Science.gov

Sample records for poor prognostic characteristics

  1. Emerging prognostic markers related to mesenchymal characteristics of poorly differentiated breast cancers.

    PubMed

    Scimeca, Manuel; Antonacci, Chiara; Colombo, Daniele; Bonfiglio, Rita; Buonomo, Oreste Claudio; Bonanno, Elena

    2016-04-01

    Despite the screening program, breast cancer is the commonest cause of cancer death in women in the industrialized world. In this study, we investigate the correlation among poorly differentiated carcinoma, epithelial to mesenchymal transition (EMT) phenomenon, and expression of NF-kB, Sonic Hedgehog (SHH), K-RAS, and PTX3 in breast cancer in 100 breast biopsies. Samples were classified as follows: 30 benign lesions (BL), 30 ductal infiltrating carcinomas low grade (MLG1), and 40 ductal infiltrating carcinomas high grade (MLG3). Expression of vimentin, CD44, β-catenin, NF-kB, SHH, K-RAS, CD44, and PTX3 was studied by immunohistochemistry. The different rate of cells with vimentin, nuclear β-catenin, and CD44 expression in MLG3 as compared with MLG1 and BL suggested that the process of de-differentiation of breast cancer cells could be related to the EMT. Our results showed a significant increase in NF-kB signal in MLG3 (2.33 ± 0.77) with respect to MLG1 (1.26 ± 0.55) and BL (0.86 ± 0.52). SHH expression appeared low in BL (1.00 ± 0.41) and homogenously widespread in MLG1 (1.23 ± 0.63) and MLG3 (1.56 ± 0.54). An important increase in K-RAS signal was observed in MLG3 compared to that in BL (2.20 ± 0.69 vs 0.82 ± 0.59). As regards PTX3, we observed a strong expression in MLG3 (2.00 ± 0.78) with respect to BL (0.58 ± 0.55) and MLG1 (1.53 ± 0.76). The recurring expression of NF-kB, SHH, K-RAS, and PTX3 in vimentin- and CD44-positive breast cancer cells allows to speculate that breast cells acquire the ability to express these molecules in concomitance to EMT phenomenon.

  2. Elovl6 is a poor prognostic predictor in breast cancer

    PubMed Central

    FENG, YIN-HSUN; CHEN, WEI-YU; KUO, YU-HSUAN; TUNG, CHAO-LING; TSAO, CHAO-JUNG; SHIAU, AI-LI; WU, CHAO-LIANG

    2016-01-01

    Elongation of long chain fatty acids family member 6 (Elovl6) has been demonstrated to be involved in insulin resistance, obesity and lipogenesis. In addition, it has been reported that the protein is upregulated in human hepatocellular carcinoma and is implicated in nonalcoholic steatohepatitis-associated liver carcinogenesis. Excess body weight has been associated with an increased risk of postmenopausal breast cancer and poor prognosis. However, the connection between Elovl6 expression and outcome of breast cancer remains uncertain. Therefore, the present study used immunohistochemical analysis to investigate the expression of Elovl6 in breast cancer tissues from patients who had undergone curative mastectomy. Out of a total of 70 patients, 37.1% of patients exhibited positive Elovl6 expression in breast cancer tissue, whilst 62.9% were considered as negative. Positive Elov16 expression correlated with positive lymph node involvement and shorter recurrence-free survival. However, Elovl6 expression had no association with primary tumor size, lymph node metastasis, stage, grade, estrogen receptor, progesterone receptor, HER2 and age. Therefore, positive Elovl6 expression is a poor prognostic factor in patients with breast cancer that have previously undergone surgery, and may function as a potential therapeutic approach in the future, particularly in the scope of obesity related disease. PMID:27347126

  3. Masquerading Bundle Branch Block: A Poor Prognostic Sign Revisited

    PubMed Central

    Dhanse, Suheil; Kareem, Hashir; Devasia, Tom

    2016-01-01

    Masquerading bundle branch block is a rare but important finding on the Electrocardiogram (ECG). It is an indication of severe and diffuse conduction system disease and usually indicates poor prognosis. The precordial leads show a Right Bundle Branch Block (RBBB) pattern while the limb leads resemble a Left Bundle Branch Block (LBBB). This finding on an ECG is almost invariably associated with severe underlying heart disease. It is extremely important to be aware of this finding as it is a marker of poor cardiac outcomes. We report the case of a 68-year-old gentleman, who presented with progressive dyspnoea on exertion over three months. ECG showed a broad QRS complex with a RBBB pattern on the precordial leads and a LBBB pattern on the limb leads (suggestive of masquerading bundle branch block). A coronary angiogram revealed severe Triple Vessel Disease (TVD). The patient was scheduled for an early Coronary Artery By-Pass Grafting Surgery. However, his clinical condition deteriorated and he died while awaiting the surgery. PMID:27790494

  4. CHKA mediates the poor prognosis of lung adenocarcinoma and acts as a prognostic indicator

    PubMed Central

    Zhang, Li; Chen, Ping; Yang, Shen; Li, Guodong; Bao, Wentao; Wu, Peng; Jiang, Shujuan

    2016-01-01

    Choline kinase α (CHKA), the enzyme that converts choline to phosphocholine, has been studied in human carcinogenesis widely. However, the expression and underlying clinicopathological characteristics of CHKA in lung adenocarcinoma remains elusive. In the present study, a tissue microarray of 119 pairs of lung adenocarcinoma samples and corresponding adjacent normal mucosae was used to analysis CHKA expression by immunohistochemistry, and CHKA was observed to exhibit enhanced expression in lung adenocarcinoma tissues. Elevated CHKA expression in lung adenocarcinoma tissues at the gene and protein level was observed. The levels of CHKA expression were closely associated with the poor prognosis status of lung adenocarcinoma patients. Furthermore, certain clinicopathological characteristics such as tumor diameter and differentiation were observed to be significant in those lung adenocarcinoma patients who displayed enhanced CHKA expression. The analysis of CHKA expression could provide a more precise way to predict the prognosis of lung adenocarcinoma patients. Collectively, the present study revealed a novel biomarker in lung adenocarcinoma, and indicated that CHKA may be a promising prognostic marker and therapeutic target for lung adenocarcinoma. PMID:27588131

  5. Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients.

    PubMed

    Simpson, K; Jones, R E; Grimstead, J W; Hills, R; Pepper, C; Baird, D M

    2015-06-01

    Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer.

  6. Poor Prognostic Outcome in Cerebral Venous Sinus Thrombosis Associated with Dyskinesia and Elevated Platelet Volume.

    PubMed

    Wang, Shousen; Xu, Bingyang; Zhao, Qingshuang; Li, Jun; Hong, Jingfang; Wei, Liangfeng; Zhao, Lin

    2016-01-01

    Although about 80% of patients with cerebral venous sinus thrombosis have a good prognosis, some patients develop severe complications and a small proportion do not survive. The study included patients who had been diagnosed with cerebral venous sinus thrombosis in our hospital from May 2008 to February 2014. Based on the modified Rankin Scale (mRS) scores at 3 months for outcome, the patients were divided into two groups: good prognosis (mRS score ≤ 2) and poor prognosis (mRS score > 2). Univariate and multivariate regression analysis were performed to identify significant prognostic factors for poor outcome. A total of 86 patients with cerebral venous sinus thrombosis, 54 males and 32 females, average age 41.3 years (range, 3-83 years), were enrolled. Of these 86 patients, 64 (74.4%) had a good prognosis and 22 (25.6%) a poor prognosis. Univariate analysis revealed that dyskinesia was a significant risk factor (factor with odds ratio >1) for poor prognosis. In multivariate analysis, the risk of poor prognosis in patients with dyskinesia was 23 times higher than for those without dyskinesia (p < 0.001). Thrombosis of the sinus transervus was found to reduce the risk of poor prognosis in both univariate and multivariate analysis. Most patients with cerebral venous sinus thrombosis have a good prognosis but patients with dyskinesia have a poorer prognosis.

  7. Clinical characteristics and prognostic factors of brain central neurocytoma

    PubMed Central

    Zhou, Xilei; Tong, Yusuo; Wang, Wanwei

    2016-01-01

    Background & Aims This study is designed for the clinical characteristics and prognostic factors of central neurocytoma (CN). Methods CN patients from 2004 to 2012 were enrolled from the Surveillance Epidemiology and End Results (SEER) data. Clinical characteristics including age, sex, race, tumor size, tumor number, surgery, and radiation therapy were summarized. Univariate and multivariate analysis were performed to explore the prognostic factors of CN. Results CN tended to be borderline malignant and single lesion. Compared with other brain tumor (NCN), Patients with CN (CNs) were more likely to be female, young, and non-white race. Surgery was the primary treatment of CN. Univariate and Multivariate analysis indicated tumor number and surgery were both independent prognostic factors of CN (P < 0.05). Unifocal CNs had a lower mortality risk than multifocal ones (HR 0.167, 95% CI 0.052-0.537), surgery significantly reduced the death risk of CNs (HR 0.284, 95% CI 0.088-0.921). Conclusions CN tend to be borderline malignant, single lesion, operated on. Most CNs are female and younger. single lesion and surgery are the independent positive prognostic factors of CN. PMID:27542237

  8. Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma

    PubMed Central

    Lee, Yi-Ying; Chao, Tung-Bo; Sheu, Ming-Jen; Tian, Yu-Feng; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Lin, Ching-Yih; Li, Chien-Feng

    2016-01-01

    Background: Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting enzyme involving in the production of γ-aminobutyric acid (GABA), exists in the GABAergic neurons in the central nervous system (CNS). Little is known about the relevance of GAD1 to nasopharyngeal carcinoma (NPC). Through data mining on a data set derived from a published transcriptome database, this study first identified GAD1 as a differentially upregulated gene in NPC. We aimed to evaluate GAD1 expression and its prognostic effect on patients with early and locoregionally advanced NPC. Methods: We evaluated GAD1 immunohistochemistry and performed an H-score analysis on biopsy specimens from 124 patients with nonmetastasized NPC receiving treatment. GAD1 overexpression was defined as an H score higher than the median value. The findings of such an analysis are correlated with clinicopathological behaviors and survival rates, namely disease-specific survival (DSS), distant-metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) rates. Results: GAD1 overexpression was significantly associated with an increase in the primary tumor status (p < 0.001) and American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.002) and was a univariate predictor of adverse outcomes of DSS (p = 0.002), DMeFS (p < 0.0001), and LRFS (p = 0.001). In the multivariate comparison, in addition to advanced AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of short DSS (p = 0.004, hazard ratio = 2.234), DMeFS (p < 0.001, hazard ratio = 4.218), and LRFS (p = 0.013, hazard ratio = 2.441) rates. Conclusions: Our data reveal that GAD1 overexpression was correlated with advanced disease status and may thus be a critical prognostic indicator of poor outcomes in NPC and a potential therapeutic target to facilitate the development of effective treatment modalities. PMID:27698909

  9. Netrin-1 Expression Is an Independent Prognostic Factor for Poor Patient Survival in Brain Metastases

    PubMed Central

    Harter, Patrick N.; Zinke, Jenny; Scholz, Alexander; Tichy, Julia; Zachskorn, Cornelia; Kvasnicka, Hans M.; Goeppert, Benjamin; Delloye-Bourgeois, Céline; Hattingen, Elke; Senft, Christian; Steinbach, Joachim P.; Plate, Karl H.; Mehlen, Patrick; Schulte, Dorothea; Mittelbronn, Michel

    2014-01-01

    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. PMID:24647424

  10. Poor prognostic factors guiding treatment decisions in rheumatoid arthritis patients: a review of data from randomized clinical trials and cohort studies.

    PubMed

    Albrecht, Katinka; Zink, Angela

    2017-03-23

    Prognostic factors are used for treatment decisions in rheumatoid arthritis (RA). High disease activity, the early presence of erosions, and autoantibody positivity are the most frequently used poor prognostic factors but other features, such as functional disability, extraarticular disease, or multibiomarkers, are also assessed. Prognostic factors are incorporated in current treatment recommendations for the management of RA and are used as inclusion criteria in randomized controlled trials. They are defined heterogeneously and the relevance of a single or combined presence of poor prognostic factors remains unclear. This review summarizes the current definitions of poor prognostic factors and their use in clinical research. Perspectives on future research are also outlined.

  11. GATA3 Expression Is a Poor Prognostic Factor in Soft Tissue Sarcomas

    PubMed Central

    Haraguchi, Toshiaki; Miyoshi, Hiroaki; Hiraoka, Koji; Yokoyama, Shintaro; Ishibashi, Yukinao; Hashiguchi, Toshihiro; Matsuda, Koutaro; Hamada, Tetsuya; Okawa, Takahiro; Shiba, Naoto; Ohshima, Koichi

    2016-01-01

    Objective Recent studies have investigated the significance of GATA3 expression in patients with various malignant tumors. However, no previous studies have evaluated the clinicopathological importance of GATA3 expression in soft tissue sarcomas (STS) patients. Methods We evaluated GATA3 expression in 76 STS cases using immunohistochemical analysis, and statistically compared clinicopathological characteristics between GATA3-positive and GATA3-negative cases. Result GATA3-positive expression was significantly associated with a higher mitotic count (P < 0.0001). Disease-free survival (DFS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0104). Overall survival (OS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0006). GATA3-positive expression was significantly associated with shorter DFS in both univariate analysis (hazard ratio [HR], 2.719; P = 0.012) and multivariate analysis (HR, 2.711; P = 0.014). GATA3-positive expression was also significantly associated with worse OS in both univariate analysis (HR, 5.730; P = 0.0007) and multivariate analysis (HR, 5.789; P = 0.0008). Conclusion These results indicate that GATA3 is an independent prognostic factor and suggest that evaluation of GATA3 expression might enable more effective clinical follow-up using prognostic stratification of STS patients. PMID:27249072

  12. Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study.

    PubMed

    Blink, Marjolein; Zimmermann, Martin; von Neuhoff, Christine; Reinhardt, Dirk; de Haas, Valerie; Hasle, Henrik; O'Brien, Maureen M; Stark, Batia; Tandonnet, Julie; Pession, Andrea; Tousovska, Katerina; Cheuk, Daniel K L; Kudo, Kazuko; Taga, Takashi; Rubnitz, Jeffrey E; Haltrich, Iren; Balwierz, Walentyna; Pieters, Rob; Forestier, Erik; Johansson, Bertil; van den Heuvel-Eibrink, Marry M; Zwaan, C Michel

    2014-02-01

    Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (± 2%), with the overall survival rate being 79% (± 2%), the cumulative incidence of relapse 12% (± 2%), and the cumulative incidence of toxic death 7% (± 1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse, we could risk-stratify patients into two groups: cases with a normal karyotype (n=103) with a higher cumulative incidence of relapse (21%± 4%) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (± 2%) (P=0.004). Multivariate analyses revealed that white blood cell count ≥ 20 × 10(9)/L and age >3 years were independent predictors for poor event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols.

  13. Autoinflammatory diseases in adults. Clinical characteristics and prognostic implications.

    PubMed

    González García, A; Patier de la Peña, J L; Ortego Centeno, N

    2017-03-01

    Autoinflammatory diseases are clinical conditions with inflammatory manifestations that present in a periodic or persistent manner and are caused by acquired or hereditary disorders of the innate immune response. In general, these diseases are more common in childhood, but cases have been reported in adults and are therefore important for all specialists. There are few references on these diseases in adults due to their low prevalence and underdiagnosis. The aim of this study is to review the scientific literature on these disorders to systematise their clinical, prognostic and treatment response characteristics in adults.

  14. A Papillary Thyroid Microcarcinoma Revealed by a Single Bone Lesion with No Poor Prognostic Factors

    PubMed Central

    Godbert, Yann; Henriques-Figueiredo, Benedicte; Cazeau, Anne-Laure; Carrat, Xavier; Stegen, Marc; Soubeyran, Isabelle; Bonichon, Francoise

    2013-01-01

    Objectives. Thyroid carcinomas incidence, in particular papillary variants, is increasing. These cancers are generally considered to have excellent prognosis, and papillary microcarcinomas are usually noninvasive. Many prognostic histopathology factors have been described to guide therapeutic decisions. Most patients are treated with total thyroidectomy without radioiodine treatment or partial surgery. Case Summary. A 65-year-old man with no significant medical history presented with pain in the left chest wall that had been present for several months. A computed tomography (CT) found a large tissue mass of 4 cm responsible for lysis of the middle arch of the 4th rib on the left. It was a single lesion, highly hypermetabolic on the 18-FDG PET/CT. The histology analysis of the biopsy and surgical specimen favored an adenocarcinoma with immunostaining positive for TTF1 and thyroglobulin (Tg). The total thyroidectomy carried out subsequently revealed a 4 mm papillary microcarcinoma with vesicular architecture of the right lobe, well delimited and distant from the capsule without vascular embolisms. After two radioiodine treatments, the patient is in complete clinical, biological, and radiological remission. Conclusion. This extremely rare case of a singular bone metastasis revealing a papillary thyroid microcarcinoma illustrates the necessity of further research to better characterize the forms of papillary thyroid microcarcinomas with potentially poor prognosis. PMID:23509641

  15. Prognostics

    NASA Technical Reports Server (NTRS)

    Goebel, Kai; Vachtsevanos, George; Orchard, Marcos E.

    2013-01-01

    Knowledge discovery, statistical learning, and more specifically an understanding of the system evolution in time when it undergoes undesirable fault conditions, are critical for an adequate implementation of successful prognostic systems. Prognosis may be understood as the generation of long-term predictions describing the evolution in time of a particular signal of interest or fault indicator, with the purpose of estimating the remaining useful life (RUL) of a failing component/subsystem. Predictions are made using a thorough understanding of the underlying processes and factor in the anticipated future usage.

  16. A 'new normal': Exploring the disruption of a poor prognostic cancer diagnosis using interviews and participant-produced photographs.

    PubMed

    Balmer, Claire; Griffiths, Frances; Dunn, Janet

    2015-09-01

    Cancer survival is increasing, and many people are living years after cancer treatment. For example, it is predicted that 46 per cent of men and 56 per cent of women diagnosed in 2007 in England and Wales will survive their cancer for 5 years or more. However, 'survivors' may be living with significant physical, psychological and social disruption caused by their illness. Furthermore, huge disparities exist in the outcomes for different cancer 'types', and there has been little investigation of those living with 'poor prognostic' cancers. Our aim was to explore the experience of living after the diagnosis of a poor prognostic cancer. Data were gathered from 30 people via interviews and participants' own photographs. Our findings suggest that a full 'recovery' may be impossible after a cancer diagnosis. Such diagnoses will continue to threaten biographical trajectory and self-identity forever. 'Returning to normal' was considered highly important for participants, but a changed normality had to be accepted in which lives were managed carefully and a constant fear of recurrence created liminality and made 'survivorship' ambiguous. Experience was often complicated by the social response associated with cancer that hindered communication and increased isolation. Participant-produced photographs, used here for the first time specifically by a sample of people with poor prognosis cancer, proved to be an acceptable data collection method and have added a poignancy and 'completeness' to the data that have arguably led to a more comprehensive understanding.

  17. Overexpression of Pleomorphic Adenoma Gene-Like 2 Is a Novel Poor Prognostic Marker of Prostate Cancer

    PubMed Central

    Guo, Jia; Wang, Min; Wang, Zhishun; Liu, Xiuheng

    2016-01-01

    Pleomorphic adenoma gene like-2 (PLAGL2) is a member of the PLAG gene family. Previous studies have revealed that overexpression of PLAGL2 is associated with many human cancers. However, it has been reported that PLAGL2 also plays as a tumor suppressor. The precise role of PLAGL2 in prostate cancer (PCa) is still unknown. The aim of this study was to investigate the expression and prognostic value of PLAGL2 in PCa. Data from microarray datasets demonstrated that the DNA copy number and mRNA level of PLAGL2 were significantly increased in PCa compared with normal prostate. qRT-PCR and western blot analysis from paired PCa samples and prostate cell lines confirmed upregulated mRNA and protein expression levels in PCa. Immunohistochemistry analysis showed that staining of PLAGL2 in PCa tissues was significantly higher than that in benign prostatic hyperplasia (BPH) tissues. In addition, the high expression of PLAGL2 was only involved in preoperative PSA, but was not related to age, Gleason score, seminal vesicle invasion, surgical margin status, clinical stage and positive lymph node metastasis. Moreover, our results showed that PLAGL2 was an independent prognostic factor for biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients, and overexpressed PLAGL2 was related to early development of BCR and poor OS. In conclusion, our findings suggest that PLAGL2 is overexpressed in PCa. The increased expression of PLAGL2 correlates to PCa progression following radical prostatectomy and may serve as a novel poor prognostic marker for PCa. PMID:27537362

  18. Aberrant phenotypic expression of CD15 and CD56 identifies poor prognostic acute promyelocytic leukemia patients.

    PubMed

    Breccia, Massimo; De Propris, Maria Stefania; Minotti, Clara; Stefanizzi, Caterina; Raponi, Sara; Colafigli, Gioia; Latagliata, Roberto; Guarini, Anna; Foà, Robin

    2014-02-01

    Limited information is available on the relationship between expression of some additional aberrant phenotypic features and outcome of acute promyelocytic leukemia (APL) patients. Here, we set out to assess the frequency of CD15 and CD56 expression, and their prognostic value in a large series of APL patients. One hundred and fourteen adult patients consecutively diagnosed with PML/RARα-positive APL and homogeneously treated with the AIDA induction schedule at a single institution were included in the study. Twelve (10.5%) and 9 (8%) of the 114 patients expressed CD15 and CD56, respectively. CD15 expression identified a subset of patients with a classic morphologic subtype (92%), a prevalent association with a bcr1 expression (67%) with an unexpectedly higher frequency of relapses (42% vs 20% for the CD15- patients, p=0.03) and a low overall survival (OS) (median OS at 5 years 58% vs 85% for the CD15- patients, p=0.01). CD56 expression was detected only in patients with a classic morphologic subtype, a prevalent bcr3 expression (67%), high incidence of differentiation syndrome (55%), higher frequency of relapse (34% vs 20% for the CD56- population, p=0.04) and a low OS (60% vs 85% for the CD56- population p=0.02). We hereby confirm the negative prognostic value of CD56 and we show that the same applies also to cases expressing CD15. These aberrant markers may be considered for the refinement of risk-adapted therapeutic strategies in APL patients.

  19. GPR48, a poor prognostic factor, promotes tumor metastasis and activates β-catenin/TCF signaling in colorectal cancer.

    PubMed

    Wu, Jinhua; Xie, Na; Xie, Ke; Zeng, Jun; Cheng, Lin; Lei, Yunlong; Liu, Yuan; Song, Linhong; Dong, Dandan; Chen, Yi; Zeng, Rui; Nice, Edouard C; Huang, Canhua; Wei, Yuquan

    2013-12-01

    G-protein-coupled receptor 48 (GPR48) is an orphan receptor belonging to the G-protein-coupled receptors family, which plays an important role in the development of various organs and cancer development and progression such as gastric cancer and colorectal cancer (CRC). However, the prognostic value of GPR48 expression in patients with CRC has not been reported. In this study, we observed that GPR48 was overexpressed in primary CRC and metastatic lymph nodes and closely correlated with tumor invasion and metastasis. Multivariate analysis indicated that high GPR48 expression was a poor prognostic factor for overall survival in CRC patients. In vitro and in vivo assays demonstrated that enforced expression of GPR48 contributed to enhance migration and invasion of cancer cells and tumor metastasis. In addition, we found that GPR48 increased nuclear β-catenin accumulation, T-cell factor 4 (TCF4) transcription activity, and expression of its target genes including Cyclin D1 and c-Myc in CRC cells. Correlation analysis showed that GPR48 expression in CRC tissues was positively associated with β-catenin expression. Upregulation of GPR48 resulted in increased phosphorylation of glycogen synthase kinase 3β, Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) in CRC cells, while inhibition of PI3K/Akt and mitogen-activated protein kinase /ERK1/2 pathways was sufficient to abolish the effect of GPR48 on β-catenin/TCF signaling. Taken together, GPR48 could serve as both a prognostic biomarker and a therapeutic target for resectable CRC patients.

  20. Family Structure and Employment Characteristics Differentiate Poor from Near-Poor Workers.

    ERIC Educational Resources Information Center

    Dagata, Elizabeth M.

    1997-01-01

    Current Population Survey data indicate that rural workers were more likely than urban workers to be poor or near-poor. Poor and near-poor rural workers were more likely than other workers to be southern, young, and in a minority group. Barriers to livable-wage employment included low educational attainment, being a single mother, and having young…

  1. Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer.

    PubMed

    Ayub, Tiyasha H; Keyver-Paik, Mignon-Denise; Debald, Manuel; Rostamzadeh, Babak; Thiesler, Thore; Schröder, Lars; Barchet, Winfried; Abramian, Alina; Kaiser, Christina; Kristiansen, Glen; Kuhn, Walther; Kübler, Kirsten

    2015-06-30

    Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes.

  2. Prognostic Factors for Poor Cognitive Development in Children Born Very Preterm or With Very Low Birth Weight: A Systematic Review

    PubMed Central

    Linsell, Louise; Malouf, Reem; Morris, Joan; Kurinczuk, Jennifer J.; Marlow, Neil

    2016-01-01

    Importance Cognitive delay is the most common form of impairment among children born very preterm (VPT) at 32 weeks or less or with very low birth weight (VLBW) of 1250 g or less. It is important to identify factors that are robust predictors of long-term outcome because the ability to predict future prognosis will assist in health care and educational service planning and provision. Objective To identify prognostic factors for poor cognitive development in children born VPT or with VLBW. Evidence Review A systematic review was conducted using MEDLINE, EMBASE, and PyscINFO databases to identify studies published between January 1, 1990, and June 1, 2014, reporting multivariable prediction models for neurodevelopment in VPT or VLBW children. Thirty-one studies comprising 98 risk factor models for cognitive outcome were identified. Two independent reviewers extracted key information on study design, outcome definition, risk factor selection, model development, and reporting and conducted a risk-of-bias assessment. Findings There was evidence that male sex, nonwhite race/ethnicity, lower level of parental education, and lower birth weight were predictive of global cognitive impairment in children younger than 5 years. In older children, only the influence of parental education was sustained. Male sex was also predictive of language impairment in early infancy, but not in middle childhood. Gestational age was a poor predictor of cognitive outcome, probably because of a reduced discriminatory power in cohorts restricted to a narrow gestational age range. The prognostic value of neonatal brain injury was unclear; however, studies adopted mixed strategies for managing children with physical or neurosensory disability. Conclusions and Relevance The influence of perinatal risk factors on cognitive development of VPT or VLBW children appears to diminish over time as environmental factors become more important. It is difficult to isolate cognitive outcomes from motor and

  3. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

    PubMed Central

    Westhovens, R; Robles, M; Ximenes, A C; Nayiager, S; Wollenhaupt, J; Durez, P; Gomez-Reino, J; Grassi, W; Haraoui, B; Shergy, W; Park, S-H; Genant, H; Peterfy, C; Becker, J-C; Covucci, A; Helfrick, R; Bathon, J

    2009-01-01

    Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile. PMID:19124524

  4. Expression of CD44v6 is an independent prognostic factor for poor survival in patients with esophageal squamous cell carcinoma.

    PubMed

    Shiozaki, Midori; Ishiguro, Hideyuki; Kuwabara, Yoshiyuki; Kimura, Masahiro; Mitsui, Akira; Naganawa, Yasuhiro; Shibata, Takahiro; Fujii, Yoshitaka; Takeyama, Hiromitsu

    2011-05-01

    CD44v6 has been causally associated with the development of metastases and with poor prognosis in various human malignancies. To elucidate the clinicopathological significance of CD44v6 expression in esophageal squamous cell carcinoma (ESCC), the present study aimed to investigate the expression of CD44v6 using immunohistological techniques. Using specific antibodies against CD44v6 and CD44s, expression of the proteins was analyzed immunohistochemically in 63 primary esophageal ESCCs, which were previously resected at the Nagoya City University Hospital without pre-operative induction therapy. Using light microscopy, the positive expression of CD44v6 was divided into a low- or high-expression group. The expression of CD44v6 in ESCC was analyzed with respect to various clinicopathological characteristics. The frequency of CD44v6 expression was 90.5% (57/63). The CD44v6 high-expression group comprised 55.6% of the patients (n=35) and the low expression group included 44.4% of the patients (n=28). In this study, no significant difference was observed between any clinicopathological factor and the immunohistochemical expression of CD44v6. In patients with high levels of CD44v6 expression, survival was markedly worse (p=0.0327). Favorable outcomes were observed for the clinicopathological characteristics of 6 patients whose tissue immunohistochemical expression of CD44v6 was not detected. Moreover, multivariate analysis confirmed that expression of CD44v6 was an independent prognostic indicator (risk ratio =2.793; p=0.0301). Overexpression of CD44v6 is a useful prognostic indicator of ESCC. Therefore, CD44v6 should be investigated as a potential target for therapy.

  5. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    SciTech Connect

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei; Lu, Su; Tang, Huamei; Peng, Zhihai

    2014-06-27

    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.

  6. CXCR2 expression in tumor cells is a poor prognostic factor and promotes invasion and metastasis in lung adenocarcinoma

    PubMed Central

    Saintigny, Pierre; Massarelli, Erminia; Lin, Steven; Chen, Yulong; Goswami, Sangeeta; Erez, Baruch; O’Reilly, Michael S.; Liu, Diane; Lee, J. Jack; Zhang, Li; Ping, Yuan; Behrens, Carmen; Soto, Luisa M. Solis; Heymach, John V.; Kim, Edward S.; Herbst, Roy S.; Lippman, Scott M.; Wistuba, Ignacio I.; Hong, Waun Ki; Kurie, Jonathan M.; Koo, Ja Seok

    2012-01-01

    CXCR2 in non-small cell lung cancer (NSCLC) has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. Here, we examined the prognostic importance of CXCR2 in NSCLC and the role of CXCR2 and its ligands in lung cancer cells. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from a murine KRAS/p53-mutant lung adenocarcinoma cell line with high metastatic potential and an orthotopic syngeneic mouse model and in vitro using a CXCR2 small molecule antagonist (SB225002). CXCR2 protein expression was analyzed in tumor cells from 262 NSCLC. Gene expression profiles for CXCR2 and its ligands (CXCR2 axis) were analyzed in 52 human NSCLC cell lines and 442 human lung adenocarcinomas. Methylation of CXCR2 axis promoters was determined in 70 human NSCLC cell lines. Invasion and metastasis were decreased in CXCR2 knockdown clones in vitro and in vivo. SB225002 decreased invasion in vitro. In lung adenocarcinomas, CXCR2 expression in tumor cells was associated with smoking and poor prognosis. CXCR2 axis gene expression profiles in human NSCLC cell lines and lung adenocarcinomas defined a cluster driven by CXCL5 and associated with smoking, poor prognosis and RAS pathway activation. Expression of CXCL5 was regulated by promoter methylation. The CXCR2 axis may be an important target in smoking-related lung adenocarcinoma. PMID:23204236

  7. TMPRSS4 as an emerging potential poor prognostic factor for solid tumors: A systematic review and meta-analysis

    PubMed Central

    Zeng, Ping; Zhang, Peng; Zhou, Li-Na; Tang, Min; Shen, Yi-Xin; Jin, Jun; Zhu, Ya-Qun; Chen, Min-Bin

    2016-01-01

    Recent studies have investigated the potential prognostic value of the transmembrane protease serine 4 (TMPRSS4) in various solid tumors. Yet, the results are inconclusive. Here, we performed this meta-analysis to clarify this issue. Relevant articles were identified by searching PubMed, Web of Science and Embase databases. The primary outcome endpoints were patients' overall survival (OS) and time to tumor progression (TTP). Twelve studies involving 1,955 participants were included. We showed that high TMPRSS4 expression in tumor tissues was significantly associated with patients' poor OS (pooled HR = 2.981, 95% CI = 2.296-3.869, P < 0.001) and short TTP (pooled HR = 2.456, 95% CI = 1.744-3.458, P < 0.001). A subgroup analysis revealed that the association between TMPRSS4 and the outcome endpoints (OS or TTP) was also significant within China region. We conclude that TMPRSS4 overexpression in solid tumors is associated with patients' poor prognosis. TMPRSS4 could be a valuable prognosis biomarker or a promising therapeutic target of solid tumor. PMID:27344186

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

    SciTech Connect

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

    2012-02-01

    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.

  9. Prognostic indicators of poor outcome in horses with laminitis at a tertiary care hospital.

    PubMed

    Orsini, James A; Parsons, Corrina Snook; Capewell, Linda; Smith, Gary

    2010-06-01

    This retrospective study investigated the factors associated with a poor outcome (death by euthanasia or from other causes) in horses treated for laminitis at a tertiary care hospital. Cases (n = 247) were defined as patients with laminitis that were euthanized or that died of other causes during hospitalization. Controls (n = 344) were patients with laminitis that survived to be discharged from the hospital. In the final multivariate analysis, the factors significantly associated with an increased risk for death and their respective odds ratios (OR) were as follows: Thoroughbred (OR = 1.57); racehorse (OR = 1.76); treatment with flunixin meglumine (OR = 1.76); vascular pathology (OR = 2.12); distal displacement of the third phalanx (OR = 2.68); pneumonia (OR = 2.87); and lameness of Obel grade II (OR = 2.99), grade III (OR = 9.63), or grade IV (OR = 20.48). The use of glue-on shoes significantly reduced the risk for death (OR = 0.36).

  10. Epidemiological, clinical and prognostic profile of childhood acute bacterial meningitis in a resource poor setting

    PubMed Central

    Kuti, Bankole Peter; Bello, Emmanuel Olasehinde; Jegede, Tolulope Opeoluwa; Olubosede, Omolayo

    2015-01-01

    Background: Childhood bacterial meningitis is a neurologic emergency that continues to kill and maims children particularly in developing countries with poor immunization coverage. Objective: This study set out to assess the hospital incidence, pattern of presentation, etiologic agents, outcome and determinants of mortality among the children admitted with bacterial meningitis at the Wesley Guild Hospital (WGH), Ilesa. Patients and Methods: We carried out a retrospective review of admitted cases of bacterial meningitis in children aged one month to 15 years at the WGH, Ilesa over a three year period by looking at the hospital records. Factors in the history and examinations were compared among survivors and those that died to determine factors significantly associated with mortality in these children. Results: Eighty-one (5.5%) of the 1470 childhood admissions during the study period had bacterial meningitis. Male preponderance was observed and two-thirds of the children were infants. More cases were admitted during the wet rainy season than during the dry harmattan season. Haemophilus influenzae type B and Streptococcus pneumoniae were the leading etiologic agents and ciprofloxacin and ceftriaxone adequately cover for these organisms. Twenty-two (27.2%) of the 81 children died, while 34 (42.0%) survived with neurologic deficits. Children with multiple seizures, coma, neck retraction, hyponatremia, hypoglycorrhachia, turbid CSF as well as Gram positive meningitis at presentation were found to more likely to die (P < 0.05). None of these factors however independently predict mortality. Conclusion: Childhood bacterial meningitis often results in death and neurologic deficit among infants and young children admitted at the WGH, Ilesa. Children diagnosed with meningitis who in addition had multiple seizures, neck retraction and coma at presentation are at increased risk of dying. PMID:26752902

  11. Poor Prognostic Factors in Patients with Parenteral Nutrition-Dependent Pediatric Intestinal Failure

    PubMed Central

    Choi, Shin Jie; Lee, Kyung Jae; Choi, Jong Sub; Yang, Hye Ran; Chang, Ju Young; Ko, Jae Sung

    2016-01-01

    Purpose Parenteral nutrition (PN) not only provides nutritional support but also plays a crucial role in the treatment of children with intestinal failure. The aim of this study was to evaluate the clinical significance and clinical outcomes of long-term PN. Methods Retrospective cohort study was conducted using the medical records of patients treated at Seoul National University Children's Hospital. This study included 19 patients who received PN for over six months. Most patients received home PN. Results The indications for PN included short bowel syndrome, chronic intestinal pseudo-obstruction, and intractable diarrhea of infancy. The median age of PN initiation was 1.3 years, and the median treatment duration was 2.9 years. Two patients were weaned from PN; 14 continued to receive PN with enteral feedings; and 3 patients died. The overall survival rates at 2 and 5 years were 93.3% and 84.0%, respectively. The incidence of catheter-related bloodstream infections was 2.7/1,000 catheter-days and was associated with younger age at PN initiation and lower initial height Z-score. Six patients developed catheter-related central vein thrombosis, with an incidence of 0.25/1,000 catheter-days. Eleven patients experienced PN-associated liver disease (PNALD), and one patient underwent multi-visceral transplant. The patients with PNALD exhibited lower final heights and body weight Z-scores. All patients experienced micronutrient deficiencies transiently while receiving PN. Conclusion PN is an important and safe treatment for pediatric intestinal failure. PNALD was linked to final anthropometric poor outcomes. Micronutrient deficiencies were common. Anthropometric measurements and micronutrient levels must be monitored for successful PN completion. PMID:27066448

  12. Phosphorylation of GSK3α/β correlates with activation of AKT and is prognostic for poor overall survival in acute myeloid leukemia patients

    PubMed Central

    Ruvolo, Peter P.; Qiu, YiHua; Coombes, Kevin R.; Zhang, Nianxiang; Neeley, E. Shannon; Ruvolo, Vivian R.; Hail, Numsen; Borthakur, Gautam; Konopleva, Marina; Andreeff, Michael; Kornblau, Steven M.

    2015-01-01

    Background Acute myeloid leukemia (AML) patients with highly active AKT tend to do poorly. Cell cycle arrest and apoptosis are tightly regulated by AKT via phosphorylation of GSK3α and β isoforms which inactivates these kinases. In the current study we examine the prognostic role of AKT mediated GSK3 phosphorylation in AML. Methods We analyzed GSK3α/β phosphorylation by reverse phase protein analysis (RPPA) in a cohort of 511 acute myeloid leukemia (AML) patients. Levels of phosphorylated GSK3 were correlated with patient characteristics including survival and with expression of other proteins important in AML cell survival. Results High levels of p-GSK3α/β correlated with adverse overall survival and a lower incidence of complete remission duration in patients with intermediate cytogenetics, but not in those with unfavorable cytogenetics. Intermediate cytogenetic patients with FLT3 mutation also fared better respectively when p-GSK3α/β levels were lower. Phosphorylated GSK3α/β expression was compared and contrasted with that of 229 related cell cycle arrest and/or apoptosis proteins. Consistent with p-GSK3α/β as an indicator of AKT activation, RPPA revealed that p-GSK3α/β positively correlated with phosphorylation of AKT, BAD, and P70S6K, and negatively correlated with β-catenin and FOXO3A. PKCδ also positively correlated with p-GSK3α/β expression, suggesting crosstalk between the AKT and PKC signaling pathways in AML cells. Conclusions These findings suggest that AKT-mediated phosphorylation of GSK3α/β may be beneficial to AML cell survival, and hence detrimental to the overall survival of AML patients. Intrinsically, p-GSK3α/β may serve as an important adverse prognostic factor for a subset of AML patients. PMID:26674329

  13. Prognostic factors and epidemiological characteristics of cutaneous and mucosal head and neck melanoma.

    PubMed

    Berzina, Anna; Azarjana, Kristine; Cema, Ingrida; Pjanova, Dace; Rivosh, Alexander

    2011-01-01

    OBJECTIVE. To describe the prognostic factors and epidemiological characteristics of cutaneous and mucosal head and neck melanoma and to identify the variables associated with mortality from this disease. MATERIAL AND METHODS. Patients treated for head and neck melanoma in the Oncology Centre of Latvia, Riga during a 10-year period were identified. Records from 124 cases were analyzed in a descriptive, retrospective study. For each patient, information regarding age, sex, tumor anatomic site, as well as ulceration, histological tumor subtypes, Breslow thickness and Clark invasion level was viewed. Disease specific survival rates were calculated. The frequencies of all study variables and their 95% confidence intervals were determined. Kaplan-Meier survival curves were produced to illustrate the survival differences for each variable. RESULTS. The patients' mean age was 67.36 years. The study included 81 females (65.32%) and 43 males (34.67%). The prevalent anatomical site for cutaneous head and neck melanoma was the cheek - 49% (n=55) and the intraocular site for mucosal melanoma (61.5%). A high percentage of thick cutaneous melanoma was detected. In 53 cases (47.3%) out of 112 cutaneous melanoma the tumor ulceration was found. Nodular melanoma subtype was predominating (38%). The incidence of cutaneous melanoma has increased unequally whereas mucosal melanoma of the head and neck is an uncommon cancer and the incidence rates in Latvia during a ten year period are decreasing. CONCLUSION. Female sex, advanced age, facial skin, tumor thickness, nodular subtype and ulceration carried a relevant risk of poor prognosis.

  14. Association of Nuclear Localization of a Long Interspersed Nuclear Element-1 Protein in Breast Tumors with Poor Prognostic Outcomes

    PubMed Central

    Harris, Chris R.; Normart, Robin; Yang, Qifeng; Stevenson, Elizabeth; Haffty, Bruce G.; Ganesan, Shridar; Cordon-Cardo, Carlos; Levine, Arnold J.; Tang, Laura H.

    2010-01-01

    Within healthy human somatic cells, retrotransposition by long interspersed nuclear element-1 (also known as LINE-1 or L1) is thought to be held in check by a variety of mechanisms, including DNA methylation and RNAi. The expression of L1-ORF1 protein, which is rarely found in normal tissue, was assayed using antibodies with a variety of clinical cancer specimens and cancer cell lines. L1-ORF1p expression was detected in nearly all breast tumors that the authors examined, and the protein was also present in a high percentage of ileal carcinoids, bladder, and pancreatic neuroendocrine tumors, as well as in a smaller percentage of prostate and colorectal tumors. Tumors generally demonstrated cytoplasmic L1-ORF1p; however, in several breast cancers, L1-ORF1p was nuclear. Patients with breast tumors displaying nuclear L1-ORF1p had a greater incidence of both local recurrence and distal metastases and also showed poorer overall survival when compared with patients with tumors displaying cytoplasmic L1-ORF1p. These data suggest that expression of L1-ORF1p is widespread in many cancers and that redistribution from cytoplasm to nucleus could be a poor prognostic indicator during breast cancer. High expression and nuclear localization of L1-ORF1p may result in a higher rate of L1 retrotransposition, which could increase genomic instability. PMID:20948976

  15. Open globe eye injury characteristics and prognostic factors in Jazan, Saudi Arabia

    PubMed Central

    Makhrash, Mashaal A.; Gosadi, Ibrahim M.

    2016-01-01

    Objectives To evaluate characteristics and prognostic factors of open globe injuries (OGI) presented to King Fahad Specialist Hospital in the Jazan region, Saudi Arabia. Methods This study is a retrospective review of medical records of OGI patients who underwent operative repair of their injuries in King Fahad Central Hospital, Jazan, Saudi Arabia between January 2011 and December 2013. Demographic information, eye injury, preoperative, and postoperative visual acuity were collected. The initial and final visual acuity outcomes were compared to identify subjects who witnessed any improvement in their visual acuity. Logistic regression was used to assess characteristics associated with improvements in the visual acuity. Results Number of included cases was 120. Most frequently reported causes of injury were blunt trauma (20%) and shattered glass (18.3%). Approximately half of the cases were reported to have iris injuries or hyphema. Most cases suffered penetration (37.5%) of the eye globe. Only zone I injury was significantly associated with better visual acuity outcomes (odds ratio [OR]: 2.447, p=0.036). Among the variables that were associated with poorer prognostic outcomes, only aphakia (OR: 0.180), retinal damage (OR: 0.062), vitreous hemorrhage (OR: 0.266), and zone III injuries (OR: 0.092) were statistically significant (p<0.05). Conclusion Zone I injury appears to have a better prognostic effect on visual acuity where injuries related to Zone III were associated with worse prognostic outcomes. PMID:27874147

  16. Clinical characteristics and prognostic factors in Chinese patients with Hodgkin's lymphoma.

    PubMed

    Zhu, Ying-Jie; Sun, Yue-Li; Xia, Yi; Jiang, Wen-Qi; Huang, Jia-Jia; Huang, Hui-Qiang; Lin, Tong-Yu; Guan, Zhong-Zhen; Li, Zhi-Ming

    2012-06-01

    The aim of our study is to investigate the clinical characteristics and prognostic factors in Chinese Hodgkin's lymphoma patients. It is known that clinical characteristics and epidemiology of Hodgkin's lymphoma in China are different from Western countries. In total, 137 consecutive, previously untreated patients with Hodgkin's lymphoma at Sun Yat-Sen University Cancer Center were enrolled. Among these patients, 92 were male and 45 were female, with a median age of 28 (range: 2-76) years. The bimodal age curve of classical Hodgkin's lymphoma analyzed from our patients was not obvious as the Western population, showing an early peak in 25 years and a second peak in 45 years. Most of the patients (41.6%) were classified as nodular sclerosis classic Hodgkin's lymphoma. Results showed that the 5-year overall survival, event-free survival, and disease-free survival rates were 97.7, 85.0, and 94.0%, respectively. Lymphopenia at diagnosis was related to poorer overall survival (P = 0.015) and event-free survival (P < 0.001) in all-stage Hodgkin's lymphoma patients. Multivariate analysis showed that lymphopenia as an independent unfavorable prognostic factor influenced event-free survival (P = 0.015). The international prognostic score ≥ 5 was also the only independent prognostic factor of disease-free survival in advanced-stage patients (P = 0.046). Our findings demonstrated that some clinical characteristics of Hodgkin's lymphoma in China were different from those in the Western countries. Lymphopenia was an effective prognostic predictor in both early stage and advanced stage.

