounting for almost 50% of all childhood brain tumors. They are a heterogeneous group of tumors with different histologic subtypes. Most treatment studies address low-grade gliomas as a single entity, depriving us of histology-specific treatment outcomes. This is mostly due to a lack of understanding of tumor biology at the molecular level. Pediatric low-grade gliomas are not benign, and most incompletely resected tumors will progress and negatively affect quality of life. The advancements made in understanding sporadic pilocytic astrocytoma and neurofibromatosis 1-associated pilocytic astrocytoma in particular have paved the way for potential targeted therapy and biological stratification. Such progress in pilocytic astrocytoma needs to be consolidated and expanded to other histologic varieties of pediatric low-grade gliomas. PMID:19164945

Clinical outcome and long-term survival of 150 consecutive patients with pancreatic neuroendocrine tumors: A comprehensive analysis by the World Health Organization 2010 grading classification.

PubMed

Deng, Ben-Yuan; Liu, Fei; Yin, Si-Neng; Chen, An-Ping; Xu, Lin; Li, Bo

2018-06-01

The World Health Organization (WHO) has revised its grading system for pancreatic neuroendocrine tumors (PNETs) in 2010 into three main group, which has not been widely and comprehensively evaluated. We aimed to validate the clinical valve of this system associated with the clinical outcome and long-term survival when applied to PNETs, which were rare and heterogeneous. We retrospectively collected and analyzed the data of 150 consecutive patients with PNETs who underwent a resection. Sixty-four males and 86 females with PNETs were enrolled in our study. The clinical stage from I to IV by European Neuroendocrine Tumor Society were respectively defined in 53, 60, 19 and 18 patients. Seventy-two patients were pathologically diagnosed as neuroendocrine tumor G1 (NET G1), 48 as neuroendocrine tumor G2 (NET G2) and 30 as neuroendocrine carcinoma G3 (NEC G3). Patients with a radical resection obtained a notably higher overall survival (OS) than that of patients who underwent a palliative surgery (P=0.001). The 5-year OS of patients with NET G1 was significantly higher than that of patients with NET G2 (P=0.015) and NEC G3 (P<0.001); the comparison of OS for patients with NET G2 and NEC G3 was also statistically significant (P=0.005). In both univariate and multivariate analysis, clinical staging by ENETS (stage I and II vs. stage III and IV), resection (radical vs. palliative) and WHO 2010 grading classification (NET G1 and G2 vs. NEC G3) were validated to be independent predictors for the survivals of PNETs. The newly-updated WHO 2010 grading classification was prognostic for the OS of PNETs and could be widely adopted in clinical practice. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

42 CFR 21.28 - Age requirements, Regular Corps, senior assistant grade and below.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Age requirements, Regular Corps, senior assistant grade and below. 21.28 Section 21.28 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... active service in the Commissioned Corps of the Public Health Service shall be increased by the period of...

Whole-Tumor Histogram and Texture Analyses of DTI for Evaluation of IDH1-Mutation and 1p/19q-Codeletion Status in World Health Organization Grade II Gliomas.

PubMed

Park, Y W; Han, K; Ahn, S S; Choi, Y S; Chang, J H; Kim, S H; Kang, S-G; Kim, E H; Lee, S-K

2018-04-01

Prediction of the isocitrate dehydrogenase 1 (IDH1)-mutation and 1p/19q-codeletion status of World Health Organization grade ll gliomas preoperatively may assist in predicting prognosis and planning treatment strategies. Our aim was to characterize the histogram and texture analyses of apparent diffusion coefficient and fractional anisotropy maps to determine IDH1 -mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas. Ninety-three patients with World Health Organization grade II gliomas with known IDH1- mutation and 1p/19q-codeletion status (18 IDH1 wild-type, 45 IDH1 mutant and no 1p/19q codeletion, 30 IDH1- mutant and 1p/19q codeleted tumors) underwent DTI. ROIs were drawn on every section of the T2-weighted images and transferred to the ADC and the fractional anisotropy maps to derive volume-based data of the entire tumor. Histogram and texture analyses were correlated with the IDH1 -mutation and 1p/19q-codeletion status. The predictive powers of imaging features for IDH1 wild-type tumors and 1p/19q-codeletion status in IDH1 -mutant subgroups were evaluated using the least absolute shrinkage and selection operator. Various histogram and texture parameters differed significantly according to IDH1 -mutation and 1p/19q-codeletion status. The skewness and energy of ADC, 10th and 25th percentiles, and correlation of fractional anisotropy were independent predictors of an IDH1 wild-type in the least absolute shrinkage and selection operator. The area under the receiver operating curve for the prediction model was 0.853. The skewness and cluster shade of ADC, energy, and correlation of fractional anisotropy were independent predictors of a 1p/19q codeletion in IDH1 -mutant tumors in the least absolute shrinkage and selection operator. The area under the receiver operating curve was 0.807. Whole-tumor histogram and texture features of the ADC and fractional anisotropy maps are useful for predicting the IDH1 -mutation and 1p/19q

Brain tumor classification using AFM in combination with data mining techniques.

PubMed

Huml, Marlene; Silye, René; Zauner, Gerald; Hutterer, Stephan; Schilcher, Kurt

2013-01-01

Although classification of astrocytic tumors is standardized by the WHO grading system, which is mainly based on microscopy-derived, histomorphological features, there is great interobserver variability. The main causes are thought to be the complexity of morphological details varying from tumor to tumor and from patient to patient, variations in the technical histopathological procedures like staining protocols, and finally the individual experience of the diagnosing pathologist. Thus, to raise astrocytoma grading to a more objective standard, this paper proposes a methodology based on atomic force microscopy (AFM) derived images made from histopathological samples in combination with data mining techniques. By comparing AFM images with corresponding light microscopy images of the same area, the progressive formation of cavities due to cell necrosis was identified as a typical morphological marker for a computer-assisted analysis. Using genetic programming as a tool for feature analysis, a best model was created that achieved 94.74% classification accuracy in distinguishing grade II tumors from grade IV ones. While utilizing modern image analysis techniques, AFM may become an important tool in astrocytic tumor diagnosis. By this way patients suffering from grade II tumors are identified unambiguously, having a less risk for malignant transformation. They would benefit from early adjuvant therapies.

The molecular biology of WHO grade I astrocytomas.

PubMed

Marko, Nicholas F; Weil, Robert J

2012-12-01

World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.

Preoperative Embolization of Extra-axial Hypervascular Tumors with Onyx

PubMed Central

Fusco, Matthew R.; Salem, Mohamed M.; Reddy, Arra S.; Ogilvy, Christopher S.; Kasper, Ekkehard M.; Thomas, Ajith J.

2016-01-01

Objective Preoperative endovascular embolization of intracranial tumors is performed to mitigate anticipated intraoperative blood loss. Although the usage of a wide array of embolic agents, particularly polyvinyl alcohol (PVA), has been described for a variety of tumors, literature detailing the efficacy, safety and complication rates for the usage of Onyx is relatively sparse. Materials and Methods We reviewed our single institutional experience with pre-surgical Onyx embolization of extra-axial tumors to evaluate its efficacy and safety and highlight nuances of individualized cases. Results Five patients underwent pre-surgical Onyx embolization of large or giant extra-axial tumors within 24 hours of surgical resection. Four patients harbored falcine or convexity meningiomas (grade I in 2 patients, grade II in 1 patient and grade III in one patient), and one patient had a grade II hemangiopericytoma. Embolization proceeded uneventfully in all cases and there were no complications. Conclusion This series augments the expanding literature confirming the safety and efficacy of Onyx in the preoperative embolization of extra-axial tumors, underscoring its advantage of being able to attain extensive devascularization via only one supplying pedicle. PMID:27114961

Effects of Obesity and Obesity-Related Molecules on Canine Mammary Gland Tumors.

PubMed

Lim, H-Y; Im, K-S; Kim, N-H; Kim, H-W; Shin, J-I; Yhee, J-Y; Sur, J-H

2015-11-01

Obesity can affect the clinical course of a number of diseases, including breast cancer in women and mammary gland tumors in female dogs, via the secretion of various cytokines and hormones. The objective of this study was to examine the expression patterns of obesity-related molecules such as aromatase, leptin, and insulin-like growth factor 1 receptor (IGF-1 R) in canine mammary carcinomas (CMCs) on the basis of the body condition score (BCS). Comparative analyses of the expression of these molecules, together with prognostic factors for CMCs, including hormone receptors (HRs; estrogen and progesterone receptors), lymphatic invasion, central necrosis of the tumor, and histologic grade, were performed on 56 CMCs. The mean age of CMC onset was lower in the overweight or obese group (8.7 ± 1.9 years) than in the lean or ideal body weight group (10.4 ± 2.7 years). The proportion of poorly differentiated (grade III) tumors was significantly higher in the overweight or obese female dogs. Aromatase expression was significantly higher in the overweight or obese group and was correlated with the expression of HRs (P = .025). These findings suggest that overweight or obese status might affect the development and behavior of CMCs by tumor-adipocyte interactions and increased HR-related tumor growth. © The Author(s) 2015.

If cytology of Warthin tumor is accurate, can management be conservative?

PubMed

Vlantis, Alexander C; Ng, Siu Kwan; Mak, Chi Keung; Cheung, Jackie M; Chan, Amy B; van Hasselt, C Andrew

2016-01-01

We conducted a retrospective study to assess the accuracy of fine-needle aspiration cytology (FNAC) in the diagnosis of Warthin tumor and to evaluate the subsequent risk of conservative nonsurgical management. We reviewed the records of 75 patients (76 tumors) with a parotid mass that had been diagnosed as a Warthin tumor by FNAC. This patient population was made up of 64 men and 11 women, aged 46 to 93 years (mean: 67). Of the 76 tumors, 40 were treated with surgical excision and 36 with conservative measures. Histology of the 40 excised parotid masses revealed that 38 (95%) were indeed Warthin tumors, 1 (2.5%) was a low-grade adenocarcinoma, and 1 was benign-not otherwise specified. None of the 36 tumors underwent malignant transformation either clinically or on repeat FNAC (if performed) during a follow-up of 4 to 120 months (mean: 55.5 ± 32.2). We conclude that conservative management of Warthin tumors confidently diagnosed on FNAC may be an option for patients who are unwilling or unable to undergo surgical excision.

Grade One Entrance Age Study. Research Report.

ERIC Educational Resources Information Center

Pain, Kerrie

This study compared the academic and social development of students who entered grade 1 very early (5:6 years or 5:7 years), in the mid range (5:8 to 6:3 years), and very late (6:4 years or older). The purpose of the study was to explore the hypothesis that the early grade 1 entrants would have continuing problems in both academic and social…

Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

ClinicalTrials.gov

2013-01-15

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors.

