WorldWideScience

Sample records for strong independent prognostic

  1. Complex karyotype in mantle cell lymphoma is a strong prognostic factor for the time to treatment and overall survival, independent of the MCL international prognostic index.

    Science.gov (United States)

    Sarkozy, Clémentine; Terré, Christine; Jardin, Fabrice; Radford, Isabelle; Roche-Lestienne, Catherine; Penther, Dominique; Bastard, Christian; Rigaudeau, Sophie; Pilorge, Sylvain; Morschhauser, Franck; Bouscary, Didier; Delarue, Richard; Farhat, Hassan; Rousselot, Philippe; Hermine, Olivier; Tilly, Hervé; Chevret, Sylvie; Castaigne, Sylvie

    2014-01-01

    Mantle cell lymphoma (MCL) is usually an aggressive disease. However, a few patients do have an "indolent" evolution (iMCL) defined by a long survival time without intensive therapy. Many studies highlight the prognostic role of additional genetic abnormalities, but these abnormalities are not routinely tested for and do not yet influence the treatment decision. We aimed to evaluate the prognostic impact of these additional abnormalities detected by conventional cytogenetic testing, as well as their relationships with the clinical characteristics and their value in identifying iMCL. All consecutive MCL cases diagnosed between 1995 and 2011 at four institutions were retrospectively selected on the basis of an informative karyotype with a t(11;14) translocation at the time of diagnosis. A total of 125 patients were included and followed for an actual median time of 35 months. The median overall survival (OS) and survival without treatment (TFS) were 73.7 and 1.3 months, respectively. In multivariable Cox models, a high mantle cell lymphoma international prognostic index score, a complex karyotype, and blastoid morphology were independently associated with a shortened OS. Spleen enlargement, nodal presentation, extra-hematological involvement, and complex karyotypes were associated with shorter TFS. A score based on these factors allowed for the identification of "indolent" patients (median TFS 107 months) from other patients (median TFS: 1 month). In conclusion, in this multicentric cohort of MCL patients, a complex karyotype was associated with a shorter survival time and allowed for the identification of iMCL at the time of diagnosis. Copyright © 2013 Wiley Periodicals, Inc.

  2. Improving Prognostic Web Calculators: Violation of Preferential Risk Independence.

    Science.gov (United States)

    Alemi, Farrokh; Levy, Cari; Citron, Bruce A; Williams, Arthur R; Pracht, Etienne; Williams, Allison

    2016-12-01

    Web-based applications are available for prognostication of individual patients. These prognostic models were developed for groups of patients. No one is the average patient, and using these calculators to inform individual patients could provide misleading results. This article gives an example of paradoxical results that may emerge when indices used for prognosis of the average person are used for care of an individual patient. We calculated the expected mortality risks of stomach cancer and its associated comorbidities. Mortality risks were calculated using data from 140,699 Veterans Administration nursing home residents. On average, a patient with hypertension has a higher risk of mortality than one without hypertension. Surprisingly, among patients with lung cancer, hypertension is protective and reduces risk of mortality. This paradoxical result is explained by how group-level, average prognosis could mislead individual patients. In particular, average prognosis of lung cancer patients reflects the impact of various comorbidities that co-occur in lung cancer patients. The presence of hypertension, a relatively mild comorbidity of lung cancer, indicates that more serious comorbidities have not occurred. It is not that hypertension is protective; it is the absence of more serious comorbidities that is protective. The article shows how the presence of these anomalies can be checked through the mathematical concept of preferential risk independence. Instead of reporting average risk scores, web-based calculators may improve accuracy of predictions by reporting the unconfounded risks.

  3. Independent prognostic value of peritoneal immunocytodiagnosis in endometrial carcinoma.

    Science.gov (United States)

    Benevolo, M; Mariani, L; Vocaturo, G; Vasselli, S; Natali, P G; Mottolese, M

    2000-02-01

    Among the clinical parameters that play a pivotal role in predicting the outcome of patients with endometrial carcinoma, intraperitoneal microscopic dissemination represents an important cause of recurrences. To date, peritoneal cytology has been incorporated into the current surgical staging system (International Federation of Gynecology and Obstetrics 88), although its predictive value remains a controversial issue. In this study the authors investigated the possibility of applying immunocytochemistry (ICC) to the diagnosis of peritoneal washing (PW) aimed at improving conventional cytology and verifying the prognostic value of peritoneal malignant cells. The authors analyzed 182 PWs sampled from endometrial cancer patients. The ICC analysis was performed using two monoclonal antibodies (MAbs)--AR-3 and B72.3--that in combination recognize more than 95% of endometrial carcinomas. The presence of peritoneal-free cancer cells was identified morphologically in 27 of 182 lavages (14.8%) and ICC in 50 of 182 (27.5%), with a significant improvement (p <0.0001). Five-year survival analysis, comparing results of ICC and cytodiagnosis, demonstrated a significant decrease of disease-free survival in patients with peritoneal microscopic disease. Furthermore, multivariate analysis showed that ICC diagnosis of PWs is an independent prognostic factor. Data indicate that the use of selected MAbs allows one to identify cytologically false-negative cases, providing results that are highly predictive of a worse clinical outcome.

  4. DAPK1 as an independent prognostic marker in liver cancer

    Directory of Open Access Journals (Sweden)

    Ling Li

    2017-07-01

    Full Text Available The death-associated protein kinase 1 (DAPK1 can act as an oncogene or a tumor suppressor gene depending on the cellular context as well as external stimuli. Our study aims to investigate the prognostic significance of DAPK1 in liver cancer in both mRNA and protein levels. The mRNA expression of DAPK1 was extracted from the Gene Expression Omnibus database in three independent liver cancer datasets while protein expression of DAPK1 was detected by immunohistochemistry in our Chinese liver cancer patient cohort. The associations between DAPK1 expression and clinical characteristics were tested. DAPK1 mRNA expression was down-regulated in liver cancer. Low levels of DAPK1 mRNA were associated with shorter survival in a liver cancer patient cohort (n = 115; p = 0.041, while negative staining of DAPK1 protein was significantly correlated with shorter time to progression (p = 0.002 and overall survival (p = 0.02. DAPK1 was an independent prognostic marker for both time to progression and overall survival by multivariate analysis. Liver cancer with the b-catenin mutation has a lower DAPK1 expression, suggesting that DAPK1 may be regulated under the b-catenin pathway. In addition, we also identified genes that are co-regulated with DAPK1. DAPK1 expression was positively correlated with IRF2, IL7R, PCOLCE and ZBTB16, and negatively correlated with SLC16A3 in both liver cancer datasets. Among these genes, PCOLCE and ZBTB16 were significantly down-regulated, while SLC16A3 was significantly upregulated in liver cancer. By using connectivity mapping of these co-regulated genes, we have identified amcinonide and sulpiride as potential small molecules that could potentially reverse DAPK1/PCOLCE/ZBTB16/SLC16A3 expression. Our study demonstrated for the first time that both DAPK1 mRNA and protein expression levels are important prognostic markers in liver cancer, and have identified genes that may contribute to DAPK1-mediated liver carcinogenesis.

  5. Fractal dimension of chromatin is an independent prognostic factor for survival in melanoma

    Directory of Open Access Journals (Sweden)

    Landman Gilles

    2010-06-01

    Full Text Available Abstract Background Prognostic factors in malignant melanoma are currently based on clinical data and morphologic examination. Other prognostic features, however, which are not yet used in daily practice, might add important information and thus improve prognosis, treatment, and survival. Therefore a search for new markers is desirable. Previous studies have demonstrated that fractal characteristics of nuclear chromatin are of prognostic importance in neoplasias. We have therefore investigated whether the fractal dimension of nuclear chromatin measured in routine histological preparations of malignant melanomas could be a prognostic factor for survival. Methods We examined 71 primary superficial spreading cutaneous melanoma specimens (thickness ≥ 1 mm from patients with a minimum follow up of 5 years. Nuclear area, form factor and fractal dimension of chromatin texture were obtained from digitalized images of hematoxylin-eosin stained tissue micro array sections. Clark's level, tumor thickness and mitotic rate were also determined. Results The median follow-up was 104 months. Tumor thickness, Clark's level, mitotic rate, nuclear area and fractal dimension were significant risk factors in univariate Cox regressions. In the multivariate Cox regression, stratified for the presence or absence of metastases at diagnosis, only the Clark level and fractal dimension of the nuclear chromatin were included as independent prognostic factors in the final regression model. Conclusion In general, a more aggressive behaviour is usually found in genetically unstable neoplasias with a higher number of genetic or epigenetic changes, which on the other hand, provoke a more complex chromatin rearrangement. The increased nuclear fractal dimension found in the more aggressive melanomas is the mathematical equivalent of a higher complexity of the chromatin architecture. So, there is strong evidence that the fractal dimension of the nuclear chromatin texture is a new

  6. Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer.

    LENUS (Irish Health Repository)

    Wang, Lai Mun

    2012-02-01

    BACKGROUND: Tumor budding along the advancing front of colorectal adenocarcinoma is an early event in the metastatic process. A reproducible, prognostic budding scoring system based on outcomes in early stage colorectal cancer has not been established. DESIGN: One hundred twenty-eight T3N0M0 colorectal carcinoma patients with known outcome were identified. Tumor budding was defined as isolated tumor cells or clusters of <5 cells at the invasive tumor front. Tumor bud counts were generated in 5 regions at 200x by 2 pathologists (conventional bud count method). The median bud count per case was used to divide cases into low (median=0) and high budding (median > or =1) groups. Forty cases were reevaluated to assess reproducibility using the conventional and a novel rapid bud count method. RESULTS: Fifty-seven (45%) carcinomas had high and 71 (55%) had low budding scores. High budding was associated with an infiltrative growth pattern (P<0.0001) and lymphovascular invasion (P=0.005). Five-year cancer-specific survival was significantly poorer in high compared with low budding groups: 63% versus 91%, respectively, P<0.0001. Multivariate analysis demonstrated tumor budding to be independently prognostic (hazard ratio=4.76, P<0.001). Interobserver agreement was at least equivalent comparing the conventional to the rapid bud count methods: 87.5% agreement (kappa=0.75) versus 92.5% agreement (kappa=0.85), respectively. CONCLUSIONS: Tumor budding is a strong, reproducible, and independent prognostic marker of outcome that is easily assessed on hematoxylin and eosin slides. This may be useful for identifying the subset of T3N0M0 patients at high risk of recurrence who may benefit from adjuvant therapy.

  7. Hypoxia inducible BHLHB2 is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Wang, Weibin; Reiser-Erkan, Carolin; Michalski, Christoph W.; Raggi, Matthias C.; Quan, Liao; Yupei, Zhao; Friess, Helmut; Erkan, Mert; Kleeff, Joerg

    2010-01-01

    Research highlights: → The expression and function of BHLHB2 (DEC1/SHARP2) in pancreatic cancer is unknown. → Hypoxia and serum starvation induces BHLHB2 expression in pancreatic ductal adenocarcinoma. → BHLHB2 inhibition in pancreatic cancer cell line SU86.86 increases ED50 of gemcitabine 2.8-fold. → BHLHB2 is an independent prognostic factor in multivariable cox analysis with a hazard ratio of 2:4. -- Abstract: Aims: The cyclic adenosine monophosphate-inducible basic helix-loop-helix (bHLH) domain containing class-B2 transcriptional factor BHLHB2 is differentially expressed in a number of human malignancies. In the present study, the expression, regulation, functions and prognostic impact of BHLHB2 in pancreatic cancer were investigated. Methods: Expression analyses were carried out in tissues of the normal pancreas (n = 10) and pancreatic ductal adenocarcinoma (n = 77) as well as in eight pancreatic cancer cell lines using quantitative RT-PCR, semiquantitative immunohistochemistry, and immunoblot analyses. In vitro functional experiments were conducted using siRNA transfection, hypoxia, serum starvation, apoptosis induction with gemcitabine and actinomycin-D, and invasion assays. Survival analysis was performed using the Kaplan-Meier method. Prognostic factors were determined in a multivariable analysis using a Cox proportional hazards model. Results: BHLHB2 mRNA and protein expressions were strongly induced by hypoxia and by serum starvation in pancreatic cancer cell lines. BHLHB2 silencing with RNAi had no significant effects on growth and invasion but increased apoptosis resistance against gemcitabine by reducing caspace-3 cleavage. In BHLHB2 silenced cells the ED50 of gemcitabine increased from 13.95 ± 1.353 to 38.70 ± 5.262 nM (p < 0.05). Ex vivo, the weak/absent nuclear staining in normal pancreatic ducts and acinar cells was replaced by moderate to strong nuclear/cytoplasmic staining in PanIN lesions and pancreatic cancer cells. Patients with

  8. Hypoxia inducible BHLHB2 is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Weibin; Reiser-Erkan, Carolin; Michalski, Christoph W.; Raggi, Matthias C. [Department of Surgery, Technische Universitaet Muenchen, Munich (Germany); Quan, Liao; Yupei, Zhao [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking (China); Friess, Helmut [Department of Surgery, Technische Universitaet Muenchen, Munich (Germany); Erkan, Mert, E-mail: erkan@chir.med.tu-muenchen.de [Department of Surgery, Technische Universitaet Muenchen, Munich (Germany); Kleeff, Joerg [Department of Surgery, Technische Universitaet Muenchen, Munich (Germany)

    2010-10-22

    Research highlights: {yields} The expression and function of BHLHB2 (DEC1/SHARP2) in pancreatic cancer is unknown. {yields} Hypoxia and serum starvation induces BHLHB2 expression in pancreatic ductal adenocarcinoma. {yields} BHLHB2 inhibition in pancreatic cancer cell line SU86.86 increases ED50 of gemcitabine 2.8-fold. {yields} BHLHB2 is an independent prognostic factor in multivariable cox analysis with a hazard ratio of 2:4. -- Abstract: Aims: The cyclic adenosine monophosphate-inducible basic helix-loop-helix (bHLH) domain containing class-B2 transcriptional factor BHLHB2 is differentially expressed in a number of human malignancies. In the present study, the expression, regulation, functions and prognostic impact of BHLHB2 in pancreatic cancer were investigated. Methods: Expression analyses were carried out in tissues of the normal pancreas (n = 10) and pancreatic ductal adenocarcinoma (n = 77) as well as in eight pancreatic cancer cell lines using quantitative RT-PCR, semiquantitative immunohistochemistry, and immunoblot analyses. In vitro functional experiments were conducted using siRNA transfection, hypoxia, serum starvation, apoptosis induction with gemcitabine and actinomycin-D, and invasion assays. Survival analysis was performed using the Kaplan-Meier method. Prognostic factors were determined in a multivariable analysis using a Cox proportional hazards model. Results: BHLHB2 mRNA and protein expressions were strongly induced by hypoxia and by serum starvation in pancreatic cancer cell lines. BHLHB2 silencing with RNAi had no significant effects on growth and invasion but increased apoptosis resistance against gemcitabine by reducing caspace-3 cleavage. In BHLHB2 silenced cells the ED50 of gemcitabine increased from 13.95 {+-} 1.353 to 38.70 {+-} 5.262 nM (p < 0.05). Ex vivo, the weak/absent nuclear staining in normal pancreatic ducts and acinar cells was replaced by moderate to strong nuclear/cytoplasmic staining in PanIN lesions and pancreatic cancer

  9. Preoperative plasma TIMP-1 is an independent prognostic indicator in patients with primary colorectal cancer

    DEFF Research Database (Denmark)

    Birgisson, Helgi; Nielsen, Hans J.; Christensen, Ib Jarle

    2010-01-01

    Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent...

  10. Hemoglobin as an independent prognostic factor in the radiotherapy of head and neck tumors

    International Nuclear Information System (INIS)

    Schaefer, U.; Micke, O.; Mueller, S.B.; Schueller, P.; Willich, N.

    2003-01-01

    Purpose: The purpose of this study was to analyze the prognostic value of baseline hemoglobin levels before radiotherapy in patients with head and neck tumors. Patients and Methods: In a retrospective study with a median follow-up of 43 months, we analyzed the results of 214 patients irradiated for head and neck cancer between January 1, 1990 and January 1, 1998 (180 men and 34 women; median age 58 years). The treatment concept consisted in adjuvant radiotherapy in 58 patients, 77 patients received definitive radiochemotherapy, 42 patients definitive radiotherapy, and 37 patients reirradiation for in-field recurrence. Baseline hemoglobin values were divided in four groups of the same patient number (quartiles). Several known prognostic factors like sex, tumor stage, histologic grading, performance status, and treatment scheme were analyzed for their influence on overall and event-free survival and correlated with pretreatment hemoglobin values (Kaplan-Meier method). In addition, univariate und multivariate logistic regression analyses were carried out to evaluate the effect of baseline hemoglobin on response rates. Results: The median survival (event-free survival) of all patients amounted to 15 months (10 months). 25%, 50%, and 75% of patients had hemoglobin values < 11.2 g/dl, < 12.7 g/dl, and < 13.9 g/dl, respectively. In the univariate analysis, the following variables were significant prognostic factors for overall/event-free survival (log-rank test): treatment concept (p < 0.001/ p < 0.001), tumor stage (p < 0.001/p < 0.001), general condition (p < 0.001/p < 0.001), and pretreatment hemoglobin (p = 0.014/p = 0.05). Multivariate analysis (Cox) proved these parameters to be independent of each other. In addition, response rate after radiation showed a strong association between hemoglobin and local control probability (p = 0.02). Conclusion: In this retrospective analysis, baseline hemoglobin level was shown to be an independent significant prognostic factor in

  11. Modified Masaoka stage and size are independent prognostic predictors in thymoma and modified Masaoka stage is superior to histopathologic classifications.

    Science.gov (United States)

    Roden, Anja C; Yi, Eunhee S; Jenkins, Sarah M; Edwards, Kelly K; Donovan, Janis L; Cassivi, Stephen D; Marks, Randolph S; Garces, Yolanda I; Aubry, Marie Christine

    2015-04-01

    The prognostic value of histopathologic classifications of thymoma is debated. Problematic reproducibility might cause this controversy. We studied the prognostic significance of three histopathologic classifications of thymomas after three thoracic pathologists agreed upon thymoma subtype and invasion. We also compared the outcome to established prognostic parameters. Patients, surgically treated for thymic epithelial neoplasm at Mayo Clinic (1942-2008), were staged according to the modified Masaoka staging and the recently proposed staging by Moran. Three thoracic pathologists independently classified all cases according to the World Health Organization, Bernatz, and proposed Suster and Moran classification. Only thymoma that all three pathologists diagnosed as the same histopathologic subtype and extent of invasion were included in outcome analysis. In 214 (proposed Suster and Moran classification), 145 (World Health Organization classification), and 120 cases (Bernatz classification), reviewers agreed upon subtype of thymoma and invasion and follow-up was available. Median follow-up time was 7.5-7.7 years (range between classifications). All histopathologic classifications were associated with overall survival (OS) and disease-free survival (p ≤ 0.0001 to p = 0.048); only Bernatz classification was independent of modified Masaoka staging associated with OS (p = 0.04). Modified Masaoka stage predicted outcome independent of all histopathologic classifications and resection status and strongly correlated with the proposed Moran stage (correlation coefficient, 0.95). Thymoma size and age were prognostic parameters for OS independent of any histopathologic classification. Histopathologic classifications of thymomas are associated with prognosis but are in general not independent predictors of outcome. Modified Masaoka stage and proposed Moran staging are independent prognostic parameters for thymoma and superior to histopathologic classifications.

  12. RECK is not an independent prognostic marker for breast cancer

    International Nuclear Information System (INIS)

    Gomes, Luciana R.; Fujita, André; Mott, Joni D.; Soares, Fernando A.; Labriola, Leticia; Sogayar, Mari C.

    2015-01-01

    The REversion-inducing Cysteine-rich protein with Kazal motif (RECK) is a well-known inhibitor of matrix metalloproteinases (MMPs) and cellular invasion. Although high expression levels of RECK have already been correlated with a better clinical outcome for several tumor types, its main function, as well as its potential prognostic value for breast cancer patients, remain unclear. The RECK expression profile was investigated in a panel of human breast cell lines with distinct aggressiveness potential. RECK functional analysis was undertaken using RNA interference methodology. RECK protein levels were also analyzed in 1040 cases of breast cancer using immunohistochemistry and tissue microarrays (TMAs). The association between RECK expression and different clinico-pathological parameters, as well as the overall (OS) and disease-free (DFS) survival rates, were evaluated. Higher RECK protein expression levels were detected in more aggressive breast cancer cell lines (T4-2, MDA-MB-231 and Hs578T) than in non-invasive (MCF-7 and T47D) and non-tumorigenic (S1) cell lines. Indeed, silencing RECK in MDA-MB-231 cells resulted in elevated levels of pro-MMP-9 and increased invasion compared with scrambled (control) cells, without any effect on cell proliferation. Surprisingly, by RECK immunoreactivity analysis on TMAs, we found no association between RECK positivity and survival (OS and DFS) in breast cancer patients. Even considering the different tumor subtypes (luminal A, luminal B, Her2 type and basal-like) or lymph node status, RECK remained ineffective for predicting the disease outcome. Moreover, by multivariate Cox regression analysis, we found that RECK has no prognostic impact for OS and DFS, relative to standard clinical variables. Although it continues to serve as an invasion and MMP inhibitor in breast cancer, RECK expression analysis is not useful for prognosis of these patients

  13. Expression of FXYD-3 is an Independent Prognostic Factor in Rectal Cancer Patients With Preoperative Radiotherapy

    International Nuclear Information System (INIS)

    Loftas, Per; Onnesjoe, Sofia; Widegren, Emma; Adell, Gunnar; Kayed, Hany; Kleeff, Joerg; Zentgraf, Hanswalter; Sun Xiaofeng

    2009-01-01

    Purpose: FXYD-3 (MAT-8) is overexpressed in several types of cancers; however, its clinical relevance in rectal cancers has not been studied. Therefore, we examined FXYD-3 expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative radiotherapy (RT) to determine whether FXYD-3 was overexpressed in rectal cancers and correlated with RT, survival, and other clinicopathologic variables. Methods and Materials: The study included 140 rectal cancer patients who participated in a clinical trial of preoperative RT, 65 with and 75 without RT before surgery. FXYD-3 expression was immunohistochemically examined in distant (n = 70) and adjacent (n = 101) normal mucosa, primary tumors (n = 140), and lymph node metastasis (n = 36). Results: In the whole cohort, strong FXYD-3 expression was correlated with infiltrative tumor growth (p = 0.02). In the RT group, strong FXYD-3 expression alone (p = 0 .02) or combined with phosphatase of regenerating liver was associated with an unfavorable prognosis (p = 0.02), independent of both TNM stage and tumor differentiation. In tumors with strong FXYD-3 expression, there was less tumor necrosis (p = 0.02) and a trend toward increased incidence of distant metastasis (p = 0.08) after RT. None of these effects was seen in the non-RT group. FXYD-3 expression in the primary tumors tended to be increased compared with normal mucosa regardless of RT. Conclusion: FXYD-3 expression was a prognostic factor independent of tumor stage and differentiation in patients receiving preoperative RT for rectal cancer.

  14. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer.

    Directory of Open Access Journals (Sweden)

    Stefanie Aust

    Full Text Available Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC. Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs ascertained by pre-operative computed tomography (CT. Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients.We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient's outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis.Muscle attenuation (MA-a well established BCM parameter-is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028. Low MA-reflecting a state of cachexia-is also associated with residual tumor after cytoreductive surgery (p = 0.046 and with an unfavorable performance status (p = 0.015. Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively.MA-ascertained by routine pre-operative CT-is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA.

  15. Hypoalbuminemia is an independent prognostic factor for overall survival in myelodysplastic syndromes.

    Science.gov (United States)

    Komrokji, Rami S; Corrales-Yepez, Maria; Kharfan-Dabaja, Mohamed A; Al Ali, Najla H; Padron, Eric; Rollison, Dana E; Pinilla-Ibarz, Javier; Zhang, Ling; Epling-Burnette, Pearlie K; Lancet, Jeffrey E; List, Alan F

    2012-11-01

    We hypothesized that hypoalbuminemia is an independent prognostic factor in patients with myelodysplastic syndromes (MDS). We analyzed records of 767 patients treated at Moffitt Cancer Center between January 2001 and December 2009 to evaluate the relationship between serum albumin (SA) at the time of presentation and overall survival (OS). Patients (median age of 69 years) were stratified into three groups based on SA concentration (≤3.5, 3.6-4.0, and >4.0 g/dL). Two-thirds of the patients had low or intermediate-1 International Prognostic Scoring System (IPSS)-based risk for MDS. Median OS by SA concentration of ≤3.5, 3.6-4.0, and >4.0 g/dL was 11, 23, and 34 months, respectively (P < 0.005), whereas rate of acute myeloid leukemia progression was highest in patients with low SA (≤3.5 g/dL). The SA level offered prognostic discrimination for outcomes within the lower and higher IPSS risk groups, as well as with the MD Anderson risk model. In multivariable analysis, SA was a significant independent co-variate for OS after adjustment for IPSS, age, serum ferritin, and transfusion dependence (hazard ratio = 0.8; 95% CI 0.6-0.9; P = 0.004). Our findings indicate that hypoalbuminemia is an independent prognostic biomarker that may serve as a surrogate representative of disease biology or comorbidities in patients with MDS. Copyright © 2012 Wiley Periodicals, Inc.

  16. Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC

    DEFF Research Database (Denmark)

    Strell, Carina; Norberg, Karin Jessica; Mezheyeuski, Artur

    2017-01-01

    Background:The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness.Methods:We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases...... of ampullary adenocarcinoma (AAC) for HMGA2 expression by IHC. The data were correlated with stroma abundance and supplemented by experimental studies.Results:HMGA2 acts as an independent prognostic marker associated with a significantly shorter overall survival in both tumour types. Overall, HMGA2-positivity...... expression. Furthermore, in vitro treatment of Panc-1 with conditioned media from PDGF-BB-activated stellate cells increased their ability to form tumour spheroids.Conclusions:This study identifies HMGA2 expression in tumour cells as an independent prognostic marker in PDAC and AAC. Correlative data analysis...

  17. Nuclear Expression of Snail Is an Independent Negative Prognostic Factor in Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    S. Muenst

    2013-01-01

    Full Text Available Background. Snail is a key regulator of epithelial-mesenchymal transition of tumor cells. Several studies have shown nuclear Snail expression to be a negative prognostic factor in human cancer, where it is generally associated with more aggressive tumor behavior and worse survival. Objectives and Methods. To further explore the role of Snail expression in breast cancer, we conducted a study on a tissue microarray, encompassing 1043 breast cancer cases. Results. A total of 265 (25.4% breast cancers were positive for Snail. Snail expression was significantly associated with greater tumor size, higher tumor stage and grade, positive lymph node status, and hormone receptor negative status and was differently expressed in the intrinsic subtypes of breast cancer, being the highest in the basal-like subtype and the lowest in the luminal A subtype. In multivariate analysis, Snail proved to be an independent negative prognostic factor for OS. In the intrinsic subtypes, Snail expression was a negative prognostic factor for OS in the luminal B HER2−, the luminal B HER2+, and the basal-like subtype. Conclusions. This is the first study demonstrating that nuclear Snail expression is an independent negative predictor of prognosis in breast cancer, thus suggesting that it may represent a potential therapeutic target.

  18. Glucose transporter-1 as an independent prognostic marker for cancer: a meta-analysis

    Science.gov (United States)

    Zhao, Zheng-Xiao; Lu, Lin-Wei; Qiu, Jian; Li, Qiu-Ping; Xu, Fei; Liu, Bao-Jun; Dong, Jing-Cheng; Gong, Wei-Yi

    2018-01-01

    Objective Glucose transporter-1 (GLUT-1) as the major glucose transporter present in human cells is found overexpressed in a proportion of human malignancies. This meta-analysis is attempted to assess the prognostic significance of GLUT-1 for survival in various cancers. Materials and Methods We conducted an electronic search using the databases PubMed, Embase and Web of Science, from inception to Oct 20th, 2016. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Results Fourty-one studies with a total of 4794 patients were included. High GLUT-1 expression was significantly associated with poorer prognosis [overall survival: HR = 1.833 (95% CI: 1.597–2.069, P GLUT-1 expression may be an independent prognostic marker to predict poor survival in various types of cancers. Further clinical trials with high quality need to be conducted to confirm our conclusion. PMID:29416806

  19. Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival.

    Directory of Open Access Journals (Sweden)

    Marte Eilertsen

    Full Text Available INTRODUCTION: Monocarboxylate transporters (MCTs 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS in both cancer and tumor stromal cells in NSCLC. METHODS: Tissue micro arrays (TMAs were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4. RESULTS: In univariate analyses; ↓ MCT1 (P = 0.021 and ↑ MCT4 (P = 0.027 expression in cancer cells, and ↑ MCT1 (P = 0.003, ↓ MCT2 (P = 0.006, ↓ MCT3 (P = 0.020 expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001, ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001, ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031 and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016 were significant independent poor prognostic markers for DSS. CONCLUSIONS: We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.

  20. Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics has received considerable attention recently as an emerging sub-discipline within SHM. Prognosis is here strictly defined as “predicting the time at...

  1. Independent radiographic prognostic factors in patients with hospital-treated community-acquired pneumonia

    International Nuclear Information System (INIS)

    Wilhelm, K.; Textor, J.; Schild, H.; Ewig, S.; Luederitz, B.; Krollmann, G.

    1999-01-01

    Purpose: To evaluate the independent prognostic impact of the chest radiograph for mortality from community-acquired pneumonia requiring hospitalization. Methods: Chest radiographs of 67 patients with hospital-treated community-acquired pneumonia were analyzed with regard to the prognostic implications of radiographic patterns, extent and density of infiltrates, and its evolution during treatment. Results: Non-survivors had a significantly higher extent of infiltrates (p=0.008), density of infiltrates (p=0.05), and radiographic spread during follow-up within 48-72 hours (p=0.0001). In multivariate analysis, persistent or progressive infiltrates were associated with a 47fold increase, and persistent or progressive density of infiltrates with an 18fold increase in risk of mortality. The presence of both parameters could correctly predict 96% of survivors and 90% of non-survivors. Conclusions: The chest radiograph is an independent predictor of the severity of pneumonia. Both persistent or progressive infiltrates and persistent or progressive density of infiltrates are independently associated with mortality from community-acquired pneumonia. (orig.) [de

  2. Comorbidity as an independent prognostic factor in elderly patients with peripheral T-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Zhao H

    2016-03-01

    Full Text Available Haifeng Zhao,1,* Tengteng Wang,1,* Yafei Wang,1 Yong Yu,1 Xiaofan Wang,1 Zhigang Zhao,1 Hongliang Yang,1 Bei Yan,2 Xiaoxiong Wu,2 Wanming Da,3 Yizhuo Zhang1,* 1Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 2Department of Hematology, First Affiliated Hospital of Chinese People’s Liberation Army General Hospital, 3Department of Hematology, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of the present study was to investigate the role of comorbidities in the outcomes of patients with peripheral T-cell lymphoma (PTCL in a Chinese population. Fifty-six newly diagnosed PTCL patients aged >60 years were enrolled in our institution between April 2008 and August 2014. Medical record details including clinical parameters, pathological status, and treatment were reviewed. Prognostic factors were assessed using univariate and multivariate analyses. Forty-one (73.2% patients with PTCL, not otherwise specified (PTCL-NOS, nine (16.1% with angioimmunoblastic T-cell lymphoma, and six (10.7% with anaplastic large cell lymphoma were recruited in this study. Twenty-eight (50% had at least one comorbidity. Univariate analysis showed that an Eastern Cooperative Oncology Group score of 2–4, the presence of B symptoms, an International Prognostic Index (IPI score of 3–5, and a Charlson Comorbidity Index (CCI score ≥2 were significantly associated with shortened overall survival (OS, whereas the presence of B symptoms, an IPI of 3–5, and a CCI ≥2 were associated with worsened progression-free survival (PFS. Multivariate analysis indicated that a high CCI (≥2 and a high IPI (3–5 were poor independent prognostic factors for OS and PFS in the elderly patients with PTCL. Comorbidity was identified as a new

  3. An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation.

    Science.gov (United States)

    Candido Dos Reis, Francisco J; Wishart, Gordon C; Dicks, Ed M; Greenberg, David; Rashbass, Jem; Schmidt, Marjanka K; van den Broek, Alexandra J; Ellis, Ian O; Green, Andrew; Rakha, Emad; Maishman, Tom; Eccles, Diana M; Pharoah, Paul D P

    2017-05-22

    PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in 'step' changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status. Multivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT. In the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease. The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age

  4. Hypoxia Marker GLUT-1 (Glucose Transporter 1) is an Independent Prognostic Factor for Survival in Bladder Cancer Patients Treated with Radical Cystectomy.

    Science.gov (United States)

    Boström, P J; Thoms, J; Sykes, J; Ahmed, O; Evans, A; van Rhijn, B W G; Mirtti, T; Stakhovskyi, O; Laato, M; Margel, D; Pintilie, M; Kuk, C; Milosevic, M; Zlotta, A R; Bristow, R G

    2016-01-07

    Tumour hypoxia, which is frequent in many cancer types, is associated with treatment resistance and poor prognosis. The role of hypoxia in surgically treated bladder cancer (BC) is not well described. We studied the role of hypoxia in two independent series of urothelial bladder cancers treated with radical cystectomy. 279 patients from the University Hospital Network (UHN), Toronto, Canada, and Turku University, Finland were studied. Hypoxia biomarkers (HIF1-α, CAIX, GLUT-1) and proliferation marker Ki-67 were analyzed with immunohistochemistry using defined tissue microarrays. Kaplan-Meier methods and Cox proportional hazards regression models were used to investigate prognostic role of the factors. In univariate analyses, strong GLUT-1 positivity and a high Ki-67 index were associated with poor survival. In multivariate model containing clinical prognostic variables, GLUT-1 was an independent prognostic factor associated with worse disease-specific survival (HR 2.9, 95% CI 0.7-12.6, Wald p  = 0.15 in the Toronto cohort and HR 3.2, 95% CI 1.3-7.5, Wald p  = 0.0085 in the Turku cohort). GLUT-1 is frequently upregulated and is an independent prognostic factor in surgically treated bladder cancer. Further studies are needed to evaluate the potential role of hypoxia-based and targeted therapies in hypoxic bladder tumours.

  5. Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Katherine J.; Patrick, Denis R.; Bissell, Mina J.; Fournier, Marcia V.

    2008-10-20

    One of the major tenets in breast cancer research is that early detection is vital for patient survival by increasing treatment options. To that end, we have previously used a novel unsupervised approach to identify a set of genes whose expression predicts prognosis of breast cancer patients. The predictive genes were selected in a well-defined three dimensional (3D) cell culture model of non-malignant human mammary epithelial cell morphogenesis as down-regulated during breast epithelial cell acinar formation and cell cycle arrest. Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasets having 295, 286, and 118 samples, respectively. Our results show that the 3D-signature accurately predicts prognosis in three unrelated patient datasets. At 10 years, the probability of positive outcome was 52, 51, and 47 percent in the group with a poor-prognosis signature and 91, 75, and 71 percent in the group with a good-prognosis signature for the three datasets, respectively (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5 (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI 1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately predicts breast cancer outcome in both ER-positive and ER-negative tumors, though individual genes differed in their prognostic ability in the two subtypes. Genes that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and VRK1, while genes prognostic in ER patients include ACTB, FOXM1 and SERPINE2 (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest dataset showed that the 3D-signature was a strong independent factor in predicting breast cancer outcome. The 3D-signature accurately predicts breast cancer outcome across multiple datasets and holds prognostic

  6. The Prostaglandin EP3 Receptor Is an Independent Negative Prognostic Factor for Cervical Cancer Patients.

    Science.gov (United States)

    Heidegger, Helene; Dietlmeier, Sebastian; Ye, Yao; Kuhn, Christina; Vattai, Aurelia; Aberl, Caroline; Jeschke, Udo; Mahner, Sven; Kost, Bernd

    2017-07-19

    We know that one of the main risk factors for cervical cancer is an infection with high-risk human papillomavirus (HR-HPV). Prostaglandins and their receptors are very important for the tumour growth and tumour-associated angiogenesis. Little is known about the expression of the Prostaglandin E receptor type 3 (EP3) or the Prostaglandin (PG)E₂-EP3 signalling in cervical cancer, so the aim of the study was to analyse the expression of the EP3 receptor in cervical cancer and find prognostic factors in relation to survival; EP3 immunohistological staining of 250 cervical cancer slides was performed and analysed with a semi-quantitative score. The statistical evaluation was performed with Statistical Package for the Social Sciences (SPSS) to evaluate the staining results and the survival analyses of the cervical cancer cases. A significant difference was observed in EP3 expression in Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stadium I versus FIGO stadium II-IV cases. High expression of EP3 (IRS ≥ 1.5) in cervical cancer patients was correlated with poor prognosis in overall survival rates. Survival in adenocarcinoma (AC) of the cervix was lower than in squamous cell carcinoma (SCC). Cox regression analysis shows that EP3 is an independent prognosticator. In this study we could show that the membrane-bound prostaglandin receptor EP3 is an independent prognosticator for cervical cancer patient survival. Targeting the EP3 receptor seems to be an interesting candidate for endocrine therapy. Therefore, more research is needed on the influence of the receptor system and its influence on cervical cancer growth.

  7. HLA-DR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients.

    Science.gov (United States)

    Dunne, Margaret R; Michielsen, Adriana J; O'Sullivan, Katie E; Cathcart, Mary Clare; Feighery, Ronan; Doyle, Brendan; Watson, Jenny A; O'Farrell, Naoimh J; Ravi, Narayanasamy; Kay, Elaine; Reynolds, John V; Ryan, Elizabeth J; O'Sullivan, Jacintha

    2017-07-01

    Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis, and incidence is increasing rapidly in the Western world. Measurement of immune markers has been shown to have prognostic significance in a growing number of cancers, but whether this is true for EAC has yet to be evaluated. This study aimed to characterize HLA-DR expression in the esophagus across the inflammation to cancer progression sequence and to assess the prognostic significance of HLA-DR expression in EAC. Tissue microarrays (TMA) were constructed from esophageal tissue taken from patients at different stages in the cancer progression sequence; normal, esophagitis, Barrett's esophagus (BE), low- and high-grade dysplasia (LGD, HGD) and EAC. HLA-DR expression in tissue epithelium and stroma was assessed by immunohistochemistry. HLA-DR expression increased early in the inflammation to cancer progression sequence; with higher expression detected in esophagitis and BE compared to normal tissue. Patients with low (HLA-DR expression in the EAC tumor epithelium had significantly worse survival outcomes, compared to those with high expression, in both the tumor core (hazard ratio, HR = 2.178, p = 0.024, n = 70) and leading edge (HR = 2.86, p = 0.013, n = 41). Multivariate analysis demonstrated that low HLA-DR expression in leading edge tumor epithelium was an independent predictor of poor survival, associated with a 2.8-fold increase in disease-associated death (p = 0.023). This study shows that HLA-DR is an independent prognostic marker in EAC tumor epithelium. This may have implications for patient stratification strategies as well as EAC tumor immunology.

  8. Left laterality is an independent prognostic factor for metastasis in N3 stage breast cancer.

    Science.gov (United States)

    Karatas, Fatih; Sahin, Sanja; Erdem, Gokmen U; Ates, Ozturk; Babacan, Taner; Akin, Serkan; Sever, Ali R; Ozisik, Yavuz; Altundag, Kadri

    2016-01-01

    Development of metastasis in patients with breast cancer (BC) is the most important negative prognostic factor and this process mainly begins with lymphatic involvement. Therefore, axillary, subclavicular, internal mammary or supraclavicular nodal involvement is a crucial step before metastasis. Anatomical differences between the right and left lymphatic drainages of the breasts may significantly affect the rate, site and time to development of distant metastasis. The purpose of this study was to investigate if laterality is an independent prognostic factor for metastasis in N3 breast cancer patients. From a total of 4215 BC patients diagnosed between 1994 and 2015 in our center, 305 non-metastatic women with pathological N3 (pN3) nodal status at presentation were enrolled in this study. Patients were divided into two groups: left and right BC. Analysis of overall survival (OS) and time to first metastasis (TTM) was performed according to Kaplan-Meier method with log-rank test. The median number of lymph node involvement and lymph node ratio (number of positive lymph nodes / total number of excised lymph nodes) between the two groups was equal (14 and 0,66 respectively). Recurrence was observed in 123 patients [53 (35%) right vs 70 (44%) left group]. Patients with left BC had significantly higher rate of axial bone metastases compared with the right BC group (55.7 vs 35.8%, p<0.02, respectively). TTM was significantly shorter in the left BC group [49.1 months (95% CI 36.5-61.8) vs 103.6 months (95% CI 47.0-160); p7equals;0.03, respectively]. Median OS did not differ between the groups, however, there was a trend towards lower OS in patients with left BC (p=0.68). Left laterality in patients with pN3 non-metastatic BC is an independent prognostic factor associated with shorter TTM, increased risk of distant metastases and axial bone involvement compared with right laterality.

  9. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target

    International Nuclear Information System (INIS)

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo JA; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-01-01

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression. The online version of this article (doi:10.1186/s12885-015-1450-3) contains supplementary material, which is available to authorized users

  10. Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC.

    Science.gov (United States)

    Strell, Carina; Norberg, Karin Jessica; Mezheyeuski, Artur; Schnittert, Jonas; Kuninty, Praneeth R; Moro, Carlos Fernández; Paulsson, Janna; Schultz, Nicolai Aagaard; Calatayud, Dan; Löhr, Johannes Matthias; Frings, Oliver; Verbeke, Caroline Sophie; Heuchel, Rainer Lothar; Prakash, Jai; Johansen, Julia Sidenius; Östman, Arne

    2017-06-27

    The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness. We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases of ampullary adenocarcinoma (AAC) for HMGA2 expression by IHC. The data were correlated with stroma abundance and supplemented by experimental studies. HMGA2 acts as an independent prognostic marker associated with a significantly shorter overall survival in both tumour types. Overall, HMGA2-positivity was more frequent in patients with PDAC than with AAC. The HMGA2 status in tumour cells significantly correlated with the abundance of PDGFRβ-defined stroma cells. In vivo co-injection of Panc-1 cancer cells with pancreatic stellate cells increased tumour growth in a manner associated with increased HMGA2 expression. Furthermore, in vitro treatment of Panc-1 with conditioned media from PDGF-BB-activated stellate cells increased their ability to form tumour spheroids. This study identifies HMGA2 expression in tumour cells as an independent prognostic marker in PDAC and AAC. Correlative data analysis gives novel tissue-based evidence for a heterotypic cross-talk with stroma cells as a possible mechanism for HMGA2 induction, which is further supported by experimental models.

  11. Concurrent deletion of 16q23 and PTEN is an independent prognostic feature in prostate cancer.

    Science.gov (United States)

    Kluth, Martina; Runte, Frederic; Barow, Philipp; Omari, Jazan; Abdelaziz, Zaid M; Paustian, Lisa; Steurer, Stefan; Christina Tsourlakis, Maria; Fisch, Margit; Graefen, Markus; Tennstedt, Pierre; Huland, Hartwig; Michl, Uwe; Minner, Sarah; Sauter, Guido; Simon, Ronald; Adam, Meike; Schlomm, Thorsten

    2015-11-15

    The deletion of 16q23-q24 belongs to the most frequent chromosomal changes in prostate cancer, but the clinical consequences of this alteration have not been studied in detail. We performed fluorescence in situ hybridization analysis using a 16q23 probe in more than 7,400 prostate cancers with clinical follow-up data assembled in a tissue microarray format. Chromosome 16q deletion was found in 21% of cancers, and was linked to advanced tumor stage, high Gleason grade, accelerated cell proliferation, the presence of lymph node metastases (p Deletion was more frequent in ERG fusion-positive (27%) as compared to ERG fusion-negative cancers (16%, p deletions including phosphatase and tensin homolog (PTEN) (p deletion of 16q was linked to early biochemical recurrence independently from the ERG status (p deletion of 16q alone. Multivariate modeling revealed that the prognostic value of 16q/PTEN deletion patterns was independent from the established prognostic factors. In summary, the results of our study demonstrate that the deletion of 16q and PTEN cooperatively drives prostate cancer progression, and suggests that deletion analysis of 16q and PTEN could be of important clinical value particularly for preoperative risk assessment of the clinically most challenging group of low- and intermediated grade prostate cancers. © 2015 UICC.

  12. HES1 is an independent prognostic factor for acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Tian C

    2015-04-01

    Full Text Available Chen Tian, Yingjun Tang, Tengteng Wang, Yong Yu, Xiaofang Wang, Yafei Wang, Yizhuo ZhangKey laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of ChinaAbstract: HES1 is the target of Notch signaling which is reported to affect cell differentiation and maintain the cells in G0 phase in various tissues including the hematopoietic tissue. HES1 expression appears to be an independent prognostic factor for survival in a heterogeneous group of acute myeloid leukemia (AML patients. To better assess its significance, we analyzed HES1 expression in a group of non-core binding factor AML patients and correlated its expression with the overall survival and relapse-free survival of AML patients. First, we detected the messenger RNA expression of HES1 in 40 patients with AML by real-time polymerase chain reaction. The top 50% of AML cases with the high HES1 expression were compared with the rest of the AML cohort. Overall survival was calculated from the date of diagnosis until the date of death from any cause or until the date of final follow-up. Relapse-free survival was determined for responders from the time of diagnosis until relapse or death from any cause. We showed that the lower-expression group had a shorter overall survival time and shorter relapse-free survival time compared with those of the high-expression group (37.6±1.6 versus 54.0±1.3 months, 28.6±1.8 months versus 44.8±2.1 months, respectively, P<0.05, and Cox regression showed that HES1 was an independent prognostic factor. In all, we conclude that expression of HES1 is a useful prognostic factor for patients with non-core binding factor AML.Keywords: acute myeloid leukemia, HES1, prognostic factor

  13. PTIP associated protein 1, PA1, is an independent prognostic factor for lymphnode negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Takashi Takeshita

    Full Text Available Pax transactivation domain interacting protein (PTIP associated protein 1, PA1, was a newly found protein participating in the modulation of transactivity of nuclear receptor super family members such as estrogen receptor (ER, androgen receptor (AR and glucocorticoid receptor (GR. Breast cancer is one of the most life threatening diseases for women and has tight association with estrogen and ER. This study was performed to understand the function of PA1 in breast cancer. The expression of PA1 had been evaluated in a total of 344 primary invasive breast cancer samples and examined the relationship with clinical output, relapse free survival (RFS, breast cancer-specific survival (BCSS. PA1 expression was observed in both nucleus and cytoplasm, however, appeared mainly in nuclear. PA1 nuclear expression was correlated with postmenopausal (P = 0.0097, smaller tumor size (P = 0.0025, negative Ki67 (P = 0.02, positive AR (P = 0.049 and positive ERβ (P = 0.0020. Kaplan-Meier analysis demonstrated PA1 nuclear positive cases seemed to have a longer survival than negative ones for RFS (P = 0.023 but not for BCSS (P = 0.23. In the Cox hazards model, PA1 nuclear protein expression proved to be a significant prognostic univariate parameter for RFS (P = 0.03, but not for BCSS (P = 0.20. In addition, for those patients without lymphnode metastasis PA1 was found to be an independent prognostic factor for RFS (P = 0.025, which was verified by univariate and multivariate analyses. These investigations suggested PA1 expression could be a potential prognostic indicator for RFS in breast cancer.

  14. Reirradiation in progressive high-grade gliomas: outcome, role of concurrent chemotherapy, prognostic factors and validation of a new prognostic score with an independent patient cohort

    International Nuclear Information System (INIS)

    Scholtyssek, Felix; Kortmann, Rolf-Dieter; Müller, Klaus; Zwiener, Isabella; Schlamann, Annika; Seidel, Clemens; Meixensberger, Jürgen; Bauer, Manfred; Hoffmann, Karl-Titus; Combs, Stephanie E; Bueren, André O von

    2013-01-01

    First, to evaluate outcome, the benefit of concurrent chemotherapy and prognostic factors in a cohort of sixty-four high-grade glioma patients who underwent a second course of radiation therapy at progression. Second, to validate a new prognostic score for overall survival after reirradiation of progressive gliomas with an independent patient cohort. All patients underwent fractionated reirradiation with a median physical dose of 36 Gy. Median planned target volume was 110.4 ml. Thirty-six patients received concurrent chemotherapy consisting in 24/36 cases (67%) of carboplatin and etoposide and in 12/36 cases (33%) of temozolomide. We used the Kaplan Meier method, log rank test and proportional hazards regression analysis for statistical assessment. Median overall survival from the start of reirradiation was 7.7 ± 0.7 months. Overall survival rates at 6 and 12 months were 60 ± 6% and 24 ± 6%, respectively. Despite relatively large target volumes we did not observe any major acute toxicity. Concurrent chemotherapy did not appear to improve outcome. In contrast, female gender, young age, WHO grade III histology, favorable Karnofsky performance score and complete resection of the tumor prior to reirradiation were identified as positive prognostic factors for overall survival. We finally validated a recent suggestion for a prognostic score with our independent but small patient cohort. Our preliminary findings suggest that its ability to discriminate between different prognostic groups is limited. Outcome of our patients was comparable to previous studies. Even in case of large target volumes reirradiation seems to be feasible without observing major toxicity. The benefit of concurrent chemotherapy is still elusive. A reassessment of the prognostic score, tested in this study, using a larger patient cohort is needed

  15. MMP-1 expression has an independent prognostic value in breast cancer

    International Nuclear Information System (INIS)

    Boström, Pia; Söderström, Mirva; Vahlberg, Tero; Söderström, Karl-Ove; Roberts, Peter J; Carpén, Olli; Hirsimäki, Pirkko

    2011-01-01

    this study was the independent prognostic value of MMP-1 as well as Ki-67 and bcl-2 expression in tumour cells. Our study showed also that both tumoural and stromal MMP-1 expression is associated with breast tumour progression and poor prognosis. A significant difference of MMP-1 expression by cancer associated stromal cells in luminal A, luminal B and triple-negative breast cancer classes was also demonstrated. Please see related commentary article http://www.biomedcentral.com/1741-7015/9/95

  16. Independent prognostic value of left ventricular mass, diastolic function, and fasting plasma glucose

    DEFF Research Database (Denmark)

    Pareek, Manan; Nielsen, Mette Lundgren; Leósdóttir, Margrét

    2016-01-01

    (LVMI), LV hypertrophy (LVH), averaged E/é, and diastolic function graded as normal, grade 1, or grade 2 + 3 diastolic dysfunction) to a prediction model with traditional cardiovascular (CV) risk factors was assessed using Cox proportional hazards regression. Cardiac events were defined as myocardial......OBJECTIVE: To explore the independent prognostic value of left ventricular (LV) mass, diastolic function, and fasting plasma glucose (FPG) for the prediction of incident cardiac events in a random population sample. DESIGN AND METHOD: 415 women and 999 men aged 56-79 years, included between 2002...... infarction, coronary revascularization, or heart failure. RESULTS: 37 % were classified as NFG, 26 % as IFG, and 37 % as DM. Median LVMI and E/é were 86 [74-102] g/m and 8 [6-10], respectively. Over a median follow-up time of 7.8 [7.2-8.7] years, 181 events occurred. The simple prediction model included age...

  17. The histone chaperone HJURP is a new independent prognostic marker for luminal A breast carcinoma.

    Science.gov (United States)

    Montes de Oca, Rocío; Gurard-Levin, Zachary A; Berger, Frédérique; Rehman, Haniya; Martel, Elise; Corpet, Armelle; de Koning, Leanne; Vassias, Isabelle; Wilson, Laurence O W; Meseure, Didier; Reyal, Fabien; Savignoni, Alexia; Asselain, Bernard; Sastre-Garau, Xavier; Almouzni, Geneviève

    2015-03-01

    Breast cancer is a heterogeneous disease with different molecular subtypes that have varying responses to therapy. An ongoing challenge in breast cancer research is to distinguish high-risk patients from good prognosis patients. This is particularly difficult in the low-grade, ER-positive luminal A tumors, where robust diagnostic tools to aid clinical treatment decisions are lacking. Recent data implicating chromatin regulators in cancer initiation and progression offers a promising avenue to develop new tools to help guide clinical decisions. Here we exploit a published transcriptome dataset and an independent validation cohort to correlate the mRNA expression of selected chromatin regulators with respect to the four intrinsic breast cancer molecular subtypes. We then perform univariate and multivariate analyses to compare the prognostic value of a panel of chromatin regulators to Ki67, a currently utilized proliferation marker. Unsupervised hierarchical clustering revealed a gene cluster containing several histone chaperones and histone variants highly-expressed in the proliferative subtypes (basal-like, HER2-positive, luminal B) but not in the luminal A subtype. Several chromatin regulators, including the histone chaperones CAF-1 (subunits p150 and p60), ASF1b, and HJURP, and the centromeric histone variant CENP-A, associated with local and metastatic relapse and poor patient outcome. Importantly, we find that HJURP can discriminate favorable and unfavorable outcome within the luminal A subtype, outperforming the currently utilized proliferation marker Ki67, as an independent prognostic marker for luminal A patients. The integration of chromatin regulators as clinical biomarkers, in particular the histone chaperone HJURP, will help guide patient substratification and treatment options for low-risk luminal A breast carcinoma patients. Copyright © 2014. Published by Elsevier B.V.

  18. Loss of 5-Hydroxymethylcytosine Is an Independent Unfavorable Prognostic Factor for Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Shi, Xuejiao; Yu, Yue; Luo, Mei; Zhang, Zhirong; Shi, Susheng; Feng, Xiaoli; Chen, Zhaoli; He, Jie

    2016-01-01

    Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine and 5-carboxylcytosine, which result in genomic DNA demethylation. It was reported that 5-hmC levels were decreased in a variety of cancers and could be regarded as an epigenetic hallmark of cancer. In the present study, 5-hmC levels were detected by immunohistochemistry (IHC) in 173 esophageal squamous cell carcinoma (ESCC) tissues and 91 corresponding adjacent non-tumor tissues; DNA dot blot assays were used to detect the 5-hmC level in another 50 pairs of ESCC tissues and adjacent non-tumor tissues. In addition, the mRNA level of TET1, TET2 and TET3 in these 50 pairs of ESCC tissues was detected by real-time PCR. The IHC and DNA dot blot results showed that 5-hmC levels were significantly lower in ESCC tissues compared with corresponding adjacent non-tumor tissues (P = 0.029). TET2 and TET3 expression was also significantly decreased in tumor tissues compared with paired non-tumor tissues (TET2, P hmC was significantly associated with the downregulation of TET2 expression (r = 0.405, P = 0.004). Moreover, the loss of 5-hmC in ESCC tissues was significantly associated with poor overall survival among patients with ESCC (P = 0.043); multivariate Cox regression analysis showed that the loss of 5-hmC in ESCC tissues was an independent unfavorable prognostic indicator for patients with ESCC (HR = 1.569, P = 0.029). In conclusion, 5-hmC levels were decreased in ESCC tissues, and the loss of 5-hmC in tumor tissues was an independent unfavorable prognostic factor for patients with ESCC.

  19. Loss of 5-Hydroxymethylcytosine Is an Independent Unfavorable Prognostic Factor for Esophageal Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Xuejiao Shi

    Full Text Available Ten-eleven translocation (TET enzymes catalyze the oxidation of 5-methylcytosine (5-mC to 5-hydroxymethylcytosine (5-hmC, 5-formylcytosine and 5-carboxylcytosine, which result in genomic DNA demethylation. It was reported that 5-hmC levels were decreased in a variety of cancers and could be regarded as an epigenetic hallmark of cancer. In the present study, 5-hmC levels were detected by immunohistochemistry (IHC in 173 esophageal squamous cell carcinoma (ESCC tissues and 91 corresponding adjacent non-tumor tissues; DNA dot blot assays were used to detect the 5-hmC level in another 50 pairs of ESCC tissues and adjacent non-tumor tissues. In addition, the mRNA level of TET1, TET2 and TET3 in these 50 pairs of ESCC tissues was detected by real-time PCR. The IHC and DNA dot blot results showed that 5-hmC levels were significantly lower in ESCC tissues compared with corresponding adjacent non-tumor tissues (P = 0.029. TET2 and TET3 expression was also significantly decreased in tumor tissues compared with paired non-tumor tissues (TET2, P < 0.0001; TET3, P = 0.009, and the decrease in 5-hmC was significantly associated with the downregulation of TET2 expression (r = 0.405, P = 0.004. Moreover, the loss of 5-hmC in ESCC tissues was significantly associated with poor overall survival among patients with ESCC (P = 0.043; multivariate Cox regression analysis showed that the loss of 5-hmC in ESCC tissues was an independent unfavorable prognostic indicator for patients with ESCC (HR = 1.569, P = 0.029. In conclusion, 5-hmC levels were decreased in ESCC tissues, and the loss of 5-hmC in tumor tissues was an independent unfavorable prognostic factor for patients with ESCC.

  20. SIRT1 overexpression is an independent prognosticator for patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Ma, Ming-Chun; Chiu, Tai-Jan; Lu, Hung-I; Huang, Wan-Ting; Lo, Chien-Ming; Tien, Wan-Yu; Lan, Ya-Chun; Chen, Yen-Yang; Chen, Chang-Han; Li, Shau-Hsuan

    2018-04-10

    Sirtuin 1 (SIRT1) regulates DNA repair and metabolism by deacetylating target proteins. SIRT1 may be oncogenic because its overexpression has been detected in many cancers. The aim of the present study was to clarify the prognostic role of SIRT1 in patients with esophageal squamous cell carcinoma (ESCC) and evaluate the effect of SIRT1 inhibitor in vitro. The expression of SIRT1 was evaluated immunohistochemically in 155 surgically resected ESCC and the staining results were evaluated semiquantitatively by the Immunoreactive Scoring System. The clinical features and treatment outcome were analyzed. The effect of SIRT1 inhibitor, SIRT 1 inhibitor IV, (S)-35, was investigated in vitro on ESCC cell lines. The expression of SIRT1 on ESCC did not correlate with age, gender, tumor location, stage, T classification, N classification, surgical margin or histology. Univariate analysis showed that SIRT1 overexpression was associated with inferior overall survival (P = 0.004) and disease-free survival (P = 0.004). In multivariate comparison, SIRT1 overexpression remained independently associated with worse overall survival (P = 0.009, hazard ratio = 1.776) and disease-free survival (P = 0.017, hazard ratio = 1.642). In cell lines, SIRT1 inhibitor inhibited ESCC growth. Our study suggests that SIRT1 overexpression is an independent prognosticator for patients with ESCC and the SIRT1 inhibitor suppressed cell proliferation of ESCC cell lines. Our findings suggest that inhibition of SIRT1 signaling may be a promising novel target for ESCC.

  1. Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.

    Directory of Open Access Journals (Sweden)

    Patrick N Harter

    Full Text Available The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to netrin-1 expression. Therefore, the aim of our study was to elucidate the association of netrin-1 expression and patient survival in brain metastases since those constitute one of the most limiting factors for patient prognosis. We investigated 104 brain metastases cases for netrin-1 expression using in-situ hybridization and immunohistochemistry with regard to clinical parameters such as patient survival and MRI data. Our data show that netrin-1 is strongly upregulated in most cancer subtypes. Univariate analyses revealed netrin-1 expression as a significant factor associated with poor patient survival in the total cohort of brain metastasis patients and in sub-entities such as non-small cell lung carcinomas. Interestingly, many cancer samples showed a strong nuclear netrin-1 signal which was recently linked to a truncated netrin-1 variant that enhances tumor growth. Nuclear netrin-1 expression was associated with poor patient survival in univariate as well as in multivariate analyses. Our data indicate both total and nuclear netrin-1 expression as prognostic factors in brain metastases patients in contrast to other prognostic markers in oncology such as patient age, number of brain metastases or Ki67 proliferation index. Therefore, nuclear netrin-1 expression constitutes one of the first reported molecular biomarkers for patient survival in brain metastases. Furthermore, netrin-1 may constitute a promising target for future anti-cancer treatment approaches in brain metastases.

  2. Cell-associated HIV DNA measured early during infection has prognostic value independent of serum HIV RNA measured concomitantly

    DEFF Research Database (Denmark)

    Katzenstein, Terese L; Oliveri, Roberto S; Benfield, Thomas

    2002-01-01

    Using data from the Danish AIDS Cohort of HIV-infected homosexual men established in the 1980s, the prognostic value of early HIV DNA loads was evaluated. In addition to DNA measurements, concomitant serum HIV RNA levels, CD4 cell counts and CCR5 genotypes were determined. The patients were divided...... into 3 groups, according to whether their cell-associated HIV DNA load was or = 2,500 DNA copies/10(6) peripheral blood mononuclear cells. Clinical progression rates differed significantly between the groups (p HIV DNA load had prognostic value independent...... of serum HIV RNA (p HIV DNA, HIV RNA and CD4 cell counts were all included in a Cox model, only serum HIV RNA had independent prognostic value. Patients heterozygous for the CCR5 delta 32 allele had significantly lower HIV DNA loads than those homozygous for the normal allele (p

  3. Cell-associated HIV DNA measured early during infection has prognostic value independent of serum HIV RNA measured concomitantly

    DEFF Research Database (Denmark)

    Katzenstein, Terese L; Oliveri, Roberto S; Benfield, Thomas

    2002-01-01

    Using data from the Danish AIDS Cohort of HIV-infected homosexual men established in the 1980s, the prognostic value of early HIV DNA loads was evaluated. In addition to DNA measurements, concomitant serum HIV RNA levels, CD4 cell counts and CCR5 genotypes were determined. The patients were divided...... of serum HIV RNA (p HIV DNA, HIV RNA and CD4 cell counts were all included in a Cox model, only serum HIV RNA had independent prognostic value. Patients heterozygous for the CCR5 delta 32 allele had significantly lower HIV DNA loads than those homozygous for the normal allele (p ... into 3 groups, according to whether their cell-associated HIV DNA load was or = 2,500 DNA copies/10(6) peripheral blood mononuclear cells. Clinical progression rates differed significantly between the groups (p HIV DNA load had prognostic value independent...

  4. An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas

    International Nuclear Information System (INIS)

    Noske, Aurelia; Denkert, Carsten; Schwabe, Michael; Weichert, Wilko; Darb-Esfahani, Silvia; Buckendahl, Ann-Christin; Sehouli, Jalid; Braicu, Elena I; Budczies, Jan; Dietel, Manfred

    2011-01-01

    In ovarian cancer, the reported rate of EGFR expression varies between 4-70% depending on assessment method and data on patient outcome are conflicting. Methods: In this study we investigated EGFR expression and its prognostic value in a cohort of 121 invasive ovarian carcinomas, using a novel antibody against the intracellular domain of the receptor. We further evaluated an association between EGFR, the nuclear transporter CRM1 as well as COX-2. Furthermore, we evaluated EGFR expression in ten ovarian cancer cell lines and incubated cancer cells with Leptomycin B, a CRM1 specific inhibitor. We observed a membranous and cytoplasmic EGFR expression in 36.4% and 64% of ovarian carcinomas, respectively. Membranous EGFR was an independent prognostic factor for poor overall survival in ovarian cancer patients (HR 2.7, CI 1.1-6.4, p = 0.02) which was also found in the serous subtype (HR 4.6, CI 1.6-13.4, p = 0.004). We further observed a significant association of EGFR with COX-2 and nuclear CRM1 expression (chi-square test for trends, p = 0.006 and p = 0.013, respectively). In addition, combined membranous EGFR/COX-2 expression was significantly related to unfavorable overall survival (HR 7.2, CI 2.3-22.1, p = 0.001). In cell culture, we observed a suppression of EGFR protein levels after exposure to Leptomycin B in OVCAR-3 and SKOV-3 cells. Our results suggest that the EGFR/COX-2/CRM1 interaction might be involved in progression of ovarian cancer and patient prognosis. Hence, it is an interesting anti-cancer target for a combination therapy. Further studies will also be needed to investigate whether EGFR is also predictive for benefit from EGFR targeted therapies

  5. Nestin-positive microvessel density is an independent prognostic factor in breast cancer.

    Science.gov (United States)

    Nowak, Aleksandra; Grzegrzolka, Jedrzej; Paprocka, Maria; Piotrowska, Aleksandra; Rys, Janusz; Matkowski, Rafal; Dziegiel, Piotr

    2017-08-01

    The process of angiogenesis based on new vessel formation within the tumour area plays a significant role in the progression of breast cancer. Nestin is an intermediate filament protein and participates in the cytoskeleton organization. Nestin expression in the endothelium of blood vessels is mainly limited to newly forming vessels, thus being a more specific marker of angiogenesis than the commonly used vascular antigens. The aim of this study was to determine the prognostic value of nestin-positive microvessel density (Nes+MVD) in breast cancer patients and to confirm that nestin expression is related to newly forming tumour vessels. In this study, 137 cases of ductal breast carcinoma and 19 cases of non-malignant breast tissue lesions (NBTLs) were examined. Immunohistochemical reactions were performed on paraffin sections using antibodies against nestin, CD34 and CD31 antigens. For each marker, the microvessel density (MVD) was determined. Nestin expression was also examined in human endothelial cell lines (HUVEC-SVT, HMEC-1 and HEPC-CB.1) representing a different level of endothelial cell maturity. HUVEC-SVT and HMEC-1 cells represent the endothelium of mature vessels, whereas HEPC-CB.1 cells represent the early endothelial progenitor cells (EPCs). We have demonstrated that high Nes+MVD may be associated with a more aggressive course of the disease and a poorer prognosis. We have also found a higher Nes+MVD in the cases with lymph node metastases, with higher histological grade, with advanced-stage disease and with the triple-negative (TN) breast cancer. In addition, nestin expression in vessels was associated with a shorter overall survival (OS) and earlier relapse, and in the case of OS nestin was an independent prognostic factor. Finally, we further confirmed that nestin expression in endothelial cells reflects a progenitor nature of newly forming vessels.

  6. Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kristensen, Lasse Sommer; Asmar, Fazila; Dimopoulos, Konstantinos

    2014-01-01

    found that DAPK1 promoter methylation was associated with shorter overall survival (p=0.017) and disease-specific survival (p=0.023). In multivariate analyses DAPK1 methylation remained as an independent prognostic factor predicting disease-specific survival (p=0.038). When only considering individuals...

  7. Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence.

    Science.gov (United States)

    den Uil, Sjoerd H; Coupé, Veerle M H; Linnekamp, Janneke F; van den Broek, Evert; Goos, Jeroen A C M; Delis-van Diemen, Pien M; Belt, Eric J Th; van Grieken, Nicole C T; Scott, Patricia M; Vermeulen, Louis; Medema, Jan Paul; Bril, Herman; Stockmann, Hein B A C; Cormier, Robert T; Meijer, Gerrit A; Fijneman, Remond J A

    2016-12-06

    Colorectal cancer (CRC) is the third most common cancer worldwide. Accurately identifying stage II CRC patients at risk for recurrence is an unmet clinical need. KCNQ1 was previously identified as a tumour suppressor gene and loss of expression was associated with poor survival in patients with CRC liver metastases. In this study the prognostic value of KCNQ1 in stage II and stage III colon cancer patients was examined. KCNQ1 mRNA expression was assessed in 90 stage II colon cancer patients (AMC-AJCCII-90) using microarray gene expression data. Subsequently, KCNQ1 protein expression was evaluated in an independent cohort of 386 stage II and stage III colon cancer patients by immunohistochemistry of tissue microarrays. Low KCNQ1 mRNA expression in stage II microsatellite stable (MSS) colon cancers was associated with poor disease-free survival (DFS) (P=0.025). Loss of KCNQ1 protein expression from epithelial cells was strongly associated with poor DFS in stage II MSS (PKCNQ1 seemed an independent prognostic value in addition to other high-risk parameters like angio-invasion, nodal stage and microsatellite instability-status. We conclude that KCNQ1 is a promising biomarker for prediction of disease recurrence and may aid stratification of patients with stage II MSS colon cancer for adjuvant chemotherapy.

  8. Integration Pattern of Human Papillomavirus Is a Strong Prognostic Factor for Disease-Free Survival After Radiation Therapy in Cervical Cancer Patients.

    Science.gov (United States)

    Joo, Jungnam; Shin, Hye-Jin; Park, Boram; Park, Seog-Yun; Yoo, Chong-Woo; Yoon, Kyong-Ah; Kong, Sun-Young; Kim, Youn-Jae; Kim, Sang Soo; Kim, Joo-Young

    2017-07-01

    The standard chemoradiation therapy currently used for locally advanced cervical cancer (LACC) patients does not reflect the biological heterogeneity of this disease, and there is an increasing need for the development of biomarkers that can help guide the individualized treatment regimens. The purpose of this study was to investigate the prognostic value of the integration pattern of human papillomavirus (HPV) in LACC patients. The HPV integration pattern was determined by in situ hybridization and polymerase chain reaction, and the tumors were classified as the episomal pattern (group A), as the single-copy integrated or multicopy tandem repetition-integrated pattern (group B), or as undetectable HPV (group C). Ninety-eight LACC patients were included in a development dataset and 106 independent patients in a validation dataset. The multivariate Cox model was used to examine the effect of the HPV integration pattern on disease-free survival (DFS). The model was validated internally by the leave-one-out cross-validation method and externally by an independent dataset. After adjustment for significant prognostic factors (stage, histologic grade, histologic type, and tumor size), the HPV integration pattern was significantly associated with DFS in the development (P=.032) and validation (P=.023) datasets. Survival was worst in group C and best in group A. The multivariate model with HPV integration pattern as an explanatory variable showed good discrimination ability and could separate patients with different risk profiles. This study identified the HPV integration pattern, as determined by in situ hybridization and polymerase chain reaction, as a strong prognostic biomarker for DFS in LACC patients treated by chemoradiation therapy. This finding may open the possibility of personalized treatment of these patients. Copyright © 2017. Published by Elsevier Inc.