  17. Clinical characteristics and prognostic indicators for metastatic melanoma: data from 446 patients in north China.

    PubMed

    Hao, Mengze; Zhao, Gang; Du, Xiaoling; Yang, Yun; Yang, Jilong

    2016-08-01

    Melanoma is an extremely rare tumor in Asia. This retrospective study aimed to identify the clinical characteristics and prognostic factors of metastatic melanoma patients at Tianjin Medical University Cancer Hospital over the last 30 years. Survival analysis was performed with Kaplan-Meier, log-rank test, and multivariate Cox regression method using SPSS 19.0 software. The 1-, 2-, and 5-year survival rates of metastatic melanoma patients were 52, 32, and 16 %, respectively. Median overall survival (OS) was 13.5 months, median progression-free survival (PFS) 9.0 months, and median disease-free survival 20.3 months. Furthermore, patients with a single metastatic site achieved better OS and PFS than those with two or more metastatic lesions (OS 21.6 vs. 8.9 months, P < 0.001; PFS 11.3 vs. 7.1 months, P < 0.001). Survival times of patients with visceral metastases were the shortest (OS 8.5 months; PFS 7.5 months). Specifically, patients with primary mucosal lesions had a worse OS (9.7 months) and PFS (6.8 months) than those with acral (19.2 and 15.6 months, respectively) or non-acral primary lesions (11.8 and 11.1 months, respectively). The treatment of advanced melanoma was unitary, and prognoses of patients with metastatic melanoma in China were poor. Visceral metastasis, multiple metastatic sites, and primary mucosal lesions were significant predictors of survival of patients with metastatic melanoma. Those with primary mucosal lesions had significantly worse survivals than those with primary cutaneous lesions. More active involvement in clinical studies and more feedback on various treatment options are required.

  18. Coalesced Multicentric Analysis of 2,351 Patients With Myelodysplastic Syndromes Indicates an Underestimation of Poor-Risk Cytogenetics of Myelodysplastic Syndromes in the International Prognostic Scoring System

    PubMed Central

    Schanz, Julie; Steidl, Christian; Fonatsch, Christa; Pfeilstöcker, Michael; Nösslinger, Thomas; Tuechler, Heinz; Valent, Peter; Hildebrandt, Barbara; Giagounidis, Aristoteles; Aul, Carlo; Lübbert, Michael; Stauder, Reinhard; Krieger, Otto; Garcia-Manero, Guillermo; Kantarjian, Hagop; Germing, Ulrich; Haase, Detlef; Estey, Elihu

    2011-01-01

    Purpose The International Prognostic Scoring System (IPSS) remains the most commonly used system for risk classification in myelodysplastic syndromes (MDSs). The IPSS gives more weight to blast count than to cytogenetics. However, previous publications suggested that cytogenetics are underweighted in the IPSS. Here we investigate the prognostic impact of cytogenetic subgroups compared with that of bone marrow blast count in a large, multicentric, international patient cohort. Patients and Methods In total, 2,351 patients with MDS who have records in the German-Austrian and the MD Anderson Cancer Center databases were included and analyzed in univariate and multivariate models regarding overall survival and risk of transformation to acute myeloid leukemia (AML). The data were analyzed separately for patients treated with supportive care without specific therapy, with AML-like chemotherapy, or with other therapy regimens (low-dose chemotherapy, demethylating agents, immune modulating agents, valproic acid, and cyclosporine). Results The prognostic impact of poor-risk cytogenetic findings (as defined by the IPSS classification) on overall survival was as unfavorable as an increased (> 20%) blast count. The hazard ratio (compared with an abnormal karyotype or a bone marrow blast count < 5%) was 3.3 for poor-risk cytogenetics, 4.8 for complex abnormalities harboring chromosomes 5 and/or 7, and 3.1 for a blast count of 21% to 30% (P < .01 for all categories). The predictive power of the IPSS cytogenetic subgroups was unaffected by type of therapy given. Conclusion The independent prognostic impact of poor-risk cytogenetics on overall survival is equivalent to the impact of high blast counts. This finding should be considered in the upcoming revision of the IPSS. PMID:21519021

  19. Prognostic value of the International Neuroblastoma Pathology Classification in Neuroblastoma (Schwannian stroma-poor) and comparison with other prognostic factors: a study of 182 cases from the Spanish Neuroblastoma Registry.

    PubMed

    Burgues, Octavio; Navarro, Samuel; Noguera, Rosa; Pellín, Antonio; Ruiz, Amparo; Castel, Victoria; Llombart-Bosch, Antonio

    2006-10-01

    In addition to clinical and biological factors, further valuable prognostic information in neuroblastoma (Schwannian stroma-poor) (NB) patients is provided by the histopathologic analysis and the application of the International Neuroblastoma Pathology Classification (INPC) system. The objective of this study was to assess the prognostic impact of the INPC classification in a series of NB (Schwannian stroma-poor) and its relation with other prognostic factors. One hundred eighty-two cases of NB were collected from the files of the Spanish Neuroblastoma Registry. Slides were reviewed, and NB cases were grouped into favorable and unfavorable categories according to INPC criteria, taking into account morphological features (mitosis-karyorrhexis index, histological subtype) and patient's age at diagnosis. Other pathological [presence of calcifications, tissular components, and number of mitotic cells per 10 high-power field (HPF)], immunohistochemical (P-glycoprotein and Ki-67 protein expression) and genetic (MYCN amplification and chromosome 1p deletion) features were also studied. Statistical analyses of overall survival with Kaplan-Meier curves and a multivariate study using Cox regression were performed (40.3% of NBs were considered favorable and 59.7% unfavorable). Unfavorable NB showed a mean survival time of 57 months compared with 89 months in favorable cases. Advanced stage, more than ten mitoses per 10 HPF, Ki-67 expression in more than 30% of tumor cells, MYCN oncogene amplification and chromosome 1p deletion were observed more frequently in unfavorable NB. The Cox regression analysis demonstrated that clinical stage (International Neuroblastoma Staging System stage 4) and histological subtype (undifferentiated NB) were the most important factors that influence the overall survival (p<0.001). INPC classification results are major prognostic indicators in NB and should be considered in the therapeutic stratification of NB patients.

  20. Clinical characteristics and prognostic factors of patients with mature T-cell lymphoid malignancies: a single-institution study of 225 cases.

    PubMed

    Xue, Wen; Sheng, Yan; Weng, Xiangqin; Zhu, Yongmei; Zhao, Yan; Xu, Pengpeng; Fei, Xiaochun; Chen, Xiaoyan; Wang, Li; Zhao, Weili

    2015-12-01

    Mature T-cell lymphoid malignancies comprise a group of heterogeneous diseases that vary in clinicopathological features, biological behavior, treatment response, and prognosis. Bone marrow (BM) infiltration is more commonly present in mature T-cell lymphoid malignancies compared with their B-cell counterparts and hence important for differential diagnosis. In this study, clinical characteristics and prognostic factors were analyzed in 225 patients with mature T-cell lymphoid malignancies treated in a single institution. These included 29 cases of T-cell lymphoproliferative disorders (T-LPD, all with BM infiltration) and 196 cases of T-/natural-killer-cell lymphoma (T/NKCL, 56 with BM infiltration and 140 without BM infiltration). The estimated 5-year overall survival (OS) rates of T-LPD and T/NKCL were 96.6% and 37.3%, respectively. T-LPD patients were less likely to exhibit poor performance status, advanced disease stage, presence of B symptoms, or abnormal level of serum β-2 microglobulin. With similar pathological characteristics, T/NKCL patients with BM infiltration showed significantly lower response rates and shorter OS than those without BM infiltration (P = 0.0264 and P < 0.0001, respectively). Multivariate analysis indicated that poor performance status, advanced disease stage, elevated serum lactate dehydrogenase level, and BM involvement were independent unfavorable prognostic factors. The Glasgow Prognostic Score may be more efficient than the International Prognostic Index in predicting disease outcome in T/NKCL. In conclusion, clinical characteristics may be useful in more effectively stratifying patients with mature T-cell lymphoid malignancies.

  1. CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia

    PubMed Central

    Palmi, Chiara; Savino, Angela M.; Silvestri, Daniela; Bronzini, Ilaria; Cario, Gunnar; Paganin, Maddalena; Buldini, Barbara; Galbiati, Marta; Muckenthaler, Martina U.; Bugarin, Cristina; Mina, Pamela Della; Nagel, Stefan; Barisone, Elena; Casale, Fiorina; Locatelli, Franco; Nigro, Luca Lo; Micalizzi, Concetta; Parasole, Rosanna; Pession, Andrea; Putti, Maria C.; Santoro, Nicola; Testi, Anna M.; Ziino, Ottavio; Kulozik, Andreas E.; Zimmermann, Martin; Schrappe, Martin; Villa, Antonello; Gaipa, Giuseppe; Basso, Giuseppe; Biondi, Andrea; Valsecchi, Maria G.; Stanulla, Martin; Conter, Valentino; te Kronnie, Geertruy; Cazzaniga, Giovanni

    2016-01-01

    Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL. We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers. Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated. Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib. In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway. PMID:27449287

  2. Up-regulation of KIF14 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer

    PubMed Central

    Wang, Wenjing; Shi, Yanhua; Li, Jing; Cui, Wei; Yang, Baozhi

    2016-01-01

    Kinesin family member 14 (KIF14) is a member of kinesin family proteins which have been found to be dysregulated in various cancer types. However, the expression of KIF14 and its potential prognostic significance have not been investigated in cervical cancer. Real-time PCR was performed to assess the expression levels of KIF14 in 47 pairs of cervical cancer tissues and their matched normal tissues from patients who had not been exposed to chemotherapy as well as tissue samples from 57 cervical cancer patients who are sensitive to paclitaxel treatment and 53 patients who are resistant. The association between KIF14 expression levels in tissue and clinicopathological features or chemosensitivity was examined. Kaplan–Meier analysis and Cox proportional hazards model were applied to assess the correlation between KIF14 expression levels and overall survival (OS) of cervical cancer patients. KIF14 expression levels were significantly increased in cervical cancer tissues compared with matched non-cancerous tissues and it was higher in tissues of patients who are chemoresistant compared with those who are chemosensitive. KIF14 expression was positively associated with high tumour stage (P=0.0044), lymph node metastasis (P=0.0034) and chemoresistance (P<0.0001). Kaplan–Meier analysis showed that high KIF14 expression levels predicted poor survival in patients with (P=0.0024) or without (P=0.0028) paclitaxel treatment. Multivariate analysis revealed that KIF14 was an independent prognostic factor for OS. Our study suggests that KIF14 may serve as a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer. PMID:27128470

  3. Human BDH2, an anti-apoptosis factor, is a novel poor prognostic factor for de novo cytogenetically normal acute myeloid leukemia

    PubMed Central

    2013-01-01

    Background The relevance of recurrent molecular abnormalities in cytogenetically normal (CN) acute myeloid leukemia (AML) was recently acknowledged by the inclusion of molecular markers such as NPM1, FLT3, and CEBPA as a complement to cytogenetic information within both the World Health Organization and the European Leukemia Net classifications. Mitochondrial metabolism is different in cancer and normal cells. A novel cytosolic type 2-hydroxybutyrate dehydrogenase, BDH2, originally named DHRS6, plays a physiological role in the cytosolic utilization of ketone bodies, which can subsequently enter mitochondria and the tricarboxylic acid cycle. Moreover, BDH2 catalyzes the production of 2, 3-DHBA during enterobactin biosynthesis and participates in 24p3 (LCN2)-mediated iron transport and apoptosis. Results We observed that BDH2 expression is an independent poor prognostic factor for CN-AML, with an anti-apoptotic role. Patients with high BDH2 expression have relatively shorter overall survival (P = 0.007) and a low complete response rate (P = 0.032). BDH2-knockdown (BDH2-KD) in THP1 and HL60 cells increased the apoptosis rate under reactive oxygen species stimulation. Decrease inducible survivin, a member of the inhibitors of apoptosis family, but not members of the Bcl-2 family, induced apoptosis via a caspase-3-independent pathway upon BDH2-KD. Conclusions BDH2 is a novel independent poor prognostic marker for CN-AML, with the role of anti-apoptosis, through surviving. PMID:23941109

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

    PubMed

    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 < adenoma > 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.

  5. Glutaminase expression is a poor prognostic factor in node-positive triple-negative breast cancer patients with a high level of tumor-infiltrating lymphocytes.

    PubMed

    Kim, Joo Young; Heo, Sun-Hee; Choi, Seul Ki; Song, In Hye; Park, In Ah; Kim, Young-Ae; Park, Hye Seon; Park, Suk Young; Bang, Won Seon; Gong, Gyungyub; Lee, Hee Jin

    2017-04-01

    Glutamine metabolism is emerging as one aspect of dysregulated metabolism of tumors. Triple-negative breast cancer (TNBC) cells are glutamine dependent, whereas luminal-type cells tend to be glutamine independent. Therefore, TNBC patients might benefit from therapies targeting glutamine metabolism. To investigate the clinical significance of glutamine metabolism, we examined expression and prognostic significance of glutaminase in tumor cells and tumor-infiltrating lymphocytes (TILs) in TNBC. We retrieved 658 surgically resected TNBCs and analyzed glutaminase expression in tumor cells and TILs by immunohistochemical staining. Glutaminase expression was observed in 237 cases (36.0%) in tumor cells and 104 cases (15.5%) in TILs. Although glutaminase expression in tumor cells was significantly associated with a low level of TILs (p = 0.018), glutaminase expression in TILs was significantly higher in cases with a high level of TILs (p = 0.031). Glutaminase expression in tumor cells was significantly associated with poor disease-free survival in patients with lymph node metastasis and high levels of TILs (p = 0.020). In addition, it was an independent poor prognostic factor (hazard ratio = 10.643, 95% confidence interval = 1.999-56.668; p = 0.006). Glutaminase expression in tumor cells was observed in a subset of TNBC patients. It was significantly associated with a low level of TILs and poor disease-free survival in TNBCs presenting with lymph node metastasis and high levels of TILs.

  6. Elevated neutrophil-to-lymphocyte ratio is an independent poor prognostic factor in patients with intrahepatic cholangiocarcinoma

    PubMed Central

    Mao, Yize; Wang, Jun; Shuang, Zeyu; Chen, Jianlin; Li, Shengping

    2016-01-01

    We investigated whether elevated neutrophil-to-lymphocyte ratio (NLR) was associated with poor anti-tumor immunity and prognosis in patients with intrahepatic cholangiocarcinoma (ICC). Clinicopathologic data of 102 patients with ICC who underwent hepatectomy was retrospectively analyzed. The Kaplan-Meier method and Cox regression model were used to analyze the survival and prognosis. The percentage of overall lymphocytes, T cells and CD8+ T cells in the high NLR group was lower than that in the low NLR group. The percentage of PD-1+CD4+ and PD-1+CD8+ T cells was higher and the percentage of IFN-γ+CD4+ and IFN-γ+CD8+ T cells was lower in the high NLR group than that in the low NLR group (p = 0.045, p = 0.008; p = 0.012, p = 0.006). Density of tumor-infiltrating CD3+ T cells in the high NLR group was lower than that in the low NLR group (p < 0.001). Elevated NLR was an independent predictor for poor overall survival (OS; p = 0.035) and recurrence-free survival (RFS; p = 0.008). These results indicate that elevated NLR is associated with poor anti-tumor immunity and could be a poor biomarker for prognosis in patients with ICC. PMID:26918355

  7. EphA2 expression is a key driver of migration and invasion and a poor prognostic marker in colorectal cancer

    PubMed Central

    Blayney, Jaine K.; McArt, Darragh G.; Redmond, Keara L.; Weir, Jessica-Anne; Bradley, Conor A.; Sasazuki, Takehiko; Shirasawa, Senji; Wang, Tingting; Srivastava, Supriya; Ong, Chee Wee; Arthur, Ken; Salto-Tellez, Manuel; Wilson, Richard H.

    2015-01-01

    Purpose EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumour initiation, neo-vascularization and metastasis in a wide range of epithelial and mesenchymal cancers, however its role in colorectal cancer (CRC) recurrence and progression is unclear. Experimental Design EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumours (N=338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive CRC cell line models. Results Colorectal tumours displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III CRC tissues, in both univariate and multivariate analyses. Pre-clinically, we found that EphA2 was highly expressed in KRASMT CRC cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines and down-regulation of EphA2 using RNAi or recombinant EFNA1, suppressed migration and invasion of KRASMT CRC cells. Conclusions These data show that EpHA2 is a poor prognostic marker in stage II/III CRC, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. PMID:26283684

  8. The Characteristics and Prognostic Effect of E-Cadherin Expression in Colorectal Signet Ring Cell Carcinoma

    PubMed Central

    Wang, Renjie; Ma, Xiaoji; Li, Yaqi; He, Yiping; Huang, Dan; Cai, Sanjun; Peng, Junjie

    2016-01-01

    Purpose Signet ring cell carcinoma (SRCC) is rare. The aim of this study is to understand the clinicopathological features and identify the possible prognostic factors in colorectal SRCC. Methods Patients with SRCC who underwent primary lesion resection at Fudan University Shanghai Cancer Center from September 2008 to July 2014 were retrospectively analyzed. Patient’s gender, age, tumor location, depth of invasion, lymph node metastasis, synchronous distant metastasis, perineural invasion, lymphovascular invasion, and E-cadherin expression were studied with prognosis, and the correlation between E-cadherin expression and clinicopathological features were analyzed. All clinicopathological and molecular factors were put into multivariate analysis using Cox proportional hazards model for detecting independent prognostic factors. Results 59 patients accounting for 0.89% of total colorectal cancer patients met the criteria and were enrolled in the study. The median survival time is 28.9 months, and the 3-year survival rate is 62.7%. SRCC were seen more common in young male patients. Advanced stage was more common in SRCC, 58 (98.3%) patients had T3/T4 lesions, 52 (88.1%) patients had lymph node metastasis, and 14 (23.7%) patients had distant metastasis. Distant metastases were seen more common in peritoneal cavity. Distant metastasis (HR = 4.194, 95% CI: 1.297–13.567), lymphovascular invasion (HR = 2.888, 95% CI: 1.115–7.483), and E-cadherin expression (HR = 0.272, 95% CI: 0.096–0.768) were independent predictors for survival. Conclusions SRCC is a rare subtype of colorectal cancer with poor prognosis. Distant metastasis, lymphovascular invasion, and E-cadherin expression can predict prognosis of colorectal SRCCs independently. More precise therapy and more close surveillance are needed for these patients. PMID:27509205

  9. Immunohistochemical and Molecular Characteristics with Prognostic Significance in Diffuse Large B-Cell Lymphoma

    PubMed Central

    Bellas, Carmen; García, Diego; Vicente, Yolanda; Kilany, Linah; Abraira, Victor; Navarro, Belen; Provencio, Mariano; Martín, Paloma

    2014-01-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We analyzed 100 cases of DLBCL to evaluate the prognostic value of immunohistochemical markers derived from the gene expression profiling-defined cell origin signature, including MYC, BCL2, BCL6, and FOXP1 protein expression. We also investigated genetic alterations in BCL2, BCL6, MYC and FOXP1 using fluorescence in situ hybridization and assessed their prognostic significance. BCL6 rearrangements were detected in 29% of cases, and BCL6 gene alteration (rearrangement and/or amplification) was associated with the non-germinal center B subtype (non-GCB). BCL2 translocation was associated with the GCB phenotype, and BCL2 protein expression was associated with the translocation and/or amplification of 18q21. MYC rearrangements were detected in 15% of cases, and MYC protein expression was observed in 29% of cases. FOXP1 expression, mainly of the non-GCB subtype, was demonstrated in 37% of cases. Co-expression of the MYC and BCL2 proteins, with non-GCB subtype predominance, was observed in 21% of cases. We detected an association between high FOXP1 expression and a high proliferation rate as well as a significant positive correlation between MYC overexpression and FOXP1 overexpression. MYC, BCL2 and FOXP1 expression were significant predictors of overall survival. The co-expression of MYC and BCL2 confers a poorer clinical outcome than MYC or BCL2 expression alone, whereas cases negative for both markers had the best outcomes. Our study confirms that DLBCL, characterized by the co-expression of MYC and BCL2 proteins, has a poor prognosis and establishes a significant positive correlation with MYC and FOXP1 over-expression in this entity. PMID:24887414

  10. RAD21 cohesin overexpression is a prognostic and predictive marker exacerbating poor prognosis in KRAS mutant colorectal carcinomas

    PubMed Central

    Deb, S; Xu, H; Tuynman, J; George, J; Yan, Y; Li, J; Ward, R L; Mortensen, N; Hawkins, N J; McKay, M J; Ramsay, R G; Fox, S B

    2014-01-01

    Background: RAD21 is a component of the cohesion complex and is integral to chromosome segregation and error-free DNA repair. RAD21 is functionally important in tumour progression but its role in colorectal carcinoma (CRC) is unclear. We therefore assessed its clinicopathological and prognostic significance in CRC, as well as its effect on chemosensitivity. Methods: A retrospective observation study examined RAD21 expression in 652 CRCs using a tissue microarray approach. Correlation with clinicopathological factors including gender, tumour grade, mucinous subtype, TNM stage, disease-specific survival (DSS), BRAF and KRAS mutation status, tumour p53 immunostaining, tumour microsatellite instability and tumour CpG island methylator phenotype was performed. Colorectal cancer cell clones with stable RAD21 knockdown were generated and tested for cellular sensitivity to conventional chemotherapeutic drugs. Results: RAD21 expression was significantly correlated with male gender (56.7% vs 43.3%, P=0.02), well-differentiated histology (14.4% vs 4.0%, P=0.0001), higher T-stage (36.1% vs 27.0%, P=0.01), presence of metastasis (18.8% vs 12.6%, P=0.03), and shorter DSS (hazard ratio (HR) 1.4, 95% CI 1.1 to 1.9, P=0.01) in both univariate and multivariate analysis. RAD21 expression was associated with shorter DSS in patients with KRAS mutant tumours (HR:2.6, 95% CI:1.4–4.3, P=0.001) and in patients receiving adjuvant chemoradiotherapy (HR:1.9, 95% CI:1.2–3.0, P=0.008). Colorectal cancer cells with RAD21 knockdown exhibited enhanced sensitivity to 5-fluorouracil, either alone or in combination with oxaliplatin. Conclusions: RAD21 expression in CRC is associated with aggressive disease especially in KRAS mutant tumours and resistance to chemoradiotherapy. RAD21 may be an important novel therapeutic target. PMID:24548858

  11. Whole-exome sequencing of muscle-invasive bladder cancer identifies recurrent copy number variation in IPO11 and prognostic significance of importin-11 overexpression on poor survival

    PubMed Central

    He, Minghui; Zhang, Zhensheng; Zeng, Shuxiong; Ma, Chong; Sun, Yinghao; Xu, Chuanliang

    2016-01-01

    Non-muscle-invasive bladder cancer (NMIBC) often has a worse prognosis following its progression to muscle-invasive bladder cancer (MIBC), despite radical cystectomy with pelvic lymph node dissection combined with chemotherapy. Therefore, the discovery of novel biomarkers for predicting the progression of this disease and of therapeutic targets for preventing it is crucial. We performed whole-exome sequencing to analyze superficial tumor tissues (Tsup) and basal tumor tissues (Tbas) from 3 MIBC patients and identified previously unreported copy number variations in IPO11 that warrants further investigation as a molecular target. In addition, we identified a significant association between the absolute copy number and mRNA expression of IPO11 and found that high importin-11 expression was correlated with poor 3-year overall survival (OS), cancer-specific survival (CSS) and cancer-free survival (CFS) compared with low expression in the BCa patients. Importin-11 overexpression was also an independent risk factor for CSS and CFS in the BCa patients. Our study has revealed that IPO11 copy number amplification contributes to its overexpression and that these changes are unfavorable prognostic factors in NMIBC. Thus, IPO11 copy number amplification and importin-11 overexpression are promising biomarkers for predicting the progression and poor prognosis of patients with NMIBC. PMID:27689332

  12. High levels of plasma malondialdehyde, protein carbonyl, and fibrinogen have prognostic potential to predict poor outcomes in patients with diabetic foot wounds: a preliminary communication.

    PubMed

    Rattan, Roma; Nayak, Debashish

    2008-12-01

    Diabetic foot ulcer (DFU) is the leading cause of lower extremity amputation and is generally known to have poor prognosis. Oxidative stress is considered important in the pathogenesis of chronic wounds. Fibrinogen is a recognized marker in peripheral vascular disease; increasing levels predict an increased mortality and risk of amputation. The aim of this study was to evaluate if plasma malondialdehyde (MDA), protein carbonyl (PC) and fibrinogen levels can be used as prognostic markers in patients with DFU. The study design was prospective, nonrandomized, and controlled. A total of 41 DFU grade 1 and 20 DFU grade 2 patients were studied in this case-control study. Diabetic controls without foot ulcers and healthy controls were also studied. Plasma MDA, PC, and fibrinogen levels were significantly higher in patients with DFU compared with those without ulcers (P < .05) and nondiabetic controls (P < .001). These parameters increased in association with DFU grade (P < .01). Increased levels of plasma fibrinogen, MDA, and PC correlated with worsened outcomes. An augmented oxidative stress and plasma fibrinogen level >300.4 mg% (95% confidence interval, 100% sensitivity, 99.2% specificity) was correlated with a high risk of amputation in DFU.

  13. Clinical characteristics and prognostic factors for relapse in patients with polymyalgia rheumatica (PMR).

    PubMed

    Lee, Jung Hwa; Choi, Sang Tae; Kim, Jin Su; Yoon, Bo Young; Kwok, Seung-Ki; Kim, Hyun-Sook; Kim, Yun Sung; Song, Jung-Soo; Lee, Sang-Heon; Kim, Hae-Rim

    2013-06-01

    Polymyalgia rheumatica (PMR) is a common inflammatory disease of the elderly in western countries, but the prevalence is apparently different between races and countries. Until now, an epidemiologic study of PMR is limited in Korea. We retrospectively evaluated the clinical data of 78 patients with PMR who were treated in 5 tertiary hospitals, and analyzed initial laboratory data, symptoms, therapeutic responses, and prognostic factors for relapse 1 year after treatments. Sixty percent of patients had pain in both shoulder and hip girdles with 10.6 weeks of duration, 75.9 ± 32.7 mm/h of erythrocyte sedimentation rate (ESR), and 6.2 ± 6.4 mg/dl of C-reactive protein. The rate of relapse and remission at 1 year was 38.4 and 2.5 %, respectively. The rate of overall relapse was 46.1 %, and the relapse occurred mostly in a year, especially between 6 and 12 months after diagnosis. There were more female in relapse group (88.9 %, p = 0.037), and cumulative steroid dose of 1 year was significantly higher in relapse group (5.5 ± 2.7 vs. 4.4 ± 2.5 g, p = 0.018). Independent risk factors for relapse were initial CRP ≥ 2.5 mg/dl (OR 6.296, p = 0.047) and the use of hydroxychloroquine (OR 6.798, p = 0.035). Initial dosage or tapering speed of steroid did not influence on prognosis. In Korean patients with PMR, baseline clinical characteristics and relapse rate were similar to previous studies, but our patients accompanied no giant cell arteritis and showed lower remission rate as well as delayed therapeutic response and later occurrence of relapse. More aggressive management would be needed according to the clinical status of patients.

  14. Clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease.

    PubMed

    Park, Jin Kyoung; Lee, Chang Hun; Kim, In Hee; Kim, Seon Min; Jang, Ji Won; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae-Ghon

    2015-05-01

    Bacterial infection is an important cause of death in patients with liver cirrhosis. The aim of this study was to investigate the clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease (ALD). We retrospectively analyzed data from 409 patients consecutively admitted to a tertiary referral center with ALD diagnosis. Of a total of 544 admissions, 133 (24.4%) cases presented with bacterial infection, of which 116 were community-acquired whereas 17 were hospital-acquired. The common types of infection were pneumonia (38%), biliary tract infection (17%), soft tissue infection (12%), and spontaneous bacterial peritonitis (9%). Diabetes, serum Na <135 mM/L, albumin <2.5 g/dL, C-reactive protein ≥20 mg/L, systemic inflammatory response syndrome (SIRS) positivity were independently associated with bacterial infection in patients with ALD. Overall 30-day and 90-day mortalities in patients with bacterial infection were significantly (P < 0.001) higher than those without infection (22.3% vs. 5.1% and 32.3% vs. 8.2%, respectively). Furthermore, bacterial infection (HR, 2.2; 95% CI, 1.049-4.579, P = 0.037), SIRS positivity (HR, 2.5; 95% CI, 1.240-4.861, P = 0.010), Maddrey's discriminant function score ≥32 (HR, 2.3; 95% CI, 1.036-5.222, P = 0.041), and hemoglobin <12 g/dL (HR, 2.4; 95% CI, 1.081-5.450, P = 0.032) were independent predictors of short-term mortality. In conclusion, bacterial infection and SIRS positivity predicted short-term prognosis in hospitalized patients with ALD. A thorough evaluation at admission or on clinical deterioration is required to detect possible infection with prompt management.

  15. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML.

    PubMed

    DiNardo, Courtney D; Ravandi, Farhad; Agresta, Sam; Konopleva, Marina; Takahashi, Koichi; Kadia, Tapan; Routbort, Mark; Patel, Keyur P; Mark Brandt; Pierce, Sherry; Garcia-Manero, Guillermo; Cortes, Jorge; Kantarjian, Hagop

    2015-08-01

    The pathophysiology of IDH mutations in tumorigenesis is increasingly described, yet the prognostic significance of IDH1 and IDH2 mutations in AML remains controversial. The primary objective of this study was to define the natural history and prognosis of patients with AML and IDH1 or IDH2 mutations and provide historical survival expectations. A total of 826 patients treated from 2010 to 2014 at a single institution were evaluated, including 167 patients (20%) with AML and IDH1 or IDH2 mutations. Median age was 62 years (range 18-92). There were 59 IDH1-R132, 83 IDH2-R140, and 23 IDH2-R172 mutations. Clinicopathologic characteristics associated with IDH-mutations included older age, less frequent therapy-related status, and increased incidence of intermediate-risk cytogenetics, FLT3-ITD mutations, and NPM1 mutations. Remission rates (CR/CRi) by AML treatment status were: induction, 68%; Salvage-1 (S1), 42%; and Salvage-2 and beyond (S2+), 27%. No difference in response was identified by IDH mutation status. Similarly, overall survival (OS) was not dependent on IDH status within any cohort. The median OS was 15.4 months in induction, 8.7 months in S1, and 4.8 months in S2+. This analysis defines the clinical outcome associated with IDH-mutations in both the front-line and salvage AML treatment settings, and confirms that response rate and OS for both IDH-mutated and IDH wild-type AML patients is comparable. This provides contemporary data to be used for comparison with results of novel investigational (e.g., selective IDH inhibitor) strategies.

  16. Different characteristics and prognostic impact of deep-vein thrombosis / pulmonary embolism and intraabdominal venous thrombosis in colorectal cancer patients.

    PubMed

    Choi, Seyoun; Lee, Keun-Wook; Bang, Soo-Mee; Kim, Sujung; Lee, Jeong-Ok; Kim, Yu Jung; Kim, Jee Hyun; Park, Young Soo; Kim, Duck-Woo; Kang, Sung-Bum; Kim, Jae-Sung; Oh, Doyeun; Lee, Jong Seok

    2011-12-01

    This study was performed to determine the incidence, risk factors, and prognostic implications of venous thromboembolism (VTE) in Asian patients with colorectal cancer (CRC). Differences in clinical characteristics and prognostic impact between extremity venous thrombosis (or deep-vein thrombosis; DVT)/pulmonary embolism (PE) and intra-abdominal venous thrombosis (IVT) were also evaluated. For this study, consecutive CRC patients (N = 2,006) were enrolled and analyses were conducted retrospectively. VTEs were classified into two categories (DVT/PE and IVT). Significant predictors of developing VTEs were advanced stage and an increased number of co-morbidities. The two-year cumulative incidence of DVT/PE was 0.3%, 0.9% and 1.4% in stages 0~1, 2 and 3, respectively; this incidence range of DVT/PE in Asian patients with loco-regional CRC was lower than in Western patients. However, the two-year incidence (6.4%) of DVT/PE in Asian patients with distant metastases was not lower than in Western patients. Although 65.2% of patients with DVT/PE were symptomatic, only 15.7% of patients with IVT were symptomatic. During chemotherapy, DVT/PE developed more frequently than IVT. Only DVT/PE had a negative effect on survival; IVT had no prognostic significance. In conclusion, despite the low incidence of DVT/PE in Asian patients with loco-regional CRC, the protective effect of Asian ethnicity on VTE development disappears as tumour stage increases in patients with distant metastases. Considering different clinical characteristics and prognostic influences between DVT/PE and IVT, the treatment approach should be also different.

  17. The prognostic impact of sex on surgically resected non-small cell lung cancer depends on clinicopathologic characteristics.

    PubMed

    Sterlacci, William; Tzankov, Alexandar; Veits, Lothar; Oberaigner, Wilhelm; Schmid, Thomas; Hilbe, Wolfgang; Fiegl, Michael

    2011-04-01

    The increasing incidence of lung cancer in women and their supposed survival advantage over men requires clarification of the significance of sex. Age, stage, histologic features, differentiation grade, and Ki-67 index were assessed in 405 surgically resected non-small cell lung cancers (NSCLCs) using a standardized tissue microarray platform. Women were associated with well/moderate tumor differentiation, a Ki-67 index of 3% or less, and adenocarcinoma histologic features. Female sex predicted increased survival time only by univariate analysis. Stratified by sex, increased survival was noted for women older than 64 years, with a tumor at postsurgical International Union Against Cancer stage I, with adenocarcinoma histologic features, with well- or moderately differentiated tumors, or with a Ki-67 index of 3% or less. Sex is not an independent prognostic parameter for patients with surgically resected NSCLC. Sex-linked differences are associated with other factors, thus simulating a prognostic impact of sex. This study elucidates sex-specific interactions between patient and tumor characteristics, which are pivotal toward improving prognostic accuracy, individualized therapies, and screening efforts.

  18. LncRNA PVT1 overexpression is a poor prognostic biomarker and regulates migration and invasion in small cell lung cancer

    PubMed Central

    Huang, Chengsuo; Liu, Shuguang; Wang, Huijun; Zhang, Zicheng; Yang, Qing; Gao, Fang

    2016-01-01

    PVT1 has been suggested as playing important roles in diverse biological processes including tumorigenesis. However, the clinical significance and biological function of PVT1 in small cell lung cancer (SCLC) is still unclear. The purpose of this study is to identify the role of PVT1 in SCLC. The expression of PVT1 was examined in SCLC tissues and cell lines through real-time PCR. Meanwhile, the relationship of PVT1 expression levels with clinical characteristics of 120 SCLC patients was analyzed. Univariate and multivariate analyses were performed to determine the association between PVT1 expression and prognosis of SCLC patient. The biological function of PVT1 on tumor cell growth and mobility were explored through MTT, colony formation, Transwell migration and invasion assays in vitro. In our results, PVT1 expression was markedly higher in SCLC tissues and cell lines than in normal lung tissues and normal bronchial epithelial cell lines (both P<0.001). High levels of PVT1 were positively associated with the status of clinical stage (Limited vs. Extensive, P<0.001), lymph node metastasis (No vs. Yes, P<0.001), and distant metastasis (No vs. Yes, P<0.001) in SCLC patients. Patients with higher PVT1 expression had a significantly poorer overall survival time than did patients with low PVT1 expression (P<0.001). Multivariate analysis showed that PVT1 overexpression was an independent prognostic indicator (P=0.024) for the survival of patients with SCLC. Knocking down PVT1 expression significantly inhibited the SCLC cell migration and invasion in vitro (both P<0.001), but has no effect on the growth of SCLC cells (both P>0.05). In conclusion, PVT1 could serve as a new biomarker and a potential therapeutic target for SCLC patients. PMID:27904703

  19. Clinicopathological characteristics and prognostic analysis of Lauren classification in gastric adenocarcinoma in China

    PubMed Central

    2013-01-01

    Background According to the Lauren classification, gastric adenocarcinomas are divided into diffuse and intestinal types. The causative attribution explaining the dismal prognosis of diffuse-type remains unknown. Methods We examined the archive of 1000 patients with gastric adenocarcinomas who received radical gastrectomy in our center and assessed the effect of the Lauren classification on survival in a multivariate approach. Moreover we compared the variation of clinical features between the diffuse-type and intestinal-type and explored the contributing factors for the prognostic difference. Results There were 805 resectable patients for the final analysis. Diffuse-type comprised of 48.7% in the gastric carcinoma in our group and showed poorer prognosis than intestinal-type (P=0.013). Multivariate analysis revealed that independent prognostic factors for gastric carcinoma patients were T stage (P<0.001), N stage (P<0.001) tumor size (P<0.001) and Lauren classification (P=0.003). For the clinical features, diffuse-type was significantly associated with younger age (p<0.001), female preponderance (p <0.001), distal location (P<0.001), advanced pT (p < 0.001), advanced pN (p < 0.001) and advanced TNM stage (p = 0.027). Conclusions Diffuse type adenocarcinoma carries a worse prognosis that may be partially explained by the tendency of this subtype to present at more advanced T and N stage. However, Lauren classification has prognostic significance that is independent of T and N stage as well as other prognostic variables based on the multivariate cox analysis. PMID:23497313

  20. Cognitive-Motivational Characteristics of Children Varying in Reading Ability: Evidence for Learned Helplessness in Poor Readers.

    ERIC Educational Resources Information Center

    Butkowsky, Irwin S.; Willows, Dale M.

    1980-01-01

    Fifth-grade boys of relatively good, average, and poor reading ability were assessed on tasks in which success and failure were manipulated. Consistent with predictions, poor readers displayed characteristics indicative of learned helplessness and low self-concepts of ability, including low expectations and less persistence. (Instructional…

  1. Clinical characteristics and prognostic impact of atrial fibrillation in patients with chronic heart failure

    PubMed Central

    Gigli, Lorenzo; Ameri, Pietro; Secco, Gianmarco; De Blasi, Gabriele; Miceli, Roberta; Lorenzoni, Alessandra; Torre, Francesco; Chiarella, Francesco; Brunelli, Claudio; Canepa, Marco

    2016-01-01

    AIM To assess the prevalence, clinical characteristics and independent prognostic impact of atrial fibrillation (AF) in chronic heart failure (CHF) patients, and the potential protective effect of disease-modifying medications, particularly beta-blockers (BB). METHODS We retrospectively reviewed the charts of patients referred to our center since January 2004, and collected all clinical information available at their first visit. We assessed mortality to the end of June 2015. We compared patients with and without AF, and assessed the association between AF and all-cause mortality by multivariate Cox regression and Kaplan-Meyer analysis, particularly accounting for ongoing treatment with BB. RESULTS A total of 903 patients were evaluated (mean age 68 ± 12 years, 73% male). Prevalence of AF was 19%, ranging from 10% to 28% in patients ≤ 60 and ≥ 77 years, respectively. Besides the older age, patients with AF had more symptoms (New York Heart Association II-III 60% vs 44%), lower prevalence of dyslipidemia (23% vs 37%), coronary artery disease (28% vs 52%) and left bundle branch block (9% vs 16%). On the contrary, they more frequently presented with an idiopathic etiology (50% vs 24%), a history of valve surgery (13% vs 4%) and received overall more devices implantation (31% vs 21%). The use of disease-modifying medications (i.e., BB and ACE inhibitors/angiotensin receptor blockers) was lower in patients with AF (72% vs 80% and 71% vs 79%, respectively), who on the contrary were more frequently treated with symptomatic and antiarrhythmic drugs including diuretics (87% vs 69%) and digoxin (51% vs 11%). At a mean follow-up of about 5 years, all-cause mortality was significantly higher in patients with AF as compared to those in sinus rhythm (SR) (45% vs 34%, P value < 0.05 for all previous comparisons). However, in a multivariate analysis including the main significant predictors of all-cause mortality, the univariate relationship between AF and death (HR = 1

  2. Characteristics and Etiologies of Chronic Scrotal Pain: A Common but Poorly Understood Condition

    PubMed Central

    Aljumaily, Aosama; Al-Khazraji, Hind; Gordon, Allan; Lau, Susan

    2017-01-01

    Chronic scrotal pain (CSP) is a common and debilitating condition, but the underlying characteristics and etiology of CSP are poorly understood. The objective of this study is to identify the characteristic and etiologies of CSP. Men presenting for management of CSP completed a standardized questionnaire and underwent a complete physical examination. From Feb 2014 to Sep 2015, a total of 131 men (mean age 43) with CSP were studied. The CSP was of long duration (mean of 4.7 ± 5.95 years) and dramatically affected men's lives, with adverse effects on normal activities (71.%), ability to work (51.90%), and sexual functioning (61.8%). 50.4% felt depressed on most days, and 67.17% felt either unhappy or terrible with their present condition. Physical examination revealed that the epididymis was the most common tender area found in 70/131 men (53.43%), though a musculoskeletal source for the pain was found in 9.9%. Neuropathic changes were found in 30%. For close to half of the men (43.5%) we were unable to identify any potential cause for the CSP. This study characterizes the dramatic impact that CSP has on the lives of men, while providing an understanding of the common etiologies. PMID:28352209

  3. Sialomucins are characteristically O-acylated in poorly differentiated and colloid prostatic adenocarcinomas.

    PubMed

    Sáez, C; Japón, M A; Conde, A F; Poveda, M A; Luna-Moré, S; Segura, D I

    1998-12-01

    Mucinous glycoproteins are secreted by prostatic adenocarcinomas and might play important roles in tumor invasion and metastasis. Their histochemical properties on routine biopsy specimens have not been fully characterized. We present a histochemical study of mucin in 21 prostatic adenocarcinomas, with particular focus on the demonstration of different types of sialomucins. We applied the following histochemical techniques to routinely processed, formalin-fixed, paraffin-embedded tissue sections: Alcian blue (pH 2.5) and periodic acid-Schiff to reveal both acidic and neutral mucins; high iron diamine and Alcian blue (pH 2.5) to show sulfated and acidic nonsulfated mucosubstances simultaneously; periodic acid borohydride, potassium hydroxide, and periodic acid-Schiff to demonstrate O-acylated sialic acids; periodic acid thionine-Schiff, potassium hydroxide, and periodic acid-Schiff to differentiate pre-existing glycols from those revealed after saponification procedures; and periodic acid borohydride and periodic acid-Schiff to show C9-O-acylated sialic acid. These techniques are useful tools for demonstrating neutral and acidic (sialo- and sulfo-) mucins and di(C8,C9- or C7,C9-)-O-acylated, tri(C7,C8,C9-)-O-acylated and mono(C9)-O-acylated sialomucins. Most prostatic adenocarcinomas showed acidic mucins, with sialomucins predominating over sulfomucins. Well-differentiated and moderately differentiated noncolloid tumors had non-O-acylated sialomucins. Poorly differentiated tumors contained mono-O-acylated (C9) sialomucins, and colloid-type tumors secreted mono-, di-, and tri-O-acylated sialoglycoproteins. Acidic mucins, mainly sialomucins, constitute the major secretory component in prostatic adenocarcinomas, and our results show that the O-acylation of these sialoglycoproteins inversely correlates with tumor differentiation. Well-differentiated and moderately differentiated tumors are not O-acylated, whereas the poorly differentiated ones characteristically have O

  4. Overexpression of Transforming Acidic Coiled Coil‑Containing Protein 3 Reflects Malignant Characteristics and Poor Prognosis of Glioma

    PubMed Central

    Sun, Ying; Tian, Yu; Wang, Guang-Zhi; Zhao, Shi-Hong; Han, Bo; Li, Yong-Li; Jiang, Chuan-Lu

    2017-01-01

    Gliomas are malignant primary brain tumors with poor prognosis. Recently, research was indicative of a tight connection between tumor malignancy and genetic alterations. Here, we propose an oncogenic implication of transforming acidic coiled-coil-containing protein 3 (TACC3) in gliomas. By comprehensively analyzing the Chinese glioma genome atlas (CGGA) and publicly available data, we demonstrated that TACC3 were overexpressed along with glioma grade and served as an independent negative prognostic biomarker for glioma patients. Functions’ annotations and gene sets’ enrichment analysis suggested that TACC3 may participate in cell cycle, DNA repair, epithelium-mesenchymal transition and other tumor-related biological processes and molecular pathways. Patients with high TACC3 expression showed CD133+ stem cell properties, glioma plasticity and shorter overall survival time under chemo-/radio-therapy. Additionally, a TACC3 associated the miRNA-mRNA network was constructed based on in silico prediction and expression pattern, which provide a foundation for further detection of TACC3-miRNA-mRNA axis function. Collectively, our observations identify TACC3 as an oncogene of tumor malignancy, as well as a prognostic and motoring biomarker for glioma patients. PMID:28273854

  5. Ecological and geographic characteristics predict nutritional status of communities: rapid assessment for poor villages.