PubMed

George, Julie; Walter, Vonn; Peifer, Martin; Alexandrov, Ludmil B; Seidel, Danila; Leenders, Frauke; Maas, Lukas; Müller, Christian; Dahmen, Ilona; Delhomme, Tiffany M; Ardin, Maude; Leblay, Noemie; Byrnes, Graham; Sun, Ruping; De Reynies, Aurélien; McLeer-Florin, Anne; Bosco, Graziella; Malchers, Florian; Menon, Roopika; Altmüller, Janine; Becker, Christian; Nürnberg, Peter; Achter, Viktor; Lang, Ulrich; Schneider, Peter M; Bogus, Magdalena; Soloway, Matthew G; Wilkerson, Matthew D; Cun, Yupeng; McKay, James D; Moro-Sibilot, Denis; Brambilla, Christian G; Lantuejoul, Sylvie; Lemaitre, Nicolas; Soltermann, Alex; Weder, Walter; Tischler, Verena; Brustugun, Odd Terje; Lund-Iversen, Marius; Helland, Åslaug; Solberg, Steinar; Ansén, Sascha; Wright, Gavin; Solomon, Benjamin; Roz, Luca; Pastorino, Ugo; Petersen, Iver; Clement, Joachim H; Sänger, Jörg; Wolf, Jürgen; Vingron, Martin; Zander, Thomas; Perner, Sven; Travis, William D; Haas, Stefan A; Olivier, Magali; Foll, Matthieu; Büttner, Reinhard; Hayes, David Neil; Brambilla, Elisabeth; Fernandez-Cuesta, Lynnette; Thomas, Roman K

2018-03-13

Pulmonary large-cell neuroendocrine carcinomas (LCNECs) have similarities with other lung cancers, but their precise relationship has remained unclear. Here we perform a comprehensive genomic (n = 60) and transcriptomic (n = 69) analysis of 75 LCNECs and identify two molecular subgroups: "type I LCNECs" with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and "type II LCNECs" enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1 high /DLL3 high /NOTCH low , type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1 low /DLL3 low /NOTCH high , and an upregulation of immune-related pathways. In conclusion, LCNECs comprise two molecularly defined subgroups, and distinguishing them from SCLC may allow stratified targeted treatment of high-grade neuroendocrine lung tumors.

Diffusion MRI: literature review in salivary gland tumors.

PubMed

Attyé, A; Troprès, I; Rouchy, R-C; Righini, C; Espinoza, S; Kastler, A; Krainik, A

2017-07-01

Surgical resection is currently the best treatment for salivary gland tumors. A reliable magnetic resonance imaging mapping, encompassing tumor grade, location, and extension may assist safe and effective tumor resection and provide better information for patients regarding potential risks and morbidity after surgical intervention. However, direct examination of the tumor grade and extension using conventional morphological MRI remains difficult, often requiring contrast media injection and complex algorithms on perfusion imaging to estimate the degree of malignancy. In addition, contrast-enhanced MRI technique may be problematic due to the recently demonstrated gadolinium accumulation in the dentate nucleus of the cerebellum. Significant developments in magnetic resonance diffusion imaging, involving voxel-based quantitative analysis through the measurement of the apparent diffusion coefficient, have enhanced our knowledge on the different histopathological salivary tumor grades. Other diffusion imaging-derived techniques, including high-order tractography models, have recently demonstrated their usefulness in assessing the facial nerve location in parotid tumor context. All of these imaging techniques do not require contrast media injection. Our review starts by outlining the physical basis of diffusion imaging, before discussing findings from diagnostic studies testing its usefulness in assessing salivary glands tumors with diffusion MRI. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Correlation of the cell surface antigens with stage and grade in cancer of the bladder.

PubMed

Emmott, R C; Javadpour, N; Bergman, S M; Soares, T

1979-01-01

We examined 76 bladder tumors of various stages and grades for the presence of the ABO (H) cell surface antigen, using the specific red cell adherence technique. Of the grade I lesions studied 70 per cent were positive for the cell surface antigen and none of the 26 grade III tumors retained the antigens. When correlated with clinical stage the tumors showed no antigens for those of stages B1 to D, while 12 of 16 stage A lesions were positive for the antigen. When stage A lesions were studied and the findings were correlated with recurrence and metastasis/invasion rates the cell surface antigen was present on the initial tumor in only 1 lesion that recurred at an invasive stage. The findings of this study show that the specific red cell adherence technique may be valuable for predicting malignant potential in low grade, low stage cancer of the bladder. If supported by further investigation this technique may offer the capability of selecting low grade, low stage bladder tumors that are destined to invade or metastasize while they are at curable stages.

High-grade endometrial carcinoma: serous and grade 3 endometrioid carcinomas have different immunophenotypes and outcomes.

PubMed

Alkushi, Abdulmohsen; Köbel, Martin; Kalloger, Steve E; Gilks, C Blake

2010-07-01

High-grade endometrial carcinomas are a heterogeneous group of tumors and include grade 3 endometrioid (EC-3), serous (SC), and clear cell carcinomas (CCC). There are conflicting data about the prognosis of these subtypes of high-grade endometrial carcinoma; this may be a result of lack of reproducibility in classifying tumor cell type. The purpose of this study was to examine differences in immunophenotype and outcome in a series of high-grade endometrial carcinomas, focusing on the comparison of EC-3 versus SC. We selected 180 endometrial carcinomas of SC, EC, or CCC type. No mixed carcinomas were included in the study. We chose the following immunohistochemical markers, estrogen receptor (ER), insulin-like growth factor 2 mRNA-binding protein 3 (IMP3), p16, p53, progesterone receptor (PR), and phosphatase and tensin homolog (PTEN) as being significantly differentially expressed in endometrial carcinoma subtypes. The tumors were stratified into 4 groups on the basis of their cell type and grade: EC grade 1 or 2, EC-3, SC, and CCC. Univariate survival analysis revealed significant differences in outcome between the 4 groups (P<0.0001), with significantly longer disease-specific survival for grade 1 or 2 EC versus EC-3 (P=0.0001), and EC-3 versus SC (P=0.0003). p16, PTEN, and IMP3 expression was observed more frequently in SC compared with EC-3 (P<0.0001, P=0.021, and P=0.031, respectively). These 3 markers showed the highest sensitivity and specificity in distinguishing between EC-3 and SC, with receiver operating characteristics area under the curve of 0.85, 0.69, and 0.71, respectively. ER and p53 approached but did not reach significance for differential expression in EC-3 versus SC (P=0.055 and P=0.068, respectively). A combination of p16 and PTEN predicts EC-3 versus SC with a sensitivity of 90.0% and specificity of 96.8%. p16 and PTEN can aid in distinguishing between EC-3 and SC of the endometrium, and are superior to ER, PR, and p53 for this purpose. EC-3

Dedifferentiated liposarcoma with inflammatory myofibroblastic tumor-like features.

PubMed

Lucas, David R; Shukla, Abhishek; Thomas, Dafydd G; Patel, Rajiv M; Kubat, Anthony J; McHugh, Jonathan B

2010-06-01

The dedifferentiated component of dedifferentiated liposarcoma shows wide histologic variation including tumors with heterologous differentiation. Myofibroblastic differentiation has been recognized in dedifferentiated liposarcoma. However, tumors closely resembling inflammatory myofibroblastic tumor have not. We report the clinicopathologic, immunohistochemical, and molecular finding in 6 cases of dedifferentiated liposarcoma with inflammatory myofibroblastic tumor-like features treated at our institution. The tumors occurred mostly in middle age or elderly men, involved mostly the inguinal/scrotal region or retroperitoneum, and behaved aggressively. Microscopically, the dedifferentiated component closely resembled or, if taken out of context, was indistinguishable from inflammatory myofibroblastic tumor. All 3 major patterns seen in inflammatory myofibroblastic tumor (myxoid, cellular, and hypocellular fibrous) were represented. Areas resembling nodular fasciitis or desmoid fibromatosis were frequent findings. One tumor had heterologous osseous differentiation. In 4 tumors the inflammatory myofibroblastic tumor-like areas were diffuse, whereas in 2 they were combined with noninflammatory myofibroblastic tumor-like high-grade sarcoma. Five tumors stained for smooth muscle actin or desmin, none stained for ALK-1, 5 stained for MDM2, and 5 had amplified MDM2 by fluorescence in situ hybridization. Well-differentiated liposarcomatous components were present in every tumor. All patients developed locally recurrent or metastatic disease. At last follow-up 2 patients had died of disease and 2 were alive with disease. Dedifferentiated liposarcoma can have prominent inflammatory myofibroblastic tumor-like features, a finding that further expands its histologic spectrum. Awareness of this finding can prevent one from misdiagnosing dedifferentiated liposarcoma as inflammatory myofibroblastic tumor, a much less aggressive neoplasm.

Autologous Tumor Lysate-pulsed Dendritic Cell Immunotherapy for Pediatric Patients with Newly Diagnosed or Recurrent High-grade Gliomas

PubMed Central

Lasky, Joseph L.; Panosyan, Eduard H.; Plant, Ashley; Davidson, Tom; Yong, William H.; Prins, Robert M.; Liau, Linda M.; Moore, Theodore B.

2014-01-01

Immunotherapy has the potential to improve clinical outcomes with little toxicity for pediatric patients with brain tumors. We conducted a pilot feasibility study of tumor lysate-pulsed dendritic cell (DC) vaccination in pediatric patients (1 to 18 years old) with newly diagnosed or recurrent high-grade glioma (HGG). A total of nine DC vaccine doses, each containing 1×106 cells per dose were administered to three out of the seven originally enrolled patients. Toxicities were limited to mild side-effects, except in one case of elevated alkaline phosphatase, which resolved without clinical consequences. Two patients with primary lesions amongst the three vaccinated were alive at the time of writing, both without evidence of disease. Pre- and post-vaccination tumor samples from a patient with an anaplastic oligoastrocytoma that recurred failed to demonstrate immune cell infiltration by immunohistochemistry. Peripheral cytokine levels were evaluated in one patient following DC vaccination and demonstrated some changes in relation to vaccination. DC vaccine is tolerable and feasible with some limitations for pediatric patients with HGG. Dendritic cell based immunotherapy may provide some clinical benefit in pediatric patients with glioma, especially for patients with minimal residual disease, but further investigation of this modality is required. PMID:23645755

Prognostic relevance of Fédération Nationale des Centres de Lutte Contre le Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: a study of 50 cases.