  9. Baseline metabolic tumour volume is an independent prognostic factor in Hodgkin lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kanoun, Salim; Berriolo-Riedinger, Alina; Dygai-Cochet, Inna; Cochet, Alexandre; Humbert, Olivier; Toubeau, Michel; Brunotte, Francois [Centre G.F. Leclerc, Medecine nucleaire, Dijon (France); Rossi, Cedric; Ferrant, Emmanuelle [Hopital Le Bocage - CHU Dijon, Hematologie Clinique, Dijon Cedex (France); Casasnovas, Rene-Olivier [Hopital Le Bocage - CHU Dijon, Hematologie Clinique, Dijon Cedex (France); Universite de Bourgogne, Inserm U866, Labex team, Faculte de medecine, Dijon (France)

    2014-09-15

    The presence of a bulky tumour at staging in Hodgkin lymphoma (HL) is a predictor of a poor outcome. The total metabolic tumour volume at baseline (TMTV0) computed on PET may improve the evaluation of tumour burden. To explore the clinical usefulness of TMTV0, we compared the prognostic value of TMTV0, tumour bulk and interim PET response in a retrospective single-centre study. From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. PET was done at baseline (PET0) and after two cycles of chemotherapy (PET2), and treatment was not modified according to the PET2 result. TMTV0 was measured with a semiautomatic method using a 41 % SUVmax threshold. SUVmax reduction between PET0 and PET2 (ΔSUVmaxPET0-2) was also computed. Based on ROC analysis, patients with a ΔSUVmaxPET0-2 >71 % were considered good responders and a TMTV0 >225 ml was considered to represent hypermetabolic bulky disease. Median TMTV0 was 117 ml and 17 patients (29 %) had a TMTV0 >225 ml. TMTV0 (>225 ml vs. ≤225 ml) and tumour bulk (<10 cm vs. ≥10 cm) were predictive of 4-year PFS: 42 % vs. 85 % (p = 0.001) and 44 % vs. 79 % (p < 0.03), respectively. In multivariate analysis, using ΔSUVmaxPET0-2, TMTV0 and bulky tumour as covariates, only ΔSUVmaxPET0-2 (p = 0.0005, RR 6.3) and TMTV0 (p < 0.006, RR 4.4) remained independent predictors of PFS. Three prognosis groups were thus identified: ΔSUVmaxPET0-2 >71 % and TMTV0 ≤225 ml (n = 37, 63 %), ΔSUVmaxPET0-2 = <71 % or TMTV0 >225 ml (n = 17, 29 %), and ΔSUVmaxPET0-2 = <71 % and TMTV0 >225 ml (n = 5, 8 %). In these three groups the 4-year PFS rates were 92 %, 49 %, and 20 % (p < 0.0001), respectively. TMTV0 is more relevant than tumour bulk for predicting the outcome in patients with HL, and adds a significant prognostic insight to interim PET response assessment. The combination of TMTV0 and ΔSUVmaxPET0-2 made it possible to identify three subsets of HL patients with different outcomes. This may

  10. Both GLUT-1 and GLUT-14 are Independent Prognostic Factors in Gastric Adenocarcinoma.

    Science.gov (United States)

    Berlth, Felix; Mönig, Stefan; Pinther, Berit; Grimminger, Peter; Maus, Martin; Schlösser, Hans; Plum, Patrick; Warnecke-Eberz, Ute; Harismendy, Olivier; Drebber, Uta; Bollschweiler, Elfriede; Hölscher, Arnulf; Alakus, Hakan

    2015-12-01

    The role of glucose transporter 14 (GLUT-14/SLC2A14) in tumor biology is entirely unknown, and the significance of hypoxia inducible factor 1-alpha (HIF1-α) for gastric adenocarcinoma is controversial. The impact of GLUT-1/SLC2A1 has never been confirmed in a Caucasian cohort. Between 1996 and 2007, 124 patients underwent gastrectomy for gastric adenocarcinoma. Tumor sections were incubated with GLUT-1, GLUT-14, and HIF1-α antibodies. Expression was analyzed for correlations with histopathology, marker coexpression, and patient survival by uni- and multivariate analyses. Expressions of GLUT-1, GLUT-14, and HIF1-α were detectable in 50, 77.4, and 27.1 %, respectively. Expression of GLUT-1 was associated with pT-category (p = 0.019), pN-category (p = 0.019), tubular (WHO, p = 0.008), and intestinal (Lauren classification; p = 0.002) histologic subtypes. Expression of GLUT-14 was correlated with pT category (p = 0.043), whereas HIF1-α did not show any correlation with histopathology or survival. The median survival period was 14 months (95 % confidence interval [CI] 9.2-18.8 months) for GLUT-1-positive patients and 55 months (95 % CI 25.8-84.2; p = 0.01) for GLUT-1-negative patients. An inferior prognosis also was seen for GLUT-14-positive cases compared with GLUT-14-negative cases (p = 0.004). Thus, worst survival was seen with both GLUT-1- and GLUT-14-positive expression followed by single-positive and then double-negative cases (p = 0.004). In multivariate analysis including International Union Against Cancer (UICC) stages, R category, Lauren classification, surgery alone versus neoadjuvant/perioperative chemotherapy, and marker expression as covariates, GLUT-1 (p = 0.011) and GLUT-14 (p = 0.025) kept their prognostic independence. The study findings suggest that detection of GLUT-1 and GLUT-14 is of high prognostic value. It gives additional information to UICC stages and identifies patients with inferior prognosis. If confirmed in prospective studies, these

  11. Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia.

    Science.gov (United States)

    Chisini, Marta; Stefanizzi, Caterina; Ceglie, Teresa; Raponi, Sara; Vozella, Federico; Colafigli, Gioia; Salaroli, Adriano; D'Angiò, Mariella; Mancini, Marco; Diverio, Daniela; Breccia, Massimo; Mancini, Francesca; Minotti, Clara; Trisolini, Silvia; Capria, Saveria; Testi, Anna Maria; Guarini, Anna; Latagliata, Roberto; De Propris, Maria Stefania; Foà, Robin

    2017-12-01

    The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9-81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6-176.0), with 2-year disease-free survival rate of 45.1% (95% confidence interval 39.6-50.6). The median overall survival was 14.4 months (range 0.3-177.0), with 2-year overall survival rate of 42.2% (95% confidence interval 37.5-46.9). At univariate analysis for CR achievement, age classification (P = .045), low-risk karyotype (P  8 g/dL (P = .020), and white blood cell < 50 × 10 9 /L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 × 10 9 /L (P = .017), and low-risk/no high-risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement. The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Decreased 5-hydroxymethylcytosine (5-hmC) is an independent poor prognostic factor in gastric cancer patients.

    Science.gov (United States)

    Yang, Qi; Wu, Kexia; Ji, Meiju; Jin, Weilin; He, Nongyue; Shi, Bingyin; Hou, Peng

    2013-09-01

    DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is involved in various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family of DNA hydroxylases. Increasing evidence suggests that large-scale loss of 5-hmC is an epigenetic hallmark of several human cancers. However, the value of 5-hmC in diagnosis and prognosis of human cancers, including gastric cancer (GC), remains largely unknown. The aim of this study is to determine 5-hmC levels in GCs and explore its association with clinicopathological characteristics and clinical outcome of GC patients. Using immunohistochemistry (IHC) and dot-blot assays, we demonstrated that 5-hmC was dramatically decreased in GCs compared with matched normal tissues. We also found a strong link between decreased 5-hmC and the reduction of TET1 gene expression, but not TET2 or 3, suggesting that decreased TET1 expression might be one of the mechanisms underlying 5-hmC loss in GCs. Wilcoxon tests showed that 5-hmC content was significantly associated with most of clinicopathological characteristics, such as tumor size (P = 0.016), Bormman type (P hmC was significantly associated with poor survival of GC patients. Collectively, our findings indicate that decreased 5-hmC may be crucial to the clinical pathology of GC and is a strong and independent poor prognostic factor in GCs.

  13. Enhancer of zeste homolog 2 as an independent prognostic marker for cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Shuling Chen

    Full Text Available Novel biomarkers are of particular interest for predicting cancer prognosis. This study aimed to explore the associations between enhancer of zeste homolog 2 (EZH2 and patient survival in various cancers.Relevant literature was retrieved from PubMed and Web of Science databases. Pooled hazard ratios (HRs, odds ratios (ORs, and 95% confidence intervals (CIs were calculated.Forty-nine studies (8,050 patients were included. High EZH2 expression was significantly associated with shorter overall (hazard ratio [HR] 1.74, 95% CI: 1.46-2.07, disease-free (HR 1.59, 95% CI: 1.27-1.99, metastasis-free (HR 2.19, 95% CI: 1.38-3.47, progression-free (HR 2.53, 95% CI: 1.52-4.21, cancer-specific (HR 3.13, 95% CI: 1.70-5.74, and disease-specific (HR 2.29, 95% CI: 1.56-3.35 survival, but not recurrence-free survival (HR 1.38, 95% CI: 0.93-2.06. Moreover, EZH2 expression significantly correlated with distant metastasis (OR 3.25, 95% CI: 1.07-9.87 in esophageal carcinoma; differentiation (OR 3.00, 95% CI: 1.37-6.55 in non-small cell lung cancer; TNM stage (OR 3.18, 95% CI: 2.49-4.08 in renal cell carcinoma; and histological grade (OR 4.50, 95% CI: 3.33-6.09, estrogen receptor status (OR 0.15, 95% CI: 0.11-0.20 and progesterone receptor status (OR 0.30, 95% CI: 0.23-0.39 in breast cancer.Our results suggested that EZH2 might be an independent prognostic factor for multiple survival measures in different cancers.

  14. Heavy quark mass effects and improved tests of the flavor independence of strong interactions

    Energy Technology Data Exchange (ETDEWEB)

    Burrows, P.N. [Univ. of Oxford (United Kingdom); SLD Collaboration

    1998-08-01

    A review is given of latest results on tests of the flavor independence of strong interactions. Heavy quark mass effects are evident in the data and are now taken into account at next-to-leading order in QCD perturbation theory. The strong-coupling ratios {alpha}{sub s}{sup b}/{alpha}{sub s}{sup uds} and {alpha}{sub s}{sup c}/{alpha}{sub s}{sup uds} are found to be consistent with unity. Determinations of the b-quark mass m{sub b} (M{sub Z}) are discussed.

  15. DNA methylation is an independent prognostic marker of survival in adrenocortical cancer

    NARCIS (Netherlands)

    Jouinot, Anne; Assie, Guillaume; Libe, Rossella; Fassnacht, Martin; Papathomas, Thomas; Barreau, Olivia; De La Villeon, Bruno; Faillot, Simon; Hamzaoui, Nadim; Neou, Mario; Perlemoine, Karine; Rene-Corail, Fernande; Rodriguez, Stephanie; Sibony, Mathilde; Tissier, Frederique; Dousset, Bertrand; Sbiera, Silviu; Ronchi, Cristina; Kroiss, Matthias; Korpershoek, Esther; De Krijger, Ronald; Waldmann, Jens; Bartsch, Detlef K.; Quinkler, Marcus; Haissaguerre, Magalie; Tabarin, Antoine; Chabre, Olivier; Sturm, Nathalie; Luconi, Michaela; Mantero, Franco; Mannelli, Massimo; Cohen, Regis; Kerlan, Veronique; Touraine, Philippe; Barrande, Gaelle; Groussin, Lionel; Bertagna, Xavier; Baudin, Eric; Amar, Laurence; Beuschlein, Felix; Clauser, Eric; Coste, Joel; Bertherat, Jerome

    2017-01-01

    Context: Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. Objective:

  16. Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer

    NARCIS (Netherlands)

    Oort, van I.M.; Witjes, J.A.; Kok, D.E.G.; Kiemeney, L.A.; Hulsbergen-van de Kaa, C.A.

    2008-01-01

    Previous studies suggest that maximum tumor diameter (MTD) is a predictor of recurrence in prostate cancer (PC). This study investigates the prognostic value of MTD for biochemical recurrence (BCR) in patients with PC, after radical prostatectomy (RP), with emphasis on high-risk localized prostate

  17. KRAS Status as an Independent Prognostic Factor for Survival after Yttrium-90 Radioembolization Therapy for Unresectable Colorectal Cancer Liver Metastases.

    Science.gov (United States)

    Lahti, Steven J; Xing, Minzhi; Zhang, Di; Lee, James J; Magnetta, Michael J; Kim, Hyun S

    2015-08-01

    To evaluate Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status as a prognostic factor for survival after yttrium-90 ((90)Y) radioembolization for colorectal cancer (CRC) liver metastases. Consecutive patients with unresectable CRC liver metastases and documented KRAS mutation status who were treated with (90)Y radioembolization during the period 2007-2014 were investigated. Patient demographics, disease characteristics, therapy regimens, and overall survival (OS) from first (90)Y radioembolization were compared between patients with KRAS wild-type (wt) and mutant status. Kaplan-Meier estimation and Cox regression were used for survival analysis and to assess independent prognostic factors for OS. Of 186 patients, 104 underwent KRAS mutation analysis before (90)Y radioembolization, with 45 (43.3%) identified as mutant. The wt and mutant groups were similar in demographics, liver status, overall performance status, and tumor characteristics (all P > .05). Mean time from liver metastasis to (90)Y radioembolization was greater in patients with KRAS wt status (P = .033). A greater percentage of wt patients received anti-epidermal growth factor receptor therapies before (90)Y radioembolization (66.1% vs 8.9%; P 90)Y radioembolization was significantly greater in KRAS wt patients (9.5 mo vs 4.8 mo; P = .041). Univariate analysis identified Child-Pugh class, carcinoembryonic antigen (CEA), chemotherapy after (90)Y radioembolization, KRAS status, and treatment-induced toxicity as prognostic factors for OS. Multivariate Cox regression analysis demonstrated Child-Pugh class, CEA, and KRAS status to be independent prognostic factors for OS, even when correcting for the effect of chemotherapy after (90)Y radioembolization. Patients with CRC and KRAS wt may derive greater survival benefit from (90)Y radioembolization therapy than patients with KRAS mutant. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

  18. Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, Arnulf; Vaupel, Peter; Stockinger, Marcus; Schmidberger, Heinz [University Medical Center, Department of Radiooncology and Radiotherapy, Mainz (Germany); Struss, Hans-Garlich [University Medical Center, Department of Laboratory Medicine, Mainz (Germany); Giese, Alf [University Medical Center, Department of Neurosurgery, Mainz (Germany)

    2014-10-15

    In comparison to normal brain tissue, glioblastomas exhibit significantly increased glucose uptake. Brain edema is a common complication during adjuvant chemoradiotherapy, leading to a requirement for glucocorticoid treatment. Glucocorticoid treatment frequently causes considerable deregulation of blood glucose levels. Therefore, episodes of hyperglycemia may contribute to radio- and/or chemoresistance. This study comprises a retrospective analysis of the influence of hyperglycemic episodes (HEs) during adjuvant therapy on the overall survival of 106 glioblastoma multiforme patients. The occurrence of one or more deregulated blood glucose value(s) > 10 mM is associated with a reduction in median overall survival from 16.7 to 8.8 months. A significantly poorer overall survival of patients with hyperglycemia could also be detected in subgroup analyses of patients with complete tumor resection and complete treatment according to the EORTC 22891/26891 trial protocol, as well as in a multivariate Cox proportional hazards analysis. A history of diabetes mellitus had no influence on prognosis. Our data suggest that the observed negative impact of elevated blood glucose levels on overall survival may not solely be explained by the patients' poorer general condition; the elevated blood glucose concentration itself may play a pathogenetic role. This could be due to increased activity of antioxidant systems, elevated expression of DNA damage response proteins and protection of hypoxic tumor cells against apoptosis combined with hypoxia-mediated radioresistance. A possible prognostic impact of elevated blood glucose levels during the period of adjuvant (chemo-) radiotherapy of glioblastoma should be evaluated in a prospective clinical trial. (orig.) [German] Glioblastome zeigen im Vergleich mit normalem Gehirngewebe eine deutlich vermehrte Glukoseaufnahme. Im Rahmen der adjuvanten Radio(chemo)therapie von Glioblastomen treten vielfach Hirnoedeme auf, die eine

  19. Revealing strong bias in common measures of galaxy properties using new inclination-independent structures

    Science.gov (United States)

    Devour, Brian M.; Bell, Eric F.

    2017-06-01

    Accurate measurement of galaxy structures is a prerequisite for quantitative investigation of galaxy properties or evolution. Yet, the impact of galaxy inclination and dust on commonly used metrics of galaxy structure is poorly quantified. We use infrared data sets to select inclination-independent samples of disc and flattened elliptical galaxies. These samples show strong variation in Sérsic index, concentration and half-light radii with inclination. We develop novel inclination-independent galaxy structures by collapsing the light distribution in the near-infrared on to the major axis, yielding inclination-independent 'linear' measures of size and concentration. With these new metrics we select a sample of Milky Way analogue galaxies with similar stellar masses, star formation rates, sizes and concentrations. Optical luminosities, light distributions and spectral properties are all found to vary strongly with inclination: When inclining to edge-on, r-band luminosities dim by >1 magnitude, sizes decrease by a factor of 2, 'dust-corrected' estimates of star formation rate drop threefold, metallicities decrease by 0.1 dex and edge-on galaxies are half as likely to be classified as star forming. These systematic effects should be accounted for in analyses of galaxy properties.

  20. Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hansen, Ulla; Christensen, Ib Jarle

    1999-01-01

    Overall peritumoural inflammatory cell infiltration is a prognostic variable in solid tumours, but the survival-related impact of the individual cell types within the infiltrate has still not been fully evaluated and compared with the conventional disease classification. In the present study......, the prognostic value of individual white cell counts in the peritumoural inflammatory infiltrate in colorectal cancer was assessed. Intra-operative tumour tissue samples from 584 patients undergoing elective surgery for colorectal cancer were included. None of the patients received pre- or post...... to dichotomize the cell counts with respect to survival. The median observation period was 61 (49-75) months. In a multivariate analysis including Dukes' stage, gender, age, peri-operative blood transfusion, tumour location, and counts of specific inflammatory cells, only advanced Dukes' stage ( p

  1. Serum tetranectin is an independent prognostic marker in colorectal cancer and weakly correlated with plasma suPAR, plasma PAI-1 and serum CEA

    DEFF Research Database (Denmark)

    Høgdall, Claus K; Christensen, Ib J; Stephens, Ross W

    2002-01-01

    PAR and CEA had a 2.43 increased risk as compared to a patient with median levels of these biochemical markers. Significant correlations were found with Dukes' stages for all the biochemical markers and between the respective biochemical markers. The findings confirm that TN is a strong prognostic factor...... activator (uPAR) and carcinoembryonic antigen (CEA). Significantly shorter survival was found for patients with TN levels below a cut-off point of 7.5 mg/l compared to patients with levels above, as illustrated by Kaplan-Meier curves. By Cox analyses, log TN, log soluble uPAR as well as log CEA were found...... to have an independent prognostic value for survival (log TN: HR = 0.47, 95% CI: 0.29-0.76); log soluble uPAR: HR = 1.65, 95% CI: 1.18-2.31; log CEA: HR = 1.I1, 95% CI: 1.03-1.20). Based on the multivariate model, a patient with a combination of low levels of TN and PAI-1 and elevated levels of soluble u...

  2. X-linked inhibitor of apoptosis positive nuclear labeling: a new independent prognostic biomarker of breast invasive ductal carcinoma

    Directory of Open Access Journals (Sweden)

    Peng Bofang

    2011-06-01

    Full Text Available Abstract Background It's well recognized that X-linked inhibitor of apoptosis (XIAP was the most potent caspase inhibitor and second mitochondria-derived activator of caspase (Smac was the antagonist of XIAP. Experiments in vitro identified that down regulation of XIAP expression or applying Smac mimics could sensitize breast cancer cells to chemotherapeutics and promote apoptosis. However, expression status and biologic or prognostic significance of XIAP/Smac in breast invasive ductal carcinoma (IDC were not clear. The present study aimed to investigate relationship among expression status of XIAP/Smac, apoptosis index (AI, clinicopathologic parameters and prognosis in IDC. Methods Immunohistochemistry and TUNEL experiment were performed to detect expression of XIAP, Smac, ER, PR, HER2 and AI in 102 cases of paraffin-embedded IDC samples respectively. Expression of XIAP/Smac were also detected in limited 8 cases of fresh IDC specimens with Western blot. Results Positive ratio and immunoscore of XIAP was markedly higher than Smac in IDC (P P s = 0.265, P = 0.017. The present study first revealed that XIAP positive nuclear labeling (XIAP-N, but not cytoplasmic staining (XIAP-C, was the apoptotic marker correlated significantly with patients' shortened overall survival (P = 0.039. Survival analysis demonstrated that XIAP-N was a new independent prognostic factor except for patient age and lymph node status. Conclusion Disturbed balance of expression between XIAP and Smac probably contributed to carcinogenesis and XIAP positive nuclear labeling was a new independent prognostic biomarker of breast IDC.

  3. Are strong empathizers better mentalizers? Evidence for independence and interaction between the routes of social cognition.

    Science.gov (United States)

    Kanske, Philipp; Böckler, Anne; Trautwein, Fynn-Mathis; Parianen Lesemann, Franca H; Singer, Tania

    2016-09-01

    Although the processes that underlie sharing others' emotions (empathy) and understanding others' mental states (mentalizing, Theory of Mind) have received increasing attention, it is yet unclear how they relate to each other. For instance, are people who strongly empathize with others also more proficient in mentalizing? And (how) do the neural networks supporting empathy and mentalizing interact? Assessing both functions simultaneously in a large sample (N = 178), we show that people's capacities to empathize and mentalize are independent, both on a behavioral and neural level. Thus, strong empathizers are not necessarily proficient mentalizers, arguing against a general capacity of social understanding. Second, we applied dynamic causal modeling to investigate how the neural networks underlying empathy and mentalizing are orchestrated in naturalistic social settings. Results reveal that in highly emotional situations, empathic sharing can inhibit mentalizing-related activity and thereby harm mentalizing performance. Taken together, our findings speak against a unitary construct of social understanding and suggest flexible interplay of distinct social functions. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  4. Strong fascin expression promotes metastasis independent of its F-actin bundling activity.

    Science.gov (United States)

    Heinz, Lisa S; Muhs, Stefanie; Schiewek, Johanna; Grüb, Saskia; Nalaskowski, Marcus; Lin, Yuan-Na; Wikman, Harriet; Oliveira-Ferrer, Leticia; Lange, Tobias; Wellbrock, Jasmin; Konietzny, Anja; Mikhaylova, Marina; Windhorst, Sabine

    2017-12-15

    High expression of the actin bundling protein Fascin increases the malignancy of tumor cells. Here we show that fascin expression is up-regulated in more malignant sub-cell lines of MDA-MB-231 cells as compared to parental cells. Since also parental MDA-MB-231 cells exhibit high fascin levels, increased fascin expression was termed as "hyperexpression". To examine the effect of fascin hyperexpression, fascin was hyperexpressed in parental MDA-MB-231 cells and metastasis was analyzed in NOD scid gamma (NSG) mice. In addition, the effect of fascin mutants with inactive or constitutively active actin bundling activity was examined. Unexpectedly, we found that hyperexpression of both, wildtype (wt) and mutant fascin strongly increased metastasis in vivo , showing that the effect of fascin hyperexpression did not depend on its actin bundling activity. Cellular assays revealed that hyperexpression of wt and mutant fascin increased adhesion of MDA-MB-231 cells while transmigration and proliferation were not affected. Since it has been shown that fascin controls adhesion by directly interacting with microtubules ( MTs), we analyzed if fascin hyperexpression affects MT dynamics. We found that at high concentrations fascin significantly increased MT dynamics in cells and in cell-free approaches. In summary our data show that strong expression of fascin in breast cancer cells increases metastasis independent of its actin bundling activity. Thus, it seems that the mechanism of fascin-stimulated metastasis depends on its concentration.

  5. The tumor-stromal ratio as a strong prognosticator for advanced gastric cancer patients: proposal of a new TSNM staging system.

    Science.gov (United States)

    Peng, Chunwei; Liu, Jiuyang; Yang, Guifang; Li, Yan

    2017-08-16

    Insufficient attention is paid to the underlying tumor microenvironment (TME) evolution, that resulting in tumor heterogeneity and driving differences in cancer aggressiveness and treatment outcomes. The morphological evaluation of the proportion of the stroma at the most invasive part of primary tumor (tumor-stromal ratio, TSR) in cancer is gaining momentum as evidence strengthens for the clinical relevance. Tissue samples from the most invasive part of the primary gastric cancer (GC) of 494 patients were analyzed for their TSR, and a new TSNM (tumor-stromal node metastasis) staging system based on patho-biological behaviors was established and assessed. TSR is a new and strong independent prognostic factor for GC patients. The likelihood of tumor invasion is increased significantly for patients in the stromal-high subgroup compared to those in the stromal-low subgroup (P = 0.011). The discrimination ability of TSR was not less than the TNM staging system and was better in patients with stages I and II GC. We integrated the TSR parameter into the TNM staging system and proposed a new TSNM staging system creatively. There were three new subgroups (IC, IIC, IIID). There were four major groups and 10 subgroups in the TSNM system. The difference in overall survival (OS) was statistically significant among all TSNM system (P system has been established to optimize risk stratification for GC. The value of the TSNM staging system should be validated in further prospective study.

  6. Global hypomethylation is an independent prognostic factor in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Wedge, Eileen; Hansen, Jakob Werner; Garde, Christian

    2017-01-01

    available kit, based on pyrosequencing of PCR amplified bisulfite-treated DNA. Global hypomethylation was detected in a subset of cases and was associated with poor overall survival in both tumor biopsies (P = .001) and cfDNA (P = .009). It was the strongest risk factor in multivariate analysis in both......Global hypomethylation has been linked to disease progression in several cancers, but has not been reported for Diffuse Large B Cell Lymphoma (DLBCL). This study aimed to assess global methylation in DLBCL and describe its prognostic value. Mean LINE1 methylation, a validated surrogate measure...... biopsies (HR: 10.65, CI: 2.03-55.81, P = .005) and cfDNA (HR: 11.87, CI: 2.80-50.20, P = .001), outperforming conventional clinical risk factors. Finally, hierarchical cluster analyses were performed for the cfDNA samples using previously published gene-specific methylation data. This analysis shows...

  7. Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder.

    Science.gov (United States)

    Hodgson, Anjelica; Xu, Bin; Satkunasivam, Raj; Downes, Michelle R

    2018-02-01

    Inflammation and necrosis have been associated with prognosis in multiple epithelial malignancies. Our objective was to evaluate inflammation and necrosis in a cohort of patients with high-grade urothelial carcinomas of the bladder to determine their association with pathological parameters and their prognostic effect on relapse-free and disease-specific survival. A retrospective cohort that underwent radical cystectomy for urothelial carcinomas (n=235) was evaluated for invasive front and central inflammation using the Klintrup-Makinen assessment method. Necrosis was scored using a four-point scale. The relationship of inflammation and necrosis with stage, nodal status, carcinoma in situ, tumour size, margin status and vascular space invasion and the impact on relapse-free and disease-specific survival were calculated using appropriate statistical tests. On multivariate analysis, invasive front inflammation (p=0.003) and necrosis (p=0.000) were independent predictors of relapse-free survival. Both invasive front inflammation (p=0.009) and necrosis (p=0.002) again were independent predictors of disease-specific survival. For pathological features, low invasive front inflammation was associated with lymphovascular space invasion (p=0.008), a positive soft tissue margin (p=0.028) and carcinoma in situ (p=0.042). Necrosis was statistically associated with tumours >3 cm in size (p=0.013) and carcinoma in situ (pinflammation are additional histological variables with independent prognostic relevance in high-grade urothelial carcinoma of the bladder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. CLIF-SOFA score and SIRS are independent prognostic factors in patients with hepatic encephalopathy due to alcoholic liver cirrhosis.

    Science.gov (United States)

    Jeong, Jin Hee; Park, In Sung; Kim, Dong Hoon; Kim, Seong Chun; Kang, Changwoo; Lee, Soo Hoon; Kim, Tae Yun; Lee, Sang Bong

    2016-06-01

    Hepatic encephalopathy (HE) is a complication associated with worst prognosis in decompensated liver cirrhosis (LC) patients. Previous studies have identified prognostic factors for HE, and recent studies reported an association between systemic inflammatory response syndrome (SIRS) and liver disease. This study aimed to identify prognostic factors for 30-day mortality in alcoholic LC patients with HE who visited the emergency department (ED).This was a retrospective study of alcoholic LC patients with HE from January 1, 2010, to April 30, 2015. The baseline characteristics, complications of portal hypertension, laboratory values, Child-Pugh class, Model for End-stage Liver Disease (MELD) score, chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score, and SIRS criteria were assessed. The presence of 2 or more SIRS criteria was considered SIRS. The primary outcomes were 30-day mortality and prognostic factors for patients with HE visiting the ED.In total, 105 patients who met the inclusion criteria were analyzed. Overall, the 30-day mortality rate was 6.7% (7 patients).Significant variables were hepatorenal syndrome, international normalized ratio, white blood cell count, total bilirubin level, MELD score CLIF-SOFA score, and SIRS in univariate analysis. CLIF-SOFA score and SIRS were the significant factors in the multivariate analysis (hazard ratio 5.56, 15.98; 95% confidence interval 1.18-26.18, 1.58-161.37; P = 0.03, P = 0.02). The mortality rates differed according to the CLIF-SOFA score (P SIRS in alcoholic LC patients with HE visiting the ED are independent predictors of 30-day mortality.

  9. Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations.

    Science.gov (United States)

    Wang, Dong-Yu; Done, Susan J; Mc Cready, David R; Leong, Wey L

    2014-07-04

    Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). The original training cohort reached a statistically significant difference (p value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups. Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments.

  10. Expression of the tyrosine kinase c-kit is an independent prognostic factor in patients with small cell lung cancer.

    Science.gov (United States)

    Rohr, Ulrich-Peter; Rehfeld, Nina; Pflugfelder, Lucy; Geddert, Helene; Müller, Wolfram; Steidl, Ulrich; Fenk, Roland; Gräf, Thorsten; Schott, Matthias; Thiele, Klaus-Peter; Gabbert, Helmut Erich; Germing, Ulrich; Kronenwett, Ralf; Haas, Rainer

    2004-08-20

    In a retrospective analysis of 203 patients with small cell lung cancer (SCLC), we examined the prognostic value of c-kit expression on survival. Expression of c-kit was examined immunohistochemically in formalin-fixed, paraffin-embedded tissue sections. c-kit was observed in 87.7% of SCLC tumors. Using the Kaplan-Meier model, we found that lack of c-kit expression was associated with significantly shorter survival time compared to the presence of c-kit expression (mean survival 151 +/- 27 vs. 358 +/- 49 days, p = 0.0084). Moreover, the proportion of c-kit(+) cells within the tumor was also related to survival time. Patients with tumors in which >75% of cells stained positive for c-kit had a mean overall survival time of 424 (+/-72) compared to 295 (+/-67) days for patients with 25-75% c-kit(+) tumor cells. Patients with tumors containing model showed that the proportion of c-kit(+) cells within the tumor specimen was one of 3 independent prognostic parameters (p = 0.004) for overall survival next to TNM classification (p = 0.001) and performance status (p < 0.001). Copyright 2004 Wiley-Liss, Inc.

  11. CD44v6 down-regulation is an independent prognostic factor for poor outcome of colorectal carcinoma.

    Science.gov (United States)

    Wang, Lili; Liu, Qin; Lin, Dongliang; Lai, Maode

    2015-01-01

    We aim to investigate the variation of CD44v6 expression in the normal-adenoma-primary carcinoma-liver metastasis sequence and its prognostic impact on colorectal carcinomas. The difference in CD44v6 expression between the tumor center and invasive front was also assessed. Immunohistochemistry was performed for CD44v6 on two cohorts. The first was tissue microarrays including 402 primary CRCs sampled from the tumor center and the invasive margin. The second was whole-tissue sections, consisting of 217 adenomas, 72 primary carcinomas, and the corresponding metastatic carcinomas. In the first cohort, we found that CD44v6 down-regulation was inclined to lymph node metastasis and perineural invasion, and had an unfavorable prognosis compared with CD44v6 up-regulation. In the second cohort, CD44v6 expression was predominant in adenoma over primary carcinoma and liver metastasis in multiple steps (normal primary carcinoma and liver metastasis). In addition, our analysis showed that CD44v6 expression was decreased at the invasion front of the CRC compared with the center of the tumor. In conclusion, the maximal expression of CD44v6 in adenoma plays a crucial role in colorectal carcinogenesis, while loss of CD44v6 expression on the cell surface of the tumor edge enhances the progression of metastasis. CD44v6 down-regulation is an independent prognostic factor for strikingly worse disease-specific survival.

  12. Novel Growth Factor as Prognostic Marker for Estrogen-Independence in Breast Cancer

    National Research Council Canada - National Science Library

    Serrero, Ginette

    2002-01-01

    ...-independence and tamoxifen resistance. Here, wave conducted a study with 206 paraffin embedded human breast cancer biopsies and measured PCDGF expression by immunohistochemistry using an anti-PCDGF developed in our laboratory...

  13. Novel Growth Factor as Prognostic Marker for Estrogen-Independence in Breast Cancer

    National Research Council Canada - National Science Library

    Serrero, Ginette

    2003-01-01

    The Concept Award focused on investigating the expression on the biomarker PCDGF/GP88 in breast cancer and its effect on the acquisition of estrogen independence and tamoxifen resistance, a hallmark...

  14. The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer

    DEFF Research Database (Denmark)

    You, Benoit; Colomban, Olivier; Heywood, Mark

    2013-01-01

    Unexpected results were recently reported about the poor surrogacy of Gynecologic Cancer Intergroup (GCIG) defined CA-125 response in recurrent ovarian cancer (ROC) patients. Mathematical modeling may help describe CA-125 decline dynamically and discriminate prognostic kinetic parameters....

  15. GSTM1 genotype is an independent prognostic factor in clear cell renal cell carcinoma.

    Science.gov (United States)

    Coric, Vesna M; Simic, Tatjana P; Pekmezovic, Tatjana D; Basta-Jovanovic, Gordana M; Savic-Radojevic, Ana R; Radojevic-Skodric, Sanja M; Matic, Marija G; Suvakov, Sonja R; Dragicevic, Dejan P; Radic, Tanja M; Dzamic, Zoran M; Pljesa-Ercegovac, Marija S

    2017-06-01

    Owing to dual functionality of cytosolic glutathione S-transferases (GSTs), they might affect both the development and the progression of renal cell carcinoma (RCC). However, the data on the prognostic value of GST polymorphism in patients with RCC are scarce. Hence, we evaluated the effect of GST gene variants on both the risk of RCC development and the postoperative prognosis in patients with clear cell RCC (ccRCC). GST genotypes were determined in 305 patients with RCC and 326 matched controls, whereas the overall survival was evaluated in patients with ccRCC only. The presence of GSTM1:ASK1 protein-protein interaction in ccRCC tissue samples was analyzed by methods of immunoprecipitation and immunoblot. We noted an increased risk of RCC development in carriers of GSTM1-null and GSTP1-variant genotype (Prisk of RCC development. On the contrary, GSTM1-null genotype is associated with favorable postoperative prognosis in ccRCC. The possible molecular mechanism underlying the role of GSTM1 protein in RCC progression might be the presence of GSTM1:ASK1 protein-protein interaction. Hence, determination of GSTM1-genotype might serve as a valuable indicator in both RCC risk assessment and postoperative prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients

    DEFF Research Database (Denmark)

    Liu, Na; Cox, Thomas R; Cui, Weiyingqi

    2017-01-01

    Emerging evidence has implicated a pivotal role for lysyl oxidase (LOX) in cancer progression and metastasis. Whilst the majority of work has focused on the extracellular matrix cross-linking role of LOX, the exact function of intracellular LOX localisation remains unclear. In this study, we anal...... the nucleus of colon cancer cell lines by confocal microscopy and Western blot. Our results show a powerful link between nuclear LOX expression in tumours and patient survival, and offer a promising prognostic biomarker for rectal cancer patients....... analysed the LOX expression patterns in the nuclei of rectal cancer patient samples and determined the clinical significance of this expression. Nuclear LOX expression was significantly increased in patient lymph node metastases compared to their primary tumours. High nuclear LOX expression in tumours......Emerging evidence has implicated a pivotal role for lysyl oxidase (LOX) in cancer progression and metastasis. Whilst the majority of work has focused on the extracellular matrix cross-linking role of LOX, the exact function of intracellular LOX localisation remains unclear. In this study, we...

  17. S100A14 is a novel independent prognostic biomarker in the triple-negative breast cancer subtype

    DEFF Research Database (Denmark)

    Ehmsen, Sidse; Hansen, Lea Tykgaard; Bak, Martin

    2015-01-01

    with high S100A14 protein expression levels were significantly correlated with poor outcome in TNBC patients (p = 0.017; p = 0.038), particularly those in the basal-like subgroup (p = 0.006; p = 0.037). Importantly, TNBC patients with high S100A14 expression, but tumor-negative axillary lymph nodes (N......-), had equally poor outcomes as those with tumor-positive axillary lymph nodes (N+), while TNBC/N- patients with low S100A14 expression had a significantly better disease free survival (p = 0.013). Multivariate analysis revealed that S100A14 is an independent prognostic factor for TNBC patients (p = 0...

  18. Enhancer of Zeste Homolog 2 Overexpression in Nasopharyngeal Carcinoma: An Independent Poor Prognosticator That Enhances Cell Growth

    International Nuclear Information System (INIS)

    Hwang, Chung-Feng; Huang, Hsuan-Ying; Chen, Chang-Han; Chien, Chih-Yen; Hsu, Yao-Chung; Li, Chien-Feng

    2012-01-01

    Purpose: As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC). Methods and Materials: In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription–polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS). Results: Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median (≥60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS). Conclusion: At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.

  19. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer.

    Science.gov (United States)

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody; Bayani, Nora; Blakely, Eleanor A; Gray, Joe W; Mao, Jian-Hua

    2010-01-01

    HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression were validated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis than those with low levels

  20. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

    International Nuclear Information System (INIS)

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E.; Pai, Melody; Bayani, Nora; Blakely, Eleanor A.; Gray, Joe W.; Mao, Jian-Hua

    2010-01-01

    HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression were validated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis than those with low levels

  1. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody; Bayani, Nora; Blakely, Eleanor A; Gray, Joe W; Mao, Jian-Hua

    2010-06-25

    Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis

  2. Serum uric acid: A strong and independent predictor of metabolic syndrome after adjusting for body composition.

    Science.gov (United States)

    Yu, Tae Yang; Jee, Jae Hwan; Bae, Ji Cheol; Jin, Sang-Man; Baek, Jong-Ha; Lee, Moon-Kyu; Kim, Jae Hyeon

    2016-04-01

    Some observational studies have suggested that serum uric acid (SUA) levels are one of the determinants of the metabolic syndrome (MetS). However, previous studies reported combined results for men and women after adjusting for sex and few studies take body composition into consideration. Therefore, we performed this sex-specific longitudinal study to investigate how baseline SUA levels influence incident MetS, including body composition as an adjusting factor in a large number of subjects. A total of 14,442 participants (8715 men and 5727 women) participating in a medical health check-up program without diagnosed MetS at baseline were enrolled. Separate analyses were performed for men and women including body composition as a confounding factor. Cox proportional hazards models were used to quantify independent associations between SUA levels and incident MetS. During 63,940person-years of follow-up, there were 4215 (2974 men, 1241 women) incident cases of MetS between 2006 and 2012. After adjustments for age, systolic BP, diastolic BP, BMI, eGFR, smoking status, TG, LDL-C, HDL-C, fasting glucose, and proportion of fat-free mass (100-fat mass, %), the hazard ratios (HR) [95% confidence interval (CI)] for incident MetS comparing the second, the third, and the fourth quartiles to the first quartile of SUA levels were 0.862 (0.770-0.965), 1.102 (0.991-1.225), and 1.246 (1.121-1.385) in men (p for trend<0.001), and 1.045 (0.862-1.266), 1.251 (1.050-1.490), and 1.321 (1.109-1.574) in women (p for trend<0.001), respectively. As a continuous variable, in fully-adjusted models, the HRs (95% CI) for incident MetS associated with each increase of 1mg/dl of SUA levels were 1.094 (1.060-1.130) in men (p<0.001) and 1.148 (1.072-1.228) in women (p<0.001), respectively. We demonstrated that SUA levels are strong and independent predictors of MetS. This relationship remained significant after full adjustments for multiple associated confounders including body composition in both

  3. Generalised model-independent characterisation of strong gravitational lenses. I. Theoretical foundations

    Science.gov (United States)

    Wagner, J.

    2017-05-01

    We extend our model-independent approach for characterising strong gravitational lenses to its most general form to leading order and use the orientation angles of a set of multiple images with respect to their connection line(s) in addition to the relative distances between the images, their ellipticities, and time-delays. For two symmetric images that straddle the critical curve, the orientation angle additionally allows us to determine the slope of the critical curve and a second (reduced) flexion coefficient at the critical point on the connection line between the images. It also allows us to drop the symmetry assumption that the axis of largest image extension is orthogonal to the critical curve. For three images almost forming a giant arc, the degree of assumed image symmetry is also reduced to the most general case, describing image configurations for which the source need not be placed on the symmetry axis of the two folds that unite at the cusp. For a given set of multiple images, we set limits on the applicability of our approach, show which information can be obtained in cases of merging images, and analyse the accuracy achievable due to the Taylor expansion of the lensing potential for the fold case on a galaxy cluster scale Navarro-Frenk-White-profile, a fold and cusp case on a galaxy cluster scale singular isothermal ellipse, and compare the generalised approach with our previously published one. The position of the critical points is reconstructed with less than 5'' deviation for multiple images closer to the critical points than 30% of the (effective) Einstein radius. The slope of the critical curve at a fold and its shape in the vicinity of a cusp deviate less than 20% from the true values for distances of the images to the critical points less than 15% of the (effective) Einstein radius.

  4. Δ133p53 is an independent prognostic marker in p53 mutant advanced serous ovarian cancer

    Science.gov (United States)

    Hofstetter, G; Berger, A; Schuster, E; Wolf, A; Hager, G; Vergote, I; Cadron, I; Sehouli, J; Braicu, E I; Mahner, S; Speiser, P; Marth, C; Zeimet, A G; Ulmer, H; Zeillinger, R; Concin, N

    2011-01-01

    Background: We aimed to evaluate the clinical relevance of p53 and p73 isoforms that modulate the function of p53. Methods: This prospective multicentre study included 154 patients with stage III and IV serous ovarian cancer. A functional yeast-based assay and subsequent sequencing were performed to analyse the p53 mutational status. Expression of p53 and p73 isoforms was determined using RT–qPCR. Results: Δ133p53 expression constituted an independent prognostic marker for recurrence-free (hazard ratio=0.571, P=0.016, 95% CI: 0.362–0.899) and overall survival (hazard ratio=0.365, P=0.004, 95% CI: 0.182–0.731) in patients with p53 mutant ovarian cancer (n=121). High Δ40p53 expression was associated with favourable tumour grading (P=0.037) and improved recurrence-free survival (33.4 vs 19.6 months, P=0.029), but not overall survival (43.1 vs 33.6 months, P=0.139), in patients with p53 wild-type cancer (n=33). Neither the p53 mutational status nor p73 isoform expression possessed prognostic significance in the examined ovarian cancer cases. Conclusion: Δ133p53 expression was associated with prognosis in the vast majority of ovarian cancer cases, that is, patients with p53 mutant advanced serous carcinomas. Thus, our findings underline the importance of considering the complex p53 regulatory network. PMID:22009029

  5. Three-question set from Michigan Neuropathy Screening Instrument adds independent prognostic information on cardiovascular outcomes

    DEFF Research Database (Denmark)

    Seferovic, Jelena P; Pfeffer, Marc A; Claggett, Brian

    2018-01-01

    Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial, we divided 8463 participants with type 2 diabetes and chronic kidney disease (CKD) and/or cardiovascular disease (CVD) into independent training (n = 3252) and validation (n = 5211) sets. In the training set, we identified specific......: In the training set, three questions ('Are your legs numb?', 'Have you ever had an open sore on your foot?' and 'Do your legs hurt when you walk?') were significantly associated with the cardiovascular composite outcome. In the validation set, after multivariable adjustment for key covariates, one or more......AIMS/HYPOTHESIS: The self-administered Michigan Neuropathy Screening Instrument (MNSI) is used to diagnose diabetic peripheral neuropathy. We examined whether the MNSI might also provide information on risk of death and cardiovascular outcomes. METHODS: In this post hoc analysis of the Aliskiren...

  6. Long non-coding RNA HOTAIR is an independent prognostic marker of metastasis in estrogen receptor-positive primary breast cancer

    DEFF Research Database (Denmark)

    Sørensen, Kristina P; Thomassen, Mads; Tan, Qihua

    2013-01-01

    that high HOTAIR expression in primary tumors is significantly associated with worse prognosis independent of prognostic markers (P = 0.012, hazard ratio (HR) 1.747). This association is even stronger when looking only at estrogen receptor (ER)-positive tumor samples (P = 0.0086, HR 1.985). In ER...

  7. Salivary gland carcinoma : Independent prognostic factors for locoregional control, distant metastases, and overall survival: Results of the Dutch Head and Neck Oncology Cooperative Group

    NARCIS (Netherlands)

    Terhaard, CHJ; Lubsen, H; Van der Tweel, [No Value; Hilgers, FJM; Eijkenboom, WMH; Marres, HAM; Tjho-Heslinga, RE; de Jong, JMA; Roodenburg, JLN

    Background. We analyzed the records of patients with malignant salivary gland tumors, as diagnosed in centers of the Dutch Head and Neck Oncology Cooperative Group, in search of independent prognostic factors for locoregional control, distant metastases, and overall survival. Methods. In 565

  8. Independent Prognostic Value of Serum Markers in Diffuse Large B-Cell Lymphoma in the Era of the NCCN-IPI.

    Science.gov (United States)

    Melchardt, Thomas; Troppan, Katharina; Weiss, Lukas; Hufnagl, Clemens; Neureiter, Daniel; Tränkenschuh, Wolfgang; Schlick, Konstantin; Huemer, Florian; Deutsch, Alexander; Neumeister, Peter; Greil, Richard; Pichler, Martin; Egle, Alexander

    2015-12-01

    Several serum parameters have been evaluated for adding prognostic value to clinical scoring systems in diffuse large B-cell lymphoma (DLBCL), but none of the reports used multivariate testing of more than one parameter at a time. The goal of this study was to validate widely available serum parameters for their independent prognostic impact in the era of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score to determine which were the most useful. This retrospective bicenter analysis includes 515 unselected patients with DLBCL who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and January 2014. Anemia, high C-reactive protein, and high bilirubin levels had an independent prognostic value for survival in multivariate analyses in addition to the NCCN-IPI, whereas neutrophil-to-lymphocyte ratio, high gamma-glutamyl transferase levels, and platelets-to-lymphocyte ratio did not. In our cohort, we describe the most promising markers to improve the NCCN-IPI. Anemia and high C-reactive protein levels retain their power in multivariate testing even in the era of the NCCN-IPI. The negative role of high bilirubin levels may be associated as a marker of liver function. Further studies are warranted to incorporate these markers into prognostic models and define their role opposite novel molecular markers. Copyright © 2015 by the National Comprehensive Cancer Network.

  9. Neutrophil-lymphocyte ratio at diagnosis is an independent prognostic factor in patients with nodular sclerosis Hodgkin lymphoma: results of a large multicenter study involving 990 patients.

    Science.gov (United States)

    Marcheselli, Raffaella; Bari, Alessia; Tadmor, Tamar; Marcheselli, Luigi; Cox, Maria Christina; Pozzi, Samantha; Ferrari, Angela; Baldini, Luca; Gobbi, Paolo; Aviv, Ariel; Pugliese, Giuseppe; Federico, Massimo; Polliack, Aaron; Sacchi, Stefano

    2017-12-01

    Several studies have demonstrated the prognostic value of neutrophil-lymphocyte ratio (NLR) in patients with solid tumors and non-Hodgkin lymphoma. In contrast, there is only sparse data on its prognostic role in patients with classical Hodgkin lymphoma (cHL). The aim of our study was to establish whether NLR could serve as an independent prognostic factor in a cohort of 990 patients with nodular sclerosis (NS)-cHL. After analysis of the log hazard ratio (HR) as a function of NLR, we chose the value 6 as cutoff. Patients with NLR >6 had a worse progression-free survival and overall survival compared to those with NLR ≤6; 84% vs 75% and 92% vs 88%, at 5 years, with an HR of 1.65 and 1.82, respectively. Multivariate analysis showed that the risk remained high with HR 1.44 and HR 1.54 in progression-free survival and overall survival, respectively. In summary, our study shows that NLR is a robust and independent prognostic parameter in NS-cHL, both in early and advanced disease. It is inexpensive and simple to apply. Thus, we conclude that NLR, possibly in combination with the international prognostic score and absolute monocyte count, is a useful guide for physicians treating NS-cHL patients. © 2016 The Authors Hematological Oncology Published by John Wiley & Sons Ltd.

  10. A model-independent description of few-body system with strong interaction

    International Nuclear Information System (INIS)

    Simenog, I.V.

    1985-01-01

    In this contribution, the authors discuss the formulation of equations that provide model-independent description of systems of three and more nucleons irrespective of the details of the interaction, substantiate the approach, estimate the correction terms with respect to the force range, and give basic qualitative results obtained by means of the model-independent procedure. They consider three nucleons in the doublet state (spin S=I/2) taking into account only S-interaction. The elastic nd-scattering amplitude may be found from the model-independent equations that follow from the Faddeev equations in the short-range-force limit. They note that the solutions of several model-independent equations and basic results obtained with the use of this approach may serve both as a standard solution and starting point in the discussion of various conceptions concerning the details of nuclear interactions

  11. β-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases.

    Science.gov (United States)

    Bleckmann, Annalen; Conradi, Lena-Christin; Menck, Kerstin; Schmick, Nadine Annette; Schubert, Antonia; Rietkötter, Eva; Arackal, Jetcy; Middel, Peter; Schambony, Alexandra; Liersch, Torsten; Homayounfar, Kia; Beißbarth, Tim; Klemm, Florian; Binder, Claudia; Pukrop, Tobias

    2016-04-01

    Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection and clinical relevance of biomarker analysis in metastatic tissue have barely been investigated. We previously demonstrated an impact of WNT signaling in breast cancer brain metastasis. This study aimed to investigate the value of established prognostic markers and WNT signaling components in liver metastases. Overall N = 34 breast cancer liver metastases (with matched primaries in 19/34 cases) were included in this retrospective study. Primaries and metastatic samples were analyzed for their expression of the estrogen (ER) and progesterone receptor, HER-2, Ki67, and various WNT signaling-components by immunohistochemistry. Furthermore, β-catenin-dependent and -independent WNT scores were generated and analyzed for their prognostic value. Additionally, the influence of the alternative WNT receptor ROR on signaling and invasiveness was analyzed in vitro. ER positivity (HR 0.09, 95 % CI 0.01-0.56) and high Ki67 (HR 3.68, 95 % CI 1.12-12.06) in the primaries had prognostic impact. However, only Ki67 remained prognostic in the metastatic tissue (HR 2.46, 95 % CI 1.11-5.44). Additionally, the β-catenin-independent WNT score correlated with reduced overall survival only in the metastasized situation (HR 2.19, 95 % CI 1.02-4.69, p = 0.0391). This is in line with the in vitro results of the alternative WNT receptors ROR1 and ROR2, which foster invasion. In breast cancer, the value of prognostic markers established in primary tumors cannot directly be translated to metastases. Our results revealed β-catenin-independent WNT signaling to be associated with poor prognosis in patients with breast cancer liver metastasis.

  12. Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide.

    Directory of Open Access Journals (Sweden)

    Alexandra Audemard-Verger

    Full Text Available To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs in lupus nephritis (LN treated with cyclophosphamide (CYC. CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST.We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline.Most patients were women (84% and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR (OR = 5.01 95% CI [1.02-24.51] and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]. No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed.This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

  13. Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

    International Nuclear Information System (INIS)

    Huang, Eng-Yen; Chanchien, Chan-Chao; Lin, Hao; Wang, Chung-Chi; Wang, Chong-Jong; Huang, Chao-Cheng

    2013-01-01

    Purpose: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. Methods and Materials: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. Results: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. Conclusion: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer

  14. Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Eng-Yen [Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Chanchien, Chan-Chao; Lin, Hao [Department of Gynecologic Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Wang, Chung-Chi; Wang, Chong-Jong [Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Huang, Chao-Cheng, E-mail: huangcc@cgmh.org.tw [Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China)

    2013-12-01

    Purpose: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. Methods and Materials: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. Results: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. Conclusion: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.

  15. Sprouty 2 is an independent prognostic factor in breast cancer and may be useful in stratifying patients for trastuzumab therapy.

    Directory of Open Access Journals (Sweden)

    Dana Faratian

    Full Text Available Resistance to trastuzumab is a clinical problem, partly due to overriding activation of MAPK/PI3K signalling. Sprouty-family proteins are negative regulators of MAPK/PI3K signalling, but their role in HER2-therapy resistance is unknown.Associations between Sprouty gene expression and clinicopathological features were investigated in a breast cancer microarray meta-analysis. Changes in expression of Spry2 and feedback inhibition on trastuzumab resistance were studied in SKBr3 and BT474 breast carcinoma cell lines using cell viability assays. Spry2 protein expression was measured by quantitative immunofluorescence in a cohort of 122 patients treated with trastuzumab.Low gene expression of Spry2 was associated with increased pathological grade, high HER2 expression, and was a significant independent prognostic factor. Overexpression of Spry2 in SKBr3s resulted in enhanced inhibition of cell viability after trastuzumab treatment, and the PI3K-inhibitor LY294002 had a similar effect. Low Spry2 expression was associated with increased risk of death (HR = 2.28, 95% CI 1.22-4.26; p = 0.008 in trastuzumab-treated patients, including in multivariate analysis. Stratification of trastuzumab-treated patients using PTEN and Spry2 was superior to either marker in isolation.In breast cancers with deficient feedback inhibition, combinatorial therapy with negative regulators of growth factor signalling may be an effective therapeutic strategy.

  16. Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients.

    Science.gov (United States)

    Karatas, Fatih; Erdem, Gokmen Umut; Sahin, Suleyman; Aytekin, Aydin; Yuce, Deniz; Sever, Ali R; Babacan, Taner; Ates, Ozturk; Ozisik, Yavuz; Altundag, Kadri

    2017-04-01

    The relation between higher body mass index (BMI) and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is a controversial issue according to the data of Western and Asian patients. The aim of this study is to evaluate BMI and pCR to NAC and discuss the importance of pCR outcomes in Turkish BC patients as a bridging country between Europe and Asia. Of the 4423 BC patients diagnosed between the years 1994 and 2015 in Hacettepe University Cancer Institute, 295 female patients with stage II and III BC were enrolled in the study. Three different group divisions were done according to patients' BMI as normal or underweight (N/U) patients (BMI <25 kg/m 2 ), overweight (OW) patients (BMI = 25-29.9 kg/m 2 ) and obese (OB) patients (BMI ≥30 kg/m 2 ). BC subtypes were defined as luminal-like (ER/PR-positive and HER2-negative), HER2/luminal (ER/PR-positive and HER2-positive), HER2-type (ER/PR-negative and HER2-positive), and triple-negative (TNBC; ER/PR- and HER2-negative). The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed according to Kaplan-Meier method. The Log-rank test was used to compare the subgroup analysis and logistic regression analysis to determine the independent prognostic factors. In this study, a total number of 93 (31.5%) patients were N/U, 107 (36.3%) patients were OW and 95 (32.2%) patients were OB. Among groups, except for the age, no baseline clinicopathological differences were found. In 70 (23.7%) patients, pCR was achieved. pCR rates in N/U, OW and OB were 31.2%, 22.4%, and 17.9% respectively, showing a considerable trend towards significance (P = 0.09 in chi-square test). In the multivariate logistic regression analysis, obesity was an independent adverse prognostic feature on pCR to NAC compared to N/U patients (OR, 0.34; 95% CI, 0.13 to 0.85, P = 0.02). The recurrence rates were slightly increased with the increase of BMI (N/U = 24.7%, OW = 29.0% and OB

  17. Survival patterns in squamous cell carcinoma of the head and neck: pain as an independent prognostic factor for survival.

    Science.gov (United States)

    Reyes-Gibby, Cielito C; Anderson, Karen O; Merriman, Kelly W; Todd, Knox H; Shete, Sanjay S; Hanna, Ehab Y

    2014-10-01

    Survival outcomes in patients with squamous cell carcinoma of the head and neck (HNSCC) vary by extent of disease, behavioral factors, and socioeconomic factors. We assessed the extent to which pretreatment pain influences survival in 2,340 newly diagnosed patients with HNSCC, adjusting for disease stage, symptoms, pain medications, comorbidities, smoking, alcohol consumption, age, sex, and race/ethnicity. Patients rated their pain at presentation to the cancer center (0 = "no pain" and 10 = "pain as bad as you can imagine"). Survival time was calculated from the date of diagnosis to the date of death of any cause or last follow-up. Five-year overall survival was calculated for all the variables assessed in the study. Severe pain (≥7) was most prevalent among those with oral cancer (20.4%; pharynx = 18.8%; larynx = 16.1%) and significantly varied by tumor stage, fatigue severity, smoking status, comorbid lung disease, and race (all P pain for oral (severe pain = 31% vs nonsevere pain = 52%; P pain = 33% vs nonsevere pain = 53%; P pain persisted as an independent prognostic factor for survival. Pain reported prior to treatment should be considered in understanding survival outcomes in HNSCC patients. Pretreatment pain was an independent predictor of survival in a large sample of HNSCC patients even after accounting for tumor node metastasis stage, fatigue, age, race/ethnicity, smoking, and alcohol intake. Therefore, symptoms at presentation and before cancer treatment are important factors to be considered in understanding survival outcomes in HNSCC patients. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. p53 nuclear accumulation and multiploidy are adverse prognostic factors in surgically resected stage II colorectal cancers independent of fluorouracil-based adjuvant therapy.

    Science.gov (United States)

    Buglioni, S; D'Agnano, I; Vasselli, S; Perrone Donnorso, R; D'Angelo, C; Brenna, A; Benevolo, M; Cosimelli, M; Zupi, G; Mottolese, M

    2001-09-01

    To identify the prognostically highest risk patients, DNA content and p53 nuclear or cytoplasmic accumulation, evaluated by monoclonal antibody DO7 and polyclonal antibody CM1, were determined in 94 surgically resected stage II (Dukes B2) colorectal cancers, treated or not with adjuvant 5-fluorouracil-based chemotherapy. Sixty-one (65%) of the tumors were aneuploid, 16 (17%) of which had a multiploid DNA content; 50 (53%) displayed DO7 nuclear p53 accumulation, and 44 (47%) showed cytoplasmic CM1 positivity. In multivariate analysis, only multiploidy and p53 nuclear positivity emerged as independent prognostic indicators of a poorer outcome. Positivity for p53 was associated with shorter survival in 5-fluorouracil-treated and untreated patients. Therefore, in patients with Dukes B2 colorectal cancer, a biologic profile based on the combined evaluation of DNA multiploidy and p53 status can provide valuable prognostic information, identifying patients to be enrolled in alternative, more aggressive therapeutic trials.

  19. Rhesus CE expression on patient red blood cells is an independent prognostic factor for adenocarcinoma of the lung.

    Science.gov (United States)

    Schulze, A B; Schmidt, L H; Baie, L; Heitkötter, B; Kuemmel, A; Mohr, M; Buhl, R; Hillmann, H; Geißler, G; Kelsch, R; Görlich, D; Berdel, W E; Hartmann, W; Wiewrodt, R

    2017-04-11

    The influence of blood group antigens on cancerogenesis is shown for distinct tumor types, yet the impact of Rhesus blood group antigens in lung cancer is not clarified. To investigate the impact of Rhesus blood groups a non-small cell lung cancer (NSCLC) collective (n = 1047) was analyzed retrospectively. Using a second cohort of n = 340 primarily operated stage I-III NSCLC patients, we evaluated immunohistochemistry of CD47-antibody stained tissue samples in correlation to histopathologic subtype and Rhesus blood group. In 516 of 1047 patients blood group data were available. Seven different RhCE phenotypes were grouped as "··ee," "ccE·," and "C·E·." Adenocarcinoma patients with Rh "··ee" revealed improved overall survival (29 (21.2-36.8) m; HR 1.00 [index]) compared with Rh "ccE·" (19 (1.9-36.1) m; HR 1.76 [1.15-2.70]) and Rh "C·E·" (10 (7.4-12.6) m; HR 2.65 [1.70-4.12]) univariately (P Rh "··ee" showed reduced incidence of CNS-metastasis (P = .014) and metastasis count (P = .032) in stage IV adenocarcinoma. Immunohistochemistry associated CD47-positivity with adenocarcinomas (n = 340, P = .048). In n = 51 cases blood group data were available. The prognostic effect of Rh "··ee" compared with Rh "ccE·" and Rh "C·E·" was stated (P = .001), foremost in CD47-positive adenocarcinomas (Rh "··ee" vs. Rh "ccE·" and Rh "C·E·," P = .008). Inversely Rh "ccE·" or Rh "C·E·" was found beneficial in CD47-negative non-adenocarcinomas (P = .046). Phenotypic RhCE expression may be an independent prognostic factor for overall survival in adeno-NSCLC. We hypothesize an erythrocytic-immunologic interaction with tumor tissue, possibly altered by RhCE and CD47, resulting in a metastatic prone condition. © 2017 John Wiley & Sons Ltd.

  20. Tumor Hypoxia is Independent of Hemoglobin and Prognostic for Loco-regional Tumor Control after Primary Radiotherapy in Advanced Head and Neck Cancer

    International Nuclear Information System (INIS)

    Nordsmark, Marianne; Overgaard, Jens

    2004-01-01

    There is evidence that tumor hypoxia adversely affects loco-regional tumor control and survival in head and neck cancer. The aim of the current study was to compare pretreatment tumor oxygenation measured by Eppendorf pO2 electrodes with known prognostic factors in advanced head and neck tumors after definitive radiotherapy, and to evaluate the prognostic significance of these parameters on loco-regional tumor control. Sixty-seven patients, median age 56 years (22-82), all with primary stage III-IV squamous cell carcinoma were available for survival analysis. Tumor oxygenation was described as the fraction of pO2 values=2.5 mmHg (HP2.5) and the median tumor pO2. By regression analysis HP2.5 was independent of known prognostic factors including stage, pretreatment hemoglobin (Hb) and the largest tumor diameter at the site of pO2 measurement. By Kaplan-Meier analysis loco-regional tumor control at 5 years was in favor of less hypoxic tumors using either HP2.5 or median tumor pO2 as descriptors and stratifying by the median values. Also, Hb was prognostic of loco-regional tumor control at 5 years using the median value as cut off. HP2.5 as continuous parameter was highly significant for loco-regional tumor control in a multivariate analysis. In conclusion both HP2.5 and total Hb were prognostic for loco-regional tumor control, but HP2.5 as continuous variable was independently the strongest prognostic indicator for loco-regional tumor control after definitive primary radiotherapy in advanced head and neck tumors

  1. Lymphopenia: A new independent prognostic factor for survival in patients treated with whole brain radiotherapy for brain metastases from breast carcinoma

    International Nuclear Information System (INIS)

    Claude, Line; Perol, David; Ray-Coquard, Isabelle; Petit, Thierry; Blay, Jean-Yves; Carrie, Christian; Bachelot, Thomas

    2005-01-01

    Background and purpose: To determine overall survival (OS) and independent prognostic factors in patients with brain metastases (BM) from breast cancer treated by whole brain radiotherapy (WBR). Patients and methods: One hundred and twenty (120) women with BM, treated in a single French cancer center between 02/91 and 06/01, were reviewed. BM were confirmed by computed tomography or magnetic resonance imaging. Survival time was defined as the time interval from the date of BM to the date of death or last follow-up. A Cox proportional hazards regression model was used to determine significant prognostic factors in a multivariate analysis. Results: Surgery was followed by WBR in 5 patients. One hundred and four (104) patients received exclusive WBR, eight received concomitant chemo-radiation, and one received chemo-radiation after surgery. The median survival time was 5 months (95% CI: 3-7 months). In the multivariate analysis, performance status over 1 and lymphopenia (<0.7 G/L) were found to be independent prognostic factors for poor survival. Based on the number of these independent prognostic factors, we propose a predictive model for survival in brain metastatic cancer patients. Median survival was 7 months for patients presenting none or one poor prognosis factor at diagnosis versus 2 months for patients with 2 poor prognosis factors (p<0.0001) Conclusion: Brain metastases from breast cancer remain associated with very poor prognosis and there is a need for better treatment procedures. If confirmed in predictive models, the identification of prognostic subgroups, based on KPS and lymphopenia, among patients with BM from breast cancer would help physicians select patients for future clinical trials

  2. High YKL-40 is associated with poor survival in patients with renal cell carcinoma: a novel independent prognostic marker.

    Science.gov (United States)

    Väänänen, Tuija; Kallio, Jukka; Vuolteenaho, Katriina; Ojala, Alexandra; Luukkaala, Tiina; Hämäläinen, Mari; Tammela, Teuvo; Kellokumpu-Lehtinen, Pirkko-Liisa; Moilanen, Eeva

    2017-10-01

    YKL-40 is an inflammation-associated glycoprotein supposed to have a role in cell survival and angiogenesis. Renal cell carcinoma (RCC) is characterized by varying prognosis and risk of relapse after a disease-free period of years. Prognostic markers are critically needed. This study investigated whether YKL-40 could be a useful biomarker in RCC patients. Blood samples from 82 patients with RCC were collected at the time of diagnosis and 3, 5 and 9 months and 2 and 3 years after nephrectomy. YKL-40 levels were determined by enzyme-linked immunosorbent assay. Survival of patients and relapse of RCC were followed up to 15 years. Circulating YKL-40 levels were increased in patients with metastatic RCC at the time of diagnosis (median 115.7 ng/ml, interquartile range 61.0-221.6 ng/ml). Among patients primarily diagnosed with non-metastatic RCC, baseline YKL-40 levels were significantly higher in patients who experienced a relapse during follow-up (103.7, 59.3-242.0 ng/ml) than in patients without relapse (50.6, 33.8-97.1 ng/ml). High baseline YKL-40 was highly associated with poor prognosis in RCC: in age-adjusted univariate analysis, YKL-40 over 120 ng/ml (highest tertile) predicted over five-fold mortality in 5 years, and in multivariate analysis high YKL-40 remained a statistically significant independent risk factor for 5 and 15 year survival. Increased circulating YKL-40 levels were significantly associated with poor survival in patients with RCC. The results suggest YKL-40 as a useful novel biomarker in evaluating prognosis and relapse risk in RCC, being especially beneficial in patients primarily diagnosed with non-metastatic RCC.

  3. Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2.

    Science.gov (United States)

    Buglioni, S; D'Agnano, I; Cosimelli, M; Vasselli, S; D'Angelo, C; Tedesco, M; Zupi, G; Mottolese, M

    1999-12-22

    About 40% of patients with colorectal carcinoma will develop local or distant tumour recurrences. Integrated analyses of bio-pathological markers, predictive of tumour aggressiveness, may offer a more rational approach to planning adjuvant therapy. To this end, we analysed the correlation between p53 accumulation, Bcl-2 expression, DNA ploidy, cell proliferation and conventional clinico-pathological parameters by testing the prognostic significance of these variables in a series of 171 colorectal carcinoma patients with long-term follow-up. The relationships among the various bio-pathological parameters, analysed by multiple correspondence analysis, showed 2 different clinico-biological profiles. The first, characterised by p53 negativity, Bcl-2 positivity, diploidy, low percentage of cells in S-phase (%S-phase), a low Ki-67 score, is associated with Dukes' A-B stage, well differentiated tumours and lack of relapse. The second, defined by p53 positivity, Bcl-2 negativity, aneuploidy, high %S-phase and elevated Ki-67 score, correlates with Dukes' C-D stage, poorly differentiated tumours and presence of relapse. When these parameters were examined according to Kaplan-Meier's method, significantly shorter disease-free (DFS) and overall survival (OS) were also observed in patients bearing p53 positive and Bcl-2 negative tumours, in Dukes' B stage. In multivariate analysis, p53 accumulation and Bcl-2 expression emerged as independent predictors of a worse and better clinical outcome, respectively. Our results indicate that, in colorectal adenocarcinomas, a biological profile, based on the combined evaluation of p53 and Bcl-2, may be useful for identifying high risk patients to be enrolled in an adjuvant setting, mainly in an early stage of the disease. Int. J. Cancer (Pred. Oncol.) 84:545-552, 1999. Copyright 1999 Wiley-Liss, Inc.

  4. A Neolithic expansion, but strong genetic structure, in the independent history of New Guinea.

    Science.gov (United States)

    Bergström, Anders; Oppenheimer, Stephen J; Mentzer, Alexander J; Auckland, Kathryn; Robson, Kathryn; Attenborough, Robert; Alpers, Michael P; Koki, George; Pomat, William; Siba, Peter; Xue, Yali; Sandhu, Manjinder S; Tyler-Smith, Chris

    2017-09-15

    New Guinea shows human occupation since ~50 thousand years ago (ka), independent adoption of plant cultivation ~10 ka, and great cultural and linguistic diversity today. We performed genome-wide single-nucleotide polymorphism genotyping on 381 individuals from 85 language groups in Papua New Guinea and find a sharp divide originating 10 to 20 ka between lowland and highland groups and a lack of non-New Guinean admixture in the latter. All highlanders share ancestry within the last 10 thousand years, with major population growth in the same period, suggesting population structure was reshaped following the Neolithic lifestyle transition. However, genetic differentiation between groups in Papua New Guinea is much stronger than in comparable regions in Eurasia, demonstrating that such a transition does not necessarily limit the genetic and linguistic diversity of human societies. Copyright © 2017, American Association for the Advancement of Science.