    PubMed

    Kusumayati, A; Gross, R

    1998-12-01

    The quality of poverty alleviation programmes relies heavily on appropriate targeting and priority setting. Major problems in assessing poverty include identification of the indicators of poverty and the methods used for its assessment. Nutritional status, expressed by anthropometric indices, has been proposed as a poverty indicator because of its validity, objectivity, reliability and feasibility. This study was conducted to explore the application of remote sensing to poverty mapping based on nutritional status at the community level. Relationships between the nutritional status within a community and the ecological characteristics of the community were investigated. Multiple linear regression tests were executed, and the resultant equations were tested for their validity in predicting communities with poor nutritional status. Among geographical and ecological indicators used, distance to the nearest market, main soil type, rice field area, and perennial cultivation area were found to be most useful predictors for the ranking of the communities by nutritional status. Among non-ecological determinants, food consumption, health service status and living conditions were also found as predictors. The highest correlation was found if total population was also taken into account in the regression model (R2 = 0.69; p < 0.0001). In the assessment of the sensitivity and specificity of the eight models studied, 'undernutrition' was defined as a condition where a community belongs in the first quartile for nutritional status (highest prevalence of undernutrition), and the baseline nutritional survey was considered as a standard method for final diagnosis. Most models which included only ecological factors in the equations had lower sensitivity and specificity than models which included all determinant factors in the equations. All models which took into account the total population had higher sensitivity and specificity than those that did not take total population into

  6. Prognostic Awareness and Communication of Prognostic Information in Malignant Glioma: A Systematic Review

    PubMed Central

    Diamond, Eli L.; Corner, Geoffrey W.; DeRosa, Antonio; Breitbart, William; Applebaum, Allison J.

    2016-01-01

    Malignant glioma (MG) is a devastating neurological disease with a uniformly poor prognosis and a clinical course characterized by progressive functional and cognitive impairment. A small body of literature addresses patients’ and caregivers’ prognostic awareness (PA), or understanding of prognosis in patients with cancer. Studies that examine PA and desire for prognostic information among patients with MG are limited. We sought to review the existing literature on PA and communication of prognostic information to patients with MG. Fourteen studies examining PA or experience and preferences regarding communication of prognostic information were included. The definition and measurement of PA across studies varied, and the prevalence of accurate PA ranged from 25% to 100% of participants. There is likely a subset of patients who do not desire accurate prognostic information, although the patient and disease characteristics that predict this preference are currently unknown. This review suggests that patients with MG desire prognostic information communicated in a manner that preserves hope. Systematic investigation to define communication needs for prognostic information in the unique clinical setting of MG is needed. PMID:24874468

  7. Prognostic awareness and communication of prognostic information in malignant glioma: a systematic review.

    PubMed

    Diamond, Eli L; Corner, Geoffrey W; De Rosa, Antonio; Breitbart, William; Applebaum, Allison J

    2014-09-01

    Malignant glioma (MG) is a devastating neurological disease with a uniformly poor prognosis and a clinical course characterized by progressive functional and cognitive impairment. A small body of literature addresses patients' and caregivers' prognostic awareness (PA), or understanding of prognosis in patients with cancer. Studies that examine PA and desire for prognostic information among patients with MG are limited. We sought to review the existing literature on PA and communication of prognostic information to patients with MG. Fourteen studies examining PA or experience and preferences regarding communication of prognostic information were included. The definition and measurement of PA across studies varied, and the prevalence of accurate PA ranged from 25 to 100 % of participants. There is likely a subset of patients who do not desire accurate prognostic information, although the patient and disease characteristics that predict this preference are currently unknown. This review suggests that patients with MG desire prognostic information communicated in a manner that preserves hope. Systematic investigation to define communication needs for prognostic information in the unique clinical setting of MG is needed.

  8. Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers.

    PubMed

    Pepper, Chris; Lin, Thet Thet; Pratt, Guy; Hewamana, Saman; Brennan, Paul; Hiller, Louise; Hills, Robert; Ward, Rachel; Starczynski, Jane; Austen, Belinda; Hooper, Laura; Stankovic, Tatjana; Fegan, Chris

    2008-11-01

    Bcl-2 family proteins play a critical role in the regulation of apoptosis in chronic lymphocytic leukemia (CLL). However, their association with established prognostic markers is unknown. In this study, we analyzed the expression of Bcl-2, Bax, and Mcl-1 in 185 CLL patients and evaluated their relationship with other prognostic markers, in vitro sensitivity to fludarabine, and clinical outcome. Mcl-1 expression was significantly correlated with stage of disease (P < .001), lymphocyte doubling time (P = .01), V(H) gene mutation status (P < .001), CD38 expression (P < .001), and ZAP-70 expression (P = .003). In addition, Mcl-1 and Mcl-1/Bax ratios showed strong correlations with in vitro resistance to fludarabine (P = .005 and P < .001, respectively). Furthermore, elevated Mcl-1 expression and Mcl-1/Bax ratios were predictive of time to first treatment in the whole cohort (P < .001 and P < .001, respectively) and in stage A patients only (P = .002 and P = .001, respectively). Taken together, our data show that Mcl-1 is a key controller of in vitro drug resistance and is an important regulator of disease progression and outcome in CLL. It therefore represents a promising therapeutic target in this incurable condition. The close correlation between Mcl-1 expression and V(H) gene mutation status, CD38 expression, and ZAP-70 expression offers a biologic explanation for their association with adverse prognosis.

  9. Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study

    PubMed Central

    Yao, Song; Sucheston, Lara E.; Millen, Amy E.; Johnson, Candace S.; Trump, Donald L.; Nesline, Mary K.; Davis, Warren; Hong, Chi-Chen; McCann, Susan E.; Hwang, Helena; Kulkarni, Swati; Edge, Stephen B.; O'Connor, Tracey L.; Ambrosone, Christine B.

    2011-01-01

    vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women. PMID:21386992

  10. Gut transport characteristics in herbivorous and carnivorous serrasalmid fish from ion-poor Rio Negro water.

    PubMed

    Pelster, Bernd; Wood, Chris M; Speers-Roesch, Ben; Driedzic, William R; Almeida-Val, Vera; Val, Adalberto

    2015-02-01

    Three closely related characids, Tambaqui (omnivore), black Piranha (carnivore), and Pacu (herbivore), all Serrasalmidae, inhabit the ion-poor, acidic Rio Negro. We compared O2-consumption and N excretion rates in vivo, and sodium, chloride, glucose, and ammonia transport characteristics of gut sac preparations in vitro. The Pacu had a significantly higher weight-specific oxygen consumption, and a lower N/Q ratio than the omnivorous Tambaqui, and a significantly lower urea-N excretion rate than the carnivorous black Piranha, suggesting N-limitation in the herbivorous Pacu. With a value of 2.62 ± 0.15, gut to fork length ratio in the Pacu was about 2.5 times higher than in the black Piranha, and 2.0 times higher than in the Tambaqui. Anterior intestinal activities of three enzymes involved in N-fixation for amino acid synthesis (glutamate dehydrogenase, glutamate-oxaloacetate transferase, and glutamate-pyruvate transferase) were generally greatest in the carnivore and lowest in the herbivore species. In all three species, sodium, chloride, glucose, and ammonia were taken up at high rates from the intestine, resulting in an isosmotic fluid flux. Comparing the area-specific fluid flux of the anterior, mid, and posterior gut sections, no difference was detected between the three sections of the Pacu, while in the Tambaqui, it was highest in the anterior section, and in the black Piranha highest in the middle section. Overall, the area-specific uptake rates for sodium, chloride, glucose, and ammonia of anterior, mid, and posterior sections were similar in all three species, indicating that there is no difference in the area-specific transport rates associated with trophic position. The net ammonia uptake flux from gut interior was not significantly different from the net ammonia efflux to the serosal fluid, so that the ammonia removed from the intestine by the mucosal epithelium was quantitatively transferred through the tissue to the serosal side in all three

  11. Expression and prognostic significance of APAF-1, caspase-8 and caspase-9 in stage II/III colon carcinoma: caspase-8 and caspase-9 is associated with poor prognosis.

    PubMed

    Sträter, Jörn; Herter, Ines; Merkel, Gaby; Hinz, Ulf; Weitz, Jürgen; Möller, Peter

    2010-08-15

    Apoptosis protease activating factor-1 (APAF-1), caspase-8 and caspase-9 are important factors in the execution of death signals. To study their prognostic influence in colon carcinoma, expression of APAF-1, caspase-8 and caspase-9 was determined by immunohistochemistry in normal colon mucosa (n = 8) and R0-resected stage II/III colon carcinomas (n >or= 124) using a semiquantitative score. Staining results were correlated with disease-free survival by Kaplan-Meier estimates, and multivariate Cox analyses were performed. In normal colon, APAF-1 and caspase-8 are most strongly expressed in the luminal surface epithelium, whereas caspase-9 is expressed all along the crypt axis. In colon carcinomas, there is considerable variability in the expression of these proapoptotic factors, although complete loss of caspase-8 and caspase-9 is rare. APAF-1 expression did not correlate with disease-free survival. Instead, both expression of caspase-9 and high-level expression of caspase-8 in a majority of tumor cells were significantly associated with adverse prognosis (p = 0.004 and p = 0.029, respectively). The influence of caspase-8 expression was mainly seen in patients with stage III colon carcinoma (p = 0.011), whereas the prognostic influence of caspase-9 expression was significant in stage II cases (p = 0.037) and just failed to be significant in stage III tumors (p = 0.0581). After adjusting for confounding factors in a multivariate Cox analysis, the effect of caspase-9 in predicting disease-free survival was confirmed (p = 0.003). Our data suggest that, in colon carcinomas, expression of caspase-8 and caspase-9 is significantly associated with poor survival. Caspase-9 may be an independent prognosticator in colon carcinoma.

  12. KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS mutation and bone metastasis

    PubMed Central

    Lohinai, Zoltan; Klikovits, Thomas; Moldvay, Judit; Ostoros, Gyula; Raso, Erzsebet; Timar, Jozsef; Fabian, Katalin; Kovalszky, Ilona; Kenessey, István; Aigner, Clemens; Renyi-Vamos, Ferenc; Klepetko, Walter; Dome, Balazs; Hegedus, Balazs

    2017-01-01

    Current guidelines lack comprehensive information on the metastatic site-specific role of KRAS mutation in lung adenocarcinoma (LADC). We investigated the effect of KRAS mutation on overall survival (OS) in this setting. In our retrospective study, 500 consecutive Caucasian metastatic LADC patients with known KRAS mutational status were analyzed after excluding 32 patients with EGFR mutations. KRAS mutation incidence was 28.6%. The most frequent metastatic sites were lung (45.6%), bone (26.2%), adrenal gland (17.4%), brain (16.8%), pleura (15.6%) and liver (11%). Patients with intrapulmonary metastasis had significantly increased KRAS mutation frequency compared to those with extrapulmonary metastases (35% vs 26.5%, p = 0.0125). In contrast, pleural dissemination and liver involvement were associated with significantly decreased KRAS mutation incidence (vs all other metastatic sites; 17% (p < 0.001) and 16% (p = 0.02) vs 33%, respectively). Strikingly, we found a significant prognostic effect of KRAS status only in the bone metastatic subcohort (KRAS-wild-type vs KRAS-mutant; median OS 9.7 v 3.7 months; HR, 0.49; 95% CI, 0.31 to 0.79; p  = 0.003). Our study suggests that KRAS mutation frequency in LADC patients shows a metastatic site dependent variation and, moreover, that the presence of KRAS mutation is associated with significantly worse outcome in bone metastatic cases. PMID:28051122

  13. Helping Poor Readers Demonstrate Their Science Competence: Item Characteristics Supporting Text-Picture Integration

    ERIC Educational Resources Information Center

    Saß, Steffani; Schütte, Kerstin

    2016-01-01

    Solving test items might require abilities in test-takers other than the construct the test was designed to assess. Item and student characteristics such as item format or reading comprehension can impact the test result. This experiment is based on cognitive theories of text and picture comprehension. It examines whether integration aids, which…

  14. Clinical characteristics and prognostic factors of patients with Stenotrophomonas maltophilia infections

    PubMed Central

    Batra, Priyam; Mathur, Purva; Misra, Mahesh C.

    2017-01-01

    INTRODUCTION: Stenotrophomonas maltophilia earlier had limited pathogenic potential, but now with growing degree of immunosuppression in general population, it is being recognized as an important nosocomial pathogen. METHODOLOGY: A retrospective 7 years study was carried out to determine the clinical characteristics of all patients with Stenotrophomonas infections, antibiotic resistance pattern, and risk factors associated with hospital mortality. All patients with Stenotrophomonas culture positivity were identified and their medical records were reviewed. Risk factor associated with hospital mortality was analyzed. RESULTS: A total of 123 samples obtained from 88 patients were culture positive. Most patients presented with bacteremia (45, 51%) followed by pneumonia (37, 42%) and skin and soft tissue infections (6, 7%). About 23 of 88 Stenotrophomonas infected patients had co-infection. Percentage resistance to cotrimoxazole; 8 (5.4%) was lower than that for levofloxacin; 18 (12%). Twenty-eight patients died during hospital stay. Intensive Care Unit admission (P = 0.0002), mechanical ventilation (P = 0.0004), central venous catheterization (P = 0.0227), urethral catheterization (P = 0.0484), and previous antibiotic intake (P = 0.0026) were independent risk factors associated with mortality. CONCLUSION: Our findings suggest that Stenotrophomonas can cause various infections irrespective of patient's immune status and irrespective of potential source. Thus, Stenotrophomonas should be thought of as potential pathogen and its isolation should be looked with clinical suspicion. PMID:28367030

  15. Collected Papers on Poverty Issues. Volume 3: Public Attitude Toward Poverty and the Characteristics of the Poor and the Near Poor.

    ERIC Educational Resources Information Center

    Yokelson, Doris, Ed.

    Volume 3 of a four volume collection, this document addresses the extent and the depth of public support in America for domestic social welfare programs and the social, moral, and economic attitudes of the poor and near poor. Specifically, three major sections focus on: the national morale and support for domestic reform; attitudes toward welfare,…

  16. Molecular characteristics and prognostic features of breast cancer in Nigerian compared with UK women.

    PubMed

    Agboola, A J; Musa, A A; Wanangwa, N; Abdel-Fatah, T; Nolan, C C; Ayoade, B A; Oyebadejo, T Y; Banjo, A A; Deji-Agboola, A M; Rakha, E A; Green, A R; Ellis, I O

    2012-09-01

    Although breast cancer (BC) incidence is lower in African-American women compared with White-American, in African countries such as Nigeria, BC is a common disease. Nigerian women have a higher risk for early-onset, with a high mortality rate from BC, prompting speculation that risk factors could be genetic and the molecular portrait of these tumours are different to those of western women. In this study, 308 BC samples from Nigerian women with complete clinical history and tumour characteristics were included and compared with a large series of BC from the UK as a control group. Immunoprofile of these tumours was characterised using a panel of 11 biomarkers of known relevance to BC. The immunoprofile and patients' outcome were compared with tumour grade-matched UK control group. Nigerian women presenting with BC were more frequently premenopausal, and their tumours were characterised by large primary tumour size, high tumour grade, advanced lymph node stage, and a higher rate of vascular invasion compared with UK women. In the grade-matched groups, Nigerian BC showed over representation of triple-negative and basal phenotypes and BRCA1 deficiency BC compared with UK women, but no difference was found regarding HER2 expression between the two series. Nigerian women showed significantly poorer outcome after development of BC compared with UK women. This study demonstrates that there are possible genetic and molecular differences between an indigenous Black population and a UK-based series. The basal-like, triple negative and BRCA1 dysfunction groups of tumours identified in this study may have implications in the development of screening programs and therapies for African patients and families that are likely to have a BRCA1 dysfunction, basal like and triple negative.

  17. Class III β-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel.

    PubMed

    Roque, Dana M; Buza, Natalia; Glasgow, Michelle; Bellone, Stefania; Bortolomai, Ileana; Gasparrini, Sara; Cocco, Emiliano; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Rutherford, Thomas J; Schwartz, Peter E; Santin, Alessandro D

    2014-01-01

    Critics have suggested that neoadjuvant chemotherapy (NACT) followed by interval debulking may select for resistant clones or cancer stem cells when compared to primary cytoreduction. β-tubulins are chemotherapeutic targets of taxanes and epothilones. Class III β-tubulin overexpression has been linked to chemoresistance and hypoxia. Herein, we describe changes in class III β-tubulin in patients with advanced ovarian carcinoma in response to NACT, in relationship to clinical outcome, and between patients who underwent NACT versus primary debulking; we characterize in vitro chemosensitivity to paclitaxel/patupilone of cell lines established from this patient population, and class III β-tubulin expression following repeated exposure to paclitaxel. Using immunohistochemistry, we observed among 22 paired specimens obtained before/after NACT decreased expression of class III β-tubulin following therapy within stroma (p=0.07), but not tumor (p=0.63). Poor median overall survival was predicted by high levels of class III β-tubulin in both tumor (HR 3.66 [1.11,12.05], p=0.03) and stroma (HR 4.53 [1.28,16.1], p=0.02). Class III β-tubulin expression by quantitative-real-time-polymerase-chain-reaction was higher among patients who received NACT (n=12) compared to primary cytoreduction (n=14) (mean±SD fold-change: 491.2±115.9 vs. 224.1±55.66, p=0.037). In vitro subculture with paclitaxel resulted in class III β-tubulin upregulation, however, cell lines that overexpressed class III β-tubulin remained sensitive to patupilone. Overexpression of class III β-tubulin in patients dispositioned to NACT may thus identify an intrinsically aggressive phenotype, and predict poor overall survival and paclitaxel resistance. Decreases in stromal expression may represent normalization of the tumor microenvironment following therapy. Epothilones warrant study for patients who have received neoadjuvant carboplatin and paclitaxel.

  18. Prognostic value of p53 mutation for poor outcome of Asian primary liver cancer patients: evidence from a cohort study and meta-analysis of 988 patients

    PubMed Central

    Wen, Xiajie; Lu, Fengmin; Liu, Shuang

    2016-01-01

    Several previous studies have investigated the association between gene p53 (p53) mutation and the poor outcome of primary liver cancer (PLC) patients; however, the results remain inconsistent. In the present study, p53 mutation in 60 paired tumor and corresponding nontumor tissues derived from a cohort of 60 PLC patients was systematically analyzed. The results showed that p53 mutation was only an independent risk factor for overall survival (OS), not for recurrence-free survival (RFS), and a meta-analysis was performed to verify this. Online databases were searched up to July 1, 2016. Studies about the association between p53 mutation and the postsurgery survival of PLC patients were collected. A total of 988 patients from eight studies were analyzed; among them, 341 (34.51%) patients had p53 mutation. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were 2.03 (1.64, 2.41) and 2.36 (1.31, 3.42) for OS and RFS, respectively. In conclusion, both the cohort study and meta-analysis suggested that the p53 mutation was associated with postsurgery OS in Asian PLC patients. However, the relationship between p53 mutation and recurrence should be confirmed by further studies. PMID:27994473

  19. Primary Tumor Characteristics Are Important Prognostic Factors for Sorafenib-Treated Patients with Metastatic Renal Cell Carcinoma: A Retrospective Multicenter Study

    PubMed Central

    Kim, Sohee; Nam, Byung-Ho; Lee, Sang Eun; Seo, Ill Young; Kim, Tae Nam; Hong, Sung-Hoo; Kwon, Tae Gyun; Seo, Seong Il; Song, Kanghyon; Kwak, Cheol

    2017-01-01

    We aimed to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with sorafenib. We investigated 177 patients, including 116 who received sorafenib as first-line therapy, using the Cox regression model. During a median follow-up period of 19.2 months, the PFS and OS were 6.4 and 32.6 months among all patients and 7.4 months and undetermined for first-line sorafenib-treated patients, respectively. Clinical T3-4 stage (hazard ratio [HR] 2.56) and a primary tumor size >7 cm (HR 0.34) were significant prognostic factors for PFS among all patients, as were tumor size >7 cm (HR 0.12), collecting system invasion (HR 5.67), and tumor necrosis (HR 4.11) for OS (p < 0.05). In first-line sorafenib-treated patients, ≥4 metastatic lesions (HR 28.57), clinical T3-4 stage (HR 4.34), collecting system invasion (univariate analysis HR 2.11; multivariate analysis HR 0.07), lymphovascular invasion (HR 13.35), and tumor necrosis (HR 6.69) were significant prognosticators of PFS, as were bone metastasis (HR 5.49) and clinical T3-4 stages (HR 4.1) for OS (p < 0.05). Our study thus identified a number of primary tumor-related characteristics as important prognostic factors in sorafenib-treated mRCC patients. PMID:28271073

  20. Metastasis-Free Interval Is Closely Related to Tumor Characteristics and Has Prognostic Value in Breast Cancer Patients with Distant Relapse

    PubMed Central

    Kim, Hee Jun; Ahn, Sung Gwe; Lee, Hak Min; Park, Jong Tae; Han, Kyunghwa; Lee, Seung Ah

    2015-01-01

    Purpose We investigated the relationships between metastasis-free interval (MFI) and tumor characteristics, and assessed the prognostic value of MFI for survival after metastasis in patients with metastatic breast cancer. Furthermore, we compared MFI among the subtypes. Methods We identified 335 patients with postoperative tumor recurrence at distant site(s). All patients underwent curative resection and had a MFI of at least 6 months. MFI was categorized as short (<2 years), intermediate (≥2 years and <5 years), or long (≥5 years). Overall survival after metastasis (OSM) was estimated. Results Patients with a shorter MFI were younger, more likely to have initial metastasis to visceral organs, and had a larger tumor with a higher stage and grade as well as a higher rate of nodal involvement at initial diagnosis. Among 136 patients with known disease subtypes, shorter MFI was associated with the triple-negative subtype while longer MFI was associated with the hormone receptor-positive/human epidermal growth factor receptor 2 negative subtype. Mortality after metastasis declined sharply with increasing MFI up to approximately 2 years, and continued gradually declining between 2 and 5 years. An MFI longer than 5 years did not add any survival benefit. MFI was a significant prognostic factor for OSM independent of nodal status, stage, metastatic site, and hormone receptor status of the metastasized cancer. Conclusion MFI is closely related to biological characteristics of both primary tumors and their metastases, and has a prognostic value for survival after metastasis. We therefore suggest investigation into treatments targeting improvement of MFI as a potential novel strategy. PMID:26770244

  1. Prognostic nutritional index is an independent prognostic factor for gastric cancer patients with peritoneal dissemination

    PubMed Central

    Nie, Runcong; Yuan, Shuqiang; Chen, Shi; Chen, Xiaojiang; Chen, Yongming; Zhu, Baoyan; Qiu, Haibo; Zhou, Zhiwei; Peng, Junsheng; Chen, Yingbo

    2016-01-01

    Objective The predictive and prognostic role of prognostic nutritional index (PNI) in gastric cancer patients with peritoneal dissemination remains unclear. This study aims to explore the role of the PNI in predicting outcomes of gastric cancer patients with peritoneal dissemination. Methods A total of 660 patients diagnosed with gastric adenocarcinoma with peritoneal metastasis between January 2000 and April 2014 at Sun Yat-sen University Cancer Center and the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. The clinicopathologic characteristics and clinical outcomes of patients with peritoneal dissemination were analyzed. Results Compared with PNI-high group, PNI-low group was correlated with advanced age (P=0.036), worse performance status (P<0.001), higher frequency of ascites (P<0.001) and higher frequency of multisite distant metastasis (P<0.001). Kaplan-Meier survival curves showed that PNI-high group had a significantly longer median overall survival than PNI-low group (13.13 vs. 9.03 months, P<0.001). Multivariate survival analysis revealed that Borrmann type IV (P=0.014), presence of ascites (P=0.017) and lower PNI (P=0.041) were independent poor prognostic factors, and palliative surgery (P<0.001) and first-line chemotherapy (P<0.001) were good prognostic factors. For patients receiving palliative surgery, the postoperative morbidity rates in the PNI-low group and PNI-high group were 9.1% and 9.9%, respectively (P=0.797). The postoperative mortality rate was not significantly different between PNI-low and PNI-high groups (2.3% vs. 0.9%, P=0.362). Conclusions PNI is a useful and practical tool for evaluating the nutritional status of gastric cancer patients with peritoneal dissemination, and is an independent prognostic factor for these patients. PMID:28174485

  2. Role of Stem Cells in Colorectal Cancer Progression and Prognostic and Predictive Characteristics of Stem Cell Markers in Colorectal Cancer.

    PubMed

    Fedyanin, Mikhail; Anna, Popova; Elizaveta, Polyanskaya; Sergei, Tjulandin

    2017-01-01

    In the last decade, an increasing number of studies on tumor stem cell theory stating that there is only a small fraction of tumor cells capable of inducing tumor growth have been published. These cells can not only differentiate into more mature tumor cells, but also can maintain their own pool, that is the capacity for self-renewal. There are distinct subpopulations of cells within a tumor that express different combinations of stem cell markers and have different functions. The following markers are typically considered as markers of colorectal adenocarcinoma stem cells: CD133, CD144, CD24, CD166, CD44, CD29, ALDH1, LGR5, and CXCR4. However, data on the role of cancer stem cells in the process of colorectal cancer progression, their prognostic and predictive role are lacking. Researches on the phenotype, molecular and functional properties of this tumor cell subpopulation in both primary site and metastases of colorectal cancer are of great interest because they can allow developing new diagnostic and therapeutic strategies in the future.

  3. Learning new movement patterns: a study on good and poor writers comparing learning conditions emphasizing spatial, timing or abstract characteristics.

    PubMed

    Overvelde, Anneloes; Hulstijn, Wouter

    2011-08-01

    In the earliest stages of motor-skill learning cognitive, visuo-spatial and dynamic processes play an important role. Which of these should be addressed first when children need to learn a new complex movement sequence? This study compares three learning methods in a within-subject design by having 18 good and 18 poor 8-year-old writers master unfamiliar, letter-like patterns by (1) tracing a trajectory on a screen, (2) tracking a moving target (pursuit), and (3) performing the pattern using written explicit instructions. Following each 10-trial learning phase, the children completed a short test phase. Besides errors and kinematic data, Dynamic Time Warping (DTW) was used to calculate the deviation for each pattern from the ideal shape (DTW-distance). As predicted, the number of errors and DTW-distance were very low during the learning phase of the tracing and pursuit conditions and higher in the explicit condition. Conversely, in the test phase, tracing yielded the highest DTW-distance and the explicit condition the lowest DTW-distance and error percentages. The results were remarkably similar for the good and poor writers. The poor learning results of the tracing condition and the good results of the explicit condition have important implications for the teaching of handwriting and remedial therapy.

  4. Morphokinetic Characteristics and Developmental Potential of In Vitro Cultured Embryos from Natural Cycles in Patients with Poor Ovarian Response

    PubMed Central

    Hojnik, N.; Vlaisavljević, V.

    2016-01-01

    Background. Patients with poor ovarian response to ovarian hyperstimulation represent an interesting group for studying the impact of embryo cleavage irregularities on clinical outcome since all embryos, regardless of their quality, are usually transferred to the uterus. The aim of our study was to follow the morphokinetics of fertilized oocytes from natural cycles in poor responders. Methods. Zygotes from 53 cycles were cultured in vitro for 3 days. The morphokinetics of their development and transfer outcomes were retrospectively analyzed for the normally and irregularly cleaved embryos. Results. Of all embryos, 30.2% had single and 20.8% multiple cleavage irregularities with the following prevalence: developmental arrest 30.2%, direct cleavage to more than two cells 24.5%, chaotic cleavage 13.2%, and reverse cleavage 11.3%. These embryos had longer pronuclear phases, first cytokinesis, second embryo cell cycles, and less synchronized divisions. The transfer of normally developing embryos resulted in an implantation rate of 30.8% and a delivery rate of 23.1%, but irregularly cleaved embryos did not implant. Conclusions. The use of time-lapse microscopy in poor responder patients identified embryos with cleavage abnormalities that are related with no or extremely low implantation potential. Gained information about embryo quality is important for counselling patients about their expectations. PMID:28097133

  5. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors.

    PubMed

    Montesinos, Pau; Bergua, Juan M; Vellenga, Edo; Rayón, Chelo; Parody, Ricardo; de la Serna, Javier; León, Angel; Esteve, Jordi; Milone, Gustavo; Debén, Guillermo; Rivas, Concha; González, Marcos; Tormo, Mar; Díaz-Mediavilla, Joaquín; González, Jose D; Negri, Silvia; Amutio, Elena; Brunet, Salut; Lowenberg, Bob; Sanz, Miguel A

    2009-01-22

    Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA). Detailed knowledge about DS has remained limited. We present an analysis of the incidence, characteristics, prognostic factors, and outcome of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Español de Tratamientos en Hematología [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) experienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 x 10(9)/L and an abnormal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic prednisone prophylaxis (LPA99 trial) in contrast to those receiving selective prophylaxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Patients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial (86% vs 88%).

  6. Prognostic value of lymphocyte/monocyte ratio in advanced Hodgkin lymphoma: correlation with International Prognostic Score and tumor associated macrophages.

    PubMed

    Jakovic, Ljubomir R; Mihaljevic, Biljana S; Andjelic, Bosko M; Bogdanovic, Andrija D; Perunicic Jovanovic, Maja D; Babic, Dragan D; Bumbasirevic, Vladimir Z

    2016-08-01

    We studied the prognostic significance of the absolute lymphocyte/monocyte count ratio (ALC/AMC), its contribution to the prognostic value of the International Prognostic Score (IPS), and evaluated if ALC/AMC could serve as a proxy for the frequency of CD68 + tumor-associated macrophages (TAMs) in 101 patients with advanced Hodgkin lymphoma (HL). The receiver operating characteristic (ROC) curve identified best cut-off values of 2.0 for ALC/AMC and 25% for CD68 + TAM. Patients with ALC/AMC < 2, IPS > 2 and > 25% CD68 + TAM had an inferior overall survival (OS) and event-free survival (EFS). Spearman's test also uncovered a significant correlation between the ALC/AMC and TAM. Multivariate analysis identified ALC/AMC < 2, IPS > 2 and > 25% CD68 + TAM as poor prognostic factors of OS and EFS. After evaluating ALC/AMC and IPS, we stratified patients into three progressively-worse-outcome groups (low-risk: 0 risk factors; intermediate: 1 risk factor; high: 2 risk factors). Our study encourages the combination of ALC/AMC with IPS, for refining risk prediction in advanced HL patients.

  7. Conceptualizing prognostic awareness in advanced cancer: A systematic review

    PubMed Central

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2015-01-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients’ understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. PMID:24157936

  8. Conceptualizing prognostic awareness in advanced cancer: a systematic review.

    PubMed

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2014-09-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients' understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness.

  9. Village characteristics and health of rural Chinese older adults: examining the CHARLS Pilot Study of a rich and poor province.

    PubMed

    Yeatts, Dale E; Pei, Xiaomei; Cready, Cynthia M; Shen, Yuying; Luo, Hao; Tan, Junxin

    2013-12-01

    Community (or village) characteristics have received growing attention as researchers have sought factors affecting health. This study examines the association between a variety of environmental, economic, and social village characteristics and health of Chinese older rural adults with health measured in terms of physical limitations. The Chinese Health and Retirement Longitudinal Survey (CHARLS) Pilot Study data were used. Older villagers from a low-income province (Gansu) and a relatively wealthy province (Zhejiang) were surveyed between July and September, 2008. The sample included 1267 respondents in 73 villages age 45 and older. The relationship between a variety of village characteristics and physical limitations of older adults was examined using negative binomial regression (NBR) with standard errors adjusted to account for non-independence of respondents in a village. A comparison of means/percentages shows that Gansu and Zhejiang were significantly different on the dependent and most independent variables. The NBR models show that at the personal-level, decreased risk of physical limitations was associated with being male, less than 60 years old, married, higher in education, and higher in household expenditures (proxy for income). At the village-level, decreased risk of limitations was associated with a continuous supply of electricity, not using coal in the household, the existence of a sewage system, low cost of electricity, and village wealth. Decreased risk of physical limitations was also associated with various characteristics of China's New Cooperative Medical Scheme (NCMS), an insurance program for rural older adults. Policy implications for improved health of rural older adults include: (1) continued use of China's NCMS, (2) establishment of village sewage systems, (3) ending the use of coal in the home, and (4) increased educational opportunities focused on health.

  10. Nano-scale Characteristics of Copper poor ordered defect compound at grain boundary of CuInGaSe2

    NASA Astrophysics Data System (ADS)

    Ma, Yaping

    This work investigates the copper poor ordered defect compound (ODC) layer at grain boundaries (GB) for CuX(Ga0.3In0.7) Se2 with different Cu composition ratio (x = 0.9 and 0.68). Same chemical composition while widened ODC layer at GBs with lower Cu ratio were first reported determined by the energy dispersive spectroscopy in scanning transmission microscopy mode. Band structure of the ODC layer was directly measured by scanning tunneling spectroscopy showing a downward offset for conduction band and valance band of 200 eV and 350 eV, respectively. This result was further confirmed by photocurrent accumulation and higher schottky barrier at GBs measured by the conducting probe atomic force microscopy (CP-AFM). Local photovoltaic performance measurements of individual grain boundaries with different ODC width were investigated, using CP-AFM and the disappearance of the differences of open circuit voltage and shunt resistance between grain interior and grain boundary at low illumination provides a direct evidence for the reduced recombination at widened ODC grain boundary which greatly supports the hole barrier theory for the high efficiency of the Copper Indium Ga Selenide solar cells.

  11. Education and Intelligence: Pity the Poor Teacher because Student Characteristics are more Significant than Teachers or Schools.

    PubMed

    Detterman, Douglas K

    2016-12-06

    Education has not changed from the beginning of recorded history. The problem is that focus has been on schools and teachers and not students. Here is a simple thought experiment with two conditions: 1) 50 teachers are assigned by their teaching quality to randomly composed classes of 20 students, 2) 50 classes of 20 each are composed by selecting the most able students to fill each class in order and teachers are assigned randomly to classes. In condition 1, teaching ability of each teacher and in condition 2, mean ability level of students in each class is correlated with average gain over the course of instruction. Educational gain will be best predicted by student abilities (up to r = 0.95) and much less by teachers' skill (up to r = 0.32). I argue that seemingly immutable education will not change until we fully understand students and particularly human intelligence. Over the last 50 years in developed countries, evidence has accumulated that only about 10% of school achievement can be attributed to schools and teachers while the remaining 90% is due to characteristics associated with students. Teachers account for from 1% to 7% of total variance at every level of education. For students, intelligence accounts for much of the 90% of variance associated with learning gains. This evidence is reviewed.

  12. Development of a Novel Milling System Using Supercritical Carbon Dioxide for Improvement of Dissolution Characteristics of Water-Poorly Soluble Drugs.

    PubMed

    Fern, Jennifer Chia Wee; Nakamura, Hideya; Watano, Satoru

    2016-01-01

    The aim of this study is to develop a novel milling system using supercritical carbon dioxide (SC-CO2) for the improvement of dissolution characteristics of water-poorly soluble drugs. SC-CO2 possesses high potential in the application of nanotechnology, due to the attractive properties of SC-CO2 fluid such as cheap, inert and non-polluting. In addition, SC-CO2 has density comparable to a liquid, viscosity similar to a gas, and high diffusion capacity. Most of all, carbon dioxide exists as gas in room temperature and pressure, which enables the removal of fluid instantaneously. In this study, a novel method of milling using SC-CO2 was proposed to produce fine-drug particles. SC-CO2 milling was conducted and its performance was compared with the ones by various milling methods such as jet milling, dry milling and wet milling. A comparison on the effect of each milling medium on its milling performance, drug size distribution, and particle morphology was conducted. Operating variables of the SC-CO2 milling system were also investigated to clarify the factors affecting the milling properties and to improve drug release characteristics of water-poorly soluble drugs.

  13. The clinical characteristics and prognostic significance of MN1 gene and MN1-associated microRNA expression in adult patients with de novo acute myeloid leukemia.

    PubMed

    Xiang, Lili; Li, Man; Liu, Yan; Cen, Jiangnong; Chen, Zixing; Zhen, Xiao; Xie, Xiaobao; Cao, Xiangshan; Gu, Weiying

    2013-08-01

    This study aimed to determine the clinical characteristics and prognostic significance of the meningioma 1 (MN1) gene and MN1-associated microRNA expression in Chinese adult de novo acute myeloid leukemia (AML) patients. The expression level of MN1, microRNA-20 (miR-20a), and microRNA-181b (miR-181b) in bone marrow mononuclear cells was measured in 158 newly diagnosed AML patients and 20 cases of normal healthy donors by real-time quantitative reverse transcriptase polymerase chain reaction. All AML patients significantly overexpressed MN1 at the level of 0.01983 (P < 0.001) compared with normal controls. High MN1 expression was associated with spleen involvement (P = 0.037), NPM1 wild type (P = 0.001), lower miR-20a expression levels (P = 0.015), and higher miR-181b expression levels (P = 0.035). MiR-20a (P = 0.029) and miR-181b (P = 0.017) overexpressed in the bone marrow cells of patients with certain subtypes of AML compared with healthy donors. High MN1 expressers had lower complete remission (CR) rates and shorter overall survival (OS) within the Southwest Oncology Group classification. In multivariable models, high MN1 expression was associated with worse CR rates (P = 0.01), relapse-free survival (RFS; P = 0.02), and OS (P = 0.02); high miR-20a expression was associated with higher CR rates (P = 0.008) and longer OS (P = 0.04), whereas high miR-181b expression was associated with lower CR rates (P = 0.03), and shorter RFS (P = 0.045) and OS (P = 0.017). High MN1 expression confers worse prognosis in Chinese adult patients with de novo AML. MN1 gene and MN1-associated microRNAs provide clinical prognosis of AML patients and may refine their molecular risk classification.

  14. Characteristics and Prognostic Impact of Pneumonitis during Systemic Anti-Cancer Therapy in Patients with Advanced Non-Small-Cell Lung Cancer

    PubMed Central

    Fujimoto, Daichi; Kato, Ryoji; Morimoto, Takeshi; Shimizu, Ryoko; Sato, Yuki; Kogo, Mariko; Ito, Jiro; Teraoka, Shunsuke; Nagata, Kazuma; Nakagawa, Atsushi; Otsuka, Kojiro; Tomii, Keisuke

    2016-01-01

    Background Data on characteristics, outcomes, and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who develop pneumonitis during systemic anti-cancer therapy (pneumonitis) are currently lacking. Methods We conducted a retrospective cohort study of 910 consecutive patients diagnosed with advanced NSCLC between January 2004 and January 2014. Of these, 140 patients were excluded because they did not receive systemic anti-cancer therapy at this hospital. Results A total of 770 patients were included in the study, of whom 44 (6%) were diagnosed with pneumonitis. The mortality rate of pneumonitis was 36%. The incidence of pneumonitis was independently associated with pre-existing ILD (adjusted odds ratio, 2.99, P = 0.008), and survivors were significantly associated with younger age (P = 0.003) and radiographic non-acute interstitial pneumonia pattern (P = 0.004). In all patients, pneumonitis was identified as an independent predictor of overall survival (OS) (adjusted hazard ratio 1.53, 95% CI, 1.09–2.09, P = 0.015). Performance status was poor in 82% of survivors of pneumonitis; in 62% of survivors, the PS worsened after the pneumonitis improved. Additionally, 54% of survivors received no further systemic anti-cancer therapy after pneumonitis. The median survival time of survivors after pneumonitis was 3.5 months (95% CI, 2.3–7.2 months). Conclusions Our study indicated that 6% of patients with advanced NSCLC developed pneumonitis during systemic anti-cancer therapy. The early mortality rate of pneumonitis is high, and the survival and PS after pneumonitis is extremely poor. Additionally, pneumonitis has an adverse impact on the survival of patients with advanced NSCLC. These data should be considered for the management of pneumonitis, and we recommend that future work focuses on pneumonitis particularly to improve the survival of patients with advanced NSCLC. PMID:28006019

  15. PROGNOSTIC FACTORS AND SURVIVAL ANALYSIS IN ESOPHAGEAL CARCINOMA

    PubMed Central

    TUSTUMI, Francisco; KIMURA, Cintia Mayumi Sakurai; TAKEDA, Flavio Roberto; UEMA, Rodrigo Hideki; SALUM, Rubens Antônio Aissar; RIBEIRO-JUNIOR, Ulysses; CECCONELLO, Ivan

    2016-01-01

    ABSTRACT Background: Despite recent advances in diagnosis and treatment, esophageal cancer still has high mortality. Prognostic factors associated with patient and with disease itself are multiple and poorly explored. Aim: Assess prognostic variables in esophageal cancer patients. Methods: Retrospective review of all patients with esophageal cancer in an oncology referral center. They were divided according to histological diagnosis (444 squamous cell carcinoma patients and 105 adenocarcinoma), and their demographic, pathological and clinical characteristics were analyzed and compared to clinical stage and overall survival. Results: No difference was noted between squamous cell carcinoma and esophageal adenocarcinoma overall survival curves. Squamous cell carcinoma presented 22.8% survival after five years against 20.2% for adenocarcinoma. When considering only patients treated with curative intent resection, after five years squamous cell carcinoma survival rate was 56.6 and adenocarcinoma, 58%. In patients with squamous cell carcinoma, poor differentiation histology and tumor size were associated with worse oncology stage, but this was not evidenced in adenocarcinoma. Conclusion: Weight loss (kg), BMI variation (kg/m²) and percentage of weight loss are factors that predict worse stage at diagnosis in the squamous cell carcinoma. In adenocarcinoma, these findings were not statistically significant. PMID:27759773

  16. Prognostics for Microgrid Components

    NASA Technical Reports Server (NTRS)

    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.

  17. Overexpression of homeobox B-13 correlates with angiogenesis, aberrant expression of EMT markers, aggressive characteristics and poor prognosis in pancreatic carcinoma.

    PubMed

    Zhai, Lu-Lu; Wu, Yang; Cai, Chong-Yang; Tang, Zhi-Gang

    2015-01-01

    To investigate the expression of homeobox B (Hoxb)-13 and analyze its relationship with tumor angiogenesis, epithelial-mesenchymal transition (EMT)-associated markers (E-cadherin and vimentin), clinicopathologic data and prognosis in pancreatic carcinoma. Immunohistochemistry was applied to determine the level of Hoxb-13 expression in tumor tissues and surrounding non-tumor tissues from 85 subjects with pancreatic carcinoma. Besides, vascular endothelial growth factor (VEGF), CD31, E-cadherin and vimentin were also detected in tumor tissues by immunostaining. We found that the level of Hoxb-13 expression was significantly higher in pancreatic carcinoma tissues than in paracarcinomatous tissues (P < 0.05). Hoxb-13 staining was positively correlated with VEGF (r = 0.429, P < 0.001) and microvessel density (MVD) (r = 0.454, P < 0.001). Likewise, Hoxb-13 staining was positively correlated with vimentin (r = 0.448, P < 0.001); while it was negatively correlated with E-cadherin (r = -0.405, P < 0.001). High Hoxb-13 expression was associated with aggressive clinicopathological characteristics, worse disease-free survival (DFS) (P < 0.001) and worse overall survival (OS) (P < 0.001). Multivariate analysis showed that Hoxb-13 was an independent predictor for poor DFS (P < 0.001) and OS (P = 0.002). In conclusion, our data show that overexpressed Hoxb-13 is correlated with tumor angiogenesis, aberrant expression of EMT-associated markers and aggressive clinicopathological characteristics, and serves as a promising marker for unfavourable prognosis in pancreatic carcinoma.

  18. Toward IVHM Prognostics

    NASA Technical Reports Server (NTRS)

    Walsh, Kevin; Venti, Mike

    2007-01-01

    This viewgraph presentation reviews the prognostics of Integrated Vehicle Health Management. The contents include: 1) Aircraft Operations-Today's way of doing business; 2) Prognostics; 3) NASA's instrumentation data-system rack; 4) Data mining for IVHM; 5) NASA GRC's C-MAPSS generic engine model; and 6) Concluding thoughts.

  19. Fuzzy logic-based prognostic score for outcome prediction in esophageal cancer.

    PubMed

    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.

  20. The recurrence frequency of breast cancer and its prognostic factors in Iranian patients

    PubMed Central

    Shahriari-Ahmadi, Ali; Arabi, Mohsen; Payandeh, Mehrdad; Sadeghi, Masoud

    2017-01-01

    Background: Recurrent breast cancer (BC) after initial treatments is usually associated with poor outcome. The objective of this study is to evaluate baseline characteristics of BC patients to determine their prognostic influence of recurrences. Materials and Methods: In this retrospective study of 481 BC patients, 182 patients who had recurrence within the first, second, or third 5 years after diagnosis were included in the study. The significant prognostic factors associated with late or very late recurrence were selected according to the Akaike Information Criterion. Early recurrence was defined as initial recurrence within 5 years following curative surgery irrespective of site. Likewise, late recurrence was defined as initial recurrence after 5 years. Also, very late recurrence was defined as initial recurrence after 10 years. Results: During the follow-up period, 182 recurrences occurred (local recurrence or distant metastasis). All patients were treated with chemotherapy and radiotherapy and the patients with estrogen receptor (ER)- or progesterone receptor (PR)-positive had hormone therapy. There was a significant correlation between histological grade and receptors status with recurrence. In binary logistic regression analysis, ER and PR were significant prognostic factors for early recurrence. Conclusion: High histological grade and immunohistochemical markers (ER- and PR-negative or human epidermal growth factor receptor 2-positive) are risk factors for recurrence, especially in early recurrence and also between of them, ER is the more significant prognostic factor in early recurrence.