PubMed

Jour, George; Gullet, Ashley; Liu, Mingdong; Hoch, Benjamin L

2015-01-01

Dedifferentiated liposarcoma represents a form of liposarcoma composed of a non-lipogenic sarcoma associated with well-differentiated liposarcoma. The prognostic significance of histological grading of the dedifferentiated component remains to be elucidated due to vague grading criteria employed in previous studies. Molecular markers of tumor behavior, including amplification levels of murine double minute-2 (MDM2) and cyclin-dependent kinase-4 (CDK4) genes, have been explored in a limited number of cases. Here we investigate whether 'Fédération Nationale des Centres de Lutte Contre le Cancer' (FNCLCC) grade and MDM2 gene amplification levels have prognostic value in dedifferentiated liposarcoma in terms of local recurrence and disease-specific survival. Fifty cases were retrieved, reviewed and FNCLCC grade was scored for the dedifferentiated component. Testing for MDM2 gene amplification was performed by fluorescence in situ hybridization. Amplification was categorized as high level (≥20 copies) and as low level (<20 copies). Follow-up data was obtained through chart review. Log-rank test and Cox proportional hazard models were used to determine the effect of grade and level of MDM2 amplification on outcomes. Our series includes 50 patients (male n=28, female n=22) with an average age of 63 years (range, 28-88) and a median follow-up of 28 months (range, 2-120). Tumors were graded as grade 1 (6%), grade 2 (58%), and grade 3 (36%). When adjusted for age, sex, site, tumor size, and margin status, grade 3 patients had a higher recurrence rate than grades 1 and 2 (HR=2.07, 95% CI: 1.24, 7.62; P=0.015). Patients with high-level MDM2 amplification had higher recurrence rate on univariate analysis (P=0.028), but not on multivariate analysis (HR=1.69, 95% CI: 0.73, 3.94; P=0.221). FNCLCC grade 3 dedifferentiation confers a worse prognosis in dedifferentiated liposarcoma in terms of local recurrence. MDM2 amplification level remains a useful diagnostic tool in

Detection of occult high graded microsatellite instabilities in MMR gene mutation negative HNPCC tumors by addition of complementary marker analysis.

PubMed

Schiemann, U; Müller-Koch, Y; Gross, M; Glas, J; Baretton, G; Muders, M; Mussack, T; Holinski-Feder, E

2005-01-28

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant tumor syndrome predisposing to predominantly colorectal and endometrial cancer. In 90% of the cases, molecular analyses reveal microsatellite instabilities due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2, among these tumors. Tumors from 40 HNPCC index patients (31 Amsterdam positive, 9 Bethesda positive; 21 females, 19 males; mean age 48.0 +/- 13.2 years) were examined. In contrast to the classical constellation, their tumors revealed only a microsatellite stable (MSS, n=31)--or low instable (MSI-L, n=9)--tumor phenotype following the international reference panel of 5 microsatellites. No MLH1 and MSH2 mutations were detectable. Complementary microsatellites (BAT40, D10S197, D13S153, D18S58, MYCL1) were investigated by PCR and fragment analysis to find other instabilities which might hint to the MIN-pathway of the tumors. Due to ten microsatellites in total tumors were now reclassified in 4 MSI-H (10%), 24 MSI-L (60%) and 12 in MSS (30%) phenotypes. The mean age of onset for CRCs was the lowest in the MSI-H group with 45.7 +/- 9.6 years (vs. 48.7 +/- 14.3 and 49.0 +/- 12.9 years in MSI-L and MSS group). MSI-H-and MSI-L tumors were often localized in the proximal colon (50 and 52%), whereas MSS tumors were preferentially localized in the distal colon (77%). - Complementary microsatellites help to subdive "non-classical" HNPCC in subgroups with different clinical appearance. It allows to detect occult MSI-H tumors with up to 10% and to confirm MSS tumors who seem to have a similar biological behaviour like sporadic CRC. Maybe that this genetic reclassification influence the decision of whether to offer patients chemotherapy or not, since it is known that patients with instable tumors do not benefit from chemotherapy as well as patients with microsatellite stable tumors.

Over-expression of mammaglobin-B in canine mammary tumors.

PubMed

Pandey, Mamta; Sunil Kumar, B V; Gupta, Kuldip; Sethi, Ram Saran; Kumar, Ashwani; Verma, Ramneek

2018-06-15

Mammaglobin, a member of secretoglobin family has been recognized as a breast cancer associated protein. Though the exact function of the protein is not fully known, its expression has been reported to be upregulated in human breast cancer.We focused on studying the expression of mammaglobin-B gene and protein in canine mammary tumor (CMT) tissue. Expression of mammaglobin-B mRNA and protein were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively. High levels of mammaglobin-B mRNA expression (6.663 ± 0.841times) was observed in CMT as compared to age and breed matched healthy controls. Further, expression of mammaglobin-B protein was detected in paraffin-embedded mammary tumor tissues from the same subjects by IHC. Mammaglobin-B protein was overexpressed only in 6.67% of healthy mammary glands while, a high level of its expression was scored in 76.7% of the CMT subjects. Moreover, no significant differences in terms of IHC score and qRT-PCR score with respect to CMT histotypes or tumor grades were observed, indicating that mammaglobin-B over-expression occurred irrespective of CMT types or grades. Overall, significantly increased expression of mammaglobin-B protein was found in CMTs with respect to healthy mammary glands, which positively correlates to its transcript. These findings suggest that overexpression of mammaglobin-B is associated with tumors of canine mammary glands.

ADC texture—An imaging biomarker for high-grade glioma?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brynolfsson, Patrik; Hauksson, Jón; Karlsson, Mikael

2014-10-15

Purpose: Survival for high-grade gliomas is poor, at least partly explained by intratumoral heterogeneity contributing to treatment resistance. Radiological evaluation of treatment response is in most cases limited to assessment of tumor size months after the initiation of therapy. Diffusion-weighted magnetic resonance imaging (MRI) and its estimate of the apparent diffusion coefficient (ADC) has been widely investigated, as it reflects tumor cellularity and proliferation. The aim of this study was to investigate texture analysis of ADC images in conjunction with multivariate image analysis as a means for identification of pretreatment imaging biomarkers. Methods: Twenty-three consecutive high-grade glioma patients were treatedmore » with radiotherapy (2 Gy/60 Gy) with concomitant and adjuvant temozolomide. ADC maps and T1-weighted anatomical images with and without contrast enhancement were collected prior to treatment, and (residual) tumor contrast enhancement was delineated. A gray-level co-occurrence matrix analysis was performed on the ADC maps in a cuboid encapsulating the tumor in coronal, sagittal, and transversal planes, giving a total of 60 textural descriptors for each tumor. In addition, similar examinations and analyses were performed at day 1, week 2, and week 6 into treatment. Principal component analysis (PCA) was applied to reduce dimensionality of the data, and the five largest components (scores) were used in subsequent analyses. MRI assessment three months after completion of radiochemotherapy was used for classifying tumor progression or regression. Results: The score scatter plots revealed that the first, third, and fifth components of the pretreatment examinations exhibited a pattern that strongly correlated to survival. Two groups could be identified: one with a median survival after diagnosis of 1099 days and one with 345 days, p = 0.0001. Conclusions: By combining PCA and texture analysis, ADC texture characteristics were identified

Parent-reported cognitive function is associated with leukoencephalopathy in children with brain tumors.

PubMed

Lai, Jin-Shei; Bregman, Corey; Zelko, Frank; Nowinski, Cindy; Cella, David; Beaumont, Jennifer J; Goldman, Stewart

2017-09-01

Cognitive dysfunction is a major concern for children with brain tumors. A valid, user-friendly screening tool could facilitate prompt referral for comprehensive neuropsychological assessments and therefore early intervention. Applications of the pediatric perceived cognitive function item bank (pedsPCF) such as computerized adaptive testing can potentially serve as such a tool given its brevity and user-friendly nature. This study aimed to evaluate whether pedsPCF was a valid indicator of cerebral compromise using the criterion of structural brain changes indicated by leukoencephalopathy grades. Data from 99 children (mean age = 12.6 years) with brain tumors and their parents were analyzed. Average time since diagnosis was 5.8 years; time since last treatment was 4.3 years. Leukoencephalopathy grade (range 0-4) was based on white matter damage and degree of deep white matter volume loss shown on MRI. Parents of patients completed the pedsPCF. Scores were based on the US general population-based T-score metric (mean = 50; SD = 10). Higher scores reflect better function. Leukoencephalopathy grade distributions were as follows: 36 grade 0, 27 grade 1, 22 grade 2, 13 grade 3, and 1 grade 4. The mean pedsPCF T-score was 48.3 (SD = 8.3; range 30.5-63.7). The pedsPCF scores significantly discriminated patients with different leukoencephalopathy grades, F = 4.14, p = 0.0084. Effect sizes ranged from 0.09 (grade 0 vs. 1) to 1.22 (grade 0 vs. 3/4). This study demonstrates that the pedsPCF is a valid indicator of leukoencephalopathy and provides support for its use as a screening tool for more comprehensive neurocognitive testing.

Quantitative genome-wide methylation analysis of high-grade non-muscle invasive bladder cancer

PubMed Central

Kitchen, Mark O.; Bryan, Richard T.; Emes, Richard D.; Glossop, John R.; Luscombe, Christopher; Cheng, K. K.; Zeegers, Maurice P.; James, Nicholas D.; Devall, Adam J.; Mein, Charles A.; Gommersall, Lyndon; Fryer, Anthony A.; Farrell, William E.

2016-01-01

ABSTRACT High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a clinically unpredictable disease with greater risks of recurrence and progression relative to their low-intermediate-grade counterparts. The molecular events, including those affecting the epigenome, that characterize this disease entity in the context of tumor development, recurrence, and progression, are incompletely understood. We therefore interrogated genome-wide DNA methylation using HumanMethylation450 BeadChip arrays in 21 primary HG-NMIBC tumors relative to normal bladder controls. Using strict inclusion-exclusion criteria we identified 1,057 hypermethylated CpGs within gene promoter-associated CpG islands, representing 256 genes. We validated the array data by bisulphite pyrosequencing and examined 25 array-identified candidate genes in an independent cohort of 30 HG-NMIBC and 18 low-intermediate-grade NMIBC. These analyses revealed significantly higher methylation frequencies in high-grade tumors relative to low-intermediate-grade tumors for the ATP5G2, IRX1 and VAX2 genes (P<0.05), and similarly significant increases in mean levels of methylation in high-grade tumors for the ATP5G2, VAX2, INSRR, PRDM14, VSX1, TFAP2b, PRRX1, and HIST1H4F genes (P<0.05). Although inappropriate promoter methylation was not invariantly associated with reduced transcript expression, a significant association was apparent for the ARHGEF4, PON3, STAT5a, and VAX2 gene transcripts (P<0.05). Herein, we present the first genome-wide DNA methylation analysis in a unique HG-NMIBC cohort, showing extensive and discrete methylation changes relative to normal bladder and low-intermediate-grade tumors. The genes we identified hold significant potential as targets for novel therapeutic intervention either alone, or in combination, with more conventional therapeutic options in the treatment of this clinically unpredictable disease. PMID:26929985

Comparison of Utility of Histogram Apparent Diffusion Coefficient and R2* for Differentiation of Low-Grade From High-Grade Clear Cell Renal Cell Carcinoma.