  5. A Neolithic expansion, but strong genetic structure, in the independent history of New Guinea

    Science.gov (United States)

    Bergström, Anders; Oppenheimer, Stephen J; Mentzer, Alexander J; Auckland, Kathryn; Robson, Kathryn; Attenborough, Robert; Alpers, Michael P; Koki, George; Pomat, William; Siba, Peter; Xue, Yali; Sandhu, Manjinder S; Tyler-Smith, Chris

    2018-01-01

    New Guinea shows human occupation since ~50 thousand years ago (kya), independent adoption of plant cultivation ~10 kya, and great cultural and linguistic diversity today. We performed genome-wide SNP genotyping on 381 individuals from 85 language groups in Papua New Guinea (PNG) and find a sharp divide originating 10-20 kya between lowland and highland groups, and a lack of non-New Guinean admixture in the latter. All highlanders share ancestry within the last 10 kya, with major population growth in the same period, suggesting population structure was reshaped following the Neolithic lifestyle transition. However, genetic differentiation between groups in PNG is much stronger than in comparable regions in Eurasia, demonstrating that such a transition does not necessarily limit the genetic and linguistic diversity of human societies. PMID:28912245

  6. Nuclear grade based on transbronchial cytology is an independent prognostic factor in patients with advanced, unresectable non-small cell lung cancer.

    Science.gov (United States)

    Kadota, Kyuichi; Miyai, Yumi; Katsuki, Naomi; Kushida, Yoshio; Matsunaga, Toru; Okuda, Masaya; Yokomise, Hiroyasu; Kanaji, Nobuhiro; Bandoh, Shuji; Haba, Reiji

    2016-09-01

    In patients with resected non-small cell lung cancer (NSCLC), the prognostic value of nuclear grade has been demonstrated. However, among patients with advanced, unresectable NSCLC, the prognostic usefulness of cytological nuclear grade to the authors' knowledge remains unknown. In the current study, the authors used transbronchial cytology to investigate whether nuclear morphometry correlated with clinical outcomes in patients with advanced NSCLC. The authors reviewed patients with advanced, unresectable NSCLC who were diagnosed on transbronchial cytology and were treated at the study institution from 2007 through 2015 (97 patients). Nuclear morphometry (including major diameter) was assessed by an image analysis system and small lymphocytes were used as a reference. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and multivariate analyses were performed using the Cox proportional hazards regression model. In the multivariate analysis, according to the nuclear major diameter as assessed by an image analysis system, a nuclear major diameter >15 μm was an independent prognostic factor of worse OS (hazard ratio [HR], 1.05; P = .003) and PFS (HR, 1.04; P = 0.011). According to the nuclear major diameter as assessed by small lymphocytes, a major diameter of >5 small lymphocytes was an independent prognostic factor of worse OS (HR, 1.32; P<.001) and PFS (HR, 1.20; P = 0.001). A moderately significant correlation between nuclear diameter measurements by an image analysis system and small lymphocytes was observed (P<.001; correlation coefficient, 0.662). Nuclear grade based on nuclear diameter was found to be independently associated with prognosis in patients with advanced, unresectable NSCLC. Cancer Cytopathol 2016;124:630-40. © 2016 American Cancer Society. © 2016 American Cancer Society.

  7. An Independent Evaluation of the Validity of a DNA-Based Prognostic Test for Adolescent Idiopathic Scoliosis.

    Science.gov (United States)

    Roye, Benjamin D; Wright, Margaret L; Matsumoto, Hiroko; Yorgova, Petya; McCalla, Daren; Hyman, Joshua E; Roye, David P; Shah, Suken A; Vitale, Michael G

    2015-12-16

    ScoliScore is a DNA-based prognostic test, designed and used to help to predict the risk of curve progression in patients with adolescent idiopathic scoliosis. The role of this test in clinical practice remains unclear as the published results of the ScoliScore have not been validated independently. The purpose of this study was to determine if the ScoliScore effectively predicted the risk of curve progression in patients with mild and moderate adolescent idiopathic scoliosis in two urban academic medical centers. One hundred and twenty-six patients with adolescent idiopathic scoliosis who met inclusion criteria at two centers were administered the ScoliScore test. Two groups were created: a progression group (those who had a Cobb angle of >40° or those who had undergone surgical fusion) and a non-progression group (those who had skeletal maturity without curve progression to 40°). ScoliScore values and risk levels were compared between the two groups. The negative predictive value was calculated for low-risk scores and the positive predictive value was calculated for high-risk scores. There was no significant difference (p = 0.706) in the mean ScoliScore (and standard deviation) between patients with curve progression (107 ± 55 points) and those without curve progression (102 ± 62 points). There was also no significant difference (p = 0.399) in curve progression between patients with high-risk scores (26.7%) and those with low-risk scores (12.9%). The positive predictive value of the test was 0.27 (95% confidence interval, 0.09 to 0.55), and the negative predictive value was 0.87 (95% confidence interval, 0.69 to 0.96). ScoliScores and rates of progression were not affected by brace-wear. ScoliScores did not differ between patients with and without curve progression, and the negative and positive predictive values were lower in our study than in the previously published validation study by the developers of the test. This may be due to differences in our test

  8. Overexpression of c-kit(CD117), relevant with microvessel density, is an independent survival prognostic factor for patients with HBV-related hepatocellular carcinoma.

    Science.gov (United States)

    Yan, Weiwei; Zhu, Zhenyu; Pan, Fei; Huang, Ang; Dai, Guang-Hai

    2018-01-01

    To explore new biomarkers for indicating the recurrence and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after tumor resection, we investigated the expression and prognostic value of c-kit(CD117) in HBV-related HCC. Immunohistochemistry was used to estimate the expression of c-kit(CD117) and CD34 in the liver cancer tissues. The correlations between the expression of these biomarkers and the clinicopathologic characteristics were analyzed. The positive rate of c-kit(CD117) expression in 206 HCC cases was 48.1%, and c-kit expression was significantly related with CD34-positive microvessel density. CD34-microvessel density numbers were much higher in c-kit(+) HCC tissues than in c-kit(-) HCC tissues (44.13±17.01 vs 26.87±13.16, P =0.003). The expression of c-kit was significantly higher in patients with Edmondson grade III-IV ( P c-kit ( P c-kit as an independent poor prognostic factor of DFS in HCC patients ( P c-kit expression could be considered as an independent unfavorable prognostic factor for predicting DFS in HBV-related HCC patients after surgery. These results could be used to identify patients at a higher risk of early tumor recurrence and poor prognosis.

  9. The ARID1A, p53 and ß-Catenin statuses are strong prognosticators in clear cell and endometrioid carcinoma of the ovary and the endometrium.

    Science.gov (United States)

    Heckl, Marlene; Schmoeckel, Elisa; Hertlein, Linda; Rottmann, Miriam; Jeschke, Udo; Mayr, Doris

    2018-01-01

    The objective of this study was to evaluate the prognostic value of ARID1A, p53, p21, p16 and ß-Catenin in endometrioid and clear cell ovarian and endometrial carcinomas. 97 tumors were available for analysis of ARID1A, p53, p21, p16 and ß-Catenin with the techniques of tissue microarray and immunohistochemistry. 32 were ovarian carcinomas and 65 were endometrial carcinomas. Endometrioid ovarian carcinomas showed negative staining for ARID1A (a) and p21 (b), aberrant expression of p53 (c) and p16 (d) and ß-Catenin positive nuclear expression (e) respectively in 19% (a), 100% (b), 28.6% (c), 52.4% (d) and 4.8% (e) of all cases. In the group of clear cell ovarian carcinomas it was 63.6% (a), 100% (b), 81.8% (c), 54.5% (d) and 0% (e). For endometrioid uterine carcinomas it was 75.7% (a), 94.9% (b), 30.5% (c), 52.1% (d) and 6.8% (e) and for clear cell uterine carcinomas it was 8.6% (a), 100% (b), 50% (c), 100% (d) and 0% (e). Survival analysis showed that negative expression of ARID1A, p53 aberrant expression and ß-Catenin nuclear positive staining are independent negative prognosticators in both, clear cell and endometrioid carcinoma, regardless of ovarian or uterine origin. Cox-Regression analysis showed them again as negative prognostic factors. Furthermore, we found a significant correlation between ARID1A and ß-Catenin expression in endometrioid uterine tumors. The analyzed gynaecological carcinoma showed a distinct expression scheme of proteins that are associated with tumor suppression. We may conclude that ARID1A, p53 and ß-Catenin are the strongest prognostic factors by analyzing a subgroup of tumor suppressor genes in clear cell and endometrioid subtypes of ovarian and endometrial cancer and may be used along with traditional morphological and clinical characteristics for prognosis.

  10. The ARID1A, p53 and ß-Catenin statuses are strong prognosticators in clear cell and endometrioid carcinoma of the ovary and the endometrium.

    Directory of Open Access Journals (Sweden)

    Marlene Heckl

    Full Text Available The objective of this study was to evaluate the prognostic value of ARID1A, p53, p21, p16 and ß-Catenin in endometrioid and clear cell ovarian and endometrial carcinomas.97 tumors were available for analysis of ARID1A, p53, p21, p16 and ß-Catenin with the techniques of tissue microarray and immunohistochemistry. 32 were ovarian carcinomas and 65 were endometrial carcinomas.Endometrioid ovarian carcinomas showed negative staining for ARID1A (a and p21 (b, aberrant expression of p53 (c and p16 (d and ß-Catenin positive nuclear expression (e respectively in 19% (a, 100% (b, 28.6% (c, 52.4% (d and 4.8% (e of all cases. In the group of clear cell ovarian carcinomas it was 63.6% (a, 100% (b, 81.8% (c, 54.5% (d and 0% (e. For endometrioid uterine carcinomas it was 75.7% (a, 94.9% (b, 30.5% (c, 52.1% (d and 6.8% (e and for clear cell uterine carcinomas it was 8.6% (a, 100% (b, 50% (c, 100% (d and 0% (e. Survival analysis showed that negative expression of ARID1A, p53 aberrant expression and ß-Catenin nuclear positive staining are independent negative prognosticators in both, clear cell and endometrioid carcinoma, regardless of ovarian or uterine origin. Cox-Regression analysis showed them again as negative prognostic factors. Furthermore, we found a significant correlation between ARID1A and ß-Catenin expression in endometrioid uterine tumors.The analyzed gynaecological carcinoma showed a distinct expression scheme of proteins that are associated with tumor suppression. We may conclude that ARID1A, p53 and ß-Catenin are the strongest prognostic factors by analyzing a subgroup of tumor suppressor genes in clear cell and endometrioid subtypes of ovarian and endometrial cancer and may be used along with traditional morphological and clinical characteristics for prognosis.

  11. Studies on the independence of the strong interactions on the flavor quantum numbers with bottom, charm, strange, and light quarks

    International Nuclear Information System (INIS)

    Biebel, O.

    1993-11-01

    A study of possible flavour dependence of the strong interaction is presented using data collected with the OPAL detector at the e + e - collider LEP. Four subsamples of events, highly enriched in bottom, charm, strange and light quarks are obtained from high momentum electrons and muons, D *± mesons, K s 0 mesons, and highly energetic stable charged particles, respectively. From the jet production rates of each of these four samples a strong coupling constant α s f for the dominant quark flavour is derived. The ratios of α s for a specific quark flavour f and its complementary flavours are determined to be α s b /α s udsc =1.017±0.036, α s c /α s udsb =0.918±0.115, α s s /α s udcb =1.158±0.164, α s uds /α s cb =1.038 ± 0.221, where the errors are combinations of statistical and systematic uncertainties. In combining the relevant data samples, a systematic study of possible dependence of the strong interaction on quark mass, weak isospin, and generation is performed. No evidence for any such dependence of the strong coupling constant α s is observed. Finally all samples are combined to determine the strong coupling constant of each flavour individually. Again the results are well consistent with the flavour independence of QCD. (orig.)

  12. Cell-associated HIV DNA measured early during infection has prognostic value independent of serum HIV RNA measured concomitantly

    DEFF Research Database (Denmark)

    Katzenstein, Terese L; Oliveri, Roberto S; Benfield, Thomas

    2002-01-01

    Using data from the Danish AIDS Cohort of HIV-infected homosexual men established in the 1980s, the prognostic value of early HIV DNA loads was evaluated. In addition to DNA measurements, concomitant serum HIV RNA levels, CD4 cell counts and CCR5 genotypes were determined. The patients were divided...

  13. Flow-mediated dilatation has no independent prognostic effect in patients with chest pain with or without ischaemic heart disease

    DEFF Research Database (Denmark)

    Ulriksen, Line Skjold; Malmqvist, Beata B; Hansen, Are

    2009-01-01

    OBJECTIVE: The purpose of this study was to assess the prognostic effect of flow-mediated dilatation (FMD) in patients with chest pain admitted to a coronary care unit. METHODS: Endothelium-dependent FMD in the brachial artery was examined in 223 patients with acute chest pain. All patients under...

  14. Elevated preoperative aspartate aminotransferase to lymphocyte ratio index as an independent prognostic factor for patients with hepatocellular carcinoma after hepatic resection

    Science.gov (United States)

    Liao, Yan; Li, Jun; Liao, Weijia; He, Songqing

    2015-01-01

    Few studies have elucidated the relationship between preoperative aspartate aminotransferase (AST) to lymphocyte ratio and high incidence of hepatocellular carcinoma (HCC). In search of a simple non-invasive prognostic marker, we investigated the prognostic significance of AST to lymphocyte ratio index (ALRI) in HCC. We reviewed retrospectively clinical parameters of 371 HCC patients who were treated with hepatectomy. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value of preoperative ALRI. The predictive value of preoperative ALRI in HCC was evaluated by univariate and multivariate analyses using Cox proportional hazards regression modeling, and the survival probability of HCC patients was acquired by the Kaplan-Meier plots. In addition, stratified analysis was used to investigate the impact of preoperative ALRI on survival in different HCC subgroups. The results showed that preoperative ALRI was closely correlated with age (p = 0.007), median size (p = 0.004), clinical tumor-node-metastasis (TNM) stage (p 25.2 have a poorer disease-free survival (DFS) and overall survival (OS) after tumor resection. Multivariate analysis further identified preoperative ALRI > 25.2 (p = 0.002), III-IV of TNM stage (p = 0.011), PVTT (p = 0.035), size of tumor > 5 cm (p 25.2 (p = 0.001), III-IV of TNM stage (p = 0.005), PVTT (p = 0.012), size of tumor > 5 cm (p < 0.001), recurrence (p < 0.001) as independent prognostic factors for OS in HCC patients. Additionally, preoperative ALRI also showed different prognostic value in various subgroups of HCC. Elevated preoperative ALRI as a noninvasive, simple, and easily assessable parameter is an independent effective predictor of prognosis for patients with HCC. PMID:26057470

  15. A comparison of prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill: a cohort study.

    Science.gov (United States)

    Ho, Kwok M; Lan, Norris S H; Williams, Teresa A; Harahsheh, Yusra; Chapman, Andrew R; Dobb, Geoffrey J; Magder, Sheldon

    2016-01-01

    This cohort study compared the prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill. The relationships between SIG, lactate, anion gap (AG), anion gap albumin-corrected (AG-corrected), base excess or strong ion difference-effective (SIDe), all obtained within the first hour of intensive care unit (ICU) admission, and the hospital mortality of 6878 patients were analysed. The prognostic significance of each acid-base marker, both alone and in combination with the Admission Mortality Prediction Model (MPM0 III) predicted mortality, were assessed by the area under the receiver operating characteristic curve (AUROC). Of the 6878 patients included in the study, 924 patients (13.4 %) died after ICU admission. Except for plasma chloride concentrations, all acid-base markers were significantly different between the survivors and non-survivors. SIG (with lactate: AUROC 0.631, confidence interval [CI] 0.611-0.652; without lactate: AUROC 0.521, 95 % CI 0.500-0.542) only had a modest ability to predict hospital mortality, and this was no better than using lactate concentration alone (AUROC 0.701, 95 % 0.682-0.721). Adding AG-corrected or SIG to a combination of lactate and MPM0 III predicted risks also did not substantially improve the latter's ability to differentiate between survivors and non-survivors. Arterial lactate concentrations explained about 11 % of the variability in the observed mortality, and it was more important than SIG (0.6 %) and SIDe (0.9 %) in predicting hospital mortality after adjusting for MPM0 III predicted risks. Lactate remained as the strongest predictor for mortality in a sensitivity multivariate analysis, allowing for non-linearity of all acid-base markers. The prognostic significance of SIG was modest and inferior to arterial lactate concentration for the critically ill. Lactate concentration should always be considered regardless whether physiological, base excess or physical-chemical approach

  16. Early clearance of peripheral blasts measured by flow cytometry during the first week of AML induction therapy as a new independent prognostic factor: a GOELAMS study.

    Science.gov (United States)

    Lacombe, F; Arnoulet, C; Maynadié, M; Lippert, E; Luquet, I; Pigneux, A; Vey, N; Casasnovas, O; Witz, F; Béné, M C

    2009-02-01

    An early appreciation of treatment efficacy could be very useful in acute myeloblastic leukemia (AML), and a prognostic value has been suggested for the morphological assessment of decrease in blasts during induction therapy. More sensitive, multiparametric flow cytometry (FCM) can detect far lower blast counts, allowing for a precise and reliable calculation of blast cell decrease rate (BDR). Such a multiparametric FCM four-colours/single-tube protocol, combining CD11b, CD45-ECD and CD16-PC5, was applied to peripheral blood samples from 130 AML patients, collected daily during induction chemotherapy. Normalized blast cell percentages were used to calculate the relevant decrease slopes. Slope thresholds (-15), or the time required to reach 90% depletion of the peripheral blast load (5 days), was strongly associated with the achievement of complete remission (P<0.0001). Log-rank test and Cox model showed that they also carried high statistical significance (P<0.0001) for disease-free survival. The prognostic value of cytogenetic features, confirmed in this series, was refined by BDR, which allowed to discriminate between good- and poor-risk patients among those with intermediate or normal karyotypes. This simple FCM protocol allows for an accurate prognostic sequential approach adapted to the determination of decrease in peripheral blast cells during induction chemotherapy.

  17. The chronic lymphocytic leukemia international prognostic index (CLL-IPI) predicts time to first treatment in early CLL: Independent Validation in a Prospective Cohort of Early Stage Patients

    Science.gov (United States)

    Molica, Stefano; Shanafelt, Tait D.; Giannarelli, Diana; Gentile, Massimo; Mirabelli, Rosanna; Cutrona, Giovanna; Levato, Luciano; Di Renzo, Nicola; Di Raimondo, Francesco; Musolino, Caterina; Angrilli, Francesco; Famà, Angelo; Recchia, Anna Grazia; Chaffee, Kari G.; Neri, Antonino; Kay, Neil E.; Ferrarini, Manlio; Morabito, Fortunato

    2016-01-01

    The chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) combines 5 parameters (age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], IGHV mutational status, serum β2-microglobulin) to predict survival and time-to-first-treatment (TTFT) in CLL patients. We performed an observational study in 337 prospectively collected, Binet stage A patients to validate the ability of the CLL-IPI to predict TTFT in an independent cohort of early stage CLL patients. The CLL-IPI score stratified Binet stage A patients into three subgroups with different outcome. Since the CLL-IPI was originally developed to predict survival, we next investigated the optimal cut-off score to predict TTFT in Binet stage A patients. Recursive partitioning analysis identified three subsets with scores of 0 (n=139), 1 (n=90), and ≥ 2(n=108). The probability of remaining free from therapy 5 years after diagnosis was 85%, 67% and 46% in these three categories (PIPI scoring for TTFT was subsequently validated in an independent cohort of Binet A patients from the Mayo Clinic (n=525). The ability of either original or optimized CLL-IPI to predict TTFT was equivalent to other prognostic models specifically designed for this endpoint (2011 MDACC score and O-CLL1 score). Although originally developed to predict suvival, the CLL-IPI is useful for predicting TTFT in early stage CLL patients. PMID:27465919

  18. What does it take to have a strong and independent profession of midwifery? Lessons from the Netherlands.

    Science.gov (United States)

    De Vries, Raymond; Nieuwenhuijze, Marianne; Buitendijk, Simone E

    2013-10-01

    In the 1970s, advocates of demedicalising pregnancy and birth 'discovered' Dutch maternity care. The Netherlands presented an attractive model because its maternity care system was characterised by a strong and independent profession of midwifery, close co-operation between obstetricians and midwives, a very high rate of births at home, little use of caesarean section, and morbidity and mortality statistics that were among the best in the developed world. Over the course of the following 40 years much has changed in the Netherlands. Although the home birth rate remains quite high when compared to other modern countries, it is half of what it was in the 1970s. Midwifery is still an independent medical profession, but a move toward 'integrated care' threatens to bring midwives into hospitals under the direction of medical specialists, more women are interested in medical pain relief, and there is a growing concern that current, albeit slight, increases in rates of intervention in physiological births foreshadow the end of the unique approach to birth in the Netherlands. The story of Dutch maternity care thus offers an ideal opportunity to examine the social, organisational, and cultural factors that work to support, and to diminish, the independent practice of midwifery in high-resource countries. We may wish to believe that providing ample and convincing evidence of the value of midwifery care will be enough to promote more and better use of midwifery, but the lessons from the Netherlands make clear that an array of social forces play a critical role determining the place of midwives in the health care system and how the care they provide is deployed. © 2013 Elsevier Ltd. All rights reserved.

  19. Mammaglobin B is an independent prognostic marker in epithelial ovarian cancer and its expression is associated with reduced risk of disease recurrence

    International Nuclear Information System (INIS)

    Tassi, Renata A; Todeschini, Paola; Romani, Chiara; Bandiera, Elisabetta; Zanotti, Laura; Pecorelli, Sergio; Santin, Alessandro D; Calza, Stefano; Ravaggi, Antonella; Bignotti, Eliana; Odicino, Franco E; Tognon, Germana; Donzelli, Carla; Falchetti, Marcella; Rossi, Elisa

    2009-01-01

    Traditional prognostic factors in epithelial ovarian cancer (EOC) are inadequate in predicting recurrence and long-term prognosis, but genome-wide cancer research has recently provided multiple potentially useful biomarkers. The gene codifying for Mammaglobin B (MGB-2) has been selected from our previous microarray analysis performed on 19 serous papillary epithelial ovarian cancers and its expression has been further investigated on multiple histological subtypes, both at mRNA and protein level. Since, to date, there is no information available on the prognostic significance of MGB-2 expression in cancer, the aim of this study was to determine its prognostic potential on survival in a large cohort of well-characterized EOC patients. MGB-2 expression was evaluated by quantitative real time-PCR in fresh-frozen tissue biopsies and was validated by immunohistochemistry in matched formalin fixed-paraffin embedded tissue samples derived from a total of 106 EOC patients and 27 controls. MGB-2 expression was then associated with the clinicopathologic features of the tumors and was correlated with clinical outcome. MGB-2 expression was found significantly elevated in EOC compared to normal ovarian controls, both at mRNA and protein level. A good correlation was detected between MGB-2 expression data obtained by the two different techniques. MGB-2 expressing tumors were significantly associated with several clinicopathologic characteristics defining a less aggressive tumor behavior. Univariate survival analysis revealed a decreased risk for cancer-related death, recurrence and disease progression in MGB-2-expressing patients (p < 0.05). Moreover, multivariate analysis indicated that high expression levels of MGB-2 transcript (HR = 0.25, 95%, 0.08–0.75, p = 0.014) as well as positive immunostaining for the protein (HR = 0.41, 95%CI, 0.17–0.99, p = 0.048) had an independent prognostic value for disease-free survival. This is the first report documenting that MGB-2

  20. hERG1 Channels and Glut-1 as Independent Prognostic Indicators of Worse Outcome in Stage I and II Colorectal Cancer: A Pilot Study.

    Science.gov (United States)

    Lastraioli, Elena; Bencini, Lapo; Bianchini, Elisa; Romoli, Maria Raffaella; Crociani, Olivia; Giommoni, Elisa; Messerini, Luca; Gasperoni, Silvia; Moretti, Renato; Di Costanzo, Francesco; Boni, Luca; Arcangeli, Annarosa

    2012-04-01

    There is a need to identify new markers to assess recurrence risk in early-stage colorectal cancer (CRC) patients. We explored the prognostic impact of ether-a-gò-gò-related gene 1 channels and some hypoxia markers, in patients with nonmetastatic (stage I, II, and III) CRC. The expression of hERG1, vascular endothelial growth factor A (VEGF-A), glucose transporter 1, carbonic anhydrase IX (CA-IX), epidermal growth factor receptor (EGF-R), and p53 was tested by immunohistochemistry in 135 patients. The median follow-up was 35 months. Clinicopathologic parameters and overall survival were evaluated. hERG1 displayed a statistically significant association with Glut-1, VEGF-A, CA-IX, and EGF-R; p53 with VEGF-A and CA-IX; Glut-1 with the age of the patients; and EGF-R with TNM and mucin content. TNM and CA-IX were prognostic factors at the univariate analysis; TNM, hERG1, and Glut-1, at the multivariate analysis. Risk scores calculated from the final multivariate model allowed to stratify patients into four different risk groups: A) stage I-II, Glut-1 positivity, any hERG1; B) stage I-II, Glut-1 and hERG1 negativity; C) stage I-II, Glut-1 negativity, hERG1 positivity; D) stage III, any Glut-1 and any hERG1. hERG1 positivity with Glut-1 negativity identifies a patient group with poor prognosis within stage I-II CRC. The possibility that these patients might benefit from adjuvant therapy, independently from the TNM stage, is discussed. More robust prognostic and predictive markers, supplementing standard clinical and pathologic staging, are needed for node-negative patients.

  1. Nadir prostate-specific antigen (PSA) level and time to PSA nadir following primary androgen deprivation therapy as independent prognostic factors in a Japanese large-scale prospective cohort study (J-CaP).

    Science.gov (United States)

    Kitagawa, Yasuhide; Ueno, Satoru; Izumi, Kouji; Mizokami, Atsushi; Hinotsu, Shiro; Akaza, Hideyuki; Namiki, Mikio

    2014-04-01

    The aim of this study was to investigate whether nadir prostate-specific antigen (PSA) level and time to PSA nadir (TTN) are independent prognostic factors equivalent to the pretreatment factors in the data of the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database of patients undergoing primary androgen deprivation therapy (PADT). A total of 10,958 patients treated with PADT were enrolled into the present study. Univariate and multivariate Cox proportional hazards regression analysis and Kaplan-Meier analysis were used to evaluate the associations of PSA nadir level and TTN with progression-free survival (PFS) and overall survival (OS), adjusting for the pretreatment factors adopted in the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score. Of the 10,958 patients, 3,451 (31.5%) had lymph node and/or distant metastases. The median PSA level was 27.0 ng/ml before treatment, and the nadir PSA level in 6,983 patients (63.7%) reached below 0.2 ng/ml. Disease progression occurred in 4,736 cases, and 2,163 patients died during a mean follow-up period of 3.86 years. Nadir PSA level and TTN were independent prognostic factors, similar to the pretreatment factors adopted in the J-CAPRA score. The probabilities of PFS and OS showed significant differences among the groups categorized by the combination of nadir PSA level and TTN in all J-CAPRA risk stratifications. The present study demonstrated that nadir PSA level and TTN are strong predictors in patients undergoing PADT in a large-scale prospective cohort study.

  2. CD4(+) tumor infiltrating lymphocytes are prognostic and independent of R-IPI in patients with DLBCL receiving R-CHOP chemo-immunotherapy.

    Science.gov (United States)

    Keane, Colm; Gill, Devinder; Vari, Frank; Cross, Donna; Griffiths, Lynn; Gandhi, Maher

    2013-04-01

    Despite the Revised International Prognostic Index's (R-IPI) undoubted utility in diffuse large B-cell lymphoma (DLBCL), significant clinical heterogeneity within R-IPI categories persists. Emerging evidence indicates that circulating host immunity is a robust and R-IPI independent prognosticator, most likely reflecting the immune status of the intratumoral microenvironment. We hypothesized that direct quantification of immunity within lymphomatous tissue would better permit stratification within R-IPI categories. We analyzed 122 newly diagnosed consecutive DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemo-immunotherapy. Median follow-up was 4 years. As expected, the R-IPI was a significant predictor of outcome with 5-year overall survival (OS) 87% for very good, 87% for good, and 51% for poor-risk R-IPI scores (P IPI and LMR. Importantly, within very good/good R-IPI patients, CD4(+) T-cells still distinguished patients with different 5 year OS (high 96% versus low 63%, P = 0.02). These results illustrate the importance of circulating and local intratumoral immunity in DLBCL treated with R-CHOP. Copyright © 2013 Wiley Periodicals, Inc.

  3. The size of retrieved lymph nodes correlates with the number of retrieved lymph nodes and is an independent prognostic factor in patients with stage II colon cancer.

    Science.gov (United States)

    Okada, Kazutake; Sadahiro, Sotaro; Suzuki, Toshiyuki; Tanaka, Akira; Saito, Gota; Masuda, Shinobu; Haruki, Yasuo

    2015-12-01

    In stage II colon cancer, patients with many retrieved lymph nodes (LNs) have been reported to have better oncological outcomes. We tested the hypothesis that the greater number of retrieved LNs is related to a larger LN size. The subjects comprised 320 patients with stage II colon cancer who underwent curative resection. All operations were elective and were performed by the same surgeons. The maximum long axis and short axis diameters of LNs were measured on hematoxylin-eosin-stained specimens. A total of 4,744 LNs were evaluated. The number of retrieved LNs was 14.8 ± 10.1 (mean ± SD). The long axis diameter was 4.8 ± 2.6 mm, with a median value of 4.3 mm, a maximum value of 20.4 mm, and a minimum value of 0.6 mm. The corresponding short axis diameters were 3.4 ± 1.7, 3.0, 15.1, and 0.5 mm, respectively. The highest correlation coefficient for the association with the number of LNs was obtained for the maximum value of the long axis diameter (0.59). Multivariate analysis revealed that age, tumor location, pathological T stage, and the maximum long axis diameter were independent prognostic factors. The number of LNs was not a significant factor. Patients with less than 12 LNs and a maximum long axis diameter of less than 10 mm had significantly poorer outcomes (p patients with stage II colon cancer, the maximum long axis diameter of LNs correlated with the number of LNs and was an independent prognostic factor.

  4. Severe hypoalbuminemia is a strong independent risk factor for acute respiratory failure in COPD: a nationwide cohort study

    Directory of Open Access Journals (Sweden)

    Chen CW

    2015-06-01

    Full Text Available Char-Wen Chen,1,* Yih-Yuan Chen,2,* Chin-Li Lu,3 Solomon Chih-Cheng Chen,3 Yi-Jen Chen,1,4 Ming-Shian Lin,1,4 Wei Chen1,5,6 1Division of Pulmonary and Critical Care Medicine, Chia-Yi Christian Hospital, Chiayi, 2Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, 3Department of Medical Research, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chiayi, 4Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi Campus; Changhua, 5College of Nursing, Dayeh University, Changhua 6Department of Respiratory Therapy, China Medical University, Taichung, Taiwan *These authors contributed equally to this work Background: Acute respiratory failure (ARF is a life-threatening event, which is frequently associated with the severe exacerbations of chronic obstructive pulmonary disease (COPD. Hypoalbuminemia is associated with increased mortality in patients with COPD. However, to date, little is known regarding whether or not hypoalbuminemia is a risk factor for developing ARF in COPD.Methods: We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan. A total of 42,732 newly diagnosed COPD patients (age ≥40 years from 1997 to 2011 were enrolled. Among them, 1,861 (4.36% patients who had received albumin supplementation were defined as hypoalbuminemia, and 40,871 (95.6% patients who had not received albumin supplementation were defined as no hypoalbuminemia.Results: Of 42,732 newly diagnosed COPD patients, 5,248 patients (12.3% developed ARF during the 6 years follow-up period. Patients with hypoalbuminemia were older, predominantly male, had more comorbidities, and required more steroid treatment and blood transfusions than patients without hypoalbuminemia. In a multivariable Cox regression analysis model, being elderly was the strongest independent risk factor for ARF (adjusted hazard ratio [HR]: 4.63, P<0.001, followed by hypoalbuminemia (adjusted HR: 2

  5. Preoperative γ-glutamyl transpeptidase to platelet ratio (GPR) is an independent prognostic factor for HBV-related hepatocellular carcinoma after curative hepatic resection.

    Science.gov (United States)

    Wang, Wan-Li; Zheng, Xing-Long; Zhang, Zhi-Yong; Zhou, Ying; Hao, Jie; Tang, Gang; Li, Ou; Xiang, Jun-Xi; Wu, Zheng; Wang, Bo

    2016-07-01

    Liver fibrosis and cirrhosis is associated with the prognosis of patients with hepatocellular carcinoma (HCC) after treatment. The γ-glutamyl transpeptidase to platelet ratio (GPR) is reported to predict significant liver fibrosis and cirrhosis. The aim of this study was to investigate the predictive value of preoperative GPR on the recurrence and survival of patients with HCC who underwent curative hepatectomy.A retrospective review of demographics, medical records, and prognosis of patients with hepatitis B virus (HBV)-related HCC was performed. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier method, and the log-rank test was used to analyze differences in recurrence and survival. Univariate and multivariate analyses were used for significance of prognostic factor.A total of 357 patients with HBV-related HCC were included in this analysis. The preoperative GPR was associated with recurrence and survival rates, independent of HCC progression or tumor marker levels, in a multivariate analysis. OS was higher in patients with a GPR GPR ≥0.84 than in those with GPR GPR score of ≥0.84 represents a major risk factor for the poor prognosis for HBV-related HCC after hepatic resection, and GPR served as an independent predictive factor for HBV-related HCC OS.

  6. Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients - a prospective study.

    Science.gov (United States)

    Hinz, Sebastian; Hendricks, Alexander; Wittig, Amke; Schafmayer, Clemens; Tepel, Jürgen; Kalthoff, Holger; Becker, Thomas; Röder, Christian

    2017-01-13

    Detection of circulating (CTC) or disseminated tumor cells (DTC) has been associated with negative prognosis and outcome in patients with colorectal cancer, though testing for these cells is not yet part of clinical routine. There are several different methodological approaches to detect tumor cells but standardized detection assays are not implemented so far. In this prospective monocentric study 299 patients with colon cancer were included. CTC and DTC were detected using CK20 RT-PCR as well as immunocytochemistry staining with anti-pan-keratin and anti-EpCAM antibodies. The primary endpoints were: Evaluation of CTC and DTC at the time of surgery and correlation with main tumor characteristics and overall (OS) and disease free survival (DFS). Patients with detectable CTC had a 5-year OS rate of 68% compared to a 5-year OS rate of 85% in patients without detectable CTC in the blood (p = 0.002). Detection of DTC in the bone marrow with CK20 RT-PCR was not associated with a worse OS or DFS. Detection of pan-cytokeratin positive DTC in the bone marrow correlated with a significantly reduced 5-year OS rate (p = 0.048), but detection of DTC in the bone marrow with the anti-EpCAM antibody did not significantly influence the 5-year OS rate (p = 0.958). By multivariate analyses only detection of CTC with CK20 RT-PCR in the blood was revealed to be an independent predictor of worse OS (HR1.94; 95% CI 1.0-3.7; p = 0.04) and DFS (HR 1.94; 95% CI 1.1-3.7; p = 0.044). Detection of CTC with CK20 RT-PCR is a highly specific and independent prognostic marker in colon cancer patients. Detection of DTC in the bone marrow with CK20 RT-PCR or immunohistochemistry with anti-EpCAM antibody is not associated with a negative prognostic influence.

  7. MRI-detected extramural vascular invasion is an independent prognostic factor for synchronous metastasis in patients with rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Beomseok; Lim, Joon-seok; Kim, Honsoul; Kim, Myeong-Jin [Yonsei University, College of Medicine, Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Seoul (Korea, Republic of); Myoung, Sungmin [Jungwon University, Department of Medical Information, Goesan (Korea, Republic of); Choi, Junjeong [Yonsei University Wonju College of Medicine, Department of Pathology, Wonju (Korea, Republic of); Kim, Nam Kyu [Yonsei University, College of Medicine, Department of Surgery, Severance Hospital, Seoul (Korea, Republic of)

    2015-05-01

    To determine whether magnetic resonance imaging (MRI)-detected extramural vascular invasion (EMVI) could predict synchronous distant metastases in rectal cancer. Patients who underwent rectal MRI between July 2011 and December 2012 were screened. This study included 447 patients with pathologically confirmed rectal adenocarcinoma who had undergone MRI without previous treatment. Distant metastases were recorded at the initial work-up and over a 6-month follow-up. Univariate/multivariate logistic regression models were used to determine the risk of metastasis. The diagnostic performance was calculated using pathologic lymphovascular invasion (LVI) as a gold standard. Among 447 patients, 79 patients (17.7 %) were confirmed to have distant metastases. Three MRI features are significantly associated with a high risk of distant metastasis: positive EMVI (odds ratio 3.02), high T stage (odds ratio 2.10) and positive regional lymph node metastasis (odds ratio 6.01). EMVI in a large vessel (≥3 mm) had a higher risk for metastasis than EMVI in a small vessel (<3 mm). Sensitivity, specificity and accuracy of MRI-detected EMVI were 28.2 %, 94.0 % and 80.3 %, respectively. MRI-detected EMVI is an independent risk factor for synchronous metastasis in rectal cancer. EMVI in large vessels is a stronger risk factor for distant metastasis than EMVI in small vessels. (orig.)

  8. Clinical and histopathologic independent prognostic factors in oral squamous cell carcinoma: a retrospective study of 334 cases.

    Science.gov (United States)

    Arduino, Paolo G; Carrozzo, Marco; Chiecchio, Andrea; Broccoletti, Roberto; Tirone, Federico; Borra, Eleonora; Bertolusso, Giorgio; Gandolfo, Sergio

    2008-08-01

    This retrospective hospital-based study reviewed and evaluated the outcome of patients with oral squamous cell carcinoma (OSCC) with the aim of identifying factors affecting the clinical course and survival rate. Patients with a follow-up of at least 12 months were included. The data collected were statistically analyzed for the presence of factors valuable for prognosis; survival curves were processed in accordance with the Kaplan-Meier method. Differences in the expression of variables in different grading levels were investigated. Cox's proportional hazard model for Z(i) covariates (grading, age, T, N) also was calculated. Mean patient age was 67.7 years in women (n = 152) and 62.4 years in men (n = 182). A total of 98 patients were identified with Broder's/World Health Organization grade 1 histology, 176 with grade 2, and 55 with grade 3; 5 patients were identified as grade 4 (carcinoma in situ). Gender and risk factors seemed to be unrelated to prognosis, whereas a significant increase in mortality was seen in patients over age 70. Histological grading, tumor size, and neck involvement were related, as independent factors, in predicting survival in patients with OSCC (QM-H > 3.9). Gender, age, and risk factors had no statistical relationship with cancer histological differentiation. Our analysis reveals a statistically significant relationship among histological Broder's grading of malignancy, tumor size, locoregional involvement, and survival rates, underscoring the utility of tumor differentiation in predicting the clinical course and outcome of OSCC.

  9. A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate.

    Science.gov (United States)

    Wone, B W M; Madsen, P; Donovan, E R; Labocha, M K; Sears, M W; Downs, C J; Sorensen, D A; Hayes, J P

    2015-04-01

    Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR, and BMR was slightly, but not significantly, higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in antagonistically selected lines, and BMR was slightly, but not significantly, lower (4.2%). Analysis of breeding values revealed no positive genetic trend for elevated BMR in high-MMR lines. A weak positive genetic correlation was detected between MMR and BMR. That weak positive genetic correlation supports the aerobic capacity model for the evolution of endothermy in the sense that it fails to falsify a key model assumption. Overall, the results suggest that at least in these mice there is significant capacity for independent evolution of metabolic traits. Whether that is true in the ancestral animals that evolved endothermy remains an important but unanswered question.

  10. c-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal Cancer.

    Science.gov (United States)

    Lee, Kyu Sang; Kwak, Yoonjin; Nam, Kyung Han; Kim, Duck-Woo; Kang, Sung-Bum; Choe, Gheeyoung; Kim, Woo Ho; Lee, Hye Seung

    2015-01-01

    The aim of this study was to determine the incidence and clinicopathological significance of c-MYC gene copy-number (GCN) gain in patients with primary colorectal cancer (CRC). The c-MYC GCN was investigated in 367 consecutive CRC patients (cohort 1) by using dual-color silver in situ hybridization. Additionally, to evaluate regional heterogeneity, we examined CRC tissue from 3 sites including the primary cancer, distant metastasis, and lymph-node metastasis in 152 advanced CRC patients (cohort 2). KRAS exons 2 and 3 were investigated for mutations. In cohort 1, c-MYC gene amplification, defined by a c-MYC:centromere of chromosome 8 ratio ≥ 2.0, was detected in 31 (8.4%) of 367 patients. A c-MYC GCN gain, defined by ≥ 4.0 c-MYC copies/nucleus, was found in 63 (17.2%) patients and was associated with poor prognosis (P = 0.015). Multivariate Cox regression analysis showed that the hazard ratio for c-MYC GCN gain was 2.35 (95% confidence interval, 1.453-3.802; P patients, c-MYC GCN gain was significantly associated with poor prognosis by univariate (P = 0.034) and multivariate (P = 0.040) analyses. c-MYC protein overexpression was observed in 201 (54.8%) out of 367 patients and weakly correlated with c-MYC GCN gain (ρ, 0.211). In cohort 2, the c-MYC genetic status was heterogenous in advanced CRC patients. Discordance between GCN gain in the primary tumor and either distant or lymph-node metastasis was 25.7% and 30.4%, respectively. A similar frequency for c-MYC GCN gain and amplification was observed in CRC patients with both wild-type and mutated KRAS. c-MYC GCN gain was an independent factor for poor prognosis in consecutive CRC patients and in the stage II-III subgroup. Our findings indicate that the status of c-MYC may be helpful in predicting the patients' outcome and for managing CRC patients.

  11. A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate

    DEFF Research Database (Denmark)

    Wone, B W M; Madsen, Per; Donovan, E R

    2015-01-01

    Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selecti...

  12. WRAP53 is an independent prognostic factor in rectal cancer- a study of Swedish clinical trial of preoperative radiotherapy in rectal cancer patients

    International Nuclear Information System (INIS)

    Zhang, Hong; Wang, Da-Wei; Adell, Gunnar; Sun, Xiao-Feng

    2012-01-01

    Expression of WRAP53 protein has oncogenic properties and it is up regulated in several types of tumors. We examined expression of WRAP53 protein in rectal cancers and analyzed its relationship to the response to preoperative radiotherapy and patient survival. The WRAP53 protein was examined by immunohistochemistry in normal mucosa, primary tumors and lymph node metastases from 143 rectal cancer patients participated in a Swedish clinical trial of preoperative radiotherapy. Frequency of WRAP53 protein expression was increased in primary rectal cancer compared to the normal mucosa (p < 0.05). In non-radiotherapy group positive WRAP53 in primary tumors (p = 0.03, RR, 3.73, 95% CI, 1.13-11.89) or metastases (p = 0.01, RR, 4.11, 95% CI, 1.25-13.14), was associated with poor prognosis independently of stages and differentiations. In radiotherapy group, positive WRAP53 in the metastasis correlated with better survival (p = 0.04). An interaction analysis showed that the correlations of WRAP53 with the prognostic significance with and without radiotherapy in the metastasis differed (p = 0.01). In the radiotherapy group, expression of WRAP53 in metastases gave a better outcome (p = 0.02, RR, 0.32, 95% CI, 0.13-0.84), and an interaction analysis showed significance between the two groups (p = 0.01). WRAP53 may be a new biomarker used to predict prognosis and to select suitable patients for preoperative radiotherapy

  13. Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue.

    LENUS (Irish Health Repository)

    Kennedy, Richard D

    2011-12-10

    Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples.

  14. Naples Prognostic Score, Based on Nutritional and Inflammatory Status, is an Independent Predictor of Long-term Outcome in Patients Undergoing Surgery for Colorectal Cancer.

    Science.gov (United States)

    Galizia, Gennaro; Lieto, Eva; Auricchio, Annamaria; Cardella, Francesca; Mabilia, Andrea; Podzemny, Vlasta; Castellano, Paolo; Orditura, Michele; Napolitano, Vincenzo

    2017-12-01

    The existing scores reflecting the patient's nutritional and inflammatory status do not include all biomarkers and have been poorly studied in colorectal cancers. The purpose of this study was to assess a new prognostic tool, the Naples prognostic score, comparing it with the prognostic nutritional index, controlling nutritional status score, and systemic inflammation score. This was an analysis of patients undergoing surgery for colorectal cancer. The study was conducted at a university hospital. A total of 562 patients who underwent surgery for colorectal cancer in July 2004 through June 2014 and 468 patients undergoing potentially curative surgery were included. MaxStat analysis dichotomized neutrophil:lymphocyte ratio, lymphocyte:monocyte ratio, prognostic nutritional index, and the controlling nutritional status score. The Naples prognostic scores were divided into 3 groups (group 0, 1, and 2). The receiver operating characteristic curve for censored survival data compared the prognostic performance of the scoring systems. Overall survival and complication rates in all patients, as well as recurrence and disease-free survival rates in radically resected patients, were measured. The Naples prognostic score correlated positively with the other scoring systems (p cancer. See Video Abstract at http://links.lww.com/DCR/A469.

  15. miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence

    DEFF Research Database (Denmark)

    Yu, Yingpu; Scheel, Troels K.H.; Luna, Joseph M.

    2017-01-01

    Hepatitis C virus (HCV) requires the liver specific micro-RNA (miRNA), miR-122, to replicate. This was considered unique among RNA viruses until recent discoveries of HCV-related hepaciviruses prompting the question of a more general miR-122 dependence. Among hepaciviruses, the closest known HCV...... generated infectious NPHV/HCV chimeric viruses with the 5’ end of NPHV replacing orthologous HCV sequences. These chimeras were viable even in cells lacking miR-122, although miR-122 presence enhanced virus production. No other miRNAs bound this region. By random mutagenesis, we isolated HCV variants...... partially dependent on miR-122 as well as robustly replicating NPHV/HCV variants completely independent of any miRNAs. These miRNA independent variants even replicate and produce infectious particles in non-hepatic cells after exogenous delivery of apolipoprotein E (ApoE). Our findings suggest that miR-122...

  16. Expression of BAFF-R, but not BAFF, is an independent prognostic factor in diffuse large B-cell lymphoma patients treated with R-CHOP.

    Science.gov (United States)

    Wang, Yu; Li, Ya-Jun; Jiang, Wen-Qi; Rao, Hui-Lan; Huang, Jia-Jia; Xia, Yi; Bi, Xiwen; Sun, Peng; Huang, Hui-Qiang; Lin, Tong-Yu; Guan, Zhong-Zhen; Li, Zhi-Ming

    2015-11-01

    B-cell activating factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the progression of malignant B-cells. The aim of the present study was to evaluate the expression profiles and the clinical significance of BAFF and BAFF-R in diffuse large B-cell lymphoma (DLBCL). Paraffin-embedded specimens from 136 patients with newly diagnosed DLBCL, treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP), were examined for BAFF and BAFF-R expression by immunohistochemistry. BAFF and BAFF-R were expressed in 72.1 % (98/136) and 47.1 % (64/136) of the DLBCL tissues, respectively. Negative BAFF-R expression was significantly correlated with elevated serum lactate dehydrogenase (LDH) levels (P = 0.036), an International Prognostic Index (IPI) score of 2 or higher (P BAFF-R expression than in those with negative BAFF-R expression (73.4 vs. 56.9 %, P = 0.045). Negative expression of BAFF-R, but not of BAFF, was significantly associated with inferior progression-free survival (PFS; P = 0.020) and overall survival (OS; P = 0.028). Only negative BAFF-R expression was correlated with inferior PFS and OS in multivariate analysis (P = 0.049 and 0.040, respectively). Taken together, our results showed that the majority and approximate one-half of patients with DLBCL were positive for BAFF and BAFF-R, respectively. Negative expression of BAFF-R, but not of BAFF, could be an independent risk factor for PFS and OS in patients with DLBCL treated with standard R-CHOP.

  17. CD133 expression is not an independent prognostic factor in stage II and III colorectal cancer but may predict the better outcome in patients with adjuvant therapy

    International Nuclear Information System (INIS)

    Mia-Jan, Khalilullah; Jung, So Young; Kim, Ik-Yong; Oh, Sung Soo; Choi, EunHee; Chang, Sei Jin; Kang, Tae Young; Cho, Mee-Yon

    2013-01-01

    Cancer stem cells (CSCs) are notorious for their capacity of tumor progression, metastasis or resistance to chemo-radiotherapy. However, the undisputed role of cancer stem marker, CD133, in colorectal cancers (CRCs) is not clear yet. We assessed 271 surgically-resected stage II and III primary CRCs with (171) and without (100) adjuvant therapy after surgery. CD133 expression was analyzed by immunohistochemical (IHC) staining and real-time RT-PCR. CD133 promoter methylation was quantified by pyrosequencing. The CD133 IHC expression was significantly correlated with mRNA expression (p=0.0257) and inversely correlated with the promoter methylation (p=0.0001). CD133 was expressed more frequently in rectal cancer (p=0.0035), and in moderately differentiated tumors (p=0.0378). In survival analysis, CD133 expression was not significantly correlated with overall survival (OS) (p=0.9689) as well as disease-free survival (DFS) (p=0.2103). However, CD133+ tumors were significantly associated with better OS in patients with adjuvant therapy compared to those without adjuvant therapy (p<0.0001, HR 0.125, 95% CI 0.052-0.299). But the patients with CD133- tumors did not show any significant difference of survival according to adjuvant therapy (p=0.055, HR 0.500, 95% CI 0.247-1.015). In stage II and III CRCs, CD133 IHC expression may signify the benefit for adjuvant therapy although it is not an independent prognostic factor

  18. A Test of the Flavor Independence of Strong Interactions in e+e- Annihilation at the Z0 Pole

    Energy Technology Data Exchange (ETDEWEB)

    Muller, David

    1999-09-03

    This thesis presents a comparison of the strong coupling of the gluons to light (ql = u + d + s), c, and b quarks, determined from multijet rates in flavor-tagged samples of approximately 150,000 hadronic Z0 decays recorded with the SLC Large Detector at the SLAC Linear Collider between 1993 and 1995. Flavor separation among primary ql {anti ql} , c{anti c} and b {anti b} final states was made on the basis of the reconstructed mass of long-lived heavy-hadron decay vertices, yielding tags with high purity and low bias against {>=} 3-jet final states. The data obtained imply no flavor dependence within our sensitivity.

  19. Independent validation of the prognostic value of cancer stem cell marker expression and hypoxia-induced gene expression for patients with locally advanced HNSCC after postoperative radiotherapy

    Directory of Open Access Journals (Sweden)

    Annett Linge

    2016-12-01

    Conclusions: The HPV status, CSC marker expression of CD44 and SLC3A2 as well as hypoxia status are potential prognostic biomarkers for patients with locally advanced HNSCC treated by postoperative radiotherapy.

  20. The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer: data from CALYPSO trial (a GINECO-GCIG study).

    Science.gov (United States)

    You, Benoit; Colomban, Olivier; Heywood, Mark; Lee, Chee; Davy, Margaret; Reed, Nicholas; Pignata, Sandro; Varsellona, Nenzi; Emons, Günter; Rehman, Khalid; Steffensen, Karina Dahl; Reinthaller, Alexander; Pujade-Lauraine, Eric; Oza, Amit

    2013-08-01

    Unexpected results were recently reported about the poor surrogacy of Gynecologic Cancer Intergroup (GCIG) defined CA-125 response in recurrent ovarian cancer (ROC) patients. Mathematical modeling may help describe CA-125 decline dynamically and discriminate prognostic kinetic parameters. Data from CALYPSO phase III trial comparing 2 carboplatin-based regimens in ROC patients were analyzed. Based on population kinetic approach, serum [CA-125] concentration-time profiles during first 50 treatment days were fit to a semi-mechanistic model with following parameters: "d[CA-125]/dt=(KPROD∗exp (BETA∗t))∗Effect-KELIM∗[CA-125]" with time, t; tumor growth rate, BETA; CA-125 tumor production rate, KPROD; CA-125 elimination rate, KELIM and K-dependent treatment indirect Effect. The predictive values of kinetic parameters were tested regarding progression-free survival (PFS) against other reported prognostic factors. Individual CA-125 kinetic profiles from 895 patients were modeled. Three kinetic parameters categorized by medians had predictive values using univariate analyses: K; KPROD and KELIM (all PCA-125 response (favoring carboplatin-paclitaxel arm), treatment arm, platinum free-interval, measurable lesions and KELIM (HR=0.53; 95% CI 0.45-0.61; PCA-125 kinetics in ROC patients enables understanding of the time-change components during chemotherapy. The contradictory surrogacy of GCIG-defined CA-125 response was confirmed. The modeled CA-125 elimination rate KELIM, potentially assessable in routine, may have promising predictive value regarding PFS. Further validation of this predictive marker is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Prognostic value of proliferation in pleomorphic soft tissue sarcomas

    DEFF Research Database (Denmark)

    Seinen, Jojanneke M; Jönsson, Mats; Bendahl, Pär-Ola O

    2012-01-01

    = 1.6-12.1), Top2a (hazard ratio = 2.2, CI = 1.2-3.5) and high S-phase fraction (hazard ratio = 1.8, CI = 1.2-3.7) significantly correlated with risk for metastasis. When combined with currently used prognostic factors, Ki-67, S-phase fraction and Top2a fraction contributed to refined identification...... of prognostic risk groups. Proliferation, as assessed by expression of Ki-67 and Top2a and evaluation of S-phase fraction and applied to statistical decision-tree models, provides prognostic information in soft tissue sarcomas of the extremity and trunk wall. Though proliferation contributes independently...... to currently applied prognosticators, its role is particularly strong when few other factors are available, which suggests a role in preoperative decision-making related to identification of high-risk individuals who would benefit from neoadjuvant therapy....

  2. Objective malignancy grading of squamous cell carcinoma of the lung. Stereologic estimates of mean nuclear size are of prognostic value, independent of clinical stage of disease

    DEFF Research Database (Denmark)

    Ladekarl, M; Bæk-Hansen, T; Henrik-Nielsen, R

    1995-01-01

    BACKGROUND: The prognostic value of quantitative histopathologic parameters was evaluated in 55 consecutively treated patients with operable lung carcinoma of squamous (N = 39) and mixed, adenosquamous (N = 16) cell type. Patients alive were followed for at least 12 years. METHODS: Using a projec...

  3. Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kristensen, Lasse Sommer; Asmar, Fazila; Dimopoulos, Konstantinos

    2014-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Improvements in overall survival have been observed with the introduction of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), however, prognostic markers...

  4. A retrospective comparative exploratory study on two methylentetrahydrofolate reductase (MTHFR) polymorphisms in esophagogastric cancer: the A1298C MTHFR polymorphism is an independent prognostic factor only in neoadjuvantly treated gastric cancer patients.

    Science.gov (United States)

    Blank, Susanne; Rachakonda, Sivaramakrishna; Keller, Gisela; Weichert, Wilko; Lordick, Florian; Langer, Rupert; Springfeld, Christoph; Bruckner, Thomas; Becker, Karen; Kumar, Rajiv; Ott, Katja

    2014-02-03

    Methylentetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism and consequently could be an important factor for the efficacy of a treatment with 5-fluorouracil. Our aim was to evaluate the prognostic and predictive value of two well characterized constitutional MTHFR gene polymorphisms for primarily resected and neoadjuvantly treated esophagogastric adenocarcinomas. 569 patients from two centers were analyzed (gastric cancer: 218, carcinoma of the esophagogastric junction (AEG II, III): 208 and esophagus (AEG I): 143). 369 patients received neoadjuvant chemotherapy followed by surgery, 200 patients were resected without preoperative treatment. The MTHFR C677T and A1298C polymorphisms were determined in DNA from peripheral blood lymphozytes. Associations with prognosis, response and clinicopathological factors were analyzed retrospectively within a prospective database (chi-square, log-rank, cox regression). Only the MTHFR A1298C polymorphisms had prognostic relevance in neoadjuvantly treated patients but it was not a predictor for response to neoadjuvant chemotherapy. The AC genotype of the MTHFR A1298C polymorphisms was significantly associated with worse outcome (p = 0.02, HR 1.47 (1.06-2.04). If neoadjuvantly treated patients were analyzed based on their tumor localization, the AC genotype of the MTHFR A1298C polymorphisms was a significant negative prognostic factor in patients with gastric cancer according to UICC 6th edition (gastric cancer including AEG type II, III: HR 2.0, 95% CI 1.3-2.0, p = 0.001) and 7th edition (gastric cancer without AEG II, III: HR 2.8, 95% CI 1.5-5.7, p = 0.003), not for AEG I. For both definitions of gastric cancer the AC genotype was confirmed as an independent negative prognostic factor in cox regression analysis. In primarily resected patients neither the MTHFR A1298C nor the MTHFR C677T polymorphisms had prognostic impact. The MTHFR A1298C polymorphisms was an independent prognostic factor in patients with

  5. KIR-HLA profiling shows presence of higher frequencies of strong inhibitory KIR-ligands among prognostically poor risk AML patients.

    Science.gov (United States)

    Shen, Meixin; Linn, Yeh-Ching; Ren, Ee-Chee

    2016-02-01

    The expression and interaction between killer cell immunoglobulin-like receptors (KIRs) and HLA are known to be associated with pathogenesis of diseases, including hematological malignancies. Presence of B haplotype KIR in donors is associated with a lower relapse risk for acute myeloid leukemia (AML) after hematopoietic stem cell transplants (HSCT). However, the association of KIR and HLA repertoire with disease development and other clinical features is not well studied for AML. In this study, 206 Chinese patients with AML were analyzed for their FAB subtypes, risk groups, and chemo-responsiveness to assess possible association with their KIR and HLA profile. The results revealed that a B-content score of 2 was significantly more prevalent in AML patients when compared to normal controls. Notably, there is also a differential frequency in the distribution of B haplotype KIR across distinct FAB subtypes, where the M3 subtype had significantly lower frequencies of B haplotype KIR compared to the M5 subtype (p KIR ligands HLA-C2 and HLA-Bw4-80I were present in significantly higher frequencies in the prognostically "poor" risk group compared to those with "favourable" risk (p KIR-HLA repertoire in the development and biological behavior of AML.

  6. Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Sidenius, N; Sier, CFM; Ullum, H

    2000-01-01

    Human immunodeficiency virus-1 (HIV-1) infection has been shown to result in up-regulation of the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes in vitro and in vivo. The objective of this study was to investigate whether this up-regulation is paralleled by higher serum...... that the serum suPAR level is a novel, strong, and independent predictor of survival in HIV-1 infection. This report is the first to demonstrate an important association between the plasminogen activator system and disease progression in HIV-1 infection....

  7. Independent effects of both right and left ventricular function on plasma brain natriuretic peptide

    DEFF Research Database (Denmark)

    Vogelsang, Thomas Wiis; Jensen, Ruben J; Monrad, Astrid L

    2007-01-01

    BACKGROUND: Brain natriuretic peptide (BNP) is increased in heart failure; however, the relative contribution of the right and left ventricles is largely unknown. AIM: To investigate if right ventricular function has an independent influence on plasma BNP concentration. METHODS: Right (RVEF), left......, which is a strong prognostic marker in heart failure, independently depends on both left and right ventricular systolic function. This might, at least in part, explain why BNP holds stronger prognostic value than LVEF alone....

  8. Long non-coding RNA expression profiles predict metastasis in lymph node-negative breast cancer independently of traditional prognostic markers

    DEFF Research Database (Denmark)

    Sørensen, Kristina P; Thomassen, Mads; Tan, Qihua

    2015-01-01

    INTRODUCTION: Patients with clinically and pathologically similar breast tumors often have very different outcomes and treatment responses. Current prognostic markers allocate the majority of breast cancer patients to the high-risk group, yielding high sensitivities in expense of specificities...... below 20%, leading to considerable overtreatment, especially in lymph node-negative patients. Seventy percent would be cured by surgery and radiotherapy alone in this group. Thus, precise and early indicators of metastasis are highly desirable to reduce overtreatment. Previous prognostic RNA...... cancer patients eligible for adjuvant therapy, as well as early breast cancer patients that could avoid unnecessary systemic adjuvant therapy. This study emphasizes the potential role of lncRNAs in breast cancer prognosis....

  9. The translational expression of ABCA2 and ABCA3 is a strong prognostic biomarker for multidrug resistance in pediatric acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Aberuyi N

    2017-07-01

    structures was revealed by protein tertiary structure prediction, whereas molecular docking analysis suggested similar binding of chemotherapy drugs and therefore a potentially similar role in determining the MDR.Conclusion: Our findings suggested, for the first time, that quantification of the protein level of ABCA2 and ABCA3 transporters had a prognostic impact on pediatric ALL MDR. Furthermore, the tertiary structure of ABCA2 was predicted for the first time, and docking analysis revealed a possible compensatory effect between ABCA2 and ABCA3 transporters, which may contribute to the efflux of cytotoxic drugs and, ultimately, to chemoresistance. Keywords: ABCA2 transporter, ABCA3 transporter, multidrug resistance, childhood acute lymphoblastic leukemia, molecular docking, tertiary structure

  10. Idade como fator independente de prognóstico no câncer de mama Age as an independent prognostic factor in breast cancer

    Directory of Open Access Journals (Sweden)

    Willian Simões Clagnan

    2008-02-01

    patients over 50, with a significant difference among groups (p<0.0001. Death caused by the disease was higher among patients under 40 (46.9% than among patients between 40 and 50 (26.9% and over 50 (22.6%, p=0.0019. The logistic analysis showed that "age under 40" and the "presence of more than one metastatic axillary node" were independent death risk factors. CONCLUSIONS: age under 40 is an independent risk factor for breast cancer. The traditional prognostic indicators, such as stage, tumoral diameter, axillary involvement and presence of hormonal receptors are not associated with the disease evolution.

  11. Local Self-Government in Central and Eastern Europe: a Strong and Independent Local-Level Management Tool or Just a Paper Tiger?

    Directory of Open Access Journals (Sweden)

    Vjekoslav Bratić

    2008-06-01

    Full Text Available The onset of the independence process in Central and Eastern European (CEE countries during the 1990s was marked by tremendous optimism and a declared wish for stronger fiscal decentralisation and the transfer of powers, responsibilities and resources to the units of local and regional self-government that were supposed to be closest to citizens in resolving their daily problems. However, this has not happened in these countries, at least not according to the basic financial decentralisation indicators, and this is the main thesis of this work. Despite numerous adjustments made in the local self-government organisation in the observed countries, an optimum level of local and regional self-government organisation has still not been achieved. The units of local and regional self-government are still heavily dependent on, or rather restricted by, the strong central governments, which reduces their autonomy and their influence on the local social and economic development.

  12. NCCN-IPI score-independent prognostic potential of pretreatment uric acid levels for clinical outcome of diffuse large B-cell lymphoma patients.

    Science.gov (United States)

    Prochazka, Katharina T; Melchardt, Thomas; Posch, Florian; Schlick, Konstantin; Deutsch, Alexander; Beham-Schmid, Christine; Weiss, Lukas; Gary, Thomas; Neureiter, Daniel; Klieser, Eckhard; Greil, Richard; Neumeister, Peter; Egle, Alexander; Pichler, Martin

    2016-11-08

    Blood-based parameters are gaining increasing interest as potential prognostic biomarkers in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this study was to comprehensively evaluate the prognostic significance of pretreatment plasma uric acid levels in patients with newly diagnosed DLBCL. The clinical course of 539 DLBCL patients, diagnosed and treated between 2004 and 2013 at two Austrian high-volume centres with rituximab-based immunochemotherapy was evaluated retrospectively. The prognostic influence of uric acid on overall survival (OS) and progression-free survival (PFS) were studied including multi-state modelling, and analysis of conditional survival. Five-year OS and PFS were 50.4% (95% CI: 39.2-60.6) and 44.0% (33.4-54.0) in patients with uric acid levels above the 75th percentile of the uric acid distribution (Q3, cut-off: 6.8 mg dl -1 ), and 66.2% (60.4-71.5) and 59.6% (53.7-65.0%) in patients with lower levels (log-rank P=0.002 and P=0.0045, respectively). In univariable time-to-event analysis, elevated uric acid levels were associated with a worse PFS (hazard ratio (HR) per 1 log increase in uric acid 1.47, 95% CI: 1.10-1.97, P=0.009) and a worse OS (HR=1.60, 95% CI: 1.16-2.19, P=0.004). These associations prevailed upon multivariable adjustment for the NCCN-IPI score. Uric acid levels significantly improved the predictive performance of the R-IPI and NCCN-IPI scores, and in multi-state analysis, it emerged as a highly significant predictor of an increased risk of death without developing recurrence (transition-HR=4.47, 95% CI: 2.17-9.23, PIPI risk index.

  13. Down-regulation of protein kinase, DNA-activated, catalytic polypeptide attenuates tumor progression and is an independent prognostic predictor of survival in prostate cancer.

    Science.gov (United States)

    Zhang, Xiang; Wang, Yanlin; Ning, Yuan

    2017-03-01

    Protein kinase, DNA-activated, catalytic polypeptide (PRKDC) is a critical component of DNA repair machinery and its dysregulated expression has been observed in various cancer types or premalignant cells. However, its role in prostate cancer (PCa) development and its prognostic significance in PCa is unknown. The mRNA and protein levels of PRKDC were analyzed in 15 pairs of PCa and benign prostatic hyperplasia tissues as well as PCa cell lines by quantitative real-time polymerase chain reaction and Western blot, respectively. Small interfering RNA and short hairpin RNA-mediated knockdown of PRKDC, followed by cell proliferation, colony formation, and soft agar assays were performed. Xenograft mouse model was used to evaluate in vivo effects of PRKDC knockdown. The association between PRKDC expression and clinicopathologic features was assessed by χ 2 tests. Kaplan-Meier analysis was performed to investigate the association between PRKDC expression and overall survival. Cox proportional hazards regression models were used to examine the prognostic significance of PRKDC. Expression of PRKDC mRNA and protein was notably higher in PCa tissues and PCa cell lines. Knockdown of PRKDC markedly reduced cell proliferation, colony formation efficiency, and soft agar growth in DU145 cells. Down-regulation of PRKDC inhibited tumor growth of DU145 xenografts and enhance mice survival. In addition, PRKDC expression in PCa was significantly associated with Gleason score (P = 0.01), tumor stage (P = 0.028), and distant metastasis (P = 0.025). Patients with PCa having higher PRKDC expression had substantially shorter survival than patients with lower PRKDC expression. Down-regulation of PRKDC attenuates tumor progression in PCa. PRKDC may potentially be a prognostic biomarker in PCa. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. NCCN-IPI score-independent prognostic potential of pretreatment uric acid levels for clinical outcome of diffuse large B-cell lymphoma patients

    Science.gov (United States)

    Prochazka, Katharina T; Melchardt, Thomas; Posch, Florian; Schlick, Konstantin; Deutsch, Alexander; Beham-Schmid, Christine; Weiss, Lukas; Gary, Thomas; Neureiter, Daniel; Klieser, Eckhard; Greil, Richard; Neumeister, Peter; Egle, Alexander; Pichler, Martin

    2016-01-01

    Background: Blood-based parameters are gaining increasing interest as potential prognostic biomarkers in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this study was to comprehensively evaluate the prognostic significance of pretreatment plasma uric acid levels in patients with newly diagnosed DLBCL. Methods: The clinical course of 539 DLBCL patients, diagnosed and treated between 2004 and 2013 at two Austrian high-volume centres with rituximab-based immunochemotherapy was evaluated retrospectively. The prognostic influence of uric acid on overall survival (OS) and progression-free survival (PFS) were studied including multi-state modelling, and analysis of conditional survival. Results: Five-year OS and PFS were 50.4% (95% CI: 39.2–60.6) and 44.0% (33.4–54.0) in patients with uric acid levels above the 75th percentile of the uric acid distribution (Q3, cut-off: 6.8 mg dl−1), and 66.2% (60.4–71.5) and 59.6% (53.7–65.0%) in patients with lower levels (log-rank P=0.002 and P=0.0045, respectively). In univariable time-to-event analysis, elevated uric acid levels were associated with a worse PFS (hazard ratio (HR) per 1 log increase in uric acid 1.47, 95% CI: 1.10–1.97, P=0.009) and a worse OS (HR=1.60, 95% CI: 1.16–2.19, P=0.004). These associations prevailed upon multivariable adjustment for the NCCN-IPI score. Uric acid levels significantly improved the predictive performance of the R-IPI and NCCN-IPI scores, and in multi-state analysis, it emerged as a highly significant predictor of an increased risk of death without developing recurrence (transition-HR=4.47, 95% CI: 2.17–9.23, Puric acid levels predict poor long-term outcomes in DLBCL patients beyond the NCCN-IPI risk index. PMID:27764838

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

    Science.gov (United States)

    Roodakker, Kenney R; Elsir, Tamador; 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

    2016-11-08

    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.

  16. Identification of high independent prognostic value of nanotechnology based circulating tumor cell enumeration in first-line chemotherapy for metastatic breast cancer patients.

    Science.gov (United States)

    Liu, Xiao-Ran; Shao, Bin; Peng, Jia-Xi; Li, Hui-Ping; Yang, Yan-Lian; Kong, Wei-Yao; Song, Guo-Hong; Jiang, Han-Fang; Liang, Xu; Yan, Ying

    2017-04-01

    Enumeration of circulating tumor cells (CTCs) is a promising tool in the management of metastatic breast cancer (MBC). This study investigated the capturing efficiency and prognostic value of our previously reported peptide-based nanomagnetic CTC isolation system (Pep@MNPs). We counted CTCs in blood samples taken at baseline (n = 102) and later at patients' first clinical evaluation after starting firstline chemotherapy (n = 72) in a cohort of women treated for MBC. Their median follow-up was 16.3 months (range: 9.0-31.0 months). The CTC detection rate was 69.6 % for the baseline samples. Patients with ≤2 CTC/2 ml at baseline had longer median progression-free survival (PFS) than did those with >2 CTC/2 ml (17.0 months vs. 8.0 months; P = 0.002). Patients with ≤2 CTC/2 ml both at baseline and first clinical evaluation had longest PFS (18.2 months) among all patient groups (P = 0.004). Particularly, among patients with stable disease (SD; per imaging evaluation) our assay could identify those with longer PFS (P 2 CTC/2 ml at baseline were also significantly more likely to suffer liver metastasis (P = 0.010). This study confirmed the prognostic value of Pep@MNPs assays for MBC patients who undergo firstline chemotherapy, and offered extra stratification regarding PFS for patients with SD, and a possible indicator for patients at risk for liver metastasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Four PTEN-targeting co-expressed miRNAs and ACTN4- targeting miR-548b are independent prognostic biomarkers in human squamous cell carcinoma of the oral tongue.