  1. Prognostic factors in cancer.

    PubMed

    Gospodarowicz, Mary; O'Sullivan, Brian

    2003-01-01

    Diagnosis, prognosis, and treatment are the three core elements of the art of medicine. Modern medicine pays more attention to diagnosis and treatment but prognosis has been a part of the practice of medicine much longer than diagnosis. Cancer is a heterogeneous group of disease characterized by growth, invasion and metastasis. To plan the management of an individual cancer patient, the fundamental knowledge base includes the site of origin of the cancer, its morphologic type, and the prognostic factors specific to that particular patient and cancer. Most prognostic factors literature describes those factors that directly relate to the tumor itself. However, many other factors, not directly related to the tumor, also affect the outcome. To comprehensively represent these factors we propose three broad groupings of prognostic factors: 'tumor'-related prognostic factors, 'host'-related prognostic factors, and 'environment'-related prognostic factors. Some prognostic factors are essential to decisions about the goals and choice treatment, while others are less relevant for these purposes. To guide the use of various prognostic factors we have proposed a grouping of factors based on their relevance in everyday practice; these comprise 'essential,' 'additional,' and 'new and promising factors.' The availability of a comprehensive classification of prognostic factors assures an ordered and deliberate approach to the subject and provide safeguard against skewed approaches that may ignore large parts of the field. The current attention to tumor factors has diminished the importance of 'patient' (i.e., 'host'), and almost completely overshadows the importance of the 'environment'. This ignores the fact that the latter presents the greatest potential for immediate impact. The acceptance of a generic prognostic factor classification would facilitate communication and education about this most important subject in oncology.

  2. Metrics for Offline Evaluation of Prognostic Performance

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

    2010-01-01

    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.

  3. On Applying the Prognostic Performance Metrics

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

    2009-01-01

    Prognostics performance evaluation has gained significant attention in the past few years. As prognostics technology matures and more sophisticated methods for prognostic uncertainty management are developed, a standardized methodology for performance evaluation becomes extremely important to guide improvement efforts in a constructive manner. This paper is in continuation of previous efforts where several new evaluation metrics tailored for prognostics were 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. Several shortcomings identified, while applying these metrics to a variety of real applications, are also summarized along with discussions that attempt to alleviate these problems. Further, these metrics have been enhanced to include the capability of incorporating probability distribution information from prognostic algorithms as opposed to evaluation based on point estimates only. Several methods have been suggested and guidelines have been provided to help choose one method over another based on probability distribution characteristics. These approaches also offer a convenient and intuitive visualization of algorithm performance with respect to some of these new metrics like prognostic horizon and alpha-lambda performance, and also quantify the corresponding performance while incorporating the uncertainty information.

  4. Gray zone lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma: characteristics, outcomes, and prognostication among a large multicenter cohort.

    PubMed

    Evens, Andrew M; Kanakry, Jennifer A; Sehn, Laurie H; Kritharis, Athena; Feldman, Tatyana; Kroll, Aimee; Gascoyne, Randy D; Abramson, Jeremy S; Petrich, Adam M; Hernandez-Ilizaliturri, Francisco J; Al-Mansour, Zeina; Adeimy, Camille; Hemminger, Jessica; Bartlett, Nancy L; Mato, Anthony; Caimi, Paolo F; Advani, Ranjana H; Klein, Andreas K; Nabhan, Chadi; Smith, Sonali M; Fabregas, Jesus C; Lossos, Izidore S; Press, Oliver W; Fenske, Timothy S; Friedberg, Jonathan W; Vose, Julie M; Blum, Kristie A

    2015-09-01

    Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease (MGZL). We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients recently treated across 19 North American centers. Forty-three percent of patients presented with MGZL, whereas 57% had non-MGZL (NMGZL). NMGZL patients were older (50 versus 37 years, P = 0.0001); more often had bone marrow involvement (19% versus 0%, P = 0.001); >1 extranodal site (27% versus 8%, P = 0.014); and advanced stage disease (81% versus 13%, P = 0.0001); but they had less bulk (8% versus 44%, P = 0.0001), compared with MGZL patients. Common frontline treatments were cyclophosphamide-doxorubicin-vincristine-prednisone +/- rituximab (CHOP+/-R) 46%, doxorubicin-bleomycin-vinblastine-dacarbazine +/- rituximab (ABVD+/-R) 30%, and dose-adjusted etoposide-doxorubicin-cyclophosphamide-vincristine-prednisone-rituximab (DA-EPOCH-R) 10%. Overall and complete response rates for all patients were 71% and 59%, respectively; 33% had primary refractory disease. At 31-month median follow-up, 2-year progression-free survival (PFS) and overall survival rates were 40% and 88%, respectively. Interestingly, outcomes in MGZL patients seemed similar compared with that of NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival for all patients. Additionally, patients treated with ABVD+/-R had markedly inferior 2-year PFS (22% versus 52%, P = 0.03) compared with DLBCL-directed therapy (CHOP+/-R and DA-EPOCH-R), which persisted on Cox regression (hazard ratio, 1.88; 95% confidence interval, 1.03-3.83; P = 0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (hazard ratio, 0.35; 95% confidence interval, 0.18-0.69; P = 0.002). Collectively, GZL is a heterogeneous

  5. Sixteen-kinase gene expression identifies luminal breast cancers with poor prognosis.

    PubMed

    Finetti, Pascal; Cervera, Nathalie; Charafe-Jauffret, Emmanuelle; Chabannon, Christian; Charpin, Colette; Chaffanet, Max; Jacquemier, Jocelyne; Viens, Patrice; Birnbaum, Daniel; Bertucci, François

    2008-02-01

    Breast cancer is a heterogeneous disease made of various molecular subtypes with different prognosis. However, evolution remains difficult to predict within some subtypes, such as luminal A, and treatment is not as adapted as it should be. Refinement of prognostic classification and identification of new therapeutic targets are needed. Using oligonucleotide microarrays, we profiled 227 breast cancers. We focused our analysis on two major breast cancer subtypes with opposite prognosis, luminal A (n = 80) and basal (n = 58), and on genes encoding protein kinases. Whole-kinome expression separated luminal A and basal tumors. The expression (measured by a kinase score) of 16 genes encoding serine/threonine kinases involved in mitosis distinguished two subgroups of luminal A tumors: Aa, of good prognosis and Ab, of poor prognosis. This classification and its prognostic effect were validated in 276 luminal A cases from three independent series profiled across different microarray platforms. The classification outperformed the current prognostic factors in univariate and multivariate analyses in both training and validation sets. The luminal Ab subgroup, characterized by high mitotic activity compared with luminal Aa tumors, displayed clinical characteristics and a kinase score intermediate between the luminal Aa subgroup and the luminal B subtype, suggesting a continuum in luminal tumors. Some of the mitotic kinases of the signature represent therapeutic targets under investigation. The identification of luminal A cases of poor prognosis should help select appropriate treatment, whereas the identification of a relevant kinase set provides potential targets.

  6. Prognostic factors and survival in patients with gastric stump cancer

    PubMed Central

    Huang, Hua; Wang, Wei; Chen, Zhong; Jin, Jie-Jie; Long, Zi-Wen; Cai, Hong; Liu, Xiao-Wen; Zhou, Ye; Wang, Ya-Nong

    2015-01-01

    AIM: To elucidate the clinicopathological characteristics and prognostic factors of gastric stump cancer (GSC). METHODS: The clinical data for 92 patients with GSC were collected at Fudan University Shanghai Cancer Center. The prognostic factors were analyzed with Cox proportional hazard models. RESULTS: GSC tended to occur within 25 years following the primary surgery, when the initial disease is benign, whereas it primarily occurred within the first 15 years post-operation for gastric cancer. Patients with regular follow-up after primary surgery had a better survival rate. The multivariate Cox regression analysis revealed that Borrmann type I/II (HR = 3.165, 95%CI: 1.055-9.500, P = 0.040) and radical resection (HR = 1.780, 95%CI: 1.061-2.987, P = 0.029) were independent prognostic factors for GSC. The overall 1-, 3-, and 5-year survival rates of the 92 patients were 78.3%, 45.6% and 27.6%, respectively. The 1-, 3-, and 5-year survival rates of those undergoing radical resection were 79.3%, 52.2%, and 37.8%, respectively. The 5-year survival rates for stages I, II, III, and IV were 85.7%, 47.4%, 16.0%, and 13.3%, respectively (P = 0.005). CONCLUSION: The appearance of GSC occurs sooner in patients with primary malignant cancer than in patients with a primary benign disease. Therefore, close follow-up is necessary. The overall survival of patients with GSC is poor, and curative resection can improve their prognosis. PMID:25684953

  7. Towards clinically useful neuroimaging in depression treatment: Is subgenual cingulate activity robustly prognostic for depression outcome in Cognitive Therapy across studies, scanners, and patient characteristics?

    PubMed Central

    Siegle, Greg J.; Thompson, Wesley K.; Collier, Amanda; Berman, Susan R.; Feldmiller, Joshua; Thase, Michael E.; Friedman, Edward S.

    2013-01-01

    Context 40–60% of unmedicated depressed individuals respond to Cognitive Therapy (CT) in controlled trials. Multiple previous studies suggest that activity in the subgenual anterior cingulate predicts outcome in CT for depression, but there have been no prospective replications. Objective This study prospectively examined whether subgenual cingulate activity is a reliable and robust prognostic outcome marker for CT for depression and whether its activity changes in treatment. Design Two inception cohorts were assessed with fMRI on different scanners on a task sensitive to sustained emotional information processing before and after 16–20 sessions of CT, along with a sample of control participants tested at comparable intervals. Setting Therapy took place in a hospital outpatient clinic. Patients Participants included 49 unmedicated depressed adults and 35 healthy control participants. Main Outcome Measures Pre-treatment subgenual anterior cingulate activity in an a priori region in response to negative words was correlated with residual severity and used to classify response and remission. Results As expected, in both samples, participants with the lowest pre-treatment sustained subgenual cingulate (sgACC; BA25) reactivity in response to negative words displayed the most improvement in CT (R2=.29, >75% correct classification of response, >70% correct classification of remission). Other a priori regions explained additional variance. Response/Remission in Cohort 2 was predicted based on thresholds from Cohort 1. sgACC activity remained low for remitters following treatment. Conclusions Neuroimaging provides a quick, valid, and clinically applicable way of assessing neural systems associated with treatment response/remission. sgACC activity, in particular, may reflect processes which interfere with treatment, e.g,. emotion generation in addition to its putative regulatory role; alternately, its absence may facilitate treatment response. PMID:22945620

  8. Prognostic value of combined preoperative lactate dehydrogenase and alkaline phosphatase levels in patients with resectable pancreatic ductal adenocarcinoma

    PubMed Central

    Ji, Fei; Fu, Shun-Jun; Guo, Zhi-Yong; Pang, Hui; Ju, Wei-Qiang; Wang, Dong-Ping; Hua, Yun-Peng; He, Xiao-Shun

    2016-01-01

    Abstract Serum enzymes, including lactate dehydrogenase (LDH) and alkaline phosphatase (ALP), have recently been reported to play important roles in tumor growth. Increases in LDH and ALP have been confirmed to predict poor prognosis in patients with various cancers. However, their prognostic value in pancreatic cancer has not been well studied. Therefore, we reviewed the preoperative data on LDH and ALP in 185 pancreatic ductal adenocarcinoma (PDAC) patients who underwent surgery between July 2005 and December 2010 to explore the prognostic value of these markers. The cutoff points were determined based on the upper limit of their normal values. The Chi-square test was used to analyze the relationships between LDH/ALP and clinical characteristics. Univariate and multivariate analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS). We found that elevation of LDH was related to carbohydrate antigen 19-9 (CA19-9), lymph node involvement, tumor size, TNM, distant metastasis, and recurrence. Additionally, ALP was correlated to perineural invasion. After multivariate analysis, LDH and ALP were identified as independent prognostic factors for DFS and OS, and elevation of LDH/ALP was correlated with poor DFS and OS. Notably, there was a positive correlation between LDH and ALP. The predictive power of LDH combined with ALP was more sensitive than that of either one alone. Therefore, we conclude that the preoperative LDH and ALP values are prognostic factors for PADC, and the prognostic accuracy of testing can be enhanced by the combination of LDH and ALP PMID:27399091

  9. Prognostic value of preoperative serum lactate dehydrogenase levels for resectable gastric cancer and prognostic nomograms

    PubMed Central

    Zhou, Yi-Xin; Wang, Feng; Zhang, Dong-Sheng; Wang, Feng-Hua; Li, Yu-Hong; Xu, Rui-Hua

    2016-01-01

    The present study aimed to evaluate the prognostic significance of preoperative serum lactate dehydrogenase (SLDH) levels for resected gastric cancer and construct prognostic nomograms for risk prediction. The study cohort consisted of 619 patients with D2-resected gastric cancer. The relationship of SLDH levels with clinicopathological features and clinical outcomes was evaluated. Prognostic nomograms were created using identified prognosticators to predict 3-year overall survival (OS) and 3-year disease-free survival (DFS), and bootstrap validation was performed. High SLDH levels were correlated with old age but not depth of invasion or lymph node metastasis. When assessed as a continuous variable, high SLDH levels were independently associated with poor OS and DFS. Internal validation of the developed nomograms revealed good predictive accuracy (bootstrap-corrected concordance indices: 0.77 and 0.75, respectively for prediction of OS and DFS). The preoperative SLDH levels, an identified unfavorable prognosticator, were incorporated into nomograms along with other clinicopathological features to refine the prediction of clinical outcomes for patients with D2-resected gastric cancer. PMID:27223065

  10. Prognostics of Power MOSFET

    NASA Technical Reports Server (NTRS)

    Celaya, Jose Ramon; Saxena, Abhinav; Vashchenko, Vladislay; Saha, Sankalita; Goebel, Kai Frank

    2011-01-01

    This paper demonstrates how to apply prognostics to power MOSFETs (metal oxide field effect transistor). The methodology uses thermal cycling to age devices and Gaussian process regression to perform prognostics. The approach is validated with experiments on 100V power MOSFETs. The failure mechanism for the stress conditions is determined to be die-attachment degradation. Change in ON-state resistance is used as a precursor of failure due to its dependence on junction temperature. The experimental data is augmented with a finite element analysis simulation that is based on a two-transistor model. The simulation assists in the interpretation of the degradation phenomena and SOA (safe operation area) change.

  11. Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study

    PubMed Central

    Emery, P; Bingham, C O; Burmester, G R; Bykerk, V P; Furst, D E; Mariette, X; van Vollenhoven, R; Arendt, C; Mountian, I; Purcaru, O; Tatla, D; VanLunen, B; Weinblatt, M E

    2017-01-01

    Objectives To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks. Methods DMARD-naïve patients with ≤1 year of active RA were randomised (3:1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)<2.6 and DAS28(ESR)≤3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints. Results Patients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): −1.00 vs −0.82, p<0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY). Conclusions CZP+dose-optimised MTX treatment of DMARD-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX. Trial registration

  12. Peripheral blood lymphocyte-to-monocyte ratio as a prognostic factor in advanced epithelial ovarian cancer: a multicenter retrospective study

    PubMed Central

    Zhu, Jia-yu; Liu, Cheng-cheng; Wang, Liang; Zhong, Mei; Tang, Hai-lin; Wang, Hua

    2017-01-01

    The lymphocyte-to-monocyte ratio (LMR), as a surrogate marker of systemic inflammation, has been found to be a novel prognostic indicator in various malignancies. Data from 672 advanced epithelial ovarian cancer (EOC) patients treated with neoadjuvant chemotherapy (NAC) followed by debulking surgery were analyzed, and the prognostic value of LMR were evaluated. The optimal cutoff point of LMR in prediction of survival was defined as 3.45 through receiver operating characteristics curve analysis. Patients with low LMR (≤3.45) at diagnosis tended to have more adverse clinical features, such as higher histological grade, chemotherapy resistance, and residual tumor >1cm after debulking surgery. No significant correlation was found between LMR level and age and histological type. Moreover, after NAC, the complete remission (CR) rate for the low-LMR group was lower than those for the high-LMR group (P<0.05). Patients with low LMR had poorer progression-free survival (PFS; P<0.001) and overall survival (OS; P<0.001). Multivariate analysis revealed that low LMR was an independent adverse predictor for PFS and OS. Results indicated that low LMR at diagnosis is a novel independent prognostic factor for advanced EOC. However, prospective study is needed to validate this prognostic factor and biological studies should further investigate the mechanisms underlying the correlation between low LMR and poor prognosis in advanced EOC.

  13. Prognostic value of the C-reactive protein/albumin ratio in patients with laryngeal squamous cell carcinoma

    PubMed Central

    Yu, Shi-tong; Zhou, Zhiwei; Cai, Qian; Liang, Faya; Han, Ping; Chen, Renhui; Huang, Xiao-ming

    2017-01-01

    Purpose The present study was designed to retrospectively evaluate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in laryngeal squamous cell carcinoma (LSCC). Methods One hundred and twenty-nine newly diagnosed LSCC patients admitted between May 2006 and October 2011 were retrospectively reviewed. Their serum CRP and ALB were quantified preoperatively. The relationship between the CRP/ALB ratio and the clinicopathologic features was analyzed. Receiver operating characteristic curve was used to calculate the prognostic value of the CRP/ALB ratio. Then, the Cox proportional hazards model was used in univariate and multivariate analyses to identify significant prognostic factors associated with disease-free survival and overall survival. Results The cutoff value for CRP/ALB ratio was 0.047. An elevated CRP/ALB ratio was significantly associated with nodal metastasis, late disease stage, and recurrence. Also, high values of CRP/ALB ratio were significant predictors for poor overall survival and disease-free survival on multivariate analysis. Conclusion Pretreatment CRP/ALB ratio may be a significant prognostic marker in LSCC. PMID:28243123

  14. The clinical characteristics and prognostic significance of AID, miR-181b, and miR-155 expression in adult patients with de novo B-cell acute lymphoblastic leukemia.

    PubMed

    Zhou, Guangquan; Cao, Yang; Dong, Weimin; Lin, Yan; Wang, Qi; Wu, Wei; Hua, Xiaoying; Ling, Yun; Xie, Xiaobao; Hu, Shaoyan; Cen, Jiannong; Gu, Weiying

    2017-01-31

    This study aimed to investigate clinical characteristics and prognostic significance of activation-induced cytidine deaminase (AID) gene, miR-181b and miR-155 expression in de novo adult B-cell acute lymphoblastic leukemia (B-ALL) patients. Results showed that AID and miR-155 expression were higher in B-ALL patients than healthy controls, while miR-181b expression was lower in B-ALL patients. In addition, Ph(+) B-ALLs had higher AID expression than Ph(-) B-ALLs, and its high expression was associated with BCR-ABL. Moreover, B-ALL patients with AID(high) or miR-181b(low) expression had a shorter overall survival (OS). AID(high) with miR-181b(low), AID(high) with miR-155(low), miR-181b(low), miR-155(low), AID(high) with miR-181b(low) and miR-155(low) expression were associated with shorter OS. Combination of the three molecules are more accurate predictors for unfavorable OS compared with univariate group. Therefore, AID, miR-181b and miR-155 provide clinical prognosis of adult de novo B-ALL patients and may refine their molecular risk classification.

  15. Significance Analysis of Prognostic Signatures

    PubMed Central

    Beck, Andrew H.; Knoblauch, Nicholas W.; Hefti, Marco M.; Kaplan, Jennifer; Schnitt, Stuart J.; Culhane, Aedin C.; Schroeder, Markus S.; Risch, Thomas; Quackenbush, John; Haibe-Kains, Benjamin

    2013-01-01

    A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that “random” gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS) which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date) of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically annotated

  16. Prognostic Aspects of Sub-seasonal Rainfall Characteristics using the Outputs of General Circulation Model: An Application of Statistical Downscaling and Temporal Disaggregation

    NASA Astrophysics Data System (ADS)

    Singh, A.; Mohanty, U. C.; Ghosh, K.

    2015-12-01

    Most regions of India experience varied rainfall duration during the southwest monsoon, changes in which exhibit major impact not only agriculture, but also other sectors like hydrology, agriculture, food and fodder storage etc. In addition, changes in sub-seasonal rainfall characteristics highly impact the rice production. As part of the endeavor seasonal climate outlook, as well as information for weather within climate may be helpful for advance planning and risk management in agriculture. The General Circulation Model (GCM) provide an alternative to gather information for weather within climate but variability is very low in comparison to observation. On the other hand, the spatial resolution of GCM predicted rainfall is not found at the observed station/grid point. To tackle the problem, initially a statistical downscaling over 19 station of Odisha state is undertaken using the atmospheric parameters predicted by a GCM (NCEP-CFSv2). For the purpose, an extended domain is taken for analyzing the significant zone for the atmospheric parameters like zonal wind at 850hPa, Sea Surface Temperature (SST), geopotential height. A statistical model using the pattern projection method is further developed based on empirical orthogonal function. The downscaled rainfall is found better in association with station observation in comparison to raw GCM prediction in view of deterministic and probabilistic skill measure. Further, the sub-seasonal and seasonal forecast from the GCMs can be used at different time steps for risk management. Therefore, downscaled seasonal/monthly rainfall is further converted to sub-seasonal/daily time scale using a non-homogeneous markov model. The simulated weather sequences are further compared with the observed sequence in view of categorical rainfall events. The outcomes suggest that the rainfall amount are overestimated for excess rainfall and henceforth larger excess rainfall events can be realized. The skill for prediction of rainfall

  17. Low Prognostic Nutritional Index (PNI) Predicts Unfavorable Distant Metastasis-Free Survival in Nasopharyngeal Carcinoma: A Propensity Score-Matched Analysis

    PubMed Central

    Hong, Shaodong; Chen, Haiyang; Liang, Shaobo; Peng, Peijian; Chen, Yong

    2016-01-01

    Background Poor nutritional status is associated with progression and advanced disease in patients with cancer. The prognostic nutritional index (PNI) may represent a simple method of assessing host immunonutritional status. This study was designed to investigate the prognostic value of the PNI for distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC). Methods A training cohort of 1,168 patients with non-metastatic NPC from two institutions was retrospectively analyzed. The optimal PNI cutoff value for DMFS was identified using the online tool “Cutoff Finder”. DMFS was analyzed using stratified and adjusted analysis. Propensity score-matched analysis was performed to balance baseline characteristics between the high and low PNI groups. Subsequently, the prognostic value of the PNI for DMFS was validated in an external validation cohort of 756 patients with NPC. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of different prognostic scores. Results The optimal PNI cutoff value was determined to be 51. Low PNI was significantly associated with poorer DMFS than high PNI in univariate analysis (P<0.001) as well as multivariate analysis (P<0.001) before propensity score matching. In subgroup analyses, PNI could also stratify different risks of distant metastases. Propensity score-matched analyses confirmed the prognostic value of PNI, excluding other interpretations and selection bias. In the external validation cohort, patients with high PNI also had significantly lower risk of distant metastases than those with low PNI (Hazards Ratios, 0.487; P<0.001). The PNI consistently showed a higher AUC value at 1-year (0.780), 3-year (0.793) and 5-year (0.812) in comparison with other prognostic scores. Conclusion PNI, an inexpensive and easily assessable inflammatory index, could aid clinicians in developing individualized treatment and follow-up strategies for patients

  18. Abnormal expression of paxillin correlates with tumor progression and poor survival in patients with gastric cancer

    PubMed Central

    2013-01-01

    Background Paxillin (PXN) has been found to be aberrantly regulated in various malignancies and involved in tumor growth and invasion. The clinicopathological and prognostic significance of PXN in gastric cancer is still unclear. Methods The expression of PXN was determined in paired gastric cancer tissues and adjacent normal tissues by Western blotting and real-time PCR. Immunohistochemistry was performed to detect the expression of PXN in 239 gastric cancer patients. Statistical analysis was applied to investigate the correlation between PXN expression and clinicopathological characteristics and prognosis in patients. Additionally, the effects of PXN on gastric cancer cell proliferation and migration were also evaluated. Results PXN was up-regulated in gastric cancer tissues and cell lines as compared with adjacent normal tissues and normal gastric epithelial cell line GES-1. Overexpression of PXN was correlated with distant metastasis (P = 0.001) and advanced tumor stage (P = 0.021) in gastric cancer patients. Patients with high PXN expression tended to have poor prognosis compared with patients with low PXN expression (P < 0.001). Multivariate analysis demonstrated that PXN expression was an independent prognostic factor (P = 0.020). Moreover, ectopic expression of PXN promotes cell proliferation and migration in AGS cells whereas knockdown of PXN inhibits cell proliferation and migration in SGC7901 cells. Conclusions PXN plays an important role in tumor progression and may be used as a potential prognostic indicator in gastric cancer. PMID:24180516

  19. Poor Americans: How the Poor White Live.

    ERIC Educational Resources Information Center

    Pilisuk, Marc; Pilisuk, Phyllis

    Contents of this book include the following essays which originally appeared in "Transaction" magazine: (1) "Poor Americans: an introduction," Marc Pilisuk and Phyllis Pilisuk; (2) "How the white poor live," Marc Pilisuk and Phyllis Pilisuk; (3) "The culture of poverty," Oscar Lewis; (4) "Life in Appalachia--the case of Hugh McCaslin," Robert…

  20. Littoral Refractivity Prognostic Advancement

    DTIC Science & Technology

    2009-09-30

    situational awareness of the 3D radio-frequency (RF) propagation environment and a quantitative diagnostic and prognostic capability for assessing sub- and...Rev. 8-98) Prescribed by ANSI Std Z39-18 2 with the benchmark showing the quantitative improvement with each stage of model development...grid point. Modified the NSWCDD littoral clutter model ( LCM ) to accept COAMPS® derived refractivity fields. Analyzed the impact on ducting of

  1. Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis.

    PubMed

    Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

    2017-01-01

    The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83-2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59-2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76-2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction.

  2. Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis

    PubMed Central

    Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

    2017-01-01

    The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83–2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59–2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76–2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction. PMID:28182725

  3. Integrative Protein-Based Prognostic Model for Early Stage Endometrioid Endometrial Cancer

    PubMed Central

    Yang, Ji-Yeon; Werner, Henrica M.J.; Li, Jie; Westin, Shannon N.; Lu, Yiling; Halle, Mari K.; Trovik, Jone; Salvesen, Helga B.; Mills, Gordon B.; Liang, Han

    2015-01-01

    Purpose Endometrioid endometrial carcinoma (EEC) is the major histological type of endometrial cancer, the most prevalent gynecologic malignancy in USA. EEC recurrence or metastasis is associated with a poor prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathological characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers. Experimental Design We employed two large, independent early-stage EEC datasets as training (n = 183) and validation cohorts (n = 333), and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. By applying an initial filtering and the elastic net to the training samples, we developed a prognostic model for overall survival containing two clinical variables and 18 protein markers and optimized the risk group classification. Results Kaplan-Meier survival analyses in the validation cohort confirmed an improved discriminating power of our prognostic model for patients with early-stage EEC over key clinical variables (log-rank test p-value = 0.565 for disease stage, 0.567 for tumor grade, 1.3×10−4 for the integrative model). Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts. Conclusions Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and improving their treatment strategies. PMID:26224872

  4. Unregulated usage of labour-inducing medication in a region of Pakistan with poor drug regulatory control: characteristics and risk patterns

    PubMed Central

    Shah, Safieh; Van den Bergh, Rafael; Prinsloo, Jeanne Rene; Rehman, Gulalai; Bibi, Amna; Shaeen, Neelam; Auat, Rosa; Daudi, Sabina Mutindi; Njenga, Joyce Wanjiru; Khilji, Tahir Bashir-ud-Din; Maïkéré, Jacob; De Plecker, Eva; Caluwaerts, Séverine; Zachariah, Rony; Van Overloop, Catherine

    2016-01-01

    Background In developing countries such as Pakistan, poor training of mid-level cadres of health providers, combined with unregulated availability of labour-inducing medication can carry considerable risk for mother and child during labour. Here, we describe the exposure to labour-inducing medication and its possible risks in a vulnerable population in a conflict-affected region of Pakistan. Methods A retrospective cohort study using programme data, compared the outcomes of obstetric risk groups of women treated with unregulated oxytocin, with those of women with regulated treatment. Results Of the 6379 women included in the study, 607 (9.5%) received labour-inducing medication prior to reaching the hospital; of these, 528 (87.0%) received unregulated medication. Out of 528 labour-inducing medication administrators, 197 (37.3%) traditional birth attendants (also known as dai) and 157 (29.7%) lady health workers provided unregulated treatment most frequently. Women given unregulated medication who were diagnosed with obstructed/prolonged labour were at risk for uterine rupture (RR 4.1, 95% CI: 1.7–9.9) and severe birth asphyxia (RR 3.9, 95% CI: 2.5–6.1), and those with antepartum haemorrhage were at risk for stillbirth (RR 1.8, 95% CI: 1.0–3.1). Conclusions In a conflict-affected region of Pakistan, exposure to unregulated treatment with labour-inducing medication is common, and carries great risk for mother and child. Tighter regulatory control of labour-inducing drugs is needed, and enhanced training of the mid-level cadres of healthcare workers is required. PMID:26276813

  5. New prognostic model for extranodal natural killer/T cell lymphoma, nasal type.

    PubMed

    Cai, Qingqing; Luo, Xiaolin; Zhang, Guanrong; Huang, Huiqiang; Huang, Hui; Lin, Tongyu; Jiang, Wenqi; Xia, Zhongjun; Young, Ken H

    2014-09-01

    Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis, requiring risk stratification in affected patients. We designed a new prognostic model specifically for ENKTL to identify high-risk patients who need more aggressive therapy. We retrospectively reviewed 158 patients who were newly diagnosed with ENKTL. The estimated 5-year overall survival rate was 39.4 %. Independent prognostic factors included total protein (TP) <60 g/L, fasting blood glucose (FBG) >100 mg/dL, and Korean Prognostic Index (KPI) score ≥2. We constructed a new prognostic model by combining these prognostic factors: group 1 (64 cases (41.0 %)), no adverse factors; group 2 (58 cases (37.2 %)), one adverse factor; and group 3 (34 cases (21.8 %)), two or three adverse factors. The 5-year overall survival (OS) rates of these groups were 66.7, 23.0, and 5.9 %, respectively (p < 0.001). Our new prognostic model had a better prognostic value than did the KPI model alone (p < 0.001). Our proposed prognostic model for ENKTL, including the newly identified prognostic indicators, TP and FBG, demonstrated a balanced distribution of patients into different risk groups with better prognostic discrimination compared with the KPI model alone.

  6. Detection of dicentric chromosome (9;20) in paediatric B-cell acute lymphoblastic leukaemia: prognostic significance.

    PubMed

    Letouzey, Mathilde; Penther, Dominique; Roche-Lestienne, Catherine; Nelken, Brigitte; Devoldère, Catherine; Vannier, Jean-Pierre; Schneider, Pascale

    2015-02-01

    The dicentric chromosome (9;20) (dic(9;20)) is described in 2 % of childhood B-acute lymphoblastic leukaemia. Fluorescence in situ hybridization (FISH) is the most reliable method to identify dic(9;20) when compared with conventional cytogenetics. To define the prognostic importance of dic(9;20), we evaluated treatment response and patient survival. This was a retrospective study in three French university centres. Patients' clinical and laboratory characteristics and treatment response are described. Nine children with dic(9;20) have been identified since 1995. All patients had at least one poor prognostic feature either among the clinical features, the initial laboratory results or in the initial treatment response: central nervous system involvement (2/9), high median leucocyte count (≥50 G/L) (8/9) and poor response to prednisone (2/9). All patients were in complete cytological remission after induction therapy but only three had a good molecular response with minimal residual disease (MRD) <10(-3). Five out of nine patients relapsed and two died, 4 and 12 months after diagnosis, respectively. The event-free survival rate in this population was 44 % (95 % confidence interval (CI) = 0.09-0.79) and overall survival 78 % (95 % CI = 0.51-1.05). In this population, dic(9;20) is associated with a relatively poor prognosis. Patients showing dic(9;20), whether this cytogenetic abnormality is associated with other poor prognostic factors or not, should be identified at the outset in order to be offered a more intensive treatment protocol.

  7. Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma

    PubMed Central

    Koh, Hyun Min; Jang, Bo Geun; Hyun, Chang Lim; Kim, Young Sill; Hyun, Jin Won; Chang, Weon Young; Maeng, Young Hee

    2017-01-01

    Background Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea. Methods AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues. Results AURKA gene amplification was found more frequently in the 20q13.2–13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001). Conclusions AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients. PMID:28013532

  8. Prognostic value of ERG, PTEN, CRISP3 and SPINK1 in predicting biochemical recurrence in prostate cancer

    PubMed Central

    NOH, BYEONG-JOO; SUNG, JI-YOUN; KIM, YOUN WHA; CHANG, SUNG-GOO; PARK, YONG-KOO

    2016-01-01

    The established prognostic factors associated with prostatic adenocarcinoma are the Gleason score, pathological T staging and serum prostatic-specific antigen (PSA) level. However, these prognostic factors alone are not sufficient for predicting prognostic characteristics, including early stage or advanced prostate cancer, presence of metastasis or disease-related mortality. The purpose of the present study was to simultaneously evaluate the prognostic value and associations of four biomarkers, namely, transcriptional regulator ERG (ERG), phosphatase and tensin homolog (PTEN), cysteine-rich secretory protein 3 (CRISP3) and serine protease inhibitor Kazal type I (SPINK1), and to conduct risk stratification of prostate cancer for use in patient management. A total of 68 formalin-fixed, paraffin-embedded, prostate cancer samples from radical prostatectomies were obtained in the Kyung Hee University Hospital (Seoul, Korea) and were studied immunohistochemically for ERG, PTEN, CRISP3 and SPINK1 to determine the proportion and intensity of staining. SPINK1 expression was mutually exclusive of ERG expression (P=0.001). The loss of PTEN and high CRISP3 expression are unfavorable indicators for prostate cancer, as PTEN loss was associated with shorter biochemical recurrence (BCR) (P=0.039), and high CRISP3 expression was associated with increased BCR (P<0.001) and cancer-related mortalities (P=0.011). Using the combination of low PTEN and high CRISP3 expression enables attention to be focused on patients who exhibit a poor prognosis. Subgrouping of patients, into high-risk and low-risk categories, was correlated with BCR-free survival in prostate cancer upon multivariate analysis (P=0.030). Overall, low PTEN and high CRISP3 expression significantly characterize the subgroups of prostate cancer that have a poor prognosis for BCR. PMID:27284364

  9. Special considerations in prognostic research in cancer involving genetic polymorphisms

    PubMed Central

    2013-01-01

    Analysis of genetic polymorphisms may help identify putative prognostic markers and determine the biological basis of variable prognosis in patients. However, in contrast to other variables commonly used in the prognostic studies, there are special considerations when studying genetic polymorphisms. For example, variable inheritance patterns (recessive, dominant, codominant, and additive genetic models) need to be explored to identify the specific genotypes associated with the outcome. In addition, several characteristics of genetic polymorphisms, such as their minor allele frequency and linkage disequilibrium among multiple polymorphisms, and the population substructure of the cohort investigated need to be accounted for in the analyses. In addition, in cancer research due to the genomic differences between the tumor and non-tumor DNA, differences in the genetic information obtained using these tissues need to be carefully assessed in prognostic studies. In this article, we review these and other considerations specific to genetic polymorphism by focusing on genetic prognostic studies in cancer. PMID:23773794

  10. High Infiltration of Tumor-Associated Macrophages Influences Poor Prognosis in Human Gastric Cancer Patients, Associates With the Phenomenon of EMT.

    PubMed

    Zhang, Jia; Yan, Yan; Yang, Ya; Wang, Li; Li, Min; Wang, Jizhao; Liu, Xu; Duan, Xiaoyi; Wang, Jiansheng

    2016-02-01

    Tumor-associated macrophages (TAMs) are associated with poor prognosis in numerous human cancers and play important roles in tumor progression. Epithelial-mesenchymal transition (EMT) contributes to invasion and metastasis in cancer. However, the associations between TAMs and EMT are not clear in gastric cancer (GC). The present study was designed to investigate the effects of TAMs on EMT in human GC.TAMs marker CD68 and EMT-related proteins were detected by immunohistochemistry (IHC) in human GC tissues and their clinical significance were evaluated.A high level of infiltration of TAMs was associated with aggressive characteristics of tumor and an independent poor prognostic factor in human GC tissues. Infiltration of TAMs was also associated with EMT-related proteins in human GC tissues.Our findings suggest that the high level of infiltration TAMs was associated with aggressive features of GC and is an independent poor prognostic factor in GC patients. TAMs are associated with EMT induction in human GC tissues. The level of TAMs infiltration may be used as a prognostic factor and even a therapeutic target in GC.

  11. Contemporary approach to neurologic prognostication of coma after cardiac arrest.

    PubMed

    Ben-Hamouda, Nawfel; Taccone, Fabio S; Rossetti, Andrea O; Oddo, Mauro

    2014-11-01

    Coma after cardiac arrest (CA) is an important cause of admission to the ICU. Prognosis of post-CA coma has significantly improved over the past decade, particularly because of aggressive postresuscitation care and the use of therapeutic targeted temperature management (TTM). TTM and sedatives used to maintain controlled cooling might delay neurologic reflexes and reduce the accuracy of clinical examination. In the early ICU phase, patients' good recovery may often be indistinguishable (based on neurologic examination alone) from patients who eventually will have a poor prognosis. Prognostication of post-CA coma, therefore, has evolved toward a multimodal approach that combines neurologic examination with EEG and evoked potentials. Blood biomarkers (eg, neuron-specific enolase [NSE] and soluble 100-β protein) are useful complements for coma prognostication; however, results vary among commercial laboratory assays, and applying one single cutoff level (eg, > 33 μg/L for NSE) for poor prognostication is not recommended. Neuroimaging, mainly diffusion MRI, is emerging as a promising tool for prognostication, but its precise role needs further study before it can be widely used. This multimodal approach might reduce false-positive rates of poor prognosis, thereby providing optimal prognostication of comatose CA survivors. The aim of this review is to summarize studies and the principal tools presently available for outcome prediction and to describe a practical approach to the multimodal prognostication of coma after CA, with a particular focus on neuromonitoring tools. We also propose an algorithm for the optimal use of such multimodal tools during the early ICU phase of post-CA coma.

  12. A Prognostic Model for Patients with Triple-Negative Breast Cancer: Importance of the Modified Nottingham Prognostic Index and Age

    PubMed Central

    Kwon, Jeanny; Eom, Keun-Yong; Koo, Tae Ryool; Kim, Byoung Hyuck; Kang, Eunyoung; Kim, Sung-Won; Kim, Yu Jung; Park, So Yeon

    2017-01-01

    Purpose Considering the distinctive biology of triple-negative breast cancer (TNBC), this study aimed to identify TNBC-specific prognostic factors and determine the prognostic value of the Nottingham Prognostic Index (NPI) and its variant indices. Methods A total of 233 patients with newly diagnosed stage I to III TNBC from 2003 to 2012 were reviewed. We retrospectively analyzed the patients' demographics, clinicopathologic parameters, treatment, and survival outcomes. The NPI was calculated as follows: tumor size (cm)×0.2+node status+Scarff-Bloom-Richardson (SBR) grade. The modified NPI (MNPI) was obtained by adding the modified SBR grade rather than the SBR grade. Results The median follow-up was 67.8 months. Five-year disease-free survival (DFS) and overall survival (OS) were 81.4% and 89.9%, respectively. Multivariate analyses showed that the MNPI was the most significant and common prognostic factor of DFS (p=0.001) and OS (p=0.019). Young age (≤35 years) was also correlated with poor DFS (p=0.006). A recursive partitioning for establishing the prognostic model for DFS was performed based on the results of multivariate analysis. Patients with a low MNPI (≤6.5) were stratified into the low-risk group (p<0.001), and patients with a high MNPI (>6.5) were subdivided into the intermediate (>35 years) and high-risk (≤35 years) groups. Age was not a prognostic factor in patients with a low MNPI, whereas in patients with a high MNPI, it was the second key factor in subdividing patients according to prognosis (p=0.023). Conclusion The MNPI could be used to stratify patients with stage I to III TNBC according to prognosis. It was the most important prognosticator for both DFS and OS. The prognostic significance of young age for DFS differed by MNPI. PMID:28382096

  13. Nuclear fractal dimension as a prognostic factor in oral squamous cell carcinoma.

    PubMed

    Goutzanis, L; Papadogeorgakis, N; Pavlopoulos, P M; Katti, K; Petsinis, V; Plochoras, I; Pantelidaki, C; Kavantzas, N; Patsouris, E; Alexandridis, C

    2008-04-01

    Strong theoretical reasons exist for using fractal geometry in measurements of natural objects, including most objects studied in pathology. Indeed, fractal dimension provides a more precise and theoretically more appropriate approximation of their structure properties and especially their shape complexity. The aim of our study was to evaluate the nuclear fractal dimension (FD) in tissue specimens from patients with oral cavity carcinomas in order to assess its potential value as prognostic factor. Relationships between FD and other factors including clinicopathologic characteristics were also investigated. Histological sections from 48 oral squamous cell carcinomas as well as from 17 non-malignant mucosa specimens were stained with Hematoxylin-Eosin for pathological examination and with Feulgen for nuclear complexity evaluation. The sections were evaluated by image analysis using fractal analysis software to quantify nuclear FD by the box-counting method. Carcinomas presented higher mean values of FD compared to normal mucosa. Well differentiated neoplasms had lower FD values than poorly differentiated ones. FD was significantly correlated with the nuclear size. Patients with FD lower than the median value of the sample had statistically significant higher survival rates. Within the sample of patients studied, FD was proved to be an independent prognostic factor of survival in oral cancer patients. In addition this study provides evidence that there are several statistically significant correlations between FD and other morphometric characteristics or clinicopathologic factors in oral squamous cell carcinomas.

  14. Prognostic value of serum carbonic anhydrase IX in testicular germ cell tumor patients

    PubMed Central

    Kalavska, Katarina; Chovanec, Michal; Zatovicova, Miriam; Takacova, Martina; Gronesova, Paulina; Svetlovska, Daniela; Baratova, Magdalena; Miskovska, Vera; Obertova, Jana; Palacka, Patrik; Rajec, Jan; Sycova-Mila, Zuzana; Cierna, Zuzana; Kajo, Karol; Spanik, Stanislav; Babal, Pavel; Mardiak, Jozef; Pastorekova, Silvia; Mego, Michal

    2016-01-01

    Despite the fact that testicular germ cell tumors (TGCTs) are one of the most chemosensitive solid tumors, a small proportion of patients fail to be cured following cisplatin-based first line chemotherapy. Upregulation of carbonic anhydrase IX (CA IX) in various solid tumors is associated with poor outcome. The current prospective study investigated the prognostic value of serum CA IX level in TGCTs. In total, 83 patients (16 non-metastatic following orchiectomy with no evidence of disease, 57 metastatic chemotherapy-naïve and 10 metastatic relapsed chemotherapy-pretreated) starting adjuvant and/or new line of chemotherapy and 35 healthy controls were enrolled in the study. Serum CA IX values were determined using an enzyme-linked immunosorbent assay, and intratumoral CA IX was analyzed by immunohistochemistry. Metastatic chemotherapy-naïve patients had significantly higher mean CA IX serum levels than healthy controls (490.6 vs. 249.6 pg/ml, P=0.005), while there was no difference in serum CA IX levels in non-metastatic or relapsed TGCT patients compared with healthy controls. There was no significant difference in the mean serum CA IX levels between different groups of patients and between the first and second cycle of chemotherapy, nor association with patients/tumor characteristics. Serum CA IX was not prognostic for progression-free survival [hazard ratio (HR)=0.81, P=0.730] or overall survival (HR=0.64, P=0.480). However, there was a significant association between intratumoral CA IX expression and serum CA IX concentration (rho=0.51, P=0.040). These results suggest that serum CA IX level correlates with tumor CA IX expression in TGCT patients, but fails to exhibit either a prognostic value or an association with patients/tumor characteristics. PMID:27698832

  15. Prognostic value of serum carbonic anhydrase IX in testicular germ cell tumor patients.

    PubMed

    Kalavska, Katarina; Chovanec, Michal; Zatovicova, Miriam; Takacova, Martina; Gronesova, Paulina; Svetlovska, Daniela; Baratova, Magdalena; Miskovska, Vera; Obertova, Jana; Palacka, Patrik; Rajec, Jan; Sycova-Mila, Zuzana; Cierna, Zuzana; Kajo, Karol; Spanik, Stanislav; Babal, Pavel; Mardiak, Jozef; Pastorekova, Silvia; Mego, Michal

    2016-10-01

    Despite the fact that testicular germ cell tumors (TGCTs) are one of the most chemosensitive solid tumors, a small proportion of patients fail to be cured following cisplatin-based first line chemotherapy. Upregulation of carbonic anhydrase IX (CA IX) in various solid tumors is associated with poor outcome. The current prospective study investigated the prognostic value of serum CA IX level in TGCTs. In total, 83 patients (16 non-metastatic following orchiectomy with no evidence of disease, 57 metastatic chemotherapy-naïve and 10 metastatic relapsed chemotherapy-pretreated) starting adjuvant and/or new line of chemotherapy and 35 healthy controls were enrolled in the study. Serum CA IX values were determined using an enzyme-linked immunosorbent assay, and intratumoral CA IX was analyzed by immunohistochemistry. Metastatic chemotherapy-naïve patients had significantly higher mean CA IX serum levels than healthy controls (490.6 vs. 249.6 pg/ml, P=0.005), while there was no difference in serum CA IX levels in non-metastatic or relapsed TGCT patients compared with healthy controls. There was no significant difference in the mean serum CA IX levels between different groups of patients and between the first and second cycle of chemotherapy, nor association with patients/tumor characteristics. Serum CA IX was not prognostic for progression-free survival [hazard ratio (HR)=0.81, P=0.730] or overall survival (HR=0.64, P=0.480). However, there was a significant association between intratumoral CA IX expression and serum CA IX concentration (rho=0.51, P=0.040). These results suggest that serum CA IX level correlates with tumor CA IX expression in TGCT patients, but fails to exhibit either a prognostic value or an association with patients/tumor characteristics.