PubMed

Zhang, Yu-Dong; Wu, Chen-Jiang; Wang, Qing; Zhang, Jing; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin

2015-08-01

The purpose of this study was to compare histogram analysis of apparent diffusion coefficient (ADC) and R2* for differentiating low-grade from high-grade clear cell renal cell carcinoma (RCC). Forty-six patients with pathologically confirmed clear cell RCC underwent preoperative BOLD and DWI MRI of the kidneys. ADCs based on the entire tumor volume were calculated with b value combinations of 0 and 800 s/mm(2). ROI-based R2* was calculated with eight TE combinations of 6.7-22.8 milliseconds. Histogram analysis of tumor ADCs and R2* values was performed to obtain mean; median; width; and fifth, 10th, 90th, and 95th percentiles and histogram inhomogeneity, kurtosis, and skewness for all lesions. Thirty-three low-grade and 13 high-grade clear cell RCCs were found at pathologic examination. The TNM classification and tumor volume of clear cell RCC significantly correlated with histogram ADC and R2* (ρ = -0.317 to 0.506; p < 0.05). High-grade clear cell RCC had significantly lower mean, median, and 10th percentile ADCs but higher inhomogeneity and median R2* than low-grade clear cell RCC (all p < 0.05). Compared with other histogram ADC and R2* indexes, 10th percentile ADC had the highest accuracy (91.3%) in discriminating low- from high-grade clear cell RCC. R2* in discriminating hemorrhage was achieved with a threshold of 68.95 Hz. At this threshold, high-grade clear cell RCC had a significantly higher prevalence of intratumor hemorrhage (high-grade, 76.9%; low-grade, 45.4%; p < 0.05) and larger hemorrhagic area than low-grade clear cell RCC (high-grade, 34.9% ± 31.6%; low-grade, 8.9 ± 16.8%; p < 0.05). A close relation was found between MRI indexes and pathologic findings. Histogram analysis of ADC and R2* allows differentiation of low- from high-grade clear cell RCC with high accuracy.

Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity

PubMed Central

Hu, Yuanjie; Ru, Ning; Xiao, Huasheng; Chaturbedi, Abhishek; Hoa, Neil T.; Tian, Xiao-Jun; Zhang, Hang; Ke, Chao; Yan, Fengrong; Nelson, Jodi; Li, Zhenzhi; Gramer, Robert; Yu, Liping; Siegel, Eric; Zhang, Xiaona; Jia, Zhenyu; Jadus, Martin R.; Limoli, Charles L.; Linskey, Mark E.; Xing, Jianhua; Zhou, Yi-Hong

2013-01-01

Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7) copy number variation (CNV) in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas. Interestingly, all Chr7-aneuploid cell types in the parental culture of established glioma cell lines reappeared in single-cell-derived subcultures. We then characterized the biology of three syngeneic glioma cultures dominated by different Chr7-aneuploid cell types. We found phenotypic divergence for cells following Chr7 mis-segregation, which benefited overall tumor growth in vitro and in vivo. Mathematical modeling suggested the involvement of chromosome instability and interactions among cell subpopulations in restoring the optimal equilibrium of tumor cell types. Both our experimental data and mathematical modeling demonstrated that the complexity of tumor heterogeneity could be enhanced by the existence of chromosomes with structural abnormality, in addition to their mis-segregations. Overall, our findings show, for the first time, the involvement of chromosome instability in maintaining tumor heterogeneity, which underlies the enhanced growth, persistence and treatment resistance of cancers. PMID:24282558

CD25 is expressed by canine cutaneous mast cell tumors but not by cutaneous connective tissue mast cells.

PubMed

Meyer, A; Gruber, A D; Klopfleisch, R

2012-11-01

Canine cutaneous mast cell tumors (MCT) of different histological grades have distinct biological behaviors. However, little is known about underlying molecular mechanisms that lead to tumor development and increasing malignancy with higher tumor grade. Recent studies have identified the interleukin-2 receptor (IL-2R) subunits CD25 and CD2 as markers that distinguish nonneoplastic from neoplastic mast cells in human systemic mastocytosis. In this study, their potential as a marker for canine MCT and their possible impact on MCT carcinogenesis were evaluated. mRNA expression levels of both genes were compared between grade 1 (n = 12) and grade 3 (n = 8) MCT, and protein expression levels of CD25 were compared in 90 MCT of different tumor grades. mRNA expression levels of both CD25 and CD2 were upregulated in grade 3 MCT. In contrast, CD25 protein was expressed by fewer tumor cells and at decreased levels in grade 3 tumors, while most grade 1 MCT had strong CD25 protein expression. Moreover, CD25 was not expressed by nonneoplastic, resting cutaneous mast cells, while few presumably activated mast cells in tissue samples from dogs with allergic dermatitis had weak CD25 expression. Taken together, these findings suggest that CD25 may play a critical role in early MCT development and may be a stimulatory factor in grade 1 MCT, while grade 3 MCT seem to be less dependent on CD25. Because of the low number of CD25-positive tumor cells in high-grade tumors, the usefulness of CD25 as a tumor marker is, however, questionable.

Pion radiation for high grade astrocytoma: results of a randomized study.

PubMed

Pickles, T; Goodman, G B; Rheaume, D E; Duncan, G G; Fryer, C J; Bhimji, S; Ludgate, C; Syndikus, I; Graham, P; Dimitrov, M; Bowen, J

1997-02-01

This study attempted to compare within a randomized study the outcome of pion radiation therapy vs. conventional photon irradiation for the treatment of high-grade astrocytomas. Eighty-four patients were randomized to pion therapy (33-34.5 Gy pi), or conventional photon irradiation (60 Gy). Entry criteria included astrocytoma (modified Kernohan high Grade 3 or Grade 4), age 18-70, Karnofsky performance status (KPS) > or = 50, ability to start irradiation within 30 days of surgery, unifocal tumor, and treatment volume < 850 cc. The high-dose volume in both arms was computed tomography enhancement plus a 2-cm margin. The study was designed with the power to detect a twofold difference between arms. Eighty-one eligible patients were equally balanced for all known prognostic variables. Pion patients started radiation 7 days earlier on average than photon patients, but other treatment-related variables did not differ. There were no significant differences for either early or late radiation toxicity between treatment arms. Actuarial survival analysis shows no differences in terms of time to local recurrence or overall survival where median survival was 10 months in both arms (p = 0.22). The physician-assessed KPS and patient-assessed quality of life (QOL) measurements were generally maintained within 10 percentage points until shortly before tumor recurrence. There was no apparent difference in the serial KPS or QOL scores between treatment arms. In contrast to high linear energy transfer (LET) therapy for central nervous system tumors, such as neutron or neon therapy, the safety of pion therapy, which is of intermediate LET, has been reaffirmed. However, this study has demonstrated no therapeutic gain for pion therapy of glioblastoma.

Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas.

PubMed

Zhang, Jinghui; Wu, Gang; Miller, Claudia P; Tatevossian, Ruth G; Dalton, James D; Tang, Bo; Orisme, Wilda; Punchihewa, Chandanamali; Parker, Matthew; Qaddoumi, Ibrahim; Boop, Fredrick A; Lu, Charles; Kandoth, Cyriac; Ding, Li; Lee, Ryan; Huether, Robert; Chen, Xiang; Hedlund, Erin; Nagahawatte, Panduka; Rusch, Michael; Boggs, Kristy; Cheng, Jinjun; Becksfort, Jared; Ma, Jing; Song, Guangchun; Li, Yongjin; Wei, Lei; Wang, Jianmin; Shurtleff, Sheila; Easton, John; Zhao, David; Fulton, Robert S; Fulton, Lucinda L; Dooling, David J; Vadodaria, Bhavin; Mulder, Heather L; Tang, Chunlao; Ochoa, Kerri; Mullighan, Charles G; Gajjar, Amar; Kriwacki, Richard; Sheer, Denise; Gilbertson, Richard J; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Baker, Suzanne J; Ellison, David W

2013-06-01

The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs.

Clinical outcomes of gamma knife radiosurgery in the salvage treatment of patients with recurrent high-grade glioma.

PubMed

Elaimy, Ameer L; Mackay, Alexander R; Lamoreaux, Wayne T; Demakas, John J; Fairbanks, Robert K; Cooke, Barton S; Lamm, Andrew F; Lee, Christopher M

2013-12-01

Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external beam radiation therapy and chemotherapy when compared to patients treated with external beam radiation therapy and chemotherapy alone. In recent years, gamma knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of gamma knife radiosurgery for patients who suffer from this malignancy. Retrospective, prospective, and randomized clinical studies published between the years 2000 and 2012 analyzing gamma knife radiosurgery for patients with high-grade glioma were reviewed. After assessing patient age, Karnofsky performance status, tumor histology, and extent of resection, gamma knife radiosurgery is a viable, minimally invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that gamma knife radiosurgery provides patients with a high local tumor control rate and a median survival after tumor recurrence ranging from 13 to 26 months. Gamma knife radiosurgery followed by chemotherapy for recurrent high-grade glioma may provide select patients with increased levels of survival. However, further investigation into this matter is needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities of fractionated gamma knife radiosurgery due to its potential to limit treatment-associated morbidity. Gamma knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating

The value of histological grading of biopsy and resection specimens in early stage oral squamous cell carcinomas.

PubMed

Dik, Eric A; Ipenburg, Norbertus A; Kessler, Peter A; van Es, Robert J J; Willems, Stefan M

2018-04-05

In oral squamous cell carcinoma (OSCC) the differentiation grade of the tumor is determined on the biopsy and the resection specimen. The relation between tumor grade, nodal metastasis and survival is debatable. The aims of this study were to determine the correlation between differentiation grade of the biopsy and the resection specimen. Furthermore, we wanted to correlate tumor differentiation grade with nodal stage and survival. One-hundred and forty-five patients with OSCC staged as T1-2, N0 of the tongue, floor of mouth or cheek with primary resection of the tumor were examined. Biopsy and resection specimen were histologically re-assessed with regard to differentiation grade, as well as infiltrative, peri-neural and vascular invasive growth. This study showed a poor correlation between differentiation grade in the incisional biopsy and the resection specimen of the same tumor. No significant relation between differentiation grade of the resection specimen and nodal involvement, as well as overall and disease-specific survival was found. In early OSCC the differentiation grade determined by biopsy is of little predictive value for the grading of the resection specimen. Poor differentiation grade could not be related to the presence of nodal metastasis or survival and seems not to have any prognostic value concerning outcome. Treatment planning must be related to these findings. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Ductal carcinoma of breast: nuclear grade as a predictor of S-phase fraction.

PubMed

Dabbs, D J

1993-06-01

Nuclear grade (NG) and S-phase fraction (SPF) are established independent prognostic variables for ductal breast carcinomas. Nuclear grade can be assigned by a pathologist in a simple fashion during histopathologic evaluation of the tumor, while SPF requires flow cytometric evaluation of tumor samples. This prospective study was undertaken to determine whether elevated SPF could be predicted from NG alone and how NG and SPF correlate with c-erbB-2 expression. Eighty-two breast carcinomas of ductal type were assigned an NG of low (grade 1 or grade 2) or high (grade 3). S-phase fraction was recorded initially from fresh-frozen tissue samples and was designated as either low SPF (below the value designated as the cutoff for elevated SPF) or high SPF (a value at or greater than the cutoff value). On fresh tissue the NG predicted the range of SPF (low or high) in 89% of cases. Four percent of the cases that did not correlate could definitely be attributed to sample error. The remaining 7% that did not correlate could have been due to sample error, specimen quality, or tumor heterogeneity, as demonstrated by reversal of SPF range as performed on paraffin blocks of tumor. Eighty-eight percent of the tumors positive for c-erbB-2 were NG 3 and 12% were NG 2. All c-erbB-2 tumors were aneuploid. This study demonstrates the importance of carefully assigning NGs on tissue and indicates the importance of reviewing flow cytometric data side by side with histopathologic parameters to detect discrepancies between these two modalities. Careful nuclear grading assignment can accurately predict the range of SPF.