    Science.gov (United States)

    Berania, Ilyes; Cardin, Guillaume B; Clément, Isabelle; Guertin, Louis; Ayad, Tareck; Bissada, Eric; Nguyen-Tan, Phuc Felix; Filion, Edith; Guilmette, Julie; Gologan, Olguta; Soulieres, Denis; Rodier, Francis; Wong, Philip; Christopoulos, Apostolos

    2017-12-01

    The purpose of this study was to determine the prognostic value and oncogenic pathways associated to miRNA expression in squamous cell carcinoma of the oral tongue and to link these miRNA candidates with potential gene targets. We performed a miRNA screening within our institutional cohort (n = 58 patients) and reported five prognostic targets including a cluster of four co-expressed miRNAs (miR-18a, miR-92a, miR-103, and miR-205). Multivariate analysis showed that expression of miR-548b (p = 0.007) and miR-18a (p = 0.004, representative of co-expressed miRNAs) are independent prognostic markers for squamous cell carcinoma of the oral tongue. These findings were validated in The Cancer Genome Atlas (TCGA) cohort (n = 131) for both miRNAs (miR-548b: p = 0.027; miR-18a: p = 0.001). Bioinformatics analysis identified PTEN and ACTN4 as direct targets of the four co-expressed miRNAs and miR-548b, respectively. Correlations between the five identified miRNAs and their respective targeted genes were validated in the two merged cohorts and were concordantly significant (miR-18a/PTEN: p PTEN: p = 0.0008; miR-103/PTEN: p = 0.008; miR-203/PTEN: p = 0.019; miR-548b/ACTN4: p = 0.009). © 2017 UICC.

  18. HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).

    Science.gov (United States)

    Lohaus, Fabian; Linge, Annett; Tinhofer, Inge; Budach, Volker; Gkika, Eleni; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Avlar, Melanie; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Bayer, Christine; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; von Neubeck, Cläre; Baretton, Gustavo B; Löck, Steffen; Thames, Howard D; Krause, Mechthild; Baumann, Michael

    2014-12-01

    To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy. For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival. In the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p=0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (p<0.01) but not with distant metastases. HPV16 DNA status appears to be a strong prognosticator of loco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. SDF-1/CXCR4 expression is an independent negative prognostic biomarker in patients with head and neck cancer after primary radiochemotherapy.

    Science.gov (United States)

    De-Colle, Chiara; Menegakis, Apostolos; Mönnich, David; Welz, Stefan; Boeke, Simon; Sipos, Bence; Fend, Falko; Mauz, Paul-Stefan; Tinhofer, Inge; Budach, Volker; Abu Jawad, Jehad; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Belka, Claus; Ganswindt, Ute; Pigorsch, Steffi; Combs, Stephanie E; Lohaus, Fabian; Linge, Annett; Krause, Mechthild; Baumann, Michael; Zips, Daniel

    2018-01-01

    Preclinical and clinical data suggest that the chemokine pathway governed by SDF-1 and CXCR4 contributes to a resistant phenotype. This retrospective biomarker study aims to explore the specific prognostic value of SDF-1 and CXCR4 expression in locally advanced head and neck squamous cell carcinomas (HNSCC) treated with primary radiochemotherapy (RT-CT). Biopsies from 141 HNSCC tumours of the oral cavity, oropharynx and hypopharynx were evaluated for SDF-1 and CXCR4 expression by immunofluorescence. SDF-1 and CXCR4 expression was correlated with clinico-pathological characteristics and outcome after RT-CT. Patients with tumours exhibiting overexpression of intracellular SDF-1 and CXCR4 have a higher risk for loco-regional relapse and a worse overall survival after RT-CT (multivariate analysis, hazard ratio 2.33, CI [1.18-4.62], p = 0.02 and hazard ratio 2.02, CI [1.13-3.59], p = 0.02, respectively). Similar results were observed when only the subgroup of HPV DNA negative patients were analysed (hazard ratio 2.23 and 2.16, p = 0.02 and p = 0.01, respectively). Our data support the importance of SDF-1 and CXCR4 expression for loco-regional control and overall survival in HNSCC after primary radiochemotherapy. Prospective multivariate validation and further studies into CXCR4 inhibition to overcome radiation resistance are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

    Directory of Open Access Journals (Sweden)

    Jerzy Laudański

    2011-04-01

    Full Text Available The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69. Positive LVI was significantly correlated with lymph node metastasis (p < 0.001, tumor size (p < 0.001, histological grading (p = 0.017, tumor depth (p = 0.001, and stage (p < 0.001. Multivariate logistic analysis identified LVI (p = 0.036 as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04 and overall survival (p = 0.032 in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 90–97

  1. Korean ethnicity as compared with white ethnicity is an independent favorable prognostic factor for overall survival in non-small cell lung cancer before and after the oral epidermal growth factor receptor tyrosine kinase inhibitor era.

    Science.gov (United States)

    Ahn, Myung-Ju; Lee, Jeeyun; Park, Yun-Hee; Ahn, Jin-Seok; Ziogas, Argyrios; Zell, Jason A; Park, Keunchil; Ou, Sai-Hong Ignatius

    2010-08-01

    We have previously demonstrated, using a regional California Cancer Registry database, that Asian ethnicity is an independent favorable prognostic factor for overall survival (OS) in non-small cell lung cancer (NSCLC). Retrospective population-based analysis of Korean and US white patients with NSCLC with known smoking status from Samsung Cancer Center, Seoul, South Korea, and a Southern California Regional Cancer Registry between 1998 and 2005 with follow-up through February 2008 to allow for even case ascertainment periods before and after 2002, when epidermal growth factor receptor tyrosine kinase inhibitors were introduced in Korea and considered as the year of reference. A total of 4622 Korean and 8846 US white patients were analyzed. Median age of diagnosis was 63 years versus 71 years for Korean and white patients, respectively (P white patients were never-smokers. There was significant OS improvement in never-smokers when compared with ever-smokers among either Korean patients (p white (p white patients (p = 0.5641). Except for stage II patients (p = 0.0723), univariate analysis revealed Korean patients had improved OS compared with US white patients among stages I, III, and IV, respectively (all p white; hazard ratio (HR) = 0.869; p white ethnicity improved during 2002-2005 (HR = 0.795; p white ethnicity is an independent favorable prognostic factor for OS in NSCLC. In addition, greater survival benefit among Korean patients with NSCLC was noted in the postepidermal growth factor receptor tyrosine kinase inhibitor era (2002 and after) compared with US white ethnicity.

  2. CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients.

    Science.gov (United States)

    Arnaud, Laurent; Hervier, Baptiste; Néel, Antoine; Hamidou, Mohamed A; Kahn, Jean-Emmanuel; Wechsler, Bertrand; Pérez-Pastor, Gemma; Blomberg, Bjørn; Fuzibet, Jean-Gabriel; Dubourguet, François; Marinho, António; Magnette, Catherine; Noel, Violaine; Pavic, Michel; Casper, Jochen; Beucher, Anne-Bérangère; Costedoat-Chalumeau, Nathalie; Aaron, Laurent; Salvatierra, Juan; Graux, Carlos; Cacoub, Patrice; Delcey, Véronique; Dechant, Claudia; Bindi, Pascal; Herbaut, Christiane; Graziani, Giorgio; Amoura, Zahir; Haroche, Julien

    2011-03-10

    Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsy-proven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality.

  3. Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria.

    Science.gov (United States)

    Turner, Natalie; Wong, Hui-Li; Templeton, Arnoud; Tripathy, Sagarika; Whiti Rogers, Te; Croxford, Matthew; Jones, Ian; Sinnathamby, Mathuranthakan; Desai, Jayesh; Tie, Jeanne; Bae, Susie; Christie, Michael; Gibbs, Peter; Tran, Ben

    2016-02-01

    In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-to-lymphocyte ratio (NLR) >5, as calculated from pre-operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p = 0.001) and recurrence-free survival (HR 0.37, p = 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer. © 2015 UICC.

  4. Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light

    Science.gov (United States)

    Nyström, Harriet; Dring, Ann M.; Svenningsson, Anders; Piehl, Fredrik; Nelson, David W.; Bellander, Bo-Michael

    2015-01-01

    Traumatic brain injury (TBI) is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L) has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s-) and cerebrospinal fluid (CSF-) NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI). A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE). CSF-NF-L was measured in a subcohort (n = 84) with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT) and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5). In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B), S-NF-L yielded an extra 0.023 pseudo-R2 and a significantly better model (p = 0.006) No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that S-NF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further studies, with volume quantification of axonal injury

  5. Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light.

    Directory of Open Access Journals (Sweden)

    Faiez Al Nimer

    Full Text Available Traumatic brain injury (TBI is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s- and cerebrospinal fluid (CSF- NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI. A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE. CSF-NF-L was measured in a subcohort (n = 84 with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5. In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B, S-NF-L yielded an extra 0.023 pseudo-R2 and a significantly better model (p = 0.006 No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that S-NF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further studies, with volume quantification of axonal

  6. Prognostic, quantitative histopathologic variables in lobular carcinoma of the breast

    DEFF Research Database (Denmark)

    Ladekarl, M; Sørensen, Flemming Brandt

    1993-01-01

    of disease, vv(nuc), MI, and NI were of significant independent, prognostic value. On the basis of the multivariate analyses, a prognostic index with highly distinguishing capacity between prognostically poor and favorable cases was constructed. CONCLUSION: Quantitative histopathologic variables are of value...

  7. Aircraft Anomaly Prognostics Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Ridgetop Group will leverage its proven Electromechanical Actuator (EMA) prognostics methodology to develop an advanced model-based actuator prognostic reasoner...

  8. Systematic review of prognostic factors predicting outcome in non-surgically treated patients with sciatica.

    Science.gov (United States)

    Verwoerd, A J H; Luijsterburg, P A J; Lin, C W C; Jacobs, W C H; Koes, B W; Verhagen, A P

    2013-09-01

    Identification of prognostic factors for surgery in patients with sciatica is important to be able to predict surgery in an early stage. Identification of prognostic factors predicting persistent pain, disability and recovery are important for better understanding of the clinical course, to inform patient and physician and support decision making. Consequently, we aimed to systematically review prognostic factors predicting outcome in non-surgically treated patients with sciatica. A search of Medline, Embase, Web of Science and Cinahl, up to March 2012 was performed for prospective cohort studies on prognostic factors for non-surgically treated sciatica. Two reviewers independently selected studies for inclusion and assessed the risk of bias. Outcomes were pain, disability, recovery and surgery. A best evidence synthesis was carried out in order to assess and summarize the data. The initial search yielded 4392 articles of which 23 articles reporting on 14 original cohorts met the inclusion criteria. High clinical, methodological and statistical heterogeneity among studies was found. Reported evidence regarding prognostic factors predicting the outcome in sciatica is limited. The majority of factors that have been evaluated, e.g., age, body mass index, smoking and sensory disturbance, showed no association with outcome. The only positive association with strong evidence was found for leg pain intensity at baseline as prognostic factor for subsequent surgery. © 2013 European Federation of International Association for the Study of Pain Chapters.

  9. Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer

    International Nuclear Information System (INIS)

    Popovici, Vlad; Budinska, Eva; Bosman, Fred T; Tejpar, Sabine; Roth, Arnaud D; Delorenzi, Mauro

    2013-01-01

    The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in colorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for overall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We investigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the patient population. We retrospectively analyzed a cohort of patients with stage II and III colorectal cancer from the PETACC-3 clinical trial (N = 1,423), by assessing the prognostic value of the BRAF and KRAS mutations in subpopulations defined by all possible combinations of the following clinico-pathological variables: T stage, N stage, tumor site, tumor grade and microsatellite instability status. In each such subpopulation, the prognostic value was assessed by log rank test for three endpoints: overall survival, relapse-free survival, and survival after relapse. The significance level was set to 0.01 for Bonferroni-adjusted p-values, and a second threshold for a trend towards statistical significance was set at 0.05 for unadjusted p-values. The significance of the interactions was tested by Wald test, with significance level of 0.05. In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in subpopulations involving microsatellite stable and left-sided tumors, with higher effects than in the whole population. There was no evidence for prognostic value in microsatellite instable or right-sided tumor groups. We found that BRAF was also prognostic for relapse-free survival in some subpopulations. We found no evidence that KRAS mutations had prognostic value, although a trend was observed in some stratifications. We also show evidence of heterogeneity in survival of patients with BRAF V600E mutation. The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal cancers, in

  10. The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck

    DEFF Research Database (Denmark)

    Nylander, K; Dabelsteen, Erik; Hall, P A

    2000-01-01

    studies have focused on the TP53 tumour suppressor gene, analysing its gene status and protein status. When looking at p53 protein expression, using immunohistochemistry, no correlation to patient outcome has been seen for the whole group of SCCHN. However, a significant association between p53 expression...... the prognostic significance of mutations in the TP53 gene, results differ. But when restricting analysis to tumours with mutations causing an obvious change in protein, TP53 mutation was found to be a strong and independent variable for prognosticating survival. This review article gives an up-to-date overview...

  11. Prognostic factors in Hodgkin's disease stage IV

    DEFF Research Database (Denmark)

    Specht, L.; Nissen, N.I.

    1988-01-01

    blood values, together with exploratory laparotomy and treatment were examined in multivariate analyses. With regard to disease-free survival, the only factors of independent prognostic significance were sex and lymphocytopenia. With regard to overall survival the factors of independent significance...

  12. Surface Prognostic Charts

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Surface Prognostic Charts are historical surface prognostic (forecast) charts created by the United States Weather Bureau. They include fronts, isobars, cloud, and...

  13. Prognostication of diffuse large B-cell lymphoma in the molecular era: moving beyond the IPI.

    Science.gov (United States)

    Wight, Joel C; Chong, Geoffrey; Grigg, Andrew P; Hawkes, Eliza A

    2018-03-26

    Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable outcomes. Despite the majority of patients being cured with combination chemoimmunotherapy, up to 30% eventually succumb to the disease. Until recently, baseline prognostic assessment has centred on the International Prognostic Index (IPI), although this index is yet to impact strongly on treatment choice. Molecular features such as cell of origin, MYC and BCL-2 genetic alterations and protein overexpression were identified over a decade ago, yet their prognostic value is still not fully elucidated. Adding complexity are the plethora of new clinical, biological and molecular prognostic markers described in the recent literature, most of which lack independent validation, likely act as surrogate markers for those already in common use and have yet to substantially impact on therapeutic decision making. This review comprehensively assesses the value of individual prognostic markers in the clinical setting and their potential to predict response to novel agents, and ways to optimise their use in future research. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Prognostic factors of complaints of arm, neck, and/or shoulder: a systematic review of prospective cohort studies.

    Science.gov (United States)

    Bruls, Vivian E J; Bastiaenen, Caroline H G; de Bie, Rob A

    2015-05-01

    Complaints of the arm, neck, or shoulder are common musculoskeletal disorders. To gain insight in prognostic factors of complaints of the arm, neck, or shoulder that are associated with recovery, we conducted a systematic review. We included longitudinal prognostic cohort studies that investigated associations between prognostic factors and recovery in terms of symptoms, disability, or sickness absence. Twenty-six papers reporting on 20 cohorts were included following a search of electronic databases (PubMed, Embase, Cinahl, and PsycINFO). The risk of bias (ROB) was independently assessed by 2 reviewers using the Quality in Prognosis Studies tool. Sixteen studies were assessed as having "low" ROB, and 10 studies were assessed as having "high" ROB. Because of heterogeneity in included studies, pooling was not possible. In the qualitative analysis, the number of studies that evaluated a factor, the ROB of each cohort, and consistency of available evidence were taken into account when summarizing the evidence. We examined whether follow-up duration altered the association of prognostic factors with recovery. The results of our best evidence synthesis showed that for short-term follow-up (coping styles, and accident as "patients' opinion regarding cause" were negatively associated with recovery. For long-term follow-up, we found that longer duration of complaints at presentation had an unfavorable prognostic value for recovery. Our evidence synthesis revealed strong evidence for no prognostic impact of many factors that are suggested to be associated with recovery according to the primary studies.

  15. Clinicopathological correlation and prognostic significance of sonic hedgehog protein overexpression in human gastric cancer.

    Science.gov (United States)

    Niu, Yanyang; Li, Fang; Tang, Bo; Shi, Yan; Hao, Yingxue; Yu, Peiwu

    2014-01-01

    This study investigated the expression of Sonic Hedgehog (Shh) protein in gastric cancer, and correlated it with clinicopathological parameters. The prognostic significance of Shh protein was analyzed. Shh protein expression was evaluated in 113 cases of gastric cancer and 60 cases of normal gastric mucosa. The immunoreactivity was scored semi quantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely non-overexpression group with score 0 or 1, and overexpression group with score 2 or 3. The overexpression of Shh protein was correlated with clinicopathological parameters. Survival analysis was then performed to determine the Shh protein prognostic significance in gastric cancer. In immunohistochemistry study, nineteen (31.7%) normal gastric mucosa revealed Shh protein overexpression, while eighty-one (71.7%) gastric cancer revealed overexpression. The expression of Shh protein were significantly higher in gastric cancer tissues than in normal gastric mucosa (P overexpression and non-expression groups P = 0.168 and 0.071). However, Shh overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 1.187, P = 0.041). Shh protein expression is upregulated and is statistically correlated with age, tumor differentiation, depth of invasion, pathologic staging, and nodal metastasis. The Shh protein overexpression is a significant independent prognostic factor in multivariate Cox regression analysis in gastric cancer.

  16. A Distributed Approach to System-Level Prognostics

    Science.gov (United States)

    Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, Indranil

    2012-01-01

    Prognostics, which deals with predicting remaining useful life of components, subsystems, and systems, is a key technology for systems health management that leads to improved safety and reliability with reduced costs. The prognostics problem is often approached from a component-centric view. However, in most cases, it is not specifically component lifetimes that are important, but, rather, the lifetimes of the systems in which these components reside. The system-level prognostics problem can be quite difficult due to the increased scale and scope of the prognostics problem and the relative Jack of scalability and efficiency of typical prognostics approaches. In order to address these is ues, we develop a distributed solution to the system-level prognostics problem, based on the concept of structural model decomposition. The system model is decomposed into independent submodels. Independent local prognostics subproblems are then formed based on these local submodels, resul ting in a scalable, efficient, and flexible distributed approach to the system-level prognostics problem. We provide a formulation of the system-level prognostics problem and demonstrate the approach on a four-wheeled rover simulation testbed. The results show that the system-level prognostics problem can be accurately and efficiently solved in a distributed fashion.

  17. Colorectal Cancer: Prognostic Values

    Directory of Open Access Journals (Sweden)

    Suzana Manxhuka-Kerliu

    2009-02-01

    Full Text Available After lung cancer colorectal cancer (Cc is ranked the second, as a cause of cancer-related death. The purpose of this study was to analyze the Cc cases in our material with respect to all prognostic values including histological type and grade, vascular invasion, perineural invasion, and tumor border features. There were investigated 149 cases of resection specimen with colorectal cancer, which were fixed in buffered neutral formalin and embedded in paraffin. Tissue sections (4(µm thick were cut and stained with H&E. Adenocarcinoma was the most frequent histological type found in 85,90% of cases, in 60,94% of males and 39,06% of females; squamous cell carcinoma in 7,38%, in 63,63% of males and 36,36% of females; mucinous carcinoma in 4,68%, in 57,15% of males and 42,85% of females; while adenosquamous carcinoma, undifferentiated carcinoma and carcinoma in situ in 0,71% of cases each. Dukes' classification was used in order to define the depth of invasion. Dukes B was found in 68,45% of cases, whereas in 31,54% of cases Dukes C was found. As far as histological grading is concerned, Cc was mostly with moderate differentiation (75,16% with neither vascular nor perineural invasion. Resection margins were in all cases free of tumor. Our data indicate that the pathologic features of the resection specimen constitute the most powerful predictors of postoperative outcome in Cc. Dukes' stage and degree of differentiation provide independent prognostic information in Cc. However, differentiation should be assessed by the worst pattern.

  18. Some interesting prognostic factors related to cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Figueroa, Alejandro Yuri Joan; Diaz Anaya, Amnia; Montero Leon, Jorge Felipe; Jimenez Mendes, Lourdes

    2009-01-01

    The aim of present research was to determine the independent prognostic value and the 3 and 5 years survival of more significant clinicopathological prognostic factors and in each stage, according to pathological staging system of tumor-nodule-metastasis (TNM) in patients with cutaneous malignant melanoma (CMM)

  19. Prognostics for Microgrid Components

    Science.gov (United States)

    Saxena, Abhinav

    2012-01-01

    Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

  20. Prognostic Performance Metrics

    Data.gov (United States)

    National Aeronautics and Space Administration — This chapter presents several performance metrics for offline evaluation of prognostics algorithms. A brief overview of different methods employed for performance...

  1. A comparison of the prognostic value of preoperative inflammation-based scores and TNM stage in patients with gastric cancer

    Directory of Open Access Journals (Sweden)

    Pan QX

    2015-06-01

    Full Text Available Qun-Xiong Pan,* Zi-Jian Su,* Jian-Hua Zhang, Chong-Ren Wang, Shao-Ying KeDepartment of Oncosurgery, Quanzhou First Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, People’s Republic of China*These authors contributed equally to this workBackground: People’s Republic of China is one of the countries with the highest incidence of gastric cancer, accounting for 45% of all new gastric cancer cases in the world. Therefore, strong prognostic markers are critical for the diagnosis and survival of Chinese patients suffering from gastric cancer. Recent studies have begun to unravel the mechanisms linking the host inflammatory response to tumor growth, invasion and metastasis in gastric cancers. Based on this relationship between inflammation and cancer progression, several inflammation-based scores have been demonstrated to have prognostic value in many types of malignant solid tumors.Objective: To compare the prognostic value of inflammation-based prognostic scores and tumor node metastasis (TNM stage in patients undergoing gastric cancer resection.Methods: The inflammation-based prognostic scores were calculated for 207 patients with gastric cancer who underwent surgery. Glasgow prognostic score (GPS, neutrophil lymphocyte ratio (NLR, platelet lymphocyte ratio (PLR, prognostic nutritional index (PNI, and prognostic index (PI were analyzed. Linear trend chi-square test, likelihood ratio chi-square test, and receiver operating characteristic were performed to compare the prognostic value of the selected scores and TNM stage.Results: In univariate analysis, preoperative serum C-reactive protein (P<0.001, serum albumin (P<0.001, GPS (P<0.001, PLR (P=0.002, NLR (P<0.001, PI (P<0.001, PNI (P<0.001, and TNM stage (P<0.001 were significantly associated with both overall survival and disease-free survival of patients with gastric cancer. In multivariate analysis, GPS (P=0.024, NLR (P=0.012, PI (P=0.001, TNM stage (P<0.001, and degree of

  2. Prognostic methods in medicine

    NARCIS (Netherlands)

    Lucas, P. J.; Abu-Hanna, A.

    1999-01-01

    Prognosis--the prediction of the course and outcome of disease processes--plays an important role in patient management tasks like diagnosis and treatment planning. As a result, prognostic models form an integral part of a number of systems supporting these tasks. Furthermore, prognostic models

  3. Aircraft Anomaly Prognostics, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Ridgetop Group will leverage its proven Electromechanical Actuator (EMA) prognostics methodology to develop an advanced model-based actuator prognostic reasoner...

  4. 5-Hydroxymethylcytosine is an independent predictor of survival in malignant melanoma.

    Science.gov (United States)

    Saldanha, Gerald; Joshi, Kushal; Lawes, Kathryn; Bamford, Mark; Moosa, Farhaan; Teo, Kah Wee; Pringle, J Howard

    2017-01-01

    Outcomes for melanoma patients vary within cancer stage. Prognostic biomarkers are potential adjuncts to provide more precise prognostic information. Simple, low-cost biomarker assays, such as those based on immunohistochemistry, have strong translational potential. 5-hydroxymethylcytosine (5 hmC) shows prognostic potential in melanoma but prior studies were small. We, therefore, analysed 5 hmC in a retrospective cohort to provide external validation of its prognostic value. Two hundred primary melanomas were evaluated for 5 hmC expression using immunohistochemistry. The primary objective was to assess the effect on overall survival while controlling for important confounders. Univariable and multivariable analyses were performed. REMARK guidelines were followed. The 5 hmC immunohistochemistry scoring showed very strong inter-observer agreement (ICC 0.88) and expression was significantly related to age, site, Breslow thickness, ulceration, mitotic rate, and stage. Kaplan-Meier analysis showed 5 hmC was associated with metastasis-free, melanoma-specific, and overall survival, PhmC hazard ratios were significant and remained so in a multivariable model. A two-step cox model was created using stage and 5 hmC, as stage is the gold standard for clinical practice. The addition of 5 hmC produced significant improvement in the model and 5 hmC and stage were independent significant predictors. This is the largest study of the prognostic value of 5 hmC immunohistochemistry in melanoma. The 5 hmC scoring was easily and reproducibly performed and it was an independent predictor of metastasis-free survival, melanoma-specific survival, and overall survival. This work supports further development of 5 hmC as a prognostic biomarker and suggests that it could add more precision to American Joint Committee on Cancer staging.

  5. GPU Accelerated Prognostics

    Science.gov (United States)

    Gorospe, George E., Jr.; Daigle, Matthew J.; Sankararaman, Shankar; Kulkarni, Chetan S.; Ng, Eley

    2017-01-01

    Prognostic methods enable operators and maintainers to predict the future performance for critical systems. However, these methods can be computationally expensive and may need to be performed each time new information about the system becomes available. In light of these computational requirements, we have investigated the application of graphics processing units (GPUs) as a computational platform for real-time prognostics. Recent advances in GPU technology have reduced cost and increased the computational capability of these highly parallel processing units, making them more attractive for the deployment of prognostic software. We present a survey of model-based prognostic algorithms with considerations for leveraging the parallel architecture of the GPU and a case study of GPU-accelerated battery prognostics with computational performance results.

  6. A strong comeback

    International Nuclear Information System (INIS)

    Marier, D.

    1992-01-01

    This article presents the results of a financial rankings survey which show a strong economic activity in the independent energy industry. The topics of the article include advisor turnover, overseas banks, and the increase in public offerings. The article identifies the top project finance investors for new projects and restructurings and rankings for lenders

  7. The Preoperative AST/ALT (De Ritis) Ratio Represents a Poor Prognostic Factor in a Cohort of Patients with Nonmetastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Bezan, Angelika; Mrsic, Edvin; Krieger, Daniel; Stojakovic, Tatjana; Pummer, Karl; Zigeuner, Richard; Hutterer, Georg C; Pichler, Martin

    2015-07-01

    Aminotransaminases, which are strongly involved in cellular metabolism and cancer cell turnover, represent easily measureable, potential blood based biomarkers. We evaluated the prognostic value of the preoperatively assessed AST/ALT (De Ritis) ratio on clinically meaningful end points in a large European cohort of patients with nonmetastatic renal cell carcinoma. We retrospectively evaluated clinicopathological data on 698 patients with nonmetastatic renal cell carcinoma operated on between 2005 and 2013 at a single tertiary academic center. The potential prognostic value of the AST/ALT ratio was analyzed using the Kaplan-Meier method, and univariate and multivariate Cox proportional regression models. The impact of the ratio on the predictive accuracy of the Leibovich prognosis score was determined by the Harrell c-index. An increased (1.26 or greater) preoperative AST/ALT ratio was statistically significantly associated with several well established prognostic factors, including pathological T stage, as well as with histological tumor necrosis (p ALT ratio was an independent prognostic factor for metastasis-free survival (HR 1.61, 95% CI 1.25-2.07, p ALT was added. In our study cohort with nonmetastatic renal cell carcinoma the preoperatively assessed AST/ALT ratio represented an independent prognostic factor. This ratio might further improve the predictive accuracy of well established prognosis scores. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  8. Younger donor's age and upfront tandem are two independent prognostic factors for survival in multiple myeloma patients treated by tandem autologous-allogeneic stem cell transplantation: a retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

    Science.gov (United States)

    Fabre, Claire; Koscielny, Serge; Mohty, Mohamad; Fegueux, Nathalie; Blaise, Didier; Maillard, Natacha; Tabrizi, Reza; Michallet, Mauricette; Socié, Gérard; Yakoub-Agha, Ibrahim; Garban, Frédéric; Uzunov, Madalina; François, Sylvie; Contentin, Nathalie; Lapusan, Simona; Bourhis, Jean-Henri

    2012-04-01

    How tandem autologous-allogeneic stem cell transplantation should be integrated in the treatment of multiple myeloma remains controversial. We examined the long-term outcome of patients with multiple myeloma managed with tandem autologous-allogeneic stem cell transplantation and present a prognostic factor analysis based on the experience of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). This French, retrospective, registry-based study included 146 patients who had undergone tandem autologous-allogeneic transplantation for multiple myeloma at 20 SFGM-TC centers between 1998 and 2010. The patients included in the study had fully completed the two steps of a planned tandem autologous-allogeneic transplantation. No treatment had to be administered between the autologous and allogeneic parts of the tandem procedure. Seventy-seven patients (53%) underwent tandem autologous-allogeneic transplantation as part of upfront treatment, i.e. after a single line of treatment not including autologous transplantation. The median follow-up from the allogeneic transplant was 47.5 months (range, 1.2-132 months). At 4 years, the overall survival and event-free survival rates were 48% (95% CI 39-57 %) and 27% (95% CI 19-36), respectively. Eighteen patients (12%) experienced grade III-IV acute graft-versus-host disease and 43 patients (30%) had chronic graft-versus-host disease. The transplant-related mortality rate at 1 year was 15% (95% CI 10-22). Patients receiving tandem transplantation as upfront treatment had significantly improved event-free survival (36% versus 11%; P=0.005) and overall survival (56% versus 34%; P=0.02). Donor's age ≤ 50 years was associated with improved event-free survival (35% versus 16%; P=0.005) and overall survival (54% versus 41%; P=0.02). In the multivariable analysis, upfront tandem transplantation, donor's age ≤ 50 years and full chimerism were independent prognostic factors for better outcome. We confirmed the

  9. Younger donor’s age and upfront tandem are two independent prognostic factors for survival in multiple myeloma patients treated by tandem autologous-allogeneic stem cell transplantation: a retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

    Science.gov (United States)

    Fabre, Claire; Koscielny, Serge; Mohty, Mohamad; Fegueux, Nathalie; Blaise, Didier; Maillard, Natacha; Tabrizi, Reza; Michallet, Mauricette; Socié, Gérard; Yakoub-Agha, Ibrahim; Garban, Frédéric; Uzunov, Madalina; François, Sylvie; Contentin, Nathalie; Lapusan, Simona; Bourhis, Jean-Henri

    2012-01-01

    Background How tandem autologous-allogeneic stem cell transplantation should be integrated in the treatment of multiple myeloma remains controversial. We examined the long-term outcome of patients with multiple myeloma managed with tandem autologous-allogeneic stem cell transplantation and present a prognostic factor analysis based on the experience of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). Design and Methods This French, retrospective, registry-based study included 146 patients who had undergone tandem autologous-allogeneic transplantation for multiple myeloma at 20 SFGM-TC centers between 1998 and 2010. The patients included in the study had fully completed the two steps of a planned tandem autologous-allogeneic transplantation. No treatment had to be administered between the autologous and allogeneic parts of the tandem procedure. Results Seventy-seven patients (53%) underwent tandem autologous-allogeneic transplantation as part of upfront treatment, i.e. after a single line of treatment not including autologous transplantation. The median follow-up from the allogeneic transplant was 47.5 months (range, 1.2–132 months). At 4 years, the overall survival and event-free survival rates were 48% (95% CI 39–57 %) and 27% (95% CI 19–36), respectively. Eighteen patients (12%) experienced grade III–IV acute graft-versus-host disease and 43 patients (30%) had chronic graft-versus-host disease. The transplant-related mortality rate at 1 year was 15% (95% CI 10–22). Patients receiving tandem transplantation as upfront treatment had significantly improved event-free survival (36% versus 11%; P=0.005) and overall survival (56% versus 34%; P=0.02). Donor’s age ≤50 years was associated with improved event-free survival (35% versus 16%; P=0.005) and overall survival (54% versus 41%; P=0.02). In the multivariable analysis, upfront tandem transplantation, donor’s age ≤50 years and full chimerism were independent

  10. The prognostic relevance of estimates of proliferative activity in early breast cancer

    DEFF Research Database (Denmark)

    Offersen, B V; Sørensen, Flemming Brandt; Knoop, A

    2003-01-01

    clinicopathological parameters at diagnosis in early breast cancer patients. MATERIALS AND METHODS: Tumour specimens from 365 consecutively treated breast cancer patients were immunostained for MIB-1 and evaluated under the microscope using systematic random sampling accomplished by the CAST-grid system. RESULTS...... and number of mitoses included in the analysis, MIB-1 estimates showed no independent prognostic impact. CONCLUSIONS: High MIB-1 estimates did not add independent prognostic information at diagnosis when evaluated together with classical prognostic markers of early breast cancer....

  11. Prognostics of Power MOSFET

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper demonstrates how to apply prognostics to power MOSFETs (metal oxide field effect transistor). The methodology uses thermal cycling to age devices and...

  12. No prognostic value added by vitamin D pathway SNPs to current prognostic system for melanoma survival.

    Directory of Open Access Journals (Sweden)

    Li Luo

    Full Text Available The prognostic improvement attributed to genetic markers over current prognostic system has not been well studied for melanoma. The goal of this study is to evaluate the added prognostic value of Vitamin D Pathway (VitD SNPs to currently known clinical and demographic factors such as age, sex, Breslow thickness, mitosis and ulceration (CDF. We utilized two large independent well-characterized melanoma studies: the Genes, Environment, and Melanoma (GEM and MD Anderson studies, and performed variable selection of VitD pathway SNPs and CDF using Random Survival Forest (RSF method in addition to Cox proportional hazards models. The Harrell's C-index was used to compare the performance of model predictability. The population-based GEM study enrolled 3,578 incident cases of cutaneous melanoma (CM, and the hospital-based MD Anderson study consisted of 1,804 CM patients. Including both VitD SNPs and CDF yielded C-index of 0.85, which provided slight but not significant improvement by CDF alone (C-index = 0.83 in the GEM study. Similar results were observed in the independent MD Anderson study (C-index = 0.84 and 0.83, respectively. The Cox model identified no significant associations after adjusting for multiplicity. Our results do not support clinically significant prognostic improvements attributable to VitD pathway SNPs over current prognostic system for melanoma survival.

  13. {sup 18}F-FDG PET/CT following chemoradiation of uterine cervix cancer provides powerful prognostic stratification independent of HPV status: a prospective cohort of 105 women with mature survival data

    Energy Technology Data Exchange (ETDEWEB)

    Siva, Shankar; Hicks, Rodney J.; Callahan, Jason [Peter MacCallum Cancer Centre, Division of Radiation Oncology and Cancer Imaging, East Melbourne, Victoria (Australia); University of Melbourne, Sir Peter MacCallum Department of Oncology, Parkville (Australia); Deb, Siddhartha [Peter MacCallum Cancer Centre, Department of Pathology, East Melbourne (Australia); Young, Richard J. [Peter MacCallum Cancer Centre, Molecular Therapeutics and Biomarkers Laboratory, East Melbourne (Australia); Bressel, Mathias [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, East Melbourne (Australia); Mileshkin, Linda [Peter MacCallum Cancer Centre, Department of Cancer Medicine, East Melbourne (Australia); Rischin, Danny [University of Melbourne, Sir Peter MacCallum Department of Oncology, Parkville (Australia); Peter MacCallum Cancer Centre, Department of Cancer Medicine, East Melbourne (Australia); Bernshaw, David; Narayan, Kailash [Peter MacCallum Cancer Centre, Division of Radiation Oncology and Cancer Imaging, East Melbourne, Victoria (Australia)

    2015-11-15

    To report 5-year outcomes of a prospective registry study investigating posttherapy FDG PET/CT in women with locally advanced cervical cancer. A secondary analysis assessing the prognostic significance of HPV infection was performed. Patients underwent definitive chemoradiation followed by a single FDG PET/CT scan for response assessment. A complete metabolic response (CMR) was defined as no evidence of FDG-avid disease. Patients were dichotomized according to HPV infection status into a 'higher-risk' group and a 'lower-risk' group, with the higher-risk group comprising those with alpha-7 strain HPV (subtypes 18, 39 and 45) and those who were HPV-negative and the lower-risk group comprising those with alpha-9 strain HPV (subtypes 16, 31, 33, 52 and 58) and those with mixed strains. Survival outcomes, patterns of failure and salvage therapy outcomes were investigated for their association with metabolic response and HPV status. In 105 patients the median prospective follow-up was 5.2 years. The 5-year cancer-specific, overall and progression-free survival rates in patients with a CMR were 97 %, 93 % and 86 %, respectively. In patients without a CMR, the corresponding 5-year survival rates were 36 %, 22 % and 0 % respectively (p < 0.01). PET response was associated with patterns of failure (p < 0.01), with the 5-year freedom from local, nodal and distant failure in patients with a CMR being 94 %, 90 % and 94 %, respectively. Of 16 patients who underwent salvage therapy, 12 had disease detected on the surveillance PET scan, and 8 achieved a post-salvage CMR of whom all were alive at a median of 4.9 years. DNA adequate for HPV analysis was extracted in 68 patients. The likelihood of a PET metabolic response was not influenced by HPV infection status, with 71 % and 75 % of higher-risk and lower-risk patients, respectively, achieving CMR (p = 0.83). Higher-risk patients had a poorer OS (HR 2.6, range 1.0 - 6.6, p = 0.05) in univariable analysis but

  14. Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer.

    Directory of Open Access Journals (Sweden)

    Sura Aziz

    Full Text Available Presence of lymph node (LN metastasis is a strong prognostic factor in breast cancer, whereas the importance of extra-nodal extension and other nodal tumor features have not yet been fully recognized. Here, we examined microscopic features of lymph node metastases and their prognostic value in a population-based cohort of node positive breast cancer (n = 218, as part of the prospective Norwegian Breast Cancer Screening Program NBCSP (1996-2009. Sections were reviewed for the largest metastatic tumor diameter (TD-MET, nodal afferent and efferent vascular invasion (AVI and EVI, extra-nodal extension (ENE, number of ENE foci, as well as circumferential (CD-ENE and perpendicular (PD-ENE diameter of extra-nodal growth. Number of positive lymph nodes, EVI, and PD-ENE were significantly increased with larger primary tumor (PT diameter. Univariate survival analysis showed that several features of nodal metastases were associated with disease-free (DFS or breast cancer specific survival (BCSS. Multivariate analysis demonstrated an independent prognostic value of PD-ENE (with 3 mm as cut-off value in predicting DFS and BCSS, along with number of positive nodes and histologic grade of the primary tumor (for DFS: P = 0.01, P = 0.02, P = 0.01, respectively; for BCSS: P = 0.02, P = 0.008, P = 0.02, respectively. To conclude, the extent of ENE by its perpendicular diameter was independently prognostic and should be considered in line with nodal tumor burden in treatment decisions of node positive breast cancer.

  15. Prognostic value of serum heavy/light chain ratios in patients with POEMS syndrome.

    Science.gov (United States)

    Wang, Chen; Su, Wei; Cai, Qian-Qian; Cai, Hao; Ji, Wei; Di, Qian; Duan, Ming-Hui; Cao, Xin-Xin; Zhou, Dao-Bin; Li, Jian

    2016-07-01

    POEMS syndrome is a rare plasma cell dyscrasia. Serum concentrations of the monoclonal protein in this disorder are typically low, and inapplicable to monitor disease activity in most cases, resulting in limited practical and prognostic values. Novel immunoassays measuring isotype-specific heavy/light chain (HLC) pairs showed its utility in disease monitoring and outcome prediction in several plasma cell dyscrasias. We report results of HLC measurements in 90 patients with POEMS syndrome. Sixty-six patients (73%; 95% confidence interval, 63-82%) had an abnormal HLC ratio at baseline. It could stratify the risk of disease relapse and was strongly associated with worse progression-free survival in a multivariate analysis (P = 0.021; hazard ratio [HR] 6.89, 95% CI 1.34-35.43). After therapy, HLC ratios improved, with 43 patients (48%) remaining abnormal. The post-therapeutic HLC ratio, if abnormal, also remained as an independent prognostic factor associated with worse progression-free survival (P = 0.019; HR 4.30, 95% CI 1.27-14.56). These results suggest the prognostic utility of HLC ratios in clinical management of POEMS patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Strong WW Interaction at LHC

    Energy Technology Data Exchange (ETDEWEB)

    Pelaez, Jose R

    1998-12-14

    We present a brief pedagogical introduction to the Effective Electroweak Chiral Lagrangians, which provide a model independent description of the WW interactions in the strong regime. When it is complemented with some unitarization or a dispersive approach, this formalism allows the study of the general strong scenario expected at the LHC, including resonances.

  17. Prognostic accuracy of electroencephalograms in preterm infants

    DEFF Research Database (Denmark)

    Fogtmann, Emilie Pi; Plomgaard, Anne Mette; Greisen, Gorm

    2017-01-01

    CONTEXT: Brain injury is common in preterm infants, and predictors of neurodevelopmental outcome are relevant. OBJECTIVE: To assess the prognostic test accuracy of the background activity of the EEG recorded as amplitude-integrated EEG (aEEG) or conventional EEG early in life in preterm infants...... for predicting neurodevelopmental outcome. DATA SOURCES: The Cochrane Library, PubMed, Embase, and the Cumulative Index to Nursing and Allied Health Literature. STUDY SELECTION: We included observational studies that had obtained an aEEG or EEG within 7 days of life in preterm infants and reported...... neurodevelopmental outcomes 1 to 10 years later. DATA EXTRACTION: Two reviewers independently performed data extraction with regard to participants, prognostic testing, and outcomes. RESULTS: Thirteen observational studies with a total of 1181 infants were included. A metaanalysis was performed based on 3 studies...

  18. Prognostic factors for acute and late skin reactions in radiotherapy patients

    International Nuclear Information System (INIS)

    Turesson, Ingela; Nyman, Jan; Holmberg, Erik; Oden, Anders

    1996-01-01

    Purpose: Patients treated with identical radiotherapy schedules show a substantial variation in the degree of acute and late normal tissue reactions. To identify any possible contributing factors to this phenomenon, we have analyzed the treatments of 402 breast cancer patients. Methods and Materials: The patients received adjuvant postoperative radiotherapy between 1972 and 1985 and have been followed up since then. Multivariate analyses were performed with peak reflectance erythema and peak acute reaction score as endpoints for the acute reactions, and with progression rate of telangiectasia as well as telangiectasia score as endpoints for the late reactions. Twenty patient- and treatment-related factors were tested such as age, menopausal status, hemoglobin level, serum calcium, smoking habits, hypothyroidism, diabetes, hypertension, blood pressure, cardiovascular and autoimmune disease, the influence of hormone therapy and chemotherapy, pretreatment reflectance value, acute skin reactions, radiation quality, individual dose, bilateral fields, and the total effect (TE) for the dose schedule applied. Results: The TE was a strong prognostic factor for all endpoints. In addition to TE, blood pressure was prognostic for the peak erythema measured by reflectance spectrophotometry, and the pretreatment reflectance value was prognostic for the acute score. The only independent prognostic factors found for the progression of skin telangiectasia and telangiectasia score except for TE were the individual dose and the acute skin reactions. Conclusions: These factors explained at most about 30% of the variance describing the total patient-to-patient variability for each endpoint. The remaining variability is still unexplained but may be related to individual differences in cellular radiosensitivity, partly determined by genetic variations and partly by unknown epigenetic factors

  19. Osteopontin is a prognostic biomarker in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Rud, Ane Kongsgaard; Mælandsmo, Gunhild M; Boye, Kjetil; Øijordsbakken, Miriam; Lund-Iversen, Marius; Halvorsen, Ann Rita; Solberg, Steinar K; Berge, Gisle; Helland, Åslaug; Brustugun, Odd Terje

    2013-01-01

    In a previously published report we characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1 in a prospectively collected panel of non-small cell lung cancer (NSCLC) tumors. The aim of the present follow-up study was to investigate the prognostic impact of these potential biomarkers in the same patient cohort. In addition, circulating serum levels of OPN were measured and single nucleotide polymorphisms (SNP) in the -443 position of the OPN promoter were analyzed. Associations between immunohistochemical expression of S100A4, OPN and ephrin-A1 and relapse free and overall survival were examined using univariate and multivariate analyses. Serum OPN was measured by ELISA, polymorphisms in the -443 position of the tumor OPN promoter were analyzed by PCR, and associations between OPN levels and promoter polymorphisms and clinicopathological parameters and patient outcome were investigated. High expression of OPN in NSCLC tumors was associated with poor patient outcome, and OPN was a strong, independent prognostic factor for both relapse free and overall survival. Serum OPN levels increased according to tumor pT classification and tumor size, and patients with OPN-expressing tumors had higher serum levels than patients with OPN-negative tumors. S100A4 was a negative prognostic factor in several subgroups of adenocarcinoma patients, but not in the overall patient cohort. There was no association between ephrin-A1 expression and patient outcome. OPN is a promising prognostic biomarker in NSCLC, and should be further explored in the selection of patients for adjuvant treatment following surgical resection

  20. Prognostic impact of cytological fluid tumor markers in non-small cell lung cancer.

    Science.gov (United States)

    Cho, Arthur; Hur, Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Hong, Sae Rom; Suh, Young Joo; Im, Dong Jin; Kim, Yun Jung; Lee, Jae Seok; Shim, Hyo Sup; Choi, Byoung Wook

    2016-03-01

    The serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) are useful in diagnosis and prognosis of non-small cell lung cancer (NSCLC). Cytologic tumor markers obtained during needle aspiration biopsies (NAB) of lung lesions are useful for NSCLC diagnosis. This study investigated the incremental prognostic value of cytologic tumor markers compared to serum tumor markers. This prospective study included 253 patients diagnosed with NSCLC by NAB with cytologic tumor marker analysis. Levels of cytologic CYFRA 21-1, CEA, SCCA, and their serum counterparts were followed up for survival analysis. Optimal cutoff values for each tumor marker were obtained for overall survival (OS) and progression-free survival (PFS) analyses. All patients were followed up for a median of 22.8 months. Using cutoff values of 0.44 ng/ml for C-SCCA, 2.0 ng/ml for S-SCCA, and 3.3 ng/ml for S-CYFRA, a multivariate analysis revealed that high S-SCCA (hazard ratio, HR, 1.84) and high C-SCCA (HR, 1.63) were independent predictive factors of OS. The 3-year overall survival rate was 55 vs. 80 % for high and low C-SCCA, respectively. Cytologic tumor marker level detection is easily obtainable and provides prognostic information for NSCLC. Cytologic tumor markers provide comparable prognostic information relative to serum tumor markers, with C-SCCA acting as a strong prognostic factor of overall survival and PFS.

  1. Impact of prognostic nutritional index on long-term outcomes in patients with breast cancer.

    Science.gov (United States)

    Mohri, Tomomi; Mohri, Yasuhiko; Shigemori, Tsunehiko; Takeuchi, Kenji; Itoh, Yoshiyuki; Kato, Toshio

    2016-06-27

    Prognostic nutritional index has been shown to be a prognostic marker for various solid tumors. However, few studies have investigated the impact of the prognostic nutritional index on survival of patients with breast cancer. The aim of this study was to investigate the impact of the prognostic nutritional index on the long-term outcomes in patients with breast cancer. This study reviewed the medical records of 212 patients with breast cancer who underwent mastectomy. The prognostic nutritional index was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm(3)). Receiver operating characteristic curve analysis was performed to determine the cutoff value of the prognostic nutritional index. The survival curves were calculated by the Kaplan-Meier method. Differences between the curves were analyzed by the log-rank test. Multivariate Cox proportional hazard model was used to evaluate the prognostic significance of prognostic nutritional index in patients with breast cancer. The mean prognostic nutritional index just before the operation was 51.9, and the median follow-up after surgery was 47.7 months. The optimal cutoff value of the prognostic nutritional index for predicting the overall survival was 52.8 from the receiver operating characteristic curve analysis. The 5-year overall survival rate was 98.3 % in the prognostic nutritional index >52.8 and 92.0 % in the prognostic nutritional index nutritional index was an independent predictor for poor overall survival (HR, 5.88; 95 % CI, 1.13-108.01; P = 0.033). The prognostic nutritional index is a simple and useful marker for predicting the long-term outcomes of breast cancer patients, independent of the tumor stage.

  2. Interleukin-8 as a prognostic serum marker in canine mammary gland neoplasias.

    Science.gov (United States)

    Gelaleti, Gabriela Bottaro; Jardim, Bruna Victorasso; Leonel, Camila; Moschetta, Marina Gobbe; Zuccari, Debora Ap Pires de Campos

    2012-04-15

    Mammary gland tumors in female dogs are an excellent model for the clinic-pathological, diagnostic and prognostic investigation of mammary neoplasias. Prognostic and predictive markers are effective in research and routine diagnosis. Interleukins play a fundamental role in cancer, with a particular function in tumor growth, invasion and metastatic potential. Interleukin-8 (IL-8) is known to possess tumorigenic and pro-angiogenic properties, and its overexpression is seen in a number of human tumors. IL-8 serum levels were determined and correlated with the clinic-pathological features and clinical evolution of mammary gland neoplasias in female dogs. IL-8 was measured by an immunoenzymatic assay in 30 female dogs with mammary neoplasias within a 12 month follow-up and in 50 control animals. The correlation between IL-8 concentration and clinical parameters was investigated. A statistically significant difference in the IL-8 serum levels was found in tumor-bearing dogs compared to the controls. In addition, when the individual parameters were evaluated, IL-8 content showed a positive correlation with the tumor progression, lymph node involvement, recurrence and death. Single and multivariate analyses showed associations between tumor recurrence, metastasis, high clinical staging and high IL-8, and also with the death risk. This was also consistent with the high IL-8 content in dogs showing tumor recurrence and metastasis. IL-8 superexpression has been detected in a number of human tumors, usually associated with a poor prognostic. Besides promoting angiogenesis, IL-8 is strongly related with the metastatic phenotype of mammary tumor cells. High IL-8 concentration was found in mammary gland cancer patients with advanced disease stages. Our results show that IL-8 can be used as a non-invasive prognostic marker for mammary gland cancer, and can be useful for the prediction of disease progression and recurrence in dogs with mammary neoplasias. The increased level of

  3. Cytologic anaplasia is a prognostic factor in osteosarcoma biopsies, but mitotic rate or extent of spontaneous tumor necrosis are not: a critique of the College of American Pathologists Bone Biopsy template.

    Science.gov (United States)

    Cates, Justin Mm; Dupont, William D

    2017-01-01

    The current College of American Pathologists cancer template for reporting biopsies of bone tumors recommends including information that is of unproven prognostic significance for osteosarcoma, such as the presence of spontaneous tumor necrosis and mitotic rate. Conversely, the degree of cytologic anaplasia (degree of differentiation) is not reported in this template. This retrospective cohort study of 125 patients with high-grade osteosarcoma was performed to evaluate the prognostic impact of these factors in diagnostic biopsy specimens in predicting the clinical outcome and response to neoadjuvant chemotherapy. Multivariate Cox regression was performed to adjust survival analyses for well-established prognostic factors. Multivariate logistic regression was used to determine odds ratios for good chemotherapy response (≥90% tumor necrosis). Osteosarcomas with severe anaplasia were independently associated with increased overall and disease-free survival, but mitotic rate and spontaneous necrosis had no prognostic impact after controlling for other confounding factors. Mitotic rate showed a trend towards increased odds of a good histologic response, but this effect was diminished after controlling for other predictive factors. Neither spontaneous necrosis nor the degree of cytologic anaplasia observed in biopsy specimens was predictive of a good response to chemotherapy. Mitotic rate and spontaneous tumor necrosis observed in pretreatment biopsy specimens of high-grade osteosarcoma are not strong independent prognostic factors for clinical outcome or predictors of response to neoadjuvant chemotherapy. Therefore, reporting these parameters for osteosarcoma, as recommended in the College of American Pathologists Bone Biopsy template, does not appear to have clinical utility. In contrast, histologic grading schemes for osteosarcoma based on the degree of cytologic anaplasia may have independent prognostic value and should continue to be evaluated.

  4. The prognostic significance of apoptosis-related biological markers in Chinese gastric cancer patients.

    Directory of Open Access Journals (Sweden)

    Xiaowen Liu

    Full Text Available BACKGROUND AND OBJECTIVE: The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as p53, bcl-2, bax, and c-myc, and clinicopathological features and their prognostic value. METHODS: From 1996 to 2007, 4426 patients had undergone curative D2 gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 501 patients, the expression levels of p53, bcl-2, bax, and c-myc were examined by immunohistochemistry. The prognostic value of biological markers and the correlation between biological markers and other clinicopathological factors were investigated. RESULTS: There were 339 males and 162 females with a mean age of 57. The percentages of positive expression of p53, bcl-2, bax, and c-myc were 65%, 22%, 43%, and 58%, respectively. There was a strong correlation between p53, bax, and c-myc expression (P=0.00. There was significant association between bcl-2, and bax expression (P<0.05. p53 expression correlated with histological grade (P=0.01; bcl-2 expression with pathological stage (P=0.00; bax expression with male (P=0.02, histological grade (P=0.01, Borrmann type (P=0.01, tumor location (P=0.00, lymph node metastasis (P=0.03, and pathological stage (P=0.03; c-myc expression with Borrmann type (P=0.00. bcl-2 expression was related with good survival in univariate analysis (P=0.01. Multivariate analysis showed that bcl-2 expression and pathological stage were defined as independent prognostic factors. There were significant differences of overall 5-year survival rates according to bcl-2 expression or not in stage IIB (P=0.03. CONCLUSION: The expression of bcl-2 was an independent prognostic factor for patients with gastric cancer; it might be a candidate for the gastric cancer staging system.

  5. Independent Directors

    DEFF Research Database (Denmark)

    Ringe, Wolf-Georg

    2013-01-01

    about board independence in Western jurisdictions, a surprising disharmony prevails about the justification, extent and purpose of independence requirements. These considerations lead me to question the benefits of the current system. Instead, this paper proposes a new, ‘functional’ concept of board...

  6. Is body temperature an independent predictor of mortality in hip fracture patients?

    Science.gov (United States)

    Faizi, Murtuza; Farrier, Adam J; Venkatesan, Murali; Thomas, Christopher; Uzoigwe, Chika Edward; Balasubramanian, Siva; Smith, Robert P

    2014-12-01

    Admission body temperature is a critical parameter in all trauma patients. Low admission temperature is strongly associated with adverse outcomes. We have previously shown, in a prospective study that low admission body temperature is common and associated with high mortality in hip fracture patients (Uzoigwe et al., 2014). However, no previous studies have evaluated whether admission temperature is an independent predictor of mortality in hip fracture patients after adjustment for the 7 recognised independent prognostic indicators (Maxwell et al., 2008). We retrospectively collated data on all patients presenting to our institution between June 2011 and February 2013 with a hip fracture. This included patients involved in the original prospective study (Uzoigwe et al., 2014). Admission tympanic temperature, measured on initial presentation at triage, was recorded. The prognosticators of age, gender, source of admission, abbreviated mental test score, haemoglobin, co-morbid disease and the presence or absence of malignancy were also recorded. Using multiple logistic regression, adjustment was made for these potentially confounding prognostic indicators of 30-day mortality, to determine if admission low body temperature were independently linked to mortality. 1066 patients were included. 781 patients, involved in the original prospective study (Uzoigwe et al., 2014), presented in the relevant time frame and were included in the retrospective study. The mean age was 81. There were 273 (26%) men and 793 (74%) women. 407 (38%) had low body temperature (temperature had an adjusted odds ratio of 30-day mortality that was 2.1 times that of the euthermic (36.5–37.5 °C). Low body temperature is strongly and independently associated with 30-day mortality in hip fracture patients.

  7. Serum Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3 Is Increased in Patients with Multiple Sclerosis and Is a Strong Independent Indicator of Disease Severity; 6.7kbp LILRA3 Gene Deletion Is Not Associated with Diseases Susceptibility.

    Directory of Open Access Journals (Sweden)

    Hongyan An

    Full Text Available Leukocyte immunoglobulin-like receptor A3 (LILRA3 is a soluble immune regulatory molecule primarily expressed by monocytes and macrophages. A homozygous 6.7kbp LILRA3 gene deletion that removes the first seven of its eight exons is predicted to lead to lack of LILRA3 protein, although this has not been experimentally confirmed. Moreover, there are conflicting results with regards to the link between the LILRA3 homozygous genetic deletion and susceptibility to multiple sclerosis (MS in different European populations. The aim of this study was to investigate whether LILRA3 gene deletion is associated with MS susceptibility in a North American cohort of European ancestry and assess if serum LILRA3 protein level is a marker of clinical subtype and/or disease severity in MS. A total of 456 patients with MS and 99 unrelated healthy controls were genotyped for the 6.7kbp LILRA3 gene deletion and levels of LILRA3 protein in sera determined by in-house sandwich ELISA. We showed that LILRA3 gene deletion was not associated with MS susceptibility and did not affect the age of disease onset, clinical subtype or disease severity. However, we discovered for the first time that homozygous LILRA3 gene deletion results in lack of production of LILRA3 protein. Importantly, LILRA3 protein level was significantly increased in sera of patients with MS when compared with control subjects, particularly in more severe type primary progressive MS. Multiple regression analysis showed that LILRA3 level in serum was one of the strongest independent markers of disease severity in MS, which potentially can be used as a diagnostic marker.

  8. Prognostic Value of E-Cadherin and β-Catenin in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Shen, Tiansheng; Zhang, Kui; Siegal, Gene P; Wei, Shi

    2016-11-01

    To analyze the expression of E-cadherin and β-catenin in triple-negative breast cancer (TNBC) to assess their prognostic significance. The expression of E-cadherin and β-catenin was examined semiquantitatively and correlated with other pathologic factors and survival outcomes. Of 72 consecutive TNBCs, 56% showed reduced membranous expression of E-cadherin or β-catenin, with a strong correlation to each other. Of the clinicopathologic factors analyzed, tumor size and nodal status were significantly associated with overall survival and disease-specific survival, while the latter remained an independent factor by multivariate analysis. Reduced E-cadherin and β-catenin were both significantly associated with a poor overall survival and disease-specific survival by univariate and multivariate analyses. E-cadherin and β-catenin expression provides discriminative prognostic power independent of conventional pathologic factors, thus further reinforcing the important role of cell adhesion molecules in the process of tumor metastasis, especially in TNBC. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  9. Prognostic factors for medulloblastoma

    International Nuclear Information System (INIS)

    Jenkin, Derek; Al Shabanah, Mohamed; Al Shail, Essam; Gray, Alan; Hassounah, Maher; Khafaga, Yasser; Kofide, Amani; Mustafa, Mahmoud; Schultz, Henrik

    2000-01-01

    Purpose: To evaluate prognostic factors for medulloblastoma. Methods and Materials: One hundred and seventy-three consecutive patients with medulloblastoma, treated at King Faisal Specialist Hospital (KFSH) from 1988-1997, were reviewed. Eighty-four percent were children less than 15 years old. From 1988-1994, treatment was at the discretion of the investigator. From 1994-1998, patients entered a single-arm best practice protocol in which, in staged patients, the surgical intent was total resection, standard radiation treatment was defined, and adjuvant chemotherapy was given to a 'high-risk' subset. Results: For 150 patients who completed surgical and radiation treatment, the 5-year survival rate was 58%, compared with 0% for 16 patients who were unable to start or complete radiation treatment. For staged patients, the 5-year survival was M0 + M1, 78% and M2 + M3, 21% (p 14 years and gross cystic/necrotic features in the primary tumor. The size of the primary tumor, the degree of hydrocephalus at diagnosis, the presence of residual tumor in the post-operative CT/MRI, and the functional status of the patient prior to radiation treatment were not significant factors. Conclusions: Stage M0 + M1 was the most powerful favorable prognostic factor. In Saudi Arabia more patients present with advanced disseminated disease, 41% M2 + M3, than in the West, and this impacts adversely on overall survival. Total resection and standard radiation treatment were not sensitive prognostic factors in a treatment environment in which 78% of patients underwent at least 90% tumor resection and 60% received standard radiation treatment. In order to improve the proportion of patients able to complete radiation treatment, consideration should be given to limiting resection when the attainment of total resection is likely to be morbid, and to delaying rather than omitting radiation treatment in the patient severely compromised postoperatively

  10. American = Independent?

    Science.gov (United States)

    Markus, Hazel Rose

    2017-09-01

    U.S. American cultures and psyches reflect and promote independence. Devos and Banaji (2005) asked, does American equal White? This article asks, does American equal independent? The answer is that when compared to people in East Asian or South Asian contexts, people in American contexts tend to show an independent psychological signature-a sense of self as individual, separate, influencing others and the world, free from influence, and equal to, if not better than, others (Markus & Conner, 2013). Independence is a reasonable description of the selves of people in the White, middle-class American mainstream. Yet it is a less good characterization of the selves of the majority of Americans who are working-class and/or people of color. A cultural psychological approach reveals that much of North American psychology is still grounded in an independent model of the self and, as such, neglects social contexts and the psychologies of a majority of Americans. Given the prominence of independence in American ideas and institutions, the interdependent tendencies that arise from intersections of national culture with social class, race, and ethnicity go unrecognized and are often misunderstood and stigmatized. This unseen clash of independence and interdependence is a significant factor in many challenges, including those of education, employment, health, immigration, criminal justice, and political polarization.

  11. Prognostic value of hemoglobin concentration in radiotherapy for cancer of supraglottic larynx

    International Nuclear Information System (INIS)

    Tarnawski, Rafal; Skladowski, Krzysztof; Maciejewski, Boguslaw

    1997-01-01

    Purpose: The aim of this work is the estimation of correlations between hemoglobin concentration either before or after radiotherapy and local tumor control probability for laryngeal cancer. Methods and Materials: Retrospective analysis of 847 cases of laryngeal supraglottic squamous cell carcinoma treated with radiation alone was performed using maximum likelihood estimations, and step-wise logistic regression. All patients were in good initial performance status (Karnofsky index >70). The minimum follow-up time was 3 years. Results: Logistic regression showed that the hemoglobin concentration after radiotherapy is an important prognostic factor. There was a very strong correlation between hemoglobin concentration and tumor local control probability. Hemoglobin concentration at the beginning of radiotherapy does not correlate with treatment outcome, but any decrease of hemoglobin during therapy is a strong prognostic factor for treatment failure. Conclusions: Although regression models with many variables may be instable, the present results suggest that hemoglobin concentration after treatment is at least as important as overall treatment time. It was not possible to find out whether the low concentration of hemoglobin is an independent cause of low TCP or whether it reflects other mechanisms that may influence both hemoglobin level and the TCP

  12. Prognostic factors in adenocarcinoma of the salivary glands.

    Science.gov (United States)

    Huang, Andrew T; Tang, Chad; Bell, Diana; Yener, Murat; Izquierdo, Luis; Frank, Steven J; El-Naggar, Adel K; Hanna, Ehab Y; Weber, Randal S; Kupferman, Michael E

    2015-06-01

    We aimed to characterize prognostic factors and outcomes in adenocarcinomas of the salivary glands. Patients were identified and retrospectively reviewed for clinical and pathologic tumor characteristics. Low and high grade adenocarcinoma histologies were separated and analyzed. Treatment regimens and patient-related outcomes were recorded and measured. A total of 51 adenocarcinomas of the salivary glands were reviewed. The most common locations of disease were the superficial lobe of the parotid gland, followed by the deep lobe. Five-year overall and disease free survival rates were 43% and 37%. Univariate analysis identified the following as negative prognostic factors: symptoms of a fixed mass or rapid growth, advanced tumor or nodal stage, and perineural or lymphovascular invasion. Facial nerve paralysis was not found to be a significant prognostic variable. Multivariate analysis confirmed the independent negative prognostic importance of the following characteristics: presentation with a fixed mass or rapid growth, diagnosis of adenocarcinoma not otherwise specified, and positive surgical margins. Our results identify several important prognostic factors associated with overall survival in adenocarcinoma of the salivary glands. These prognostic variables encompass symptoms on presentation, clinical and pathologic tumor stage characteristics, and treatment-related factors; all of which are important in patient counseling and may provide impetus for determining treatment escalation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. The prognostic value of FET PET at radiotherapy planning in newly diagnosed glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Hoejklint Poulsen, Sidsel [The Finsen Center, Rigshospitalet, Department of Radiation Biology, Copenhagen (Denmark); Center of Diagnostic Investigation, Rigshospitalet, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark); Urup, Thomas; Grunnet, Kirsten; Skovgaard Poulsen, Hans [The Finsen Center, Rigshospitalet, Department of Radiation Biology, Copenhagen (Denmark); The Finsen Center, Rigshospitalet, Department of Oncology, Copenhagen (Denmark); Jarle Christensen, Ib [University of Copenhagen, Hvidovre Hospital, Laboratory of Gastroenterology, Copenhagen (Denmark); Larsen, Vibeke Andree [Center of Diagnostic Investigation, Rigshospitalet, Department of Radiology, Copenhagen (Denmark); Lundemann Jensen, Michael; Munck af Rosenschoeld, Per [The Finsen Center, Rigshospitalet, Department of Oncology, Copenhagen (Denmark); The Finsen Center, Rigshospitalet, Section of Radiotherapy, Copenhagen (Denmark); Law, Ian [Center of Diagnostic Investigation, Rigshospitalet, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark)

    2017-03-15

    Glioblastoma patients show a great variability in progression free survival (PFS) and overall survival (OS). To gain additional pretherapeutic information, we explored the potential of O-(2-{sup 18}F-fluoroethyl)-L-tyrosine (FET) PET as an independent prognostic biomarker. We retrospectively analyzed 146 consecutively treated, newly diagnosed glioblastoma patients. All patients were treated with temozolomide and radiation therapy (RT). CT/MR and FET PET scans were obtained postoperatively for RT planning. We used Cox proportional hazards models with OS and PFS as endpoints, to test the prognostic value of FET PET biological tumor volume (BTV). Median follow-up time was 14 months, and median OS and PFS were 16.5 and 6.5 months, respectively. In the multivariate analysis, increasing BTV (HR = 1.17, P < 0.001), poor performance status (HR = 2.35, P < 0.001), O(6)-methylguanine-DNA methyltransferase protein status (HR = 1.61, P = 0.024) and higher age (HR = 1.32, P = 0.013) were independent prognostic factors of poor OS. For poor PFS, only increasing BTV (HR = 1.18; P = 0.002) was prognostic. A prognostic index for OS was created based on the identified prognostic factors. Large BTV on FET PET is an independent prognostic factor of poor OS and PFS in glioblastoma patients. With the introduction of FET PET, we obtain a prognostic index that can help in glioblastoma treatment planning. (orig.)

  14. Lifecycle Prognostics Architecture for Selected High-Cost Active Components

    Energy Technology Data Exchange (ETDEWEB)

    N. Lybeck; B. Pham; M. Tawfik; J. B. Coble; R. M. Meyer; P. Ramuhalli; L. J. Bond

    2011-08-01

    There are an extensive body of knowledge and some commercial products available for calculating prognostics, remaining useful life, and damage index parameters. The application of these technologies within the nuclear power community is still in its infancy. Online monitoring and condition-based maintenance is seeing increasing acceptance and deployment, and these activities provide the technological bases for expanding to add predictive/prognostics capabilities. In looking to deploy prognostics there are three key aspects of systems that are presented and discussed: (1) component/system/structure selection, (2) prognostic algorithms, and (3) prognostics architectures. Criteria are presented for component selection: feasibility, failure probability, consequences of failure, and benefits of the prognostics and health management (PHM) system. The basis and methods commonly used for prognostics algorithms are reviewed and summarized. Criteria for evaluating PHM architectures are presented: open, modular architecture; platform independence; graphical user interface for system development and/or results viewing; web enabled tools; scalability; and standards compatibility. Thirteen software products were identified and discussed in the context of being potentially useful for deployment in a PHM program applied to systems in a nuclear power plant (NPP). These products were evaluated by using information available from company websites, product brochures, fact sheets, scholarly publications, and direct communication with vendors. The thirteen products were classified into four groups of software: (1) research tools, (2) PHM system development tools, (3) deployable architectures, and (4) peripheral tools. Eight software tools fell into the deployable architectures category. Of those eight, only two employ all six modules of a full PHM system. Five systems did not offer prognostic estimates, and one system employed the full health monitoring suite but lacked operations and

  15. Prognostic impact of autophagy biomarkers for cutaneous melanoma.

    Directory of Open Access Journals (Sweden)

    Diana Yao Li Tang

    2016-11-01

    Full Text Available Prognosis and survival for malignant melanoma is highly dependent on early diagnosis and treatment. While the American Joint Committee on Cancer (AJCC criteria provides a means of staging melanomas and guiding treatment approaches, it is unable to identify the risk of disease progression of early stage tumours or provide reliable stratification for novel adjuvant therapies. The demand for credible prognostic/companion biomarkers able to identify high risk melanoma subgroups as well as guide more effective personalised/precision based therapy is therefore of paramount importance. Autophagy, the principle lysosomal-mediated process for the degradation/recycling of cellular debris, is a hot topic in cancer medicine and observations of its deregulation in melanoma have brought its potential as a prognostic biomarker to the forefront of current research. Key regulatory proteins, including Atg8/microtubule-associated light chain 3 (LC3 and BECN1 (Beclin 1 have been proposed as potential prognostic biomarkers. However, given the dynamic nature of autophagy, their expression in vitro does not translate to their use as a prognostic biomarker for melanoma in vivo. We have recently identified the expression levels of Sequestosome1/SQSTM1 (p62 and activating molecule in Beclin 1 regulated autophagy protein 1 (AMBRA1 as novel independent prognostic biomarkers for early stage melanomas. While increasing followed by subsequent decreasing levels of p62 expression reflects the paradoxical role of autophagy in melanoma, expression levels additionally define a novel prognostic biomarker for AJCC stage II tumours. Conversely, loss of AMBRA1 in the epidermis overlying primary melanomas defines a novel prognostic biomarker for AJCC stage I tumours. Collectively, the definition of AMBRA1 and p62 as prognostic biomarkers for early stage melanomas provides novel and accurate means through which to identify tumours at risk of disease progression, facilitating earlier

  16. Lifecycle Prognostics Architecture for Selected High-Cost Active Components

    International Nuclear Information System (INIS)

    Lybeck, N.; Pham, B.; Tawfik, M.; Coble, J.B.; Meyer, R.M.; Ramuhalli, P.; Bond, L.J.