  16. Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Español de Citogenética Hematológica.

    PubMed

    Solé, F; Espinet, B; Sanz, G F; Cervera, J; Calasanz, M J; Luño, E; Prieto, F; Granada, I; Hernández, J M; Cigudosa, J C; Diez, J L; Bureo, E; Marqués, M L; Arranz, E; Ríos, R; Martínez Climent, J A; Vallespí, T; Florensa, L; Woessner, S

    2000-02-01

    Recently, a consensus International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in the myelodysplastic syndromes (MDS) has been developed. However, the intermediate-risk cytogenetic subgroup defined by the IPSS includes a miscellaneous number of different single abnormalities for which real prognosis at present is uncertain. The main aims of this study were to evaluate in an independent series the prognostic value of the IPSS and to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in 640 patients. In univariate analyses, cases with single 1q abnormalities experienced poor survival, whereas those with trisomy 8 had a higher risk of acute leukaemic transformation than the remaining patients (P = 0.004 and P = 0.009 respectively). Patients with single del(12p) had a similar survival to patients with a normal karyotype and showed some trend for a better survival than other cases belonging to the IPSS intermediate-risk cytogenetic subgroup (P = 0.045). Multivariate analyses demonstrated that IPSS cytogenetic prognostic subgroup, proportion of bone marrow blasts and haemoglobin level were the main prognostic factors for survival, and the first two characteristics and platelet count were the best predictors of acute leukaemic transformation risk. A large international co-operative study should be carried out to clarify these findings.

  17. Methylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma

    PubMed Central

    Sharmab, Anup; Xie, Fei; Liu, Yanliang; Li, Kai; Wan, Weiwei; Baylin, Stephen B.; Wolfgang, Christopher L.; Ahuja, Nita

    2016-01-01

    Background O6-methylguanine-DNA methyltransferase (MGMT) methylation status has not been extensively investigated in duodenal adenocarcinoma (DA). The aim of this study was to evaluate the MGMT methylation status and examine its possible prognostic value in patients with stage III DA. Methods Demographics, tumor characteristics and survival were available for 64 patients with stage III DA. MGMT methylation was detected by using MethyLight. A Cox proportional hazard model was built to predict survival, adjusted for clinicopathological characteristics and tumor molecular features, including the CpG island methylator phenotype (CIMP), microsatellite instability (MSI), and KRAS mutations. Results MGMT methylation was detected in 17 of 64 (26.6%) patients, and was not correlated with sex, age, tumor differentiation, CIMP, MSI, or KRAS mutations. MGMT methylation was the only one factor associated with both overall survival (OS) and disease-free survival (DFS) on both univariate and multivariate analyses. In patients treated with surgery alone, MGMT-methylated group had worse OS and DFS when compared with MGMT-unmethylated group. However, in patients treated with chemotherapy/radiotherapy, outcomes became comparable between the two groups. Conclusions Our results demonstrate MGMT methylation is a reliable and independent prognostic factor in DAs. Methylation of MGMT is associated with poor prognosis in patients with stage III DAs. PMID:27643594

  18. Mixed Carcinoma as an Independent Prognostic Factor in Submucosal Invasive Gastric Carcinoma.

    PubMed

    Park, Hyung Kyu; Lee, Kyung-Yung; Yoo, Moon-Won; Hwang, Tae Sook; Han, Hye Seung

    2016-06-01

    Mixed carcinoma shows a mixture of glandular and signet ring/poorly cohesive cellular histological components and the prognostic significance of each component is not fully understood. This study aimed to investigate the significance of the poorly cohesive cellular histological component as a risk factor for lymph node metastasis and to examine the diagnostic reliability of endoscopic biopsy. Clinicopathologic characteristics of 202 patients who underwent submucosal invasive gastric carcinoma resection with lymph node dissection in 2005-2012 were reviewed. Mixed carcinoma accounted for 27.2% (56/202) of cases. The overall prevalence of lymph node metastasis was 17.3% (35/202). Lymphatic invasion (P < 0.001), family history of carcinoma (P = 0.025), tumor size (P = 0.004), Lauren classification (P = 0.042), and presence of any poorly cohesive cellular histological component (P = 0.021) positively correlated with the lymph node metastasis rate on univariate analysis. Multivariate analyses revealed lymphatic invasion, family history of any carcinoma, and the presence of any poorly cohesive cellular histological component to be significant and independent factors related to lymph node metastasis. Review of preoperative biopsy slides showed that preoperative biopsy demonstrated a sensitivity of 63.6% and a specificity of 100% in detecting the presence of the poorly cohesive cellular histological component, compared with gastrectomy specimens. The presence of any poorly cohesive cellular histological component was an independent risk factor associated with lymph node metastasis in submucosal invasive gastric carcinoma. Endoscopic biopsy had limited value in predicting the presence and proportion of the poorly cohesive cellular histologic component due to the heterogeneity of mixed carcinoma.

  19. Inclusion of hemoglobin level in prognostic score provides better prognostic stratification in patients with acute promyelocytic leukemia (APL).

    PubMed

    Park, Silvia; Lee, Su Jin; Kim, Kihyun; Jang, Jun Ho; Kim, Dong Hwan; Lee, Kyu Hyung; Lee, Je Hwan; Lee, Jung Hee; Kim, Dae Young; Jang, Dae-Young; Kim, Hawk; Park, Jae Hoo; Ryoo, Hun Mo; Bae, Sung Hwa; Kim, Min Kyung; Hyun, Myung Soo; Joo, Young Don; Lee, Won Sik; Lee, Sang Min; Jung, Chul Won

    2013-03-01

    The clinical outcomes of acute promyelocytic leukemia (APL) have improved greatly, but treatment failure still occurs. Identification of patients with poor prognosis is fundamental, and we propose a new clinical prognostic system (CBC-score) consisting of WBC, platelet count, and hemoglobin level. Between 1995 and 2009, 156 patients with APL from seven institutes in Korea were retrospectively reviewed. In the new CBC-score system, each of the following (WBC ≥ 10 × 109/L, platelet <40 × 109/L, hemoglobin <8.0 g/dL) was considered as a risk factor; the sum of each was designated as the CBC-score. With a median follow-up of 8.4 years, the complete remission (CR) rate was 81.4 % (127/156), while 24 (15.4 %) were considered as treatment failures due to early death (ED). The 5-year overall survival (OS), leukemia-free survival, and cumulative incidence of relapse were 73.8, 82.8, and 13.5 %, respectively. Compared to the individual CBC parameters, combined prognostic systems such as PETHEMA or CBC-score provided better prognostic stratification. Compared to PETHEMA stratification, the proposed prognostic CBC-score system showed better stratification of APL patients in terms of CR rates (p = 0.004), OS (p = 0.004), and ED (p = 0.008). This retrospective study suggests that the proposed CBC-score may provide better prognostic stratification of APL patients.

  20. Prognostic value of Muc5AC in gastric cancer: A meta-analysis

    PubMed Central

    Zhang, Chuan-Tao; He, Ke-Cheng; Pan, Fei; Li, Yuan; Wu, Jiang

    2015-01-01

    AIM: To assess the correlation between decreased Muc5AC expression and patients’ survival and clinicopathological characteristics by conducting a meta-analysis. METHODS: Literature searches were performed in PubMed and EMBASE, and 11 studies met our criteria. Summary hazard ratios or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the effect. For the pooled analysis of the correlation between decreased Muc5AC expression and clinicopathological characteristics (tumour invasion depth, lymph node metastasis, tumour-node-metastasis stage, tumour size, venous invasion and lymphatic invasion), ORs and their variance were combined to estimate the effect. RESULTS: Eleven retrospective cohort studies comprising 2135 patients were included to assess the association between Muc5AC expression and overall survival and/or clinicopathological characteristics. Decreased Muc5AC expression was significantly correlated with poor overall survival of gastric cancer patients (pooled HR = 1.35, 95%CI: 1.08-1.7). Moreover, decreased Muc5AC expression was also significantly associated with tumour invasion depth (pooled OR = 2.12, 95%CI: 1.56-2.87) and lymph node metastasis (pooled OR = 1.56, 95%CI: 1.00-2.44) in gastric cancer. CONCLUSION: Decreased Muc5AC expression might be a poor prognostic predictor for gastric cancer. PMID:26420972

  1. Rich Donors, Poor Countries

    ERIC Educational Resources Information Center

    Thomas, M. A.

    2012-01-01

    The shifting ideological winds of foreign aid donors have driven their policy towards governments in poor countries. Donors supported state-led development policies in poor countries from the 1940s to the 1970s; market and private-sector driven reforms during the 1980s and 1990s; and returned their attention to the state with an emphasis on…

  2. Inference in `poor` languages

    SciTech Connect

    Petrov, S.

    1996-10-01

    Languages with a solvable implication problem but without complete and consistent systems of inference rules (`poor` languages) are considered. The problem of existence of finite complete and consistent inference rule system for a ``poor`` language is stated independently of the language or rules syntax. Several properties of the problem arc proved. An application of results to the language of join dependencies is given.

  3. Prognostic Biomarkers in Ovarian Cancer

    PubMed Central

    Huang, Jie; Hu, Wei; Sood, Anil K

    2014-01-01

    Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy despite several decades of progress in diagnosis and treatment. Taking advantage of the robust development of discovery and utility of prognostic biomarkers, clinicians and researchers are developing personalized and targeted treatment strategies. This review encompasses recently discovered biomarkers of ovarian cancer, the utility of published prognostic biomarkers for EOC (especially biomarkers related to angiogenesis and key signaling pathways), and their integration into clinical practice. PMID:22045356

  4. Recurrent Bleeding in Hemorrhagic Moyamoya Disease : Prognostic Implications of the Perfusion Status

    PubMed Central

    Jo, Kyung-Il; Kim, Min Soo; Yeon, Je Young; Kim, Jong-Soo

    2016-01-01

    Objective Hemorrhagic moyamoya disease (hMMD) is associated with a poor clinical course. Furthermore, poorer clinical outcomes occur in cases of recurrent bleeding. However, the effect of hemodynamic insufficiency on rebleeding risk has not been investigated yet. This study evaluated the prognostic implications of the perfusion status during the clinical course of adult hMMD. Methods This retrospective study enrolled 52 adult hMMD patients between April 1995 and October 2010 from a single institute. Demographic data, clinical and radiologic characteristics, including hemodynamic status using single photon emission computed tomography (SPECT), and follow up data were obtained via a retrospective review of medical charts and imaging. Statistical analyses were performed to explore potential prognostic factors. Results Hemodynamic abnormality was identified in 44 (84.6%) patients. Subsequent revascularization surgery was performed in 22 (42.3%) patients. During a 58-month (median, range 3–160) follow-up assessment period, 17 showed subsequent stroke (hemorrhagic n=12, ischemic n=5, Actuarial stroke rate 5.8±1.4%/year). Recurrent hemorrhage was associated with decreased basal perfusion (HR 19.872; 95% CI=1.196–294.117) and omission of revascularization (10.218; 95%; CI=1.532–68.136). Conclusion Decreased basal perfusion seems to be associated with recurrent bleeding. Revascularization might prevent recurrent stroke in hMMD by rectifying the perfusion abnormality. A larger-sized, controlled study is required to address this issue. PMID:26962416

  5. Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma.

    PubMed

    Matsumoto, Yasunori; Kano, Masayuki; Akutsu, Yasunori; Hanari, Naoyuki; Hoshino, Isamu; Murakami, Kentaro; Usui, Akihiro; Suito, Hiroshi; Takahashi, Masahiko; Otsuka, Ryota; Xin, Hu; Komatsu, Aki; Iida, Keiko; Matsubara, Hisahiro

    2016-11-01

    Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established. Fluorescence imaging was performed on tumors and plasma exosomes harvested from mice. GFP-positive small vesicles were confirmed in the plasma obtained from TE2-CD63-GFP tumor-bearing mice. Patient plasma was collected in Chiba University Hospital (n=86). Exosomes were extracted from 100 µl of the plasma and quantified by acetylcholinesterase (AChE) activity. The relationship between exosome quantification and the patient clinical characteristics was assessed. The quantification of exosomes isolated from the patient plasma revealed that esophageal cancer patients (n=66) expressed higher exosome levels than non-malignant patients (n=20) (P=0.0002). Although there was no correlation between the tumor progression and the exosome levels, exosome number was the independent prognostic marker and low levels of exosome predicted a poor prognosis (P=0.03). In conclusion, exosome levels may be useful as an independent prognostic factor for ESCC patients.

  6. Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis

    PubMed Central

    Xu, Feng; Li, Mengxin; Zhang, Chao; Cui, Jianxiu; Liu, Jun; Li, Jie; Jiang, Hongchuan

    2017-01-01

    The prognostic significance of COX-2 in patients with breast cancer remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic value in patients with breast cancer. PubMed, EMBASE, Web of Science, the Ovid Database and Grey literature were systematically searched up to May 2016. Twenty-one studies including 6739 patients with breast cancer were analyzed. The meta-analysis indicated that the incidence difference of COX-2 expression was significant when comparing the lymph node positive group to negative group (OR = 1.76, 95% CI [1.30, 2.39]) and the tumor size ≥ 2cm group to the tumor size < 2cm group (OR = 1.71, 95% CI [1.22, 2.39]). None of other clinicopathological parameters such as the ER status, PR status, HER2 status and the vascular invasion status were associated with COX-2 overexpression. The detection of COX-2 was significantly correlated with the disease-free survival (DFS) of patients (HR = 1.58, 95% CI [1.23, 2.03]) and the overall survival (OS) of patients (HR = 1.51, 95% CI [1.31, 1.72]). Our meta-analysis demonstrates that the presence of high levels of COX-2 is associated with poor prognosis for breast cancer patients and predicts bigger tumor size and lymph node metastasis. PMID:27999206

  7. The value of prognostic screening for patients with low back pain in secondary care.

    PubMed

    Karran, Emma L; Traeger, Adrian C; McAuley, James H; Hillier, Susan L; Yau, Yun-Hom; Moseley, G Lorimer

    2017-01-30

    Prognostic screening in patients with low back pain (LBP) offers a practical approach to guiding clinical decisions. Whether screening is helpful in secondary care is unclear. This prospective cohort study in adults with LBP placed on outpatient clinic waiting lists, compared the performance of the short-form Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ), the PICKUP Tool (PICKUP) and the STarT Back Tool (SBT). We assessed predictive validity for outcome at 4-month follow-up, by calculating estimates of discrimination, calibration and overall performance. We applied a decision curve analysis (DCA) approach to describe the clinical value of screening in this setting via comparison with a 'treat-all' strategy. Complete data were available for 89% of enrolled participants (n=195). 84% reported 'poor outcome' at follow-up. The area under the receiver operating characteristic curve (95% confidence interval) was 0.66(0.54-0.78) for the OMPSQ; 0.61(0.49-0.73) for the PICKUP and 0.69(0.51-0.80) for the SBT. All instruments were miscalibrated and underestimated risk. DCA indicated that, in this setting, prognostic screening does not add value over and above a treat-all approach. The potential for LBP patients to be misclassified by screening and the high incidence of non-recovery indicate that care decisions should be made with the assumption that all patients are 'at risk'.

  8. The Chronically Poor: Breaking the Cycle.

    ERIC Educational Resources Information Center

    Morris-Bilotti, Sharon

    This question-and-answer format paper looks at some of the basic issues surrounding the chronically poor and initiatives and services designed to break the poverty cycle. A first section explores some of the myths and realities surrounding the characteristics of the chronically poor population and notes that this population is comprised of…

  9. Expression of hypoxic markers and their prognostic significance in soft tissue sarcoma

    PubMed Central

    KIM, JEUNG IL; CHOI, KYUNG UN; LEE, IN SOOK; CHOI, YOUNG JIN; KIM, WON TACK; SHIN, DONG HOON; KIM, KYUNGBIN; LEE, JEONG HEE; KIM, JEE YEON; SOL, MEE YOUNG

    2015-01-01

    Tumor hypoxia is significant in promoting tumor progression and resistance to therapy, and hypoxia-inducible factor 1α (HIF-1α) is essential in the adaptive response of cells to hypoxia. The aim of the present study was to investigate the expression of hypoxic markers and evaluate their prognostic significance in soft tissue sarcoma (STS). A retrospective analysis of 55 patients with STS from Pusan National University Hospital (Busan, Korea) between 1998 and 2007 was conducted, using immunohistochemistry to analyze the expression of HIF-1α, carbonic anhydrase 9 (CA9), glucose transporter-1 (GLUT1) and vascular endothelial growth factor (VEGF). The association between the overexpression of these markers and clinicopathological characteristics, including the overall survival (OS) and progression-free survival (PFS) in cases of STS, were investigated. Overexpression of HIF-1α, CA9, GLUT1 and VEGF was shown in 54.5, 32.7, 52.7 and 25.5% of tumors, respectively, and all exhibited a significant association with high French Federation of Cancer Centers (FNCLCC) grade and high American Joint Committee on Cancer (AJCC) stage. Overexpression of HIF-1α and CA9 was associated with a shorter OS and a shorter PFS. On multivariate analysis, AJCC stage and HIF-1α overexpression had independent prognostic significance. In the group receiving chemotherapy (n=27), HIF-1α overexpression was independently associated with a decreased OS. These results indicate that overexpression of HIF-1α and CA9 is associated with poor prognosis, and that HIF-1α overexpression is an independent unfavorable prognostic factor in STS. PMID:25789026

  10. Prognostic implications of PIK3CA amplification in curatively resected liposarcoma

    PubMed Central

    Kim, Eo Jin; Park, Kyu Hyun; Kim, Ki Hyang; Yi, Seong Yoon; Kim, Han Seong; Cho, Yong Jin; Shin, Kyoo-Ho; Ahn, Joong Bae; Hu, Hyuk; Kim, Kyung Sik; Choi, Young Deuk; Kim, Sunghoon; Lee, Young Han; Suh, Jin-Suck; Noh, Sung Hoon; Rha, Sun Young; Kim, Hyo Song

    2016-01-01

    Background We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutations/amplifications in curative resected liposarcoma. Patients and methods A total of 125 liposarcoma tissue samples were collected over a 12-year period. PIK3CA mutations and gene copy number amplifications were analyzed by pyrosequencing and fluorescence in situ hybridization (FISH). Results Nine of the 105 liposarcomas (8.6%) had activating PIK3CA mutation. PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic tumors compared with well-differentiated/dedifferentiated tumors (13.3% vs. 2.2%, P=0.043). In FISH PIK3CA analysis, copy number gain was detected in 14 of the 101 tumors (13.9%): 11 (10.9%) tumors had increased gene copy number (polysomy) and 3 (3.0%) exhibited gene amplification. In survival analysis, patients with PIK3CA copy number gain had a worse prognosis compared to patients without PIK3CA amplification (median disease-free survival [DFS] 22.2 vs. 107.6 months p=0.005). By multivariate analysis, PIK3CA copy number gain was an independent prognostic factor for worse DFS (P=0.027; hazard ratio, 2.400; 95% confidence interval 1.105 to 5.213). PIK3CA mutation was not associated with DFS and overall survival. Conclusions We demonstrated PIK3CA mutation and amplification in liposarcoma. PIK3CA copy number gain was an independent poor prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutations and amplifications in liposarcoma. PMID:27016421

  11. Rectal Adenocarcinoma: Proposal for a Model Based on Pretreatment Prognostic Factors

    PubMed Central

    Cabanillas, Fernando; Freire, Viviana; Nieves-Plaza, Mariely; Quevedo, Gerardo; Echenique, Ignacio A.

    2012-01-01

    Objective Currently the choice of chemotherapy regimen in rectal cancer is made prior to surgery in contrast to colon cancer where it is made postoperatively after the pathological stage has been determined. If we could identify which are the important pretreatment prognostic factors in rectal cancer, we could then target those patients with unfavorable features to investigate potentially more effective preoperative chemotherapy regimens aimed at those with unfavorable features. The present study aims to determine pre-treatment prognostic factors that are associated with an unfavorable outcome. Methods A retrospective review of 99 rectal cancer patients operated at the Hospital Auxilio Mutuo and Hospital San Pablo was done. Sociodemographic characteristics, clinical and treatment data was collected. Results 54% were males. The mean ± sd age was 62.2 ± 10.4. In age-adjusted Cox model, male gender [HR (95%CI): 3.32 (1.09–10.13)], mucinous carcinoma [HR (95%CI): 3.67 (1.25–10.77)], and clinical stages II & III [HR (95%CI): 8.19 (1.08–62.08)] were predictors of poor prognosis. In multivariate age-adjusted analysis, a tendency towards a poorer prognosis was observed for male patients [HR: 2.60] CEA level ≥ 5ng/ml [HR: 2.55], mucinous carcinoma [HR:2.96], and clinical stages II & III [HR:4.96], although results were not statistically significant (p>0.05), Conclusion Although current therapeutic results are relatively favorable with preoperative 5-Fluorouracil (5FU) and radiotherapy, future clinical trials should address the management of those cases with adverse pretreatment prognostic factors so that they can be treated with potentially more effective albeit more toxic chemotherapy regimens. PMID:22783696

  12. Clinical implications of serum N-glycan profiling as a diagnostic and prognostic biomarker in germ-cell tumors.

    PubMed

    Narita, Takuma; Hatakeyama, Shingo; Yoneyama, Tohru; Narita, Shintaro; Yamashita, Shinichi; Mitsuzuka, Koji; Sakurai, Toshihiko; Kawamura, Sadafumi; Tochigi, Tatsuo; Takahashi, Ippei; Nakaji, Shigeyuki; Tobisawa, Yuki; Yamamoto, Hayato; Koie, Takuya; Tsuchiya, Norihiko; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara

    2017-03-20

    Serum biomarker monitoring is essential for management of germ-cell tumors (GCT). However, not all GCT are positive for conventional tumor markers. We examined whether serum N-glycan-based biomarkers can be applied for detection and prognosis in patients with GCT. We performed a comprehensive N-glycan structural analysis of sera from 54 untreated GCT patients and 103 age-adjusted healthy volunteers using glycoblotting methods and mass spectrometry. Candidate N-glycans were selected from those with the highest association; cutoff concentration values were established, and an N-glycan score was created based on the number of positive N-glycans present. The validity of this score for diagnosis and prognosis was analyzed using a receiver operating characteristic (ROC) curve. We identified five candidate N-glycans significantly associated with GCT patients. The accuracy of the N-glycan score for GCT was significant with an area-under-the-curve (AUC) value of 0.87. Diagnostically, the N-glycan score detected 10 of 12 (83%) patients with negative conventional tumor markers. Prognostically, the N-glycan score comprised four candidate N-glycans. The predictive value of the prognostic N-glycan score was significant, with an AUC value of 0.89. A high value prognostic N-glycan score was significantly associated with poor prognosis. Finally, to identify a potential carrier protein, immunoglobulin (Ig) fractions of sera were subjected to N-glycan analysis and compared to whole sera. Candidate N-glycans in Ig-fractions were significantly decreased; therefore, the carrier protein for candidate N-glycans is likely not an immunoglobulin. In summary, our newly developed N-glycan score seems to be a practical diagnostic and prognostic method for GCT.

  13. Long-term survival in glioblastoma: methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factor

    PubMed Central

    Smrdel, Uros; Zwitter, Matjaz; Bostjancic, Emanuela; Zupan, Andrej; Kovac, Viljem; Glavac, Damjan; Bokal, Drago; Jerebic, Janja

    2016-01-01

    Abstract Background In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma. Patients and methods Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescent in situ hybridization). Results Methylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p = 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups. Conclusions Molecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored. PMID:27904447

  14. Clinical Significance of the Prognostic Nutritional Index for Predicting Short- and Long-Term Surgical Outcomes After Gastrectomy

    PubMed Central

    Lee, Jee Youn; Kim, Hyoung-Il; Kim, You-Na; Hong, Jung Hwa; Alshomimi, Saeed; An, Ji Yeong; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon; Kim, Choong-Bai

    2016-01-01

    Abstract To evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy. Assessing a patient's immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer. We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups. Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212–1.869, P <0.001), old age, male sex, high body mass index, medical comorbidity, total gastrectomy, and combined resection to be independent predictors of postoperative complications. Among these, only low PNI (OR = 4.279, 95% CI = 1.760–10.404, P = 0.001) and medical comorbidity were independent predictors of postoperative mortality. For long-term outcomes, low PNI was a poor prognostic factor for overall survival, but not recurrence (overall survival: hazard ratio [HR] = 1.383, 95% CI = 1.221–1.568, P < 0.001; recurrence-free survival: HR = 1.142, 95% CI = 0.985–1.325, P = 0.078). PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. Although PNI was an independent prognostic factor for overall survival, the index was not associated with cancer recurrence. PMID:27149460

  15. Acute Escherichia coli Mastitis in Dairy Cattle: Diagnostic Parameters Associated with Poor Prognosis

    PubMed Central

    HAGIWARA, Seiichi; MORI, Kouichiro; OKADA, Hiroyuki; OIKAWA, Shin; NAGAHATA, Hajime

    2014-01-01

    ABSTRACT This study aimed to identify the diagnostic characteristics associated with poor prognosis and mortality in dairy cows with acute clinical Escherichia coli mastitis. On 17 dairy farms, 24 dairy cows with acute E. coli mastitis that had received therapeutic treatment were categorized into 2 groups by outcome: 17 cows that recovered (survivors) and 7 cows that died or were euthanized (non-survivors). Two days after onset of acute E. coli mastitis, dysstasia was observed in non-survivors, but not in survivors. Compared with survivors, significantly increased hematocrit (HCT) values and non-esterified fatty acid (NEFA) concentrations, and significantly decreased antithrombin activity and platelet counts were found in non-survivors on days 2 and 3 after therapy. Dysstasia, associated with decreased antithrombin activity and platelet counts, and with increased HCT and NEFA concentrations, was considered to be the major prognostic indicator associated with high mortality after therapeutic treatment in acute E. coli mastitis. PMID:25056677

  16. MACC1 upregulation promotes gastric cancer tumor cell metastasis and predicts a poor prognosis*

    PubMed Central

    Xie, Qiu-ping; Xiang, Cheng; Wang, Gang; Lei, Ke-feng; Wang, Yong

    2016-01-01

    In various studies, metastasis associated with colon cancer 1 (MACC1) has been frequently reported to be abnormally highly expressed in human lung cancer, colon cancer, and hepatocellular carcinoma. Our study focuses on the association of MACC1 expression with gastric cancer (GC). During our experiment, the MACC1 expression was tested in 105 GC samples using an immunohistochemical (IHC) method. The clinical characteristics and prognosis of these patients were summarized. During analysis, MACC1 distribution in GC samples with distant metastasis was higher than that in normal samples and in tumors with no dissemination. Subsequently, a lower 5-year survival rate had a strong correlation with high MACC1 expression. As a consequence, the present results suggest that MACC1 is more frequently expressed in a poor prognosis phenotype of GC and acts as a promising prognostic prediction parameter for GC. PMID:27143263

  17. MACC1 upregulation promotes gastric cancer tumor cell metastasis and predicts a poor prognosis.

    PubMed

    Xie, Qiu-Ping; Xiang, Cheng; Wang, Gang; Lei, Ke-Feng; Wang, Yong

    2016-05-01

    In various studies, metastasis associated with colon cancer 1 (MACC1) has been frequently reported to be abnormally highly expressed in human lung cancer, colon cancer, and hepatocellular carcinoma. Our study focuses on the association of MACC1 expression with gastric cancer (GC). During our experiment, the MACC1 expression was tested in 105 GC samples using an immunohistochemical (IHC) method. The clinical characteristics and prognosis of these patients were summarized. During analysis, MACC1 distribution in GC samples with distant metastasis was higher than that in normal samples and in tumors with no dissemination. Subsequently, a lower 5-year survival rate had a strong correlation with high MACC1 expression. As a consequence, the present results suggest that MACC1 is more frequently expressed in a poor prognosis phenotype of GC and acts as a promising prognostic prediction parameter for GC.

  18. Review and Analysis of Algorithmic Approaches Developed for Prognostics on CMAPSS Dataset

    NASA Technical Reports Server (NTRS)

    Ramasso, Emannuel; Saxena, Abhinav

    2014-01-01

    Benchmarking of prognostic algorithms has been challenging due to limited availability of common datasets suitable for prognostics. In an attempt to alleviate this problem several benchmarking datasets have been collected by NASA's prognostic center of excellence and made available to the Prognostics and Health Management (PHM) community to allow evaluation and comparison of prognostics algorithms. Among those datasets are five C-MAPSS datasets that have been extremely popular due to their unique characteristics making them suitable for prognostics. The C-MAPSS datasets pose several challenges that have been tackled by different methods in the PHM literature. In particular, management of high variability due to sensor noise, effects of operating conditions, and presence of multiple simultaneous fault modes are some factors that have great impact on the generalization capabilities of prognostics algorithms. More than 70 publications have used the C-MAPSS datasets for developing data-driven prognostic algorithms. The C-MAPSS datasets are also shown to be well-suited for development of new machine learning and pattern recognition tools for several key preprocessing steps such as feature extraction and selection, failure mode assessment, operating conditions assessment, health status estimation, uncertainty management, and prognostics performance evaluation. This paper summarizes a comprehensive literature review of publications using C-MAPSS datasets and provides guidelines and references to further usage of these datasets in a manner that allows clear and consistent comparison between different approaches.

  19. Poorly controlled gout: who is doing poorly?

    PubMed Central

    Chia, Faith Li-Ann

    2016-01-01

    Gout, an inflammatory arthritis caused by the deposition of monosodium urate crystals, is commonly seen in primary care and specialist clinics. In recent years, there has been a resurgence of interest in gout due to advances in therapies and the understanding of pathophysiology, with new guidelines being published by international bodies. However, there is still a gap between the goals of treatment and actual day-to-day practice. Barriers that result in poorly controlled gout include patient factors such as lack of understanding of the disease, stigma and nonadherence to treatment, as well as physician factors such as knowledge gaps, inadequate use of allopurinol and lack of ownership of the disease. The medical profession needs to do more to bridge the gap through physician and patient education, identification of treatment targets with appropriate use of drugs, and dissemination of guidelines. PMID:27549096

  20. Prognostic and clinicopathologic significance of neutrophil-to-lymphocyte ratio in esophageal squamous cell carcinoma: evidence from a meta-analysis

    PubMed Central

    Huang, Yu; Sun, Yue; Peng, Ping; Zhu, Sixian; Sun, Wei; Zhang, Peng

    2017-01-01

    Purpose Evidence from an increasing number of studies has demonstrated that the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor for various cancers. However, it is unclear whether NLR predicts prognosis in esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis to investigate the prognostic and clinicopathologic significance of NLR in patients with ESCC. Patients and methods Selected studies were identified by searches in PubMed, Embase, and Web of Science databases and filtered using our prepared criteria. The hazard ratio (HR) and odds ratio were chosen as effect measures to assess the prognostic role of NLR and its clinicopathologic significance in ESCC. In total, nine studies containing 2,513 patients were enrolled. Results We demonstrated that elevated NLR was associated with worse overall survival in ESCC patients (pooled HR =1.314; 95% confidence interval, 1.164–1.484; P<0.001). Elevated NLR was also associated with unfavorable characteristics regarding depth of tumor invasion, tumor size, clinical stage, and differentiation degree. Conclusion The results of our meta-analysis suggest that a high NLR value might represent a poor prognosis and worse clinicopathologic characteristics for patients with ESCC. PMID:28260931

  1. Nodal metastases in thyroid cancer: prognostic implications and management.

    PubMed

    Wang, Laura Y; Ganly, Ian

    2016-04-01

    The significance of cervical lymph node metastases in differentiated thyroid cancer has been controversial and continues to evolve. Current staging systems consider nodal metastases to confer a poorer prognosis, particularly in older patients. Increasingly, the literature suggests that characteristics of the metastatic lymph nodes such as size and number are also prognostic. There is a growing trend toward less aggressive treatment of low-volume nodal disease. The aim of this review is to summarize the current literature and discuss prognostic and management implications of lymph node metastases in differentiated thyroid cancer.

  2. Clinical importance of F-waves as a prognostic factor in Guillain-Barré syndrome in children

    PubMed Central

    Lee, Eung-Bin; Lee, Yun Young; Lee, Jae Min; Son, Su Min; Hwang, Su-Kyeong; Kwon, Soonhak

    2016-01-01

    Purpose A limited number of studies have examined the link between F-wave abnormalities and clinical presentation in pediatric Guillain-Barré syndrome (GBS). Therefore, this study examined the importance of F-wave abnormalities as a prognostic factor in pediatric GBS patients. Methods The records and electrodiagnostic studies (EDS) of 70 GBS patients were retrospectively evaluated, and divided into 2 groups according to the results of EDS. Group A (n=33) presented with F-wave abnormalities, and group B (n=26) exhibited normal findings. We compared laboratory reports, clinical features, response to treatment, and prognosis between the 2 groups. Results Motor weakness was the most frequently observed symptom for either group. Clinically, the incidence of fever and upper respiratory symptoms differed between the 2 groups, while the prevalence of abnormal deep tendon reflex (DTR) was significantly higher in group A than B (P<0.05). Patients diagnosed with GBS had received intravenous immunoglobulin treatment: 94% in group A and 58% in group B. Furthermore, significantly greater numbers of patients in group A showed H-reflex abnormalities and poor prognosis compared with group B (P<0.05). Conclusion This study demonstrated that F-waves are a clinically important prognostic factor in GBS. F-wave abnormalities were associated with abnormal DTR and poor prognosis in patients. Limited studies have examined the link between F-wave abnormalities and clinical results; therefore, further randomized controlled studies are needed to confirm the clinical characteristics and efficacy of treatments. PMID:27462356

  3. C-reactive protein/albumin ratio as prognostic score in oral squamous cell carcinoma

    PubMed Central

    2016-01-01

    Objectives Many studies have examined histopathological factors and various prognostic scores related to inflammation to predict outcomes. Here, we examined the prognostic value of the C-reactive protein/albumin (CRP/alb) ratio in oral squamous cell carcinoma (OSCC). Materials and Methods This retrospective study included 40 patients with OSCC. Using univariate and multivariate analyses, we focused on the correlation of the CRP/alb ratio with clinicopathological characteristics and with overall survival. We then compared five inflammation-based prognostic scores, CRP/alb ratio, modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and prognostic nutritional index (PNI), based on receiver operating characteristic (ROC) curves. Results The optimal cut-off value for the CRP/alb ratio was 0.085. The group with a high CRP/alb ratio had a high TNM clinical stage (P=0.002) and larger primary tumors (P=0.029), with statistically significant differences in lymph node metastasis and distant metastasis. In addition, when the CRP/alb ratio was high, multivariate analysis showed a lower survival rate (P=0.002; hazard ratio=6.078), and the ROC curve showed more outstanding discriminatory ability regarding overall survival compared to other inflammation-based prognostic scores. Conclusion The CRP/alb ratio can be an independent prognostic factor when predicting prognosis in OSCC and has good prognostic ability. PMID:27847731

  4. Long-Term Prognostic Analysis after Endoscopic Endonasal Surgery for Olfactory Neuroblastoma: A Retrospective Study of 13 Cases

    PubMed Central

    Zhang, Luyao; Zhu, Kang; Xia, Cui; Yan, Jing; Zhao, Wei; Wei, Junrong; Duan, Maoli; Zheng, Guoxi

    2016-01-01

    Objectives To summarize the characteristics and long–term outcomes of olfactory neuroblastoma through the analysis of 13 cases in single institution, with the assessment of treatment modality, prognostic factors. Method A retrospective study of thirteen cases diagnosed as olfactory neuroblastoma and underwent combined treatments during the period 2000–2010. Statistical analysis was performed to search for prognostic factors and compared different treatment modalities. Results 13 patients were enrolled in this study, including 8 male and 5 female, ranging from 15 to 69 (median 43) years old. One patient at stage A was only treated with endoscopic endonasal surgery (EES). Seven patients were treated with preoperative radiotherapy and EES, two with EES and postoperative radiotherapy, and the other three with combined radiotherapy and chemotherapy. The range of follow-up time varied from 23 to 116 months (median 65 months). The 5-year overall survival rate was 46.2% (6/13). To date, these thirteen patients have not suffered local recurrences while two patients had lymph node recurrences and one had distant metastasis in the bone marrow. In 13 patients, 61.5% were diagnosed as late T stage (T3/4), 69.2% late Kadish stage (C/D) and 53.8% were high Hyams grade (I/ II), which indicated poor prognosis. Related prognostic factors were the TNM stage (T stage P = 0.028, N stage P = 0.000, M stage P = 0.007), Kadish stage (P = 0.025) and treatment modality (P = 0.015). Conclusion Late stage of TNM and Kadish staging system indicated a poor prognosis. Combined treatment modality, including endoscopic endonasal surgery, achieved a better outcome than non-surgical approach. PMID:27806104

  5. Breast cancer in neurofibromatosis type 1: overrepresentation of unfavourable prognostic factors

    PubMed Central

    Uusitalo, Elina; Kallionpää, Roope A; Kurki, Samu; Rantanen, Matti; Pitkäniemi, Janne; Kronqvist, Pauliina; Härkönen, Pirkko; Huovinen, Riikka; Carpen, Olli; Pöyhönen, Minna; Peltonen, Sirkku; Peltonen, Juha

    2017-01-01

    Background: An increased breast cancer incidence and poor survival have been reported for women with neurofibromatosis 1 (NF1). To explain the poor survival, we aimed to link the histopathology and clinical characteristics of NF1-associated breast cancers. Methods: The Finnish Cancer Registry and the Finnish NF Registry were cross-referenced to identify the NF1 patients with breast cancer. Archival NF1 breast cancer specimens were retrieved for histopathological typing and compared with matched controls. Results: A total of 32 breast cancers were diagnosed in 1404 NF1 patients during the follow-up. Women with NF1 had an estimated lifetime risk of 18.0% for breast cancer, and this is nearly two-fold compared with that of the general Finnish female population (9.74%). The 26 successfully retrieved archival NF1 breast tumours were more often associated with unfavourable prognostic factors, such as oestrogen and progesterone receptor negativity and HER2 amplification. However, survival was worse in the NF1 group (P=0.053) even when compared with the control group matched for age, diagnosis year, gender and oestrogen receptor status. Scrutiny of The Cancer Genome Atlas data set showed that NF1 mutations and deletions were associated with similar characteristics in the breast cancers of the general population. Conclusions: These results emphasise the role of the NF1 gene in the pathogenesis of breast cancer and a need for active follow-up for breast cancer in women with NF1. PMID:27931045

  6. Prognostic Factors After Extraneural Metastasis of Medulloblastoma

    SciTech Connect

    Mazloom, Ali; Zangeneh, Azy H.; Paulino, Arnold C.

    2010-09-01

    Purpose: To review the existing literature regarding the characteristics, prognostic factors, treatment, and survival of patients with medulloblastoma, who develop extraneural metastasis (ENM). Methods and Materials: A PubMed search of English language articles from 1961 to 2007 was performed, yielding 47 articles reporting on 119 patients. Factors analyzed included age, time interval to development of ENM, ENM location, central nervous system (CNS) involvement, treatment, and outcome. Results: Sites of ENM included bone in 84% of patients, bone marrow in 27% of patients, lymph nodes in 15% of patients, lung in 6% of patients, and liver in 6% of patients. Median survival was 8 months after diagnosis of ENM. The 1-, 2-, and 5-year overall survival (OS) rates after diagnosis of ENM were 41.9%, 31.0%, and 26.0%, respectively. The 1-, 2-, and 5-year progression-free survival (PFS) rates after diagnosis of ENM were 34.5%, 23.2%, and 13.4%, respectively. For patients without CNS involvement at the time of ENM diagnosis, the 1-, 2-, and 5-year OS rates for those treated with and without radiotherapy (RT) were 82.4%, 64.8%, and 64.8% vs. 51.0%, 36.6%, and 30.5%, respectively (p = 0.03, log-rank test). RT did not significantly improve OS or PFS rates for those with CNS involvement. Concurrent CNS involvement, ENM in the lung or liver, a time interval of <18 months to development of ENM, and a patient age of <16 years at ENM diagnosis were found to be negative prognostic factors for both OS and PFS. Conclusions: Several prognostic factors were identified for patients with ENM from medulloblastoma. Patients without concurrent CNS involvement, who received RT after ENM diagnosis had an OS and PFS benefit compared to those who did not receive RT.

  7. Towards Prognostics of Electrolytic Capacitors

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Kulkarni, Chetan; Biswas, Gautam; Goegel, Kai

    2011-01-01

    A remaining useful life prediction algorithm and degradation model for electrolytic capacitors is presented. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management research. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. In particular, experimental results of an accelerated aging test under electrical stresses are presented. The capacitors used in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors.

  8. Histopathologic Features of Prognostic Significance in High-Grade Osteosarcoma.

    PubMed

    Chui, Michael Herman; Kandel, Rita A; Wong, Marcus; Griffin, Anthony M; Bell, Robert S; Blackstein, Martin E; Wunder, Jay S; Dickson, Brendan C

    2016-08-23

    Context .- In osteosarcoma treated with neoadjuvant chemotherapy the extent of tumor necrosis on resection is considered an indicator of treatment response, and this has been shown to correlate with survival in most but not all studies. Objective .- To identify additional histologic variables of prognostic significance in high-grade osteosarcoma. Design .- Slides of pretreatment biopsy and primary postneoadjuvant chemotherapy resections from 165 patients with high-grade osteosarcoma were reviewed. Univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were performed to identify clinical and histomorphologic attributes associated with overall survival. Results .- Univariate analyses confirmed the prognostic significance of metastatic status on presentation, primary tumor size, anatomic site, and histologic subtype. Additionally, the identification of lymphovascular invasion, 10% or more residual viable tumor, and 10 or more mitoses per 10 high-powered fields assessed in posttreatment resections were associated with poor survival, retaining significance in multivariate analyses. Based on results from multivariate analysis, we developed a prognostic index incorporating primary tumor size and site, and significant histologic features assessed on resection (ie, lymphovascular invasion status, mitotic rate, and extent of viable tumor). This scoring system segregates patients into 3 risk categories with significant differences in overall survival and retained significance in an independent validation set of 42 cases. Conclusions .- The integration of clinical and microscopic features improves prognostication of patients with osteosarcoma.

  9. The Poor Pay More.

    ERIC Educational Resources Information Center

    Folse, Kimberly A.

    2002-01-01

    Describes a sociology experiential learning assignment where students learned why people living in poverty can sometimes pay more for products than people with better incomes. Focuses specifically on the rent to own concept. States students achieved the goal of learning how life constraints of poverty can hinder the poor from overcoming their…

  10. Confronting Poor Performance.

    ERIC Educational Resources Information Center

    Dennis, Bruce L.