SU-D-207B-02: Early Grade Classification in Meningioma Patients Combining Radiomics and Semantics Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coroller, T; Bi, W; Abedalthagafi, M

Purpose: The clinical management of meningioma is guided by its grade and biologic behavior. Currently, diagnosis of tumor grade follows surgical resection and histopathologic review. Reliable techniques for pre-operative determination of tumor behavior are needed. We investigated the association between imaging features extracted from preoperative gadolinium-enhanced T1-weighted MRI and meningioma grade. Methods: We retrospectively examined the pre-operative MRI for 139 patients with de novo WHO grade I (63%) and grade II (37%) meningiomas. We investigated the predictive power of ten semantic radiologic features as determined by a neuroradiologist, fifteen radiomic features, and tumor location. Conventional (volume and diameter) imaging featuresmore » were added for comparison. AUC was computed for continuous and χ{sup 2} for discrete variables. Classification was done using random forest. Performance was evaluated using cross validation (1000 iterations, 75% training and 25% validation). All p-values were adjusted for multiple testing. Results: Significant association was observed between meningioma grade and tumor location (p<0.001) and two semantic features including intra-tumoral heterogeneity (p<0.001) and overt hemorrhage (p=0.01). Conventional (AUC 0.61–0.67) and eleven radiomic (AUC 0.60–0.70) features were significant from random (p<0.05, Noether test). Median AUC values for classification of tumor grade were 0.57, 0.71, 0.72 and 0.77 respectively for conventional, radiomic, location, and semantic features after using random forest. By combining all imaging data (semantic, radiomic, and location), the median AUC was 0.81, which offers superior predicting power to that of conventional imaging descriptors for meningioma as well as radiomic features alone (p<0.05, permutation test). Conclusion: We demonstrate a strong association between radiologic features and meningioma grade. Pre-operative prediction of tumor behavior based on imaging features

Prognostic factors of phyllodes tumor of the breast.

PubMed

Roa, Juan Carlos; Tapia, Oscar; Carrasco, Paula; Contreras, Enrique; Araya, Juan Carlos; Muñoz, Sergio; Roa, Iván

2006-06-01

The phyllodes tumor is characterized by its tendency to recur locally and occasionally to metastasize. The purpose of the present paper was to assess the prognostic value of clinical-morphological characteristics in patients with phyllodes tumor. Forty-seven cases of phyllodes tumors was studied; the World Health Organization classification was used and follow up was obtained. A total of 51%, 28% and 21% of the tumors were classified as benign, borderline and malignant, respectively. The adherence (P = 0.01), size >10 cm (P = 0.001), high mitotic activity (P = 0.03), infiltrative tumor margin (P = 0.0002) and type of surgery in malignant tumors (P = 0.02) proved to be good predictors of relapse. The presence of pain (P = 0.03), postmenopausal status (P < 0.04), heavy cellular pleomorphism (P = 0.007), high mitotic activity (P = 0.002), tumoral grade (P = 0.006) and metastasis (P < 0.00001) were prognostic factors of poor survival. Tumoral grade and some clinical-morphological characteristics of patients with phyllodes tumors have a significant impact on the prediction of its biological behavior.

Radiofrequency Ablation Using a Multiple-Electrode Switching System for Lung Tumors with 2.0-5.0-cm Maximum Diameter: Phase II Clinical Study.

PubMed

Kodama, Hiroshi; Yamakado, Koichiro; Hasegawa, Takaaki; Fujimori, Masashi; Yamanaka, Takashi; Takaki, Haruyuki; Uraki, Junji; Nakatsuka, Atsuhiro; Sakuma, Hajime

2015-12-01

To prospectively evaluate the safety and effectiveness of radiofrequency ablation (RFA) by using a multiple-electrode switching system to treat 2.0-5.0-cm lung tumors. The institutional review board approved this prospective phase II study. Written informed consent was obtained from all patients. Between September 2009 and July 2011, RFA using two or three radiofrequency (RF) electrodes and a multiple-electrode switching system was performed for malignant lung tumors with a maximum tumor diameter of 2.0-5.0 cm in nonsurgical candidates. The primary endpoint was safety, as evaluated using the Common Terminology Criteria for Adverse Events. Patients were observed for at least 1 year. Local tumor progression and overall survival were analyzed with the Kaplan-Meier method. Thirty-three patients (26 men, seven women; mean age, 70.5 years ± 10.0; age range, 46-87 years) with 35 lung tumors with a mean maximum diameter of 3.0 cm ± 0.7 (standard deviation; range, 2.0-4.4 cm) underwent treatment in 35 sessions. No procedure-related death or grade 4 adverse events (AEs) occurred. Grade 3 AEs occurred in four patients (12%), with pleural effusion requiring chest tube placement in two patients, pneumothorax requiring pleural adhesion in one patient, and pulmonary hemorrhage requiring pulmonary artery coil embolization in one patient. Grade 2 AEs were detected in 13 patients (39%). The 1-year local tumor progression and overall survival rates were 12.7% (95% confidence interval [CI]: 1.0, 25.5) and 81.2% (95% CI: 67.6, 94.8). RFA with a multiple-electrode switching system may be a safe therapeutic option with which to treat 2.0-5.0-cm lung cancer tumors.

Conditional survival of all primary brain tumor patients by age, behavior, and histology.

PubMed

Porter, Kimberly R; McCarthy, Bridget J; Berbaum, Michael L; Davis, Faith G

2011-01-01

Survival statistics commonly reflect survival from the time of diagnosis but do not take into account survival already achieved after a diagnosis. The objective of this study was to provide conditional survival estimates for brain tumor patients as a more accurate measure of survival for those who have already survived for a specified amount of time after diagnosis. Data on primary malignant and nonmalignant brain tumor cases diagnosed from 1985-2005 from selected SEER state cancer registries were obtained. Relative survival up to 15 years postdiagnosis and varying relative conditional survival rates were computed using the life-table method. The overall 1-year relative survival estimate derived from time of diagnosis was 67.8% compared to the 6-month relative conditional survival rate of 85.7% for 6-month survivors (the probability of surviving to 1 year given survival to 6 months). The 10-year overall relative survival rate was 49.5% from time of diagnosis compared to the 8-year relative conditional survival rate of 79.2% for 2-year survivors. Conditional survival estimates and standard survival estimates varied by histology, behavior, and age at diagnosis. The 5-year relative survival estimate derived from time of diagnosis for glioblastoma was 3.6% compared to the 3-year relative conditional survival rate of 36.4% for 2-year survivors. For most nonmalignant tumors, the difference between relative survival and the corresponding conditional survival estimates were minimal. Older age groups had greater numeric gains in survival but lower conditional survival estimates than other age groups. Similar findings were seen for other conditional survival intervals. Conditional survival is a useful disease surveillance measure for clinicians and brain tumor survivors to provide them with better 'real-time' estimates and hope. Copyright © 2011 S. Karger AG, Basel.

A Novel Candidate Molecule in Pathological Grading Of Gliomas: ELABELA.

PubMed

Artas, Gokhan; Ozturk, Sait; Kuloglu, Tuncay; Dagli, Adile Ferda; Gonen, Murat; Artas, Hakan; Aydin, Suleyman; Erol, Fatih Serhat

2018-04-06

This study aimed to investigate the possible role of ELABELA (ELA) in the histopathological grading of gliomas. We retrospectively assessed pathological specimens of patients who underwent surgery for intracranial space-occupying lesions. Only primary glioma specimens were included in this study. We enrolled 11 patients histologically diagnosed with low-grade glioma and 22 patients with high-grade glioma. The ELA antibody was applied to 4-6-µm-thick sections obtained from paraffin blocks. Histoscores were calculated using the distribution and intensity of staining immunoreactivity. An independent sample t-test was used for two-point inter-group assessments, whereas one-way analysis of variance was used for the other assessments. P 0.05 was considered statistically significant. The histoscores of the control brain, low-grade glioma, and high-grade glioma tissues were found to be 0.08, 0.37, and 0.92, respectively. The difference in ELA immunoreactivity between the control brain tissue and glioma tissue was statistically significant (p 0.05). In addition, a statistically significant increase was observed in ELA immunoreactivity in high-grade glioma tissues compared with that in low-grade glioma tissues (p 0.05). ELA has an angiogenetic role in the progression of glial tumors. ELA, which is an endogenous ligand of the apelin receptor, activates the apelinergic system and causes the progression of glial tumors. Further studies with a large number of patients are necessary to investigate the angiogenetic role of ELA in glial tumors.

Oncofertility in patients with stage I epithelial ovarian cancer: fertility-sparing surgery in young women of reproductive age.

PubMed

Jiang, Xuan; Yang, Jiaxin; Yu, Mei; Xie, Weimin; Cao, Dongyan; Wu, Ming; Pan, Lingya; Huang, Huifang; You, Yan; Shen, Keng

2017-08-15

Fertility-sparing surgery is indicated for patients with stage I epithelial ovarian cancers. We sought to evaluate the clinical outcomes and oncofertility in a cohort of patients of reproductive age with stage I epithelial ovarian cancer (EOC). Overall, 108 patients of reproductive age (≤ 40 years) diagnosed with stage I EOC who were treated at Peking Union Medical College Hospital between 1999 and 2013 were included in the study. The Kaplan-Meier model and Cox regression analyses were used for the survival analysis. The type of surgery included fertility-sparing surgery (FSS) (48.1%) and radical surgery (RS) (51.9%). After a median follow-up of 83 months, we observed that grade 3 or clear-cell carcinoma was the only independent risk factor for disease-free survival and tumor-specific survival in the multivariate analysis. Patients with grade 3 or clear-cell carcinoma tended to be older than 30 years, have endometriosis, and undergo RS (p < 0.05). Fertility-sparing surgery did not affect disease-free survival or tumor-specific survival among patients of reproductive age with stage I EOC and among high-risk patients with stage IC2-3, grade 3, or clear-cell carcinoma. Thirty-four out of 52 (65.4%) FSS patients attempted to get pregnant. Twenty-eight (82.4%) achieved a successful pregnancy with a full-term delivery. Grade 3 or clear-cell carcinoma was the only independent risk factor for survival of patients of reproductive age with stage I EOC. FSS can be safely performed on patients of reproductive age with grade 1-2, stage I EOC. The safety of FSS for grade 3 and clear-cell carcinoma warrants further investigation.

Immunohistochemical expression of galectin-3 is significantly associated with grade, stage and differentiation of endometrial carcinomas.