    2011-01-01

    There are an extensive body of knowledge and some commercial products available for calculating prognostics, remaining useful life, and damage index parameters. The application of these technologies within the nuclear power community is still in its infancy. Online monitoring and condition-based maintenance is seeing increasing acceptance and deployment, and these activities provide the technological bases for expanding to add predictive/prognostics capabilities. In looking to deploy prognostics there are three key aspects of systems that are presented and discussed: (1) component/system/structure selection, (2) prognostic algorithms, and (3) prognostics architectures. Criteria are presented for component selection: feasibility, failure probability, consequences of failure, and benefits of the prognostics and health management (PHM) system. The basis and methods commonly used for prognostics algorithms are reviewed and summarized. Criteria for evaluating PHM architectures are presented: open, modular architecture; platform independence; graphical user interface for system development and/or results viewing; web enabled tools; scalability; and standards compatibility. Thirteen software products were identified and discussed in the context of being potentially useful for deployment in a PHM program applied to systems in a nuclear power plant (NPP). These products were evaluated by using information available from company websites, product brochures, fact sheets, scholarly publications, and direct communication with vendors. The thirteen products were classified into four groups of software: (1) research tools, (2) PHM system development tools, (3) deployable architectures, and (4) peripheral tools. Eight software tools fell into the deployable architectures category. Of those eight, only two employ all six modules of a full PHM system. Five systems did not offer prognostic estimates, and one system employed the full health monitoring suite but lacked operations and

  17. Prognostic impact of electrocardiographic signs in patients with Type 2 diabetes and cardiovascular disease

    DEFF Research Database (Denmark)

    Pfister, R; Cairns, R; Erdmann, E

    2011-01-01

    Although a resting electrocardiograph is broadly applied in clinical practice for evaluating patients with Type 2 diabetes and cardiovascular disease, the independent prognostic relevance of electrocardiographic signs has not thoroughly been examined.......Although a resting electrocardiograph is broadly applied in clinical practice for evaluating patients with Type 2 diabetes and cardiovascular disease, the independent prognostic relevance of electrocardiographic signs has not thoroughly been examined....

  18. Prognostic factors in lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Starklint, Henrik; Halberg, Poul

    2006-01-01

    To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis.......To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis....

  19. Requirements Specifications for Prognostics: An Overview

    Data.gov (United States)

    National Aeronautics and Space Administration — With recent advancements in prognostics methodologies there has been a significant interest in maturing Prognostics and Health Management (PHM) to increase its...

  20. Metrics for Offline Evaluation of Prognostic Performance

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostic performance evaluation has gained significant attention in the past few years.*Currently, prognostics concepts lack standard definitions and suffer from...

  1. On Applying the Prognostic Performance Metrics

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics performance evaluation has gained significant attention in the past few years. *As prognostics technology matures and more sophisticated methods for...

  2. Prognostic value of serum Epstein-Barr virus antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment Epstein-Barr virus DNA.

    Science.gov (United States)

    Yao, Ji-Jin; Lin, Li; Jin, Ya-Nan; Wang, Si-Yang; Zhang, Wang-Jian; Zhang, Fan; Zhou, Guan-Qun; Cheng, Zhi-Bin; Qi, Zhen-Yu; Sun, Ying

    2017-08-01

    Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum IgA antibodies against early antigen (EA-IgA) and viral capsid antigen (VCA-IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA-IgA and VCA-IgA in patients with NPC is less clear. We hypothesize that serum EA-IgA and VCA-IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non-metastatic NPC and undetectable pEBV DNA were included. Serum EA-IgA and VCA-IgA were determined by ELISA. After analysis, serum EA-IgA and VCA-IgA loads correlated positively with T, N, and overall stage (all P 1:120 had significantly inferior 5-year progression-free survival (80.4% vs 89.6%, P = 0.025), distant metastasis-free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse-free survival (88.4% vs 95.6%, P = 0.023; log-rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA-IgA became insignificant. Further analyses revealed that serum VCA-IgA was not an independent prognostic factor in early N (N0-1) or advanced N (N2-3) stage NPC. In summary, although both EA-IgA and VCA-IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  3. The prognostic relevance of estimates of proliferative activity in early breast cancer

    DEFF Research Database (Denmark)

    Offersen, B V; Sørensen, Flemming Brandt; Knoop, A

    2003-01-01

    clinicopathological parameters at diagnosis in early breast cancer patients.MATERIALS AND METHODS: Tumour specimens from 365 consecutively treated breast cancer patients were immunostained for MIB-1 and evaluated under the microscope using systematic random sampling accomplished by the CAST-grid system...... and number of mitoses included in the analysis, MIB-1 estimates showed no independent prognostic impact.CONCLUSIONS: High MIB-1 estimates did not add independent prognostic information at diagnosis when evaluated together with classical prognostic markers of early breast cancer....

  4. Strong Decomposition of Random Variables

    DEFF Research Database (Denmark)

    Hoffmann-Jørgensen, Jørgen; Kagan, Abram M.; Pitt, Loren D.

    2007-01-01

    A random variable X is stongly decomposable if X=Y+Z where Y=Φ(X) and Z=X-Φ(X) are independent non-degenerated random variables (called the components). It is shown that at least one of the components is singular, and we derive a necessary and sufficient condition for strong decomposability...

  5. [Uterine Carcinosarcoma: Clinicopathological Features and Prognostic Factors].

    Science.gov (United States)

    Luz, Rita; Ferreira, Joana; Rocha, Mara; Jorge, Ana Francisca; Félix, Ana

    2016-10-01

    Uterine carcinosarcoma is a rare and aggressive biphasic malignancy and is currently included in the high risk endometrial carcinoma group. The aims of this study were to determine the clinicopathological profile, treatment, recurrence/progression patterns, survival and prognostic factors. Retrospective study of 42 patients, surgically staged and followed-up at a cancer centre, between 2005 and 2013. Clinical data was retrieved from records and pathological characteristics were reviewed for this study. Median age was 72 years (61 - 78) and the majority presented comorbid diseases. Stage distribution as follows: 13 (31.0%) stage I; eight (19.0%) stage II; nine (21.4%) stage III; and 12 (28.6%) stage IV. Chemotherapy was instituted in 12 patients and 21 received radiotherapy. Disease progressed in 16 patients and recurred in nine after a short interval. Median overall survival was 18 months (6.8 - 40) and median disease-free survival was 6 months (0 - 22.8). The only independent prognostic factor related with poor survival was serosal invasion (p = 0.02; HR adjusted 4.22; IC 95% 1.29 - 13.79). In accordance to other studies, diagnosis of uterine carcinosarcoma is frequently done with advanced disease and presents a high rate of progression/recurrence. The variable which has been consistently identified as main prognostic factor is stage, but in this study the only independent factor was serosal invasion. The present study represents the larger series of uterine carcinosarcoma studied in Portugal and reflects the clinical presentation, histopathological characteristics and stage at diagnosis and confirms the aggressiveness of this rare tumor.

  6. [Prognostic factors in diagnosed endometrial cancers determining the type of radical surgery].

    Science.gov (United States)

    Ivanov, S; Tomov, S

    2009-01-01

    Our aim was to research and evaluate for 10 years period the most important prognostic factors, related and determining the choice of suitable type of radical surgical treatment. It was performed in diagnosed endometrial cancer patients. We researched 460 patients with endometrial cancer for 10 years period. All of them were operated by radical programme. We evaluated the following prognostic factors: stage, age, histological type, tumor grading, invasion of the tumor in myometrium, tumor volume, peritoneal cytology, LVSI, hormonal receptor status, nuclear grading, DNA--ploidy, the extent of the lymph node dissection (number of lymph nodes) and specific genetic alterations connected with endometrial cancers. The surgical determined stage was the most important prognostic factor. The age was independent factor. The histological type was very important prognostic factor--the endometrioid cancers were with better survival rate (89%) in comparison with the rare papillary-serous and clear cell cancers (30%). The tumor grading and myometrical invasion had a very important prognostic significance. When the patients were with grade 3 and infiltration in the outer third of myometrium--the positive pelvic lymph nodes were 30% and the paraaortal--20%. The tumor volume according to us is an independent prognostic factor. When the diameter of the tumor was less than 2 cm--the metastases in the lymph nodes were 3% and when the diameter was more than 2 cm--the metastases were 18%. If the tumor volume occupied the whole endometrial cavity and invasion in myometrium was deep, we had 40% metastases in the lymph nodes. The peritoneal cytology had a relative risk. The LVSI was independent prognostic factor. The ER and PR were independent prognostic factors. The nuclear grading--according to our results is a significant prognostic factor. The aneuploidy was the strongest independent factor for bad survival after age and stage. The extent (the volume) of the lymph node dissection was

  7. Listeriolysin o is strongly immunogenic independently of its cytotoxic activity.

    Directory of Open Access Journals (Sweden)

    Javier A Carrero

    Full Text Available The presentation of microbial protein antigens by Major Histocompatibility Complex (MHC molecules is essential for the development of acquired immunity to infections. However, most biochemical studies of antigen processing and presentation deal with a few relatively inert non-microbial model antigens. The bacterial pore-forming toxin listeriolysin O (LLO is paradoxical in that it is cytotoxic at nanomolar concentrations as well as being the source of dominant CD4 and CD8 T cell epitopes following infection with Listeria monocytogenes. Here, we examined the relationship of LLO toxicity to its antigenicity and immunogenicity. LLO offered to antigen presenting cells (APC as a soluble protein, was presented to CD4 T cells at picomolar to femtomolar concentrations- doses 3000-7000-fold lower than free peptide. This presentation required a dose of LLO below the cytotoxic level. Mutations of two key tryptophan residues reduced LLO toxicity by 10-100-fold but had no effect on its presentation to CD4 T cells. Thus there was a clear dissociation between the cytotoxic properties of LLO and its very high antigenicity. Presentation of LLO to CD8 T cells was not as robust as that seen in CD4 T cells, but still occurred in the nanomolar range. APC rapidly bound and internalized LLO, then disrupted endosomal compartments within 4 hours of treatment, allowing endosomal contents to access the cytosol. LLO was also immunogenic after in vivo administration into mice. Our results demonstrate the strength of LLO as an immunogen to both CD4 and CD8 T cells.

  8. Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer

    DEFF Research Database (Denmark)

    Martens-Uzunova, E S; Jalava, S E; Dits, N F

    2011-01-01

    Prostate cancer (PCa) is the most frequent male malignancy and the second most common cause of cancer-related death in Western countries. Current clinical and pathological methods are limited in the prediction of postoperative outcome. It is becoming increasingly evident that small non-coding RNA...... signatures of 102 fresh-frozen patient samples during PCa progression by miRNA microarrays. Both platforms were cross-validated by quantitative reverse transcriptase-PCR. Besides the altered expression of several miRNAs, our deep sequencing analyses revealed strong differential expression of small nucleolar...... RNAs (snoRNAs) and transfer RNAs (tRNAs). From microarray analysis, we derived a miRNA diagnostic classifier that accurately distinguishes normal from cancer samples. Furthermore, we were able to construct a PCa prognostic predictor that independently forecasts postoperative outcome. Importantly...

  9. Towards Prognostics for Electronics Components

    Data.gov (United States)

    National Aeronautics and Space Administration — Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is...

  10. Standardizing Research Methods for Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics and health management (PHM) is a maturing system engineering discipline. As with most maturing disciplines, PHM does not yet have a universally accepted...

  11. Prognostic factors and scoring system for survival in colonic perforation.

    Science.gov (United States)

    Komatsu, Shuhei; Shimomatsuya, Takumi; Nakajima, Masayuki; Amaya, Hirokazu; Kobuchi, Taketsune; Shiraishi, Susumu; Konishi, Sayuri; Ono, Susumu; Maruhashi, Kazuhiro

    2005-01-01

    No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal output (24h). According to the logistic regression model, BE was a significant independent variable. Concerning the prognostic scoring systems, an APACHE II score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more were significantly related to poor prognosis. Preoperative BE and postoperative white blood cell count were reliable prognostic factors and early classification using prognostic scoring systems at specific points in the disease process are useful to improve our understanding of the problems involved.

  12. Modeling for Battery Prognostics

    Science.gov (United States)

    Kulkarni, Chetan S.; Goebel, Kai; Khasin, Michael; Hogge, Edward; Quach, Patrick

    2017-01-01

    For any battery-powered vehicles (be it unmanned aerial vehicles, small passenger aircraft, or assets in exoplanetary operations) to operate at maximum efficiency and reliability, it is critical to monitor battery health as well performance and to predict end of discharge (EOD) and end of useful life (EOL). To fulfil these needs, it is important to capture the battery's inherent characteristics as well as operational knowledge in the form of models that can be used by monitoring, diagnostic, and prognostic algorithms. Several battery modeling methodologies have been developed in last few years as the understanding of underlying electrochemical mechanics has been advancing. The models can generally be classified as empirical models, electrochemical engineering models, multi-physics models, and molecular/atomist. Empirical models are based on fitting certain functions to past experimental data, without making use of any physicochemical principles. Electrical circuit equivalent models are an example of such empirical models. Electrochemical engineering models are typically continuum models that include electrochemical kinetics and transport phenomena. Each model has its advantages and disadvantages. The former type of model has the advantage of being computationally efficient, but has limited accuracy and robustness, due to the approximations used in developed model, and as a result of such approximations, cannot represent aging well. The latter type of model has the advantage of being very accurate, but is often computationally inefficient, having to solve complex sets of partial differential equations, and thus not suited well for online prognostic applications. In addition both multi-physics and atomist models are computationally expensive hence are even less suited to online application An electrochemistry-based model of Li-ion batteries has been developed, that captures crucial electrochemical processes, captures effects of aging, is computationally efficient

  13. Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance of FLT3 mutations and complex karyotype.

    Science.gov (United States)

    Poiré, Xavier; Moser, Barry K; Gallagher, Robert E; Laumann, Kristina; Bloomfield, Clara D; Powell, Bayard L; Koval, Gregory; Gulati, Kabir; Holowka, Nicholas; Larson, Richard A; Tallman, Martin S; Appelbaum, Frederick R; Sher, Dorie; Willman, Cheryl; Paietta, Elisabeth; Stock, Wendy

    2014-07-01

    The addition of arsenic trioxide (ATO) to frontline therapy of acute promyelocytic leukemia (APL) has been shown to result in significant improvements in disease-free survival (DFS). FLT3 mutations are frequently observed in APL, but its prognostic significance remains unclear. We analyzed 245 newly diagnosed adult patients with APL treated on intergroup trial C9710 and evaluated previously defined biological and prognostic factors and their relationship to FLT3 mutations and to additional karyotypic abnormalities. FLT3 mutations were found in 48% of patients, including 31% with an internal tandem duplication (FLT3-ITD), 14% with a point mutation (FLT3-D835) and 2% with both mutations. The FLT3-ITD mutant level was uniformly low, karyotype was strongly associated with an inferior OS independently of post-remission treatment. In conclusion, the addition of ATO to frontline therapy overcomes the impact of previously described adverse prognostic factors including FLT3 mutations. However, complex karyotype is strongly associated with an inferior OS despite ATO therapy.

  14. Prognostic Impact of Circulating Tumor Cell Detected Using a Novel Fluidic Cell Microarray Chip System in Patients with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Takeshi Sawada

    2016-09-01

    Full Text Available Various types of circulating tumor cell (CTC detection systems have recently been developed that show a high CTC detection rate. However, it is a big challenge to find a system that can provide better prognostic value than CellSearch in head-to-head comparison. We have developed a novel semi-automated CTC enumeration system (fluidic cell microarray chip system, FCMC that captures CTC independently of tumor-specific markers or physical properties. Here, we compared the CTC detection sensitivity and the prognostic value of FCMC with CellSearch in breast cancer patients. FCMC was validated in preclinical studies using spike-in samples and in blood samples from 20 healthy donors and 22 breast cancer patients in this study. Using spike-in samples, a statistically higher detection rate (p = 0.010 of MDA-MB-231 cells and an equivalent detection rate (p = 0.497 of MCF-7 cells were obtained with FCMC in comparison with CellSearch. The number of CTC detected in samples from patients that was above a threshold value as determined from healthy donors was evaluated. The CTC number detected using FCMC was significantly higher than that using CellSearch (p = 0.00037. CTC numbers obtained using either FCMC or CellSearch had prognostic value, as assessed by progression free survival. The hazard ratio between CTC+ and CTC− was 4.229 in CellSearch (95% CI, 1.31 to 13.66; p = 0.01591; in contrast, it was 11.31 in FCMC (95% CI, 2.245 to 57.0; p = 0.000244. CTC detected using FCMC, like the CTC detected using CellSearch, have the potential to be a strong prognostic factor for cancer patients.

  15. Some interesting prognostic factors related to cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Joan Figueroa, AlejandroYuri; Diaz Anaya, Amnia; Montero Leon, Jorge Felipe; Jimenez Mendes, Lourdes

    2010-01-01

    INTRODUCTION: The aim of present research was to determine the independent prognostic value and the 3 and 5 years survival of more significant clinicopathological prognostic factors and in each stage, according to pathological staging system of tumor-nodule-metastasis (TNM) in patients with cutaneous malignant melanoma (CMM). METHODS: A longitudinal, descriptive and retrospective study was conducted applying the Cox proportional risk form and the Kaplan-Meier method, aimed to search of different risk variables in patients with CMM. We studied 157 patients with CMM, seen during 8 years (1993 to 2001), diagnosed and treated in National Institute of Oncology and Radiobiology of La Habana. RESULTS: The more powerful prognostic variables related to localized disease (stage I and II) were the Breslow density (P: 0,000), the mitosis rate (P: 0,004), and the Clark level (P: 0,04); among the variables related to the regional disease (stage III) the number of lymphatic ganglia involved was the more weighthy (P:0,000) and the more important in Stage IV was the distant visceral metastasis (P:0,003). Survival was decreasing according to the advance of the pathological stage of disease. CONCLUSIONS: The more involved independent prognostic factors were the Breslow rate, the number of involved regional lymphatic nodules and the distant visceral metastasis, which is endorsed by a world consensus. However, variables as age, sex, lesion site, ulceration, host-tumor inflammatory response, histological subtype, satellitosis and transient metastasis, considered as independent prognostic indicators in big casuistries, had not statistical significance in present paper. (author)

  16. The Practicability of a Novel Prognostic Index (PI) Model and Comparison with Nottingham Prognostic Index (NPI) in Stage I-III Breast Cancer Patients Undergoing Surgical Treatment.

    Science.gov (United States)

    Wen, Jiahuai; Ye, Feng; Li, Shuaijie; Huang, Xiaojia; Yang, Lu; Xiao, Xiangsheng; Xie, Xiaoming

    2015-01-01

    Previous studies have indicated the prognostic value of various laboratory parameters in cancer patients. This study was to establish a prognostic index (PI) model for breast cancer patients based on the potential prognostic factors. A retrospective study of 1661 breast cancer patients who underwent surgical treatment between January 2002 and December 2008 at Sun Yat-sen University Cancer Center was conducted. Multivariate analysis (Cox regression model) was performed to determine the independent prognostic factors and a prognostic index (PI) model was devised based on these factors. Survival analyses were used to estimate the prognostic value of PI, and the discriminatory ability of PI was compared with Nottingham Prognostic Index (NPI) by evaluating the area under the receiver operating characteristics curves (AUC). The mean survival time of all participants was 123.6 months. The preoperative globulin >30.0g/L, triglyceride >1.10mmol/L and fibrinogen >2.83g/L were identified as risk factors for shorter cancer-specific survival. The novel prognostic index model was established and enrolled patients were classified as low- (1168 patients, 70.3%), moderate- (410 patients, 24.7%) and high-risk groups (83 patients, 5.0%), respectively. Compared with the low-risk group, higher risks of poor clinical outcome were indicated in the moderate-risk group [Hazard ratio (HR): 1.513, 95% confidence interval (CI): 1.169-1.959, p = 0.002] and high-risk group (HR: 2.481, 95%CI: 1.653-3.724, p< 0.001). The prognostic index based on three laboratory parameters was a novel and practicable prognostic tool. It may serve as complement to help predict postoperative survival in breast cancer patients.

  17. The prognostic value of MRI in determining reinjury risk following acute hamstring injury: a systematic review.

    Science.gov (United States)

    van Heumen, Moniek; Tol, Johannes L; de Vos, Robert-Jan; Moen, Maarten H; Weir, Adam; Orchard, John; Reurink, Gustaaf

    2017-09-01

    A challenge for sports physicians is to estimate the risk of a hamstring re-injury, but the current evidence for MRI variables as a risk factor is unknown. To systematically review the literature on the prognostic value of MRI findings at index injury and/or return to play for acute hamstring re-injuries. Databases of PubMed, Embase, MEDLINE, Scopus, CINAHL, Google Scholar, Web of Science, LILACS, SciELO, ScienceDirect, ProQuest, SPORTDiscus and Cochrane Library were searched until 20 June 2016. Studies evaluating MRI as a prognostic tool for determining the risk of re-injury for athletes with acute hamstring injuries were eligible for inclusion. Two authors independently screened the search results and assessed risk of bias using standardised criteria from a consensus statement. A best-evidence synthesis was used to identify the level of evidence. Post hoc analysis included correction for insufficient sample size. Of the 11 studies included, 7 had a low and 4 had a high risk of bias. No strong evidence for any MRI finding as a risk factor for hamstring re-injury was found. There was moderate evidence that intratendinous injuries were associated with increased re-injury risk. Post hoc analysis showed moderate evidence that injury to the biceps femoris was a moderate to strong risk factor for re-injury. There is currently no strong evidence for any MRI finding in predicting hamstring re-injury risk. Intratendinous injuries and biceps femoris injuries showed moderate evidence for association with a higher re-injury risk. Registration in the PROSPERO International prospective register of systematic reviews was performed prior to study initiation (registration number CRD42015024620). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Multi-level gene expression signatures, but not binary, outperform Ki67 for the long term prognostication of breast cancer patients.

    Science.gov (United States)

    Tobin, Nicholas P; Lindström, Linda S; Carlson, Joseph W; Bjöhle, Judith; Bergh, Jonas; Wennmalm, Kristian

    2014-05-01

    Proliferation-related gene signatures have been proposed to aid breast cancer management by providing reproducible prognostic and predictive information on a patient-by-patient basis. It is unclear however, whether a less demanding assessment of cell division rate (as determined in clinical setting by expression of Ki67) can function in place of gene profiling. We investigated agreement between literature-, distribution-based, as well as signature-derived values for Ki67, relative to the genomic grade index (GGI), 70-gene signature, p53 signature, recurrence score (RS), and the molecular subtype models of Sorlie, Hu, and Parker in representative sets of 253 and 159 breast cancers with a median follow-up of 13 and 14.5 years, respectively. The relevance for breast cancer specific survival was also addressed in uni- and bivariate Cox models. Taking both cohorts into account, our broad approach identified ROC optimized Ki67 cutoffs in the range of 8-28%. With optimum signature-reproducing cutoffs, similarity in classification of individual tumors was higher for binary signatures (72-85%), than multi-level signatures (67-73%). Consistent with strong agreement, no prognostic superiority was noted for either Ki67 or the binary GGI, 70-gene and p53 signatures in the Uppsala dataset by bivariate analyses. In contrast, Ki67-independent prognostic capacity could be demonstrated for RS and molecular subtypes according to Sorlie, Hu and Parker in both datasets. Our results show that the added prognostic value of binary proliferation-related gene signatures is limited for Ki67-assessed breast cancers. More complex, multi-level descriptions have a greater potential in short- and long-term prognostication for biologically relevant breast cancer subgroups. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  19. Prognostic scores for sorafenib-treated hepatocellular carcinoma patients: A new application for the hepatoma arterial embolisation prognostic score.

    Science.gov (United States)

    Edeline, J; Blanc, J-F; Campillo-Gimenez, B; Ma, Y-T; King, J; Faluyi, O; Mathurin, J; Ghazi, S; Palmer, D H; Meyer, T

    2017-11-01

    No prognostic classification is currently used for patients treated with systemic therapies for Hepatocellular Carcinoma (HCC). We retrospectively analysed data from patients treated with sorafenib for HCC from five centres in France and in the United Kingdom (UK). The training set comprised data from two centres and the validation set from three. Variables independently associated with Overall Survival (OS) in the training set were used to build the SAP (Sorafenib Advanced HCC Prognosis) score. The score was tested in the validation set, then compared with other prognostication systems. The training set and validation set included 370 and 468 patients respectively. In the training set, variables independently associated with OS in multivariable analysis were: performance status (PS) >0, alpha-fetoprotein (AFP) >400 ng/ml, tumour size >7 cm, bilirubin >17 μmol/l and albumin Cancer (BCLC) and albumin-bilirubin (ALBI) scores. However, the hepatoma arterial embolisation prognostic (HAP) score showed greater discriminative abilities than the SAP score. In European patients treated with sorafenib, the HAP was the most discriminant prognostic score and may facilitate stratification in trials and inform clinical decision making. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An Individual Patient Data Meta-Analysis.

    Science.gov (United States)

    Aimo, Alberto; Januzzi, James L; Vergaro, Giuseppe; Ripoli, Andrea; Latini, Roberto; Masson, Serge; Magnoli, Michela; Anand, Inder S; Cohn, Jay N; Tavazzi, Luigi; Tognoni, Gianni; Gravning, Jørgen; Ueland, Thor; Nymo, Ståle H; Brunner-La Rocca, Hans-Peter; Bayes-Genis, Antoni; Lupón, Josep; de Boer, Rudolf A; Yoshihisa, Akiomi; Takeishi, Yasuchika; Egstrup, Michael; Gustafsson, Ida; Gaggin, Hanna K; Eggers, Kai M; Huber, Kurt; Tentzeris, Ioannis; Tang, Wai H W; Grodin, Justin; Passino, Claudio; Emdin, Michele

    2018-01-16

    Most patients with chronic heart failure have detectable troponin concentrations when evaluated by high-sensitivity assays. The prognostic relevance of this finding has not been clearly established so far. We aimed to assess high-sensitivity troponin assay for risk stratification in chronic heart failure through a meta-analysis approach. Medline, EMBASE, Cochrane Library, and Scopus were searched in April 2017 by 2 independent authors. The terms were "troponin" AND "heart failure" OR "cardiac failure" OR "cardiac dysfunction" OR "cardiac insufficiency" OR "left ventricular dysfunction." Inclusion criteria were English language, clinical stability, use of a high-sensitivity troponin assay, follow-up studies, and availability of individual patient data after request to authors. Data retrieved from articles and provided by authors were used in agreement with the PRISMA statement. The end points were all-cause death, cardiovascular death, and hospitalization for cardiovascular cause. Ten studies were included, reporting data on 11 cohorts and 9289 patients (age 66±12 years, 77% men, 60% ischemic heart failure, 85% with left ventricular ejection fraction failure, high-sensitivity troponin T is a strong and independent predictor of all-cause and cardiovascular mortality, and of hospitalization for cardiovascular causes, as well. This biomarker then represents an additional tool for prognostic stratification. © 2018 American Heart Association, Inc.

  1. Prognostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography in Patients with Resectable Pancreatic Cancer

    Science.gov (United States)

    Choi, Hye Jin; Kang, Chang Moo; Lee, Woo Jung; Song, Si Young; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Kim, Joo Hang

    2013-01-01

    Purpose We evaluated the prognostic value of 18F-2-fluoro-2-deoxyglucose positron emission tomography (FDG PET) in patients with resectable pancreatic cancer. Materials and Methods We retrospectively reviewed the medical records of pancreatic cancer patients who underwent curative resection, which included 64 consecutive patients who had preoperative FDG PET scans. For statistical analysis, the maximal standardized uptake value (SUVmax) of primary pancreatic cancer was measured. Survival time was estimated by the Kaplan-Meier method, and Cox's proportional hazard model was used to determine whether SUVmax added new predictive information concerning survival together with known prognostic factors. p3.5) showed significantly shorter OS and DFS than the low SUVmax group. Multivariate analysis of OS and DFS showed that both high SUVmax and poor tumor differentiation were independent poor prognostic factors. Conclusion Our study showed that degree of FDG uptake was an independent prognostic factor in pancreatic cancer patients who underwent curative resection. PMID:24142641

  2. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Spindler, Karen-Lise Garm; Andersen, Rikke Fredslund

    2010-01-01

    for this effect, was present in approximately 30% of the patients and demonstrated a significant relationship with poor survival, and it remained an independent prognostic marker after multivariate analysis, hazard ratio 2.46 (95% confidence interval 1.49-4.06), p ...Abstract: New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study...

  3. Prognostic significance of aberrantly silenced ANPEP expression in prostate cancer

    DEFF Research Database (Denmark)

    Sørensen, Karina Dalsgaard; Abildgaard, Mette Opstrup; Haldrup, Christa

    2013-01-01

    Background:Novel biomarkers for prostate cancer (PC) are urgently needed. This study investigates the expression, epigenetic regulation, and prognostic potential of ANPEP in PC.Methods:Aminopeptidase N (APN; encoded by ANPEP) expression was analysed by immunohistochemistry using tissue microarrays...... in three hypermethylated prostate cell lines, suggesting epigenetic silencing. Negative APN immunoreactivity was significantly associated with short RFS and short CSS in the RP and CT cohort, respectively, independently of routine clinicopathological predictors. Combining APN with a known angiogenesis...... marker (vascular endothelial growth factor or microvessel density) improved risk prediction significantly in both cohorts.Conclusion:Our results suggest negative APN immunoreactivity as a new independent adverse prognostic factor for patients with clinically localised PC and, furthermore, that epigenetic...

  4. Gene expression risk signatures maintain prognostic power in multiple myeloma despite microarray probe set translation

    DEFF Research Database (Denmark)

    Hermansen, N E U; Borup, R; Andersen, M K

    2016-01-01

    INTRODUCTION: Gene expression profiling (GEP) risk models in multiple myeloma are based on 3'-end microarrays. We hypothesized that GEP risk signatures could retain prognostic power despite being translated and applied to whole-transcript microarray data. METHODS: We studied CD138-positive bone...... signatures maintain significant prognostic power in HDT myeloma patients. We suggest probe set matching for GEP risk signature translation as part of the efforts towards a microarray-independent GEP risk standard. (ClicinalTrials.gov identifier: NCT00639054)....

  5. Prognostic impact of postoperative, pre-irradiation 18F-fluoroethyl-L-tyrosine uptake in glioblastoma patients treated with radiochemotherapy

    International Nuclear Information System (INIS)

    Piroth, Marc D.; Holy, Richard; Pinkawa, Michael; Stoffels, Gabriele; Kaiser, Hans J.; Galldiks, Norbert; Herzog, Hans; Coenen, Heinz H.; Eble, Michael J.; Langen, Karl J.

    2011-01-01

    Background and purpose: Resection is considered as essential for the efficacy of modern adjuvant treatment of glioblastoma multiforme (GBM). Previous studies have indicated that amino acid PET is more specific than contrast enhancement on MRI for detecting residual tumor tissue after surgery. In a prospective study we investigated the prognostic impact of postoperative tumor volume and tumor/brain ratios (TBR) in PET using O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) in comparison with MRI. Materials and methods: Forty-four patients with GBM were investigated by FET PET and MRI after surgery. Tumor volume in FET PET with a tumor/brain ratio (TBR) > 1.6 and a TBR > 2, mean and maximum TBR and gadolinium contrast-enhancement on MRI (Gd-volume) were determined. Thereafter patients received a fractionated radiotherapy with concomitant temozolomide (RCX). The median follow-up was 15.4 (3-35) months. The prognostic value of postoperative residual tumor volume in FET PET, TBR mean, TBR max and Gd-volume was evaluated using Kaplan-Maier estimates for disease-free survival (DFS) and overall survival (OS). Results: Postoperative tumor volume in FET PET had a significant independent influence on OS and DFS (OS 20.0 vs. 6.9 months; DFS 9.6 vs. 5.1 months, p 18 F-FET PET. The TBR mean and TBR max of FET uptake had a significant influence on DFS (p < 0.05). Gd-volume in MRI had significant effect on OS and DFS in the univariate analysis. No independent significant influence in OS or DFS could be observed for Gd-volume in MRI. Conclusions: Our data indicate that the tumor volume in FET PET after surgery of GBM has a strong prognostic impact for these patients. FET PET appears to be helpful to determine the residual tumor volume after surgery of GBM and may serve as a valuable tool for optimal planning of radiation treatment.

  6. Prognostic meta-signature of breast cancer developed by two-stage mixture modeling of microarray data

    Directory of Open Access Journals (Sweden)

    Ghosh Debashis

    2004-12-01

    Full Text Available Abstract Background An increasing number of studies have profiled tumor specimens using distinct microarray platforms and analysis techniques. With the accumulating amount of microarray data, one of the most intriguing yet challenging tasks is to develop robust statistical models to integrate the findings. Results By applying a two-stage Bayesian mixture modeling strategy, we were able to assimilate and analyze four independent microarray studies to derive an inter-study validated "meta-signature" associated with breast cancer prognosis. Combining multiple studies (n = 305 samples on a common probability scale, we developed a 90-gene meta-signature, which strongly associated with survival in breast cancer patients. Given the set of independent studies using different microarray platforms which included spotted cDNAs, Affymetrix GeneChip, and inkjet oligonucleotides, the individually identified classifiers yielded gene sets predictive of survival in each study cohort. The study-specific gene signatures, however, had minimal overlap with each other, and performed poorly in pairwise cross-validation. The meta-signature, on the other hand, accommodated such heterogeneity and achieved comparable or better prognostic performance when compared with the individual signatures. Further by comparing to a global standardization method, the mixture model based data transformation demonstrated superior properties for data integration and provided solid basis for building classifiers at the second stage. Functional annotation revealed that genes involved in cell cycle and signal transduction activities were over-represented in the meta-signature. Conclusion The mixture modeling approach unifies disparate gene expression data on a common probability scale allowing for robust, inter-study validated prognostic signatures to be obtained. With the emerging utility of microarrays for cancer prognosis, it will be important to establish paradigms to meta

  7. Multigene prognostic tests in breast cancer: past, present, future.

    Science.gov (United States)

    Győrffy, Balázs; Hatzis, Christos; Sanft, Tara; Hofstatter, Erin; Aktas, Bilge; Pusztai, Lajos

    2015-01-27

    There is growing consensus that multigene prognostic tests provide useful complementary information to tumor size and grade in estrogen receptor (ER)-positive breast cancers. The tests primarily rely on quantification of ER and proliferation-related genes and combine these into multivariate prediction models. Since ER-negative cancers tend to have higher proliferation rates, the prognostic value of current multigene tests in these cancers is limited. First-generation prognostic signatures (Oncotype DX, MammaPrint, Genomic Grade Index) are substantially more accurate to predict recurrence within the first 5 years than in later years. This has become a limitation with the availability of effective extended adjuvant endocrine therapies. Newer tests (Prosigna, EndoPredict, Breast Cancer Index) appear to possess better prognostic value for late recurrences while also remaining predictive of early relapse. Some clinical prediction problems are more difficult to solve than others: there are no clinically useful prognostic signatures for ER-negative cancers, and drug-specific treatment response predictors also remain elusive. Emerging areas of research involve the development of immune gene signatures that carry modest but significant prognostic value independent of proliferation and ER status and represent candidate predictive markers for immune-targeted therapies. Overall metrics of tumor heterogeneity and genome integrity (for example, homologue recombination deficiency score) are emerging as potential new predictive markers for platinum agents. The recent expansion of high-throughput technology platforms including low-cost sequencing of circulating and tumor-derived DNA and RNA and rapid reliable quantification of microRNA offers new opportunities to build extended prediction models across multiplatform data.

  8. HER3 protein expression in relation to HER2 positivity in patients with primary colorectal cancer: clinical relevance and prognostic value.

    Science.gov (United States)

    Seo, An Na; Kwak, Yoonjin; Kim, Woo Ho; Kim, Duck-Woo; Kang, Sung-Bum; Choe, Gheeyoung; Lee, Hye Seung

    2015-06-01

    The clinical and prognostic significance of HER3 expression and its relation to HER2 status in primary colorectal cancer (pCRC) were investigated. We retrospectively analysed 365 consecutive cases of pCRC that had been previously evaluated for HER2 status and included their 143 matched lymph node metastases. Immunohistochemistry (IHC) was performed to assess HER3 expression using tissue array methods. Of 364 eligible patients, HER3 overexpression was detected in 251 cases (69 %) (IHC 2+, n = 186 and IHC 3+, n = 65). HER3 overexpression was inversely correlated with histologic grade (p = 0.006), tumour size (p < 0.001), tumour depth (p < 0.001), TNM stage (p = 0.002), lymphatic invasion (p = 0.004), lymph node metastasis (p = 0.013) and distant metastasis (p = 0.039). Moreover, it positively correlated with both HER2 overexpression (p = 0.007) and HER2 gene amplification (p = 0.006). Although HER3 overexpression was associated with longer survival in univariate analysis (p = 0.026), it was not an independent prognostic factor in multivariate analysis (p = 0.359). Moreover, co-alteration of HER3 and HER2 was associated with neither survival nor any clinicopathologic parameter except tumour location in the rectum. Although not an independent prognostic factor for overall survival, HER3 overexpression was associated with several favourable prognostic clinicopathologic parameters. Additionally, HER3 overexpression strongly correlated with HER2 positivity in this cohort of patients.

  9. <strong>Neuroeconomics and Human Resource Developmentstrong>/>

    DEFF Research Database (Denmark)

    Larsen, Torben

    2009-01-01

    threats and personal stress. So far, the evidence-based findings on human resource development (HRD) seem not to match these huge challenges. The aim of this study is to identify cost-effective means of mental training to recover sufficiently from the present bias to enable more sustainable decisions...... making as required to meet the global challenges in study as confirmed by an intercultural neuroeconomic comparative study between Asian and Western cultures. However, a cultural barrier in the Western cultural tradition against meditative introversion has to be overcome to improve the time horizon...... meditation, Harvard relaxation procedure, ACEM meditation and Autogenic training. IV. Broad health effects of regular medical meditation are evidenced by RCT and even reviews/meta-analysis in more medical meditation settings: Recovery from basal anxiety Stabilization of plasma cortisol Independence...

  10. Assessment and implication of prognostic imbalance in randomized controlled trials with a binary outcome--a simulation study.

    Directory of Open Access Journals (Sweden)

    Rong Chu

    Full Text Available Chance imbalance in baseline prognosis of a randomized controlled trial can lead to over or underestimation of treatment effects, particularly in trials with small sample sizes. Our study aimed to (1 evaluate the probability of imbalance in a binary prognostic factor (PF between two treatment arms, (2 investigate the impact of prognostic imbalance on the estimation of a treatment effect, and (3 examine the effect of sample size (n in relation to the first two objectives.We simulated data from parallel-group trials evaluating a binary outcome by varying the risk of the outcome, effect of the treatment, power and prevalence of the PF, and n. Logistic regression models with and without adjustment for the PF were compared in terms of bias, standard error, coverage of confidence interval and statistical power.For a PF with a prevalence of 0.5, the probability of a difference in the frequency of the PF≥5% reaches 0.42 with 125/arm. Ignoring a strong PF (relative risk = 5 leads to underestimating the strength of a moderate treatment effect, and the underestimate is independent of n when n is >50/arm. Adjusting for such PF increases statistical power. If the PF is weak (RR = 2, adjustment makes little difference in statistical inference. Conditional on a 5% imbalance of a powerful PF, adjustment reduces the likelihood of large bias. If an absolute measure of imbalance ≥5% is deemed important, including 1000 patients/arm provides sufficient protection against such an imbalance. Two thousand patients/arm may provide an adequate control against large random deviations in treatment effect estimation in the presence of a powerful PF.The probability of prognostic imbalance in small trials can be substantial. Covariate adjustment improves estimation accuracy and statistical power, and hence should be performed when strong PFs are observed.

  11. Testing strong interaction theories

    International Nuclear Information System (INIS)

    Ellis, J.

    1979-01-01

    The author discusses possible tests of the current theories of the strong interaction, in particular, quantum chromodynamics. High energy e + e - interactions should provide an excellent means of studying the strong force. (W.D.L.)

  12. Incidence, 10-year recidivism rate and prognostic factors for cholesteatoma.

    Science.gov (United States)

    Britze, A; Møller, M L; Ovesen, T

    2017-04-01

    Cholesteatoma patients have a high risk of recurrence with complications, and knowledge exchange is a prerequisite for improving treatment. This study aimed to apply appropriate statistics to provide meaningful and transferable results from cholesteatoma surgery, to highlight independent prognostic factors, and to assess the incidence rate. Incidence rates were assessed for the district of Aarhus, Denmark. From 147 patients operated on mainly with canal wall up mastoidectomies for debuting cholesteatomas, 10-year Kaplan-Meier recidivism rates were calculated and independent prognostic factors for the recidivism were identified by Cox multivariate regression analyses. Incidence rate was 6.8 per 100 000 per year. The 10-year cumulative recidivism rate was 0.44 (95 per cent confidence interval, 0.37-0.53). Independent prognostic factors for the recidivism were: age below 15 years (hazard ratio = 2.2; p > z = 0.002), cholesteatoma localised to the mastoid (hazard ratio = 1.7; p > z = 0.04), stapes erosion (hazard ratio = 1.9; p > z = 0.02) and incus erosion (hazard ratio = 1.9; p > z = 0.04). The recidivism rate is influenced by several factors that are important to observe, both in the clinic and when comparing results from surgery.

  13. Clinicopathological Features and Prognostic Factors of Colorectal Neuroendocrine Neoplasms

    Directory of Open Access Journals (Sweden)

    Mengjie Jiang

    2017-01-01

    Full Text Available Background. Limited research is available regarding colorectal NENs and the prognostic factors remain controversial. Materials and Methods. A total of 68 patients with colorectal NENs were studied retrospectively. Clinical characteristics and prognosis between colonic and rectal NENs were compared. The Cox regression models were used to evaluate the predictive capacity. Results. Of the 68 colorectal NENs patients, 43 (63.2% had rectal NENs, and 25 (36.8% had colonic NENs. Compared with rectal NENs, colonic NENs more frequently exhibited larger tumor size (P<0.0001 and distant metastasis (P<0.0001. Colonic NENs had a worse prognosis (P=0.027, with 5-year overall survival rates of 66.7% versus 88.1%. NET, NEC, and MANEC were noted in 61.8%, 23.5%, and 14.7% of patients, respectively. Multivariate analyses revealed that tumor location was not an independent prognostic factor (P=0.081, but tumor size (P=0.037 and pathological classification (P=0.012 were independent prognostic factors. Conclusion. Significant differences exist between colonic and rectal NENs. Multivariate analysis indicated that tumor size and pathological classification were associated with prognosis. Tumor location was not an independent factor. The worse outcome of colonic NENs observed in clinical practice might be due not only to the biological differences, but also to larger tumor size in colonic NENs caused by the delayed diagnosis.

  14. Prognostic Factors in Hodgkin's Disease

    DEFF Research Database (Denmark)

    Specht

    1996-01-01

    regions and the tumor mass in each region are important, and an estimate of the total tumor burden has proved significant. B symptoms, histological subtype, age, and gender are also generally significant but less important. Prognostic factors for laparotomy findings in clinical stages I and II are: number...... of involved regions, disease confined to upper cervical nodes, B symptoms, gender, histology, age, and mediastinal disease (variable influence). In clinical stages I and II, the same prognostic factors apply as for pathological stages I and II and for laparotomy findings, and also some indirect indicators...

  15. Distributed Prognostics Based on Structural Model Decomposition

    Data.gov (United States)

    National Aeronautics and Space Administration — Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based...

  16. A Generic Software Architecture For Prognostics

    Science.gov (United States)

    Teubert, Christopher; Daigle, Matthew J.; Sankararaman, Shankar; Goebel, Kai; Watkins, Jason

    2017-01-01

    Prognostics is a systems engineering discipline focused on predicting end-of-life of components and systems. As a relatively new and emerging technology, there are few fielded implementations of prognostics, due in part to practitioners perceiving a large hurdle in developing the models, algorithms, architecture, and integration pieces. As a result, no open software frameworks for applying prognostics currently exist. This paper introduces the Generic Software Architecture for Prognostics (GSAP), an open-source, cross-platform, object-oriented software framework and support library for creating prognostics applications. GSAP was designed to make prognostics more accessible and enable faster adoption and implementation by industry, by reducing the effort and investment required to develop, test, and deploy prognostics. This paper describes the requirements, design, and testing of GSAP. Additionally, a detailed case study involving battery prognostics demonstrates its use.

  17. Repeated measurement of the intermountain risk score enhances prognostication for mortality.

    Directory of Open Access Journals (Sweden)

    Benjamin D Horne

    Full Text Available BACKGROUND: The Intermountain Risk Score (IMRS, composed of the complete blood count (CBC and basic metabolic profile (BMP, predicts mortality and morbidity in medical and general populations. Whether longitudinal repeated measurement of IMRS is useful for prognostication is an important question for its clinical applicability. METHODS: Females (N = 5,698 and males (N = 5,437 with CBC and BMP panels measured 6 months to 2.0 years apart (mean 1.0 year had baseline and follow-up IMRS computed. Survival analysis during 4.0±2.5 years (maximum 10 years evaluated mortality (females: n = 1,255 deaths; males: n = 1,164 deaths and incident major events (myocardial infarction, heart failure [HF], and stroke. RESULTS: Both baseline and follow-up IMRS (categorized as high-risk vs. low-risk were independently associated with mortality (all p<0.001 in bivariable models. For females, follow-up IMRS had hazard ratio (HR = 5.23 (95% confidence interval [CI] = 4.11, 6.64 and baseline IMRS had HR = 3.66 (CI = 2.94, 4.55. Among males, follow-up IMRS had HR = 4.28 (CI = 3.51, 5.22 and baseline IMRS had HR = 2.32 (CI = 1.91, 2.82. IMRS components such as RDW, measured at both time points, also predicted mortality. Baseline and follow-up IMRS strongly predicted incident HF in both genders. CONCLUSIONS: Repeated measurement of IMRS at baseline and at about one year of follow-up were independently prognostic for mortality and incident HF among initially hospitalized patients. RDW and other CBC and BMP values were also predictive of outcomes. Further research should evaluate the utility of IMRS as a tool for clinical risk adjustment.

  18. Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Krause Alexander

    2006-08-01

    Full Text Available Abstract Background One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1. In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. Methods The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. Results uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS and Breast Cancer specific Survival (BCS were significantly shorter in patients expressing high levels of PAI-1 mRNA (p PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR = 10.12; p = 0.0002 and for BCS (HR = 13.17; p = 0.0003. Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41 nor with BCS (p = 0.19. In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. Conclusion These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer patients.

  19. Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

    International Nuclear Information System (INIS)

    Leissner, Philippe; Verjat, Thibault; Bachelot, Thomas; Paye, Malick; Krause, Alexander; Puisieux, Alain; Mougin, Bruno

    2006-01-01

    One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS) and Breast Cancer specific Survival (BCS) were significantly shorter in patients expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer

  20. Homogeneous datasets of triple negative breast cancers enable the identification of novel prognostic and predictive signatures.

    Directory of Open Access Journals (Sweden)

    Thomas Karn

    Full Text Available BACKGROUND: Current prognostic gene signatures for breast cancer mainly reflect proliferation status and have limited value in triple-negative (TNBC cancers. The identification of prognostic signatures from TNBC cohorts was limited in the past due to small sample sizes. METHODOLOGY/PRINCIPAL FINDINGS: We assembled all currently publically available TNBC gene expression datasets generated on Affymetrix gene chips. Inter-laboratory variation was minimized by filtering methods for both samples and genes. Supervised analysis was performed to identify prognostic signatures from 394 cases which were subsequently tested on an independent validation cohort (n = 261 cases. CONCLUSIONS/SIGNIFICANCE: Using two distinct false discovery rate thresholds, 25% and <3.5%, a larger (n = 264 probesets and a smaller (n = 26 probesets prognostic gene sets were identified and used as prognostic predictors. Most of these genes were positively associated with poor prognosis and correlated to metagenes for inflammation and angiogenesis. No correlation to other previously published prognostic signatures (recurrence score, genomic grade index, 70-gene signature, wound response signature, 7-gene immune response module, stroma derived prognostic predictor, and a medullary like signature was observed. In multivariate analyses in the validation cohort the two signatures showed hazard ratios of 4.03 (95% confidence interval [CI] 1.71-9.48; P = 0.001 and 4.08 (95% CI 1.79-9.28; P = 0.001, respectively. The 10-year event-free survival was 70% for the good risk and 20% for the high risk group. The 26-gene signatures had modest predictive value (AUC = 0.588 to predict response to neoadjuvant chemotherapy, however, the combination of a B-cell metagene with the prognostic signatures increased its response predictive value. We identified a 264-gene prognostic signature for TNBC which is unrelated to previously known prognostic signatures.

  1. Prognostic stratification of ulcerated melanoma

    DEFF Research Database (Denmark)

    Bønnelykke-Behrndtz, Marie L; Schmidt, Henrik; Christensen, Ib J

    2014-01-01

    OBJECTIVES: For patients with melanoma, ulceration is an important prognostic marker and interestingly also a predictive marker for the response of adjuvant interferon. A consensual definition and accurate assessment of ulceration are therefore crucial for proper staging and clinical management. We...

  2. Cytogenetic prognostication within medulloblastoma subgroups.

    Science.gov (United States)

    Shih, David J H; Northcott, Paul A; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M; Garzia, Livia; Peacock, John; Mack, Stephen C; Wu, Xiaochong; Rolider, Adi; Morrissy, A Sorana; Cavalli, Florence M G; Jones, David T W; Zitterbart, Karel; Faria, Claudia C; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G; Liau, Linda M; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K; Thompson, Reid C; Bailey, Simon; Lindsey, Janet C; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M C; Scherer, Stephen W; Phillips, Joanna J; Gupta, Nalin; Fan, Xing; Muraszko, Karin M; Vibhakar, Rajeev; Eberhart, Charles G; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F; Weiss, William A; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R; Rubin, Joshua B; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M; Gajjar, Amar; Packer, Roger J; Rutkowski, Stefan; Pomeroy, Scott L; French, Pim J; Kloosterhof, Nanne K; Kros, Johan M; Van Meir, Erwin G; Clifford, Steven C; Bourdeaut, Franck; Delattre, Olivier; Doz, François F; Hawkins, Cynthia E; Malkin, David; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T; Pfister, Stefan M; Taylor, Michael D

    2014-03-20

    Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

  3. Cytogenetic Prognostication Within Medulloblastoma Subgroups

    Science.gov (United States)

    Shih, David J.H.; Northcott, Paul A.; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M.; Garzia, Livia; Peacock, John; Mack, Stephen C.; Wu, Xiaochong; Rolider, Adi; Morrissy, A. Sorana; Cavalli, Florence M.G.; Jones, David T.W.; Zitterbart, Karel; Faria, Claudia C.; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A.; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G.; Liau, Linda M.; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K.; Thompson, Reid C.; Bailey, Simon; Lindsey, Janet C.; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M.C.; Scherer, Stephen W.; Phillips, Joanna J.; Gupta, Nalin; Fan, Xing; Muraszko, Karin M.; Vibhakar, Rajeev; Eberhart, Charles G.; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J.; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F.; Weiss, William A.; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R.; Rubin, Joshua B.; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M.; Gajjar, Amar; Packer, Roger J.; Rutkowski, Stefan; Pomeroy, Scott L.; French, Pim J.; Kloosterhof, Nanne K.; Kros, Johan M.; Van Meir, Erwin G.; Clifford, Steven C.; Bourdeaut, Franck; Delattre, Olivier; Doz, François F.; Hawkins, Cynthia E.; Malkin, David; Grajkowska, Wieslawa A.; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

    2014-01-01

    Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID

  4. Prognostic value of biochemical variables for survival after surgery for metastatic bone disease of the extremities.

    Science.gov (United States)

    Sørensen, Michala Skovlund; Hovgaard, Thea Bechman; Hindsø, Klaus; Petersen, Michael Mørk

    2017-03-01

    Prediction of survival in patients having surgery for metastatic bone disease in the extremities (MBDex) has been of interest in more than two decades. Hitherto no consensus on the value of biochemical variables has been achieved. Our purpose was (1) to investigate if standard biochemical variables have independent prognostic value for survival after surgery for MBDex and (2) to identify optimal prognostic cut off values for survival of biochemical variables. In a consecutive cohort of 270 patients having surgery for MBDex, we measured preoperative biochemical variables: hemoglobin, alkaline phosphatase, C-reactive protein and absolute, neutrophil and lymphocyte count. ROC curve analyses were performed to identify optimal cut off levels. Independent prognostic factors for variables were addressed with multiple Cox regression analyses. Optimal cut off levels were identified as: hemoglobin 7.45 mmol/L, absolute lymphocyte count 8.5 × 10 9 /L, neutrophil 5.68 × 10 9 /L, lymphocyte 1.37 × 10 9 /L, C-reactive protein 22.5 mg/L, and alkaline phosphatase 129 U/L. Regression analyses found alkaline phosphatase (HR 2.49) and neutrophil count (HR 2.49) to be independent prognostic factors. We found neutrophil count and alkaline phosphatase to be independent prognostic variables in predicting survival in patients after surgery for MBDex. © 2016 Wiley Periodicals, Inc.

  5. Prognostics for Steam Generator Tube Rupture using Markov Chain model

    International Nuclear Information System (INIS)

    Kim, Gibeom; Heo, Gyunyoung; Kim, Hyeonmin

    2016-01-01

    This paper will describe the prognostics method for evaluating and forecasting the ageing effect and demonstrate the procedure of prognostics for the Steam Generator Tube Rupture (SGTR) accident. Authors will propose the data-driven method so called MCMC (Markov Chain Monte Carlo) which is preferred to the physical-model method in terms of flexibility and availability. Degradation data is represented as growth of burst probability over time. Markov chain model is performed based on transition probability of state. And the state must be discrete variable. Therefore, burst probability that is continuous variable have to be changed into discrete variable to apply Markov chain model to the degradation data. The Markov chain model which is one of prognostics methods was described and the pilot demonstration for a SGTR accident was performed as a case study. The Markov chain model is strong since it is possible to be performed without physical models as long as enough data are available. However, in the case of the discrete Markov chain used in this study, there must be loss of information while the given data is discretized and assigned to the finite number of states. In this process, original information might not be reflected on prediction sufficiently. This should be noted as the limitation of discrete models. Now we will be studying on other prognostics methods such as GPM (General Path Model) which is also data-driven method as well as the particle filer which belongs to physical-model method and conducting comparison analysis

  6. The prognostic values of EGFR expression and KRAS mutation in patients with synchronous or metachronous metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Huang, Ching-Wen; Wang, Jaw-Yuan; Tsai, Hsiang-Lin; Chen, Yi-Ting; Huang, Chun-Ming; Ma, Cheng-Jen; Lu, Chien-Yu; Kuo, Chao-Hung; Wu, Deng-Chyang; Chai, Chee-Yin

    2013-01-01

    The epidermal growth factor receptor (EGFR)/RAS/RAF/MEK/MAPK pathway is an important pathway in the carcinogenesis, invasion and metastasis of colorectal cancers (CRCs). We conducted a retrospective study to determine the prognostic values of EGFR expression and KRAS mutation in patients with metastatic CRC (mCRC) based on synchronous or metachronous status. From October 2002 to March 2012, 205 patients with mCRC were retrospectively analyzed; 98 were found to have metachronous mCRC while 107 were found to have synchronous mCRC. The EGFR expressions were determinate by IHC (immunohistochemistry) analysis and categorized 1+ (weak intensity), 2+ (moderate intensity), and 3+ (strong intensity). Genomic DNA was isolated from frozen primary CRC tissues and direct sequencing of KRAS was performed. The clinicopathological features of these mCRC patients were retrospectively investigated according to EGFR expression and KRAS mutation status. Moreover, we analyzed the prognostic values of EGFR expression and KRAS mutation among these patients. Of the 205 patients with mCRC, EGFR expression was analyzed in 167 patients, and positive EGFR expression was noted in 140 of those patients (83.8%). KRAS mutation was investigated in 205 patients and mutations were noted in 88 of those patients (42.9%). In patients with metachronous mCRC, positive EGFR expression was significantly correlated with well-and moderately-differentiated tumors (P = 0.028), poorer disease-free survival (DFS) (P < 0.001), and overall survival (OS) (P < 0.001). Furthermore, positive EGFR expression was a significant independent prognostic factor of DFS (P = 0.006, HR: 4.012, 95% CI: 1.130–8.445) and OS (P = 0.028, HR: 3.090, 95% CI: 1.477–10.900) in metachronous mCRC patients. KRAS mutation status was not significantly related to DFS and OS of patients with metachronous mCRC; likewise, KRAS mutation status was not significantly different in the progression-free survival (PFS) and OS of patients with

  7. Is diabetes mellitus a negative prognostic factor for the treatment of advanced non-small-cell lung cancer?

    Science.gov (United States)

    Inal, Ali; Kaplan, M Ali; Kucukoner, Mehmet; Urakcı, Zuhat; Kılınc, Faruk; Isıkdogan, Abdurrahman

    2014-01-01

    It has been demonstrated that there are a lot of different prognostic factors which are worthy of consideration whereas diabetes mellitus (DM) has not been clearly or consistently identified as a prognostic value in advanced non-small cell lung cancer (NSCLC). The aim of this study was to investigate the prognostic significance of the characteristics of patients in advanced NSCLC. Specifically, we investigated the impact of DM for progression-free survival (PFS) and overall survival (OS) in patients receiving first-line platinum-based doublets chemotherapy. We retrospectively reviewed 442 patients with advanced NSCLC. DM and other potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. The results of univariate analysis for OS were identified as having prognostic significance: performance status (p<0.001), stage (p<0.001), DM (p<0.001), liver metastasis (p=0.02) and brain metastasis (p<0.001). Stage, diabetes mellitus, and liver metastasis were identified as having prognostic significance for PFS. Multivariate analysis showed that poor performance status, presence of DM and advanced stage were considered independent negative prognostic factors for OS (p 0.001, p<0.001 and p<0.001 respectively). Furthermore, DM and stage were considered independent negative prognostic factors for PFS (p 0.005 and p 0.001 respectively). In conclusion, DM at the time of diagnosis was associated with the negative prognostic importance for PFS and OS in the advanced stage patients who were receiving first-line platinum-based doublets chemotherapy. In addition poor performance status and advanced stage were identified as negative prognostic factors. Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  8. A generic cycling hypoxia-derived prognostic gene signature: application to breast cancer profiling

    Science.gov (United States)

    Helleputte, Thibault; Rubio, Laila Illan; Dupont, Pierre; Feron, Olivier

    2014-01-01

    Background Temporal and local fluctuations in O2 in tumors require adaptive mechanisms to support cancer cell survival and proliferation. The transcriptome associated with cycling hypoxia (CycHyp) could thus represent a prognostic biomarker of cancer progression. Methods We exposed 20 tumor cell lines to repeated periods of hypoxia/reoxygenation to determine a transcriptomic CycHyp signature and used clinical data sets from 2,150 breast cancer patients to estimate a prognostic Cox proportional hazard model to assess its prognostic performance. Results The CycHyp prognostic potential was validated in patients independently of the receptor status of the tumors. The discriminating capacity of the CycHyp signature was further increased in the ER+ HER2- patient populations including those with a node negative status under treatment (HR=3.16) or not (HR=5.54). The CycHyp prognostic signature outperformed a signature derived from continuous hypoxia and major prognostic metagenes (Psignature could also identify ER+HER2 node-negative breast cancer patients at high risk based on clinicopathologic criteria but who could have been spared from chemotherapy and inversely those patients classified at low risk based but who presented a negative outcome. Conclusions The CycHyp signature is prognostic of breast cancer and offers a unique decision making tool to complement anatomopathologic evaluation. PMID:25216520

  9. DNA level, tumor thickness, and stereological estimates of nuclear volume in stage I cutaneous malignant melanomas. A comparative study with analysis of prognostic impact

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Kristensen, I B; Grymer, F

    1991-01-01

    The mutual relation and prognostic value of three quantitative variables were investigated in a retrospective series of 56 stage I cutaneous malignant melanomas. Unbiased stereological estimates of nuclear volume, nuclear nu v were obtained along with measurements of melanoma thickness. The DNA......, nuclear nu v was the only independent, prognostically significant variable. Physical, three-dimensional nuclear volume is not solely a reflection of nuclear DNA content, and may represent a valuable, quantitative prognostic indicator in cutaneous malignant melanomas....

  10. Prognostic factors of three dimensional conformal radiation therapy in treating non-small lung cancer

    International Nuclear Information System (INIS)

    Liu Fei; Li Guang; Dang Jun; Cai Feng; Xia Bing; Zhang Shuo; Yao Lei

    2007-01-01

    Objective: To analyze the prognosis of patients with non-small lung cancer (NSCLC) treated with three -dimension conformal radiation therapy(3DCRT). Methods: From January 2003 to December 2004, 178 patients with NSCLC were treated, including 136 males and 42 females. Their median age was 65. Radiotherapy was delivered at 2 - 3 Gy per fraction, 6 fractions per week with a total dose of 60 -75 Gy. The impact of related prognostic factors on survival was evaluated by univariate and multivariate analyses. The treatment outcome was analyzed by prognostic index model. Results: With a median follow-up of 16 months, the 1 - and 2 -year survival rates were 62.4% and 39.7%, respectively. Logrank analysis showed that gender, weight loss, histology, tumor stage, tumor diameter, Gross tumor volume (GTV) and total irradiation dose were prognostic factors for the survival. COX model multivariate analysis showed that weight loss, histology, GTV and total dose were independent prognostic factors. Conclusions: Weight loss, histology, total dose and gross tumor volume are independent prognostic factors of patients with non-small lung cancer treated with radiation therapy. Prognostic index model is able to predict the prognosis more effectively than single variable. (authors)

  11. Prognostic significance of XRCC4 expression in hepatocellular carcinoma

    Science.gov (United States)

    Huang, Xiao-Ying; Yao, Jin-Guang; Wang, Chao; Wei, Zhong-Hong; Ma, Yun; Wu, Xue-Min; Luo, Chun-Ying; Xia, Qiang; Long, Xi-Dai

    2017-01-01

    Background Our previous investigations have shown that the variants of X-ray repair complementing 4 (XRCC4) may be involved in hepatocellular carcinoma (hepatocarcinoma) tumorigenesis. This study aimed to investigate the possible prognostic significance of XRCC4 expression for hepatocarcinoma patients and possible value for the selection of transarterial chemoembolization (TACE) treatment. Materials and Methods We conducted a hospital-based retrospective analysis (including 421 hepatocarcinoma cases) to analyze the effects of XRCC4 on hepatocarcinoma prognosis and TACE. The levels of XRCC4 expression were tested using immunohistochemistry. The sensitivity of cancer cells to anti-cancer drug doxorubicin was evaluated using the half-maximal inhibitory concentration (IC50). Results XRCC4 expression was significantly correlated with pathological features including tumor stage, liver cirrhosis, and micro-vessel density. XRCC4 expression was an independent prognostic factor of hepatocarcinoma, and TACE treatments had no effects on prognosis of hepatocarcinoma patients with high XRCC4 expression. More intriguingly, TACE improved the prognosis of hepatocarcinoma patients with low XRCC4 expression. Functionally, XRCC4 overexpression increased while XRCC4 knockdown reduced the IC50 of cancer cells to doxorubicin. Conclusions These results suggest that XRCC4 may be an independent prognostic factor for hepatocarcinoma patients, and that decreasing XRCC4 expression may be beneficial for post-operative adjuvant TACE treatment in hepatocarcinoma. PMID:29152133

  12. Nuclear receptor expression defines a set of prognostic biomarkers for lung cancer.

    Directory of Open Access Journals (Sweden)

    Yangsik Jeong

    2010-12-01

    Full Text Available The identification of prognostic tumor biomarkers that also would have potential as therapeutic targets, particularly in patients with early stage disease, has been a long sought-after goal in the management and treatment of lung cancer. The nuclear receptor (NR superfamily, which is composed of 48 transcription factors that govern complex physiologic and pathophysiologic processes, could represent a unique subset of these biomarkers. In fact, many members of this family are the targets of already identified selective receptor modulators, providing a direct link between individual tumor NR quantitation and selection of therapy. The goal of this study, which begins this overall strategy, was to investigate the association between mRNA expression of the NR superfamily and the clinical outcome for patients with lung cancer, and to test whether a tumor NR gene signature provided useful information (over available clinical data for patients with lung cancer.Using quantitative real-time PCR to study NR expression in 30 microdissected non-small-cell lung cancers (NSCLCs and their pair-matched normal lung epithelium, we found great variability in NR expression among patients' tumor and non-involved lung epithelium, found a strong association between NR expression and clinical outcome, and identified an NR gene signature from both normal and tumor tissues that predicted patient survival time and disease recurrence. The NR signature derived from the initial 30 NSCLC samples was validated in two independent microarray datasets derived from 442 and 117 resected lung adenocarcinomas. The NR gene signature was also validated in 130 squamous cell carcinomas. The prognostic signature in tumors could be distilled to expression of two NRs, short heterodimer partner and progesterone receptor, as single gene predictors of NSCLC patient survival time, including for patients with stage I disease. Of equal interest, the studies of microdissected histologically normal

  13. Cell Proliferation Activity and Prognostic Index in Squamous Cell Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    José Antonio Alvarez-Riesgo

    1998-01-01

    Full Text Available Flow Cytometry (FC has been incorporated into cancer research in relation to its prognostic value together with histological parameters and TNM stages. We have studied by means of FC the cell cycle of 132 samples from male patients with Squamous Cell Lung Carcinoma (SQCLC. All of the patients received curative surgery and the clinical follow-up was 60 months. The clinical and cytometric parameters were evaluated in order to predict the patients’ outcome. The presence of tumoural recurrence and the tumoural stage showed statistical significance associated with survival. The multivariant analysis reveals radiotherapy (p = 0.004 as protective variable and the high S-phase fraction (SPF (p = 0.001 and stage IIIA (p = 0.012 as risk factors. The SPF appears as an independent prognostic factor for overall survival time. We can build a prognostic index representative of different prognostic groups, which allows us to improve the individual monitoring of these patients.

  14. Maintenance-based prognostics of nuclear plant equipment for long-term operation

    International Nuclear Information System (INIS)

    Welz, Zachary; Coble, Jamie; Upadhyaya, Belle; Hines, Wes

    2017-01-01

    While industry understands the importance of keeping equipment operational and well maintained, the importance of tracking maintenance information in reliability models is often overlooked. Prognostic models can be used to predict the failure times of critical equipment, but more often than not, these models assume that all maintenance actions are the same or do not consider maintenance at all. This study investigates the influence of integrating maintenance information on prognostic model prediction accuracy. By incorporating maintenance information to develop maintenance-dependent prognostic models, prediction accuracy was improved by more than 40% compared with traditional maintenance-independent models. This study acts as a proof of concept, showing the importance of utilizing maintenance information in modern prognostics for industrial equipment

  15. Maintenance-based prognostics of nuclear plant equipment for long-term operation

    Energy Technology Data Exchange (ETDEWEB)

    Welz, Zachary; Coble, Jamie; Upadhyaya, Belle; Hines, Wes [University of Tennessee, Knoxville (United States)

    2017-08-15

    While industry understands the importance of keeping equipment operational and well maintained, the importance of tracking maintenance information in reliability models is often overlooked. Prognostic models can be used to predict the failure times of critical equipment, but more often than not, these models assume that all maintenance actions are the same or do not consider maintenance at all. This study investigates the influence of integrating maintenance information on prognostic model prediction accuracy. By incorporating maintenance information to develop maintenance-dependent prognostic models, prediction accuracy was improved by more than 40% compared with traditional maintenance-independent models. This study acts as a proof of concept, showing the importance of utilizing maintenance information in modern prognostics for industrial equipment.

  16. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

    Mora-Jensen, H.; Jendholm, J.; Rapin, N.

    2015-01-01

    of these aberrations occur in normal hematopoietic stem and progenitor cells (HSCs/HPCs) before definitive leukemic transformation through additional acquisition of a few (that is, mostly 1 or 2) leukemia-promoting driver aberrations. NGS studies on sorted bone marrow (BM) populations of AML patients with a normal......Acute myeloid leukemia (AML) represents an aggressive cancer entity, whose malignant cells respond abnormally to regulatory stimuli and have lost the ability to differentiate and become fully mature blood cells.1, 2 AML evolves through accumulation of independent genetic aberrations, including...... karyotype have demonstrated the presence of prognostic driver aberrations (that is, NPM1, FLT3-ITD and FLT3-TKD) in committed HPCs but not in multipotent HSCs. However, the HSC populations lacking the prognostic driver aberrations contained preleukemic clones harboring a series of recurrent molecular...

  17. A Comparison of Systemic Inflammation-Based Prognostic Scores in Patients on Regular Hemodialysis

    Directory of Open Access Journals (Sweden)

    Akihiko Kato

    2013-10-01

    Full Text Available Background/Aims: Systemic inflammation-based prognostic scores have prognostic power in patients with cancer, independently of tumor stage and site. Although inflammatory status is associated with mortality in hemodialysis (HD patients, it remains to be determined as to whether these composite scores are useful in predicting clinical outcomes. Methods: We calculated the 6 prognostic scores [Glasgow prognostic score (GPS, modified GPS (mGPS, neutrophil-lymphocyte ratio (NLR, platelet lymphocyte ratio (PLR, prognostic index (PI and prognostic nutritional index (PNI], which have been established as a useful scoring system in cancer patients. We enrolled 339 patients on regular HD (age: 64 ± 13 years; time on HD: 129 ± 114 months; males/females = 253/85 and followed them for 42 months. The area under the receiver-operating characteristics curve was used to determine which scoring system was more predictive of mortality. Results: Elevated GPS, mGPS, NLR, PLR, PI and PNI were all associated with total mortality, independent of covariates. If GPS was raised, mGPS, NLR, PLR and PI were also predictive of all-cause mortality and/or hospitalization. GPS and PNI were associated with poor nutritional status. Using overall mortality as an endpoint, the area under the curve (AUC was significant for a GPS of 0.701 (95% CI: 0.637-0.765; p Conclusion: GPS, based on serum albumin and highly sensitive C-reactive protein, has the most prognostic power for mortality prediction among the prognostic scores in HD patients. However, as the determination of serum albumin reflects mortality similarly to GPS, other composite combinations are needed to provide additional clinical utility beyond that of albumin alone in HD patients.