    Responsible and effective administrative leadership requires confronting those members of the teaching staff who are a negative influence on the institution. Importantly, the absence of expressed appreciation for good work can have a devastating impact on a principal's image if he or she suddenly begins to confront poor performances. Actually, the…

  11. The infiltration, and prognostic importance, of Th1 lymphocytes vary in molecular subgroups of colorectal cancer

    PubMed Central

    Ling, Agnes; Lundberg, Ida V; Eklöf, Vincy; Wikberg, Maria L; Öberg, Åke; Palmqvist, Richard

    2015-01-01

    Abstract Giving strong prognostic information, T‐cell infiltration is on the verge of becoming an additional component in the routine clinical setting for classification of colorectal cancer (CRC). With a view to further improving the tools for prognostic evaluation, we have studied how Th1 lymphocyte infiltration correlates with prognosis not only by quantity, but also by subsite, within CRCs with different molecular characteristics (microsatellite instability, CpG island methylator phenotype status, and BRAF and KRAS mutational status). We evaluated the Th1 marker T‐bet by immunohistochemistry in 418 archival tumour tissue samples from patients who underwent surgical resection for CRC. We found that a high number of infiltrating Th1 lymphocytes is strongly associated with an improved prognosis in patients with CRC, irrespective of intratumoural subsite, and that both extent of infiltration and patient outcome differ according to molecular subgroup. In brief, microsatellite instability, CpG island methylator phenotype‐high and BRAF mutated tumours showed increased infiltration of Th1 lymphocytes, and the most pronounced prognostic effect of Th1 infiltration was found in these tumours. Interestingly, BRAF mutated tumours were found to be more highly infiltrated by Th1 lymphocytes than BRAF wild‐type tumours whereas the opposite was seen for KRAS mutated tumours. These differences could be explained at least partly by our finding that BRAF mutated, in contrast to KRAS mutated, CRC cell lines and tumour specimens expressed higher levels of the Th1‐attracting chemokine CXCL10, and reduced levels of CCL22 and TGFB1, stimulating Th2/Treg recruitment and polarisation. In conclusion, the strong prognostic importance of Th1 lymphocyte infiltration in CRC was found at all subsites evaluated, and it remained significant in multivariable analyses, indicating that T‐bet may be a valuable marker in the clinical setting. Our results also indicate that T‐bet is of

  12. Bio-pathologic characteristics related to chromosome 11 aneusomy and cyclin D1 gene status in surgically resected stage I and II breast cancer: Identification of an adverse prognostic profile.

    PubMed

    Mottolese, Marcella; Orlandi, Giulia; Sperduti, Isabella; Merola, Roberta; Buglioni, Simonetta; Di Benedetto, Anna; Pinnarò, Paola; Perracchio, Letizia; Venturo, Irene; Cognetti, Francesco; Cianciulli, AnnaMaria

    2007-02-01

    We aimed at developing a more detailed understanding of cyclin D1 in early stage human breast cancer and defining the biologic profiles with different prognostic value correlating cyclin D1 gene amplification and chromosome 11 aneusomy with bio-pathologic variables of known clinical importance. Cyclin D1 gene amplification and chromosome 11 aneusomy were investigated using fluorescence in situ hybridization whereas cyclin D1, PgR, HER-2, Bcl2, p53, and Ki-67 expressions were analyzed by immunohistochemistry in 121 stage I or II breast cancer patients uniformly treated with cyclophosphamide/metotrexate/5-fluorouracil-based chemotherapy. Cyclin D1 was amplified in 6.6% and overexpressed in 32.2% of cases. Amplification was not associated with any selected bio-pathologic variables, whereas the chromosome 11 aneusomy level significantly increased in tumors with higher histologic grade (P < 0.01), higher tumor size (P < 0.003), p53 nuclear accumulation (P < 0.04), and ERalpha negativity (P < 0.049). Multiple correspondence analysis showed 4 different biologic tumor profiles. The first, characterized by high Ki-67 score, p53+, cyclin D1+, HER-2+, aneusomy level > 30%, ratio (cyclin D1 gene/CEP11) > 2, was associated with tumor relapse defining the most unfavorable biologic profile. Kaplan-Meier's method showed significantly shorter disease-free survival in patients with at least 3 variables positive out of the 6 detected by multiple correspondence analysis. In multivariate analysis, the identified biologic profile emerged as the only significant prognostic indicator. Our findings are of particular clinical interest for early stage breast cancer patients, because the assessment of biologic factors predictive of tumor aggressiveness may influence postoperative therapeutic strategies.

  13. Prognostic Value of Neutrophil-Related Factors in Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin-Based Concurrent Chemoradiotherapy.

    PubMed

    Wang, Yan-Yang; Bai, Zhou-Lan; He, Jian-Li; Yang, Yan; Zhao, Ren; Hai, Ping; Zhe, Hong

    2016-01-01

    The aim of this study was to explore the relationship between neutrophil-related factors, including neutrophil-lymphocyte ratio (NLR) and the responses of neutrophil to granulocyte colony-stimulating factors (RNG), and the prognosis of patients with locally advanced cervical squamous cell carcinoma (LACSCC) undergoing cisplatin-based concurrent chemoradiotherapy (CCCRT). A total of sixty LACSCC patients were enrolled in this study. We analyzed the association of NLR or RNG with clinicopathologic characteristics of these patients. The prognostic factors were evaluated by univariate and multivariate survival analysis. The optimal cut-off value of the NLR was determined to be 2.0 for the overall survival (OS). A higher level of the NLR was associated with younger age (P = 0.017) and higher baseline platelet count (P = 0.040). NLR was identified to be the only independent prognostic factor for OS by multivariate analysis (P = 0.037). The median RNG was 3.01, with a range of 1.19-16.84. RNG level was significantly associated with lymph node metastasis of these patients (P = 0.023). And higher RNG was identified as being a closely independent poor prognostic factor for OS (P = 0.055). This study showed that NLR and RNG may be used as potential biomarkers for survival prediction in patients with LACSCC receiving CCCRT.

  14. Letting the poor speak.

    PubMed

    2000-09-29

    This paper comments on two documents prepared by the Washington-based World Bank: the "World Development Report" and the three-volume study "Voices of the Poor." The author provides a brief overview of these documents then examines their potential impact on the delegates to the annual meetings of the World Bank and the International Monetary Fund in Prague on September 19-28, 2000. The author further examines the implication of the new strategies embraced by the global lenders--"opportunity, empowerment, security." Apart from these strategies, the World Bank sets out other strategies like spreading the benefits of technology, as it calls for the elimination of absolute poverty by 2015. However, the most crucial tack is the one illustrated by the way the reports were made: letting the poor speak and responding to their cries.

  15. Factors prognosticating the outcome of decompressive craniectomy in severe traumatic brain injury: A Malaysian experience

    PubMed Central

    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 < 0.001). In biochemical status the significant statistics included evidence of coagulopathy (P < 0.001), evidence of acidosis (P = 0.003) and evidence of hypoxia (P = 0.030). In Radiological sector, significant univariate analysis proved in location of the subdural clot (P < 0.010), location of the contusion (P = 0.045), site of existence of both type of clots (P = 0.031) and the evidence of edema (P = 0.041). The timing of injury was noted to be significant as well (P = 0.061). In the post operative care was, there were significance in the overall stability in intensive care (P < 0.001), the stability of blood pressure, cerebral perfusion pressure, pulse rates and oxygen saturation (all P < 0.001)seen individually, post operative ICP monitoring in the immediate (P = 0.002), within 24 hours (P < 0.001) and within 24-48 hours (P < 0.001) period, along with post operative pupillary size (P < 0.001) and motor score (P < 0.001). Post operatively, radiologically significant statistics included evidence of midline shift post operatively in the CT scan

  16. Cytogenetic Prognostication Within Medulloblastoma Subgroups

    PubMed Central

    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

  17. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  18. Prognostic Value of Brain Diffusion Weighted Imaging After Cardiac Arrest

    PubMed Central

    Wijman, Christine A.C.; Mlynash, Michael; Caulfield, Anna Finley; Hsia, Amie W.; Eyngorn, Irina; Bammer, Roland; Fischbein, Nancy; Albers, Gregory W.; Moseley, Michael

    2009-01-01

    Objective Outcome prediction is challenging in comatose post-cardiac arrest survivors. We assessed the feasibility and prognostic utility of brain diffusion-weighted MRI (DWI) during the first week. Methods Consecutive comatose post-cardiac arrest patients were prospectively enrolled. MRI data of patients who met predefined specific prognostic criteria were used to determine distinguishing ADC thresholds. Group 1: death at 6 months and absent motor response or absent pupillary reflexes or bilateral absent cortical responses at 72 hours, or vegetative at 1 month. Group 2A: Glasgow outcome scale (GOS) score of 4 or 5 at 6 months. Group 2B: GOS of 3 at 6 months. The percentage of voxels below different apparent diffusion coefficient (ADC) thresholds was calculated at 50 × 10−6 mm2/sec intervals. Results Overall, 86% of patients underwent MR imaging. Fifty-one patients with 62 brain MRIs were included in the analyses. Forty patients met the specific prognostic criteria. The percentage of brain volume with an ADC value below 650–700 × 10−6 mm2/sec best differentiated between group 1 and groups 2A and 2B combined (p<0.001), while the 400–450 × 10−6 mm2/sec threshold best differentiated between groups 2A and 2B (p=0.003). The ideal time window for prognostication using DWI was between 49 to 108 hours after the arrest. When comparing MRI in this time window with the 72 hour neurological examination MRI improved the sensitivity for predicting poor outcome by 38% while maintaining 100% specificity (p=0.021). Interpretation Quantitative DWI in comatose post-cardiac arrest survivors holds great promise as a prognostic adjunct. PMID:19399889

  19. Sensor systems for prognostics and health management.

    PubMed

    Cheng, Shunfeng; Azarian, Michael H; Pecht, Michael G

    2010-01-01

    Prognostics and health management (PHM) is an enabling discipline consisting of technologies and methods to assess the reliability of a product in its actual life cycle conditions to determine the advent of failure and mitigate system risk. Sensor systems are needed for PHM to monitor environmental, operational, and performance-related characteristics. The gathered data can be analyzed to assess product health and predict remaining life. In this paper, the considerations for sensor system selection for PHM applications, including the parameters to be measured, the performance needs, the electrical and physical attributes, reliability, and cost of the sensor system, are discussed. The state-of-the-art sensor systems for PHM and the emerging trends in technologies of sensor systems for PHM are presented.

  20. Sensor Systems for Prognostics and Health Management

    PubMed Central

    Cheng, Shunfeng; Azarian, Michael H.; Pecht, Michael G.

    2010-01-01

    Prognostics and health management (PHM) is an enabling discipline consisting of technologies and methods to assess the reliability of a product in its actual life cycle conditions to determine the advent of failure and mitigate system risk. Sensor systems are needed for PHM to monitor environmental, operational, and performance-related characteristics. The gathered data can be analyzed to assess product health and predict remaining life. In this paper, the considerations for sensor system selection for PHM applications, including the parameters to be measured, the performance needs, the electrical and physical attributes, reliability, and cost of the sensor system, are discussed. The state-of-the-art sensor systems for PHM and the emerging trends in technologies of sensor systems for PHM are presented. PMID:22219686

  1. Prognostic value of early features in rheumatoid disease.

    PubMed Central

    Fleming, A; Crown, J M; Corbett, M

    1976-01-01

    Extensive data on 102 patients who presented with rheumatoid disease within a year of onset were gathered by a prospective study to assess the prognostic value of early features. Outcome was evaluated at a mean 4-5 years from onset on the basis of functional grade, extent of joint disease, early morning stiffness, and grip strength. Twenty-six patients improved, 14 pursued a mild steady course, and 62 had a persistently severe or deteriorating condition. The features recorded at the first visit were correlated with outcome. Those indicating a poor prognosis were: older age at onset, being underweight, poor grip strength, many affected joints, involvement of wrist or metatarsophalangeal joints, poor functional status, fulfilment of many of the American Rheumatism Association criteria for rheumatoid disease, raised erythrocyte sedimentation rate, seropositivity on sheep cell agglutination or latex tests, low haemoglobin level, raised blood urea level, and early erosions on x-ray films. PMID:1083760

  2. Towards Prognostics for Electronics Components

    NASA Technical Reports Server (NTRS)

    Saha, Bhaskar; Celaya, Jose R.; Wysocki, Philip F.; Goebel, Kai F.

    2013-01-01

    Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is becoming a very important research field as a result of the need to provide aircraft systems with system level health management information. This paper focuses on a prognostics application for electronics components within avionics systems, and in particular its application to an Isolated Gate Bipolar Transistor (IGBT). This application utilizes the remaining useful life prediction, accomplished by employing the particle filter framework, leveraging data from accelerated aging tests on IGBTs. These tests induced thermal-electrical overstresses by applying thermal cycling to the IGBT devices. In-situ state monitoring, including measurements of steady-state voltages and currents, electrical transients, and thermal transients are recorded and used as potential precursors of failure.

  3. The challenge of poor-prognosis germ cell tumors.

    PubMed

    Toner, Guy C

    2007-05-01

    Patients who have a poor prognosis can be identified at presentation by well-defined prognostic factors. Prognostic groups as defined by the International Germ Cell Consensus Classification should be used in the clinic, in clinical trials, and when reporting results. No systemic treatment has been shown to improve outcome compared with four cycles of chemotherapy composed of bleomycin, etoposide, and cisplatin, which remains the standard of care. Surgery to resect residual masses after chemotherapy and in the salvage setting is a vital component of optimal care. The best outcomes occur with treatment at a center with experience and expertise in their management. Further major improvements are likely to require novel systemic therapies rather than modifications of existing approaches.

  4. Elevated Red Blood Cell Distribution Width as a Simple Prognostic Factor in Patients with Symptomatic Multiple Myeloma

    PubMed Central

    Lee, Hyewon; Kong, Sun-Young; Sohn, Ji Yeon; Shim, Hyoeun; Youn, Hye Sun; Lee, Sangeun; Kim, Hyun Ju; Eom, Hyeon-Seok

    2014-01-01

    Red blood cell distribution width (RDW) is a parameter reported in complete blood cell count tests, and has been reported as an inflammatory biomarker. Multiple myeloma (MM) is known to be associated with inflammatory microenvironments. However, the importance of RDW has been seldom studied in MM. For this study, 146 symptomatic myeloma patients with available RDW at diagnosis were retrospectively reviewed, and their characteristics were compared between two groups, those with high (>14.5%) and normal (≤14.5%) RDW. RDW was correlated to hemoglobin, MM stage, β2-microglobulin, M-protein, bone marrow plasma cells, and cellularity (P < 0.001). During induction, overall response rates of the two groups were similar (P = 0.195); however, complete response rate was higher in the normal-RDW group than it was in the high-RDW group (P = 0.005). With a median follow-up of 47 months, the normal-RDW group showed better progression-free survival (PFS) (24.2 versus 17.0 months, P = 0.029) compared to the high-RDW group. Overall survival was not different according to the RDW level (P = 0.236). In multivariate analysis, elevated RDW at diagnosis was a poor prognostic factor for PFS (HR 3.21, 95% CI 1.24–8.32) after adjustment with other myeloma-related prognostic factors. RDW would be a simple and immediately available biomarker of symptomatic MM, reflecting the systemic inflammation. PMID:24963470

  5. Prognostic Value of Plasma Intermedin Level in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

    PubMed

    Li, Pengyang; Shi, Lin; Han, Yalei; Zhao, Yuntao; Qi, Yongfen; Wang, Bin

    2016-04-01

    Intermedin (IMD), an autocrine/paracrine biologically active peptide, plays a critical role in maintaining vascular homeostasis. Recent research has shown that high plasma levels of IMD are associated with poor outcomes for patients with ST-segment elevation acute myocardial infarction. However, the prognostic utility of IMD levels in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) has not yet been investigated. We hypothesized that the level of plasma IMD would have prognostic value in patients with NSTE-ACS. Plasma IMD was determined by radioimmunoassay in 132 NSTE-ACS patients on admission to hospital and 132 sex- and age-matched healthy-control subjects. Major adverse cardiovascular events (MACEs), including death, heart failure, hospitalization, and acute myocardial infarction, were noted during follow-up. In total, 23 patients suffered MACEs during the follow-up period (mean 227 ± 118 days, range 2-421 days). Median IMD levels were higher in NSTE-ACS patients than control [320.0 (250.9/384.6) vs. 227.2 (179.7/286.9) pg/mL, P <0.001]. The area under the receiver-operating characteristic curve for IMD and N-terminal pro-B-type brain natriuretic peptide (NT-proBNP) did not significantly differ (0.73 and 0.79, both P <0.001, respectively; P = 0.946). ROC curve analysis revealed a cut-off value for IMD at 340.7 pg/mL. Cox regression analysis with cardiovascular risk variables and NT-proBNP showed that the risk of MACEs increased by a factor of 12.96 (95% CI, 3.26-49.42; P <0.001) with high IMD levels (at the cut-off value). IMD has potential as a prognostic biomarker for predicting MACEs in patients with NSTE-ACS.

  6. Analysis on therapeutic outcomes and prognostic factors of intracranial ependymoma: a report of 49 clinical cases in a single center.

    PubMed

    Ye, Jingliang; Zhu, Junle; Yan, Jiayi; Chen, Peiqin; Wan, Zhiping; Chen, Feng; Zhang, Lei; Qian, Jun; Luo, Chun

    2015-12-01

    Although intracranial ependymoma is relatively rare, it is often associated with great clinical aggressiveness and poor overall survival. There are controversies over factors affecting the prognosis of the disease. The aim of this retrospective study was to evaluate factors that may affect the therapeutic outcome and prognosis of intracranial ependymoma by reviewing the medical records of 49 patients who were surgically treated in our hospital between 2001 and 2014. Univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumor characteristics, and treatment modalities. All 49 patients (24 men and 25 women; mean age 27.6 years) underwent surgical resection, of whom 14 patients also underwent postoperative radiotherapy. Local recurrence was found in 15 (48.8 %) patients, and 22 (51.2 %) patients died during the follow-up periods. The 5-year recurrence rate was 65 % and the survival rate was 51 %. The results of statistical analysis suggested that preoperative extraventricular drainage and surgical resection extent were prognostic factors related to progression-free survival, and that age, surgical resection extent and histological grade were closely associated with survival. Interestingly, there was a significant correlation between the symptom of hydrocephalus and age (P = 0.010), and patients with a better clinical status (KPS ≥ 80) were significantly associated with a lower WHO grade (P = 0.007). In conclusion, we confirmed that surgical resection extent was the major independent factor affecting both recurrence and survival of patients with intracranial ependymoma, while age and WHO grade were prognostic factors affecting survival but not recurrence.

  7. Prognostic Value of Plasma Intermedin Level in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

    PubMed Central

    Li, Pengyang; Shi, Lin; Han, Yalei; Zhao, Yuntao; Qi, Yongfen; Wang, Bin

    2016-01-01

    Abstract Intermedin (IMD), an autocrine/paracrine biologically active peptide, plays a critical role in maintaining vascular homeostasis. Recent research has shown that high plasma levels of IMD are associated with poor outcomes for patients with ST-segment elevation acute myocardial infarction. However, the prognostic utility of IMD levels in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) has not yet been investigated. We hypothesized that the level of plasma IMD would have prognostic value in patients with NSTE-ACS. Plasma IMD was determined by radioimmunoassay in 132 NSTE-ACS patients on admission to hospital and 132 sex- and age-matched healthy-control subjects. Major adverse cardiovascular events (MACEs), including death, heart failure, hospitalization, and acute myocardial infarction, were noted during follow-up. In total, 23 patients suffered MACEs during the follow-up period (mean 227 ± 118 days, range 2–421 days). Median IMD levels were higher in NSTE-ACS patients than control [320.0 (250.9/384.6) vs. 227.2 (179.7/286.9) pg/mL, P <0.001]. The area under the receiver-operating characteristic curve for IMD and N-terminal pro-B-type brain natriuretic peptide (NT-proBNP) did not significantly differ (0.73 and 0.79, both P <0.001, respectively; P = 0.946). ROC curve analysis revealed a cut-off value for IMD at 340.7 pg/mL. Cox regression analysis with cardiovascular risk variables and NT-proBNP showed that the risk of MACEs increased by a factor of 12.96 (95% CI, 3.26–49.42; P <0.001) with high IMD levels (at the cut-off value). IMD has potential as a prognostic biomarker for predicting MACEs in patients with NSTE-ACS. PMID:27100434

  8. Usefulness of Midregional Proadrenomedullin to Predict Poor Outcome in Patients with Community Acquired Pneumonia

    PubMed Central

    Gordo-Remartínez, Susana; Sevillano-Fernández, José A.; Álvarez-Sala, Luis A.; Andueza-Lillo, Juan A.; de Miguel-Yanes, José M.

    2015-01-01

    Background midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP). We sought to confirm whether MR-proADM added to Pneumonia Severity Index (PSI) improves the potential prognostic value of PSI alone, and tested to what extent this combination could be useful in predicting poor outcome of patients with CAP in an Emergency Department (ED). Methods Consecutive patients diagnosed with CAP were enrolled in this prospective, single-centre, observational study. We analyzed the ability of MR-proADM added to PSI to predict poor outcome using receiver operating characteristic (ROC) curves, logistic regression and risk reclassification and comparing it with the ability of PSI alone. The primary outcome was “poor outcome”, defined as the incidence of an adverse event (ICU admission, hospital readmission, or mortality at 30 days after CAP diagnosis). Results 226 patients were included; 33 patients (14.6%) reached primary outcome. To predict primary outcome the highest area under curve (AUC) was found for PSI (0.74 [0.64-0.85]), which was not significantly higher than for MR-proADM (AUC 0.72 [0.63-0.81, p > 0.05]). The combination of PSI and MR-proADM failed to improve the predictive potential of PSI alone (AUC 0.75 [0.65-0.85, p=0.56]). Ten patients were appropriately reclassified when the combined PSI and MR-proADM model was used as compared with the model of PSI alone. Net reclassification improvement (NRI) index was statistically significant (7.69%, p = 0.03) with an improvement percentage of 3.03% (p = 0.32) for adverse event, and 4.66% (P = 0.02) for no adverse event. Conclusion MR-proADM in combination with PSI may be helpful in individual risk stratification for short-term poor outcome of CAP patients, allowing a better reclassification of patients compared with PSI alone. PMID:26030588

  9. Clinical Significance of the Prognostic Nutritional Index for Predicting Short- and Long-Term Surgical Outcomes After Gastrectomy: A Retrospective Analysis of 7781 Gastric Cancer Patients.

    PubMed

    Lee, Jee Youn; Kim, Hyoung-Il; Kim, You-Na; Hong, Jung Hwa; Alshomimi, Saeed; An, Ji Yeong; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon; Kim, Choong-Bai

    2016-05-01

    To evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy.Assessing a patient's immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer.We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups.Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212-1.869, P <0.001), old age, male sex, high body mass index, medical comorbidity, total gastrectomy, and combined resection to be independent predictors of postoperative complications. Among these, only low PNI (OR = 4.279, 95% CI = 1.760-10.404, P = 0.001) and medical comorbidity were independent predictors of postoperative mortality. For long-term outcomes, low PNI was a poor prognostic factor for overall survival, but not recurrence (overall survival: hazard ratio [HR] = 1.383, 95% CI = 1.221-1.568, P < 0.001; recurrence-free survival: HR = 1.142, 95% CI = 0.985-1.325, P = 0.078).PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. Although PNI was an independent prognostic factor for overall survival, the index was not associated with cancer recurrence.

  10. Poor ovarian reserve

    PubMed Central

    Jirge, Padma Rekha

    2016-01-01

    Poor ovarian reserve (POR) is an important limiting factor for the success of any treatment modality for infertility. It indicates a reduction in quantity and quality of oocytes in women of reproductive age group. It may be age related as seen in advanced years of reproductive life or may occur in young women due to diverse etiological factors. Evaluating ovarian reserve and individualizing the therapeutic strategies are very important for optimizing the success rate. Majority or women with POR need to undergo in vitro fertilization to achieve pregnancy. However, pregnancy rate remains low despite a plethora of interventions and is associated with high pregnancy loss. Early detection and active management are essential to minimize the need for egg donation in these women. PMID:27382229

  11. NEK2 serves as a prognostic biomarker for hepatocellular carcinoma

    PubMed Central

    Li, Gang; Zhong, Yanping; Shen, Qingrong; Zhou, Yi; Deng, Xiaofang; Li, Cuiping; Chen, Jiagui; Zhou, Ying; He, Min

    2017-01-01

    Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is a microtubule-associated protein that regulates spindle assembly in human cells and is overexpressed in various malignancies. However, the role of NEK2 in hepatocellular carcinoma (HCC) remains undetermined. We performed RNA-seq of the HCC cell line SMMC-7721 and the normal liver cell line HL-7702 using the Ion Proton System. NEK2 expression was detected using quantitative reverse transcription polymerase chain reaction in two cell lines and 5 matched HCC and adjacent non-tumorous liver tissues. The correlation between survival and NEK2 expression was analyzed in 359 patients with HCC using RNASeqV2 data available from The Cancer Genome Atlas (TCGA) website (https://tcga-data.nci.nih.gov/tcga/). The expression of NEK2, phospho-AKT and MMP-2 was evaluated by immunohistochemistry in 63 cases of HCC and matched adjacent non-tumorous liver tissues. Relationships between protein expression and clinicopathological parameters were assessed, and the correlations between NEK2 with phospho-AKT and MMP-2 expressions were evaluated. A total of 610 differentially expressed genes (DEGs) were revealed in the transcriptome comparison, 297 of which were upregulated and 313 were downregulated in HCC. NEK2, as the most obviously different DEG in cells and tissues from the RNA-seq data, was listed as an HCC candidate biomarker for further verification. NEK2 was overexpressed in HCC cells and tissues (P=0.002, P=0.013) and HCC patients with a high expression of NEK2 had a poor prognosis (P=0.0145). Clinical analysis indicated that the overexpression of NEK2 in HCC was significantly correlated with diolame complete (P<0.001), tumor nodule number (P=0.012) and recurrence (P=0.004). NEK2 expression was positively correlated with the expression of phospho-AKT (r=0.883, P<0.01) and MMP-2 (r=0.781, P<0.01). Overexpression of NEK2 was associated with clinicopathological characteristics and poor patient outcomes, suggesting that NEK2

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

    NASA Technical Reports Server (NTRS)

    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.

  13. Prognostic impact of metallothionein on oral squamous cell carcinoma.

    PubMed

    Cardoso, Sérgio V; Barbosa, Hugo M; Candellori, Ignez M; Loyola, Adriano M; Aguiar, Maria Cássia F

    2002-08-01

    Metallothionein (MT), a low-molecular-weight protein with high cysteine content, seems to be related to neoplastic resistance to oncologic treatment and therefore has been studied as a prognostic factor for a variety of human malignant tumors. MT overexpression in neoplasms of ectodermal origin is usually associated with a poor prognosis. MT expression was evaluated in 60 samples of oral squamous cell carcinoma by immunohistochemistry to study its prognostic influence on oral cancer. Possible associations of MT immunoexpression were also investigated with respect to clinical stage (TNM), histological grading, and proliferation index (Ki-67) of the lesions. No significant statistical correlation was observed among these variables. The impact on overall survival was assessed by uni and multivariate statistical tests. Mean MT labeling index was 60%. High MT labeling indexes (over 76%) predicted shorter survival in univariate statistical analysis. In multivariate analysis, MT labeling index and clinical stage were independent prognostic factors. MT overexpression in oral squamous cell carcinoma seems to be related to a worse prognosis for patients.

  14. Lipoprotein Lipase as a Prognostic Marker in Chronic Lymphocytic Leukemia.

    PubMed

    Mátrai, Zoltán; Andrikovics, Hajnalka; Szilvási, Anikó; Bors, András; Kozma, András; Ádám, Emma; Halm, Gabriella; Karászi, Éva; Tordai, Attila; Masszi, Tamás

    2017-01-01

    The marked clinical heterogeneity of CLL makes early prognosis assessment important. Lipoprotein lipase (LPL) has been shown to confer adverse prognosis in CLL, recent data indicating it might also contribute to CLL cell survival and metabolism. We determined LPL mRNA expression in unselected peripheral blood of 84 CLL patients by RT PCR. Results were correlated with other prognostic markers and outcome. 30/84 (40 %) of cases were LPL positive based on the cutoff established by ROC analysis. In LPL positive patients significantly shorter median survival (136 vs 258 months, p < 0.0001) and time to first treatment intervals (36 vs 144 months, p < 0.002) were documented. LPL values correlated with male gender, higher stages, more treatment requirement, CD38 positivity and unmutated IgVH genes. Among cases with 13q deletion, LPL positivity identified a subcohort with poor outcome (median survival 108 months vs NR, p < 0.0001). In multivariate analysis, cytogenetic aberrations and LPL had significant impact on survival. Our results confirm that LPL is a strong predictor of outcome in CLL, able to improve prognostic accuracy in good risk cytogenetic subgroups. The relationship between its prognostic and functional role in CLL needs to be explored further.

  15. Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer

    PubMed Central

    2012-01-01

    Background Results from large epidemiologic studies on the association between vitamin D and gastric cancer are controversial. Vitamin D significantly promotes apoptosis in the undifferentiated gastric cancer cell, but the prognostic effects of its levels are unknown. Methods 197 gastric carcinoma patients who received treatment in the cancer centre of Sun Yat-sen University from January 2002 to January 2006 were involved in the study. The stored blood drawn before any treatment was assayed for 25-hydroxyvitamin D levels. The clinicopathologic data were collected to examine the prognostic effects of vitamin D. Results The mean vitamin D levels of the 197 gastric patients was 49.85 ± 23.68 nmol/L, among whom 114(57.9%) were deficient in Vitamin D(< 50 nmol/L), 67(34%) were insufficient (50-75 nmol/L) and 16(8.1%) were sufficient (> 75 nmol/L). Clinical stage (P = 0.004) and lymph node metastasis classification (P = 0.009) were inversely associated with vitamin D levels. The patients with high vitamin D levels group (≥ 50 nmol/L) had a higher overall survival compared with the low vitamin D levels group (< 50 nmol/L)(P = 0.018). Multivariate analysis indicated that vitamin D levels were an independent prognostic factor of gastric cancer (P = 0.019). Conclusions Vitamin D deficiency may be associated with poor prognosis in gastric cancer. PMID:22284859

  16. Prognostic Indexes for Brain Metastases: Which Is the Most Powerful?

    SciTech Connect

    Arruda Viani, Gustavo; Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose

    2012-07-01

    Purpose: The purpose of the present study was to compare the prognostic indexes (PIs) of patients with brain metastases (BMs) treated with whole brain radiotherapy (WBRT) using an artificial neural network. This analysis is important, because it evaluates the prognostic power of each PI to guide clinical decision-making and outcomes research. Methods and Materials: A retrospective prognostic study was conducted of 412 patients with BMs who underwent WBRT between April 1998 and March 2010. The eligibility criteria for patients included having undergone WBRT or WBRT plus neurosurgery. The data were analyzed using the artificial neural network. The input neural data consisted of all prognostic factors included in the 5 PIs (recursive partitioning analysis, graded prognostic assessment [GPA], basic score for BMs, Rotterdam score, and Germany score). The data set was randomly divided into 300 training and 112 testing examples for survival prediction. All 5 PIs were compared using our database of 412 patients with BMs. The sensibility of the 5 indexes to predict survival according to their input variables was determined statistically using receiver operating characteristic curves. The importance of each variable from each PI was subsequently evaluated. Results: The overall 1-, 2-, and 3-year survival rate was 22%, 10.2%, and 5.1%, respectively. All classes of PIs were significantly associated with survival (recursive partitioning analysis, P < .0001; GPA, P < .0001; basic score for BMs, P = .002; Rotterdam score, P = .001; and Germany score, P < .0001). Comparing the areas under the curves, the GPA was statistically most sensitive in predicting survival (GPA, 86%; recursive partitioning analysis, 81%; basic score for BMs, 79%; Rotterdam, 73%; and Germany score, 77%; P < .001). Among the variables included in each PI, the performance status and presence of extracranial metastases were the most important factors. Conclusion: A variety of prognostic models describe the

  17. Specimen banks for cancer prognostic factor research.

    PubMed

    Burke, H B; Henson, D E

    1998-10-01

    Prognostic factors are necessary for determining whether a patient will require therapy, for selecting the optimal therapy, and for evaluating the effectiveness of the therapy chosen. Research in prognostic factors has been hampered by long waiting times and a paucity of outcomes. Specimen banks can solve these problems, but their implementation and use give rise to many important and complex issues. This paper presents an overview of some of the issues related to the use of specimen banks in prognostic factor research.

  18. Clinicopathological and prognostic significance of aberrant Arpin expression in gastric cancer

    PubMed Central

    Li, Tao; Zheng, Hong-Mei; Deng, Nai-Mei; Jiang, Ying-Jian; Wang, Jiang; Zhang, Dian-Liang

    2017-01-01

    AIM To detect the expression of Arpin, and determine its correlation with clinicopathological characteristics and the prognosis of gastric cancer (GC) patients. METHODS A total of 176 GC patients were enrolled as study subjects and classified into groups according to different clinicopathological variables. GC mucosal tissues were obtained via surgery. Another 43 paraffin-embedded tissue blocks of normal gastric epithelium (> 5 cm away from the edge of the tumor) were included in the control group. Immunohistochemistry (IHC) for the Arpin and Arp3 proteins was performed on the formalin-fixed, paraffin-embedded GC tissues. Additionally, expression of the Arpin protein in 43 normal gastric tissues was also determined using IHC. RESULTS Expression of the Arpin protein in GC was lower than that in normal gastric mucosa (30.68% vs 60.47%, P < 0.001). A χ2 test of the 176 GC samples used for IHC showed that decreased Arpin expression was associated with advanced TNM stage (P < 0.01) and the presence or absence of lymph node metastasis (80.92% vs 35.56%, P < 0.001). Additionally, a significant correlation was observed between the expression of Arpin and the presence of the Arp2/3 complex in GC tissues (χ2 = 30.535, P < 0.001). Moreover, a multivariate Cox regression analysis revealed that Arpin expression [hazard ratio (HR) = 0.551, P = 0.029] and TNM stage (HR = 5.344, P = 0.001) were independent prognostic markers for overall survival of GC patients. Regarding the 3-year disease-free survival (DFS), the recurrence rate of GC patients with low Arpin expression levels (median DFS 19 mo) was higher than that in the high-Arpin-expression group (median DFS 34 mo, P = 0.022). CONCLUSION Low Arpin levels are associated with clinicopathological variables and a poor prognosis in GC patients. Arpin may be regarded as a potential prognostic indicator in GC. PMID:28293092

  19. PAI-1 -675 4G/5G polymorphism as a prognostic biomarker in breast cancer.

    PubMed

    Lei, Haixin; Hemminki, Kari; Johansson, Robert; Altieri, Andrea; Enquist, Kerstin; Henriksson, Roger; Lenner, Per; Försti, Asta

    2008-05-01

    Extracellular matrix degradation, mediated by the urokinase plasminogen activation (uPA) system, is a critical step in tumor invasion and metastasis. High tumor levels of uPA and its inhibitor PAI-1 have been correlated with poor prognosis in breast cancer. We examined whether genetic variation in the genes of the uPA system affect breast cancer susceptibility and prognosis. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in six genes of the uPA system in 959 Swedish breast cancer patients with detailed clinical data and up to 15 years of follow-up together with 952 matched controls. We used the unconditional logistic regression models to evaluate the associations between genotypes and breast cancer risk and tumor characteristics. The Kaplan-Meier method was used to estimate the survival probabilities; the log-rank test was used to test differences between subgroups. None of the SNPs conferred an increased breast cancer risk, but correlation with some traditional prognostic factors was observed for several SNPs. Most importantly, we identified the -675 4G/5G SNP in the PAI-1 gene as a promising prognostic biomarker for breast cancer. Compared to the 4G/4G and 4G/5G genotypes 5G/5G homozygosity correlated significantly with worse survival (RR 2.04, 95% CI 1.45-2.86, P<0.001), especially in patients with more aggressive tumors. 5G/5G homozygotes were also the group with worse survival among lymph node negative cases. Our finding suggests that genotyping PAI-1 -675 4G/5G may help in clinical prognosis of breast cancer.

  20. 25-Hydroxyvitamin D and TSH as Risk Factors or Prognostic Markers in Thyroid Carcinoma

    PubMed Central

    Danilovic, Debora Lucia Seguro; Ferraz-de-Souza, Bruno; Fabri, Amanda Wictky; Santana, Nathalie Oliveira; Kulcsar, Marco Aurelio; Cernea, Claudio Roberto; Marui, Suemi; Hoff, Ana Oliveira

    2016-01-01

    Objective The increasing incidence of thyroid nodules demands identification of risk factors for malignant disease. Several studies suggested the association of higher TSH levels with cancer, but influence of 25-hydroxyvitamin D (25OHD) is controversial. This study aimed to identify the relationship of thyroid cancer with higher TSH levels and hypovitaminosis D and to evaluate their influence on prognostic characteristics of papillary thyroid carcinomas (PTC). Methods We retrospectively evaluated 433 patients submitted to thyroidectomy for thyroid nodules. Patients were categorized according to quartiles of TSH and 25OHD levels. Clinicopathological features were analyzed. Results Subjects with thyroid carcinomas were more frequently male and younger compared to those with benign disease. Their median TSH levels were higher and adjusted odds-ratio (OR) for cancer in the highest-quartile of TSH (> 2.4 mUI/mL) was 2.36 (1.36–4.09). Although vitamin D deficiency/insufficiency was prevalent in our cohort (84%), no significant differences in 25OHD levels or quartile distribution were observed between benign and malignant cases. Among 187 patients with PTC, analyses of prognostic features revealed increased risk of lymph nodes metastases for subjects with highest-quartile TSH levels (OR = 3.7, p = 0.029). Decreased 25OHD levels were not overtly associated with poor prognosis in PTC. Conclusions In this cross-sectional cohort, higher TSH levels increased the risk of cancer in thyroid nodules and influenced its prognosis, particularly favoring lymph nodes metastases. On the other hand, no association was found between 25OHD levels and thyroid carcinoma risk or prognosis, suggesting that serum 25OHD determination may not contribute to risk assessment workup of thyroid nodules. PMID:27737011

  1. Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer.

    PubMed

    Labovsky, Vivian; Martinez, Leandro Marcelo; Calcagno, María de Luján; Davies, Kevin Mauro; García-Rivello, Hernán; Wernicke, Alejandra; Feldman, Leonardo; Giorello, María Belén; Matas, Ayelén; Borzone, Francisco Raúl; Howard, Scott C; Chasseing, Norma Alejandra

    2016-10-01

    Spindle-shaped stromal cells, like carcinoma-associated fibroblasts and mesenchymal stem cells, influence tumor behavior and can serve as parameters in the clinical diagnosis, therapy, and prognosis of early breast cancer. Therefore, the aim of this study is to explore the clinicopathological significance of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) receptors (Rs) 2 and 4 (TRAIL-R2 and R4), and interleukin-6 R (IL-6R) in spindle-shaped stromal cells, not associated with the vasculature, as prognostic determinants of early breast cancer patients. Receptors are able to trigger the migratory activity, among other functions, of these stromal cells. We conducted immunohistochemical analysis for the expression of these receptors in spindle-shaped stromal cells, not associated with the vasculature, of primary tumors from early invasive breast cancer patients, and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated levels of TRAIL-R2, TRAIL-R4, and IL-6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence (p = 0.034, 0.026, and 0.006; respectively). Moreover, high expression of TRAIL-R4 was associated with shorter disease-free survival and metastasis-free survival (p = 0.013 and 0.019; respectively). Also, high expression of IL-6R was associated with shorter disease-free survival, metastasis-free survival, and overall survival (p = 0.003, 0.001, and 0.003; respectively). Multivariate analysis showed that IL-6R expression was an independent prognostic factor for disease-free survival and metastasis-free survival (p = 0.035). This study is the first to demonstrate that high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes.

  2. Prognostic Factors of Clinical Outcomes in Patients with Spontaneous Thalamic Hemorrhage

    PubMed Central

    Lee, Sang-Hoon; Park, Kyung-Jae; Kang, Shin-Hyuk; Jung, Yong-Gu; Park, Jung-Yul; Park, Dong-Hyuk

    2015-01-01

    Background Intracerebral hemorrhage (ICH) is a well-known condition, but ICH restricted to the thalamus is less widely studied. We investigated the prognostic factors of thalamic ICHs. Material/Methods Seventy patients from January 2009 to November 2014 were retrospectively reviewed. Patients who demonstrated spontaneous ICH primarily affecting the thalamus on initial brain computed tomography (CT) were enrolled. Patients were categorized into 2 groups based on their Glasgow Outcome Scale (GOS) scores. Various presumptive prognostic factors were analyzed to investigate relationships between various clinical characteristics and outcomes. Results Of the enrolled patients, 39 showed a GOS of 4–5, and were categorized as the good outcome group, while another 31 patients showed a GOS of 1–3 and were categorized as the poor outcome group. Initial GCS score, calculated volume of hematoma, presence of intraventricular hemorrhage (IVH), coexisting complications, hydrocephalus, performance of external ventricular drainage, and modified Graeb’s scores of patients with IVH were significantly different between the 2 groups. In multivariate analysis, among the factors above, initial GCS score (P=0.002, Odds ratio [OR]=1.761, Confidence interval [CI]=1.223–2.536) and the existence of systemic complications (P=0.015, OR=0.059, CI=0.006–0.573) were independently associated with clinical outcomes. Calculated hematoma volume showed a borderline relationship with outcomes (P=0.079, OR=0.920, CI=0.839–1.010). Conclusions Initial GCS score and the existence of systemic complications were strong predictive factors for prognosis of thalamic ICH. Calculated hematoma volume also had predictive value for clinical outcomes. PMID:26343784

  3. β-Catenin Expression Negatively Correlates with WIF1 and Predicts Poor Clinical Outcomes in Patients with Cervical Cancer

    PubMed Central

    Liang, Jinxiao; Zhou, Hui; Peng, Yongpai; Xie, Xiaofei; Li, Ruixin; Liu, Yunyun

    2016-01-01

    Aberrant activation of the canonical Wnt pathway plays a significant role in cervical cancer (CC). However, limited data show the correlation between the cancer clinicopathological characteristics and the key molecules such as β-catenin and Wnt inhibitory factor 1 (WIF1). In this study, β-catenin and WIF1 expression were analyzed by immunohistochemistry for 196 patients with CC, 39 with cervical intraepithelial neoplasia (CIN), and 41 with normal cervical epithelium (NCE). Significant overexpression of β-catenin was detected in CC (67.9%) when compared to CIN (43.6%) or NCE (34.1%), p < 0.01, while low WIF1 expression was detected in CC (24.0%) when compared to CIN (59.0%) or NCE (58.5%), p < 0.001. Negative correlation was shown between β-catenin and WIF1 expression (r = −0.637, p < 0.001). In addition, multivariate analysis revealed that both lymph node metastasis and β-catenin expression were the independent prognostic factors not only for disease-free survival (HR = 5.029, p < 0.001; HR = 2.588, p = 0.035, resp.), but also for overall survival (HR = 5.058, p < 0.001; HR = 2.873, p = 0.031, resp.). Our findings indicate that, besides lymph node metastasis, β-catenin expression may also be a poor prognostic factor for CC while WIF1 could be a potential drug target for treatment of advanced CC. PMID:27843945

  4. Morphosyntax in Poor Comprehenders

    PubMed Central

    Adlof, Suzanne M.; Catts, Hugh W.

    2016-01-01

    Children described as poor comprehenders (PCs) have reading comprehension difficulties in spite of adequate word reading abilities. PCs are known to display weakness with semantics and higher-level aspects of oral language, but less is known about their grammatical skills, especially with regard to morphosyntax. The purpose of this study was to examine morphosyntax in fourth grade PCs and typically developing readers (TDs), using three experimental tasks involving finiteness marking. Participants also completed standardized, norm-referenced assessments of phonological memory, vocabulary, and broader language skills. PCs displayed weakness relative to TDs on all three morphosyntax tasks and on every other assessment of oral language except phonological memory, as indexed by nonword repetition. These findings help to clarify the linguistic profile of PCs, suggesting that their language weaknesses include grammatical weaknesses that cannot be fully explained by semantic factors. Because finiteness markers are usually mastered prior to formal schooling in typical development, we call for future studies to examine whether assessments of morphosyntax could be used for the early identification of children at risk for future reading comprehension difficulty. PMID:27397969

  5. Distilling the Verification Process for Prognostics Algorithms

    NASA Technical Reports Server (NTRS)

    Roychoudhury, Indranil; Saxena, Abhinav; Celaya, Jose R.; Goebel, Kai

    2013-01-01

    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 is verified and validated before it can be successfully deployed. Prognostics algorithms are integral parts of PHM systems. This paper investigates a systematic process of verification of such prognostics algorithms. To this end, first, this paper distinguishes between technology maturation and product development. Then, the paper describes the verification process for a prognostics algorithm as it moves up to higher maturity levels. This process is shown to be an iterative process where verification activities are interleaved with validation activities at each maturation level. In this work, we adopt the concept of technology readiness levels (TRLs) to represent the different maturity levels of a prognostics algorithm. It is shown that at each TRL, the verification of a prognostics algorithm depends on verifying the different components of the algorithm according to the requirements laid out by the PHM system that adopts this prognostics algorithm. Finally, using simplified examples, the systematic process for verifying a prognostics algorithm is demonstrated as the prognostics algorithm moves up TRLs.