PubMed

Al-Maghrabi, Jaudah; Abdelrahman, Amer Shafie; Ghabrah, Tawfik; Butt, Nadeem Shafique; Al-Maghrabi, Basim; Khabaz, Mohamad Nidal

2017-04-01

This study describes galectin-3 immunohistochemical phenotype and its association with clinicopathological factors in the carcinoma of endometrium. Seventy one cases of endometrial carcinoma and 30 cases of benign and normal endometrium were employed for the detection of galectin-3 protein using tissue microarrays and immunohistochemistry staining. Thirty nine (55%) cases, including 54.2% of endometrioid adenocarcinomas and 55.5% serous carcinomas, were positively stained for galectin-3. Brown granular expression of this glycoprotein was detected in transformed epithelial cells of 36 cases including 28 cases with membranous and cytoplasmic staining and 8 cases with only cytoplasmic staining; nuclear expression was present in stromal cells of the remaining 3 cases. Twenty-four (80%) control cases showed granular cytoplasmic and membranous expression, and six control cases were negative. Tumor grade, stage and differentiation were significantly associated with galectin-3 immunoreactivity (p-values are 0.043, 0.016, and 0.044 respectively), cases with membranous and cytoplasmic staining is significantly associated with grade I and stage II, while cases with loss of staining are more frequent in grade II, III and poorly differentiated tumors. No significant association of galectin-3 staining was observed with age, diagnosis, recurrence and alive status. The current study supports the tumor suppression role of galectin-3 in endometrial carcinoma. Greater galectin-3 immunostaining has been found in control endometrial tissues compared to endometrial tumors. Loss or decreased galectin-3 immunoexpression gives a sign for poor prognoses in endometrial carcinoma patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

SJDAWN: St. Jude Children's Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors

ClinicalTrials.gov

2018-04-09

Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Ganglioglioma; Anaplastic Meningioma; Anaplastic Oligodendroglioma; Pleomorphic Xanthoastrocytoma, Anaplastic; Atypical Teratoid/Rhabdoid Tumor; Brain Cancer; Brain Tumor; Central Nervous System Neoplasms; Choroid Plexus Carcinoma; CNS Embryonal Tumor With Rhabdoid Features; Ganglioneuroblastoma of Central Nervous System; CNS Tumor; Embryonal Tumor of CNS; Ependymoma; Glioblastoma; Glioma; Glioma, Malignant; Medulloblastoma; Medulloblastoma; Unspecified Site; Medulloepithelioma; Neuroepithelial Tumor; Neoplasms; Neoplasms, Neuroepithelial; Papillary Tumor of the Pineal Region (High-grade Only); Pediatric Brain Tumor; Pineal Parenchymal Tumor of Intermediate Differentiation (High-grade Only); Pineoblastoma; Primitive Neuroectodermal Tumor; Recurrent Medulloblastoma; Refractory Brain Tumor; Neuroblastoma. CNS; Glioblastoma, IDH-mutant; Glioblastoma, IDH-wildtype; Medulloblastoma, Group 3; Medulloblastoma, Group 4; Glioma, High Grade; Neuroepithelial Tumor, High Grade; Medulloblastoma, SHH-activated and TP53 Mutant; Medulloblastoma, SHH-activated and TP53 Wildtype; Medulloblastoma, Chromosome 9q Loss; Medulloblastoma, Non-WNT Non-SHH, NOS; Medulloblastoma, Non-WNT/Non-SHH; Medulloblastoma, PTCH1 Mutation; Medulloblastoma, WNT-activated; Ependymoma, Recurrent; Glioma, Recurrent High Grade; Glioma, Recurrent Malignant; Embryonal Tumor, NOS; Glioma, Diffuse Midline, H3K27M-mutant; Embryonal Tumor With Multilayered Rosettes (ETMR); Ependymoma, NOS, WHO Grade III; Ependymoma, NOS, WHO Grade II; Medulloblastoma, G3/G4; Ependymoma, RELA Fusion Positive

Interpretation of 40Ar/39Ar Age-spectra in Low-grade Polymetamorphic Rocks: The Importance of Petrologic constraints

NASA Astrophysics Data System (ADS)

Kunk, M. J.

2007-12-01

40Ar/39Ar age-spectra of white micas from low-grade polymetamorphic terranes can be difficult to interpret, because these low-grade rocks frequently have multiple generations of cleavage-forming white mica that grew at temperatures below their closure for diffusion of argon (~350°C). Under such conditions, each generation of cleavage-forming white mica will retain its original growth age. In addition, rocks from metamorphic terranes can also contain populations of detrital and diagenetic white micas which also have distinct ages associated with them. A final complication, frequently found in these low-grade polymetamorphic samples is the presence of inseparable, intergrown chlorite and the problems with associated 39Ar recoil during irradiation of the samples, prior to sample analysis. The shapes of 40Ar/39Ar age spectra of white micas separated from such samples are frequently complex and are quite variable in shape. Some age spectra show a steady increase in age with increase in the temperature of release, while others have sigmoidal or saddle-shaped patterns. The age of most of the steps in such age spectra are mixtures of the various age populations of white mica in the sample, and as such are geologically meaningless. Nonetheless, useful constraints on the ages of at least some events recorded in these complex low-grade polymetamorphic rocks can be discerned with the help of petrographic observations, and by placing the results in a spatial context to test for reproducibility and/or the occurrence of meaningful patterns. If no chlorite is present and the sample contains no detrital white mica, an estimate of the maximum age of the youngest component and the minimum age of the oldest cleavage forming white mica populations can frequently be discerned. If the sample contains detrital white mica, a minimum age for its cooling or crystallization can be estimated. The presence of a small amount of intimately intergrown chlorite masks the age of the youngest white

Stochastic modelling of slow-progressing tumors: Analysis and applications to the cell interplay and control of low grade gliomas

NASA Astrophysics Data System (ADS)

Rodríguez, Clara Rojas; Fernández Calvo, Gabriel; Ramis-Conde, Ignacio; Belmonte-Beitia, Juan

2017-08-01

Tumor-normal cell interplay defines the course of a neoplastic malignancy. The outcome of this dual relation is the ultimate prevailing of one of the cells and the death or retreat of the other. In this paper we study the mathematical principles that underlay one important scenario: that of slow-progressing cancers. For this, we develop, within a stochastic framework, a mathematical model to account for tumor-normal cell interaction in such a clinically relevant situation and derive a number of deterministic approximations from the stochastic model. We consider in detail the existence and uniqueness of the solutions of the deterministic model and study the stability analysis. We then focus our model to the specific case of low grade gliomas, where we introduce an optimal control problem for different objective functionals under the administration of chemotherapy. We derive the conditions for which singular and bang-bang control exist and calculate the optimal control and states.

Intra-operative visualization of brain tumors with 5-aminolevulinic acid-induced fluorescence.

PubMed

Widhalm, Georg

2014-01-01

Precise histopathological diagnosis of brain tumors is essential for the correct patient management. Furthermore, complete resection of brain tumors is associated with an improved patient prognosis. However, histopathological undergrading and incomplete tumor removal are not uncommon, especially due to insufficient intra-operative visualization of brain tumor tissue. The fluorescent dye 5-aminolevulinic acid (5-ALA) is currently applied for fluorescence-guided resections of high-grade gliomas. The value of 5-ALA-induced protoporphyrin (PpIX) fluorescence for intra-operative visualization of other tumors than high-grade gliomas remains unclear. Within the frame of this thesis, we found a significantly higher rate of complete resections of our high-grade gliomas as compared to control cases by using the newly established 5-ALA fluorescence technology at our department. Additionally, we showed that MRI spectroscopy-based chemical shift imaging (CSI) is capable to identify intratumoral high-grade glioma areas (= anaplastic foci) during navigation guided resections to avoid histopathological undergrading. However, the accuracy of navigation systems with integrated pre-operative imaging data such as CSI declines during resections due to intra-operative brainshift. In two further studies, we found that 5-ALA induced PpIX fluorescence is capable as a novel intra-operative marker to detect anaplastic foci within initially suspected low-grade gliomas independent of brainshift. Finally, we showed that the application of 5-ALA is also of relevance in needle biopsies for intra-operative identification of representative brain tumor tissue. These data indicate that 5-ALA is not only of major importance for resection of high-grade gliomas, but also for intra-operative visualization of anaplastic foci as well as representative brain tumor tissue in needle biopsies unaffected by brainshift. Consequently, this new technique might become a novel standard in brain tumor surgery that

Racial variation in tumor stage at diagnosis among Department of Defense beneficiaries.

PubMed

Enewold, Lindsey; Zhou, Jing; McGlynn, Katherine A; Devesa, Susan S; Shriver, Craig D; Potter, John F; Zahm, Shelia H; Zhu, Kangmin

2012-03-01

Tumor stage at diagnosis often varies by racial/ethnic group, possibly because of inequitable health care access. Within the Department of Defense (DoD) Military Health System, beneficiaries have equal health care access. The objective of this study was to determine whether tumor stage differed between whites and blacks with breast, cervical, colorectal, and prostate cancers, which have effective screening regimens, based on data from the DoD Automated Cancer Tumor Registry from 1990 to 2003. Distributions of tumor stage (localized vs nonlocalized) between whites and blacks in the military were compared stratified by sex, active duty status, and age at diagnosis. Logistic regression was used to further adjust for age, marital status, year of diagnosis, geographic region, military service branch, and tumor grade. Distributions of tumor stage were then compared between the military and general populations. Racial differences in the distribution of stage were significant only among nonactive duty beneficiaries. After adjusting for covariates, earlier stages of breast cancer after age 49 years and prostate cancer after age 64 years were significantly more common among white than black nonactive duty beneficiaries (P < .05), although the absolute difference was minimal for prostate cancer. Racial differences in stage for cervical and colorectal cancers were not significant after adjustment. Compared with the general population, racial differences in the military were similar or were slightly attenuated. Racial disparities in stage at diagnosis were apparent in the DoD equal-access health care system among older nonactive duty beneficiaries. Socioeconomic status, supplemental insurance, cultural beliefs, and biologic factors may be related to these results. Copyright © 2011 American Cancer Society.

E4206: AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors.