  18. Predicting sequelae and death after bacterial meningitis in childhood: A systematic review of prognostic studies

    Directory of Open Access Journals (Sweden)

    Gemke Reinoud JBJ

    2010-08-01

    Full Text Available Abstract Background Bacterial meningitis (BM is a severe infection responsible for high mortality and disabling sequelae. Early identification of patients at high risk of these outcomes is necessary to prevent their occurrence by adequate treatment as much as possible. For this reason, several prognostic models have been developed. The objective of this study is to summarize the evidence regarding prognostic factors predicting death or sequelae due to BM in children 0-18 years of age. Methods A search in MEDLINE and EMBASE was conducted to identify prognostic studies on risk factors for mortality and sequelae after BM in children. Selection of abstracts, full-text articles and assessment of methodological quality using the QUIPS checklist was performed by two reviewers independently. Data on prognostic factors per outcome were summarized. Results Of the 31 studies identified, 15 were of moderate to high quality. Due to substantial heterogeneity in study characteristics and evaluated prognostic factors, no quantitative analysis was performed. Prognostic factors found to be statistically significant in more than one study of moderate or high quality are: complaints >48 hours before admission, coma/impaired consciousness, (prolonged duration of seizures, (prolonged fever, shock, peripheral circulatory failure, respiratory distress, absence of petechiae, causative pathogen Streptococcus pneumoniae, young age, male gender, several cerebrospinal fluid (CSF parameters and white blood cell (WBC count. Conclusions Although several important prognostic factors for the prediction of mortality or sequelae after BM were identified, the inability to perform a pooled analysis makes the exact (independent predictive value of these factors uncertain. This emphasizes the need for additional well-conducted prognostic studies.

  19. Perioperative blood transfusion as a poor prognostic factor after aggressive surgical resection for hilar cholangiocarcinoma.

    Science.gov (United States)

    Kimura, Norihisa; Toyoki, Yoshikazu; Ishido, Keinosuke; Kudo, Daisuke; Yakoshi, Yuta; Tsutsumi, Shinji; Miura, Takuya; Wakiya, Taiichi; Hakamada, Kenichi

    2015-05-01

    Blood transfusion is linked to a negative outcome for malignant tumors. The aim of this study was to evaluate aggressive surgical resection for hilar cholangiocarcinoma (HCCA) and assess the impact of perioperative blood transfusion on long-term survival. Sixty-six consecutive major hepatectomies with en bloc resection of the caudate lobe and extrahepatic bile duct for HCCA were performed using macroscopically curative resection at our institute from 2002 to 2012. Clinicopathologic factors for recurrence and survival were retrospectively assessed. Overall survival rates at 1, 3, and 5 years were 86.7, 47.3, and 35.7 %, respectively. In univariate analysis, perioperative blood transfusion and a histological positive margin were two of several variables found to be significant prognostic factors for recurrence or survival (Pblood transfusion was independently associated with recurrence (hazard ratio (HR)=2.839 (95 % confidence interval (CI), 1.370-5.884), P=0.005), while perioperative blood transfusion (HR=3.383 (95 % CI, 1.499-7.637), P=0.003) and R1 resection (HR=3.125 (95 % CI, 1.025-9.530), P=0.045) were independent risk factors for poor survival. Perioperative blood transfusion is a strong predictor of poor survival after radical hepatectomy for HCCA. We suggest that circumvention of perioperative blood transfusion can play an important role in long-term survival for patients with HCCA.

  20. Strongly Correlated Topological Insulators

    Science.gov (United States)

    2016-02-03

    Strongly Correlated Topological Insulators In the past year, the grant was used for work in the field of topological phases, with emphasis on finding...surface of topological insulators. In the past 3 years, we have started a new direction, that of fractional topological insulators. These are materials...in which a topologically nontrivial quasi-flat band is fractionally filled and then subject to strong interactions. The views, opinions and/or

  1. Prognostic implication of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma: a tissue microarray study

    Directory of Open Access Journals (Sweden)

    Wang Facheng

    2008-10-01

    Full Text Available Abstract Background p27Kip1 plays a major role as a negative regulator of the cell cycle. The regulation of p27Kip1 degradation is mediated by its specific ubiquitin ligase subunits S-phase kinase protein (Skp 2 and cyclin-dependent kinase subunit (Cks 1. However, little is known regarding the prognostic utility of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma. Methods Immunohistochemistry was performed for p27Kip1, Skp2 and Cks1 in tissue microarrays of 482 renal cell carcinomas with follow-up. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance. Results Immunoreactivity of p27Kip1, Skp2 and Cks1 was noted in 357, 71 and 82 patients, respectively. Skp2 and Cks1 expression were not noted in chromophobe cancers. A strong correlation was found between Skp2 and Cks1 expression (P Kip1 levels (P = 0.006 and P Kip1 expression and Skp2 expression were correlated with larger tumor size and higher stage, as well as tumor necrosis. Cks1 expression was only correlated with tumor size. In univariate analysis, low p27Kip1 expression, Skp2 and Cks1 expression were all associated with a poor prognosis, while in multivariate analysis, only low p27Kip1 expression were independent prognostic factors for both cancer specific survival and recurrence-free survival in patients with RCC. Conclusion Our results suggest that immunohistochemical expression levels of p27Kip1, Skp2 and Cks1 may serve as markers with prognostic value in renal cell carcinoma.

  2. Strong Cosmic Censorship

    Science.gov (United States)

    Isenberg, James

    2017-01-01

    The Hawking-Penrose theorems tell us that solutions of Einstein's equations are generally singular, in the sense of the incompleteness of causal geodesics (the paths of physical observers). These singularities might be marked by the blowup of curvature and therefore crushing tidal forces, or by the breakdown of physical determinism. Penrose has conjectured (in his `Strong Cosmic Censorship Conjecture`) that it is generically unbounded curvature that causes singularities, rather than causal breakdown. The verification that ``AVTD behavior'' (marked by the domination of time derivatives over space derivatives) is generically present in a family of solutions has proven to be a useful tool for studying model versions of Strong Cosmic Censorship in that family. I discuss some of the history of Strong Cosmic Censorship, and then discuss what is known about AVTD behavior and Strong Cosmic Censorship in families of solutions defined by varying degrees of isometry, and discuss recent results which we believe will extend this knowledge and provide new support for Strong Cosmic Censorship. I also comment on some of the recent work on ``Weak Null Singularities'', and how this relates to Strong Cosmic Censorship.

  3. Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Frei, E; Visco, C; Xu-Monette, Z Y

    2013-01-01

    High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab...

  4. Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model

    DEFF Research Database (Denmark)

    Schmidt, H; Bastholt, L; Geertsen, P

    2005-01-01

    We aimed to create a prognostic model in metastatic melanoma based on independent prognostic factors in 321 patients receiving interleukin-2 (IL-2)-based immunotherapy with a median follow-up time for patients currently alive of 52 months (range 15-189 months). The patients were treated as part...... factors in univariate analyses. Subsequently, a multivariate Cox's regression analysis identified elevated LDH (P

  5. Prognostic Biomarker Identification Through Integrating the Gene Signatures of Hepatocellular Carcinoma Properties

    Directory of Open Access Journals (Sweden)

    Jialin Cai

    2017-05-01

    Full Text Available Many molecular classification and prognostic gene signatures for hepatocellular carcinoma (HCC patients have been established based on genome-wide gene expression profiling; however, their generalizability is unclear. Herein, we systematically assessed the prognostic effects of these gene signatures and identified valuable prognostic biomarkers by integrating these gene signatures. With two independent HCC datasets (GSE14520, N = 242 and GSE54236, N = 78, 30 published gene signatures were evaluated, and 11 were significantly associated with the overall survival (OS of postoperative HCC patients in both datasets. The random survival forest models suggested that the gene signatures were superior to clinical characteristics for predicting the prognosis of the patients. Based on the 11 gene signatures, a functional protein-protein interaction (PPI network with 1406 nodes and 10,135 edges was established. With tissue microarrays of HCC patients (N = 60, we determined the prognostic values of the core genes in the network and found that RAD21, CDK1, and HDAC2 expression levels were negatively associated with OS for HCC patients. The multivariate Cox regression analyses suggested that CDK1 was an independent prognostic factor, which was validated in an independent case cohort (N = 78. In cellular models, inhibition of CDK1 by siRNA or a specific inhibitor, RO-3306, reduced cellular proliferation and viability for HCC cells. These results suggest that the prognostic predictive capacities of these gene signatures are reproducible and that CDK1 is a potential prognostic biomarker or therapeutic target for HCC patients.

  6. Generic Software Architecture for Prognostics (GSAP) User Guide

    Science.gov (United States)

    Teubert, Christopher Allen; Daigle, Matthew John; Watkins, Jason; Sankararaman, Shankar; Goebel, Kai

    2016-01-01

    The Generic Software Architecture for Prognostics (GSAP) is a framework for applying prognostics. It makes applying prognostics easier by implementing many of the common elements across prognostic applications. The standard interface enables reuse of prognostic algorithms and models across systems using the GSAP framework.

  7. Strong Arcwise Connectedness

    OpenAIRE

    Espinoza, Benjamin; Gartside, Paul; Kovan-Bakan, Merve; Mamatelashvili, Ana

    2012-01-01

    A space is `n-strong arc connected' (n-sac) if for any n points in the space there is an arc in the space visiting them in order. A space is omega-strong arc connected (omega-sac) if it is n-sac for all n. We study these properties in finite graphs, regular continua, and rational continua. There are no 4-sac graphs, but there are 3-sac graphs and graphs which are 2-sac but not 3-sac. For every n there is an n-sac regular continuum, but no regular continuum is omega-sac. There is an omega-sac ...

  8. Abortion: Strong's counterexamples fail

    DEFF Research Database (Denmark)

    Di Nucci, Ezio

    2009-01-01

    This paper shows that the counterexamples proposed by Strong in 2008 in the Journal of Medical Ethics to Marquis's argument against abortion fail. Strong's basic idea is that there are cases--for example, terminally ill patients--where killing an adult human being is prima facie seriously morally......'s scenarios have some valuable future or admitted that killing them is not seriously morally wrong. Finally, if "valuable future" is interpreted as referring to objective standards, one ends up with implausible and unpalatable moral claims....

  9. Health Monitoring and Prognostics for Computer Servers

    Data.gov (United States)

    National Aeronautics and Space Administration — Abstract Prognostics solutions for mission critical systems require a comprehensive methodology for proactively detecting and isolating failures, recommending and...

  10. A DISTRIBUTED PROGNOSTIC HEALTH MANAGEMENT ARCHITECTURE

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper introduces a generic distributed prognostic health management (PHM) architecture with specific application to the electrical power systems domain. Current...

  11. Embedded Diagnostics & Prognostics Wireless Sensing Platforms

    National Research Council Canada - National Science Library

    Ousachi, Mark; Scott, Andrew; Yee, David; Hosmer, Thomas; Daniszewski, Dave

    2004-01-01

    An embedded diagnostics and prognostics architecture affects several aspects associated with military ground vehicles such as improved safety, reduction in maintenance times, weapon system readiness...

  12. Metrics for Evaluating Performance of Prognostic Techniques

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics is an emerging concept in condition basedmaintenance(CBM)ofcriticalsystems.Alongwith developing the fundamentals of being able to confidently predict...

  13. Simulating Degradation Data for Prognostic Algorithm Development

    Data.gov (United States)

    National Aeronautics and Space Administration — PHM08 Challenge Dataset is now publicly available at the NASA Prognostics Respository + Download INTRODUCTION - WHY SIMULATE DEGRADATION DATA? Of various challenges...

  14. A Survey of Artificial Intelligence for Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Integrated Systems Health Management includes as key elements fault detection, fault diagnostics, and failure prognostics. Whereas fault detection and diagnostics...

  15. The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate cancer is limited to ERG-fusion positive tumors lacking PTEN deletion

    International Nuclear Information System (INIS)

    Burdelski, Christoph; Menan, Devi; Tsourlakis, Maria Christina; Kluth, Martina; Hube-Magg, Claudia; Melling, Nathaniel; Minner, Sarah; Koop, Christina; Graefen, Markus; Heinzer, Hans; Wittmer, Corinna; Sauter, Guido; Simon, Ronald; Schlomm, Thorsten; Steurer, Stefan; Krech, Till

    2015-01-01

    Posttranscriptional protein modification by SUMOylation plays an important role in tumor development and progression. In the current study we analyzed prevalence and prognostic impact of the de-SUMOylation enzyme SENP1 in prostate cancer. SENP1 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancer specimens. Results were compared to tumor phenotype, ERG status, genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence. SENP1 immunostaining was detectable in 34.5 % of 9,516 interpretable cancers and considered strong in 7.3 %, moderate in 14.9 % and weak in 12.3 % of cases. Strong SENP1 expression was linked to advanced pT stage (p < 0.0001), high Gleason grade (p < 0.0001), positive lymph node status (p = 0.0019), high pre-operative PSA levels (p = 0.0037), and PSA recurrence (p < 0.0001). SENP1 expression was strongly associated with positive ERG fusion status as determined by both in situ hybridization (FISH) and immunohistochemistry as well as with PTEN deletions. Detectable SENP1 immunostaining was found in 41 % of ERG positive and in 47 % of PTEN deleted cancers but in only 30 % of ERG negative and 30 % of PTEN non-deleted cancers (p < 0.0001 each). Deletions of 3p, 5q, and 6q were unrelated to SENP1 expression. Subset analyses revealed that the prognostic impact of SENP1 expression was solely driven by the subgroup of ERG positive, PTEN undeleted cancers. In this subgroup, the prognostic role of SENP1 expression was independent of the preoperative PSA level, tumor stage, Gleason grade, and the status of the resection margin. SENP1 expression has strong prognostic impact in a molecularly defined subset of cancers. This is per se not surprising as the biologic impact of each individual molecular event is likely to be dependent on its cellular environment. However, such findings challenge the concept of finding clinically relevant molecular signatures that are equally applicable to all

  16. Diagnostic and prognostic value of long noncoding RNAs as biomarkers in urothelial carcinoma.

    Directory of Open Access Journals (Sweden)

    Johanna Droop

    Full Text Available Many long noncoding RNAs (lncRNAs are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC, several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1 was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106. Additionally, publicly available TCGA data was investigated for differential expression in UC tissues (set 2: N n = 19; T n = 252, and correlation to overall survival (OS. All proposed candidates tended to be upregulated in tumour tissues, with the exception of MALAT1, which was rather diminished in cancer tissues of both data sets. However, strong overexpression was generally limited to individual tumour tissues and statistically significant overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue set 2, but for no candidate in set 1. Altered expression of individual lncRNAs was associated with overall survival, but not consistently between both patient cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with muscle-invasive tumours was significantly correlated with worse OS in both cohorts. Further analysis revealed that tumours with low TUG1 expression are characterized by a basal-squamous-like subtype signature accounting for the association with poor outcome. In conclusion, our study demonstrates that overexpression of the candidate lncRNAs is found in many UC cases, but does not occur consistently and strongly enough to provide reliable diagnostic or prognostic value as an individual biomarker. Subtype-dependent expression patterns of lncRNAs like TUG1 could

  17. Diagnostic and prognostic value of long noncoding RNAs as biomarkers in urothelial carcinoma.

    Science.gov (United States)

    Droop, Johanna; Szarvas, Tibor; Schulz, Wolfgang A; Niedworok, Christian; Niegisch, Günter; Scheckenbach, Kathrin; Hoffmann, Michèle J

    2017-01-01

    Many long noncoding RNAs (lncRNAs) are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC), several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1) was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106). Additionally, publicly available TCGA data was investigated for differential expression in UC tissues (set 2: N n = 19; T n = 252,) and correlation to overall survival (OS). All proposed candidates tended to be upregulated in tumour tissues, with the exception of MALAT1, which was rather diminished in cancer tissues of both data sets. However, strong overexpression was generally limited to individual tumour tissues and statistically significant overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue set 2, but for no candidate in set 1. Altered expression of individual lncRNAs was associated with overall survival, but not consistently between both patient cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with muscle-invasive tumours was significantly correlated with worse OS in both cohorts. Further analysis revealed that tumours with low TUG1 expression are characterized by a basal-squamous-like subtype signature accounting for the association with poor outcome. In conclusion, our study demonstrates that overexpression of the candidate lncRNAs is found in many UC cases, but does not occur consistently and strongly enough to provide reliable diagnostic or prognostic value as an individual biomarker. Subtype-dependent expression patterns of lncRNAs like TUG1 could become useful to

  18. Undertreatment strongly decreases prognosis of breast cancer in elderly women.

    Science.gov (United States)

    Bouchardy, Christine; Rapiti, Elisabetta; Fioretta, Gérald; Laissue, Paul; Neyroud-Caspar, Isabelle; Schäfer, Peter; Kurtz, John; Sappino, André-Pascal; Vlastos, Georges

    2003-10-01

    No consensus exists on therapy of elderly cancer patients. Treatments are influenced by unclear standards and are usually less aggressive. This study aims to evaluate determinants and effect of treatment choice on breast cancer prognosis among elderly patients. We reviewed clinical files of 407 breast cancer patients aged >/= 80 years recorded at the Geneva Cancer Registry between 1989 and 1999. Patient and tumor characteristics, general health status, comorbidity, treatment, and cause of death were considered. We evaluated determinants of treatment by logistic regression and effect of treatment on mortality by Cox model, accounting for prognostic factors. Age was independently linked to the type of treatment. Overall, 12% of women (n = 48) had no treatment, 32% (n = 132) received tamoxifen only, 7% (n = 28) had breast-conserving surgery only, 33% (n = 133) had mastectomy, 14% (n = 57) had breast-conserving surgery plus adjuvant therapy, and 2% (n = 9) received miscellaneous treatments. Five-year specific breast cancer survival was 46%, 51%, 82%, and 90% for women with no treatment, tamoxifen alone, mastectomy, and breast-conserving surgery plus adjuvant treatment, respectively. Compared with the nontreated group, the adjusted hazard ratio of breast cancer mortality was 0.4 (95% CI, 0.2 to 0.7) for tamoxifen alone, 0.4 (95% CI, 0.1 to 1.4) for breast-conserving surgery alone, 0.2 (95% CI, 0.1 to 0.7) for mastectomy, and 0.1 (95% CI, 0.03 to 0.4) for breast-conserving surgery plus adjuvant treatment. Half of elderly patients with breast cancer are undertreated, with strongly decreased specific survival as a consequence. Treatments need to be adapted to the patient's health status, but also should offer the best chance of cure.

  19. Tumour burden in early stage Hodgkin's disease: the single most important prognostic factor for outcome after radiotherapy

    DEFF Research Database (Denmark)

    Specht, L; Nordentoft, A M; Cold, Søren

    1987-01-01

    --from 15 to 146 months after initiation of therapy. The initial tumour burden of each patient was assessed, combining tumour size of each involved region and number of regions involved. Tumour burden thus assessed proved to be the single most important prognostic factor with regard to disease free survival....... Other known prognostic factors such as number of involved regions, mediastinal size, pathological stage, systemic symptoms, and ESR were related to tumour burden and lost their prognostic significance in a multivariate analysis. The only other factors of independent significance were histologic subtype...

  20. Prognostic Factors in Hodgkin's Disease

    DEFF Research Database (Denmark)

    Specht

    1996-01-01

    Prognostic factors in Hodgkin's disease (HD) are reviewed. The Ann Arbor staging classification remains the basis for evaluation of patients with HD. However, subgroups of patients with differing prognoses exist within the individual stages. In pathological stages I and II, the number of involved...... of extent of disease such as erythrocyte sedimentation rate, anemia, and serum albumin. In advanced disease the number of involved nodal and extranodal regions, the total tumor burden, B symptoms, age, gender, histology, and a number of hematologic and biochemical indicators are significant. Research...

  1. Detection of prognostic methylation markers by methylC-capture sequencing in acute myeloid leukemia.

    Science.gov (United States)

    Li, Yan; Zhao, Hongmei; Xu, Qingyu; Lv, Na; Jing, Yu; Wang, Lili; Wang, Xiaowen; Guo, Jing; Zhou, Lei; Liu, Jing; Chen, Guofeng; Chen, Chongjian; Li, Yonghui; Yu, Li

    2017-12-15

    Clinical and genetic features incompletely predict outcome in acute myeloid leukemia (AML). The value of clinical methylation assays for prognostic markers has not been extensively explored. We assess the prognostic implications of methylC-capture sequencing (MCC-Seq) in patients with de novo AML by integrating DNA methylation and genetic risk stratification. MCC-Seq assessed DNA methylation level in 44 samples. The differentially methylated regions associated with prognostic genetic information were identified. The selected prognostic DNA methylation markers were independently validated in two sets. MCC-Seq exhibited good performance in AML patients. A panel of 12 differentially methylated genes was identified with promoter hyper-differentially methylated regions associated with the outcome. Compared with a low M-value, a high M-value was associated with failure to achieve complete remission ( p = 0.024), increased hazard for disease-free survival in the study set ( p = 0.039) and poor overall survival in The Cancer Genome Atlas set ( p = 0.038). Hematopoietic stem cell transplantation and survival outcomes were not adversely affected by a high M-value ( p = 0.271). Our study establishes that MCC-Seq is a stable, reproducible, and cost-effective methylation assay in AML. A 12-gene M-value encompassing epigenetic and genetic prognostic information represented a valid prognostic marker for patients with AML.

  2. Simultaneous analysis of the expression of 14 genes with individual prognostic value in myelodysplastic syndrome patients at diagnosis: WT1 detection in peripheral blood adversely affects survival.

    Science.gov (United States)

    Santamaría, Carlos; Ramos, Fernando; Puig, Noemi; Barragán, Eva; de Paz, Raquel; Pedro, Carme; Insunza, Andrés; Tormo, Mar; Del Cañizo, Consuelo; Diez-Campelo, María; Xicoy, Blanca; Salido, Eduardo; Sánchez del Real, Javier; Hernández, Montserrat; Chillón, Carmen; Sanz, Guillermo F; García-Sanz, Ramón; San Miguel, Jesús F; González, Marcos

    2012-12-01

    Several studies have evaluated the prognostic value of the individual expression of certain genes in patients with myelodysplastic syndromes (MDS). However, none of them includes their simultaneous analysis by quantitative polymerase chain reaction (PCR). We evaluated relative expression levels of 14 molecular markers in 193 peripheral blood samples from untreated MDS patients using real-time PCR. Detectable WT1 expression levels, low TET2, and low IER3 gene expression were the only markers showing in univariate analysis a poor prognostic value for all treatment-free (TFS), progression-free (PFS), and overall survival (OS). In multivariate analysis, molecular parameters associated with a shorter TFS were: WT1 detection (p = 0.014), low TET2 (p = 0.002), and low IER3 expression (p = 0.025). WT1 detection (p = 0.006) and low TET2 (p = 0.006) expression were associated with a shorter PFS when multivariate analysis was carried out by including only molecular markers. Molecular values with an independent value in OS were: WT1 detection (p = 0.003), high EVI1 expression (p = 0.001), and undetectatable p15-CDKN2B (p = 0.037). WT1 expressers were associated with adverse clinical-biological features, high IPSS and WPSS scoring, and unfavorable molecular expression profile. In summary, detectable WT1 expression levels, and low TET2 and low IER3 expression in peripheral blood showed a strong association with adverse prognosis in MDS patients at diagnosis. However, WT1 was the only molecular marker displaying an independent prognostic value in both OS and TFS.

  3. IDH Mutations: Genotype-Phenotype Correlation and Prognostic Impact

    Directory of Open Access Journals (Sweden)

    Xiao-Wei Wang

    2014-01-01

    Full Text Available IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1R132H, IDH1nonR132H, and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1nonR132H in astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q and IDH mutation to define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated—which contains mostly TP53 mutated tumors, and none of these alterations. We confirmed that IDH mutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge on IDH mutation prognostic impact and genotype-phenotype associations.

  4. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Wu, Lin; Visco, Carlo

    2012-01-01

    TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. ...

  5. Prognostic Significance of Frontal QRS-T Angle in Patients with Idiopathic Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Sheng-Na Li

    2016-01-01

    Conclusions: The frontal QRS-T angle is a powerful predictor of all-cause mortality, cardiac mortality, and worsening heart failure in IDC patients, independent of well-established prognostic factors. Optimized therapy significantly narrows the QRS-T angle, which might be an indicator of medication compliance, but this requires further investigation.

  6. Urokinase plasminogen activator receptor on invasive cancer cells: A prognostic factor in distal gastric adenocarcinoma

    DEFF Research Database (Denmark)

    Alpizar, Warner Enrique Alpizar; Christensen, Ib Jarle; Santoni-Rugiu, Eric

    2012-01-01

    association between the expression of uPAR on tumor cells in the peripheral invasion zone and overall survival of gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate analysis showed that uPAR immunoreactivity in cancer cells at the invasive front is an independent prognostic factor...

  7. Circulating brain-derived neurotrophic factor has diagnostic and prognostic value in traumatic brain injury

    NARCIS (Netherlands)

    F.K. Korley (Frederick K.); R. Diaz-Arrastia (Ramon); A.H.B. Wu (Alan H. B.); J.K. Yue (John); G. Manley (Geoffrey); H.I. Sair (Haris I.); J.E. van Eyk (Jennifer); A.D. Everett (Allen D.); D. Okonkwo (David); A.B. Valadka (Alex); W.A. Gordon (Wayne A.); A.I.R. Maas (Andrew I.R.); P. Mukherjee (Pratik); E.L. Yuh (Esther); H.F. Lingsma (Hester); A.M. Puccio (Ava); D.M. Schnyer (David)

    2016-01-01

    textabstractBrain-derived neurotrophic factor (BDNF) is important for neuronal survival and regeneration. We investigated the diagnostic and prognostic values of serum BDNF in traumatic brain injury (TBI). We examined serum BDNF in two independent cohorts of TBI cases presenting to the emergency

  8. Prognostic markers of short-term mortality in AIDS-associated Pneumocystis carinii pneumonia

    DEFF Research Database (Denmark)

    Benfield, T L; Helweg-Larsen, J; Bang, D

    2001-01-01

    independent predictors of a poor outcome. In contrast, neither PO(2) nor serum lactate dehydrogenase, which in earlier studies were identified as prognostic markers, were predictors of mortality. CONCLUSION: Age, initial anti-PCP therapy, use of PCP prophylaxis, and BAL CMV status may be useful predictors...

  9. Validation of existing prognostic models in patients with early-stage cervical cancer

    NARCIS (Netherlands)

    Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J.; Stalpers, Lukas J. A.; Schilthuis, Marten S.; van der Steeg, Jan Willem; Burger, Matthé P. M.; Buist, Marrije R.

    2009-01-01

    Objective. Models that predict survival and recurrence in patients with early-stage cervical cancer are important tools in patient management, We validated 12 existing prognostic models in an independent population of patients with early-stage cervical cancer. Materials and Methods. We searched the

  10. Prognostic significance of detection of microscopic peritoneal disease in colorectal cancer: a systematic review.

    LENUS (Irish Health Repository)

    Mohan, Helen M

    2013-06-01

    Free intraperitoneal tumour cells are an independent indicator of poor prognosis, and are encorporated in current staging systems in upper gastrointestinal cancers, but not colorectal cancer. This systematic review aimed to evaluate the role and prognostic significance of positive peritoneal lavage in colorectal cancer.

  11. Prediction of risk of recurrence of venous thromboembolism following treatment for a first unprovoked venous thromboembolism: systematic review, prognostic model and clinical decision rule, and economic evaluation.

    Science.gov (United States)

    Ensor, Joie; Riley, Richard D; Jowett, Sue; Monahan, Mark; Snell, Kym Ie; Bayliss, Susan; Moore, David; Fitzmaurice, David

    2016-02-01

    Unprovoked first venous thromboembolism (VTE) is defined as VTE in the absence of a temporary provoking factor such as surgery, immobility and other temporary factors. Recurrent VTE in unprovoked patients is highly prevalent, but easily preventable with oral anticoagulant (OAC) therapy. The unprovoked population is highly heterogeneous in terms of risk of recurrent VTE. The first aim of the project is to review existing prognostic models which stratify individuals by their recurrence risk, therefore potentially allowing tailored treatment strategies. The second aim is to enhance the existing research in this field, by developing and externally validating a new prognostic model for individual risk prediction, using a pooled database containing individual patient data (IPD) from several studies. The final aim is to assess the economic cost-effectiveness of the proposed prognostic model if it is used as a decision rule for resuming OAC therapy, compared with current standard treatment strategies. Standard systematic review methodology was used to identify relevant prognostic model development, validation and cost-effectiveness studies. Bibliographic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched using terms relating to the clinical area and prognosis. Reviewing was undertaken by two reviewers independently using pre-defined criteria. Included full-text articles were data extracted and quality assessed. Critical appraisal of included full texts was undertaken and comparisons made of model performance. A prognostic model was developed using IPD from the pooled database of seven trials. A novel internal-external cross-validation (IECV) approach was used to develop and validate a prognostic model, with external validation undertaken in each of the trials iteratively. Given good performance in the IECV approach, a final model was developed using all trials data. A Markov patient-level simulation was used to consider the economic cost

  12. Strong Electroweak Symmetry Breaking

    CERN Document Server

    Grinstein, Benjamin

    2011-01-01

    Models of spontaneous breaking of electroweak symmetry by a strong interaction do not have fine tuning/hierarchy problem. They are conceptually elegant and use the only mechanism of spontaneous breaking of a gauge symmetry that is known to occur in nature. The simplest model, minimal technicolor with extended technicolor interactions, is appealing because one can calculate by scaling up from QCD. But it is ruled out on many counts: inappropriately low quark and lepton masses (or excessive FCNC), bad electroweak data fits, light scalar and vector states, etc. However, nature may not choose the minimal model and then we are stuck: except possibly through lattice simulations, we are unable to compute and test the models. In the LHC era it therefore makes sense to abandon specific models (of strong EW breaking) and concentrate on generic features that may indicate discovery. The Technicolor Straw Man is not a model but a parametrized search strategy inspired by a remarkable generic feature of walking technicolor,...

  13. Outcomes and prognostic factors in nodular melanomas.

    Science.gov (United States)

    Egger, Michael E; Dunki-Jacobs, Erik M; Callender, Glenda G; Quillo, Amy R; Scoggins, Charles R; Martin, Robert C G; Stromberg, Arnold J; McMasters, Kelly M

    2012-10-01

    The nodular subtype of cutaneous melanoma has a more pronounced vertical phase and less of a radial growth phase compared with other histologic subtypes. This study was performed to determine prognostic factors and outcomes for nodular melanomas. A post hoc analysis of a prospective clinical trial was performed in all patients with nodular histologic subtype. Univariate and multivariate analyses of factors associated with disease-free survival (DFS), overall survival (OS), and local and in-transit recurrence-free survival (LITRFS) were performed. Kaplan-Meier survival analyses were performed. There were 736 patients available for analysis, and 189 (25.7%) were sentinel lymph node (SLN) positive. Breslow thickness of ≥2.3 mm, presence of ulceration, nonextremity tumor location, positive SLN, and non-SLN-positive status were independent risk factors for worse OS and DFS. Kaplan-Meier analysis demonstrated that ulceration predicted worse OS and DFS in all nodular melanoma patients, and in both SLN-positive and -negative subsets. The presence of ulceration and a positive SLN together predicted significantly worse DFS and OS. The most important risk factors that determine prognosis in nodular melanomas are SLN status and ulceration. The presence of both a positive SLN and ulceration significantly affect DFS and OS, and to a lesser degree LITRFS. Copyright © 2012 Mosby, Inc. All rights reserved.

  14. Plasmons in strong superconductors

    International Nuclear Information System (INIS)

    Baldo, M.; Ducoin, C.

    2011-01-01

    We present a study of the possible plasmon excitations that can occur in systems where strong superconductivity is present. In these systems the plasmon energy is comparable to or smaller than the pairing gap. As a prototype of these systems we consider the proton component of Neutron Star matter just below the crust when electron screening is not taken into account. For the realistic case we consider in detail the different aspects of the elementary excitations when the proton, electron components are considered within the Random-Phase Approximation generalized to the superfluid case, while the influence of the neutron component is considered only at qualitative level. Electron screening plays a major role in modifying the proton spectrum and spectral function. At the same time the electron plasmon is strongly modified and damped by the indirect coupling with the superfluid proton component, even at moderately low values of the gap. The excitation spectrum shows the interplay of the different components and their relevance for each excitation modes. The results are relevant for neutrino physics and thermodynamical processes in neutron stars. If electron screening is neglected, the spectral properties of the proton component show some resemblance with the physical situation in high-T c superconductors, and we briefly discuss similarities and differences in this connection. In a general prospect, the results of the study emphasize the role of Coulomb interaction in strong superconductors.

  15. [Useful tests to assess the clinical usefulness of new prognostic markers: the example of heart failure].

    Science.gov (United States)

    Jenei, Zsigmond Máté; Prohászka, Zoltán

    2013-09-01

    Identification of risk factors is one of the most frequent questions in medical research currently. Several reports showed "significant" and "independent" prognostic factors in a variety of human conditions, however, those were not tested about predictive information in addition to standard risk markers. Recently novel statistical approaches (reclassification) have been developed to test the performance and usefulness of new risk factors and prognostic markers. There are several established methods to test the prognostic models. The aim of this work was to present the application of these novel statistical approaches by re-analyzing previously reported results of the authors. The authors analyzed the prognostic role of two markers: red cell distribution width and heat shock protein 70 in patients with heart failure. Using Cox regression analyses the authors have reported previously that both markers are independent predictors. In the present study they re-analyzed the role of red cell distribution width and heat shock protein 70 by reclassification tests. Incorporating red cell distribution width to the reference model the authors found a significant improvement in discrimination . However, the reclassification analysis provided ambiguous results with heat shock protein 70. Interpretation of results on new prognostic factors has to be done carefully, and appropriate reclassification approaches may help to confirm clinical usefulness only.

  16. Novel lincRNA SLINKY is a prognostic biomarker in kidney cancer.

    Science.gov (United States)

    Gong, Xue; Siprashvili, Zurab; Eminaga, Okyaz; Shen, Zhewei; Sato, Yusuke; Kume, Haruki; Homma, Yukio; Ogawa, Seishi; Khavari, Paul A; Pollack, Jonathan R; Brooks, James D

    2017-03-21

    Clear cell renal cell carcinomas (ccRCC) show a broad range of clinical behavior, and prognostic biomarkers are needed to stratify patients for appropriate management. We sought to determine whether long intergenic non-coding RNAs (lincRNAs) might predict patient survival. Candidate prognostic lincRNAs were identified by mining The Cancer Genome Atlas (TCGA) transcriptome (RNA-seq) data on 466 ccRCC cases (randomized into discovery and validation sets) annotated for ~21,000 lncRNAs. A previously uncharacterized lincRNA, SLINKY (Survival-predictive LINcRNA in KidneY cancer), was the top-ranked prognostic lincRNA, and validated in an independent University of Tokyo cohort (P=0.004). In multivariable analysis, SLINKY expression predicted overall survival independent of tumor stage and grade [TCGA HR=3.5 (CI, 2.2-5.7), P SLINKY knockdown reduced cancer cell proliferation (with cell-cycle G1 arrest) and induced transcriptome changes enriched for cell proliferation and survival processes. Notably, the genes affected by SLINKY knockdown in cell lines were themselves prognostic and correlated with SLINKY expression in the ccRCC patient samples. From a screen for binding partners, we identified direct binding of SLINKY to Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK), whose knockdown recapitulated SLINKY knockdown phenotypes. Thus, SLINKY is a robust prognostic biomarker in ccRCC, where it functions possibly together with HNRNPK in cancer cell proliferation.

  17. Prognostic

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-10-01

    Conclusion: Our study suggests that lactate clearance could be used as a useful biomarker which is inexpensive and a reliable predictor of patient outcome in critically ill patients admitted to ICU with severe community-acquired pneumonia.

  18. Hypoxia and hypoxia-regulated proteins in gastric cancer: prognostic significance for clinical outcome

    International Nuclear Information System (INIS)

    Osinsky, S.; Gumenjuk, L.; Bubnovskaya, L.; Merentsev, S.; Kovelskaya, A.; Shalimov, S.; Osinsky, D.; Olijnichenko, G.

    2005-01-01

    Full text: To examine the relationship between hypoxia level, hypoxia-inducible factor-1α (HIF-1α) expression, tumor vascularity, and clinicopathologic parameters in gastric cancer; to assess the impact of hypoxia-associated events on the prognosis of clinical outcome. High hypoxia levels were found in 29 % of pts., and low - in 71 % of pts. Strong nuclear expressions of HIF-1α were found in 7 % of pts., moderate - in 80 % of pts., and weak - in 13 % of pts. Strong microvessel densities were observed in 54 % of pts. and moderate - in 46 % of pts. It was revealed a close association between the hypoxia level in tumor assessed by 31 P NMR spectroscopy and expression of HIF-1α in tumor cells (P 0.05). Hypoxia level and microvessel density in tumor tissue correlated with clinical stage (P<0.05). High hypoxia levels positively correlated with decreased overall survival (P=0.044). For overall survival, hypoxia level and HIF-1α expression (hazard ratio, 2.10; 95 % CI, 0.67-4.67; P=0.035 and 3.45; 0.89-3.01, 0.047, respectively) were independently predictive in multivariate analysis for lymph-node negative patients; and hypoxia level (hazard ratio, 4.50; 95 % CI, 0.42-2.57; P=0.027) for lymph-node positive patients. Statistical analysis has indicated that PME/Pi ratio in tumor tissue may be used as an parameter of hypoxia level as well as independent prognostic factor of clinical outcome in patients with gastric cancer. Methodological approaches are started now to be used in the analysis of head and neck tumors treated with hyperthermia combined with radiation/chemotherapy. (author)

  19. Prognostic radiographic aspects of spondylolisthesis

    Energy Technology Data Exchange (ETDEWEB)

    Saraste, H.; Brostroem, L.A.; Aparisi, T.

    1984-01-01

    A series of 202 patients (133 men, 69 women) with lumbar spondylolysis were examined radiographically on two occasions, first at the time of diagnosis and later at a follow-up, after an observation period of 20 years or more. The films from patients in groups without and with moderate and severe olisthesis were evaluated with respect to variables describing lumbosacral lordosis, wedging of the spondylolytic vertebra, lengths of the transverse processes and iliolumbar ligaments, disk height, progression of slipping, and influence on measured olisthesis of lumbar spine flexion and extension at the radiographic examination. The evaluation was made with special attention to possible signs which could be predictive for the prognosis of vertebral slipping. Progression of slipping did not differ between patients diagnosed as adults or adolescents. Reduction of disk height was correlated to the degree of slipping present at the initial examination and to the progression of olisthesis. Flexion and extension of the lumbar spine did not modify the degree of olisthesis. Data concerning the lengths of the transverse processes and the iliolumbar ligaments, and lumbar lordosis, cannot be used for prognostic purposes. The lumbar index reflecting the degree of wedge deformity of the spondylolytic vertebra was shown to be the only variable of prognostic value for the development of vertebral slipping.

  20. Prognostic radiographic aspects of spondylolisthesis

    International Nuclear Information System (INIS)

    Saraste, H.; Brostroem, L.A.; Aparisi, T.

    1984-01-01

    A series of 202 patients (133 men, 69 women) with lumbar spondylolysis were examined radiographically on two occasions, first at the time of diagnosis and later at a follow-up, after an observation period of 20 years or more. The films frompatients in groups without and with moderate and severe olisthesis were evaluated with respect to variables describing lumbosacral lordosis, wedging of the spondylolytic vertebra, lengths of the transverse processes and iliolumbar ligaments, disk height, progression of slipping, and influence on measured olisthesis of lumbar spine flexion and extension at the radiographic examination. The evaluation was made with special attention to possible signs which could be predictive for the prognosis of vertebral slipping. Progression of slipping did not differ between patients diagnosed as adults or adolescents. Reduction of disk height was correlated to the degree of slipping present at the initial examination and to the progression of olisthesis. Flexion and extension of the lumbar spine did not modify the degree of olisthesis. Data concerning the lengths of the transverse processes and the iliolumbar ligaments, and lumbar lordosis, cannot be used for prognostic purposes. The lumbar index reflecting the degree of wedge deformity of the spondylolytic vertebra was shown to be the only variable of prognostic value for the development of vertebral slipping. (orig.)

  1. Prognostic factors in Fournier gangrene.

    Science.gov (United States)

    Ruiz-Tovar, Jaime; Córdoba, Luis; Devesa, Jose Manuel

    2012-01-01

    Fournier gangrene is a necrotizing fasciitis, arising in the genital and perineal area. This entity is still associated with a high mortality rate despite improvements in antibiotic and surgical treatment. This is a retrospective study of all the patients diagnosed and surgically treated for Fournier gangrene at General University Hospital Ramon y Cajal between 1988 and 2008. Possible prognostic factors that could have any influence on the evolution of Fournier gangrene were analyzed. Seventy patients were analyzed, 62 males (88.6%) and 8 females (11.4%) with a mean age of 57.9 ± 13.5 years. Most frequent clinical manifestations were perineal pain (82.9%) and fever (60%). Physical examination revealed edema (91.4%), erythema (88.6%) and perineal skin necrosis (60%). All the patients underwent surgical debridement of necrotic tissue. In 54.3% reoperations were necessary for new surgical debridements. Medical complications rate was 27.1% and mortality one 22.9%. Ethylism, coexistence of neoplasms, presence of skin necrosis, myonecrosis, abdominal wall affection, number of debrided areas, reoperations, concentration of creatinine in serum>1.4 mg/dL, and hemoglobin <10 g/dL, and platelet count <150 × 10(9)/L in whole blood are associated with higher mortality rates. Identification of prognostic factors may help to determine high-risk patients in order to establish an optimal treatment, according to severity of the infection and general status. Copyright © 2012. Published by Elsevier B.V.

  2. Development of a prognostic scoring system for resectable hepatocellular carcinoma.

    Science.gov (United States)

    Sposito, Carlo; Di Sandro, Stefano; Brunero, Federica; Buscemi, Vincenzo; Battiston, Carlo; Lauterio, Andrea; Bongini, Marco; De Carlis, Luciano; Mazzaferro, Vincenzo

    2016-09-28

    To develop a prognostic scoring system for overall survival (OS) of patients undergoing liver resection (LR) for hepatocellular carcinoma (HCC). Consecutive patients who underwent curative LR for HCC between 2000 and 2013 were identified. The series was randomly divided into a training and a validation set. A multivariable Cox model for OS was fitted to the training set. The beta coefficients derived from the Cox model were used to define a prognostic scoring system for OS. The survival stratification was then tested, and the prognostic scoring system was compared with the European Association for the Study of the Liver (EASL)/American Association for the Study of Liver Diseases (AASLD) surgical criteria by means of Harrell's C statistics. A total of 917 patients were considered. Five variables independently correlated with post-LR survival: Model for End-stage Liver Disease score, hepatitis C virus infection, number of nodules, largest diameter and vascular invasion. Three risk classes were identified, and OS for the three risk classes was significantly different both in the training (P < 0.0001) and the validation set (P = 0.0002). Overall, 69.4% of patients were in the low-risk class, whereas only 37.8% were eligible to surgery according to EASL/AASLD. Survival of patients in the low-risk class was not significantly different compared with surgical indication for EASL/AASLD guidelines (77.2 mo vs 82.5 mo respectively, P = 0.22). Comparison of Harrell's C statistics revealed no significant difference in predictive power between the two systems (-0.00999, P = 0.667). This study established a new prognostic scoring system that may stratify HCC patients suitable for surgery, expanding surgical eligibility with respect to EASL/AASLD criteria with no harm on survival.

  3. Expression and prognostic significance of lysozyme in male breast cancer

    International Nuclear Information System (INIS)

    Serra, Carlos; Baltasar, Aniceto; Medrano, Justo; Vizoso, Francisco; Alonso, Lorena; Rodríguez, Juan C; González, Luis O; Fernández, María; Lamelas, María L; Sánchez, Luis M; García-Muñiz, José L

    2002-01-01

    Lysozyme, one of the major protein components of human milk that is also synthesized by a significant percentage of breast carcinomas, is associated with lesions that have a favorable outcome in female breast cancer. Here we evaluate the expression and prognostic value of lysozyme in male breast cancer (MBC). Lysozyme expression was examined by immunohistochemical methods in a series of 60 MBC tissue sections and in 15 patients with gynecomastia. Staining was quantified using the HSCORE (histological score) system, which considers both the intensity and the percentage of cells staining at each intensity. Prognostic value of lysozyme was retrospectively evaluated by multivariate analysis taking into account conventional prognostic factors. Lysozyme immunostaining was negative in all cases of gynecomastia. A total of 27 of 60 MBC sections (45%) stained positively for this protein, but there were clear differences among them with regard to the intensity and percentage of stained cells. Statistical analysis showed that lysozyme HSCORE values in relation to age, tumor size, nodal status, histological grade, estrogen receptor status, metastasis and histological type did not increase the statistical significance. Univariate analysis confirmed that both nodal involvement and lysozyme values were significant predictors of short-term relapse-free survival. Multivariate analysis, according to Cox's regression model, also showed that nodal status and lysozyme levels were significant independent indicators of short-term relapse-free survival. Tumor expression of lysozyme is associated with lesions that have an unfavorable outcome in male breast cancer. This milk protein may be a new prognostic factor in patients with breast cancer

  4. Prognostic Analysis System and Methods of Operation

    Science.gov (United States)

    MacKey, Ryan M. E. (Inventor); Sneddon, Robert (Inventor)

    2014-01-01

    A prognostic analysis system and methods of operating the system are provided. In particular, a prognostic analysis system for the analysis of physical system health applicable to mechanical, electrical, chemical and optical systems and methods of operating the system are described herein.

  5. Bacterial brain abscesses: prognostic value of an imaging severity index

    International Nuclear Information System (INIS)

    Demir, M.K.; Hakan, T.; Kilicoglu, G.; Ceran, N.; Berkman, M.Z.; Erdem, I.; Goektas, P.

    2007-01-01

    Aim: To assess the correlation between imaging findings [computed tomography (CT) or magnetic resonance imaging (MRI)] and neurological status before and after the treatment of bacterial brain abscesses. Materials and methods: CT and MRI images of 96 patients with brain abscesses were retrospectively evaluated in terms of the number, location and size of lesions, and the presence and extent of perilesional oedema and midline shift. An imaging severity index (ISI) based on these different radiological parameters was calculated. Initial Glasgow Coma Scale (GCS) scores and ISI were assessed and the prognostic value of these two indices was calculated. The Pearson correlation test, Mann-Whitney test, Chi-square test, receiver-operating characteristic (ROC) analysis, together with comparison of ROC analyses and Fisher's exact test were used. Results: There was a negative correlation between ISI and the initial GCS values: ISI increased as the GCS score decreased, indicating an inverse relationship (r = -0.51, p < 0.0001). There was a significant difference between the ISI and GCS scores of patients with an adverse event compared with patients with good recovery. Outcome was significantly worse in patients with initial ISI over the calculated cut-off values of 8 points or GCS scores under the cut-off value of 13 points. Conclusion: ISI is a useful prognostic indicator for bacterial brain abscess patients and correlates strongly with the patient outcome for all parameters studied. ISI score had a better prognostic value than GCS

  6. Prognostic value of heart rate response during regadenoson stress myocardial perfusion imaging in patients with end stage renal disease.

    Science.gov (United States)

    AlJaroudi, Wael; Campagnoli, Tania; Fughhi, Ibtihaj; Wassouf, Marwan; Ali, Amjad; Doukky, Rami

    2016-06-01

    Blunted heart rate response (HRR) to vasodilator stress agents is associated with worse outcomes. There are limited data assessing the effect of impaired HRR to regadenoson among patients with end-stage renal disease (ESRD) undergoing stress myocardial perfusion imaging (MPI). We prospectively followed patients with ESRD enrolled in the ASSUAGE and ASSUAGE-CKD trials. HRR was defined as 100*(peak stress heart rate-resting heart rate)/resting heart rate. Study cohort was dichotomized to blunted and normal HRR groups according to an established median HRR value 90 days) coronary revascularization. There were 303 patients followed for 35 ± 10 months. In the entire cohort, there was a stepwise increase in the rates of death and all secondary endpoints with worsening HRR (P values ≤.001). Blunted HRR (<28%) was associated with increased risk of death (unadjusted hazard ratio 4.10 [1.98-8.46], P < .001) and all secondary endpoints (P ≤ .001). After multivariate adjustment, HRR remained an independent predictor of mortality and secondary endpoints whether used as continuous or dichotomous variable, and added incremental prognostic value for all-cause death (P = .046). Blunted HRR was associated with increased event rate among patients with normal myocardial perfusion (P = .001) and abnormal perfusion (P = .053). In the propensity-matched cohort of 132 patients (66 in each group), blunted HRR was associated with significant increase in all-cause death (21% vs. 5%, HR 5.09 [1.46-17.7], P=.011), and similarly for the secondary endpoints. Blunted HRR (<28%) to regadenoson is a strong and independent predictor of death and cardiovascular events in patients with ESRD and adds incremental prognostic value.

  7. Comparison of prognostic impact of absolute lymphocyte count, absolute monocyte count, absolute lymphocyte count/absolute monocyte count prognostic score and ratio in patients with diffuse large B cell lymphoma.

    Science.gov (United States)

    Markovic, Olivera; Popovic, Lazar; Marisavljevic, Dragomir; Jovanovic, Darjana; Filipovic, Branka; Stanisavljevic, Dejana; Matovina-Brko, Gorana; Hajder, Jelena; Matkovic, Tatjana; Živkovic, Radmila; Stanisavljevic, Natasa; Todorović, Milena; Petrovic, Dragana; Mihaljevic, Biljana

    2014-03-01

    The combination of absolute lymphocyte count (ALC) and absolute monocyte count (AMC) at diagnosis has prognostic relevance in patients with diffuse large B cell lymphoma (DLBCL). The present study was designed to investigate the prognostic significance of ALC and AMC and to determine whether ALC/AMC ratio or ALC/AMC prognostic score is better predictor of outcome in DLBCL. We retrospectively analyzed the prognostic significance of ALC and AMC, ALC/AMC ratio and ALC/AMC prognostic score at diagnosis in 222 DLBCL patients treated with R-CHOP. ROC analysis showed that optimal cut-off values of AMC and ALC/AMC ratio with the best sensitivity and specificity were 0.59×10(9)/L and 2.8, respectively. Cut-off of ALC was determined according to the literature data (1×10(9)/L). Low ALC, high AMC, low ALC/AMC ratio and high ALC/AMC prognostic score were in significant association with lower rate of therapy response and survival. In contrast, these parameters were not in significant correlation with relapse rate. The patients with low ALC, "high" AMC, low ALC/AMC ratio and high ALC/AMC prognostic score at diagnosis had significantly shorter EFS and OS. In multivariate analysis all tested parameters (ALC, AMC, ALC/AMC prognostic score and ALC/AMC ratio) are independent risk factors along with "bulky" disease and IPI. All tested parameters (ALC, AMC, ALC/AMC score and ALC/AMC ratio) may be useful prognostic factors in DLBCL patients. ALC/AMC score has a slight advantage as it allows the classification of patients into three prognostic groups. Further studies are needed to determine which of these parameters has the highest predictive value. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  8. Prognostic significance of erythropoietin in pancreatic adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Thilo Welsch

    Full Text Available BACKGROUND: Erythropoietin (Epo administration has been reported to have tumor-promoting effects in anemic cancer patients. We investigated the prognostic impact of endogenous Epo in patients with pancreatic ductal adenocarcinoma (PDAC. METHODOLOGY: The clinico-pathological relevance of hemoglobin (Hb, n = 150, serum Epo (sEpo, n = 87 and tissue expression of Epo/Epo receptor (EpoR, n = 104 was analyzed in patients with PDAC. Epo/EpoR expression, signaling, growth, invasion and chemoresistance were studied in Epo-exposed PDAC cell lines. RESULTS: Compared to donors, median preoperative Hb levels were reduced by 15% in both chronic pancreatitis (CP, p<0.05 and PDAC (p<0.001, reaching anemic grade in one third of patients. While inversely correlating to Hb (r = -0.46, 95% of sEPO values lay within the normal range. The individual levels of compensation were adequate in CP (observed to predicted ratio, O/P = 0.99 but not in PDAC (O/P = 0.85. Strikingly, lower sEPO values yielding inadequate Epo responses were prominent in non-metastatic M0-patients, whereas these parameters were restored in metastatic M1-group (8 vs. 13 mU/mL; O/P = 0.82 vs. 0.96; p<0.01--although Hb levels and the prevalence of anemia were comparable. Higher sEpo values (upper quartile ≥ 16 mU/ml were not significantly different in M0 (20% and M1 (30% groups, but were an independent prognostic factor for shorter survival (HR 2.20, 10 vs. 17 months, p<0.05. The pattern of Epo expression in pancreas and liver suggested ectopic release of Epo by capillaries/vasa vasorum and hepatocytes, regulated by but not emanating from tumor cells. Epo could initiate PI3K/Akt signaling via EpoR in PDAC cells but failed to alter their functions, probably due to co-expression of the soluble EpoR isoform, known to antagonize Epo. CONCLUSION/SIGNIFICANCE: Higher sEPO levels counteract anemia but worsen outcome in PDAC patients. Further trials are required to clarify how overcoming a sEPO threshold

  9. Strong-coupling approximations

    International Nuclear Information System (INIS)

    Abbott, R.B.

    1984-03-01

    Standard path-integral techniques such as instanton calculations give good answers for weak-coupling problems, but become unreliable for strong-coupling. Here we consider a method of replacing the original potential by a suitably chosen harmonic oscillator potential. Physically this is motivated by the fact that potential barriers below the level of the ground-state energy of a quantum-mechanical system have little effect. Numerically, results are good, both for quantum-mechanical problems and for massive phi 4 field theory in 1 + 1 dimensions. 9 references, 6 figures

  10. Strong interaction and QFD

    International Nuclear Information System (INIS)

    Ebata, T.

    1981-01-01

    With an assumed weak multiplet structure for bosonic hadrons, which is consistent with the ΔI = 1/2 rule, it is shown that the strong interaction effective hamiltonian is compatible with the weak SU(2) x U(1) gauge transformation. Especially the rho-meson transforms as a triplet under SU(2)sub(w), and this is the origin of the rho-photon analogy. It is also shown that the existence of the non-vanishing Cabibbo angle is a necessary condition for the absence of the exotic hadrons. (orig.)

  11. Prognostic significance of perioperative nutritional parameters in patients with gastric cancer.

    Science.gov (United States)

    Oh, Sung Eun; Choi, Min-Gew; Seo, Jeong-Meen; An, Ji Yeong; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung

    2018-02-20

    It has been suggested that nutritional status is related to the survival outcomes of cancer patients. The purpose of the current research is to evaluate the importance of the prognosis of various nutritional parameters during the perioperative period in patients with gastric cancer. This study enrolled patients with gastric cancer who underwent D2 gastrectomy at the Department of Surgery, Samsung Medical Center, in 2008. The prognostic significance of nutritional parameters was analyzed, along with other clinical and pathological variables, preoperatively and postoperatively at 3, 6, and 12 months. The total number of patients was 1415. The mean values of nutritional parameters, weight, body mass index (BMI), hemoglobin, total cholesterol, and total lymphocyte count (TLC) decreased significantly over time after surgery. On the contrary, albumin and prognostic nutritional index (PNI) score increased significantly during the postoperative follow-up period. Preoperatively, low BMI (<18.5 kg/m 2 ) and low TLC level (<1000 per mm 3 ) were revealed as independent prognostic factors in multivariate analysis. Low preoperative TLC level and decline in PNI (ΔPNI < -2.2) at postoperative 3 months; low preoperative TLC level and decline in TLC (ΔTLC < -279.9 per mm 3 ) at postoperative 6 months; and low preoperative BMI, albumin, and TLC levels at postoperative 12 months were independent nutritional prognostic indicators. Various perioperative nutritional parameters were confirmed as independent prognostic factors in patients with gastric cancer. Our results imply prognostic benefit from careful nutritional support for patients with poor nutritional parameters. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  12. Strong Coupling Holography

    CERN Document Server

    Dvali, Gia

    2009-01-01

    We show that whenever a 4-dimensional theory with N particle species emerges as a consistent low energy description of a 3-brane embedded in an asymptotically-flat (4+d)-dimensional space, the holographic scale of high-dimensional gravity sets the strong coupling scale of the 4D theory. This connection persists in the limit in which gravity can be consistently decoupled. We demonstrate this effect for orbifold planes, as well as for the solitonic branes and string theoretic D-branes. In all cases the emergence of a 4D strong coupling scale from bulk holography is a persistent phenomenon. The effect turns out to be insensitive even to such extreme deformations of the brane action that seemingly shield 4D theory from the bulk gravity effects. A well understood example of such deformation is given by large 4D Einstein term in the 3-brane action, which is known to suppress the strength of 5D gravity at short distances and change the 5D Newton's law into the four-dimensional one. Nevertheless, we observe that the ...

  13. The strong law of large numbers for random quadratic forms

    NARCIS (Netherlands)

    Mikosch, T

    1996-01-01

    The paper establishes strong laws of large numbers for the quadratic forms [GRAPHICS] and the bilinear forms [GRAPHICS] where X = (X(n)) is a sequence of independent random variables and Y = (Y-n) is an independent copy of it. In the case of independent identically distributed symmetric p-stable

  14. Introduction to algebraic independence theory

    CERN Document Server

    Philippon, Patrice

    2001-01-01

    In the last five years there has been very significant progress in the development of transcendence theory. A new approach to the arithmetic properties of values of modular forms and theta-functions was found. The solution of the Mahler-Manin problem on values of modular function j(tau) and algebraic independence of numbers pi and e^(pi) are most impressive results of this breakthrough. The book presents these and other results on algebraic independence of numbers and further, a detailed exposition of methods created in last the 25 years, during which commutative algebra and algebraic geometry exerted strong catalytic influence on the development of the subject.

  15. Prognostic factors of choroidal melanoma in Slovenia, 1986–2008

    International Nuclear Information System (INIS)

    Jancar, Boris; Budihna, Marjan; Drnovsek-Olup, Brigita; Andrejcic, Katrina Novak; Zupancic, Irena Brovet; Pahor, Dusica

    2016-01-01

    Choroidal melanoma is the most common primary malignancy of the eye, which frequently metastasizes. The Cancer Registry of Slovenia reported the incidence of choroid melanoma from 1983 to 2009 as stable, at 7.8 cases/million for men and 7.4/million for women. The aim of the retrospective study was to determinate the prognostic factors of survival for choroidal melanoma patients in Slovenia. From January 1986 to December 2008 we treated 288 patients with malignant choroidal melanoma; 127 patients were treated by brachytherapy with beta rays emitting ruthenium-106 applicators; 161 patients were treated by enucleation. Patients with tumours thickness < 7.2 mm and base diameter < 16 mm were treated by brachytherapy and had 5- and 10-year overall mortality 13% and 32%, respectively. In enucleated patients, 5- and 10-year mortality was higher, 46% and 69%, respectively, because their tumours were larger. Thirty patients treated by brachytherapy developed local recurrence. Twenty five of 127 patients treated by brachytherapy and 86 of 161 enucleated patients developed distant metastases. Patients of age ≥ 60 years had significantly lower survival in both treatment modalities. For patients treated by brachytherapy the diameter of the tumour base and treatment time were independent prognostic factors for overall survival, for patients treated by enucleation age and histological type of tumour were independent prognosticators. In first few years after either of treatments, the melanoma specific annual mortality rate increased, especially in older patients, and then slowly decreased. It seems that particularly younger patients with early tumours can be cured, whereby preference should be given to eyesight preserving brachytherapy over enucleation

  16. Prognostic implication of NQO1 overexpression in hepatocellular carcinoma.

    Science.gov (United States)

    Lin, Lijuan; Sun, Jie; Tan, Yan; Li, Zhenling; Kong, Fanyong; Shen, Yue; Liu, Chao; Chen, Litian

    2017-11-01

    To explore the role of NQO1 overexpression for prognostic implication in hepatocellular carcinoma (HCC), NQO1 mRNA levels were detected in HCC fresh tissue samples of HCC and nontumor tissues, respectively. One hundred fifty-six cases of HCC meeting strict follow-up criteria were selected for immunohistochemical staining of NQO1 protein. Correlations between NQO1 overexpression and clinicopathological features of HCC were evaluated using χ 2 tests, survival rates were calculated using the Kaplan-Meier method, and the relationship between prognostic factors and patient 5-year survival was analyzed using Cox proportional hazards analysis. In results, the levels of NQO1 mRNA were significantly up-regulated in 14 fresh tissue samples of HCC. Immunohistochemical analysis showed that the NQO1 expression and overexpression rates were significantly higher in HCC samples compared with either adjacent nontumor tissues or normal liver tissues. NQO1 overexpression correlated to tumor size, venous infiltration and late pTNM stage of HCC. NQO1 overexpression was also related to low disease-free survival and 5-year survival rates. In the late-stage group, disease-free and 5-year survival rates of patients with NQO1 overexpression were significantly lower than those of patients without NQO1 expression. Further analysis using a Cox proportional hazards regression model revealed that NQO1 expression emerged as a significant independent hazard factor for the 5-year survival rate of patients with HCC. Therefore, NQO1 plays an important role in the progression of HCC. NQO1 may potentially be used as an independent biomarker for prognostic evaluation of HCC. Copyright © 2017. Published by Elsevier Inc.

  17. LIGO: The strong belief

    CERN Multimedia

    Antonella Del Rosso

    2016-01-01

    Twenty years of designing, building and testing a number of innovative technologies, with the strong belief that the endeavour would lead to a historic breakthrough. The Bulletin publishes an abstract of the Courier’s interview with Barry Barish, one of the founding fathers of LIGO.   The plots show the signals of gravitational waves detected by the twin LIGO observatories at Livingston, Louisiana, and Hanford, Washington. (Image: Caltech/MIT/LIGO Lab) On 11 February, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo collaborations published a historic paper in which they showed a gravitational signal emitted by the merger of two black holes. These results come after 20 years of hard work by a large collaboration of scientists operating the two LIGO observatories in the US. Barry Barish, Linde Professor of Physics, Emeritus at the California Institute of Technology and former Director of the Global Design Effort for the Internat...

  18. Comparison of Myelodysplastic Syndrome Prognostic Scoring Systems

    Directory of Open Access Journals (Sweden)

    Özlen Bektaş

    2016-05-01

    Full Text Available Objective: Myelodysplastic syndrome (MDS is a clonal hematopoietic stem cell disease. Patients are at risk of developing cytopenias or progression to acute myeloid leukemia. Different classifications and prognostic scoring systems have been developed. The aim of this study was to compare the different prognostic scoring systems. Materials and Methods: One hundred and one patients who were diagnosed with primary MDS in 2003-2011 in a tertiary care university hospital’s hematology department were included in the study. Results: As the International Prognostic Scoring System (IPSS, World Health Organization Classification-Based Prognostic Scoring System (WPSS, MD Anderson Prognostic Scoring System (MPSS, and revised IPSS (IPSS-R risk categories increased, leukemia-free survival and overall survival decreased (p<0.001. When the IPSS, WPSS, MPSS, and IPSS-R prognostic systems were compared by Cox regression analysis, the WPSS was the best in predicting leukemia-free survival (p<0.001, and the WPSS (p<0.001 and IPSS-R (p=0.037 were better in predicting overall survival. Conclusion: All 4 prognostic systems were successful in predicting overall survival and leukemia-free survival (p<0.001. The WPSS was found to be the best predictor for leukemia-free survival, while the WPSS and IPSS-R were found to be the best predictors for overall survival.

  19. Intraarterial therapy for acute ischemic stroke. Investigation of prognostic factors

    International Nuclear Information System (INIS)

    Noguchi, Tomoyuki; Yoshiura, Takashi; Oguri, Shuichi

    2007-01-01

    Intraarterial therapy (IAT) for acute cerebral infarction has been proven to be profitable. However, the criteria for the indications, the choice of the thrombolytic agents, and the use of adjunctive agents are controversial. We retrospectively analyzed the prognostic factors of IAT. From 1994 to 2003, 28 patients underwent IAT due to middle cerebral artery occlusion (17 women and 11 men; median age, 69 years old). We evaluated the following prognostic parameters: institution of treatment, degree of paralysis at visit, size of high-intensity area on diffusion-weighted images, dose of intraarterial urokinase administration, elapsed time from symptom onset to completion of IAT, presence of penetration of embolus by microcatheter and microguidewire, recanalization after IAT, intracranial hemorrhage (ICH) within 24 hours after IAT, and intravenous heparin administration after IAT. The outcome was evaluated at discharge and was classified into the following categories according to the modified Rankin Scale: independence (0 to 2), dependence (3 to 5), and death (6). Seven patients were judged to be independent, 16 patients were judged to be dependent, and five patients died. Patients with recanalization after IAT had a better outcome than those without (p<0.05); patients with intracranial hemorrhage had a worse outcome than those without (p<0.05); and patients with intravenous heparin administration after IAT had a better outcome in activities of daily living than those without (p<0.05). In addition to ICH and recanalization, our results suggested that intravenous heparin administration after IAT had a favorable effect on patient outcome. (author)

  20. Morbidity and prognostic factors in chronic chagasic cardiopathy

    Directory of Open Access Journals (Sweden)

    Manoel Otávio C Rocha

    2009-07-01

    Full Text Available Chagas disease is a pleomorphic clinical entity that has several unique features. The aim of this study is to summarise some of the recent contributions from our research group to knowledge of the morbidity and prognostic factors in Chagas heart disease. A retrospective study suggested that ischaemic stroke associated with left ventricular (LV apical thrombi is the first clinical manifestation of Chagas disease observed in a large proportion of patients. LV function and left atrial volume (LAV are independent risk factors for ischaemic cerebrovascular events during follow-up of Chagas heart disease patients. Pulmonary congestion in Chagas-related dilated cardiomyopathy is common but usually mild. Although early right ventricular (RV involvement has been described, we have shown by Doppler echocardiography that RV dysfunction is evident almost exclusively when it is associated with left ventricle dilatation and functional impairment. In addition, RV dysfunction is a powerful predictor of survival in patients with heart failure secondary to Chagas disease. We have also demonstrated that LAV provides incremental prognostic information independent of clinical data and conventional echocardiographic parameters that predict survival.

  1. Prognostic factors in childhood-acquired brain injury.

    Science.gov (United States)

    Shaklai, Sharon; Peretz Fish, Relly; Simantov, M; Groswasser, Z

    2018-01-01

    A long-term follow-up study comparing children after anoxic brain injury (AnBI) with those after traumatic brain injury (TBI) was conducted, and prognostic factors were mapped. A prospective historical study following long-term functional outcome after childhood brain injury was conducted in two phases. The first phase included patients suffering from moderate-severe TBI. The second phase assessed children after AnBI, and the results were compared. Functional outcome was recorded and factors influencing prognosis were outlined. On admission vegetative state (VS) was twice as prevalent in the AnBI subgroup. Approximately 90% of children with TBI and 60% of patients with AnBI gained independency in activities of daily living (ADL) and mobility. Long-term positive outcome, i.e., return to school and open-market employment, were higher in patients with TBI when compared with AnBI (61% and 48.1%, respectively). Significant outcome-predicting factors were VS at admission to rehabilitation, length of loss of consciousness (LOC) up to 11 days and functional independence measure (FIM) score at admission and discharge. Aetiology was not found to be a predicting factor. Duration of unconsciousness is the main long-term negative prognostic outcome factor. Anoxic brain damage, associated with longer periods of unconsciousness also heralds a less favourable outcome.

  2. Prognostic value of multicenter flow cytometry harmonized assessment of minimal residual disease in acute myeloblastic leukemia.

    Science.gov (United States)

    Lacombe, Francis; Campos, Lydia; Allou, Kaoutar; Arnoulet, Christine; Delabarthe, Adrienne; Dumezy, Florent; Feuillard, Jean; Geneviève, Franck; Guérin, Estelle; Guy, Julien; Jouault, Hélène; Lepelley, Pascale; Maynadié, Marc; Solly, Françoise; Ballon, Orianne Wagner; Preudhomme, Claude; Baruchel, André; Dombret, Hervé; Ifrah, Norbert; Béné, Marie C

    2017-12-07

    The assessment of minimal residual disease (MRD) in acute myeloblastic leukemia is of growing interest as a prognostic marker of patients' outcome. Multiparameter flow cytometry (MFC), tracking leukemia-associated immunophenotypic patterns, has been shown in several studies to be a useful tool to investigate MRD. Here, we report a multicenter prospective study which allowed to define a harmonized analysis strategy, as well as the efficacy of MFC MRD to predict outcome. This study included 276 patients, in 10 different MFC centers, of whom 268 had at least 1 MRD check point. The combination of a CD45, CD34, and CD33 backbone, with the addition of CD117, CD13, CD7, and CD15 in 2 five-color tubes allowed to define each patient's multiparameter immunophenotypic characteristics at diagnosis, according to a Boolean combination of gates. The same individual diagnosis gating strategy was then applied at each MRD time point for each patient. MRD levels were stratified according to log by log thresholds, from 5 × 10 -2 (the classical morphological threshold to define remission) down to MRD1) as well as when considering all time points together. Finally, MRD levels were independent of cytogenetics and allowed in fact to further stratify all cytogenetics risk groups. In summary, this multicenter study demonstrates that a simple combination of immunophenotypic markers successfully allows for the detection of MRD in acute myeloblastic leukemia patients, with a strong correlation to outcome. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Percutaneous Endoscopic Lumbar Reoperation for Recurrent Sciatica Symptoms: A Retrospective Analysis of Outcomes and Prognostic Factors in 94 Patients.