  6. Prognostic stratification in the treatment of AML.

    PubMed

    Asou, Norio

    Current treatment of acute myeloid leukemia (AML) still relies on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). AML is a heterogeneous neoplasm characterized by distinct chromosomal and genetic abnormalities. Recent comprehensive gene analyses have highlighted distinct genetic subgroups that are associated with different responses to chemotherapy. Therefore, the molecular landscape of AML is fundamental to the development of novel therapeutic approaches and provides opportunities for individualization of therapy. In addition, the age-related incidence of clonal hematopoiesis is high, affecting nearly 10% of healthy people more than 65 years of age. Clonal hematopoiesis is confirmed by the presence of mutations related to AML including genes involved in DNA methylation, chromatin modification and RNA splicing. In the analysis of gene mutation profiles in secondary AML (s-AML) from myelodysplastic syndromes and myeloproliferative neoplasms, secondary-type gene mutations were identified with >95% specificity in s-AML as compared with de novo AML, including RNA splicing, chromatin modification and cohesion complex genes, and were highly associated with poor responses to chemotherapy as well as TP53 mutation. It is important to identify genetic subgroups at relatively high-risk of relapses who should receive allogeneic HSCT during the first remission. In this review, prognostic stratification for individualized treatment of AML is discussed.

  7. Prognostic value of sarcopenia in liver surgery.

    PubMed

    Cornet, M; Lim, C; Salloum, C; Lazzati, A; Compagnon, P; Pascal, G; Azoulay, D

    2015-11-01

    Current knowledge indicates that malnutrition increases the rate of post-operative complications, particularly respiratory and infectious, after major surgery. Almost all liver surgery is performed in patients with cancer, a factor that increases the risk of malnutrition. The primary risk factors for post-operative complications are pre-operative hypo-albuminemia and a body mass index less than 20 kg/m(2). To improve the prediction of complications in these patients, some teams have suggested measurement of muscle thickness by computed tomography. Muscular mass can thus be quantified by measuring the total surface of the psoas muscle or the total surface of all muscles (i.e. external and internal oblique, transverse, psoas and paravertebral muscles) seen on an axial CT slice at L3. As well, data exist suggesting that sarcopenia is an independent predictive factor of post-operative morbidity and poor long-term survival after resection for cancer. Nonetheless, the literature on the subject is limited, there are no standardized definitions for sarcopenia, and the need of special software to calculate the surfaces limits its usefulness. Lastly, there are little if any data concerning the nutritional or pharmacologic means to treat sarcopenia. This update, based on a literature review, deals with the value and the prognostic impact of sarcopenia in surgery for liver tumors. The current definition of sarcopenia, validated internationally, the methods of measurement, and the consequences of sarcopenia on the outcome of liver resections are detailed in this review.

  8. Prognostic Assessment in Patients with Hepatic Encephalopathy

    PubMed Central

    García-Martínez, Rita; Simón-Talero, Macarena; Córdoba, Juan

    2011-01-01

    Hepatic encephalopathy (HE) is a common complication of liver failure that is associated with poor prognosis. However, the prognosis is not uniform and depends on the underlying liver disease. Acute liver failure is an uncommon cause of HE that carries bad prognosis but is potentially reversible. There are several prognostic systems that have been specifically developed for selecting patients for liver transplantation. In patients with cirrhosis the prognosis of the episode of HE is usually dictated by the underlying precipitating factor. Acute-on-chronic liver failure is the most severe form of decompensation of cirrhosis, the prognosis depends on the number of associated organ failures. Patients with cirrhosis that have experienced an episode of HE should be considered candidates for liver transplant. The selection depends on the underlying liver function assessed by the Model for End-stage Liver Disease (MELD) index. There is a subgroup that exhibits low MELD and recurrent HE, usually due to the coexistence of large portosystemic shunts. The recurrence of HE is more common in patients that develop progressive deterioration of liver function and hyponatremia. The bouts of HE may cause sequels that have been shown to persist after liver transplant. PMID:22045403

  9. Prognostic value of perioperative leukocyte count in resectable gastric cancer

    PubMed Central

    Chen, Xiao-Feng; Qian, Jing; Pei, Dong; Zhou, Chen; Røe, Oluf Dimitri; Zhu, Fang; He, Shao-Hua; Qian, Ying-Ying; Zhou, Yue; Xu, Jun; Xu, Jin; Li, Xiao; Ping, Guo-Qiang; Liu, Yi-Qian; Wang, Ping; Guo, Ren-Hua; Shu, Yong-Qian

    2016-01-01

    AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer. METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and adjuvant chemotherapy were enrolled in this study. The relationship between pre- and postoperative hematologic parameters and overall survival was assessed statistically, adjusted for known prognostic factors. RESULTS: The mean white blood cell count (WBC) significantly decreased after surgery, and 107/614 (17.4%) patients developed p-leukopenia, which was defined as a preoperative WBC ≥ 4.0 × 109/L and postoperative WBC < 4.0 × 109/L, with an absolute decrease ≥ 0.5 × 109/L. The neutrophil count decreased significantly more than the lymphocyte count. P-leukopenia significantly correlated with poor tumor differentiation and preoperative WBC. A higher preoperative WBC and p-leukopenia were independent negative prognostic factors for survival [hazard ratio (HR) = 1.602, 95% confidence interval (CI): 1.185-2.165; P = 0.002, and HR = 1.478, 95%CI: 1.149-1.902; P = 0.002, respectively] after adjusting for histology, Borrmann type, pTNM stage, vascular or neural invasion, gastrectomy method, resection margins, chemotherapy regimens, and preoperative WBC count. The patients with both higher preoperative WBC and p-leukopenia had a worse prognosis compared to those with lower baseline WBC and no p-leukopenia (27.5 mo vs 57.3 mo, P < 0.001). CONCLUSION: Preoperative leukocytosis alone or in combination with postoperative leukopenia could be independent prognostic factors for survival in patients with resectable gastric cancer. PMID:26973420

  10. LGALS3 as a prognostic factor for classical Hodgkin's lymphoma.

    PubMed

    Koh, Young Wha; Jung, Se Jin; Park, Chan-Sik; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

    2014-10-01

    LGALS3, a member of the lectin family, has an important role in tumor progression through inhibition of apoptosis. LGALS3 shares several significant structural properties with BCL2. In this study, we examined the prognostic significance of LGALS3 and BCL2 in uniformly treated classical Hodgkin's lymphoma. Diagnostic tissues from 110 patients with uniformly treated classical Hodgkin's lymphoma were evaluated retrospectively by immunohistochemical analysis of LGALS3 and BCL2 expression. The median follow-up time was 6.2 years (range, 0.2-17.3 years). Twenty-seven patients (25%) expressed LGALS3 protein in Hodgkin/Reed-Sternberg cells, which was associated with poor overall survival and event-free survival (P=0.007 and P<0.001). Fifteen patients (14%) expressed BCL2 protein in Hodgkin/Reed-Sternberg cells, which was not associated with overall survival and event-free survival (P=0.928 and P=0.900).There was no correlation between LGALS3 and BCL2 expression (P=0.193). Multivariate analysis identified LGALS3 protein as an independent prognostic factor for event-free survival (P=0.007). Subgroup analysis according to the Ann Arbor stage of classical Hodgkin's lymphoma showed that LGALS3 protein expression had a prognostic value in limited-stage classical Hodgkin's lymphoma (P<0.001). The results of this study suggest that LGALS3 is an independent prognostic factor in classical Hodgkin's lymphoma, and may allow the identification of a subgroup of patients with limited-stage classical Hodgkin's lymphoma who require more intensive therapy.

  11. Dynamic assessment of RBC-transfusion dependency improves the prognostic value of the revised-IPSS in MDS patients.

    PubMed

    Hiwase, Devendra K; Singhal, Deepak; Strupp, Corinna; Chhetri, Rakchha; Kutyna, Monika M; Wee, L Amilia; Harrison, Peter B; Nath, Shriram V; Wickham, Nicholas; Hui, Chi-Hung; Gray, James X; Bardy, Peter; Ross, David M; Lewis, Ian D; Reynolds, John; To, L Bik; Germing, Ulrich

    2017-03-01

    RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor overall survival (OS) in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International Prognostic Scoring System (IPSS-R) did not include RBC-TD. Thus, neither of these prognostic scoring systems incorporates both cytopenia and RBC-TD. We aimed to test whether RBC-TD adds prognostic value to the IPSS-R. We analyzed MDS patients not treated with disease-modifying therapy, and enrolled in SA-MDS Registry (derivation cohort; n = 295) and Dusseldorf registry (Germany; validation cohort; n = 113) using time-dependent Cox proportional regression and serial landmark analyses. In the derivation cohort, RBC-TD patients had inferior OS compared to RBC transfusion-independent (RBC-TI) patients (P < 0.0001) at 6- (18 vs. 64 months), 12- (24 vs. 71 months), and 24-months (40 vs. 87 months). In a Cox proportional regression analysis, RBC-TD was an independent adverse prognostic marker in addition to age, sex, and IPSS-R variables (P < 0.0001). A prognostic index (PI) was derived using these Cox-proportional regression model variables. In the validation cohort, this PI classified patients into four prognostic groups with significantly different OS (P < 0.001) as in the derivation cohort. In conclusion, multivariate analysis by Cox proportional hazards regression and serial landmark analyses clearly demonstrates that development of RBC-TD at any time during the course of MDS is associated with poor OS, independent of IPSS-R. This study demonstrates that dynamic assessment of RBC-TD provides additional prognostic value to IPSS-R and should be included in treatment decision algorithms for MDS patients.

  12. Hybrid Bearing Prognostic Test Rig

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.; Certo, Joseph M.; Handschuh, Robert F.; Dimofte, Florin

    2005-01-01

    The NASA Glenn Research Center has developed a new Hybrid Bearing Prognostic Test Rig to evaluate the performance of sensors and algorithms in predicting failures of rolling element bearings for aeronautics and space applications. The failure progression of both conventional and hybrid (ceramic rolling elements, metal races) bearings can be tested from fault initiation to total failure. The effects of different lubricants on bearing life can also be evaluated. Test conditions monitored and recorded during the test include load, oil temperature, vibration, and oil debris. New diagnostic research instrumentation will also be evaluated for hybrid bearing damage detection. This paper summarizes the capabilities of this new test rig.

  13. MET tyrosine kinase receptor expression and amplification as prognostic biomarkers of survival in gastroesophageal adenocarcinoma

    PubMed Central

    Ang, Agnes; Liao, Wei‐Li; Shen, Jing; O'Day, Emily; Loberg, Robert D.; Cecchi, Fabiola; Hembrough, Todd; Ruzzo, Annamaria; Graziano, Francesco

    2016-01-01

    BACKGROUND MET gene amplification and Met protein overexpression may be associated with a poor prognosis. The MET/Met status is typically determined with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Targeted proteomics uses mass spectrometry–based selected reaction monitoring (SRM) to accurately quantitate Met expression. FISH, IHC, and SRM analyses were compared to characterize the prognostic value of MET/Met in gastroesophageal adenocarcinoma (GEC). METHODS Samples from 447 GEC patients were analyzed for MET gene amplification (FISH) and Met protein expression (IHC and SRM). Cox proportional hazards models and Kaplan‐Meier estimates were applied to explore relations between Met, overall survival (OS), and clinical/pathological characteristics. Spearman's rank coefficient was used to assess the correlation between parameters. RESULTS Patients with MET‐amplified tumors had worse OS when: the MET/centromere enumeration probe for chromosome 7 FISH ratio was ≥ 2 (hazard ratio [HR], 3.13; 95% confidence interval [CI], 1.84‐5.33), the MET gene copy number was ≥5 (HR, 2.51; 95% CI, 1.45‐4.34), or ≥ 10% of the cells had ≥15 copies (HR, 4.28; 95% CI, 2.18‐8.39). Similar observations were made with Met protein overexpression by IHC (≥1 + intensity in ≥ 25% of the tumor cell membrane: HR, 1.39; 95% CI, 1.04‐1.86) or SRM (≥400 amol/μg: HR, 1.76; 95% CI, 1.06‐2.90). A significant correlation was observed between MET FISH/Met IHC, MET FISH/Met SRM, and Met IHC/Met SRM; only MET FISH and Met SRM were independent negative prognostic biomarkers in multivariate analyses. CONCLUSIONS MET amplification and overexpression, assessed by multiple methods, were associated with a worse prognosis in univariate analyses. However, only MET amplification by FISH and Met expression by SRM were independent prognostic biomarkers. Compared with IHC, SRM may provide an added benefit for informed decisions

  14. Causes of Death and Prognostic Factors in Multiple Endocrine Neoplasia Type 1: A Prospective Study

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Uehara, Hirotsugu; Berna, Marc J.; Jensen, Robert T.

    2013-01-01

    literature series, the main causes of MEN1-related deaths were due to the malignant nature of the PETs, followed by the malignant nature of thymic carcinoid tumors. These results differ from the results of a number of the literature series, especially those reported before the 1990s. The causes of non-MEN1-related death for the 2 series, in decreasing frequency, were cardiovascular disease, other nonendocrine tumors > lung diseases, cerebrovascular diseases. The most frequent non-MEN1-related tumor deaths were colorectal, renal > lung > breast, oropharyngeal. Although both overall and disease-related survival are better than in the past (30-yr survival of NIH series: 82% overall, 88% disease-related), the mean age at death was 55 years, which is younger than expected for the general population. Detailed analysis of causes of death correlated with clinical, laboratory, and tumor characteristics of patients in the 2 series allowed identification of a number of prognostic factors. Poor prognostic factors included higher fasting gastrin levels, presence of other functional hormonal syndromes, need for >3 parathyroidectomies, presence of liver metastases or distant metastases, aggressive PET growth, large PETs, or the development of new lesions. The results of this study have helped define the causes of death of MEN1 patients at present, and have enabled us to identify a number of prognostic factors that should be helpful in tailoring treatment for these patients for both short- and long-term management, as well as in directing research efforts to better define the natural history of the disease and the most important factors determining long-term survival at present. PMID:23645327

  15. The predictive and prognostic value of the Glasgow Prognostic Score in metastatic colorectal carcinoma patients receiving bevacizumab.

    PubMed

    Maillet, Marianne; Dréanic, Johann; Dhooge, Marion; Mir, Olivier; Brezault, Catherine; Goldwasser, François; Chaussade, Stanislas; Coriat, Romain

    2014-11-01

    The Glasgow Prognostic Score (GPS), based on C-reactive protein and albumin levels, has shown its prognostic value in metastatic colorectal carcinoma (mCRC) patients receiving conventional cytotoxic therapy. Bevacizumab, a monoclonal antibody to vascular epidermal growth factor, improves the overall survival in mCRC. The aim of the present study was to assess the prognostic value of GPS in mCRC patients receiving antivascular epidermal growth factor therapy. From August 2005 to August 2012, consecutive patients with mCRC who received chemotherapy plus bevacizumab were eligible for the present analysis. The clinical stage, C-reactive protein, albumin and the Eastern Cooperative Oncology Group performance status were recorded at the time of initiation of bevacizumab. Patients received 5-fluorouracil-based chemotherapy plus bevacizumab in accordance with the digestive oncology multidisciplinary staff proposal and in line with the French recommendations for the treatment of mCRC. Eighty patients were eligible (colon n = 59, rectum n = 21), with a median follow-up of 14 months (range 1-58 months). Chemotherapy given with bevacizumab and 5-fluorouracil was oxaliplatin (n = 41, 51%) or irinotecan (n = 27, 34%). At baseline, 56, 31 and 13% of patients had a GPS of 0 (n = 45), 1 (n = 25) and 2 (n = 10), respectively. The median progression-free survival in these groups was 10.1, 6.5 and 5.6 months (P = 0.16), respectively. The median overall survival was 20.1, 11.4 and 6.5 months, respectively (P = 0.004). Our study confirmed the prognostic value of GPS in mCRC patients receiving chemotherapy plus bevacizumab. Given the poor survival observed in patients with an GPS of 2, studies dedicated to these patients could identify optimal treatment modalities.

  16. AIB1 Genomic Amplification Predicts Poor Clinical Outcomes in Female Glioma Patients

    PubMed Central

    Chen, Lihong; Wang, Changwei; Zhang, Xinyuan; Gao, Ke; Liu, Rui; Shi, Bingyin; Hou, Peng

    2016-01-01

    Amplified in breast cancer 1 (AIB1) gene, a coactivator for steroid receptor, is frequently amplified in diverse cancers and is considered as an oncogene in tumorigenesis. However, the prognostic significance of AIB1 amplification in gliomas remains totally unclear. In this study, 115 gliomas and 16 benign meningiomas as control subjects were enrolled, and the copy number of AIB1 was analyzed in these samples. In addition, we explored potential correlation of AIB1 amplification with clinicopathological characteristics and clinical outcomes of glioma patients. Our data showed that glioma samples exhibited a significantly higher AIB1 copy number than control subjects as determined by quantitative polymerase chain reaction (qPCR) approach. Moreover, univariate analysis showed that AIB1 amplification (≥3.5 copies) was strongly correlated with cancer-related death (P =0.03). Interestingly, our data revealed a significant association of AIB1 amplification with WHO grade (P =0.03), tumor recurrence (P =0.03) and survival status (P =0.03) in female patients but not in male patients. Multivariate analysis further demonstrated that AIB1 amplification was independent factor for cancer-related death in female patients. Importantly, AIB1 amplification was closely relevant to worse survival in female patients (P =0.001), but not in male patients (P =1.00). In addition, the patients with AIB1 amplification were resistant to radiotherapy. Altogether, our data demonstrate that AIB1 amplification is a common genetic event in glioma tumorigenesis, and suggest that AIB1 amplification is not only a prognostic factor for poor clinical outcomes in glioma patients, but also a predictor of radiotherapy resistance in gliomas. PMID:27877220

  17. Consequences of Growing Up Poor.

    ERIC Educational Resources Information Center

    Duncan, Greg J., Ed.; Brooks-Gunn, Jeanne, Ed.

    The consequences and correlates of growing up poor as well as the mechanisms through which poverty influences children are explored. This book is organized with a primary focus on research findings and a secondary concern with policy implications. The chapters are: (1) "Poor Families, Poor Outcomes: The Well-Being of Children and Youth" (Jeanne…

  18. Characterization of Desmoglein Expression in the Normal Prostatic Gland. Desmoglein 2 Is an Independent Prognostic Factor for Aggressive Prostate Cancer

    PubMed Central

    Barber, Alison G.; Castillo-Martin, Mireia; Bonal, Dennis M.; Rybicki, Benjamin A.; Christiano, Angela M.; Cordon-Cardo, Carlos

    2014-01-01

    Purpose The expression of desmogleins (DSGs), which are known to be crucial for establishing and maintaining the cell-cell adhesion required for tissue integrity, has been well characterized in the epidermis and hair follicle; however, their expression in other epithelial tissues such as prostate is poorly understood. Although downregulation of classical cadherins, such as E-cadherin, has been described in prostate cancer tissue samples, the expression of desmogleins has only been previously reported in prostate cancer cell lines. In this study we characterized desmoglein expression in normal prostate tissues, and further investigated whether Desmoglein 2 (DSG2) expression specifically can serve as a potential clinical prognostic factor for patients diagnosed with primary prostate cancer. Experimental Design We utilized immunofluorescence to examine DSG2 expression in normal prostate (n = 50) and in a clinically well-characterized cohort of prostate cancer patients (n = 414). Correlation of DSG2 expression with clinico-pathological characteristics and biochemical recurrence was analyzed to assess its clinical significance. Results These studies revealed that DSG2 and DSG4 were specifically expressed in prostatic luminal cells, whereas basal cells lack their expression. In contrast, DSG1 and DSG3 were not expressed in normal prostate epithelium. Further analyses of DSG2 expression in prostate cancer revealed that reduced levels of this biomarker were a significant independent marker of poor clinical outcome. Conclusion Here we report for the first time that a low DSG2 expression phenotype is a useful prognostic biomarker of tumor aggressiveness and may serve as an aid in identifying patients with clinically significant prostate cancer. PMID:24896103

  19. Symptoms at diagnosis as independent prognostic factors in retroperitoneal liposarcoma.

    PubMed

    Taguchi, Satoru; Kume, Haruki; Fukuhara, Hiroshi; Morikawa, Teppei; Kakutani, Shigenori; Takeshima, Yuta; Miyazaki, Hideyo; Suzuki, Motofumi; Fujimura, Tetsuya; Nakagawa, Tohru; Ishikawa, Akira; Igawa, Yasuhiko; Homma, Yukio

    2016-02-01

    The prognostic factors of retroperitoneal liposarcoma have yet to be clearly determined due to its rarity, whereas the prognostic value of symptoms at diagnosis has never been evaluated to date. In this context, we reviewed 24 consecutive patients with primary retroperitoneal liposarcoma who underwent surgical resection with curative intent at our institution. The Kaplan-Meier analysis and the log-rank test were used to estimate progression-free survival (PFS; primary endpoint) and sarcoma-specific survival (SSS; secondary endpoint). The effect of various clinicopathological factors, including symptoms at diagnosis, on these two endpoints was assessed with a Cox proportional hazards model. During the study period, 11 patients (45.8%) developed recurrence after the initial surgery and 8 (33.3%) succumbed to retroperitoneal liposarcoma, with a median follow-up of 64 months. A total of 16 patients (66.7%) had symptoms at diagnosis, while the remaining 8 (33.3%) were diagnosed incidentally. The symptoms were palpability of the tumor (n=8); abdominal pain/fullness (n=3); flank pain/fullness (n=2); lower extremity pain (n=1); testicular pain due to varicocele (n=1); and discomfort on urination (n=1). Patients with symptoms at diagnosis were significantly more likely to develop recurrence (log-rank test, P=0.0196) and were also more likely to succumb to sarcoma (P=0.0778) compared with asymptomatic patients. On the multivariate analysis, symptoms at diagnosis and dedifferentiated components were independent predictors of poor PFS, while positive surgical margins were predictors of poor SSS. Given that symptoms at diagnosis are easily accessible for physicians, they may prove to be useful additional prognostic factors for primary retroperitoneal liposarcoma.

  20. Natural History and Prognostic Value of Corticospinal Tract Wallerian Degeneration in Intracerebral Hemorrhage

    PubMed Central

    Venkatasubramanian, Chitra; Kleinman, Jonathan T.; Fischbein, Nancy J.; Olivot, Jean‐Marc; Gean, Alisa D.; Eyngorn, Irina; Snider, Ryan W.; Mlynash, Michael; Wijman, Christine A. C.

    2013-01-01

    Background The purpose of this study was to define the incidence, imaging characteristics, natural history, and prognostic implication of corticospinal tract Wallerian degeneration (CST‐WD) in spontaneous intracerebral hemorrhage (ICH) using serial MR imaging. Methods and Results Consecutive ICH patients with supratentorial ICH prospectively underwent serial MRIs at 2, 7, 14, and 21 days. MRIs were analyzed by independent raters for the presence and topographical distribution of CST‐WD on diffusion‐weighted imaging (DWI). Baseline demographics, hematoma characteristics, ICH score, and admission National Institute of Health Stroke Score (NIHSS) were systematically recorded. Functional outcome at 3 months was assessed by the modified Rankin Scale (mRS) and the motor‐NIHSS. Twenty‐seven patients underwent 93 MRIs; 88 of these were serially obtained in the first month. In 13 patients (48%), all with deep ICH, CST‐WD changes were observed after a median of 7 days (interquartile range, 7 to 8) as reduced diffusion on DWI and progressed rostrocaudally along the CST. CST‐WD changes evolved into T2‐hyperintense areas after a median of 11 days (interquartile range, 6 to 14) and became atrophic on MRIs obtained after 3 months. In univariate analyses, the presence of CST‐WD was associated with poor functional outcome (ie, mRS 4 to 6; P=0.046) and worse motor‐NIHSS (5 versus 1, P=0.001) at 3 months. Conclusions Wallerian degeneration along the CST is common in spontaneous supratentorial ICH, particularly in deep ICH. It can be detected 1 week after ICH on DWI and progresses rostrocaudally along the CST over time. The presence of CST‐WD is associated with poor motor and functional recovery after ICH. PMID:23913508

  1. Prognostic markers in acute pancreatitis.

    PubMed

    Gomatos, Ilias P; Xiaodong, Xu; Ghaneh, Paula; Halloran, Christopher; Raraty, Michael; Lane, Brian; Sutton, Robert; Neoptolemos, John P

    2014-04-01

    Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.

  2. [Prognostic study of liver abscess].

    PubMed

    Nouira, Ramzi; Bedoui, Riadh; Miaadi, Naoufel; Guesmi, Fethi; Ben Achour, Jamel; Hani, Mohamed; Daghfous, Mounir; Ben Osman, Samia; Zoghlami, Ayoub; Najah, Nabil

    2003-04-01

    The objective of this work is to study factors of prognostic of mortality of abscesses of the liver. We have treated between 1990 and 2000 in our service, 38 patient for abscess of the liver. The symptoms are dominated by the pain of the right hypochondria (37 cases) and the fever (34 cases). An unique abscess has been recovered in 25 cases. Some multiple localizations have been observed in 12 cases. 21 patients have been operated. The bacteriological study at all patients revealed the presence of germ in 27 cases. In 6 cases, there were two germs. It was a bacillus negative gram in 26 cases and a cocci positive gram in 7 cases. Six complications have been observed at the operated patients. In 5 cases, it was a septic shock having leads to the death. After survey univariate and multivariate the only factor of bad prognostic recovered is the septic shock. The aetiology was identified in only 9 cases; it was abscess cholangiotis.

  3. Prognostic Analysis System and Methods of Operation

    NASA Technical Reports Server (NTRS)

    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.

  4. Distributed Prognostics based on Structural Model Decomposition

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

    Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based models are constructed that describe the operation of a system and how it fails. Such approaches consist of an estimation phase, in which the health state of the system is first identified, and a prediction phase, in which the health state is projected forward in time to determine the end of life. Centralized solutions to these problems are often computationally expensive, do not scale well as the size of the system grows, and introduce a single point of failure. In this paper, we propose a novel distributed model-based prognostics scheme that formally describes how to decompose both the estimation and prediction problems into independent local subproblems whose solutions may be easily composed into a global solution. The decomposition of the prognostics problem is achieved through structural decomposition of the underlying models. The decomposition algorithm creates from the global system model a set of local submodels suitable for prognostics. Independent local estimation and prediction problems are formed based on these local submodels, resulting in a scalable distributed prognostics approach that allows the local subproblems to be solved in parallel, thus offering increases in computational efficiency. Using a centrifugal pump as a case study, we perform a number of simulation-based experiments to demonstrate the distributed approach, compare the performance with a centralized approach, and establish its scalability. Index Terms-model-based prognostics, distributed prognostics, structural model decomposition ABBREVIATIONS

  5. Prognostic value of circulating tumor cells in esophageal cancer

    PubMed Central

    Xu, Hai-Tao; Miao, Jing; Liu, Jian-Wei; Zhang, Lian-Guo; Zhang, Qing-Guang

    2017-01-01

    AIM To perform a meta-analysis of the related studies to assess whether circulating tumor cells (CTCs) can be used as a prognostic marker of esophageal cancer. METHODS PubMed, Embase, Cochrane Library and references in relevant studies were searched to assess the prognostic relevance of CTCs in patients with esophageal cancer. The primary outcome assessed was overall survival (OS). The meta-analysis was performed using the random effects model, with hazard ratio (HR), risk ratio (RR) and 95% confidence intervals (95%CIs) as effect measures. RESULTS Nine eligible studies were included involving a total of 911 esophageal cancer patients. Overall analyses revealed that CTCs-positivity predicted disease progression (HR = 2.77, 95%CI: 1.75-4.40, P < 0.0001) and reduced OS (HR = 2.67, 95%CI: 1.99-3.58, P < 0.00001). Further subgroup analyses demonstrated that CTCs-positive patients also had poor OS in different subsets. Moreover, CTCs-positivity was also significantly associated with TNM stage (RR = 1.48, 95%CI: 1.07-2.06, P = 0.02) and T stage (RR = 1.44, 95%CI: 1.13-1.84, P = 0.003) in esophageal cancer. CONCLUSION Detection of CTCs at baseline indicates poor prognosis in patients with esophageal cancer. However, this finding relies on data from observational studies and is potentially subject to selection bias. Prospective trials are warranted. PMID:28275311

  6. CEA Level, Radical Surgery, CD56 and CgA Expression Are Prognostic Factors for Patients With Locoregional Gastrin-Independent GNET.

    PubMed

    Li, Yuan; Bi, Xinyu; Zhao, Jianjun; Huang, Zhen; Zhou, Jianguo; Li, Zhiyu; Zhang, Yefan; Li, Muxing; Chen, Xiao; Hu, Xuhui; Chi, Yihebali; Zhao, Dongbing; Zhao, Hong; Cai, Jianqiang

    2016-05-01

    Gastrin-independent gastric neuroendocrine tumors (GNETs) are highly malignant. Radical resections and lymphadenectomy are considered to be the only possible curative treatment for these tumors. However, the prognosis of gastrin-independent GNETs is not well defined. In this study, we identified prognostic factors of locoregional gastrin-independent GNETs.All patients diagnosed with locoregional gastrin-independent GNETs between 2000 and 2014 were included in this retrospective study. Clinical characteristics, blood tests, pathological characteristics, treatments, and follow-up data of the patients were collected and analyzed.Of the 66 patients diagnosed with locoregional gastrin-independent GNETs, 57 (86.4%) received radical resections, 7 (10.6%) with palliative resection, 1 (1.5%) with gastrojejunostomy, and 1 (1.5%) with exploration surgeries. The median survival time for these patients was 19.0 months (interquartile range, 11.0-38.0). The 1-, 3-, and 5-year survival rates were 72%, 34%, and 28%, respectively. Multivariate analysis indicated that carcinoembryonic antigen (CEA) level (P = 0.04), radical resection (P = 0.04), and positive Cluster of Differentiation 56 (CD56) expression (P = 0.016) were significant prognostic factors on overall survival rate. Further univariate and multivariate analysis of 57 patients who received radical resections found that CgA expression (P = 0.35) and CEA level (P = 0.33) are independent prognostic factors.Gastrin-independent GNETs had poor prognosis. Serum CEA level, radical surgery, CD56 and CgA expression are markers to evaluate the survival of patients with locoregional gastrin-independent GNETs.

  7. Model-Based Prognostics of Hybrid Systems

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew; Roychoudhury, Indranil; Bregon, Anibal

    2015-01-01

    Model-based prognostics has become a popular approach to solving the prognostics problem. However, almost all work has focused on prognostics of systems with continuous dynamics. In this paper, we extend the model-based prognostics framework to hybrid systems models that combine both continuous and discrete dynamics. In general, most systems are hybrid in nature, including those that combine physical processes with software. We generalize the model-based prognostics formulation to hybrid systems, and describe the challenges involved. We present a general approach for modeling hybrid systems, and overview methods for solving estimation and prediction in hybrid systems. As a case study, we consider the problem of conflict (i.e., loss of separation) prediction in the National Airspace System, in which the aircraft models are hybrid dynamical systems.

  8. Elevated expression of USP9X correlates with poor prognosis in human non-small cell lung cancer

    PubMed Central

    Wang, You; Liu, Yu; Yang, Bo; Cao, Hong; Yang, Chun-Xu; Ouyang, Wen; Zhang, Shi-Min; Yang, Gui-Fang; Zhou, Fu-Xiang; Zhou, Yun-Feng

    2015-01-01

    Background The aim of this study was to investigate the expression of ubiquitin-specific peptidase 9, X-linked (USP9X) in non-small cell lung cancer (NSCLC) patients and to evaluate the relevance of USP9X expression to tumor prognosis. Methods Ninety-five patients who underwent surgical resection for clinical stage I-IIIA NSCLC between July 2008 and July 2011 were included in this study. Immunohistochemical analysis of USP9X expression was performed on 95 NSCLC tissues and 32 adjacent normal lung parenchymal tissues from these patients. The Chi-squared test was used to compare the clinicopathological characteristics between different groups. Kaplan-Meier analysis and a Cox regression model were used to determine the independent prognostic factors. A P value <0.05 was considered to be significant. Results The expression of USP9X was found to be significantly higher in NSCLC tissue (44.2%) than in adjacent normal lung parenchymal tissue (6.3%) (P<0.001). High USP9X expression was significantly associated with positive lymph node metastasis (P<0.001), clinical stage (P<0.001) and a reduced overall survival rate (P=0.001) in patients with NSCLC. Based on the multivariate analysis, the elevated expression of the USP9X protein was a significant predictor of poor prognosis for NSCLC patients (HR =2.244, P=0.028). Conclusions The current study demonstrated that the expression of USP9X in NSCLC tissue was significantly higher than that in normal lung tissue and that this elevated expression level of USP9X was associated with poor prognosis among NSCLC patients, suggesting that USP9X might serve as a prognostic biomarker for NSCLC. PMID:25973233

  9. Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer

    PubMed Central

    Castro, Elena; Goh, Chee; Olmos, David; Saunders, Ed; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Dadaev, Tokhir; Govindasami, Koveela; Guy, Michelle; Sawyer, Emma; Wilkinson, Rosemary; Ardern-Jones, Audrey; Ellis, Steve; Frost, Debra; Peock, Susan; Evans, D. Gareth; Tischkowitz, Marc; Cole, Trevor; Davidson, Rosemarie; Eccles, Diana; Brewer, Carole; Douglas, Fiona; Porteous, Mary E.; Donaldson, Alan; Dorkins, Huw; Izatt, Louise; Cook, Jackie; Hodgson, Shirley; Kennedy, M. John; Side, Lucy E.; Eason, Jacqueline; Murray, Alex; Antoniou, Antonis C.; Easton, Douglas F.; Kote-Jarai, Zsofia; Eeles, Rosalind

    2013-01-01

    Purpose To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. Patients and Methods This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1). Results PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Conclusion Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients. PMID:23569316

  10. Low T3 syndrome is a strong prognostic predictor in diffuse large B cell lymphoma.

    PubMed

    Gao, Rui; Liang, Jin-Hua; Wang, Li; Zhu, Hua-Yuan; Wu, Wei; Wu, Jia-Zhu; Xia, Yi; Cao, Lei; Fan, Lei; Yang, Tao; Li, Jian-Yong; Xu, Wei

    2017-02-01

    The aim of this study was to evaluate the prognostic effect of low triiodothyronine (T3) syndrome on patients with diffuse large B cell lymphoma (DLBCL). A hundred and eighty-eight patients with detailed thyroid hormone levels at diagnosis of DLBCL were enrolled. Low T3 syndrome was defined as a low serum free T3 (FT3) level with low or normal serum free tetraiodothyronine (FT4) and thyroid stimulating hormone levels. Multivariate Cox regression analysis was used to screen prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver-operator characteristic curves and the corresponding areas under the curve were calculated to assess the predictive accuracy of International Prognostic Index (IPI) and low T3 syndrome. Twenty-four patients were diagnosed with low T3 syndrome, which was associated with worse PFS and OS in the rituximab era. It was an independent prognostic factor for PFS and OS, especially for those with IPI 0-2, extranodal sites ≤1 and stage III-IV. Synchronously low FT3 and FT4 had poorer survival outcome compared to only low FT3 and adding criterion of low T3 syndrome improved the prognostic capacity of IPI for predicting PFS and OS in DLBCL. Low T3 syndrome was found to be a strong prognostic predictor in DLBCL.

  11. CDH1 promoter methylation correlates with decreased gene expression and poor prognosis in patients with breast cancer.

    PubMed

    Liu, Jian; Sun, Xin; Qin, Sida; Wang, Huangzhen; DU, Ning; Li, Yanbo; Pang, Yamei; Wang, Cuicui; Xu, Chongwen; Ren, Hong

    2016-04-01

    The E-cadherin gene (CDH1) is associated with poor prognosis and metastasis in patients with breast cancer, and methylation of its promoter is correlated with decreased gene expression. However, there is currently no direct evidence that CDH1 promoter methylation indicates poor prognosis in patients with breast cancer. In the present study, methylation-specific polymerase chain reaction (PCR) was applied to detect the methylation status of the CDH1 promoter in 137 primary breast cancer, 85 matched normal breast tissue and 13 lung metastasis specimens. Reverse transcription-quantitative PCR was used to assess the relative expression levels of CDH1 mRNA, and correlation analysis between CDH1 methylation status, and gene expression, clinicopathological characteristics and patient survival was performed. Methylation of CDH1 was identified in 40.9% (56/137) of primary breast cancer specimens, 61.5% (8/13) of lung metastasis specimens and none of the matched normal breast specimens. The downregulation of CDH1 mRNA and E-cadherin protein expression were identified to be significantly correlated with CDH1 methylation (P<0.05). In addition, CDH1 methylation was significantly associated with lymph node metastasis and estrogen receptor status of patients (P<0.05). In univariate analyses, patients with CDH1 methylation exhibited poor overall survival (OS) and disease-free survival (DFS; P<0.05). Furthermore, multivariate analyses revealed that CDH1 methylation was an independent prognostic factor predicting poor OS (HR, 1.737; 95% CI, 0.957-3.766; P=0.041) and DFS (HR, 2.018; 95% CI, 2.057-3.845; P=0.033) in patients with breast cancer. Therefore, the present study suggests that CDH1 promoter methylation may be correlated with breast carcinogenesis and indicates poor prognosis in patients with breast cancer.

  12. Clinicopathological Features and Prognostic Factors of Colorectal Neuroendocrine Neoplasms

    PubMed Central

    Jiang, Mengjie; Tan, Yinuo; Li, Xiaofen; Fu, Jianfei; Hu, Hanguang; Ye, Xianyun; Cao, Ying; Xu, Jinghong

    2017-01-01

    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. PMID:28194176

  13. A prognostic gene expression signature in infratentorial ependymoma.

    PubMed

    Wani, Khalida; Armstrong, Terri S; Vera-Bolanos, Elizabeth; Raghunathan, Aditya; Ellison, David; Gilbertson, Richard; Vaillant, Brian; Goldman, Stewart; Packer, Roger J; Fouladi, Maryam; Pollack, Ian; Mikkelsen, Tom; Prados, Michael; Omuro, Antonio; Soffietti, Riccardo; Ledoux, Alicia; Wilson, Charmaine; Long, Lihong; Gilbert, Mark R; Aldape, Ken

    2012-05-01

    Patients with ependymoma exhibit a wide range of clinical outcomes that are currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggest that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors.

  14. A population based analysis of prognostic factors in advanced biliary tract cancer

    PubMed Central

    Renouf, Daniel; Lim, Howard

    2014-01-01

    Background Data regarding prognostic factors in advanced biliary tract cancer (BTC) remains scarce. The aim of this study was to review our institutional experience with cisplatin and gemcitabine in advanced BTC as well as to evaluate potential prognostic factors for overall survival (OS). Material and methods Consecutive patients with advanced BTC who initiated palliative chemotherapy with cisplatin and gemcitabine from 2009 to 2012 at the BC Cancer Agency were identified using the pharmacy database. Clinicopathologic variables and treatment outcome were retrospectively collected. Potential prognostic factors were assessed by univariate and multivariate analyses. Results A total of 106 patients were included in the analysis. Median OS was 8.5 months (95% CI: 6.5-10.5). On univariate analysis, poor ECOG performance status (ECOG PS) at diagnosis, primary tumor location (extra-hepatic cholangiocarcinoma, and unknown biliary cancer), and sites of advanced disease (extra-hepatic metastasis) were significantly associated with worse OS (P<0.001, 0.036 and 0.034, respectively). Age, gender, CA19-9, CEA, hemoglobin, neutrophil count, and prior stent were not significantly associated with OS. On multivariate analysis, ECOG PS 2/3 was the only predictor of poor OS (P<0.001), while primary location (P=0.089) and sites of advanced disease (P=0.079) had a non-significant trend towards prognostic significance. Conclusions In this population based analysis, a poorer performance status was significantly prognostic of worse OS. Although not significant in our analysis, primary tumor location and sites of advanced disease may also have prognostic relevance. PMID:25436121

  15. [Estimation of poor prognostic factors in patients with pulmonary artery thromboembolism].

    PubMed

    Vasil'tseva, O Ya; Vorozhtsova, I N; Lavrov, A G; Karpov, R S

    2016-01-01

    Резюме Цель исследования. Выявить предикторы летального исхода у госпитализированных пациентов с факторами риска (ФР) развития тромбоэмболии легочной артерии (ТЭЛА) при ее возникновении. Материалы и методы. Для определения предикторов летального исхода у пациентов с ТЭЛА по данным 10-летнего городского госпитального Регистра легочной эмболии проанализированы ФР развития ТЭЛА (согласно европейским и российским рекомендациям), жалобы, анамнез, лабораторные и инструментальные данные, которые можно определить в общехирургическом или общетерапевтическом стационаре, а также имеющаяся у них нозологическая патология. Результаты. У пациентов с ТЭЛА проведен отбор 137 показателей, согласно имеющимся представлениям о тромбообразовании, ФР развития ТЭЛА и ее летального исхода, информации о назначенном лечении, а также данным аутопсии. С помощью логистического регрессионного анализа построена математическая модель для оценки вероятности летального исхода у пациентов с ТЭЛА, в которую вошли 10 показателей: постельный режим; наличие/отсутствие заболеваний легких, хронической венозной недостаточности, ожирения, симптомокомплекса легочного сердца, постинфарктного кардиосклероза левого желудочка, жидкости в полости перикарда, дилатации правого предсердия, правого желудочка, систолическое давление в правом желудочке >36 мм рт.ст. по данным эхокардиографии. Заключение. Созданная в исследовании математическая модель дает возможность расчета вероятности летального исхода при развитии ТЭЛА для конкретного больного с учетом его индивидуальных характеристик.

  16. Yes associated protein is a poor prognostic factor in well-differentiated lung adenocarcinoma.

    PubMed

    Kim, Mi Hyun; Kim, Young Keum; Shin, Dong Hoon; Lee, Hyun Jeong; Shin, Nari; Kim, Arong; Lee, Jung Hee; Choi, Kyung Un; Kim, Jee Yeon; Lee, Chang Hun; Sol, Mee Young

    2015-01-01

    The Hippo pathway is a highly conserved potent regulator of cell growth and apoptosis including large tumor suppressor (LATS) and Yes-associated protein (YAP). LATS has been regarded as a tumor suppressor gene and YAP as either of a tumor suppressor gene or an oncogene. We investigated their expression in lung adenocarcinoma. YAP and LATS protein expression was assessed in 167 surgically resected lung adenocarcinomas and compared with clinicopathologic factors. Disease free survival and overall survival were also evaluated. YAP expression was noted in cytoplasm (48 cases; 28.7%), nuclear (34; 20.4%) and both locations (4; 2.4%). The nuclear expression was typically observed in well differentiated adenocarcinoma. LATS was expressed in cytoplasm when its signal is weak. Perinuclear expression of LATS was observed when it is strongly expressed. While cytoplasmic and nuclear YAP expressions were inversely related. In well differentiated adenocarcinoma patients, YAP nuclear expression was related with more frequent relapse. Both of nuclear YAP and LATS expression were more frequently observed in well differentiated adenocarcinoma. Furthermore, YAP expression exhibited more frequent relapse in well differentiated adenocarcinoma group. We suggest that YAP may act as an oncogene and predict poorer prognosis in well differentiated lung adenocarcinoma.

  17. Clinicopathological characteristics of TERT promoter mutation and telomere length in hepatocellular carcinoma

    PubMed Central

    Lee, Hye Won; Park, Tae In; Jang, Se Young; Park, Soo Young; Park, Won-Jin; Jung, Soo-Jung; Lee, Jae-Ho

    2017-01-01

    Abstract Promoter mutations in telomerase reverse transcriptase (TERT) and telomere length have been studied in various tumors. In the present study, the frequency and clinical characteristics of TERT promoter mutation and telomere length were studied in hepatocellular carcinoma (HCC). TERT promoter mutation and telomere length were analyzed in 162 tumor samples of the patients with HCC by sequencing and real-time PCR, respectively. The TERT promoter mutation rate was 28.8% (46/160) in HCC and was associated with males (P = 0.027). The telomere length was not significantly different in the presence of a TERT promoter mutation but was shorter in high-grade tumor stages (P = 0.048). Survival analyses showed that poor overall survival was associated with longer telomere length (P = 0.013). However, the TERT promoter mutation did not have a prognostic value for HCC. Multivariate survival analyses demonstrated that the telomere length was an independent prognostic marker for poor overall survival (hazard ratio = 1.75, 95% confidence interval: 1.046–2.913, P = 0.033). These data demonstrated that TERT promoter mutation is a frequent event in HCC; however, telomere length, but not the presence of a TERT promoter mutation, might have potential value as a prognostic indicator of HCC. PMID:28151853

  18. Clinicopathological characteristics of TERT promoter mutation and telomere length in hepatocellular carcinoma.

    PubMed

    Lee, Hye Won; Park, Tae In; Jang, Se Young; Park, Soo Young; Park, Won-Jin; Jung, Soo-Jung; Lee, Jae-Ho

    2017-02-01

    Promoter mutations in telomerase reverse transcriptase (TERT) and telomere length have been studied in various tumors. In the present study, the frequency and clinical characteristics of TERT promoter mutation and telomere length were studied in hepatocellular carcinoma (HCC). TERT promoter mutation and telomere length were analyzed in 162 tumor samples of the patients with HCC by sequencing and real-time PCR, respectively. The TERT promoter mutation rate was 28.8% (46/160) in HCC and was associated with males (P = 0.027). The telomere length was not significantly different in the presence of a TERT promoter mutation but was shorter in high-grade tumor stages (P = 0.048). Survival analyses showed that poor overall survival was associated with longer telomere length (P = 0.013). However, the TERT promoter mutation did not have a prognostic value for HCC. Multivariate survival analyses demonstrated that the telomere length was an independent prognostic marker for poor overall survival (hazard ratio = 1.75, 95% confidence interval: 1.046-2.913, P = 0.033). These data demonstrated that TERT promoter mutation is a frequent event in HCC; however, telomere length, but not the presence of a TERT promoter mutation, might have potential value as a prognostic indicator of HCC.