PubMed

Lubner, Sam; Feng, Yang; Mulcahy, Mary; O'Dwyer, Peter; Giang, Guang-Yu; Louis Hinshaw, J; Deming, Dustin; Klein, Leonard; Teitelbaum, Ursina; Payne, Jennifer; Engstrom, Paul; Stella, Philip; Meropol, Neal; Benson, Al

2018-05-31

Rate of progression-free survival at a particular point in time, i.e., a landmark analysis, is a difficult endpoint for a heterogenous malignancy such as neuroendocrine cancer.Landmark analyses can also be complicated by evolution in the standard of care during the conduct of a clinical trial.Improvements in biomarker development would be useful in developing future clinical trials in NET to better tailor individualized therapies and assess for possible efficacy endpoints. Neuroendocrine tumors (NETs) are rare malignancies of the gastrointestinal (GI) tract that are highly vascularized and overexpress vascular-endothelial growth factor (VEGF). Sunitinib has demonstrated efficacy in the pancreatic subset of NET. This study explored the activity of another oral VEGF inhibitor, AMG 706 or motesanib, a multikinase inhibitor that targets receptor tyrosine kinases, including VEGFR1, VEGFR2, VEGFR3, KIT, RET, and PDGFR (IC50s = 2, 3, 6, 8, 59, and 84 nM, respectively). This was a single-arm, first-line, phase II study run through the Eastern Cooperative Oncology Group. Patients with low-grade NET (as defined by central confirmation of Ki-67 of 0%-2%) were administered a flat dose of 125 mg per day orally combined with octreotide long acting-repeatable (LAR) for patients who had been on a stable dose. The primary objective was to determine the 4-month progression-free survival (PFS). Forty-four patients were evaluated per protocol. The 4-month PFS was 78.5%. The partial response rate was 13.6% (6/44), stable disease was 54.5% (24/44), 9.1% (4/44) had progressive disease, and 10/44 were not evaluable for response. Common toxicities included fatigue, hypertension, nausea, and headache, and most were grade 1-2. Median PFS was 8.7 months, and overall survival was 27.5 months. Motesanib (AMG 706) demonstrated a 4-month PFS that met the per-protocol definition of efficacy. Fatigue and hypertension were the most common toxicities, and few grade 3-4 toxicities were encountered

Tumor-Protective Mechanism Identified from Premature Aging Disease | Center for Cancer Research

Cancer.gov

Hutchinson-Gilford Progeria Syndrome (HGPS) is an extraordinarily rare genetic disorder caused by a mutation in the LMNA gene, which encodes architectural proteins of the human cell nucleus. The mutation causes the production of a mutant protein called progerin. Patients with HGPS display signs of premature aging, such as hair loss, slowed growth, weakening of bone and joint integrity, and cardiovascular disease. Most die in their mid-teens of heart disease or stroke. Intriguingly, these patients do not develop another aging-related disease, cancer, despite having dramatically elevated levels of DNA damage. Tom Misteli, Ph.D., of CCR’s Laboratory of Receptor Biology and Gene Expression, and his colleagues hypothesized that, rather than patients not living long enough to develop cancer, a resistance mechanism was operating in HGPS cells to prevent cancer formation. To begin testing this idea, the researchers transformed fibroblasts from HGPS patients or age-matched, healthy controls with telomerase, constitutively-activated HRAS, and SV40 large and small T antigens. Transformed HGPS cells displayed morphological changes and increased proliferation similar to transformed controls but formed fewer colonies in soft agar and fewer tumors when injected into mice. When the investigators examined global gene expression in the two populations of cells, they found that transformed HGPS cells failed to activate many of the genes that are induced in response to transformation in controls, including oncogenic and proliferation pathways. In addition the transformed HGPS cells were unable to undergo oncogenic de-differentiation. Importantly, the tumor resistance in HGPS cells was due to the presence of the progerin protein, which was both necessary and sufficient to protect cells from oncogenic transformation. Together these results suggested that HGPS cells resist cancer-inducing stimuli by not undergoing the genetic reprogramming necessary for tumor initiation. The scientists

A Novel Method to Generate and Expand Clinical-Grade, Genetically Modified, Tumor-Infiltrating Lymphocytes

PubMed Central

Forget, Marie-Andrée; Tavera, René J.; Haymaker, Cara; Ramachandran, Renjith; Malu, Shuti; Zhang, Minying; Wardell, Seth; Fulbright, Orenthial J.; Toth, Chistopher Leroy; Gonzalez, Audrey M.; Thorsen, Shawne T.; Flores, Esteban; Wahl, Arely; Peng, Weiyi; Amaria, Rodabe N.; Hwu, Patrick; Bernatchez, Chantale

2017-01-01

Following the clinical success achieved with the first generation of adoptive cell therapy (ACT) utilizing in vitro expanded tumor-infiltrating lymphocytes (TILs), the second and third generations of TIL ACT are evolving toward the use of genetically modified TIL. TIL therapy generally involves the transfer of a high number of TIL, ranging from 109 to 1011 cells. One of the technical difficulties in genetically modifying TIL, using a retroviral vector, is the ability to achieve large expansion of transduced TIL, while keeping the technique suitable to a Good Manufacturing Practices (GMP) environment. Consequently, we developed and optimized a novel method for the efficient production of large numbers of GMP-grade, gene-modified TIL for the treatment of patients with ACT. The chemokine receptor CXCR2 was used as the gene of interest for methodology development. The optimized procedure is currently used in the production of gene-modified TIL for two clinical trials for the treatment of metastatic melanoma at MD Anderson Cancer Center. PMID:28824634

[The heterogeneity of blood flow on magnetic resonance imaging: a biomarker for grading cerebral astrocytomas].

PubMed

Revert Ventura, A J; Sanz Requena, R; Martí-Bonmatí, L; Pallardó, Y; Jornet, J; Gaspar, C

2014-01-01

To study whether the histograms of quantitative parameters of perfusion in MRI obtained from tumor volume and peritumor volume make it possible to grade astrocytomas in vivo. We included 61 patients with histological diagnoses of grade II, III, or IV astrocytomas who underwent T2*-weighted perfusion MRI after intravenous contrast agent injection. We manually selected the tumor volume and peritumor volume and quantified the following perfusion parameters on a voxel-by-voxel basis: blood volume (BV), blood flow (BF), mean transit time (TTM), transfer constant (K(trans)), washout coefficient, interstitial volume, and vascular volume. For each volume, we obtained the corresponding histogram with its mean, standard deviation, and kurtosis (using the standard deviation and kurtosis as measures of heterogeneity) and we compared the differences in each parameter between different grades of tumor. We also calculated the mean and standard deviation of the highest 10% of values. Finally, we performed a multiparametric discriminant analysis to improve the classification. For tumor volume, we found statistically significant differences among the three grades of tumor for the means and standard deviations of BV, BF, and K(trans), both for the entire distribution and for the highest 10% of values. For the peritumor volume, we found no significant differences for any parameters. The discriminant analysis improved the classification slightly. The quantification of the volume parameters of the entire region of the tumor with BV, BF, and K(trans) is useful for grading astrocytomas. The heterogeneity represented by the standard deviation of BF is the most reliable diagnostic parameter for distinguishing between low grade and high grade lesions. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

MR imaging in staging of bone tumors

PubMed Central

Ehara, Shigeru

2006-01-01

For staging of bone tumors, TNM and Enneking’s systems are used with some differences. Magnetic resonance imaging is particularly useful for defining the extent of high-grade tumors, including transcortical and intertrabecular infiltration and periosteal extension. The concepts of compartment and curative surgical margins are important for bone tumor staging. PMID:17098647

Semiquantitative Analysis Using Thallium-201 SPECT for Differential Diagnosis Between Tumor Recurrence and Radiation Necrosis After Gamma Knife Surgery for Malignant Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsunaga, Shigeo, E-mail: shigeo-m@mui.biglobe.ne.jp; Shuto, Takashi; Takase, Hajime

Purpose: Semiquantitative analysis of thallium-201 chloride single photon emission computed tomography ({sup 201}Tl SPECT) was evaluated for the discrimination between recurrent brain tumor and delayed radiation necrosis after gamma knife surgery (GKS) for metastatic brain tumors and high-grade gliomas. Methods and Materials: The medical records were reviewed of 75 patients, including 48 patients with metastatic brain tumor and 27 patients with high-grade glioma who underwent GKS in our institution, and had suspected tumor recurrence or radiation necrosis on follow-up neuroimaging and deteriorating clinical status after GKS. Analysis of {sup 201}Tl SPECT data used the early ratio (ER) and the delayedmore » ratio (DR) calculated as tumor/normal average counts on the early and delayed images, and the retention index (RI) as the ratio of DR to ER. Results: A total of 107 tumors were analyzed with {sup 201}Tl SPECT. Nineteen lesions were removed surgically and histological diagnoses established, and the other lesions were evaluated with follow-up clinical and neuroimaging examinations after GKS. The final diagnosis was considered to be recurrent tumor in 65 lesions and radiation necrosis in 42 lesions. Semiquantitative analysis demonstrated significant differences in DR (P=.002) and RI (P<.0001), but not in ER (P=.372), between the tumor recurrence and radiation necrosis groups, and no significant differences between metastatic brain tumors and high-grade gliomas in all indices (P=.926 for ER, P=.263 for DR, and P=.826 for RI). Receiver operating characteristics analysis indicated that RI was the most informative index with the optimum threshold of 0.775, which provided 82.8% sensitivity, 83.7% specificity, and 82.8% accuracy. Conclusions: Semiquantitative analysis of {sup 201}Tl SPECT provides useful information for the differentiation between tumor recurrence and radiation necrosis in metastatic brain tumors and high-grade gliomas after GKS, and the RI may be the

Prediction of tumor differentiation using sequential PET/CT and MRI in patients with breast cancer.

PubMed

Choi, Joon Ho; Lim, Ilhan; Noh, Woo Chul; Kim, Hyun-Ah; Seong, Min-Ki; Jang, Seonah; Seol, Hyesil; Moon, Hansol; Byun, Byung Hyun; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo

2018-05-23

The aim of this study is to assess tumor differentiation using parameters from sequential positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in patients with breast cancer. This retrospective study included 78 patients with breast cancer. All patients underwent sequential PET/CT and MRI. For fluorodeoxyglucose (FDG)-PET image analysis, the maximum standardized uptake value (SUV max ) of FDG was assessed at both 1 and 2 h and metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The kinetic analysis of dynamic contrast-enhanced MRI parameters was performed using dynamic enhancement curves. We assessed diffusion-weighted imaging (DWI)-MRI parameters regarding apparent diffusion coefficient (ADC) values. Histologic grades 1 and 2 were classified as low-grade, and grade 3 as high-grade tumor. Forty-five lesions of 78 patients were classified as histologic grade 3, while 26 and 7 lesions were grade 2 and grade 1, respectively. Patients with high-grade tumors showed significantly lower ADC-mean values than patients with low-grade tumors (0.99 ± 0.19 vs.1.12 ± 0.32, p = 0.007). With respect to SUV max 1, MTV2.5, and TLG2.5, patients with high-grade tumors showed higher values than patients with low-grade tumors: SUV max 1 (7.92 ± 4.5 vs.6.19 ± 3.05, p = 0.099), MTV2.5 (7.90 ± 9.32 vs.4.38 ± 5.10, p = 0.095), and TLG2.5 (40.83 ± 59.17 vs.19.66 ± 26.08, p = 0.082). However, other parameters did not reveal significant differences between low-grade and high-grade malignancies. In receiver-operating characteristic (ROC) curve analysis, ADC-mean values showed the highest area under the curve of 0.681 (95%CI 0.566-0.782) for assessing high-grade malignancy. Lower ADC-mean values may predict the poor differentiation of breast cancer among diverse PET-MRI functional parameters.

Multimodal fiber-probe spectroscopy for the diagnostics and classification of bladder tumors

NASA Astrophysics Data System (ADS)

Anand, Suresh; Cicchi, Riccardo; Fantechi, Riccardo; Gacci, Mauro; Nesi, Gabriella; Carini, Marco; Pavone, Francesco S.