    Science.gov (United States)

    Wu, Junlong; Zhang, Chao; Lu, Kang; Li, Changqing; Zhou, Yue

    2018-01-01

    Recurrent symptoms of sciatica after previous surgical intervention is a relatively common and troublesome clinical problem. Percutaneous endoscopic lumbar decompression has been proved to be an effective method for recurrent lumbar disc herniation. However, the prognostic factors and outcomes of percutaneous endoscopic lumbar reoperation (PELR) for recurrent sciatica symptoms were still unknown. The purpose of this study was to evaluate the outcomes and prognostic factors of patients who underwent PELR for recurrent sciatica symptoms. From 2009 to 2015, 94 patients who underwent PELR for recurrent sciatica symptoms were enrolled. The primary surgeries include transforaminal lumbar interbody fusion (n = 16), microendoscopic discectomy (n = 31), percutaneous endoscopic lumbar decompression (PELD, n = 17), and open discectomy (n = 30). The mean follow-up period was 36 months, and 86 (91.5%) patients had obtained at least 24 months' follow-up. Of the 94 patients with adequate follow-up, 51 (54.3%) exhibited excellent improvement, 23 (24.5%) had good improvement, and 7 (7.4%) had fair improvement according to modified Macnab criteria. The average re-recurrence rate was 9.6%, with no difference among the different primary surgery groups (PELD, 3/17; microendoscopic discectomy, 2/31; open discectomy, 3/30; transforaminal lumbar interbody fusion, 1/16). There was a trend toward greater rates of symptom recurrence in the primary group of PELD who underwent percutaneous endoscopic lumbar reoperation compared with other groups, but this did not reach statistical significance (P > 0.05). Multivariate analysis suggested that age, body mass index, and surgeon level was independent prognostic factors. Obesity (hazard ratio 13.98, 95% confidence interval 3.394-57.57; P sciatica symptoms regardless of different primary operation type. Obesity, inferior surgeon level, and patient age older than 40 years were associated with a worse prognosis. Obesity was also a strong and

  4. Independence and Product Systems

    OpenAIRE

    Skeide, Michael

    2003-01-01

    Starting from elementary considerations about independence and Markov processes in classical probability we arrive at the new concept of conditional monotone independence (or operator-valued monotone independence). With the help of product systems of Hilbert modules we show that monotone conditional independence arises naturally in dilation theory.

  5. John Strong (1941 - 2006)

    CERN Multimedia

    Wickens, F

    Our friend and colleague John Strong was cruelly taken from us by a brain tumour on Monday 31st July, a few days before his 65th birthday John started his career working with a group from Westfield College, under the leadership of Ted Bellamy. He obtained his PhD and spent the early part of his career on experiments at Rutherford Appleton Laboratory (RAL), but after the early 1970s his research was focussed on experiments in CERN. Over the years he made a number of notable contributions to experiments in CERN: The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras to record the sparks in the spark chambers; He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems; He was responsible for the second level trigger system for the ALEPH detector and spent five years leading a team that designed and built the system, which ran for twelve years with only minor interventions. Following ALEPH he tur...

  6. Stirring Strongly Coupled Plasma

    CERN Document Server

    Fadafan, Kazem Bitaghsir; Rajagopal, Krishna; Wiedemann, Urs Achim

    2009-01-01

    We determine the energy it takes to move a test quark along a circle of radius L with angular frequency w through the strongly coupled plasma of N=4 supersymmetric Yang-Mills (SYM) theory. We find that for most values of L and w the energy deposited by stirring the plasma in this way is governed either by the drag force acting on a test quark moving through the plasma in a straight line with speed v=Lw or by the energy radiated by a quark in circular motion in the absence of any plasma, whichever is larger. There is a continuous crossover from the drag-dominated regime to the radiation-dominated regime. In the crossover regime we find evidence for significant destructive interference between energy loss due to drag and that due to radiation as if in vacuum. The rotating quark thus serves as a model system in which the relative strength of, and interplay between, two different mechanisms of parton energy loss is accessible via a controlled classical gravity calculation. We close by speculating on the implicati...

  7. Strong-interaction nonuniversality

    International Nuclear Information System (INIS)

    Volkas, R.R.; Foot, R.; He, X.; Joshi, G.C.

    1989-01-01

    The universal QCD color theory is extended to an SU(3) 1 direct product SU(3) 2 direct product SU(3) 3 gauge theory, where quarks of the ith generation transform as triplets under SU(3)/sub i/ and singlets under the other two factors. The usual color group is then identified with the diagonal subgroup, which remains exact after symmetry breaking. The gauge bosons associated with the 16 broken generators then form two massive octets under ordinary color. The interactions between quarks and these heavy gluonlike particles are explicitly nonuniversal and thus an exploration of their physical implications allows us to shed light on the fundamental issue of strong-interaction universality. Nonuniversality and weak flavor mixing are shown to generate heavy-gluon-induced flavor-changing neutral currents. The phenomenology of these processes is studied, as they provide the major experimental constraint on the extended theory. Three symmetry-breaking scenarios are presented. The first has color breaking occurring at the weak scale, while the second and third divorce the two scales. The third model has the interesting feature of radiatively induced off-diagonal Kobayashi-Maskawa matrix elements

  8. Prognostic Predictors for Ambulation in Thai Children With Cerebral Palsy Aged 2 to 18 Years.

    Science.gov (United States)

    Keeratisiroj, Orawan; Thawinchai, Nuanlaor; Siritaratiwat, Wantana; Buntragulpoontawee, Montana

    2015-11-01

    The objectives of this study were to determine prognostic predictors for ambulation among Thai children with cerebral palsy and identify their ambulatory status. A retrospective cohort study was performed at 6 special schools or hospitals for children with physical disabilities. The prognostic predictors for ambulation were analyzed by multivariable ordinal continuation ratio logistic regression. The 533 participants aged 2 to 18 years were divided into 3 groups: 186 with independent ambulation (Gross Motor Function Classification System [GMFCS I-II]), 71 with assisted ambulation (Gross Motor Function Classification System III), and 276 with nonambulation (Gross Motor Function Classification System IV-V). The significant positive predictors for ambulation were type of cerebral palsy (spastic diplegia, spastic hemiplegia, dyskinesia, ataxia, hypotonia, and mixed type), sitting independently at age 2 years, and eating independently. These predictors were used to develop clinical scoring for predicting the future ability to walk among Thai children with cerebral palsy. © The Author(s) 2015.

  9. Short and long term prognostic importance of regional dyskinesia versus akinesia in acute myocardial infarction

    DEFF Research Database (Denmark)

    Kjøller, E; Køber, L; Jørgensen, S

    2002-01-01

    the nine segment model, scoring 3 for hyperkinesia, 2 for normokinesia, 1 for hypokinesia, 0 for akinesia, and -1 for dyskinesia. Calculation of WMI either included information on dyskinesia or excluded this information by giving dyskinesia the same score as akinesia. MAIN OUTCOME MEASURES: Long term...... outcome (up to seven years) with respect to mortality. RESULTS: Dyskinesia occurred in 673 patients (10.8%). In multivariate analysis, WMI was an important prognostic factor, with a relative risk of 2.4 (95% confidence interval (CI), 2.2 to 2.7), while dyskinesia had no independent long term prognostic...... when WMI is estimated for prognostic purposes following acute myocardial infarction. DESIGN: Multicentre prospective study. PATIENTS: 6676 consecutive patients, screened one to six days after acute myocardial infarction in 27 Danish hospitals. INTERVENTIONS: WMI was measured in 6232 patients, applying...

  10. The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rolff, Hans Christian; Christensen, Ib Jarle; Vainer, Ben

    2016-01-01

    PURPOSE: To investigate the prognostic and predictive biomarker value of type IV collagen in colorectal cancer. EXPERIMENTAL DESIGN: Retrospective evaluation of two independent cohorts of patients with colorectal cancer included prospectively in 2004-2005 (training set) and 2006-2008 (validation...... and validation set, respectively. The prognostic impact was present both in patients with metastatic and nonmetastatic disease. The predictive value of the marker was investigated in stage II and III patients. In the training set, type IV collagen was prognostic both in the subsets of patients receiving...... set). Plasma samples were available from 297 (training set) and 482 (validation set) patients. Type IV collagen determinations were performed using an ELISA. From the training set, 222 tumors were available for IHC. Clinical and follow-up data were retrieved from patient files and national registries...

  11. Prognostic predictors for non-small cell lung cancer patients with brain metastasis after radiotherapy

    Directory of Open Access Journals (Sweden)

    Qiuhong FAN

    2008-06-01

    proved to be effective for NSCLC patients with BM. KPS, control of primary tumor, interval from the beginning of diagnostic to BM and solitary BM are independent prognostic factors. PI model can well predict the prognostic of patients with BM from NSCLC.

  12. Long-term performance of interstial fluid pressure and hypoxia as prognostic factors in cervix cancer

    International Nuclear Information System (INIS)

    Fyles, Anthony; Milosevic, Michael; Pintilie, Melania; Syed, Ami; Levin, Wilf; Manchul, Lee; Hill, Richard P.

    2006-01-01

    impact of HP 5 in addition to tumor size in node negative patients (HR 1.01, p = 0.06). These results were similar when local or distant relapse was used as an endpoint. Conclusions: These results confirm our initial finding of the strong independent prognostic impact of IFP for relapse and survival in patients with cervix cancer. In contrast, the independent prognostic impact of HP 5 is of borderline significance and is limited to patients without imaging evidence of nodal metastases. However, these findings do not diminish the biologic significance of hypoxia, or the role of hypoxia and IFP as biomarkers of treatment response and as therapeutic targets

  13. The prognostic value of AJCC staging in uveal melanoma is enhanced by adding chromosome 3 and 8q status

    DEFF Research Database (Denmark)

    Dogrusöz, Mehmet; Bagger, Mette; Van Duinen, Sjoerd G.

    2017-01-01

    PURPOSE. The American Joint Committee on Cancer (AJCC) staging system has been validated for use as a prognostic parameter in uveal melanoma (UM). We studied whether adding information regarding chromosome 3 and 8q status further enhances the prognostic value of this staging system. METHODS. We...... retrospectively studied a cohort of 522 patients who had been treated for UM in two different centers between 1999 and 2015. The mean follow-up time was 47.7 months. Cumulative incidence curves were generated and regression analyses were performed for different combinations of AJCC staging and chromosome status....... Multivariable regression analyses demonstrated that AJCC staging and chromosome 3 and 8q status contain independent information about survival status. CONCLUSIONS. Combining information on AJCC staging and chromosome 3 and 8q status allows a more accurate prognostication in UM. We conclude that the prognostic...

  14. The expression and prognostic significance of retinoic acid metabolising enzymes in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Gordon T Brown

    cohort and in those tumours which are mismatch repair proficient. CYP26B1 was independently prognostic in a multivariate model both in the whole patient cohort (HR = 1.177, 95%CI = 1.020-1.216, p = 0.026 and in mismatch repair proficient tumours (HR = 1.255, 95%CI = 1.073-1.467, p = 0.004.

  15. Cell-free DNA in healthy individuals, noncancerous disease and strong prognostic value in colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Appelt, Ane L; Pallisgaard, Niels

    2014-01-01

    of healthy controls with and without comorbidity (n = 70 and 100, respectively) were included. cfDNA was quantified by an in-house developed quantitative polymerase chain reaction from plasma samples drawn prior to the first cycle of chemotherapy and at time of progression. cfDNA levels were significantly...... higher in CRC compared to controls, with a clear capability for discriminating between the groups (receiver operation curve analysis; area under the curve 0.82, p ....8 months (95% CI 11.9-18.9; HR 2.52; 95% CI 1.54-4.13, p analysis showed a PFS HR of 1.4 (95% CI 1.1-1.7) for each increase in cfDNA quartile, p = 0.03 and 1.6 (1.3-2.0) for OS, p analysis with plasma KRAS...

  16. Tackling V&V for Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — We believe our approach to gathering and organizing prognostics V the descriptive text recorded proved on occasion to be insufficient to serve as a standalone...

  17. Prognostic Factors for Refractory Status Epilepticus

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2013-03-01

    Full Text Available Researchers at the Mayo Clinic, Rochester, MN studied the outcome and identified prognostic factors for refractory status epilepticus (RSE in 54 adult patients, median age 52 years [range 18-93].

  18. Detection and Prognostics on Low Dimensional Systems

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper describes the application of known and novel prognostic algorithms on systems that can be described by low dimensional, potentially nonlinear dynamics....

  19. Precursor Parameter Identification for IGBT Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Precursor parameters have been identified to enable development of a prognostic approach for insulated gate bipolar transistors (IGBT). The IGBT were subjected to...

  20. Distilling the Verification Process for Prognostics Algorithms

    Data.gov (United States)

    National Aeronautics and Space Administration — The goal of prognostics and health management (PHM) systems is to ensure system safety, and reduce downtime and maintenance costs. It is important that a PHM system...

  1. Metrics for Evaluating Performance of Prognostics Techniques

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics is an emerging concept in condition based maintenance (CBM) of critical systems. Along with developing the fundamentals of being able to confidently...

  2. Requirements Flowdown for Prognostics and Health Management

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics and Health Management (PHM) principles have considerable promise to change the game of lifecycle cost of engineering systems at high safety levels by...

  3. Evaluating Algorithm Performance Metrics Tailored for Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics has taken center stage in Condition Based Maintenance (CBM) where it is desired to estimate Remaining Useful Life (RUL) of a system so that remedial...

  4. Model-based Prognostics under Limited Sensing

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics is crucial to providing reliable condition-based maintenance decisions. To obtain accurate predictions of component life, a variety of sensors are often...

  5. Results of chemo-radiotherapy and prognostic factors of small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shikaura, Sachiko; Kawa, Sokichi; Yoshida, Masanori; Yonezu, Seibun (Kansai Medical School, Moriguchi, Osaka (Japan))

    We studied the therapeutic results and prognostic factors in 63 cases of small cell lung cancer (SCLC) experienced in our hospital over the past eight years. In the group initially treated with combination chemotherapy using COMP-VAD, the survival period was significantly prolonged. Use of adjuvant radiotherapy from the beginning had no effect on improvement in the survival period, but the period until local recurrences tended to be prolonged. Prognostic factors influencing survival were analyzed by the log rank test and generalized Wilcoxon test and multivariate analysis by the proportional hazard model of Cox. Statistical significance using univariate analysis was found for six factors (PS, clinical stage, LDH, albumin, treatment protocols, treatment response). The strong prognostic factors determined by multivariate analysis were, in the order of importance, chemotherapy protocol, initial PS, and treatment response. (author).

  6. Designing a Prognostic Scoring System for Predicting the Outcomes of Proximal Fifth Metatarsal Fractures at 20 Weeks

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Tahririan

    2015-03-01

    Full Text Available Background: Fractures of the proximal fifth metatarsal bone are among the most common fractures observed in the foot and their classification and management has been subject to much discussion and disagreement. In this study, we aim to identify and quantify the effect of possible predictors of the outcome of the treatment of proximal fifth metatarsal fractures. Methods: Patients with established proximal fifth metatarsal fractures were enrolled in this prospective cohort and the outcome of their treatment was assessed using the AOFAS mid foot scale at 6 and 20 weeks. Results: 143 patients were included in the study. Our study showed that displacement, weight and type III fractures were significant independent predictors of poor outcome at 6 weeks while at 20 weeks in addition to these factors, gender and diabetes mellitus were also shown to be significant independent predictors of poor outcome. A scoring system was designed by assigning weight to these factors and it was shown to be a strong predictor of outcome at 20 weeks. Conclusion: We recommend that our scoring system would help surgeons to decide whether patients’ prognostic factors are significant enough for him/her to opt for a surgical approach to treatment rather than a conservative approach.

  7. Vehicle Integrated Prognostic Reasoner (VIPR) Metric Report

    Science.gov (United States)

    Cornhill, Dennis; Bharadwaj, Raj; Mylaraswamy, Dinkar

    2013-01-01

    This document outlines a set of metrics for evaluating the diagnostic and prognostic schemes developed for the Vehicle Integrated Prognostic Reasoner (VIPR), a system-level reasoner that encompasses the multiple levels of large, complex systems such as those for aircraft and spacecraft. VIPR health managers are organized hierarchically and operate together to derive diagnostic and prognostic inferences from symptoms and conditions reported by a set of diagnostic and prognostic monitors. For layered reasoners such as VIPR, the overall performance cannot be evaluated by metrics solely directed toward timely detection and accuracy of estimation of the faults in individual components. Among other factors, overall vehicle reasoner performance is governed by the effectiveness of the communication schemes between monitors and reasoners in the architecture, and the ability to propagate and fuse relevant information to make accurate, consistent, and timely predictions at different levels of the reasoner hierarchy. We outline an extended set of diagnostic and prognostics metrics that can be broadly categorized as evaluation measures for diagnostic coverage, prognostic coverage, accuracy of inferences, latency in making inferences, computational cost, and sensitivity to different fault and degradation conditions. We report metrics from Monte Carlo experiments using two variations of an aircraft reference model that supported both flat and hierarchical reasoning.

  8. Metrics for Offline Evaluation of Prognostic Performance

    Directory of Open Access Journals (Sweden)

    Sankalita Saha

    2010-01-01

    Full Text Available Prognostic performance evaluation has gained significant attention in the past few years.Currently, prognostics concepts lack standard definitions and suffer from ambiguous and inconsistent interpretations. This lack of standards is in part due to the varied end-user requirements for different applications, time scales, available information, domain dynamics, etc. to name a few. The research community has used a variety of metrics largely based on convenience and their respective requirements. Very little attention has been focused on establishing a standardized approach to compare different efforts. This paper presents several new evaluation metrics tailored for prognostics that were recently introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. These metrics have the capability of incorporating probabilistic uncertainty estimates from prognostic algorithms. In addition to quantitative assessment they also offer a comprehensive visual perspective that can be used in designing the prognostic system. Several methods are suggested to customize these metrics for different applications. Guidelines are provided to help choose one method over another based on distribution characteristics. Various issues faced by prognostics and its performance evaluation are discussed followed by a formal notational framework to help standardize subsequent developments.

  9. Predicting Overall Survival After Stereotactic Ablative Radiation Therapy in Early-Stage Lung Cancer: Development and External Validation of the Amsterdam Prognostic Model

    Energy Technology Data Exchange (ETDEWEB)

    Louie, Alexander V., E-mail: Dr.alexlouie@gmail.com [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, Massachusetts (United States); Haasbeek, Cornelis J.A. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Mokhles, Sahar [Department of Cardio-Thoracic Surgery, Erasmus University Medical Center, Rotterdam (Netherlands); Rodrigues, George B. [Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Stephans, Kevin L. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Lagerwaard, Frank J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Palma, David A. [Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Videtic, Gregory M.M. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Warner, Andrew [Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Takkenberg, Johanna J.M. [Department of Cardio-Thoracic Surgery, Erasmus University Medical Center, Rotterdam (Netherlands); Reddy, Chandana A. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Maat, Alex P.W.M. [Department of Cardio-Thoracic Surgery, Erasmus University Medical Center, Rotterdam (Netherlands); Woody, Neil M. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Slotman, Ben J.; Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)

    2015-09-01

    Purpose: A prognostic model for 5-year overall survival (OS), consisting of recursive partitioning analysis (RPA) and a nomogram, was developed for patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). Methods and Materials: A primary dataset of 703 ES-NSCLC SABR patients was randomly divided into a training (67%) and an internal validation (33%) dataset. In the former group, 21 unique parameters consisting of patient, treatment, and tumor factors were entered into an RPA model to predict OS. Univariate and multivariate models were constructed for RPA-selected factors to evaluate their relationship with OS. A nomogram for OS was constructed based on factors significant in multivariate modeling and validated with calibration plots. Both the RPA and the nomogram were externally validated in independent surgical (n=193) and SABR (n=543) datasets. Results: RPA identified 2 distinct risk classes based on tumor diameter, age, World Health Organization performance status (PS) and Charlson comorbidity index. This RPA had moderate discrimination in SABR datasets (c-index range: 0.52-0.60) but was of limited value in the surgical validation cohort. The nomogram predicting OS included smoking history in addition to RPA-identified factors. In contrast to RPA, validation of the nomogram performed well in internal validation (r{sup 2}=0.97) and external SABR (r{sup 2}=0.79) and surgical cohorts (r{sup 2}=0.91). Conclusions: The Amsterdam prognostic model is the first externally validated prognostication tool for OS in ES-NSCLC treated with SABR available to individualize patient decision making. The nomogram retained strong performance across surgical and SABR external validation datasets. RPA performance was poor in surgical patients, suggesting that 2 different distinct patient populations are being treated with these 2 effective modalities.

  10. Prognostic significance of stress myocardial ECG-gated perfusion imaging in asymptomatic patients with diabetic chronic kidney disease on initiation of haemodialysis

    Energy Technology Data Exchange (ETDEWEB)

    Momose, Mitsuru; Kondo, Chisato; Kobayashi, Hideki; Kusakabe, Kiyoko [Tokyo Women' s Medical University, School of Medicine, Department of Radiology, Shinjuku-ku, Tokyo (Japan); Babazono, Tetsuya [Tokyo Women' s Medical University, School of Medicine, Diabetes Centre, Shinjuku-ku, Tokyo (Japan); Nakajima, Takatomo [Tokyo Women' s Medical University, School of Medicine, Department of Cardiology, Shinjuku-ku, Tokyo (Japan)

    2009-08-15

    Diabetic patients with chronic kidney disease (CKD) frequently develop cardiac events within several years of the initiation of haemodialysis. The present study assesses the prognostic significance of stress myocardial ECG-gated perfusion imaging (MPI) in patients with diabetic CKD requiring haemodialysis. Fifty-five asymptomatic patients with diabetic stage V CKD and no history of heart disease scheduled to start haemodialysis were enrolled in this study (56{+-}11 years old; 49 with type 2 diabetes mellitus). All patients underwent {sup 201}Tl stress ECG-gated MPI 1 month before or after the initiation of haemodialysis to assess myocardial involvement. We evaluated SPECT images using 17-segment defect scores graded on a 5-point scale, summed stress score (SSS) and summed difference scores (SDS). The patients were followed up for at least 2 years (42{+-}15 months) to determine coronary intervention (CI) and heart failure (HF) as soft events and acute myocardial infarction (AMI) and all causes of deaths as hard events. The frequencies of myocardial ischaemia, resting perfusion defects, low ejection fraction and left ventricular (LV) dilatation were 24,20,29 and 49%, respectively. Ten events (18%) developed during the follow-up period including four CI, one HF, one AMI and four sudden deaths. Multivariate Cox analysis selected SDS (p=0.0011) and haemoglobin A{sub 1c} (HbA{sub 1c}) (p=0.0076) as independent prognostic indicators for all events. Myocardial ischaemia, in addition to glycaemic control, is a strong prognostic marker for asymptomatic patients with diabetic CKD who are scheduled to start haemodialysis. Stress MPI is highly recommended for the management and therapeutic stratification of such patients. (orig.)

  11. Clinical and prognostic significance of plasma fibrinogen in lung cancer

    Directory of Open Access Journals (Sweden)

    Chen YS

    2014-01-01

    concentration (median, 19 months versus 35 months; P <0.001. In addition, a similar result was observed in 194 early stage NSCLC (stage I -IIIA (P <0.001. Univariate and multivariate analysis revealed that higher levels of fibrinogen (FIB≥4.20 g/L, age, distant metastases and pathological types were positively associated with shorter overall survival (OS. 3 In addition, there was a significant link between the elevation by more than 15% in the plasma fibrinogen level after receiving short-term chemotherapy and shorter overall survival (OS. Conclusion: 1 This study shows high plasma fibrinogen concentration is associated with lymph nodes or distant organ metastases in lung cancer. 2 Furthermore, our results indicate a significant relevance between high pre-treatment plasma fibrinogen concentration and poor prognosis in patients with lung cancer. 3 In addition, we find that the patients with a low plasma fibrinogen level will have a shorter OS if the plasma fibrinogen level increases significantly after receiving short-term chemotherapy. Interestingly, we also find that the patients with a high plasma fibrinogen level will have a longer OS if the plasma fibrinogen level decreases significantly after receiving short-term chemotherapy, which indicate the change of the plasma fibrinogen level after receiving short-term chemotherapy may be used as an independent prognostic factor.

  12. Prognostic markers of canine pyometra

    Directory of Open Access Journals (Sweden)

    M.C. Sant'Anna

    2014-12-01

    Full Text Available The pyometra is a disease that affects middle age and elderly female dogs during diestrus. Hormonal, microbiological, biochemical and hematological aspects are well described. However, few studies have evaluated the role of each in the prognosis of canine pyometra. The aim of this study was to identify markers associated with clinical worsening of dogs with pyometra. We prospectively evaluated 80 dogs with pyometra treated surgically. Group 1 consisted of dogs that were discharged within 48 hours after surgery and Group 2 consisted of those who required prolonged hospitalization or died. The findings of hematological, biochemical and blood lactate levels were compared between groups and variables such as bacterial multidrug resistance, systemic inflammatory response syndrome (SIRS, hyperlactatemia and increased creatinine were analyzed through the dispersion of frequencies between groups. Among the variables studied, the presence of SIRS and elevated serum creatinine >2.5mg/mL were effective in predicting the worsening of the disease and can be used as prognostic markers of canine pyometra.

  13. Frictional Coulomb drag in strong magnetic fields

    DEFF Research Database (Denmark)

    Bønsager, Martin Christian; Flensberg, Karsten; Hu, Ben Yu-Kuang

    1997-01-01

    A treatment of frictional Coulomb drag between two two-dimensional electron layers in a strong perpendicular magnetic field, within the independent electron picture, is presented. Assuming fully resolved Landau levels, the linear response theory expression for the transresistivity rho(21) is eval......A treatment of frictional Coulomb drag between two two-dimensional electron layers in a strong perpendicular magnetic field, within the independent electron picture, is presented. Assuming fully resolved Landau levels, the linear response theory expression for the transresistivity rho(21......) is evaluated using diagrammatic techniques. The transresistivity is given by an integral over energy and momentum transfer weighted by the product of the screened interlayer interaction and the phase space for scattering events. We demonstrate, by a numerical analysis of the transresistivity, that for well...

  14. Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network

    DEFF Research Database (Denmark)

    Hoster, Eva; Klapper, Wolfram; Hermine, Olivier

    2014-01-01

    PURPOSE: Mantle-cell lymphoma (MCL) is a distinct B-cell lymphoma associated with poor outcome. In 2008, the MCL International Prognostic Index (MIPI) was developed as the first prognostic stratification tool specifically directed to patients with MCL. External validation was planned...... to be performed on the cohort of the two recently completed randomized trials of the European MCL Network. PATIENTS AND METHODS: Data of 958 patients with MCL (median age, 65 years; range, 32 to 87 years) treated upfront in the trials MCL Younger or MCL Elderly were pooled to assess the prognostic value of MIPI.......9) and 2.6 (2.0 to 3.3), respectively. MIPI was similarly prognostic for TTF. All four clinical baseline characteristics constituting the MIPI, age, performance status, lactate dehydrogenase level, and WBC count, were confirmed as independent prognostic factors for OS and TTF. The validity of MIPI...

  15. Are Independent Fiscal Institutions Really Independent?

    Directory of Open Access Journals (Sweden)

    Slawomir Franek

    2015-08-01

    Full Text Available In the last decade the number of independent fiscal institutions (known also as fiscal councils has tripled. They play an important oversight role over fiscal policy-making in democratic societies, especially as they seek to restore public finance stability in the wake of the recent financial crisis. Although common functions of such institutions include a role in analysis of fiscal policy, forecasting, monitoring compliance with fiscal rules or costing of spending proposals, their roles, resources and structures vary considerably across countries. The aim of the article is to determine the degree of independence of such institutions based on the analysis of the independence index of independent fiscal institutions. The analysis of this index values may be useful to determine the relations between the degree of independence of fiscal councils and fiscal performance of particular countries. The data used to calculate the index values will be derived from European Commission and IMF, which collect sets of information about characteristics of activity of fiscal councils.

  16. Prognostic significance of standardized uptake value on preoperative 18F-FDG PET/CT in patients with ampullary adenocarcinoma

    International Nuclear Information System (INIS)

    Choi, Hye Jin; Kang, Chang Moo; Lee, Woo Jung; Jo, Kwanhyeong; Lee, Jong Doo; Lee, Jae-Hoon; Ryu, Young Hoon

    2015-01-01

    The purpose of this study was to investigate the prognostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with ampullary adenocarcinoma (AAC) after curative surgical resection. Fifty-two patients with AAC who had undergone 18 F-FDG PET/CT and subsequent curative resections were retrospectively enrolled. The maximum standardized uptake value (SUV max ) and tumor to background ratio (TBR) were measured on 18 F-FDG PET/CT in all patients. The prognostic significances of PET/CT parameters and clinicopathologic factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. Of the 52 patients, 19 (36.5 %) experienced tumor recurrence during the follow-up period and 18 (35.8 %) died. The 3-year RFS and OS were 62.3 and 61.5 %, respectively. Preoperative CA19-9 level, tumor differentiation, presence of lymph node metastasis, SUV max , and TBR were significant prognostic factors for both RFS and OS (p < 0.05) on univariate analyses, and patient age showed significance only for predicting RFS (p < 0.05). On multivariate analyses, SUV max and TBR were independent prognostic factors for RFS, and tumor differentiation, SUV max , and TBR were independent prognostic factors for OS. SUV max and TBR on preoperative 18 F-FDG PET/CT are independent prognostic factors for predicting RFS and OS in patients with AAC; patients with high SUV max (>4.80) or TBR (>1.75) had poor survival outcomes. The role of and indications for adjuvant therapy after curative resection of AAC are still unclear. 18 F-FDG uptake in the primary tumor could provide additive prognostic information for the decision-making process regarding adjuvant therapy. (orig.)

  17. Prognostic Model to Predict Post-Autologous Stem-Cell Transplantation Outcomes in Classical Hodgkin Lymphoma.

    Science.gov (United States)

    Chan, Fong Chun; Mottok, Anja; Gerrie, Alina S; Power, Maryse; Nijland, Marcel; Diepstra, Arjan; van den Berg, Anke; Kamper, Peter; d'Amore, Francesco; d'Amore, Alexander Lindholm; Hamilton-Dutoit, Stephen; Savage, Kerry J; Shah, Sohrab P; Connors, Joseph M; Gascoyne, Randy D; Scott, David W; Steidl, Christian

    2017-11-10

    Purpose Our aim was to capture the biology of classical Hodgkin lymphoma (cHL) at the time of relapse and discover novel and robust biomarkers that predict outcomes after autologous stem-cell transplantation (ASCT). Materials and Methods We performed digital gene expression profiling on a cohort of 245 formalin-fixed, paraffin-embedded tumor specimens from 174 patients with cHL, including 71 with biopsies taken at both primary diagnosis and relapse, to investigate temporal gene expression differences and associations with post-ASCT outcomes. Relapse biopsies from a training cohort of 65 patients were used to build a gene expression-based prognostic model of post-ASCT outcomes (RHL30), and two independent cohorts were used for validation. Results Gene expression profiling revealed that 24% of patients exhibited poorly correlated expression patterns between their biopsies taken at initial diagnosis and relapse, indicating biologic divergence. Comparative analysis of the prognostic power of gene expression measurements in primary versus relapse specimens demonstrated that the biology captured at the time of relapse contained superior properties for post-ASCT outcome prediction. We developed RHL30, using relapse specimens, which identified a subset of high-risk patients with inferior post-ASCT outcomes in two independent external validation cohorts. The prognostic power of RHL30 was independent of reported clinical prognostic markers (both at initial diagnosis and at relapse) and microenvironmental components as assessed by immunohistochemistry. Conclusion We have developed and validated a novel clinically applicable prognostic assay that at the time of first relapse identifies patients with unfavorable post-ASCT outcomes. Moving forward, it will be critical to evaluate the clinical use of RHL30 in the context of positron emission tomography-guided response assessment and the evolving cHL treatment landscape.

  18. A robust gene expression-based prognostic risk score predicts overall survival of lung adenocarcinoma patients.

    Science.gov (United States)

    Chen, En-Guo; Wang, Pin; Lou, Haizhou; Wang, Yunshan; Yan, Hong; Bi, Lei; Liu, Liang; Li, Bin; Snijders, Antoine M; Mao, Jian-Hua; Hang, Bo

    2018-01-23

    Identification of reliable predictive biomarkers and new therapeutic targets is a critical step for significant improvement in patient outcomes. Here, we developed a multi-step bioinformatics analytic strategy to mine large omics and clinical data to build a prognostic scoring system for predicting the overall survival (OS) of lung adenocarcinoma (LuADC) patients. In latter we first identified 1327 significantly and robustly deregulated genes, 600 of which were significantly associated with the OS of LuADC patients. Gene co-expression network analysis revealed the biological functions of these 600 genes in normal lung and LuADCs, which were found to be enriched for cell cycle-related processes, blood vessel development, cell-matrix adhesion and metabolic processes. Finally, we implemented a multiple resampling method combined with Cox regression analysis to identify a 27-gene signature associated with OS, and then created a prognostic scoring system based on this signature. This scoring system robustly predicted OS of LuADC patients in 100 sampling test sets and was further validated in four independent LuADC cohorts. In addition, in comparison to other existing prognostic gene signatures published in the literature, our signature was significantly superior in predicting OS of LuADC patients. In summary, our multi-omics and clinical data integration study created a 27-gene prognostic risk score that can predict OS of LuADC patients independent of age, gender and clinical stage. This score could guide therapeutic selection and allow stratification in clinical trials.

  19. Clinical determinants and prognostic significance of the electrocardiographic strain pattern in chronic kidney disease patients.

    Science.gov (United States)

    Cordeiro, Antonio C; Moraes, Aline A I; Cerutti, Virginia; França, Faustino; Quiroga, Borja; Amodeo, Celso; Picotti, Juliano C; Dutra, Lucas V; Rodrigues, Gabriel D; Amparo, Fernanda C; Lindholm, Bengt; Carrero, Juan Jesús

    2014-05-01

    The electrocardiographic (ECG) strain pattern (Strain) is a marker of left ventricular hypertrophy (LVH) severity that provides additional prognostic information beyond echocardiography (ECHO) in the community level. We sought to evaluate its clinical determinants and prognostic usefulness in chronic kidney disease (CKD) patients. We evaluated 284 non-dialysis-dependent patients with CKD stages 3 to 5 (mean age, 61 years [interquartile range, 53-67 years]; 62% men). Patients were followed for 23 months (range, 13-32 months) for cardiovascular (CV) events and/or death. Strain patients (n = 37; 13%) were using more antihypertensive drugs, had higher prevalence of peripheral vascular disease and smoking, and higher levels of C-reactive protein, cardiac troponin, and brain natriuretic peptide (BNP). The independent predictors of Strain were: left ventricular mass index (LVMI), BNP, and smoking. During follow-up, there were 44 cardiovascular events (fatal and non-fatal) and 22 non-CV deaths; and Strain was associated with a worse prognosis independently of LVMI. Adding Strain to a prognostic model of LVMI improved in 15% the risk discrimination for the composite endpoint and in 12% for the CV events. Strain associates with CV risk factors and adds prognostic information over and above that of ECHO-assessed LVMI. Its routine screening may allow early identification of high risk CKD patients. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  20. Histology-Based Expression Profiling Yields Novel Prognostic Markers in Human Glioblastoma

    Science.gov (United States)

    Dong, Shumin; Nutt, Catherine L.; Betensky, Rebecca A.; Stemmer-Rachamimov, Anat O.; Denko, Nicholas C.; Ligon, Keith L.; Rowitch, David H.; Louis, David N.

    2006-01-01

    Although the prognosis for patients with glioblastoma is poor, survival is variable, with some patients surviving longer than others. For this reason, there has been longstanding interest in the identi-fication of prognostic markers for glioblastoma. We hypothesized that specific histologic features known to correlate with malignancy most likely express molecules that are directly related to the aggressive behavior of these tumors. We further hypothesized that such molecules could be used as biomarkers to predict behavior in a manner that might add prognostic power to sole histologic observation of the feature. We reasoned that perinecrotic tumor cell palisading, which denotes the most aggressive forms of malignant gliomas, would be a striking histologic feature on which to test this hypothesis. We therefore used laser capture microdissection and oligonucleotide arrays to detect molecules differentially expressed in perinecrotic palisades. A set of RNAs (including POFUT2, PTDSR, PLOD2, ATF5, and HK2) that were differentially expressed in 3 initially studied, micro-dissected glioblastomas also provided prognostic information in an independent set of 28 glioblastomas that did not all have perinecrotic palisades. On validation in a second, larger independent series, this approach could be applied to other human glioma types to derive tissue biomarkers that could offer ancillary prognostic and predictive information alongside standard histopathologic examination. PMID:16254489

  1. PAI-1 and EGFR expression in adult glioma tumors: toward a molecular prognostic classification

    International Nuclear Information System (INIS)

    Muracciole, Xavier; Romain, Sylvie; Dufour, Henri; Palmari, Jacqueline; Chinot, Olivier; Ouafik, L'Houcine; Grisoli, Francois; Figarella-Branger, Dominique; Martin, Pierre-Marie

    2002-01-01

    Purpose: Molecular classification of gliomas is a major challenge in the effort to improve therapeutic decisions. The plasminogen activator system, including plasminogen activator inhibitor type 1 (PAI-1), plays a key role in tumor invasion and neoangiogenesis. Epidermal growth factor receptor (EGFR) is involved in the control of proliferation. The contribution of PAI-1 and EGFR to the survival of gliomas was retrospectively investigated. Methods and Materials: Fifty-nine adult gliomas treated by neurosurgery and conventional irradiation were analyzed, including 9 low-grade (2) and 50 high-grade (3-4) tumors (WHO classification). PAI-1 was measured on cytosols and EGFR on solubilized membranes using ELISA methods. Results: High PAI-1 levels were strongly associated with high histologic grade (p<0.001) and histologic necrosis (p<0.001). PAI-1 also correlated positively with patient age (p=0.05) and negatively with Karnofsky index (p=0.01). By univariate analysis of the high-grade population, higher PAI-1 (p<0.0001) and EGFR values (p=0.02) were associated with shorter overall survival. Only PAI-1 was an independent factor in multivariate analysis. Grade 3 tumors with low PAI-1 (100% 3-year overall survival rate) presented the same clinical outcome as the low-grade tumors. Conclusions: In this prognostic study, PAI-1 and EGFR expression revealed similarities and differences between high-grade gliomas that were not apparent by traditional clinical criteria. These data strongly support that biologic factors should be included in glioma classification and the design of clinical trials to treat more homogeneous populations

  2. Clinical implications of six inflammatory biomarkers as prognostic indicators in Ewing sarcoma

    Directory of Open Access Journals (Sweden)

    Li YJ

    2017-09-01

    Full Text Available Yong-Jiang Li, Xi Yang, Wen-Biao Zhang, Cheng Yi, Feng Wang, Ping Li Department of Oncology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil–lymphocyte ratio (NLR, platelet–lymphocyte ratio (PLR, Glasgow Prognostic Score (GPS, C-reactive protein to albumin ratio (CRP/Alb ratio, lymphocyte–monocyte ratio (LMR, and neutrophil–platelet score (NPS, were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC analysis was generated to determine optimal cutoff values; areas under the curves (AUCs were assessed to show the discriminatory ability of the biomarkers; Kaplan–Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005, GPS (HR 2.27, P=0.006, NLR (HR 2.07, P=0.013, and PLR (HR 1.85, P=0.032 were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and

  3. Prognostic value of Ki67 expression in HR-negative breast cancer before and after neoadjuvant chemotherapy.

    Science.gov (United States)

    Tan, Qi-Xing; Qin, Qing-Hong; Yang, Wei-Ping; Mo, Qin-Guo; Wei, Chang-Yuan

    2014-01-01

    Immunohistochemical (IHC) expression of Ki67 has been identified as a prognostic and predictive marker in hormone receptor (HR)-positive breast cancer, however, there is little evidence of the association of Ki67 with prognosis in HR-negative patients. We aimed to assess the benefit of Ki67 assessment in HR-negative breast cancers after neoadjuvant chemotherapy (NAC). In the present study, a total of 183 HR-negative breast cancer patients with Stage II to III that treated with anthracycline and/or taxane-based neoadjuvant chemotherapy between 2004 and 2011 were retrospectively analyzed. Endocrine therapy and trastuzumab was not administered to any patients in this study. Clinical and pathological features of the patients with breast cancer were retrieved from the hospital records. Predictive factors for NAC response and survival were analyzed. Of the 183 patients, 122 (66.6%) were HR- HER2+, and 61 (33.3%) were triple-negative. The clinical response rates were similar across breast cancer subtype. Patients whose tumors contained high Ki67 expression effectively responded to NAC. Ki67 labeling index was a predictive marker for pathologic complete response (pCR). Ki67 expression showed a positive correlation with HER2 status, tumor size, lymph node status, lymphovascular invasion and tumor grade. Furthermore, high Ki67 expression in post-treatment tumors was strongly correlated with poor disease-free survival (DFS), but no correlation of Ki-67 expression with overall survival (OS) was observed. Our results suggest that Ki67 expression in HR-negative breast cancer may improve the assessment of pathological response after NAC, and Ki67 score in residual tumor was an independent prognosticator for DFS in the HR-negative breast cancer patients.

  4. Prognostic implications of tissue Doppler imaging-derived e/ea ratio in acute heart failure patients.

    Science.gov (United States)

    Santas, Enrique; García-Blas, Sergio; Miñana, Gema; Sanchis, Juan; Bodí, Vicent; Escribano, David; Muñoz, Jaime; Chorro, Francisco J; Núñez, Julio

    2015-02-01

    Tissue Doppler-derived transmitral to mitral annular early diastolic velocity ratio (E/Ea), as a noninvasive estimation of left ventricular (LV) filling pressures, is a strong prognosticator in various cardiac scenarios including chronic heart failure; nevertheless, its utility for risk stratification in the whole spectrum of acute heart failure (AHF) patients remains elusive. Thus, the aim of this study was to determine the association between E/Ea ratio and 1-year mortality in nonselected patients with AHF. The study included 417 consecutive patients admitted for AHF. Twenty-two patients were excluded due to nonaccurate Ea measurements, leaving the final sample to be 395 patients. E-wave, septal, and lateral Ea velocities were measured following initial stabilization and according to current recommendations. The association of mean E/Ea ratio with all-cause mortality was assessed using Cox regression analysis. At a median follow-up of 306 days (interquartile range, 118-564), 89 deaths (22.5%) were registered. Mean age and E/Ea ratio were 72 ± 11.5 and 20 ± 3. Proportion of LV ejection fraction ≥50% was 47%. In multivariate analysis, after adjusting for well-known prognostic factors, including natriuretic peptides, E/Ea ratio was linearly associated with an increase risk of all-cause mortality (HR 1.04, 95% CI 1.03-1.05; P < 0.001, per increase in one unit of E/Ea). The threshold of risk was identified above 20. No significant interactions among the most important subgroups were found. In AHF patients, tissue Doppler imaging derived E/Ea ratio is independently associated with an increased risk of all-cause mortality. © 2014, Wiley Periodicals, Inc.

  5. Determinants and Prognostic Impact of Heart Failure and Left Ventricular Ejection Fraction in Acute Coronary Syndrome Settings.

    Science.gov (United States)

    Agra Bermejo, Rosa; Cordero, Alberto; García-Acuña, José M; Gómez Otero, Inés; Varela Román, Alfonso; Martínez, Álvaro; Álvarez Rodríguez, Leyre; Abou-Jokh, Charigan; Rodríguez-Mañero, Moisés; Cid Álvarez, Belén; López-Palop, Ramón; Carrillo, Pilar; González-Juanatey, José R

    2017-12-15

    Contemporary data on the incidence and prognosis of heart failure (HF) and the influence of left ventricular ejection fraction (LVEF) in the setting of acute coronary syndrome (ACS) are scant. The aim of this study was to examine the relationship between LVEF and HF with long-term prognosis in a cohort of patients with ACS. This is a retrospective observational study of 6208 patients consecutively admitted for ACS to 2 different Spanish hospitals. Baseline characteristics were examined and a follow-up period was established for registration of death and HF rehospitalization as the primary endpoint. Among the study participants, 5064 had ACS without HF during hospitalization: 290 (5.8%) had LVEF<40%, 540 (10.6%) LVEF 40% to 49%, and 4234 (83.6%) LVEF ≥ 50%. The remaining 1144 patients developed HF in the acute phase: 395 (34.6%) had LVEF<40%, 251 (21.9%) LVEF 40% to 49%, and 498 (43.5%) LVEF ≥ 50%. Patients with LVEF 40% to 49% had a demographic and clinical profile with intermediate features between the LVEF <40% and LVEF ≥ 50% groups. Kaplan-Meier curves showed that mortality and HF readmissions were statistically different depending on LVEF in the non-HF group but not in the HF group. Left ventricular ejection fraction ≥ 50% was an independent prognostic factor in the non-HF group only. In ACS, long-term prognosis is considerably worse in patients who develop HF during hospitalization than in patients without HF, irrespective of LVEF. This parameter is a strong prognostic predictor only in patients without HF. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  6. Central Bank independence

    Directory of Open Access Journals (Sweden)

    Vasile DEDU

    2012-08-01

    Full Text Available In this paper we present the key aspects regarding central bank’s independence. Most economists consider that the factor which positively influences the efficiency of monetary policy measures is the high independence of the central bank. We determined that the National Bank of Romania (NBR has a high degree of independence. NBR has both goal and instrument independence. We also consider that the hike of NBR’s independence played an important role in the significant disinflation process, as headline inflation dropped inside the targeted band of 3% ± 1 percentage point recently.

  7. Prognostic models in male breast cancer.

    Science.gov (United States)

    van der Pol, Carmen C; Lacle, Miangela M; Witkamp, Arjen J; Kornegoor, Robert; Miao, Hui; Bouchardy, Christine; Borel Rinkes, Inne; van der Wall, Elsken; Verkooijen, Helena M; van Diest, Paul J

    2016-11-01

    Breast cancer in men is uncommon; it accounts for 1 % of all patients with primary breast cancer. Its treatment is mostly extrapolated from its female counterpart. Accurate predictions are essential for adjuvant systemic treatment decision-making and informing patients. Several predictive models are available for female breast cancer (FBC) including the Morphometric Prognostic Index (MPI), Nottingham Prognostic Index (NPI), Adjuvant! Online and Predict. The aim of this study was to examine and compare the prognostic performance of these models for male breast cancer (MBC). The population of this study consists of 166 MBC patients. The prognostic scores of the patients are categorized by good, (moderate) and poor, defined by the test itself (MPI and NPI) or based on tertiles (Adjuvant! Online and Predict). Survival according to prognostic score was compared by Kaplan-Meier analysis and differences were tested by logRank. The prognostic performances were evaluated with C-statistics. Calibration was done with the aim to estimate to what extent the survival rates predicted by Predict were similar to the observed survival rates. All prediction models were capable of discriminating between good, moderate and poor survivors. P-values were highly significant. Comparison between the models using C-statistics (n = 88) showed equal performance of MPI (0.67), NPI (0.68), Adjuvant! Online (0.69) and Predict (0.69). Calibration of Predict showed overestimation for MBC patients. In conclusion, MPI, NPI, Adjuvant! and Predict prognostic models, originally developed and validated for FBC patients, also perform quite well for MBC patients.

  8. Mantle cell lymphoma: prognostic capacity of the Follicular Lymphoma International Prognostic Index

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Christensen, Bjarne Egelund; Pedersen, Niels Tinggaard

    2006-01-01

    The International Prognostic Index (IPI) is the most commonly used prognostic model for mantle cell lymphoma (MCL). However, the prognostic value of the IPI is limited. The recently published Follicular Lymphoma International Prognostic Index (FLIPI) is built on variables, which are pertinent...... to MCL. This study was conducted to evaluate the prognostic value of FLIPI in a population-based series of 93 patients with MCL diagnosed in a 7-year period. End points of the study were response to therapy, overall survival, and disease-free survival (DFS) according to the IPI and FLIPI. Applied...... to the whole series, the FLIPI identified three risk groups with markedly different outcome with 5-year overall survival rates of 65%, 42%, and 8% respectively. Notably, the high-risk group comprised 53% of patients. In contrast, the IPI only allocated 16% of cases to the high-risk group and had a lower...

  9. Leptomeningeal carcinomatosis: prognostic implications of clinical and cerebrospinal fluid features.

    Science.gov (United States)

    Bruna, Jordi; González, Laura; Miró, Júlia; Velasco, Roser; Gil, Miguel; Tortosa, Avelina

    2009-01-15

    Leptomeningeal carcinomatosis (LC) represents a devastating complication of systemic cancer, and patients with LC have a dismal prognosis and increased mortality. The few studies that have focused on the evaluation of prognostic factors in patients with LC have resulted in contradictory results. Thus, the treatment of LC remains controversial, and no straightforward guidelines exist in the literature. The objective of the current study was to identify prognostic markers related to LC survival to better select patients who are eligible for intensive treatment. Seventy patients who had a diagnosis of LC were reviewed, and clinical data, cerebrospinal fluid (CSF) parameters, tumor-related characteristics, and treatment information were registered. The impact of single parameters on overall survival was determined by both univariate and multivariate analyses. The multivariate analysis revealed that Radiation Therapy Oncology Group scoreor=2.7 mmol/L (P=.001), the presence of infratentorial symptoms at onset (P=.026), and intrathecal treatment (P<.001) were associated independently with longer overall survival in patients with LC. In addition, the same clinical factors also predicted response to treatment in such patients. The predictive factors for patients with LC that were identified in this study could help to better select patients who are more likely to benefit from chemotherapy. Copyright (c) 2009 American Cancer Society.

  10. Prognostic value of 18F-FDG PET image-based parameters in oesophageal cancer and impact of tumour delineation methodology

    International Nuclear Information System (INIS)

    Hatt, Mathieu; Visvikis, Dimitris; Tixier, Florent; Albarghach, Nidal M.; Pradier, Olivier; Cheze-le Rest, Catherine

    2011-01-01

    18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) image-derived parameters, such as standardized uptake value (SUV), functional tumour length (TL) and tumour volume (TV) or total lesion glycolysis (TLG), may be useful for determining prognosis in patients with oesophageal carcinoma. The objectives of this work were to investigate the prognostic value of these indices in oesophageal cancer patients undergoing combined chemoradiotherapy treatment and the impact of TV delineation strategies. A total of 45 patients were retrospectively analysed. Tumours were delineated on pretreatment 18 F-FDG scans using adaptive threshold and automatic (fuzzy locally adaptive Bayesian, FLAB) methodologies. The maximum standardized uptake value (SUV max ), SUV peak , SUV mean , TL, TV and TLG were computed. The prognostic value of each parameter for overall survival was investigated using Kaplan-Meier and Cox regression models for univariate and multivariate analyses, respectively. Large differences were observed between methodologies (from -140 to +50% for TV). SUV measurements were not significant prognostic factors for overall survival, whereas TV, TL and TLG were, irrespective of the segmentation strategy. After multivariate analysis including standard tumour staging, only TV (p < 0.002) and TL (p = 0.042) determined using FLAB were independent prognostic factors. Whereas no SUV measurement was a significant prognostic factor, TV, TL and TLG were significant prognostic factors for overall survival, irrespective of the delineation methodology. Only functional TV and TL derived using FLAB were independent prognostic factors, highlighting the need for accurate and robust PET tumour delineation tools for oncology applications. (orig.)

  11. Prognostic DNA Methylation Markers for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Siri H. Strand

    2014-09-01

    Full Text Available Prostate cancer (PC is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181 and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC.

  12. Concordance for prognostic models with competing risks

    DEFF Research Database (Denmark)

    Wolbers, Marcel; Blanche, Paul; Koller, Michael T

    2014-01-01

    The concordance probability is a widely used measure to assess discrimination of prognostic models with binary and survival endpoints. We formally define the concordance probability for a prognostic model of the absolute risk of an event of interest in the presence of competing risks and relate i...... of the working model. We further illustrate the methods by computing the concordance probability for a prognostic model of coronary heart disease (CHD) events in the presence of the competing risk of non-CHD death.......The concordance probability is a widely used measure to assess discrimination of prognostic models with binary and survival endpoints. We formally define the concordance probability for a prognostic model of the absolute risk of an event of interest in the presence of competing risks and relate...... it to recently proposed time-dependent area under the receiver operating characteristic curve measures. For right-censored data, we investigate inverse probability of censoring weighted (IPCW) estimates of a truncated concordance index based on a working model for the censoring distribution. We demonstrate...

  13. Prognostic modeling in pediatric acute liver failure.

    Science.gov (United States)

    Jain, Vandana; Dhawan, Anil

    2016-10-01

    Liver transplantation (LT) is the only proven treatment for pediatric acute liver failure (PALF). However, over a period of time, spontaneous native liver survival is increasingly reported, making us wonder if we are overtransplanting children with acute liver failure (ALF). An effective prognostic model for PALF would help direct appropriate organ allocation. Only patients who would die would undergo LT, and those who would spontaneously recover would avoid unnecessary LT. Deriving and validating such a model for PALF, however, encompasses numerous challenges. In particular, the heterogeneity of age and etiology in PALF, as well as a lack of understanding of the natural history of the disease, contributed by the availability of LT has led to difficulties in prognostic model development. Several prognostic laboratory variables have been identified, and the incorporation of these variables into scoring systems has been attempted. A reliable targeted prognostic model for ALF in Wilson's disease has been established and externally validated. The roles of physiological, immunological, and metabolomic parameters in prognosis are being investigated. This review discusses the challenges with prognostic modeling in PALF and describes predictive methods that are currently available and in development for the future. Liver Transplantation 22 1418-1430 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

  14. Terminal-stage prognostic analysis in candidemia.

    Science.gov (United States)

    Takuma, Takahiro; Shoji, Hisashi; Niki, Yoshihito

    2015-05-01

    Candidemia has an extremely high mortality rate but is not always the direct cause of death. Therefore, determining the effect of candidemia on death is extremely difficult. We investigated prognostic factors in patients with culture-proven candidemia at 2 Japanese university teaching hospitals from April 2009 through May 2013. To examine the effects of comorbid conditions, the Charlson comorbidity index was determined, and patients were subjectively classified into 3 clinical prognostic stages (terminal [death expected within 1 month], semiterminal [death expected within 6 months], and nonterminal [expected to live more than 6 months]). The Cox proportional hazard model was used for univariate and multivariate analyses of factors possibly affecting survival. On univariate analysis, factors identified as associated with an increased mortality rate were: admission to an internal medicine department, Candida glabrata, immunosuppression, hypotension, hypoxemia, and a terminal prognostic stage. Factors associated with a decreased mortality rate were: serum albumin, endophthalmitis investigation, and nonterminal prognostic stage. The mortality rate was significantly related to the prognostic stage on multivariate analysis (P candidemia. More important than candidemia in causing the deaths of patients with candidemia were the patients' background and comorbidity status. Therefore, rigorous methods should be used when investigating causes of death in terminally ill patients with candidemia. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  15. Prognostic role of tumor-associated macrophages and angiogenesis in classical Hodgkin lymphoma.

    Science.gov (United States)

    Panico, Luigi; Ronconi, Fioravante; Lepore, Marianna; Tenneriello, Valentina; Cantore, Nicola; Dell'Angelo, Antonietta Carmela; Ferbo, Umberto; Ferrara, Felicetto

    2013-11-01

    We studied by immunohistochemistry CD68 + tumor-associated macrophages (TAMs) and angiogenesis in 121 consecutive cases of uniformly treated classical Hodgkin lymphoma (cHL). High TAM count showed a significant correlation with age ≥ 45, mixed cellularity subtype and high β₂-microglobulin level. Vessel density (VD) was unrelated to clinicopathological features, while a significant correlation was found between TAM count and VD. Patients with high TAMs showed a trend toward reduced progression-free survival and significantly shorter overall survival (OS). No correlation was found between VD and survival. At multivariate analysis, bulky disease was an independent predictor of reduced progression-free survival, while independent adverse prognostic factors for OS were male sex, age ≥ 45, advanced stage and bulky disease. High TAM count results in an adverse overall outcome in cHL and is significantly correlated to VD. Since VD has no prognostic relevance, the adverse effect of TAMs is presumably unrelated to angiogenesis.

  16. Survival and prognostic factors in patients treated with stereotactic radiotherapy for brain metastases

    DEFF Research Database (Denmark)

    Leth, Thomas; Oettingen, Gorm von; Lassen-Ramshad, Yasmin A.

    2015-01-01

    Abstract Background. Stereotactic radiation therapy (SRT) of brain metastases is used with good effect around the world, but no consensus exists regarding which prognostic factors that are related to favourable or unfavourable prognosis after the treatment. A better definition of these factors...... will ensure a more precise application of the treatment. Material and methods. A consecutive cohort of the 198 patients treated for brain metastases with SRT without concurrent whole-brain radiation therapy at our department from 2001 to 2012 was retrospectively analysed. Results. Median survival was seven...... months and median time to clinical cerebral progression was eight months. The multivariate analysis revealed age ≥ 65 years, Performance Status ≥ 2, extracranial metastases and size of metastasis > 20 mm as independent prognostic factors related to shorter survival. No factors were independently related...

  17. Systematic Evaluation of the Prognostic Impact and Intratumour Heterogeneity of Clear Cell Renal Cell Carcinoma Biomarkers

    DEFF Research Database (Denmark)

    Gulati, Sakshi; Martinez, Pierre; Joshi, Tejal

    2014-01-01

    of published biomarkers to predict the survival of patients with clear cell kidney cancer in an independent patient cohort. Only one molecular test adds prognostic information to routine clinical assessments. This marker showed good and poor prognosis results within most individual cancers. Future biomarkers......BackgroundCandidate biomarkers have been identified for clear cell renal cell carcinoma (ccRCC) patients, but most have not been validated. ObjectiveTo validate published ccRCC prognostic biomarkers in an independent patient cohort and to assess intratumour heterogeneity (ITH) of the most promising...... markers to guide biomarker optimisation. Design, setting, and participantsCancer-specific survival (CSS) for each of 28 identified genetic or transcriptomic biomarkers was assessed in 350 ccRCC patients. ITH was interrogated in a multiregion biopsy data set of 10 ccRCCs. Outcome measurements...

  18. Assessment of published models and prognostic variables in epithelial ovarian cancer at Mayo Clinic.

    Science.gov (United States)

    Wahner Hendrickson, Andrea E; Hawthorne, Kieran M; Goode, Ellen L; Kalli, Kimberly R; Goergen, Krista M; Bakkum-Gamez, Jamie N; Cliby, William A; Keeney, Gary L; Visscher, Daniel W; Tarabishy, Yaman; Oberg, Ann L; Hartmann, Lynn C; Maurer, Matthew J

    2015-04-01

    Epithelial ovarian cancer (EOC) is an aggressive disease in which first line therapy consists of a surgical staging/debulking procedure and platinum based chemotherapy. There is significant interest in clinically applicable, easy to use prognostic tools to estimate risk of recurrence and overall survival. In this study we used a large prospectively collected cohort of women with EOC to validate currently published models and assess prognostic variables. Women with invasive ovarian, peritoneal, or fallopian tube cancer diagnosed between 2000 and 2011 and prospectively enrolled into the Mayo Clinic Ovarian Cancer registry were identified. Demographics and known prognostic markers as well as epidemiologic exposure variables were abstracted from the medical record and collected via questionnaire. Six previously published models of overall and recurrence-free survival were assessed for external validity. In addition, predictors of outcome were assessed in our dataset. Previously published models validated with a range of c-statistics (0.587-0.827), though application of models containing variables which are not part of routine practice were somewhat limited by missing data; utilization of all applicable models and comparison of results are suggested. Examination of prognostic variables identified only the presence of ascites and ASA score to be independent predictors of prognosis in our dataset, albeit with marginal gain in prognostic information, after accounting for stage and debulking. Existing prognostic models for newly diagnosed EOC showed acceptable calibration in our cohort for clinical application. However, modeling of prospective variables in our dataset reiterates that stage and debulking remains the most important predictors of prognosis in this setting. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Prognostic classification of MDS is improved by the inclusion of FISH panel testing with conventional cytogenetics.

    Science.gov (United States)

    Kokate, Prajakta; Dalvi, Rupa; Koppaka, Neeraja; Mandava, Swarna

    2017-10-01

    Cytogenetics is a critical independent prognostic factor in myelodysplastic syndromes (MDS). Conventional cytogenetics (CC) and Fluorescence in situ hybridization (FISH) Panel Testing are extensively used for the prognostic stratification of MDS, although the FISH test is not yet a bona fide component of the International Prognostic Scoring System (IPSS). The present study compares the utility of CC and FISH to detect chromosomal anomalies and in prognostic categorization. GTG-Banding and FISH Panel Testing specifically for -5/-5q, -7/-7q, +8 and -20q was performed on whole blood or bone marrow samples from 136 patients with MDS. Chromosomal anomalies were found in 40 cases by CC, including three novel translocations. FISH identified at least one anomaly in 54/136 (39.7%) cases. More than one anomaly was found in 18/54 (33.3%) cases, therefore, overall FISH identified 75 anomalies of which 32 (42.6%) were undetected by CC. FISH provided additional information in cases with CC failure and in cases with a normal karyotype. Further, in ten cases with an abnormal karyotype, FISH could identify additional anomalies, increasing the number of abnormalities per patient. Although CC is the gold standard in the cytogenetic profiling of MDS, FISH has proven to be an asset in identifying additional abnormalities. The number of anomalies per patient can predict the prognosis in MDS and hence, FISH contributed towards prognostic re-categorization. The FISH Panel testing should be used as an adjunct to CC, irrespective of the adequacy of the number of metaphases in CC, as it improves the prognostic classification of MDS. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Clinical prognostic factors in non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Joensuu, H.

    1986-01-01

    Hospital records of 201 consecutive and histologically diagnosed non-Hodgkin's lymphoma patients were retrospectively analysed in an effort to determine the clinical prognostic factors affecting survival. The uncorrected five-year survival was 45%, and when corrected for other causes of death than lymphoma 48%. Response to the primary treatment, stage of the disease at diagnosis, occurrence of B-symptoms and age were strongly correlated to the final outcome. B-symptoms had negative effect on survival during the first year after the diagnosis, but not afterwards. Survival decreased with advancing age except in children, who had as poor survival as patients over 60 years of age. The primary site, sex or occurrence of extranodal lymphoma (43%) did not have influence on survival. Patients with a positive bone marrow aspiration biopsy did not have less favourable survival than other patients with stage IV lymphoma. Patients with a positive bipedal lymphangiogram had similar prognosis as those with a negative one. It is concluded that the most important prognostic factors other than histology in non-Hodgkin's lymphomas are response to the primary treatment, stage, age and occurrence of B-symptoms. (orig.) [de

  1. Prognostic factors for perioperative myocardial infarction and immediate mortality in patients who underwent coronary artery bypass graft surgery

    Directory of Open Access Journals (Sweden)

    Mirtha López Ramírez

    2016-03-01

    Conclusions: Older age and higher body mass index were protective prognostic factors for perioperative acute myocardial infarction events. Prolonged surgical time and complications were independently associated with perioperative infarction and mortality after coronary artery bypass graft surgery. Low preoperative glomerular filtration rate was also associated with mortality.

  2. A novel prognostic index in colorectal cancer defined by serum carcinoembryonic antigen and plasma tissue inhibitor of metalloproteinases-1

    DEFF Research Database (Denmark)

    Nielsen, Hans J.; Christensen, Ib J.; Brunner, Nils

    2010-01-01

    The introduction of stage-independent prognostic markers may play a significant role in future selection for adjuvant treatment for early-stage colorectal cancer (CRC). The purpose of this study was to assess the combination of preoperative serum carcinoembryonic antigen (CEA) and plasma tissue...

  3. Renal function at the time of a myocardial infarction maintains prognostic value for more than 10 years

    DEFF Research Database (Denmark)

    Kümler, Thomas; Gislason, Gunnar H; Kober, Lars

    2011-01-01

    Renal function is an important predictor of mortality in patients with myocardial infarction (MI), but changes in the impact over time have not been well described.We examined the importance of renal function by estimated GFR (eGFR) and se-creatinine as an independent long-term prognostic factor....

  4. Occurrence and prognostic relevance of CD30 expression in post-transplant lymphoproliferative disorders

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Maksten, Eva Futtrup; Bendix, Knud

    2015-01-01

    Post-transplant lymphoproliferative disorders (PTLDs) are potentiallyfatal, often Epstein-Barr virus (EBV)-driven neoplasias developing in immunocompromised hosts. Initial treatment usually consists of a reduction in immunosuppressive therapy and/or rituximab with or without chemotherapy. However...... favorable outcome. For diffuse large B-cell lymphoma (DLBCL)-type PTLD this was regardless of EBV status, and remained significant in multivariate analysis. Cell-of-origin had no independent prognostic value in our series of DLBCL PTLD....

  5. Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Doyen, J. [Department of Radiation Oncology, Centre A. Lacassagne, Nice (France); Trastour, C. [Department of Gynecology, Archet II Hospital, 06202 Nice (France); Ettore, F.; Peyrottes, I.; Toussant, N. [Department of Pathology, Centre A. Lacassagne, Nice (France); Gal, J. [Department of Medical Statistics, Centre A. Lacassagne, Nice (France); Ilc, K.; Roux, D. [Institute for Research on Cancer and Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice (France); Parks, S.K. [Centre Scientifique de Monaco (CSM) (Monaco); Ferrero, J.M. [Department of Medical Oncology, Centre A. Lacassagne, Nice (France); Pouysségur, J., E-mail: jacques.pouyssegur@unice.fr [Institute for Research on Cancer and Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice (France); Centre Scientifique de Monaco (CSM) (Monaco)

    2014-08-15

    Highlights: • Glycolytic markers are highly expressed in triple negative breast cancers. • Lactate/H{sup +} symporter MCT4 demonstrated the strongest deleterious impact on survival. • MCT4 should serve as a new prognostic factor in node-negative breast cancers. - Abstract: Background: {sup 18}Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer. Methods: Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively. Results: In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR = 0.47, P = 0.02) and overall-survival (HR = 0.38, P = 0.002). These results were confirmed in the independent cohort of 127 cancer patients. Conclusion: Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H{sup +} symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.

  6. Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome

    International Nuclear Information System (INIS)

    Doyen, J.; Trastour, C.; Ettore, F.; Peyrottes, I.; Toussant, N.; Gal, J.; Ilc, K.; Roux, D.; Parks, S.K.; Ferrero, J.M.; Pouysségur, J.

    2014-01-01

    Highlights: • Glycolytic markers are highly expressed in triple negative breast cancers. • Lactate/H + symporter MCT4 demonstrated the strongest deleterious impact on survival. • MCT4 should serve as a new prognostic factor in node-negative breast cancers. - Abstract: Background: 18 Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer. Methods: Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively. Results: In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR = 0.47, P = 0.02) and overall-survival (HR = 0.38, P = 0.002). These results were confirmed in the independent cohort of 127 cancer patients. Conclusion: Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H + symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors

  7. Novel prognostic tissue markers in congestive heart failure.

    Science.gov (United States)

    Stone, James R

    2015-01-01

    Heart failure is a relatively common disorder associated with high morbidity, mortality, and economic burden. Better tools to predict outcomes for patients with heart failure could allow for better decision making concerning patient treatment and management and better utilization of health care resources. Endomyocardial biopsy offers a mechanism to pathologically diagnose specific diseases in patients with heart failure, but such biopsies can often be negative, with no specific diagnostic information. Novel tissue markers in endomyocardial biopsies have been identified that may be useful in assessing prognosis in heart failure patients. Such tissue markers include ubiquitin, Gremlin-1, cyclophilin A, and heterogeneous nuclear ribonucleoprotein C. In some cases, tissue markers have been found to be independent of and even superior to clinical indices and serum markers in predicting prognosis for heart failure patients. In some cases, these novel tissue markers appear to offer prognostic information even in the setting of an otherwise negative endomyocardial biopsy. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Prognostic significance of smac/DIABLO in endometrioid endometrial cancer

    Directory of Open Access Journals (Sweden)

    Bozena Dobrzycka

    2010-04-01

    Full Text Available Apoptosis may occur via a death receptor-dependent or independent (mitochondrial pathway. The mitochondrialpathway is regulated by small molecules, such as smac/Diablo, which activates caspase cascades. This study examinedsmac/DIABLO expression in 76 patients with endometrioid endometrial cancers. Presence of smac/DIABLO was quantifiedby Western blot analysis using nonfixed fresh frozen tissues. Its appearance was found in 55 (72% of examined tumors.Smac/DIABLO expression significantly correlated with tumor grade (p<0.001. Patients with positive smac/DIABLOtumors had a longer disease-specific survival when compared with those with negative tumors in the 10-year follow-up(p=0.043. The study demonstrated that negative smac/DIABLO expression was a poor prognostic sign.

  9. Prognostic significance of smac/DIABLO in endometrioid endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Magdalena Garbowicz

    2011-04-01

    Full Text Available Apoptosis may occur via a death receptor-dependent or independent (mitochondrial pathway. The mitochondrial pathway is regulated by small molecules, such as smac/Diablo, which activates caspase cascades. This study examined smac/DIABLO expression in 76 patients with endometrioid endometrial cancers. Presence of smac/DIABLO was quantified by Western blot analysis using nonfixed fresh frozen tissues. Its appearance was found in 55 (72% of examined tumors. Smac/DIABLO expression significantly correlated with tumor grade (p<0.001. Patients with positive smac/DIABLO tumors had a longer disease-specific survival when compared with those with negative tumors in the 10-year follow-up (p=0.043. The study demonstrated that negative smac/DIABLO expression was a poor prognostic sign.