2017-02-01

The gold standard for the detection of bladder cancer is white light cystoscopy, followed by an invasive biopsy and pathological examination. Tissue pathology is time consuming and often prone to sampling errors. Recently, optical spectroscopy techniques have evolved as promising techniques for the detection of neoplasia. The specific goal of this study is to evaluate the application of combined auto-fluorescence (excited using 378 nm and 445 nm wavelengths) and diffuse reflectance spectroscopy to discriminate normal bladder tissue from tumor at different grades. The fluorescence spectrum at both excitation wavelengths showed an increased spectral intensity in tumors with respect to normal tissues. Reflectance data indicated an increased reflectance in the wavelength range 610 nm - 700 nm for different grades of tumors, compared to normal tissues. The spectral data were further analyzed using principal component analysis for evaluating the sensitivity and specificity for diagnosing tumor. The spectral differences observed between various grades of tumors provides a strong genesis for the future evaluation on a larger patient population to achieve statistical significance. This study indicates that a combined spectroscopic strategy, incorporating fluorescence and reflectance spectroscopy, could improve the capability for diagnosing bladder tumor as well as for differentiating tumors in different grades.

Differences in fluorescence profiles from breast cancer tissues due to changes in relative tryptophan content via energy transfer: tryptophan content correlates with histologic grade and tumor size but not with lymph node metastases

NASA Astrophysics Data System (ADS)

Sordillo, Laura A.; Sordillo, Peter P.; Budansky, Yury; Pu, Yang; Alfano, Robert R.

2014-12-01

The correlation between histologic grade, an increasingly important measure of prognosis for patients with breast cancer, and tryptophan levels from tissues of 15 breast carcinoma patients was investigated. Changes in the relative content of key native organic biomolecule tryptophan were seen from the fluorescence spectra of cancerous and paired normal tissues with excitation wavelengths of 280 and 300 nm. Due to a large spectral overlap and matching excitation-emission spectra, fluorescence resonance energy transfer from tryptophan-donor to reduced nicotinamide adenine dinucleotides-acceptor was noted. We used the ratios of fluorescence intensities at their spectral emission peaks, or spectral fingerprint peaks, at 340, 440, and 460 nm. Higher ratios correlated strongly with high histologic grade, while lower-grade tumors had low ratios. Large tumor size also correlated with high ratios, while the number of lymph node metastases, a major factor in staging, was not correlated with tryptophan levels. High histologic grade correlates strongly with increased content of tryptophan in breast cancer tissues and suggests that measurement of tryptophan content may be useful as a part of the evaluation of these patients.

Intranasal mast cell tumor in the dog: A case series

PubMed Central

Khoo, Alison; Lane, Amy; Wyatt, Ken

2017-01-01

The medical records of 4 dogs with histologically confirmed intranasal mast cell tumors (MCTs) were retrospectively evaluated to determine their biological behavior. Information on signalment, presenting clinical signs, tumor grade, treatment administered, and survival times was obtained from the medical record. All 4 patients had high grade tumors and received chemotherapy. Survival times ranged from 27 to 134 days. All 4 dogs showed signs of local or distant disease progression, suggestive of an aggressive behavior of intranasal MCTs. PMID:28761193

Correlation between Standardized Uptake Value of 68Ga-DOTA-NOC Positron Emission Tomography/Computed Tomography and Pathological Classification of Neuroendocrine Tumors.

PubMed

Kaewput, Chalermrat; Suppiah, Subapriya; Vinjamuri, Sobhan

2018-01-01

The aim of our study was to correlate tumor uptake of 68 Ga-DOTA-NOC positron emission tomography/computed tomography (PET/CT) with the pathological grade of neuroendocrine tumors (NETs). 68 Ga-DOTA-NOC PET/CT examinations in 41 patients with histopathologically proven NETs were included in the study. Maximum standardized uptake value (SUV max ) and averaged SUV SUV mean of "main tumor lesions" were calculated for quantitative analyses after background subtraction. Uptake on main tumor lesions was compared and correlated with the tumor histological grade based on Ki-67 index and pathological differentiation. Classification was performed into three grades according to Ki-67 levels; low grade: Ki-67 <2, intermediate grade: Ki-67 3-20, and high grade: Ki-67 >20. Pathological differentiation was graded into well- and poorly differentiated groups. The values were compared and evaluated for correlation and agreement between the two parameters was performed. Our study revealed negatively fair agreement between SUV max of tumor and Ki-67 index ( r = -0.241) and negatively poor agreement between SUV mean of tumor and Ki-67 index ( r = -0.094). SUV max of low-grade, intermediate-grade, and high-grade Ki-67 index is 26.18 ± 14.56, 30.71 ± 24.44, and 6.60 ± 4.59, respectively. Meanwhile, SUV mean of low-grade, intermediate-grade, and high-grade Ki-67 is 8.92 ± 7.15, 9.09 ± 5.18, and 3.00 ± 1.38, respectively. As expected, there was statistically significant decreased SUV max and SUV mean in high-grade tumors (poorly differentiated NETs) as compared with low- and intermediate-grade tumors (well-differentiated NETs). SUV of 68 Ga-DOTA-NOC PET/CT is not correlated with histological grade of NETs. However, there was statistically significant decreased tumor uptake of 68 Ga-DOTA-NOC in poorly differentiated NETs as compared with the well-differentiated group. As a result of this pilot study, we confirm that the lower tumor uptake of 68 Ga-DOTA-NOC may be associated with

Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer.

PubMed

Kündig, Pascale; Giesen, Charlotte; Jackson, Hartland; Bodenmiller, Bernd; Papassotirolopus, Bärbel; Freiberger, Sandra Nicole; Aquino, Catharine; Opitz, Lennart; Varga, Zsuzsanna

2018-05-08

Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas. We analyzed immunohistochemical expression and/or gene amplification status of conventional prognostic tumor markers (ER, PR, HER2, CK5/6), tumor progression markers (PTEN, PIK3CA, p53, Ki-67) and stem cell markers (mTOR, SOX2, SOX9, SOX10, SLUG, CD44, CD24, TWIST) in 372 tissue-micro-array samples from 72 breast cancer patients. Expression levels were compared between central and peripheral tumor tissue areas and were correlated to histopathological grading. 15 selected cases additionally underwent RNA sequencing for transcriptome analysis. No significant difference in any of the analyzed between central and peripheral tumor areas was seen with any of the analyzed methods/or results that showed difference. Except mTOR, PIK3CA and SOX9 (nuclear) protein expression, all markers correlated significantly (p < 0.05) with histopathological grading both in central and peripheral areas. Our results suggest that intra-tumoral heterogeneity of stem-cell and tumor-progression markers cannot be reliably addressed in tissue-micro-array samples in breast cancer. However, most markers correlated strongly with histopathological grading confirming prognostic information as expression profiles were independent on the site of the

High-Grade Hydronephrosis Predicts Poor Outcomes After Radical Cystectomy in Patients with Bladder Cancer

PubMed Central

Kim, Dong Suk; Cho, Kang Su; Lee, Young Hoon; Cho, Nam Hoon; Oh, Young Taek

2010-01-01

We examined whether the presence and severity of preoperative hydronephrosis have prognostic significance in patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. The medical records of 457 patients who underwent radical cystectomy for bladder cancer between 1986 and 2005 were retrospectively reviewed. Following the Society for Fetal Urology grading system, patients were divided into low-, and high-grade hydronephrosis groups. Clinicopathologic factors associated with preoperative hydronephrosis and survival were evaluated. Of a total of 406 patients, unilateral hydronephrosis was found in 74 (18.2%), bilateral hydronephrosis in 11 (2.7%), and no hydronephoris in 321 (79.1%). Low-grade hydronephrosis was found in 57 (12.2%) patients and high-grade hydronephrosis in 28 (6%). Preoperative hydronephrosis was related to higher pT stage and lymph node invasion. In univariate analysis, the presence of hydronephrosis, hydronephrosis grade, age, pT and pN stage, tumor grade, surgical margin, number of retrieved nodes, carcinoma in situ, and lymphovascular invasion were significant prognostic factors for cancer-specific survival. In multivariate analysis, bilateral hydronephrosis and high-grade hydronephrosis remained significant predictors for decreased survival. The presence of preoperative hydronephrosis, and high-grade hydronephrosis are significant prognostic factors in patients with bladder cancer after radical cystectomy. PMID:20191034

Prognostic Value of the New Prostate Cancer International Society of Urological Pathology Grade Groups.

PubMed

Offermann, Anne; Hohensteiner, Silke; Kuempers, Christiane; Ribbat-Idel, Julika; Schneider, Felix; Becker, Finn; Hupe, Marie Christine; Duensing, Stefan; Merseburger, Axel S; Kirfel, Jutta; Reischl, Markus; Lubczyk, Verena; Kuefer, Rainer; Perner, Sven

2017-01-01

Gleason grading is the best independent predictor for prostate cancer (PCa) progression. Recently, a new PCa grading system has been introduced by the International Society of Urological Pathology (ISUP) and is recommended by the World Health Organization (WHO). Following studies observed more accurate and simplified grade stratification of the new system. Aim of this study was to compare the prognostic value of the new grade groups compared to the former Gleason Grading and to determine whether re-definition of Gleason Pattern 4 might reduce upgrading from prostate biopsy to radical prostatectomy (RP) specimen. A cohort of men undergoing RP from 2002 to 2015 at the Hospital of Goeppingen (Goeppingen, Germany) was used for this study. In total, 339 pre-operative prostatic biopsies and corresponding RP specimens, as well as additional 203 RP specimens were re-reviewed for Grade Groups according to the ISUP. Biochemical recurrence-free survival (BFS) after surgery was used as endpoint to analyze prognostic significance. Other clinicopathological data included TNM-stage and pre-operative PSA level. Kaplan-Meier analysis revealed risk stratification of patients based on both former Gleason Grading and ISUP Grade Groups, and was statistically significant using the log-rank test ( p  < 0.001). Both grading systems significantly correlated with TNM-stage and pre-operative PSA level ( p  < 0.001). Higher tumor grade in RP specimen compared to corresponding pre-operative biopsy was observed in 44 and 34.5% of cases considering former Gleason Grading and ISUP Grade Groups, respectively. Both, former Gleason Grading and ISUP Grade Groups predict survival when applied on tumors in prostatic biopsies as well as RP specimens. This is the first validation study on a large representative German community-based cohort to compare the former Gleason Grading with the recently introduced ISUP Grade Groups. Our data indicate that the ISUP Grade Groups do not improve predictive

Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL Nephrometry score.

PubMed

Kutikov, Alexander; Smaldone, Marc C; Egleston, Brian L; Manley, Brandon J; Canter, Daniel J; Simhan, Jay; Boorjian, Stephen A; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

2011-08-01

Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology. We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features. We retrospectively queried Fox Chase Cancer Center's prospectively maintained database for consecutive renal masses where a Nephrometry score was available. All patients in the cohort underwent either partial or radical nephrectomy. The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors. Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p < 0.0001) and histology (p < 0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study. The current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Endometrial stromal tumors: the new WHO classification.

PubMed

Conklin, Christopher M J; Longacre, Teri A

2014-11-01