  10. 11C-methionine PET as a prognostic marker in patients with glioma: comparison with18F-FDG PET

    International Nuclear Information System (INIS)

    Kim, Sungeun; Chung, June-Key; Jeong, Jae Min; Im, So-Hyang; Kim, Dong Gyu; Jung, Hee Won; Lee, Dong Soo; Lee, Myung Chul

    2005-01-01

    The purpose of this study was to compare the prognostic value of 11 C-methionine (MET) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in glioma patients. The study population comprised 47 patients with gliomas (19 glioblastoma, 28 others). Pretreatment magnetic resonance imaging, MET PET and FDG PET were performed within a time interval of 2 weeks in all patients. The uptake ratio and standard uptake values were calculated. Univariate and multivariate analyses were done to determine significant prognostic factors. Ki-67 index was measured by immunohistochemical staining, and compared with FDG and MET uptake in glioma. Among the several clinicopathological prognostic factors, tumour pathology (glioblastoma or not), age (≥60 or <60 years), Karnofsky performance status (KPS) (≥70 or <70) and MET PET (higher uptake or not compared with normal cortex) were found to be significant predictors by univariate analysis. In multivariate analysis, tumour pathology, KPS and MET PET were identified as significant independent predictors. The Ki-67 proliferation index was significantly correlated with MET uptake (r=0.64), but not with FDG uptake. Compared with FDG PET in glioma, MET PET was an independent significant prognostic factor and MET uptake was correlated with cellular proliferation. MET PET may be a useful biological prognostic marker in glioma patients. (orig.)

  11. Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome.

    Science.gov (United States)

    Lee, J-H; Lee, J-H; Shin, Y-R; Lee, J-S; Kim, W-K; Chi, H-S; Park, C-J; Seo, E-J; Lee, K-H

    2003-02-01

    We retrospectively studied 227 patients with MDS (1) to identify the prognostic factors of survival and acute leukemia evolution in Korean patients with MDS, (2) to apply different prognostic scoring systems to the same group of patients, and (3) to compare the FAB with the WHO classification. Six scoring systems were applied to the patients, and the FAB and WHO classifications were compared. The patients' median age was 57 years. The median survival time was 21 months, and age, dysgranulopoiesis and the IPSS cytogenetic groups were independent prognostic factors for survival. Acute leukemia occurred in 34 patients, and the cumulative incidence was 27.1% at 3 years. Marrow blast percentage was the only independent prognostic factor for acute leukemia evolution. Most scoring systems successfully discriminated risk groups for survival and acute leukemia evolution, but patient distribution into risk groups varied according to the scoring systems. Refractory cytopenia with multilineage dysplasia and RAEB II seemed to have different prognoses from RA or RARS and RAEB I, respectively. In summary, our MDS patients had different disease natures from those of Western countries regarding clinical features, prognostic factors and cytogenetic profiles. Although the WHO classification seems to improve the FAB classification, further studies are warranted to validate the utility of the WHO classification before it is accepted for routine clinical use. Our study has the limitations of retrospective analysis, and our results should be verified in future prospective studies.

  12. The Prognostic Value of C-Reactive Protein Serum Levels in Patients with Uterine Leiomyosarcoma.

    Directory of Open Access Journals (Sweden)

    Richard Schwameis

    Full Text Available C-reactive protein (CRP has previously been shown to serve as a prognostic parameter in women with gynecologic malignancies. Due to the lack of valid prognostic markers for uterine leiomyosarcoma (ULMS this study set out to investigate the value of pre-treatment CRP serum levels as prognostic parameter.Data of women with ULMS were extracted from databases of three Austrian centres for gynaecologic oncology. Pre-treatment CRP serum levels were measured and correlated with clinico-pathological parameters. Univariate and multivariable survival analyses were performed.In total, 53 patients with ULMS were included into the analysis. Mean (SD CRP serum level was 3.46 mg/dL (3.96. Solely, an association between pre-treatment CRP serum levels and tumor size (p = 0.04 but no other clinic-pathologic parameter such as tumor stage (p = 0.16, or histological grade (p = 0.07, was observed. Univariate and multivariable survival analyses revealed that CRP serum levels (HR 2.7 [1.1-7.2], p = 0.037 and tumor stage (HR 6.1 [1.9-19.5], p = 0.002 were the only independent prognostic factors for overall survival (OS in patients with ULMS. Patients with high pre-treatment CRP serum levels showed impaired OS compared to women with low levels (5-year-OS rates: 22.6% and 52.3%, p = 0.007.High pre-treatment CRP serum levels were independently associated with impaired prognosis in women with ULMS and might serve as a prognostic parameter in these patients.

  13. Prognostic characteristics of surgical stage I endometrial adenocarcinoma

    International Nuclear Information System (INIS)

    Konski, Andre; Domenico, Don; Tyrkus, Michael; Irving, Douglas; Neisler, James; Phibbs, Garth; Zeidner, Steven; Eggleston, William

    1996-01-01

    Purpose: To evaluate and correlate the expression of pathologic characteristics, flow cytometric DNA content analysis, and estrogen and progesterone receptor levels with survival in patients with surgical Stage I endometrial carcinoma. Methods and Materials: Hospital tumor registry records were surveyed, and this identified 232 patients diagnosed with endometrial adenocarcinoma between July 1, 1989, and December 30, 1993. DNA content analysis was performed on either paraffin-embedded or fresh tissue samples. Survival was calculated from the date of diagnosis by the Kaplan-Meier method. Postoperative irradiation (whole pelvis external beam therapy and low dose rate vaginal cuff brachytherapy) was delivered to patients felt to be at high risk of failure. Results: One hundred seventy-one patients had Stage I tumors and were available for analysis. Patients with Stage IC tumors had a statistically significant lower survival rate compared to patients with Stages IA or IB (p = 0.03 and p < 0.01, respectively). Patients with DNA content diploid tumors had a slightly increased (but nonsignificantly so) survival compared to patients with non-DNA content diploid tumors (p = 0.12). Logistic regression analysis failed to identify an independent prognostic factor that could predict for disease specific survival in patients with Stage I cancers. Conclusion: Logistic regression analysis did not identify a single independent prognostic factor in patients with Stage I tumors. Pathologic characteristics reported to predict survival advantage correlated with pathologic stage. Additional translational research is needed to identify molecular characteristics of tumors that may indicate more aggressive treatment for patients at high risk for recurrence

  14. Prognostic and Predictive Values of Subcellular Localisation of RET in Renal Clear-Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2016-01-01

    Full Text Available Metastatic renal cell carcinoma (RCC presents a poor prognosis and an unpredictable course. To date, no validated biomarkers can predict the outcome of RCC. Ongoing efforts are conducted to identify the molecular markers of RCC progression, as well as the targets for novel therapeutic approaches. RET is a tyrosine kinase receptor which has been investigated as a possible target in other cancers because it is involved in oncogenic activation. To evaluate the predictive and prognostic functions of RET in ccRCC, a tissue microarray study was conducted on 273 ccRCC patients. Results showed that both RET cytoplasmic and nuclear expression were independently associated with PFS and OS, and the combined RET cytoplasmic and nuclear statuses demonstrated that the ratio of high nuclear RET and cytoplasmic RET was the strongest predictor of both PFS and OS. The high cytoplasmic RET expression retained its independent poor prognostic value in targeted drug treated patients. The RET nuclear expression was associated with distant metastasis. Moreover, the RET nuclear expression was an independent predictor of ccRCC postoperative metastasis. In conclusion, RET may be useful in prognostication and can be used at initial diagnosis to identify patients with high potential to develop metastasis.

  15. Tumor-Associated Macrophages Provide Significant Prognostic Information in Urothelial Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Minna M Boström

    Full Text Available Inflammation is an important feature of carcinogenesis. Tumor-associated macrophages (TAMs can be associated with either poor or improved prognosis, depending on their properties and polarization. Current knowledge of the prognostic significance of TAMs in bladder cancer is limited and was investigated in this study. We analyzed 184 urothelial bladder cancer patients undergoing transurethral resection of a bladder tumor or radical cystectomy. CD68 (pan-macrophage marker, MAC387 (polarized towards type 1 macrophages, and CLEVER-1/Stabilin-1 (type 2 macrophages and lymphatic/blood vessels were detected immunohistochemically. The median follow-up time was 6.0 years. High macrophage counts associated with a higher pT category and grade. Among patients undergoing transurethral resection, all studied markers apart from CLEVER-1/Stabilin-1 were associated with increased risk of progression and poorer disease-specific and overall survival in univariate analyses. High levels of two macrophage markers (CD68/MAC387+/+ or CD68/CLEVER-1+/+ groups had an independent prognostic role after transurethral resection in multivariate analyses. In the cystectomy cohort, MAC387, alone and in combination with CD68, was associated with poorer survival in univariate analyses, but none of the markers were independent predictors of outcome in multivariate analyses. In conclusion, this study demonstrates that macrophage phenotypes provide significant independent prognostic information, particularly in bladder cancers undergoing transurethral resection.

  16. Histopathological prognostic factors in patients with cervical cancer treated with radical hysterectomy and postoperative radiotherapy

    International Nuclear Information System (INIS)

    Shinohara, Syuichi; Ochi, Takashi; Miyazaki, Tatsuhiko; Fujii, Takashi; Mochizuki, Teruhito; Ito, Masaharu

    2004-01-01

    Many studies have been performed, on the clinical outcome and prognostic factors in patients with cervical cancer treated with radical hysterectomy and postoperative radiotherapy, but no useful method for predicting the risk of recurrence has been established. The purpose of this study was to analyze histopathological prognostic factors. In addition, we proposed a new risk classification and evaluated its usefulness. One hundred and thirty patients with stage I-II uterine cervical cancer were treated with radical hysterectomy and postoperative radiotherapy at Ehime University Hospital between 1978 and 1997. All surgical specimens were reviewed, and the relationship between histopathological factors and the clinical outcome was analyzed. Of the histopathological prognostic factors of the surgical specimens analyzed, six factors (parametrial invasion, venous infiltration, pelvic lymph node metastases, thickness of the residual muscular layer, tumor depth, and tumor growth pattern) were significant prognostic factors. In particular, venous infiltration and pelvic lymph node metastases were strongly correlated with recurrence. Using the above five factors (excluding the thickness of the residual muscle layer), all patients were scored based on the total number of poor prognostic factors, and were classified into three groups. Patients with a score of 0-1 were classified as the low-risk group, those with a score of 2 as the intermediate group, and those with a score of 3-5 as the high-risk group. The 5-year disease-free survival rates were 93% in the low-risk group, 82% in the intermediate group, and 56% in the high-risk group (p<0.05). Six prognostic factors were found. Our risk classification seems to be clinically useful to predict which patients are at risk of recurrence. (author)

  17. Prognostics-Enabled Power Supply for ADAPT Testbed, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Ridgetop's role is to develop electronic prognostics for sensing power systems in support of NASA/Ames ADAPT testbed. The prognostic enabled power systems from...

  18. A Model-based Prognostics Approach Applied to Pneumatic Valves

    Data.gov (United States)

    National Aeronautics and Space Administration — Within the area of systems health management, the task of prognostics centers on predicting when components will fail. Model-based prognostics exploits domain...

  19. Distributed Prognostics System Implementation on Wireless Embedded Devices

    Data.gov (United States)

    National Aeronautics and Space Administration — Distributed prognostics is the next step in the evolution of prognostic methodologies. It is an important enabling technology for the emerging Condition Based...

  20. A Model-Based Prognostics Approach Applied to Pneumatic Valves

    Data.gov (United States)

    National Aeronautics and Space Administration — Within the area of systems health management, the task of prognostics centers on predicting when components will fail. Model-based prognostics exploits domain...

  1. Communication Optimizations for a Wireless Distributed Prognostic Framework

    Data.gov (United States)

    National Aeronautics and Space Administration — Distributed architecture for prognostics is an essential step in prognostic research in order to enable feasible real-time system health management. Communication...

  2. PROGNOSTIC SIGNIFICANCE OF CD56 EXPRESSION IN ACUTE LEUKEMIAS

    Directory of Open Access Journals (Sweden)

    B. M. Ahmed

    2014-12-01

    Conclusions. CD56 antigenic expression in AML cases represents an adverse prognostic factor. It should be regularly investigated in cases of AML for better prognostic stratification and assessment. KEY WORDS: CD56; leukemia, myeloid; prognosis

  3. Prognostic value of intact and cleaved forms of the urokinase plasminogen activator receptor in a retrospective study of 518 colorectal cancer patients

    DEFF Research Database (Denmark)

    Lomholt, Anne Fog; Christensen, Ib J; Høyer-Hansen, Gunilla

    2010-01-01

    The levels of the soluble urokinase plasminogen activator receptor (suPAR) in blood have been shown to correlate with prognosis in various cancers. Plasma levels of the combined suPAR forms have previously shown to be a strong prognostic marker in the present cohort of CRC patients and could...... potentially identify high-risk patients among those with early stage disease. In order to investigate whether the individual suPAR forms are stronger prognostic markers than the combined amount we measured the different uPAR forms in serum from the same cohort and evaluated their prognostic significance....

  4. The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy ± chemotherapy

    Directory of Open Access Journals (Sweden)

    Goethals Laurence

    2005-04-01

    Full Text Available Abstract Background Several parameters of the tumor microenvironment, such as hypoxia, inflammation and angiogenesis, play a critical role in tumor aggressiveness and treatment response. A major question remains if these markers can be used to stratify patients to certain treatment protocols. The purpose of this study was to investigate the inter-relationship and the prognostic significance of several biological and clinicopathological parameters in patients with head and neck squamous cell carcinoma (HNSCC treated by radiotherapy ± chemotherapy. Methods We used two subgroups of a retrospective series for which CT-determined tumoral perfusion correlated with local control. In the first subgroup (n = 67, immunohistochemistry for carbonic anhydrase IX (CA IX and glucose transporter-1 (GLUT-1 was performed on the pretreatment tumor biopsy. In the second subgroup (n = 34, enzyme linked immunosorbent assay (ELISA was used to determine pretreatment levels of the cytokines vascular endothelial growth factor (VEGF and interleukin-6 (IL-6 in serum. Correlation was investigated between tumoral perfusion and each of these biological markers, as well as between the markers mutually. The prognostic value of these microenvironmental parameters was also evaluated. Results For CA IX and GLUT-1, the combined assessment of patients with both markers expressed above the median showed an independent correlation with local control (p = 0.02 and disease-free survival (p = 0.04 with a trend for regional control (p = 0.06. In the second subgroup, IL-6 pretreatment serum level above the median was the only independent predictor of local control (p = 0.009, disease-free survival (p = 0.02 and overall survival (p = 0.005. Conclusion To our knowledge, we are the first to report a link in HNSCC between IL-6 pretreatment serum levels and radioresistance in vivo. This link is supported by the strong prognostic association of pretreatment IL-6 with local control, known to be

  5. The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy ± chemotherapy

    International Nuclear Information System (INIS)

    De Schutter, Harlinde; Landuyt, Willy; Verbeken, Erik; Goethals, Laurence; Hermans, Robert; Nuyts, Sandra

    2005-01-01

    Several parameters of the tumor microenvironment, such as hypoxia, inflammation and angiogenesis, play a critical role in tumor aggressiveness and treatment response. A major question remains if these markers can be used to stratify patients to certain treatment protocols. The purpose of this study was to investigate the inter-relationship and the prognostic significance of several biological and clinicopathological parameters in patients with head and neck squamous cell carcinoma (HNSCC) treated by radiotherapy ± chemotherapy. We used two subgroups of a retrospective series for which CT-determined tumoral perfusion correlated with local control. In the first subgroup (n = 67), immunohistochemistry for carbonic anhydrase IX (CA IX) and glucose transporter-1 (GLUT-1) was performed on the pretreatment tumor biopsy. In the second subgroup (n = 34), enzyme linked immunosorbent assay (ELISA) was used to determine pretreatment levels of the cytokines vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in serum. Correlation was investigated between tumoral perfusion and each of these biological markers, as well as between the markers mutually. The prognostic value of these microenvironmental parameters was also evaluated. For CA IX and GLUT-1, the combined assessment of patients with both markers expressed above the median showed an independent correlation with local control (p = 0.02) and disease-free survival (p = 0.04) with a trend for regional control (p = 0.06). In the second subgroup, IL-6 pretreatment serum level above the median was the only independent predictor of local control (p = 0.009), disease-free survival (p = 0.02) and overall survival (p = 0.005). To our knowledge, we are the first to report a link in HNSCC between IL-6 pretreatment serum levels and radioresistance in vivo. This link is supported by the strong prognostic association of pretreatment IL-6 with local control, known to be the most important parameter to judge radiotherapy

  6. Accounting for Independent Schools.

    Science.gov (United States)

    Sonenstein, Burton

    The diversity of independent schools in size, function, and mode of operation has resulted in a considerable variety of accounting principles and practices. This lack of uniformity has tended to make understanding, evaluation, and comparison of independent schools' financial statements a difficult and sometimes impossible task. This manual has…

  7. Independence of Internal Auditors.

    Science.gov (United States)

    Montondon, Lucille; Meixner, Wilda F.

    1993-01-01

    A survey of 288 college and university auditors investigated patterns in their appointment, reporting, and supervisory practices as indicators of independence and objectivity. Results indicate a weakness in the positioning of internal auditing within institutions, possibly compromising auditor independence. Because the auditing function is…

  8. The prognostic significance of early and late right precordial lead (V4 R) ST-segment elevation in patients with acute anterior myocardial infarction.

    Science.gov (United States)

    Keskin, Muhammed; Uzun, Ahmet Okan; Börklü, Edibe Betül; Hayıroğlu, Mert İlker; Türkkan, Ceyhan; Tekkeşin, Ahmet İlker; Kozan, Ömer

    2018-03-01

    The predictive significance of ST-segment elevation (STE) in lead V 4 R in patients with anterior ST-segment elevation myocardial infarction (STEMI) has not been well-understood. In this study, we evaluated the prognostic value of early and late STE in lead V 4 R in patients with anterior STEMI. A total 451 patients with anterior STEMI who treated with primary percutaneous coronary intervention (PPCI) were prospectively enrolled in this study. All patients were classified according to presence of STE (>1 mm) in lead V 4 R at admission and/or 60 min after PPCI. Based on this classification, all patients were divided into three subgroups as no V 4 R STE (Group 1), early but not late V 4 R STE (Group 2) and late V 4 R STE (Group 3). In-hospital mortality had higher rates at group 2 and 3 and that had 2.1 and 4.1-times higher mortality than group 1. Late V 4 R STE remained as an independent risk factor for cardiogenic shock (odds ratio [OR] 2.6; 95% confidence interval [CI] 1.9-4.3; p < .001) and in-hospital mortality (OR 2.3; 95% CI 1.8-4.1; p < .001). The 12-month overall survival for group 1, 2, and 3 were 91.1%, 82.4%, and 71.4% respectively. However, the long-term mortality also had the higher rate at group 3; late V 4 R STE did not remain as an independent risk factor for long-term mortality (OR 1.5; 95% CI 0.8-4.1; p: .159). Late V 4 R STE in patients with anterior STEMI is strongly associated with poor prognosis. The record of late V 4 R in patients with anterior STEMI has an important prognostic value. © 2017 Wiley Periodicals, Inc.

  9. Prognostic immune-related gene models for breast cancer: a pooled analysis

    Directory of Open Access Journals (Sweden)

    Zhao J

    2017-09-01

    LN+ breast cancer, four models showed predictive advantage, with C-indices between 0.56 and 0.61. Predicted prognostic values were positively correlated with ER status when evaluated using univariate analyses in most of the models under investigation. Multivariate analyses indicated that prognostic values of the three models were independent of known clinical prognostic factors. Collectively, these analyses provided a comprehensive evaluation of immune-related prognostic gene signatures. By synthesizing C-indices in multiple independent data sets, immune-related gene signatures were ranked for ER+, ER-, LN+, and LN- breast cancer subtypes. Taken together, these data showed that immune-related gene signatures have good prognostic values in breast cancer, especially for ER- and LN+ tumors. Keywords: breast cancer, prognostic models, immune-related gene

  10. Prognostic factors in papillary and follicular thyroid carcinomas

    DEFF Research Database (Denmark)

    Godballe, C; Asschenfeldt, P; Jørgensen, K E

    1998-01-01

    To identify clinical and histologic prognostic factors and to investigate whether immunohistochemical detection of p53 expression might contain prognostic information, a retrospective study of patient and tumor characteristics was performed in 225 cases of papillary and follicular thyroid...... prognostic indicator, which might be of value in the treatment planning in patients with papillary or follicular thyroid carcinomas....

  11. Prognostic Bayesian networks I: Rationale, learning procedure, and clinical use

    NARCIS (Netherlands)

    Verduijn, Marion; Peek, Niels; Rosseel, Peter M. J.; de Jonge, Evert; de Mol, Bas A. J. M.

    2007-01-01

    Prognostic models are tools to predict the future outcome of disease and disease treatment, one of the fundamental tasks in clinical medicine. This article presents the prognostic Bayesian network (PBN) as a new type of prognostic model that builds on the Bayesian network methodology, and implements

  12. Prognostic risk estimates of patients with multiple sclerosis and their physicians: comparison to an online analytical risk counseling tool.

    Science.gov (United States)

    Heesen, Christoph; Gaissmaier, Wolfgang; Nguyen, Franziska; Stellmann, Jan-Patrick; Kasper, Jürgen; Köpke, Sascha; Lederer, Christian; Neuhaus, Anneke; Daumer, Martin

    2013-01-01

    Prognostic counseling in multiple sclerosis (MS) is difficult because of the high variability of disease progression. Simultaneously, patients and physicians are increasingly confronted with making treatment decisions at an early stage, which requires taking individual prognoses into account to strike a good balance between benefits and harms of treatments. It is therefore important to understand how patients and physicians estimate prognostic risk, and whether and how these estimates can be improved. An online analytical processing (OLAP) tool based on pooled data from placebo cohorts of clinical trials offers short-term prognostic estimates that can be used for individual risk counseling. The aim of this study was to clarify if personalized prognostic information as presented by the OLAP tool is considered useful and meaningful by patients. Furthermore, we used the OLAP tool to evaluate patients' and physicians' risk estimates. Within this evaluation process we assessed short-time prognostic risk estimates of patients with MS (final n = 110) and their physicians (n = 6) and compared them with the estimates of OLAP. Patients rated the OLAP tool as understandable and acceptable, but to be only of moderate interest. It turned out that patients, physicians, and the OLAP tool ranked patients similarly regarding their risk of disease progression. Both patients' and physicians' estimates correlated most strongly with those disease covariates that the OLAP tool's estimates also correlated with most strongly. Exposure to the OLAP tool did not change patients' risk estimates. While the OLAP tool was rated understandable and acceptable, it was only of modest interest and did not change patients' prognostic estimates. The results suggest, however, that patients had some idea regarding their prognosis and which factors were most important in this regard. Future work with OLAP should assess long-term prognostic estimates and clarify its usefulness for patients and physicians

  13. Prognostic risk estimates of patients with multiple sclerosis and their physicians: comparison to an online analytical risk counseling tool.

    Directory of Open Access Journals (Sweden)

    Christoph Heesen

    Full Text Available BACKGROUND: Prognostic counseling in multiple sclerosis (MS is difficult because of the high variability of disease progression. Simultaneously, patients and physicians are increasingly confronted with making treatment decisions at an early stage, which requires taking individual prognoses into account to strike a good balance between benefits and harms of treatments. It is therefore important to understand how patients and physicians estimate prognostic risk, and whether and how these estimates can be improved. An online analytical processing (OLAP tool based on pooled data from placebo cohorts of clinical trials offers short-term prognostic estimates that can be used for individual risk counseling. OBJECTIVE: The aim of this study was to clarify if personalized prognostic information as presented by the OLAP tool is considered useful and meaningful by patients. Furthermore, we used the OLAP tool to evaluate patients' and physicians' risk estimates. Within this evaluation process we assessed short-time prognostic risk estimates of patients with MS (final n = 110 and their physicians (n = 6 and compared them with the estimates of OLAP. RESULTS: Patients rated the OLAP tool as understandable and acceptable, but to be only of moderate interest. It turned out that patients, physicians, and the OLAP tool ranked patients similarly regarding their risk of disease progression. Both patients' and physicians' estimates correlated most strongly with those disease covariates that the OLAP tool's estimates also correlated with most strongly. Exposure to the OLAP tool did not change patients' risk estimates. CONCLUSION: While the OLAP tool was rated understandable and acceptable, it was only of modest interest and did not change patients' prognostic estimates. The results suggest, however, that patients had some idea regarding their prognosis and which factors were most important in this regard. Future work with OLAP should assess long-term prognostic

  14. Favorable prognostic value of SOCS2 and IGF-I in breast cancer

    Directory of Open Access Journals (Sweden)

    Daxenbichler Günter

    2007-07-01

    Full Text Available Abstract Background Suppressor of cytokine signaling (SOCS proteins comprise a protein family, which has initially been described as STAT induced inhibitors of the Jak/Stat pathway. Recent in vivo and in vitro studies suggest that SOCS proteins are also implicated in cancer. The STAT5 induced IGF-I acts as an endocrine and para/autocrine growth and differentiation factor in mammary gland development. Whereas high levels of circulating IGF-I have been associated with increased cancer risk, the role of autocrine acting IGF-I is less clear. The present study is aimed to elucidate the clinicopathological features associated with SOCS1, SOCS2, SOCS3, CIS and IGF-I expression in breast cancer. Methods We determined the mRNA expression levels of SOCS1, SOCS2, SOCS3, CIS and IGF-I in 89 primary breast cancers by reverse transcriptase PCR. SOCS2 protein expression was further evaluated by immuno-blot and immunohistochemistry. Results SOCS2 expression inversely correlated with histopathological grade and ER positive tumors exhibited higher SOCS2 levels. Patients with high SOCS2 expression lived significantly longer (108.7 vs. 77.7 months; P = 0.015 and high SOCS2 expression proved to be an independent predictor for good prognosis (HR = 0.45, 95% CI 0.23 – 0.91, P = 0.026. In analogy to SOCS2, high IGF-I expression was an independent predictor for good prognosis in the entire patient cohort. In the subgroup of patients with lymph-node negative disease, high IGF-I was a strong predictor for favorable outcome in terms of overall survival and relapse free survival (HR = 0.075, 95% CI 0.014 – 0.388, P = 0.002. Conclusion This is the first report on the favorable prognostic value of high SOCS2 expression in primary mammary carcinomas. Furthermore a strong association of high IGF-I expression levels with good prognosis was observed especially in lymph-node negative patients. Our results suggest that high expression of the STAT5 target genes SOCS2 and IGF

  15. Fuzzy logic-based prognostic score for outcome prediction in esophageal cancer.

    Science.gov (United States)

    Wang, Chang-Yu; Lee, Tsair-Fwu; Fang, Chun-Hsiung; Chou, Jyh-Horng

    2012-11-01

    Given the poor prognosis of esophageal cancer and the invasiveness of combined modality treatment, improved prognostic scoring systems are needed. We developed a fuzzy logic-based system to improve the predictive performance of a risk score based on the serum concentrations of C-reactive protein (CRP) and albumin in a cohort of 271 patients with esophageal cancer before radiotherapy. Univariate and multivariate survival analyses were employed to validate the independent prognostic value of the fuzzy risk score. To further compare the predictive performance of the fuzzy risk score with other prognostic scoring systems, time-dependent receiver operating characteristic curve (ROC) analysis was used. Application of fuzzy logic to the serum values of CRP and albumin increased predictive performance for 1-year overall survival (AUC=0.773) compared with that of a single marker (AUC=0.743 and 0.700 for CRP and albumin, respectively), where the AUC denotes the area under curve. This fuzzy logic-based approach also performed consistently better than the Glasgow Prognostic Score (GPS) (AUC=0.745). Thus, application of fuzzy logic to the analysis of serum markers can more accurately predict the outcome for patients with esophageal cancer.

  16. Prognostic value of lymph node ratio in node-positive breast cancer in Egyptian patients

    International Nuclear Information System (INIS)

    Elkhodary, T.R.; Ebrahim, M.A.; Hatata, E.E.; Niazy, N.A.

    2014-01-01

    Background: Breast cancer in Egypt is the most common cancer among women and is the leading cause of cancer mortality. Traditionally, axillary lymph node involvement is considered among the most important prognostic factors in breast cancer. Nonetheless, accumulating evidence suggests that axillary lymph node ratio should be considered as an alternative to classical pN classification. Materials and methods: We performed a retrospective analysis of patients with operable node positive breast cancer, to investigate the prognostic significance of axillary lymph node ratio. Results: Five-hundred patients were considered eligible for the analysis. Median follow-up was 35 months (95% Cl 32-37 months), the median disease-free survival (DFS) was 49 months (95% Cl, 46.4-52.2 months). The classification of patients based on pN staging system failed to prognosticate DFS in the multivariate analysis. Conversely, grade 3 tumors, and the intermediate (> 0.20 to <0.65) and high (>0.65) LNR were the only variables that were independently associated with adverse DFS. The overall survival (OS) in this series was 69 months (95% Cl 60-77). Conclusion: The analysis of outcome of patients with early breast cancer in Egypt identified the adverse prognostic effects of high tumor grade, ER negativity and intermediate and high LNR on DFS. If the utility of the LNR is validated in other studies, it may replace the use of absolute number of axillary lymph nodes.

  17. Prognostic value of long non-coding RNA MALAT1 in cancer patients.

    Science.gov (United States)

    Wu, Yihua; Lu, Wei; Xu, Jinming; Shi, Yu; Zhang, Honghe; Xia, Dajing

    2016-01-01

    Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) was identified to be the first long non-coding RNA as a biomarker of independent prognostic value for early stage non-small cell lung cancer patient survival. In recent years, the association between upregulated tissue MALAT1 level and incidence of various cancers including bladder cancer, colorectal cancer, and renal cancer has been widely discussed. The aim of our present study was to assess the potential prognostic value of MALAT1 in various human cancers. PubMed, Embase, Ovid, and Cochrane Library databases were systematically searched, and eligible studies evaluating the prognostic value of MALAT1 in various cancers were included. Finally, 11 studies encompassing 1216 participants reporting with sufficient data were enrolled in the current meta-analysis. The pooled hazard ratio (HR) was 2.05 (95 % confidence interval (CI) 1.64-2.55, p < 0.01) for overall survival (OS) and 2.66 (95 % CI 1.86-3.80, p < 0.01) for disease-free survival (DFS). In conclusion, high tissue MALAT1 level was associated with an inferior clinical outcome in various cancers, suggesting that MALAT1 might serve as a potential prognostic biomarker for various cancers.

  18. Prognostic Impact of DNA-Image-Cytometry in Neuroendocrine (Carcinoid Tumours

    Directory of Open Access Journals (Sweden)

    H. Raatz

    2004-01-01

    Full Text Available Establishing prognosis proves particularly difficult with neuroendocrine tumours (NETs as a benign looking histology can be associated with a malignant behaviour. In order to identify prognostic factors we examined 44 gastrointestinal and pulmonary, paraffin‐embedded NETs histologically and immunohistochemically. DNA‐image‐cytometry was used to examine 40 of these. We found that poor differentiation (corresponding to a Soga and Tazawa type D and infiltrative growth correlated with a poorer prognosis. Moreover, parameters determined by diagnostic DNA cytometry like the 5c‐exceeding rate, the 2c‐deviation index, DNA‐grade of malignancy, DNA‐entropy and the type of DNA histogram were found to be of prognostic relevance. Morphometric parameters like the form factor and the mean nuclear area were relevant for survival, tumour recurrence and metastasis. However, in the multivariate analysis the only independent risk factor was the histological differentiation. The 5c‐exceeding rate is a good objective risk factor, which can be used particularly in cases in which only a fine needle biopsie is available. Direct comparison of the histology and the 5c‐exceeding rate in the multivariate analysis suggests that the 5c‐exceeding rate taken as sole prognostic factor might be of higher prognostic relevance than the histology but larger studies are needed to confirm this.

  19. Prognostic significance of preoperative serum CA125, CA19-9 and CEA in gastric carcinoma

    Science.gov (United States)

    Wang, Wei; Chen, Xiao-Long; Zhao, Shen-Yu; Xu, Yu-Hui; Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Yang, Kun; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-01-01

    The prognostic significance of preoperative serum CA125, CA19-9 and CEA in gastric carcinoma (GC) has been widely reported and is still under debate. Here, we evaluated the prognostic significance of preoperative serum CA125, CA19-9 and CEA in patients with GC. 1692 patients with GC who underwent gastrectomy were divided into the training (from January 2005 to December 2011, n = 1024) and the validation (from January 2012 to December 2013, n = 668) cohorts. Positive groups of CA125 (> 13.72 U/ml), CA19-9 (> 23.36 U/ml) and CEA (> 4.28 ng/ml) were significantly associated with more advanced clinicopathological traits and worse outcomes than that of negative groups (all P tumor size (P tumor markers (NPTM) were more accurate in prognostic prediction than TNM stage alone. Our findings suggested that elevated preoperative serum CA125, CA19-9 and CEA were associated with more advanced clinicopathological traits and less favorable outcomes. In addition, CA125 as an independent prognostic factor should be further investigated. Nomogram based on NPTM could accurately predict the prognosis of GC patients. PMID:27097114

  20. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Ying Chen

    2015-01-01

    Full Text Available Tumor-stroma ratio (TSR has recently been identified as a promising prognostic parameter for several solid tumors. This study aimed to evaluate the prognostic role of TSR in epithelial ovarian cancer (EOC and 838 EOC patients were enrolled in this study. TSR was estimated on hematoxylin-and-eosin-stained tissue sections from the most invasive part of the primary tumor. Patients were classified as stroma-rich or stroma-poor according to the proportion of stroma ≥50% or <50%. Chi-square test analysis revealed that TSR were significantly associated with FIGO stage, LN status, and recurrence or not (all of them P<0.001. The higher stroma-rich proportions were found in EOC patients with advanced stage (36.13% versus 19.75%, LN metastasis (51.93% versus 27.25%, and recurrence (34.27% versus 6.82%. Stroma-rich EOC patients had obvious shorter median time of progression-free survival (29 versus 39 months and overall survival (50 versus 58 months, respectively. TSR was an independent prognostic factor for the evaluation of PFS in EOC. Stroma-rich tumors had worse prognosis and higher risk of relapse compared with those in stroma-poor tumors in EOC patients. Considered easy to determine for routine pathological examination, TSR may serve as a new prognostic histological parameter in EOC.

  1. Prognostic value of quantitative liver function tests in viral cirrhosis: a prospective study.

    Science.gov (United States)

    Addario, Luigi; Scaglione, Giuseppe; Tritto, Giovanni; Di Costanzo, Giovan Giuseppe; De Luca, Massimo; Lampasi, Filippo; Galeota Lanza, Alfonso; Picciotto, Francesco P; Tartaglione, Maria Teresa; Utech, Wanda; Macr, Michela; Giannelli, Eduardo; Ascione, Antonio

    2006-07-01

    Widespread application of quantitative liver function tests as a prognostic tool is controversial. In this study we assessed the predictivity of serial evaluations of galactose elimination capacity (GEC) and the monoethylglycinexylidide (MEGX) test on survival in viral cirrhosis, and secondarily we compared these tests with Child-Turcotte-Pugh (CTP) and Model for End Stage Liver Disease (MELD) scores. In a cohort of 35 patients with viral cirrhosis, GEC and MEGX were evaluated every 6 months for 24 months and compared with CTP and MELD scores at the same time intervals. The end points were patient death or liver transplantation. Statistically significant differences between dead/transplanted patients and survivors were found for basal values of GEC, MEGX, CTP and MELD. Receiver-operating characteristics curves of CTP and MELD scores showed a higher prognostic accuracy than GEC and MEGX. On multivariate analysis, neither GEC nor MEGX were independent predictors of survival. Repeated-measures analysis of GEC and MEGX did not increase the prognostic accuracy of these tests and did not add useful prognostic information on patient outcome during the following 6 months. Our data suggest that neither single nor repeated determinations of GEC and MEGX are superior to CTP and MELD scores in predicting prognosis of patients with viral cirrhosis.

  2. Factors prognosticating the outcome of decompressive craniectomy in severe traumatic brain injury: A Malaysian experience

    Science.gov (United States)

    Sharda, Priya; Haspani, Saffari; Idris, Zamzuri

    2014-01-01

    Objective: The objective of this prospective cohort study was to analyse the characteristics of severe Traumatic Brain Injury (TBI) in a regional trauma centre Hospital Kuala Lumpur (HKL) along with its impact of various prognostic factors post Decompressive Craniectomy (DC). Materials and Methods: Duration of the study was of 13 months in HKL. 110 consecutive patients undergoing DC and remained in our centre were recruited. They were then analysed categorically with standard analytical software. Results: Age group have highest range between 12-30 category with male preponderance. Common mechanism of injury was motor vehicle accident involving motorcyclist. Univariate analysis showed statistically significant in referral area (P = 0.006). In clinical evaluation statistically significant was the motor score (P = 0.040), pupillary state (P = 0.010), blood pressure stability (P = 0.013) and evidence of Diabetes Insipidus (P population, noted to be the largest series in severe TBI in this region. Severe head injury accounts for significant proportion of neurosurgical admissions, resources with its impact on socio-economic concerns to a growing population like Malaysia. This study concludes that the predictors of outcome in severe TBI post DC were postoperative hypoxia, unmaintained cerebral perfusion pressure and unstable blood pressure as independent predictors of poor outcome. Key words: Decompressive craniectomy, prognostication of decompressive craniectomy, prognostication of severe head injury, prognostication of traumatic brain injury, severe head injury, severe traumatic brain injury, traumatic brain injury. PMID:25685217

  3. Nodal Stage: Is It a Prognostic Factor for Submandibular Gland Cancer?

    Science.gov (United States)

    Liu, Yanbin; Qin, Lizheng; Zhuang, RunTao; Huang, Xin; Su, Ming; Han, Zhengxue

    2017-11-21

    Submandibular gland cancer is relatively rare. The purpose of this study was to estimate 5-year overall survival (OS) and disease-free survival (DFS) and to identify prognostic factors associated with OS and DFS for submandibular cancer. The authors implemented a retrospective cohort study and enrolled a sample of patients with submandibular gland cancer. The predictor variables were age, gender, tumor stage, nodal stage, margin status, and extracapsular spread. The outcome variables were 5-year OS and 5-year DFS. Kaplan-Meier methods were used to estimate survival and Cox hazards models were used to identify prognostic variables. The sample was composed of 52 patients with submandibular gland cancer (mean age, 47.4 yr; 51.9% men). The median follow-up was 81 months (range, 11 to 159 months). The 5-year OS and DFS rates were 76.9 and 67.3%, respectively. Fixed mass, positive neck node, and positive margin status were relevant predictors of OS and DFS. Nodal stage was the relevant independent predictor affecting the disease outcome of submandibular gland cancer. These results identified several important prognostic factors associated with survival rate in patients with submandibular gland cancer. These prognostic variables include symptoms at presentation, pathologic nodal status, and margin status. These outcomes suggest that heightening vigilance of clinical characteristics for this disease might provide the impetus for improving the survival rate. Copyright © 2017. Published by Elsevier Inc.

  4. The Analysis of Investment Environment and Foreign Direct Investment Prognostication: Lithuanian Case

    OpenAIRE

    Gaspareniene, L

    2015-01-01

    The aim of this article is to research the investment environment and to prognosticate the trends of FDI in Lithuania. The methods of the research include systematic and comparative analysis of the scientific literature and linear regression and trend analysis. The results of the research have revealed that the trend and amount of FDI in Lithuania strongly correlate. The linear regression equation is also growing, which proposes that over the next two years FDI in Lithuan...

  5. Quantum electrodynamics of strong fields

    International Nuclear Information System (INIS)

    Greiner, W.

    1983-01-01

    Quantum Electrodynamics of Strong Fields provides a broad survey of the theoretical and experimental work accomplished, presenting papers by a group of international researchers who have made significant contributions to this developing area. Exploring the quantum theory of strong fields, the volume focuses on the phase transition to a charged vacuum in strong electric fields. The contributors also discuss such related topics as QED at short distances, precision tests of QED, nonperturbative QCD and confinement, pion condensation, and strong gravitational fields In addition, the volume features a historical paper on the roots of quantum field theory in the history of quantum physics by noted researcher Friedrich Hund

  6. The biology of melanoma prognostic factors.

    NARCIS (Netherlands)

    Spatz, A.; Stock, N.; Batist, G.; Kempen, L.C.L.T. van

    2010-01-01

    Cutaneous melanoma still represents a paradox among all solid tumors. It is the cancer for which the best prognostic markers ever identified in solid tumors are available, yet there is very little understanding of their biological significance. This review focuses on recent biological data that shed

  7. Prognostic factors affecting outcome of intrauterine insemination ...

    African Journals Online (AJOL)

    Background: There is a recent resurgence in the use of intrauterine insemination (IUI) in Nigeria. However, there is a need for a rational use of the procedure so that couples do not waste time and money on ineffective therapy if it is not indicated. Objective: The objective of this study was to identify the possible prognostic ...

  8. Prognostic factors in Guillain-Barre syndrome

    Directory of Open Access Journals (Sweden)

    Semra Mungan

    2014-12-01

    Full Text Available Objective: Guillain–Barre syndrome (GBS is an immune-mediated disorder of peripheral nerves resulting as acute inflammatory demyelinating polyradiculoneuropathy. GBS has a heterogeneous clinical course and laboratory findings. Acute onset and progressive course, and is usually associated with a good prognosis but some forms have a poor prognosis. Factors that can affect the prognosis of GBS have been investigated in several studies. Assessment of poor prognostic factors of GBS plays a vital role in the management and monitorization of patients. Methods: In this retrospective study of patients admitted to the acute phase of GBS removing clinical and laboratory profiles and was planned to investigate the prognostic factors. Results: Totally 23 patients (Female/male: 16/7 were recruited. Mean age was 47 (range: 17-70 years. Statistically significant poor prognostic factors were advanced age (p=0.042, erythrocyte sedimentation rate (p=0.027 and serum albumin level (p=0.007. Conclusion: Advanced age, increased ESR and decreased albumin levels were found as poor prognostic factors in GBS.

  9. EVALUATION OF THE PROGNOSTIC VALUE OF THE ...

    African Journals Online (AJOL)

    Objectives To evaluate the role and prognostic value of the expression of epidermal growth factor receptors (EGFR) in serum and urine for the detection of human bladder cancer. Patients and Methods The study comprised 30 patients with newly diagnosed transitional cell carcinoma of the bladder and 10 normal volunteers ...

  10. Prognostic factors for neckpain in general practice.

    NARCIS (Netherlands)

    Hoving, J.L.; Vet, H.C.W. de; Twisk, J.W.R.; Devillé, W.L.J.M.; Windt, D. van der; Koes, B.W.; Bouter, L.M.

    2004-01-01

    Prognostic studies on neck pain are scarce and are typically restricted to short-term follow-up only. In this prospective cohort study, indicators of short- and long-term outcomes of neck pain were identified that can easily be measured in general practice. Patients between 18 and 70 years of age,

  11. Prognostic Factors and Treatment Outcome for Thymoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hak Jae; Park, Charn Il; Shin, Seong Soo; Kim, Joo Hyun; Seo, Jeong Wook [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2001-12-15

    Purpose : In this retrospective study, we attempted to evaluate the treatment outcome and the prognostic factors of thymoma treated with surgery, radiotherapy and chemotherapy. Methods and materials : Between 1979 and 1998, 55 patients with thymoma were treated at the Seoul National University Hospital. Of these, 11 patients underwent surgery only, 33 patients received postoperative radiotherapy and 11 patients received radiotherapy only. Twenty-three patients had gross total resection and 21 patients subtotal resection. For postoperative radiotherapy, the radiation dose consisted of 41.4{approx}55.8 Gy. The average follow-up was 64 months, and ranged from 2 to 160 months. The sex ratio was 1:1 and the median age was 48 years (15{approx}74 years). Overall survival and disease-free survival were determined via the Kaplan-Meier method, and the log-rank was employed to evaluate for differences in prognostic factor. Results : The five- and 10-year survival rates were 87% and 65% respectively, and the median survival was 103 months. By univariate analysis, only stage ( p=0.0017) turned out to be significant prognostic factors of overall survival. Also, stage ( p=0.0007) was significantly predictive for overall survival in mutivariated analysis. Conclusion : This study showed the stage was found to be important prognostic factors, which influenced survival. Especially, as incomplete resection is related with poor results, complete resection is important to cure the invasive thymoma.

  12. Prognostic Factors and Treatment Outcome for Thymoma

    International Nuclear Information System (INIS)

    Kim, Hak Jae; Park, Charn Il; Shin, Seong Soo; Kim, Joo Hyun; Seo, Jeong Wook

    2001-01-01

    Purpose : In this retrospective study, we attempted to evaluate the treatment outcome and the prognostic factors of thymoma treated with surgery, radiotherapy and chemotherapy. Methods and materials : Between 1979 and 1998, 55 patients with thymoma were treated at the Seoul National University Hospital. Of these, 11 patients underwent surgery only, 33 patients received postoperative radiotherapy and 11 patients received radiotherapy only. Twenty-three patients had gross total resection and 21 patients subtotal resection. For postoperative radiotherapy, the radiation dose consisted of 41.4∼55.8 Gy. The average follow-up was 64 months, and ranged from 2 to 160 months. The sex ratio was 1:1 and the median age was 48 years (15∼74 years). Overall survival and disease-free survival were determined via the Kaplan-Meier method, and the log-rank was employed to evaluate for differences in prognostic factor. Results : The five- and 10-year survival rates were 87% and 65% respectively, and the median survival was 103 months. By univariate analysis, only stage ( p=0.0017) turned out to be significant prognostic factors of overall survival. Also, stage ( p=0.0007) was significantly predictive for overall survival in mutivariated analysis. Conclusion : This study showed the stage was found to be important prognostic factors, which influenced survival. Especially, as incomplete resection is related with poor results, complete resection is important to cure the invasive thymoma

  13. Prognostic factors affecting outcome of intrauterine insemination ...

    African Journals Online (AJOL)

    DOI: 10.4103/TJOG.TJOG_55_17. How to cite this article: Loto OM, Akindojutimi JA, Akinwole KD,. Ademulegun TV, Akinmade O. Prognostic factors affecting outcome ... follicle-stimulating hormone (FSH), prolactin, and estradiol on day 2 or day 3 of the ... were also screened for HIV, hepatitis B and C, and syphilis using the ...

  14. The prognostic significance of lung function in stable heart failure outpatients

    DEFF Research Database (Denmark)

    Plesner, Louis Lind; Dalsgaard, Morten; Schou, Morten

    2017-01-01

    BACKGROUND: This study investigated the impact on all-cause mortality of airflow limitation indicative of chronic obstructive pulmonary disease or restrictive spirometry pattern (RSP) in a stable systolic heart failure population. HYPOTHESIS: Decreased lung function indicates poor survival in heart...... failure. METHODS: Inclusion criteria: NYHA class II-IV and left ventricular ejection fraction (LVEF) criteria of obstructive airflow limitation were applied: FEV1 /FVC ... independent prognostic factors (pcriteria (HRGOLD 2.07 [95% CI 1.45-2.95] pcriteria (HR 1.74 [1.17-2.59] p=0.006). RSP was independently associated...

  15. Probabilistic conditional independence structures

    CERN Document Server

    Studeny, Milan

    2005-01-01

    Probabilistic Conditional Independence Structures provides the mathematical description of probabilistic conditional independence structures; the author uses non-graphical methods of their description, and takes an algebraic approach.The monograph presents the methods of structural imsets and supermodular functions, and deals with independence implication and equivalence of structural imsets.Motivation, mathematical foundations and areas of application are included, and a rough overview of graphical methods is also given.In particular, the author has been careful to use suitable terminology, and presents the work so that it will be understood by both statisticians, and by researchers in artificial intelligence.The necessary elementary mathematical notions are recalled in an appendix.

  16. The Biochemical Prognostic Factors of Subclinical Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Myung Won Lee

    2014-06-01

    Full Text Available BackgroundPatients with subclinical hypothyroidism (SHT are common in clinical practice. However, the clinical significance of SHT, including prognosis, has not been established. Further clarifying SHT will be critical in devising a management plan and treatment guidelines for SHT patients. Thus, the aim of this study was to investigate the prognostic factors of SHT.MethodsWe reviewed the medical records of Korean patients who visited the endocrinology outpatient clinic of Severance Hospital from January 2008 to September 2012. Newly-diagnosed patients with SHT were selected and reviewed retrospectively. We compared two groups: the SHT maintenance group and the spontaneous improvement group.ResultsThe SHT maintenance group and the spontaneous improvement group had initial thyroid-stimulating hormone (TSH levels that were significantly different (P=0.035. In subanalysis for subjects with TSH levels between 5 to 10 µIU/mL, the spontaneous improvement group showed significantly lower antithyroid peroxidase antibody (anti-TPO-Ab titer than the SHT maintenance group (P=0.039. Regarding lipid profiles, only triglyceride level, unlike total cholesterol and low density lipoprotein cholesterol, was related to TSH level, which is correlated with the severity of SHT. Diffuse thyroiditis on ultrasonography only contributed to the severity of SHT, not to the prognosis. High sensitivity C-reactive protein and urine iodine excretion, generally regarded as possible prognostic factors, did not show any significant relation with the prognosis and severity of SHT.ConclusionOnly initial TSH level was a definite prognostic factor of SHT. TPO-Ab titer was also a helpful prognostic factor for SHT in cases with mildly elevated TSH. Other than TSH and TPO-Ab, we were unable to validate biochemical prognostic factors in this retrospective study for Korean SHT patients.

  17. [Prognostic factors of mortality in a cohort of patients with in-hospital cardiorespiratory arrest].

    Science.gov (United States)

    de-la-Chica, R; Colmenero, M; Chavero, M J; Muñoz, V; Tuero, G; Rodríguez, M

    2010-04-01

    To define the prognostic factors related with mortality of patients who suffer cardiorespiratory arrest (CRA) in the hospital, according to Utstein style guidelines. A descriptive and prospective study covering a 30-month consecutive period of all the patients who suffered at least one episode of in-hospital CRA. A Cox regression multivariate analysis was made to identify the independent factors associated with mortality. A medical-surgical center in Hospital "Virgen de las Nieves" (HUVN), Granada (Spain). All the patients attended due to CRA in the hospital, except for those occurring in the operating and recovery room areas. They were followed-up to hospital discharge. Mortality on hospital discharge. 203 patients who suffered at least one cardiorespiratory arrest in the hospital, with a median age of 67 years and preponderance of male (60.6%). The most common location was in intensive care medicine unit (48%) and cardiac etiology (62%). Hospital survival rate was 23.15%. In multivariate analysis, strong predictors of mortality were administration of any dose of epinephrine during resuscitation maneuvers (OR 3.4; CI 95%. 1.6-7), total duration of resuscitation (HR 1.018; CI 95%, 1.012-1.024) and as protective factors the first ventricular fibrillation/ventricular tachycardia rhythm with no pulse (HR 0.6; CI 95%, 0.4-0.9) and witnessed by a doctor (HR 0.6; CI 95%, 0.5-0.9). The type of witness was identified among the predictors of mortality on hospital discharge after an episode of cardiac arrest. This becomes important because the qualification of healthcare personnel can be improved through adequate training. Copyright 2008 Elsevier España, S.L. y SEMICYUC. All rights reserved.

  18. The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia.

    Science.gov (United States)

    Samra, Mohamed A; Mahmoud, Hossam K; Abdelhamid, Thoraya M; El Sharkawy, Nahla M; Elnahass, Yasser H; Elgammal, Mossaad; Abdelfattah, Rafaat M; Eid, Salem; Ghaleb, Fayek M; Kamel, Azza M

    2013-09-01

    Minimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse. We aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients. Bone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS). Study included 57 adult ALL patients (44 males and 13 females) with a median age of 22 years (18-49). DFS showed no significant difference with age, gender and initial TLC (p=0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2 years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p = 0.057). Cumulative DFS at 2 years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p MRD1, OS at 2 years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p < 0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p = 0.017). MRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients. Copyright © 2013. Production and hosting by Elsevier B.V.

  19. Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis

  20. The prognostic role of preoperative serum CA 125 levels in patients with endometrial carcinoma.

    Science.gov (United States)

    Nikolaou, Marinos; Kourea, Helen P; Tzelepi, Vasiliki; Adonakis, Georgios; Scopa, Chrisoula D; Tsapanos, Vasilios; Kardamakis, Dimitrios; Kalofonos, Charalambos; Decavalas, Georgios

    2014-01-01

    Previous studies have shown that elevated preoperative serum CA 125 levels strongly correlate with various clinical and pathological variables and prognosis of patients with endometrial carcinoma (EC). The aim of the present study was to evaluate the clinical significance of preoperative serum CA 125 levels in patients with EC. A retrospective study of all EC patients treated at our institution between 1995 and 2010 with available follow-up was conducted. The preoperative serum level of CA 125 was measured in 99 patients and evaluated in relation to various clinical and pathological variables and outcome. We used the cut-off level of 20 U/ml for CA 125 on chi-square test for categorical variables. Survival analysis was performed with the use of Kaplan Meier method, the log rank test and Cox proportional hazards regression analysis. In the early stages of disease the mean values of CA 125 were 35 U/ml (SD±70) for stages IA-IB and 21 U/ml (SD±29) for stage IC (Mann-Whitney test for continuous variables). In advanced stages of disease (III-IV), the values of preoperative serum CA 125 levels were statistically increased, with mean value 54 U/ml (SD±44), in comparison to stages IA-IB (p=0.02) and IC (p=0.007). According to the multivariate analysis, elevated preoperative serum CA 125 level (p=0.043) and histological tumor type (p=0.004) were independent prognostic factors for disease free survival (DFS) and overall survival (OS) of patients with EC. The current study suggests that measurement of preoperative serum CA 125 is a useful clinical tool in the prognosis of patients with EC.

  1. Strong-back safety latch

    International Nuclear Information System (INIS)

    DeSantis, G.N.

    1995-01-01

    The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch

  2. Strong-back safety latch

    Energy Technology Data Exchange (ETDEWEB)

    DeSantis, G.N.

    1995-03-06

    The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch.

  3. Isocitrate Dehydrogenase-1 Mutations as Prognostic Biomarker in Glioblastoma Multiforme Patients in West Bohemia

    Directory of Open Access Journals (Sweden)

    J. Polivka

    2014-01-01

    Full Text Available Introduction. Glioblastoma multiforme (GBM is the most malignant primary brain tumor in adults. Recent whole-genome studies revealed novel GBM prognostic biomarkers such as mutations in metabolic enzyme IDH—isocitrate dehydrogenases (IDH1 and IDH2. The distinctive mutation IDH1 R132H was uncovered to be a strong prognostic biomarker for glioma patients. We investigated the prognostic role of IDH1 R132H mutation in GBM patients in West Bohemia. Methods. The IDH1 R132H mutation was assessed by the RT-PCR in the tumor samples from 45 GBM patients treated in the Faculty Hospital in Pilsen and was correlated with the progression free and overall survival. Results. The IDH1 R132H mutation was identified in 20 from 44 GBM tumor samples (45.4%. The majority of mutated tumors were secondary GBMs (16 in 18, 89.9%. Low frequency of IDH1 mutations was observed in primary GBMs (4 in 26, 15.3%. Patients with IDH R132H mutation had longer PFS, 136 versus 51 days (P<0.021, Wilcoxon, and OS, 270 versus 130 days (P<0.024, Wilcoxon test. Summary. The prognostic value of IDH1 R132H mutation in GBM patients was verified. Patients with mutation had significantly longer PFS and OS than patients with wild-type IDH1 and suffered more likely from secondary GBMs.

  4. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    International Nuclear Information System (INIS)

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei; Lu, Su; Tang, Huamei; Peng, Zhihai

    2014-01-01

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation

  5. The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Stühmer Walter

    2010-01-01

    Full Text Available Abstract Background The voltage-gated potassium channel hEag1 (KV10.1 has been related to cancer biology. The physiological expression of the human channel is restricted to the brain but it is frequently and abundantly expressed in many solid tumors, thereby making it a promising target for a specific diagnosis and therapy. Because chronic lymphatic leukemia has been described not to express hEag1, it has been assumed that the channel is not expressed in hematopoietic neoplasms in general. Results Here we show that this assumption is not correct, because the channel is up-regulated in myelodysplastic syndromes, chronic myeloid leukemia and almost half of the tested acute myeloid leukemias in a subtype-dependent fashion. Most interestingly, channel expression strongly correlated with increasing age, higher relapse rates and a significantly shorter overall survival. Multivariate Cox regression analysis revealed hEag1 expression levels in AML as an independent predictive factor for reduced disease-free and overall survival; such an association had not been reported before. As a functional correlate, specific hEag1 blockade inhibited the proliferation and migration of several AML cell lines and primary cultured AML cells in vitro. Conclusion Our observations implicate hEag1 as novel target for diagnostic, prognostic and/or therapeutic approaches in AML.

  6. The Relationship Between Human Papillomavirus Status and Other Molecular Prognostic Markers in Head and Neck Squamous Cell Carcinomas

    International Nuclear Information System (INIS)

    Kong, Christina S.; Narasimhan, Balasubramanian; Cao Hongbin; Kwok, Shirley; Erickson, Julianna P.; Koong, Albert; Pourmand, Nader; Le, Quynh-Thu

    2009-01-01

    Purpose: To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status. Methods and Materials: HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16 INK4a staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO 2 and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining). Results: Forty-four percent of evaluable tumors had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16 INK4a staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16 INK4a staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO 2 or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(-) tumors. Conclusion: HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(-) tumors.

  7. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    International Nuclear Information System (INIS)

    Vainshtein, Jeffrey M.; Schipper, Matthew; Zalupski, Mark M.; Lawrence, Theodore S.; Abrams, Ross; Francis, Isaac R.; Khan, Gazala; Leslie, William; Ben-Josef, Edgar

    2013-01-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  8. Satellite lymphovascular space invasion: An independent risk factor in early stage cervical cancer

    NARCIS (Netherlands)

    Pol, F.J.M.; Zusterzeel, P.L.M.; Ham, M.A. van; Kuijpers, D.A.; Bulten, J.; Massuger, L.F.

    2015-01-01

    OBJECTIVE: This study was performed to determine whether satellite LVSI in women with early stage cervical carcinoma is an independent prognostic factor for recurrence and survival. METHODS: A total of 210 eligible patients with FIGO stages IA2 and IB1 cervical carcinoma, who underwent radical

  9. Serum YKL-40 independently predicts outcome after transcatheter arterial chemoembolization of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Cheng-Bao Zhu

    Full Text Available Transcatheter arterial chemoembolization (TACE is the most widely used treatment option for unresectable hepatocellular carcinoma (HCC. Elevated serum YKL-40 level has been shown to predict poor prognosis in HCC patients undergoing resection. This study was designed to validate the prognostic significance of serum YKL-40 in patients with HCC undergoing TACE treatment.Serum YKL-40 level was determined by enzyme-linked immunosorbent assay. Overall survival (OS was evaluated with the Kaplan-Meier method and compared by the log-rank test. Multivariate study with Cox proportional hazard model was used to evaluate independent prognostic variables of OS.The median pretreatment serum YKL-40 in HCC patients with was significantly higher than that in healthy controls (P<0.001. The YKL-40 could predict survival precisely either in a dichotomized or continuous fashion (P<0.001 and P = 0.001, respectively. Multivariate Cox regression analysis indicated that serum YKL-40 was an independent prognostic factor for OS in HCC patients (P = 0.001. In further stratified analyses, YKL-40 could discriminate the outcomes of patients with low and high alpha-fetoprotein (AFP level (P = 0.006 and 0.016, respectively. Furthermore, the combination of serum YKL-40 and AFP had more capacity to predict patients' outcomes.Serum YKL-40 was demonstrated to be an independent prognostic biomarker in HCC patients treated with TACE. Our results need confirmation in an independent study.

  10. Distributed Prognostic Health Management with Gaussian Process Regression

    Science.gov (United States)

    Saha, Sankalita; Saha, Bhaskar; Saxena, Abhinav; Goebel, Kai Frank

    2010-01-01

    Distributed prognostics architecture design is an enabling step for efficient implementation of health management systems. A major challenge encountered in such design is formulation of optimal distributed prognostics algorithms. In this paper. we present a distributed GPR based prognostics algorithm whose target platform is a wireless sensor network. In addition to challenges encountered in a distributed implementation, a wireless network poses constraints on communication patterns, thereby making the problem more challenging. The prognostics application that was used to demonstrate our new algorithms is battery prognostics. In order to present trade-offs within different prognostic approaches, we present comparison with the distributed implementation of a particle filter based prognostics for the same battery data.

  11. Prognostic Effect of Complex Karyotype, Monosomal Karyotype, and Chromosome 17 Abnormalities in B-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Khoral, Priya; Atenafu, Eshetu G; Craddock, Kenneth J; Schimmer, Aaron; Chang, Hong

    2017-04-01

    The effect of monosomal karyotype (MK), complex karyotype (CK), and chromosome 17 abnormalities (abnl 17) on prognosis in B-cell acute lymphoid leukemia (B-ALL) has not yet been established. We conducted a retrospective analysis of prognostic factors on 237 adult patients with B-ALL treated at our institution. Older age (older than 60 years), higher white blood cell count (> 30), and abnl 17 were associated with shorter overall survival in univariate analysis, but multivariable analysis only identified older age as an independent poor prognostic actor. There was a significant correlation between abnl 17 and older age. In contrast to the patients with acute myeloid leukemia, our results show that MK and CK do not play a predictive role in patients with B-ALL, but further study is required to determine whether specific changes on chromosome 17 might have prognostic value when investigated separately. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

    Science.gov (United States)

    Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

    2011-06-01

    A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

  13. Prognostic role of ABO blood type in patients with extranodal natural killer/T cell lymphoma, nasal type: a triple-center study.

    Science.gov (United States)

    Li, Ya-Jun; Yi, Ping-Yong; Li, Ji-Wei; Liu, Xian-Ling; Tang, Tian; Zhang, Pei-Ying; Jiang, Wen-Qi

    2017-07-31

    The prognostic significance of ABO blood type for lymphoma is largely unknown. We evaluated the prognostic role of ABO blood type in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed clinical data of 697 patients with newly diagnosed ENKTL from three cancer centers. The prognostic value of ABO blood type was evaluated using Kaplan-Meier curves and Cox proportional hazard models. The prognostic values of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were also evaluated. Compared with patients with blood type O, those with blood type non-O tended to display elevated baseline serum C-reactive protein levels (P = 0.038), lower rate of complete remission (P = 0.005), shorter progression-free survival (PFS, P blood type O/AB had longer PFS (P blood type A/B. Multivariate analysis demonstrated that age >60 years (P blood type non-O were independent adverse predictors of OS (P = 0.001). ABO blood type was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the intermediate-to-low- and high-to-intermediate-risk groups. ABO blood type was an independent predictor of clinical outcome for patients with ENKTL.

  14. Titanium: light, strong, and white

    Science.gov (United States)

    Woodruff, Laurel; Bedinger, George

    2013-01-01

    Titanium (Ti) is a strong silver-gray metal that is highly resistant to corrosion and is chemically inert. It is as strong as steel but 45 percent lighter, and it is twice as strong as aluminum but only 60 percent heavier. Titanium dioxide (TiO2) has a very high refractive index, which means that it has high light-scattering ability. As a result, TiO2 imparts whiteness, opacity, and brightness to many products. ...Because of the unique physical properties of titanium metal and the whiteness provided by TiO2, titanium is now used widely in modern industrial societies.

  15. Comorbidity is an independent prognostic factor for the survival of ovarian cancer

    DEFF Research Database (Denmark)

    Sperling, Cecilie; Noer, Mette Calundann; Christensen, Ib Jarle

    2013-01-01

    the patients' comorbidity based on the registration in DGCD. The overall mortality (OS) from the date of surgery to death or censoring was the outcome measure. RESULTS: The hazard ratio (HR) for patients with comorbidity was 3.31 (1.14-1.50) compared to patients without comorbidity after adjustment for age...

  16. Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC

    NARCIS (Netherlands)

    Strell, Carina; Norberg, Karin Jessica; Mezheyeuski, Artur; Schnittert, Jonas; Kuninty, Praneeth R.; Moro, Carlos Fernández; Paulsson, Janna; Schultz, Nicolai Aagaard; Calatayud, Dan; Löhr, Johannes Matthias; Frings, Oliver; Verbeke, Caroline Sophie; Heuchel, Rainer Lothar; Prakash, Jai; Johansen, Julia Sidenius; Östman, Arne

    2017-01-01

    Background:The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness. Methods:We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases

  17. Prognostic value of 24-hour ambulatory ECG (Holter) monitoring in Boxer dogs.

    Science.gov (United States)

    Mõtsküla, P F; Linney, C; Palermo, V; Connolly, D J; French, A; Dukes McEwan, J; Fuentes, V Luis

    2013-01-01

    Boxer dogs are reported to be predisposed to arrhythmogenic right ventricular cardiomyopathy (ARVC), but the natural history has not been well characterized and inconsistent diagnostic criteria have been applied to identify affected dogs. Echocardiographic examination findings are unremarkable in many affected Boxer dogs, and in these dogs, 24-hour ambulatory ECG (Holter) monitoring often is used for diagnostic and prognostic purposes, despite limited information available relating Holter findings to outcome. Boxers with complex ventricular arrhythmias at initial presentation will have shorter survival times. The objective was to investigate the prognostic value of Holter monitoring in Boxer dogs. One hundred and twenty-two Boxer dogs seen at 3 university referral hospitals. Retrospective study. Survival times were obtained for Boxer dogs evaluated by echocardiography and a 24-hour Holter ECG. Kaplan-Meier survival analysis was used to estimate the median survival time and Cox proportional hazards analysis was used to identify variables independently associated with cardiac mortality. Outcome data were obtained for 122/163 dogs meeting the inclusion criteria. Of the 70 dogs that had died, 45 were considered to have suffered cardiac-related deaths. Median survival was significantly longer in dogs with a left ventricular systolic diameter (LVIDs) ≤ 35 mm compared with those with LVIDs > 35 mm (P 4.5 years, and male sex were independent predictors of cardiac mortality. Holter monitoring in Boxer dogs provides valuable prognostic information. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  18. A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer.

    Science.gov (United States)

    Kadalayil, L; Benini, R; Pallan, L; O'Beirne, J; Marelli, L; Yu, D; Hackshaw, A; Fox, R; Johnson, P; Burroughs, A K; Palmer, D H; Meyer, T

    2013-10-01

    The prognosis for patients with hepatocellular cancer (HCC) undergoing transarterial therapy (TACE/TAE) is variable. We carried out Cox regression analysis of prognostic factors using a training dataset of 114 patients treated with TACE/TAE. A simple prognostic score (PS) was developed, validated using an independent dataset of 167 patients and compared with Child-Pugh, CLIP, Okuda, Barcelona Clinic Liver Cancer (BCLC) and MELD. Low albumin, high bilirubin or α-fetoprotein (AFP) and large tumour size were associated with a two- to threefold increase in the risk of death. Patients were assigned one point if albumin 17 μmol/l, AFP >400 ng/ml or size of dominant tumour >7 cm. The Hepatoma arterial-embolisation prognostic (HAP) score was calculated by summing these points. Patients were divided into four risk groups based on their HAP scores; HAP A, B, C and D (scores 0, 1, 2 and >2, respectively). The median survival for the groups A, B, C and D was 27.6, 18.5, 9.0 and 3.6 months, respectively. The HAP score validated well with the independent dataset and performed better than other scoring systems in differentiating high- and low-risk groups. The HAP score predicts outcomes in patients with HCC undergoing TACE/TAE and may help guide treatment selection, allow stratification in clinical trials and facilitate meaningful comparisons across reported series.

  19. Prognostic factors in gastric carcinoma. Results of the German Gastric Carcinoma Study 1992.

    Science.gov (United States)

    Roder, J D; Böttcher, K; Siewert, J R; Busch, R; Hermanek, P; Meyer, H J

    1993-10-01

    The impact of patient- and tumor-dependent factors and the postoperative course on the prognosis of patients who underwent resection for gastric carcinoma between 1986 and 1989 were analyzed in a prospective multicenter observation study. Resection techniques, the extent of lymph node dissection, and the histopathologic assessment of the specimen were standardized at all participating centers. A total of 1654 patients were enrolled. Follow-up is complete for 99.2% of the patients, with a median follow-up time of 48 months. Prognostic factors were assessed by multivariate analysis. In the total patient population there was an independent prognostic effect of nodal status, a International Union Against Cancer (UICC)-R0 resection, distant metastases, the pT category, three or more risk factors on preoperative risk analysis, and the presence of postoperative complications. Multivariate analysis in the subgroup of patients who had a UICC-R0 resection confirmed the nodal status as the major independent prognostic factor. These data suggest that the prognosis of patients who undergo gastrectomy for gastric carcinoma may be improved by a complete resection of the primary tumor and its lymphatic drainage, resulting in a UICC-R0 resection. In addition, a detailed preoperative risk analysis and identification of high-risk patients and meticulous attention to the technical details of the surgical procedure to reduce the frequency of postoperative complications may improve the prognosis.

  20. Prognostic Factors of Peritoneal Metastases from Colorectal Cancer following Cytoreductive Surgery and Perioperative Chemotherapy

    Directory of Open Access Journals (Sweden)

    Yutaka Yonemura

    2013-01-01

    Full Text Available Background. Prolonged survival of patients affected by peritoneal metastasis (PM of colorectal origin treated with complete cytoreduction followed by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC has been reported. However, two-thirds of the patients after complete cytoreduction and perioperative chemotherapy (POC develop recurrence. This study is to analyze the prognostic factors of PM from colorectal cancer following the treatment with cytoreductive surgery (CRS + POC. Patients and Methods. During the last 8 years, 142 patients with PM of colorectal origin have been treated with CRS and perioperative chemotherapy. The surgical resections consisted of a combination of peritonectomy procedures. Results. Complete cytoreduction (CCR-0 was achieved at a higher rate in patients with peritoneal cancer index (PCI score less than 10 (94.7%, 71/75 than those of PCI score above 11 (40.2%, 37/67. Regarding the PCI of small bowel (SB-PCI, 89 of 94 (91.5% patients with ≤2 and 22 of 48 (45.8% patients with SB-PCI ≥ 3 rec