  19. Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study

    PubMed Central

    2012-01-01

    Background Disseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer. Methods Between 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately. Results DTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63–2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09–8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples. Conclusions The detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients

  20. Prognostic value of hedgehog signaling pathway in patients with colon cancer.

    PubMed

    Xu, Meihua; Li, Xinhua; Liu, Ting; Leng, Aimin; Zhang, Guiying

    2012-06-01

    Hedgehog signaling pathway plays an important role in normal mammalian gastrointestinal development and is implicated in the oncogenesis of various tumors. However, its correlation with progression and prognosis of colon cancer has not been well documented. This study was designed to investigate expression patterns of related proteins in hedgehog signaling pathway in colon cancer to elucidate its prognostic value in this tumor. Using human colon cancer and their corresponding non-diseased colon from 228 patients' biopsies, the expression of sonic hedgehog, its receptor Patched, and downstream transcription factor Gli1 was investigated by immunohistochemical staining to assess their association with the clinicopathological characteristics of colon cancer. Disease-free survival and overall survival were examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by multivariate Cox analysis. One hundred and thirty-eight patients (59.6%) had sonic hedgehog-positive tumors and that the disease-free survival (43.5 vs. 73.3%, P < 0.001), and overall survival rates (50.7 vs. 88.9%, P < 0.001) of patients with sonic hedgehog-positive tumors were much lower than those of patients with sonic hedgehog-negative tumors. In addition, 163 patients (71.5%) had Patched-positive tumors, and the disease-free survival (41.7 vs. 76.9%, P < 0.001) and overall survival rates (55.2 vs. 80.0%, P = 0.002) of patients with Patched-positive tumors were also lower than those of patients with Patched-negative tumors. Moreover, positive Gli1 expression had a bad effect on the disease-free survival (41.9 vs. 73.2%, P < 0.001) and overall survival rate of patients with colon cancer (50.0 vs. 89.3%, P < 0.001). In a multivariate analysis, sonic hedgehog, Patched, and Gli1 status were indicators for poor disease-free survival and overall survival. These results have shown that the increasing expression of sonic hedgehog, Patched, and Gli1 are indicators for a poor

  1. Stochastic Prognostics for Rolling Element Bearings

    NASA Astrophysics Data System (ADS)

    Li, Y.; Kurfess, T. R.; Liang, S. Y.

    2000-09-01

    The capability to accurately predict the remaining life of a rolling element bearing is prerequisite to the optimal maintenance of rotating machinery performance in terms of cost and productivity. Due to the probabilistic nature of bearing integrity and operation condition, reliable estimation of a bearing's remaining life presents a challenging aspect in the area of maintenance optimisation and catastrophic failure avoidance. Previous study has developed an adaptive prognostic methodology to estimate the rate of bearing defect growth based on a deterministic defect-propagation model. However, deterministic models are inadequate in addressing the stochastic nature of defect-propagation. In this paper, a stochastic defect-propagation model is established by instituting a lognormal random variable in a deterministic defect-propagation rate model. The resulting stochastic model is calibrated on-line by a recursive least-squares (RLS) approach without the requirement of a priori knowledge on bearing characteristics. An augmented stochastic differential equation vector is developed with the consideration of model uncertainties, parameter estimation errors, and diagnostic model inaccuracies. It involves two ordinary differential equations for the first and second moments of its random variables. Solving the two equations gives the mean path of defect propagation and its dispersion at any instance. This approach is suitable for on-line monitoring, remaining life prediction, and decision making for optimal maintenance scheduling. The methodology has been verified by numerical simulations and the experimental testing of bearing fatigue life.

  2. SHISA3 Promoter Methylation Is a Potential Diagnostic and Prognostic Biomarker for Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Zhou, Chongchang; Li, Jinyun; Ye, Dong; Deng, Hongxia; Cao, Bin; Hao, Wenjuan; Lin, Lexi

    2017-01-01

    The purpose of this study was to evaluate the contribution of SHISA3 promoter methylation to laryngeal squamous cell carcinoma (LSCC). SHISA3 promoter methylation status and expression were determined using methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (qRT-PCR) in 93 paired LSCC and adjacent normal tissues, respectively. Furthermore, the regulatory function of the SHISA3 promoter fragment was analyzed using a luciferase reporter assay. The results reveal that there is a significant increase in SHISA3 methylation in LSCC tissues compared with corresponding nontumor tissues (P = 4.58E − 12). The qRT-PCR results show a significant association between SHISA3 methylation and expression in LSCC (P = 1.67E − 03). In addition, the area under the receiver operating characteristic curve was 0.91. Consequently, a log-rank test and multivariate Cox analysis suggest that SHISA3 promoter hypermethylation is a predictor of poor overall survival for LSCC (log-rank P = 0.024; HR = 2.71; 95% CI = 1.024–7.177; P = 0.047). The results indicate that SHISA3 promoter hypermethylation might increase the risk of LSCC through regulation of gene expression and is a potential diagnostic and prognostic biomarker for LSCC. PMID:28299336

  3. Prognostic Impact of the Signet Ring Cell Type in Node-Negative Gastric Cancer

    PubMed Central

    Kong, Pengfei; Wu, Ruiyan; Yang, Chenlu; Geng, Qirong; Liu, Jianjun; Chen, Shangxiang; Liu, Xuechao; Ye, Minting; He, Wenzhuo; Yang, Qiong; Xia, Liangping; Xu, Dazhi

    2016-01-01

    Little is known regarding the prognostic impact of the signet ring cell (SRC) histotype on negative lymph nodes (LNs) in gastric cancer (GC). In this study, we aimed to investigate the differences between SRC and non-SRC GC patients without LN metastasis. The medical records of patients with GC who underwent gastrectomy at Sun Yat-Sen University Cancer Centre from 1996 to 2012 were reviewed to analyse the clinicopathologic characteristics associated with survival. A total of 480 cases of GC patients without LN metastasis were identified, which included 90 SRC GC patients and 390 non-SRC GC patients. Between the two groups, there were a host of significant differences in the American Joint Committee on Cancer, 7th edition (AJCC) stage. We found that SRC histology was correlated with a poor prognosis in terms of recurrence in node-negative GC patients and that SRC histologic analysis combined with AJCC staging maybe an effectual method for prediction of the recurrence rate. Additionally, we found that SRC GC presents a more dismal overall prognosis in patients with perineural or vascular invasion. PMID:27381549

  4. Expression and prognostic significance of CCL11/CCR3 in glioblastoma.

    PubMed

    Tian, Min; Chen, Lina; Ma, Li; Wang, Dandan; Shao, Bin; Wu, Jianyu; Wu, Hangyu; Jin, Yimin

    2016-05-31

    Glioblastoma (GBM) is the most lethal primary nervous system cancer, but due to its rarity and complexity, its pathogenesis is poorly understood. To identify potential tumorigenic factors in GBM, we screened antibody-based cytokine arrays and found that CCL11 was upregulated. We then demonstrated in vitro that both CCL11 and its receptor, CCR3, were overexpressed and promoted the proliferation, migration and invasion of cancer cells. To examine the clinical significance of CCL11/CCR3, 458 GBM samples were divided into a training cohort with 225 cases and a test cohort containing 233 cases. In the training set, immunohistochemical analysis showed overexpression of CCL11 and CCR3 were correlated with unfavorable overall survival (OS). We further developed a prognostic classifier combining CCL11 and CCR3 expression and Karnofsky performance status (KPS) for predicting one-year survival in GBM patients. Receiver operating characteristic (ROC) analysis demonstrated that this predictor achieved 90.7% sensitivity and 73.4% specificity. These results were validated with the test sample set. Our findings suggest that CCL11-CCR3 binding is involved in the progression of GBM and may prompt a novel therapeutic approach. In addition, CCL11 and CCR3 expression, combined with KPS, may be used as an accurate predictor of one-year survival in GBM patients.

  5. Forkhead box protein A1 is a prognostic predictor and promotes tumor growth of gastric cancer

    PubMed Central

    Ren, Hongyu; Zhang, Pei; Tang, Yong; Wu, Mengping; Zhang, Weikang

    2015-01-01

    Previous studies have demonstrated the cancer-type specific role of forkhead box protein A1 (FOXA1) in human malignancies. However, the clinical significance of FOXA1 and its biological function in gastric cancer remain unknown. In this study, the expression of FOXA1 in 80 pairs of gastric cancer tissues and corresponding non-tumor tissues was analyzed using immunohistochemistry and quantitative real-time polymerase chain reaction. We found that the levels of FOXA1 protein and mRNA in gastric cancer tissues were significantly higher than those in matched tumor-adjacent tissues. Furthermore, clinical association analysis indicated that the positive expression of FOXA1 was associated with adverse clinicopathological characteristics of gastric cancer patients including poor tumor differentiation, large tumor size, and advanced tumor-node-metastasis tumor stage. Notably, gastric cancer patients with positive expression of FOXA1 had a poorer 5-year overall survival and recurrence-free survival. In addition, FOXA1 knockdown remarkably inhibited cell proliferation and induced apoptosis in both SGC-7901 and MGC-803 cells. In vivo studies indicated that FOXA1 knockdown prominently suppressed tumor growth of gastric cancer in a nude mouse xenograft model. Mechanistically, we disclosed that the expression of Yes-associated protein was decreased accordingly after FOXA1 knockdown in both SGC-7901 and MGC-803 cells. Taken together, our data suggest that FOXA1 may serve as a promising prognostic indicator and an attractive therapeutic target of gastric cancer. PMID:26527889

  6. Estimating the Risk of Chronic Pain: Development and Validation of a Prognostic Model (PICKUP) for Patients with Acute Low Back Pain

    PubMed Central

    Traeger, Adrian C.; Henschke, Nicholas; Hübscher, Markus; Williams, Christopher M.; Kamper, Steven J.; Maher, Christopher G.; Moseley, G. Lorimer; McAuley, James H.

    2016-01-01

    Background Low back pain (LBP) is a major health problem. Globally it is responsible for the most years lived with disability. The most problematic type of LBP is chronic LBP (pain lasting longer than 3 mo); it has a poor prognosis and is costly, and interventions are only moderately effective. Targeting interventions according to risk profile is a promising approach to prevent the onset of chronic LBP. Developing accurate prognostic models is the first step. No validated prognostic models are available to accurately predict the onset of chronic LBP. The primary aim of this study was to develop and validate a prognostic model to estimate the risk of chronic LBP. Methods and Findings We used the PROGRESS framework to specify a priori methods, which we published in a study protocol. Data from 2,758 patients with acute LBP attending primary care in Australia between 5 November 2003 and 15 July 2005 (development sample, n = 1,230) and between 10 November 2009 and 5 February 2013 (external validation sample, n = 1,528) were used to develop and externally validate the model. The primary outcome was chronic LBP (ongoing pain at 3 mo). In all, 30% of the development sample and 19% of the external validation sample developed chronic LBP. In the external validation sample, the primary model (PICKUP) discriminated between those who did and did not develop chronic LBP with acceptable performance (area under the receiver operating characteristic curve 0.66 [95% CI 0.63 to 0.69]). Although model calibration was also acceptable in the external validation sample (intercept = −0.55, slope = 0.89), some miscalibration was observed for high-risk groups. The decision curve analysis estimated that, if decisions to recommend further intervention were based on risk scores, screening could lead to a net reduction of 40 unnecessary interventions for every 100 patients presenting to primary care compared to a “treat all” approach. Limitations of the method include the model being

  7. Brain metastases at the time of presentation of non-small cell lung cancer: a multi-centric AERIO analysis of prognostic factors

    PubMed Central

    Jacot, W; Quantin, X; Boher, J-M; Andre, F; Moreau, L; Gainet, M; Depierre, A; Quoix, E; Chevalier, T Le; Pujol, J-L

    2001-01-01

    A multi-centre retrospective study involving 4 French university institutions has been conducted in order to identify routine pre-therapeutic prognostic factors of survival in patients with previously untreated non-small cell lung cancer and brain metastases at the time of presentation. A total of 231 patients were recorded regarding their clinical, radiological and biological characteristics at presentation. The accrual period was January 1991 to December 1998. Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The median survival of the whole population was 28 weeks. Univariate analysis (log-rank), showed that patients affected by one of the following characteristics proved to have a shorter survival in comparison with the opposite status of each variable: male gender, age over 63 years, poor performance status, neurological symptoms, serum neuron-specific enolase (NSE) level higher than 12.5 ng ml−1, high serum alkaline phosphatase level, high serum LDH level and serum sodium level below 132 mmol l−1. In the Cox's model, the following variables were independent determinants of a poor outcome: male gender: hazard ratio (95% confidence interval): 2.29 (1.26–4.16), poor performance status: 1.73 (1.15–2.62), age: 1.02 (1.003–1.043), a high serum NSE level: 1.72 (1.11–2.68), neurological symptoms: 1.63 (1.05–2.54), and a low serum sodium level: 2.99 (1.17–7.62). Apart from 4 prognostic factors shared in common with other stage IV NSCLC patients, whatever the metastatic site (namely sex, age, gender, performance status and serum sodium level) this study discloses 2 determinants specifically resulting from brain metastasis: i.e. the presence of neurological symptoms and a high serum NSE level. The latter factor could be in relationship with the extent of normal brain tissue damage caused by the tumour as has been demonstrated after strokes. Additionally, the observation of a high NSE level as a prognostic

  8. An Integrated Approach for Gear Health Prognostics

    NASA Technical Reports Server (NTRS)

    He, David; Bechhoefer, Eric; Dempsey, Paula; Ma, Jinghua

    2012-01-01

    In this paper, an integrated approach for gear health prognostics using particle filters is presented. The presented method effectively addresses the issues in applying particle filters to gear health prognostics by integrating several new components into a particle filter: (1) data mining based techniques to effectively define the degradation state transition and measurement functions using a one-dimensional health index obtained by whitening transform; (2) an unbiased l-step ahead RUL estimator updated with measurement errors. The feasibility of the presented prognostics method is validated using data from a spiral bevel gear case study.

  9. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer

    PubMed Central

    Chen, Ying; Zhang, Lei; Liu, Wenxin; Liu, Xiangyu

    2015-01-01

    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. PMID:26609529

  10. Federal Supervisors and Poor Performers

    DTIC Science & Technology

    1999-07-01

    This report looks at the prevalence of poor performance in the Federal workplace from the perspective of employees and supervisors. The report also...examines what supervisors do about poor performers, the effects of supervisors’ actions, and the factors that influence supervisors’ decisions about how they will handle inadequate performance.

  11. The Etiology of Poor Neighborhoods.

    ERIC Educational Resources Information Center

    Greenberg, Stanley B.

    The inner city aggregations of blacks, Appalachian whites, and Mexicans are not simply the focal points for short-term instability or remedial governmental programs: they are the first native American urban poor. The poor neighborhoods of America's inner city are a result of three great population movements. One originated in the Atlantic Coastal…

  12. Prognostic markers of acute decompensated heart failure: the emerging roles of cardiac biomarkers and prognostic scores.

    PubMed

    Cohen-Solal, Alain; Laribi, Said; Ishihara, Shiro; Vergaro, Giuseppe; Baudet, Mathilde; Logeart, Damien; Mebazaa, Alexandre; Gayat, Etienne; Vodovar, Nicolas; Pascual-Figal, Domingo A; Seronde, Marie-France

    2015-01-01

    Rapidly assessing outcome in patients with acute decompensated heart failure is important but prognostic factors may differ from those used routinely for stable chronic heart failure. Multiple plasma biomarkers, besides the classic natriuretic peptides, have recently emerged as potential prognosticators. Furthermore, prognostic scores that combine clinical and biochemical data may also be useful. However, compared with the scores used in chronic heart failure, scores for acute decompensated heart failure have not been validated. This article reviews potential biomarkers, with a special focus on biochemical biomarkers, and possible prognostic scores that could be used by the clinician when assessing outcome in patients with acute heart failure.

  13. Diagnostic and Prognostic Biomarkers in Melanoma

    PubMed Central

    Leininger, Jennifer; Hamby, Carl; Safai, Bijan

    2014-01-01

    Melanoma is a lethal melanocytic neoplasm. Unfortunately, the histological diagnosis can be difficult at times. Distinguishing ambiguous melanocytic neoplasms that are benign nevi from those that represent true melanoma is important both for treatment and prognosis. Diagnostic biomarkers currently used to assist in the diagnosis of melanoma are usually specific only for melanocytic neoplasms and not necessarily for their ability to metastasize. Traditional prognostic biomarkers include depth of invasion and mitotic count. Newer diagnostic and prognostic biomarkers utilize immunohistochemical staining as well as ribonucleic acid, micro-ribonucleic acid, and deoxyribonucleic acid assays and fluorescence in situ hybridization. Improved diagnostic and prognostic biomarkers are of increasing importance in the treatment of melanoma with the development of newer and more targeted therapies. Herein, the authors review many of the common as well as newer diagnostic and prognostic biomarkers used in melanoma. PMID:25013535

  14. The Prevalence of Poor Reading in Dutch Special Elementary Education

    ERIC Educational Resources Information Center

    van Bon, Wim H. J.; Bouwmans, Mieke; Broeders, Ivy N. L. D. C.

    2006-01-01

    The relative frequency of poor readers in Dutch general elementary education (GEE) and special elementary education (SEE) and the characteristics of their reading performance were investigated using a lexical decision procedure. According to the same norms that identified 9% of students as poor readers in GEE, no less than 73% of the students in…

  15. The prognostic value of systemic and local inflammation in patients with laryngeal squamous cell carcinoma

    PubMed Central

    Wang, Jie; Wang, Shengzi; Song, Xinmao; Zeng, Wenjiao; Wang, Shuyi; Chen, Fu; Ding, Hao

    2016-01-01

    Background Cancer-related systemic inflammation has been demonstrated to be associated with poor outcome in multiple types of cancers. Meanwhile, the local inflammation, which is characterized by dense intratumoral immune infiltrate, is a favorable predictor of survival outcome. Purpose To evaluate the role of systemic and local inflammation in predicting outcome in patients with laryngeal squamous cell carcinoma. Patients and methods In this retrospective study, 120 patients who had undergone postoperative radiotherapy were enrolled. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as calculated from pretreatment whole blood counts, were used to indicate systemic inflammation. The optimal cutoff values of NLR and PLR were determined using receiver operating characteristic curve analysis. Tumor infiltrating lymphocytes (TILs) density, as assessed by pathologist review of hematoxylin and eosin-stained slides, was used to represent local inflammation. Overall survival (OS) and recurrence-free survival (RFS) were assessed using the Kaplan–Meier method and multivariate Cox regression analysis. Results The best cutoff was 2.79 for NLR and 112 for PLR. Kaplan–Meier analysis revealed that high NLR, high PLR, and low TILs density were significantly correlated with inferior OS and RFS, respectively (all P<0.05). The Cox proportional multivariate hazard model showed that a high pretreatment PLR and a low TILs density were both independently correlated with poor OS and RFS, respectively (all P<0.05). Conclusion Markers of systemic and local inflammation, especially PLR and TILs density, are reliable prognostic factors in patients with laryngeal squamous cell carcinoma. PMID:27920556

  16. A Prognostic Model Using Inflammation- and Nutrition-Based Scores in Patients With Metastatic Gastric Adenocarcinoma Treated With Chemotherapy.

    PubMed

    Hsieh, Meng-Che; Wang, Shih-Hor; Chuah, Seng-Kee; Lin, Yu-Hung; Lan, Jui; Rau, Kun-Ming

    2016-04-01

    The outcomes of patients with metastatic gastric cancer (mGC) are poor. Recent studies have identified the prognostic impact of inflammatory response and nutritional status on survival for patients with gastric cancer. This study aims to create a prognostic model using inflammatory- and nutrition-based scores to predict survival in patients with mGC treated with chemotherapy.After institutional review board approval, patients who had mGC and were treated with chemotherapy from 2007 to 2012 at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Significantly predictive factors were identified by multivariate Cox regression analyses. Based on these variables, a prognostic model using inflammatory- and nutrition-based scores was constructed to predict survival. Kaplan-Meier curves were plotted to estimate overall survival. The c-statistic values with 95% confidence interval (CI) were also calculated to access their predicting performances.Our study consisted of 256 patients with a median age of 60 years and a median follow-up visit of 18.5 months. Multivariate analyses showed that neutrophil to lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), and Patient-Generated Subjective Global Assessment (PG-SGA) were independently related to survival. After computing these scores, patients were classified into favorable-, intermediate-, and poor-risk groups. The median overall survival were 27.6 versus 13.2 versus 8.2 months in favorable, intermediate, and poor-risk groups, respectively. The 2-year survival rate was 52% versus 16% versus 3% in favorable-, intermediate-, and poor-risk groups, respectively. (P < 0.001). The c-statistic value of our model at 2 years is 0.8 (95% CI, 0.75-0.86).NLR, mGPS, and PG-SGA were independently related to survival. Our prognostic model using inflammatory- and nutrition-based scores could provide prognostic information to patients and physicians.

  17. Upregulation of spondin-2 predicts poor survival of colorectal carcinoma patients

    PubMed Central

    Wang, Jie; Cui, Shu-Jian; Lou, Xiao-Min; Yan, Bing; Qiao, Jie; Jiang, Ying-Hua; Zhang, Li-Jun; Yang, Peng-Yuan; Liu, Feng

    2015-01-01

    Colorectal cancer (CRC) is the third and second most common cancer in males and females worldwide, respectively. Spondin-2 is a conserved secreted extracellular matrix protein and a candidate cancer biomarker. Here we found that Spondin-2 mRNA was upregulated in CRC tissues using quantitative RT-PCR and data-mining of public Oncomine microarray datasets. Spondin-2 protein was increased in CRC tissues, as revealed by immunohistochemistry analyses of two tissue microarrays containing 180 cases. Spondin-2 gene expression was significantly associated with CRC stage, T stage, M stage and Dukes stage, while its protein was associated with age and M stage. Kaplan-Meier analysis revealed that the upregulated Spondin-2 mRNA and protein predicted poor prognosis of CRC patients. Univariate and multivariate Cox regression analyses indicated that grade, recurrence, N stage and high Spondin-2 were independent predictors of overall survival of CRC patients. ELISA revealed that plasma Spondin-2 was upregulated in CRC and dropped after surgery. Receiver operating characteristic curve analysis demonstrated that plasma Spondin-2 has superior predictive performance for CRC with an area under the curve of 0.959 and the best sensitivity/specificity of 100%/90%. Furthermore, ectopic expression of Spondin-2 enhanced colon cancer cell proliferation. Spondin-2 could be an independent diagnostic and prognostic biomarker of colon cancer. PMID:25945835

  18. Vehicle Integrated Prognostic Reasoner (VIPR) Metric Report

    NASA Technical Reports Server (NTRS)

    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.

  19. The prognostic value of a seven-microRNA classifier as a novel biomarker for the prediction and detection of recurrence in glioma patients

    PubMed Central

    Chen, Wanghao; Yu, Qiang; Chen, Bo; Lu, Xingyu; Li, Qiaoyu

    2016-01-01

    Glioma is often diagnosed at a later stage, and the high risk of recurrence remains a major challenge. We hypothesized that the microRNA expression profile may serve as a biomarker for the prognosis and prediction of glioblastoma recurrence. We defined microRNAs that were associated with good and poor prognosis in 300 specimens of glioblastoma from the Cancer Genome Atlas. By analyzing microarray gene expression data and clinical information from three random groups, we identified 7 microRNAs that have prognostic and prognostic accuracy: microRNA-124a, microRNA-129, microRNA-139, microRNA-15b, microRNA-21, microRNA-218 and microRNA-7. The differential expression of these miRNAs was verified using an independent set of glioma samples from the Affiliated People's Hospital of Jiangsu University. We used the log-rank test and the Kaplan-Meier method to estimate correlations between the miRNA signature and disease-free survival/overall survival. Using the LASSO model, we observed a uniform significant difference in disease-free survival and overall survival between patients with high-risk and low-risk miRNA signature scores. Furthermore, the prognostic capability of the seven-miRNA signature was demonstrated by receiver operator characteristic curve analysis. A Circos plot was generated to examine the network of genes and pathways predicted to be targeted by the seven-miRNA signature. The seven-miRNA-based classifier should be useful in the stratification and individualized management of patients with glioma. PMID:27438144

  20. Influence of Prognostic Factors for Recurrence of Adenocarcinoma of the Stomach

    PubMed Central

    Mehmedagic, Indira; Hasukic, Sefik; Agic, Mirha; Kadric, Nedzad; Hasukic, Ismar

    2016-01-01

    Introduction: Gastric cancer is the second most important neoplasm in the world. Surgical resection is the treatment of choice for gastric cancer, and recognized by the International Union against Cancer (International Union Against Cancer – UICC) TNM classification of the parameters of the tumor and lymph node. Prognostic factors related to characteristics of the tumor by histopathologic findings have an impact on the planning of the operation. According to the results of most studies it is possible to predict survival and recurrence based on histological type and TNM classification of tumors on the one hand and the surgical procedure on the other. Aim: The aim of the research was to analyze prognostic factors that influenced the frequency of recurrence in gastric surgery patients. Patients and methods: The five year study covered a population of 100 treated patients of adenocarcinoma of the stomach at the Department of Surgery, University Clinical Center Tuzla. The first group were characteristics of tumors in patients with gastric adenocarcinoma. Lymphadenectomy and splenectomy, types of surgery were the second group of prognostic factors. Results: Histological type and TNM stage of tumor as prognostic factors had a significant impact on local tumor recurrence. The type of surgery had no statistically significant value for tumor recurrence (p = 0.7520). Conclusion: Statistical analysis of prognostic factors related to histopathologic characteristics of tumors and the type of surgery gave the results that had an impact on recurrence in gastric surgery patients. The most important prognostic factors were TNM stage of tumor and histological type of tumor that influenced the incidence of recurrence. PMID:28210017

  1. Cryocooler Prognostic Health Management System

    NASA Astrophysics Data System (ADS)

    Shah, A.; Penswick, L.; Dodson, C.; Roberts, T.

    2008-03-01

    High performance sensors are playing an increasingly important role in all aspects of all critical DoD missions. There is a family of sensors that operate with improved sensitivities if cooled to very low (cryogenic) temperatures. For these sensors, a healthy and reliable mechanical refrigeration system (cryocooler) is required. The ability to accurately predict the "health" or remaining useful life of the cryocooler has significant benefits from the viewpoint of ensuring that mission critical functions can be carried out with a high probability of success. The paper provides an overview and approaches used for the development of a Cryocooler Prognostic Health Management System (CPHMS) capable of assessing the cryocooler "health" from the viewpoint of the level of performance degradation and/or the potential for near term failure. Additionally, it quantifies the reliable remaining useful life of the cryocooler. While the proposed system is focused on the specific application to linear drive cryocoolers, especially for DoD, many of the attributes of the system can be applied to other specialized system hardware in both commercial and U.S. Government agency for situations where it is critical that all aspects of the hardware "health" and "remaining useful life" be fully understood. Several benefits of the health monitoring system are also described in the paper.

  2. EZH2 overexpression is associated with poor prognosis in patients with glioma

    PubMed Central

    Chen, Ling; Zhang, Zhibin; Feng, Shiyu

    2017-01-01

    Previous studies have investigated the prognostic value of enhancer of zeste homolog 2 (EZH2) expression in patients with glioma but conclude contradictory results. We aimed to comprehensively evaluate the prognostic role of EZH2 in glioma by meta-analysis. The databases of PubMed, Embase and Web of Science were searched. Hazard ratio (HR) and 95% confidence interval (CI) were combined to assess the association between EZH2 and overall survival (OS) as well as progression-free survival (PFS). Odd ratio (OR) and 95% CI were calculated to investigate the relevance of EZH2 on clinical factors. Six studies with 575 patients were included for meta-analysis. The results showed that EZH2 overexpression was correlated with poor OS (n = 6, HR = 2.23, 95% CI: 1.56–3.19, p < 0.001) and PFS (n = 3, HR = 2.23, 95% CI: 1.56–3.19, p < 0.001). Subgroup analysis showed that EZH2 had enhanced prognostic value in Asian patients, for WHO grade I-IV and when using immunohistochemistry (IHC) method. In addition, EZH2 was associated with KPS score < 80. No evidence of publication bias was found in this meta-analysis. In conclusion, the present study showed that EZH2 was a potential prognostic marker for poor OS, PFS and lower KPS score in glioma patients. PMID:27880940

  3. SOCIAL CLASS RESEARCH AND IMAGES OF THE POOR, A BIBLIOGRAPHIC REVIEW.

    ERIC Educational Resources Information Center

    BLUM, ZAHAVA D.; ROSSI, PETER H.

    DRAWING UPON RECENT STUDIES OF SOCIOECONOMIC STATUS, THIS PAPER DISCUSSES THE BASIC CLASS-RELATED CHARACTERISTICS OF THE POOR. THE POOR ARE DESCRIBED SPECIFICALLY IN TERMS OF COMMUNITY CHARACTERISTICS, HEALTH CHARACTERISTICS, DELINQUENCY, AND SEX AND FAMILY CHARACTERISTICS. OTHER CORRELATES OF SOCIAL CLASS POSITION WHICH ARE DISCUSSED INCLUDE THE…

  4. Prognostic significance of WNT signaling in pancreatic ductal adenocarcinoma.

    PubMed

    Nakamoto, Mitsuhiro; Matsuyama, Atsuji; Shiba, Eisuke; Shibuya, Ryo; Kasai, Takahiko; Yamaguchi, Koji; Hisaoka, Masanori

    2014-10-01

    Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is associated with a variety of molecular abnormalities. Although WNT signaling through its canonical/non-canonical pathways is one of the major factors involved in oncogenesis or progression of PDA, the prognostic significance of WNT signaling still remains poorly investigated. In this study, the status of the WNT signaling pathways was immunohistochemically analyzed in 101 PDAs, and its potential association with patient postoperative survival was assessed. Nuclear expression of beta-catenin, a hallmark of the activated canonical pathway, was identified in 59 cases, and was associated with reduced survival compared to the patients lacking nuclear beta-catenin expression (P = 0.002). In contrast, activation of the non-canonical pathway (25 cases), as indicated by co-expression of WNT2/5a and nuclear NFATc1, was not correlated with reduced survival (P = 0.268). Co-activation of both pathways (16 cases) was associated with worse prognosis in comparison with cases with an activated non-canonical pathway (P = 0.034). In addition, nuclear beta-catenin expression was an independent unfavorable prognostic factor (P = 0.006). Our data indicate that activated WNT signaling through its canonical pathway has a significantly negative effect on the clinical course of PDA, and the canonical WNT pathway should be considered as a future therapeutic target for PDA.

  5. Prognostic and survival analysis of presbyopia: The healthy twin study

    NASA Astrophysics Data System (ADS)

    Lira, Adiyani; Sung, Joohon

    2015-12-01

    Presbyopia, a vision condition in which the eye loses its flexibility to focus on near objects, is part of ageing process which mostly perceptible in the early or mid 40s. It is well known that age is its major risk factor, while sex, alcohol, poor nutrition, ocular and systemic diseases are known as common risk factors. However, many other variables might influence the prognosis. Therefore in this paper we developed a prognostic model to estimate survival from presbyopia. 1645 participants which part of the Healthy Twin Study, a prospective cohort study that has recruited Korean adult twins and their family members based on a nation-wide registry at public health agencies since 2005, were collected and analyzed by univariate analysis as well as Cox proportional hazard model to reveal the prognostic factors for presbyopia while survival curves were calculated by Kaplan-Meier method. Besides age, sex, diabetes, and myopia; the proposed model shows that education level (especially engineering program) also contribute to the occurrence of presbyopia as well. Generally, at 47 years old, the chance of getting presbyopia becomes higher with the survival probability is less than 50%. Furthermore, our study shows that by stratifying the survival curve, MZ has shorter survival with average onset time about 45.8 compare to DZ and siblings with 47.5 years old. By providing factors that have more effects and mainly associate with presbyopia, we expect that we could help to design an intervention to control or delay its onset time.

  6. Vasculogenic mimicry is a major feature and novel predictor of poor prognosis in patients with orbital rhabdomyosarcoma.

    PubMed

    Chen, Luxia; He, Yanjin; Sun, Shizhen; Sun, Baocun; Tang, Xin

    2015-09-01

    Vasculogenic mimicry (VM) is a key developmental program, frequently activated during cancer invasion and metastasis. The aim of the present study was to evaluate the role of VM in orbital rhabdomyosarcoma (RMS), the correlation between VM and tumor differentiation, recurrence and survival duration, as well as the contribution of epithelial cell kinase (EphA2) and matrix metalloproteinase-2 (MMP-2) in VM initiation. A total of 32 patients were enrolled to investigate the associations between VM in orbital RMS tumors and clinical characteristics, as well as its impact on overall survival. VM was identified and confirmed by CD31/periodic acid-Schiff double staining, while the presence of EphA2 and MMP-2 were examined by immunohistochemical analysis. VM was identified in eleven patients, particularly those with poorly differentiated orbital RMS (P=0.001). Patients with VM exhibited significantly worse survival rates (P=0.001, log-rank test), a significantly increased risk of mortality (P=0.008) and EphA2 and MMP-2 expression levels were enhanced (P=0.005 and 0.001, respectively). The VM and mitotic rate were independent predictors of poor prognosis (P=0.001 and 0.004, respectively), indicated by multivariate Cox proportional hazards models. These results demonstrated that VM is present in orbital RMS and represents an independent prognostic factor for overall survival. In addition, overexpression of EphA2 and MMP-2 may promote VM formation in orbital RMS.

  7. The Glasgow Prognostic Score (GPS) as a novel and significant predictor of extranodal natural killer/T-cell lymphoma, nasal type.

    PubMed

    Li, Ya-Jun; Jiang, Wen-Qi; Huang, Jia-Jia; Xia, Zhong-Jun; Huang, Hui-Qiang; Li, Zhi-Ming

    2013-05-01

    The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score including C-reactive protein and albumin, shows significant prognostic value in several types of solid tumors. The prognostic value of GPS in lymphoma remains unclear. We performed this study to evaluate the prognostic significance of GPS in extranodal natural killer (NK)/T-cell lymphoma (ENKL). We retrospectively analyzed 164 patients with newly diagnosed ENKL. The prognostic value of GPS was evaluated and compared with that of International Prognostic Index (IPI), Prognostic Index for Peripheral T-cell lymphoma unspecified (PIT), and Korean Prognostic Index (KPI). Patients with higher GPS tended to have more adverse clinical characteristics, lower rates of complete remission (P < 0.001), inferior progression-free survival (PFS, P < 0.001), and inferior overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS, age > 60 years, and elevated LDH were independent adverse predictors of OS. GPS was found superior to IPI, PIT, and KPI in discriminating patients with different outcomes in low-risk groups (all P < 0.05). GPS is an independent predictor of survival outcomes in ENKL. Inflammatory response might play an important role in the progression of ENKL and survival of patients with ENKL.

  8. Evaluation of miR-21 and miR-375 as prognostic biomarkers in oesophageal cancer in high-risk areas in China.

    PubMed

    He, Yutong; Jin, Jing; Wang, LiQun; Hu, Yuejiao; Liang, Di; Yang, Huichai; Liu, Yueping; Shan, Baoen

    2017-01-01

    MicroRNAs have been associated with prognosis in oesophageal cancer (EC), suggesting that miRNAs could play a role in guiding treatment decisions. The aim of this study was to evaluate the prognostic potential of miRNAs found to be associated with zinc deficiency in a geographical area with a high incidence of EC. miRNAs found to be associated with zinc deficiency were isolated from EC cell lines cultured with various Zn levels. The expression levels of the miRNAs were quantified using qRT-PCR. The potential prognostic value of the selected miRNAs was assessed in a cohort study of 88 patients from an area in China with a high incidence of EC. Correlations between miRNAs and patient characteristics were assessed using χ(2) statistical tests or Fisher's exact test. A Cox proportional hazards model was used to assess the correlations between miRNAs and overall survival (OS). Forest plots were performed to evaluate the prognostic impact of the miRNAs examined in the present study in the Asian population. The expression levels of miR-21, miR-31, miR-93 and miR-375 were different when Zn levels were varied in EC cell lines, but only miR-21 and miR-375 were associated with patient characteristics and prognosis in patients with EC from an area of China with a high incidence of EC. The patients expressing high levels of miR-21 had poor OS (HR 2.15, 95% CI 1.16-3.97), whereas those with high levels of miR-375 had improved OS (HR 0.47, 95% CI 0.26-0.87).The patients with both a high level of miR-375 and a low level of miR-21 had significantly better outcomes. Forest plots based on an analysis of this Asian population indicated that a high level of miR-21 significantly predicted a shortened OS (HR 1.83, 95% CI 1.42-2.37), whereas a high level of miR-375 was significantly correlated with increased survival (HR 0.56, 95% CI 0.43-0.73). MiR-21 and miR-375 could be used as prognostic biomarkers in areas with a high incidence of EC, and combining these markers may results in a

  9. Educational attainment in poor comprehenders

    PubMed Central

    Ricketts, Jessie; Sperring, Rachael; Nation, Kate

    2014-01-01

    To date, only one study has investigated educational attainment in poor (reading) comprehenders, providing evidence of poor performance on national UK school tests at age 11 years relative to peers (Cain and Oakhill, 2006). In the present study, we adopted a longitudinal approach, tracking attainment on such tests from 11 years to the end of compulsory schooling in the UK (age 16 years). We aimed to investigate the proposal that educational weaknesses (defined as poor performance on national assessments) might become more pronounced over time, as the curriculum places increasing demands on reading comprehension. Participants comprised 15 poor comprehenders and 15 controls; groups were matched for chronological age, nonverbal reasoning ability and decoding skill. Children were identified at age 9 years using standardized measures of nonverbal reasoning, decoding and reading comprehension. These measures, along with a measure of oral vocabulary knowledge, were repeated at age 11 years. Data on educational attainment were collected from all participants (n = 30) at age 11 and from a subgroup (n = 21) at 16 years. Compared to controls, educational attainment in poor comprehenders was lower at ages 11 and 16 years, an effect that was significant at 11 years. When poor comprehenders were compared to national performance levels, they showed significantly lower performance at both time points. Low educational attainment was not evident for all poor comprehenders. Nonetheless, our findings point to a link between reading comprehension difficulties in mid to late childhood and poor educational outcomes at ages 11 and 16 years. At these ages, pupils in the UK are making key transitions: they move from primary to secondary schools at 11, and out of compulsory schooling at 16. PMID:24904464

  10. Generic prognostic factors for musculoskeletal pain in primary care: a systematic review

    PubMed Central

    Artus, Majid; Campbell, Paul; Mallen, Christian D; van der Windt, Danielle A W

    2017-01-01

    Objectives To summarise the evidence for generic prognostic factors across a range of musculoskeletal (MSK) conditions. Setting primary care. Methods and outcomes Comprehensive systematic literature review. MEDLINE, CINAHL, PsychINFO and EMBASE were searched for prospective cohort studies, based in primary care (search period—inception to December 2015). Studies were included if they reported on adults consulting with MSK conditions and provided data on associations between baseline characteristics (prognostic factors) and outcome. A prognostic factor was identified as generic when significantly associated with any outcome for 2 or more different MSK conditions. Evidence synthesis focused on consistency of findings and study quality. Results 14 682 citations were identified and 78 studies were included (involving more than 48 000 participants with 18 different outcome domains). 51 studies were on spinal pain/back pain/low back pain, 12 on neck/shoulder/arm pain, 3 on knee pain, 3 on hip pain and 9 on multisite pain/widespread pain. Total quality scores ranged from 5 to 14 (mean 11) and 65 studies (83%) scored 9 or more. Out of a total of 78 different prognostic factors for which data were provided, the following factors are considered to be generic prognostic factors for MSK conditions: widespread pain, high functional disability, somatisation, high pain intensity and presence of previous pain episodes. In addition, consistent evidence was found for use of pain medications not to be associated with outcome, suggesting that this factor is not a generic prognostic factor for MSK conditions. Conclusions This large review provides new evidence for generic prognostic factors for MSK conditions in primary care. Such factors include pain intensity, widespread pain, high functional disability, somatisation and movement restriction. This information can be used to screen and select patients for targeted treatment in clinical research as well as to inform the

  11. Prognostic factors for disease progression in advanced Hodgkin's disease: an analysis of patients aged under 60 years showing no progression in the first 6 months after starting primary chemotherapy.

    PubMed Central

    Lee, S. M.; Radford, J. A.; Ryder, W. D.; Collins, C. D.; Deakin, D. P.; Crowther, D.

    1997-01-01

    The aim of this study was to determine whether a very high-risk group based on presenting characteristics could be identified in patients with advanced Hodgkin's disease who may benefit from high-dose chemotherapy (HDCT). Between 1975 and 1992, 453 previously untreated patients aged under 60 years who did not progress in the first 6 months after the start of standard chemotherapy had their hospital notes reviewed. The outcomes analysed were early disease progression (in the 6- to 18-month window following the start of chemotherapy) and disease progression in the whole of the follow-up period. A Cox regression analysis was used to investigate the combined effects of a number of presenting characteristics on these outcomes. Despite the presence of factors with significant effects on the relative rate of progression, the absolute effects in a group identified as having the poorest prognosis were not especially poor. No group could be defined with a freedom from progression rate of less than 70% over 6-18 months, and the worst prognostic group, which included only 53 patients, had an overall freedom from progression rate of 57% at 5 years. Four other reported prognostic indices were evaluated using our data set, but none of the indices was more successful in identifying a very high-risk group. It has not been possible to define a sufficiently high-risk group of patients with Hodgkin's disease based on presenting characteristics for whom HDCT could be advised as part of primary treatment. The search for more discriminating prognostic factors identifying vulnerable patients with a high risk of relapse must continue before a role can be found for HDCT following conventional chemotherapy in patients without disease progression. PMID:9000607

  12. Clinicopathological and prognostic significance of platelet to lymphocyte ratio in patients with gastric cancer

    PubMed Central

    Gu, Xiaobin; Gao, Xian-Shu; Cui, Ming; Xie, Mu; Peng, Chuan; Bai, Yun; Guo, Wei; Han, Linjun; Gu, Xiaodong; Xiong, Wei

    2016-01-01

    The present study was aim to investigate the prognostic role of platelet to lymphocyte ratio (PLR) for patients with gastric cancer (GC) using meta-analysis. A total of 13 studies (14 cohorts) with 6,280 subjects were included. By pooling hazard ratios (HRs) and 95% confidence intervals (CIs) and odds ratios (ORs) and 95% CIs from each study, we found that elevated PLR was significantly associated with poorer overall survival (OS) (HR: 1.3, 95% CI: 1.1–1.52, p = 0.001; I2 = 68.5%, Ph < 0.001) but not with poor disease-free survival (DFS) (HR: 1.6, 95% CI: 0.88–2.9, p = 0.122; I2 = 87.8%, Ph < 0.001). Subgroup analysis showed that a high PLR significantly predicted poor OS in Caucasian populations, patients receiving chemotherapy and patients at advanced stage. In addition, the cut-off value of PLR > 160 showed adequately prognostic value. Furthermore, elevated PLR was associated with lymph node metastasis and CEA levels in GC. Our meta-analysis showed that elevated PLR could be a significant prognostic biomarker for poor OS in patients with GC. PMID:27409665

  13. Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients

    PubMed Central

    Pilanci, Kezban N.; Avcı, Nilüfer; Yıldız, İbrahim; Alço, Gül; Demirhan, Özkan; Köksal, Ülkühan I.; Elbüken, Filiz; Tecimer, Coskun; Demir, Gökhan

    2016-01-01

    Aim of the study Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. Material and methods Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. Results Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12–61) and 19 months (5–45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. Conclusions As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients. PMID:27358594

  14. Promoter CpG island methylation of RET predicts poor prognosis in stage II colorectal cancer patients.

    PubMed

    Draht, Muriel X G; Smits, Kim M; Tournier, Benjamin; Jooste, Valerie; Chapusot, Caroline; Carvalho, Beatriz; Cleven, Arjen H G; Derks, Sarah; Wouters, Kim A D; Belt, Eric J T; Stockmann, Hein B A C; Bril, Herman; Weijenberg, Matty P; van den Brandt, Piet A; de Bruïne, Adriaan P; Herman, James G; Meijer, Gerrit A; Piard, Françoise; Melotte, Veerle; van Engeland, Manon

    2014-05-01

    Improved prognostic stratification of patients with TNM stage II colorectal cancer (CRC) is desired, since 20-30% of high-risk stage II patients may die within five years of diagnosis. This study was conducted to investigate REarranged during Transfection (RET) gene promoter CpG island methylation as a possible prognostic marker for TNM stage II CRC patients. The utility of RET promoter CpG island methylation in tumors of stage II CRC patients as a prognostic biomarker for CRC related death was studied in three independent series (including 233, 231, and 294 TNM stage II patients, respectively) by using MSP and pyrosequencing. The prognostic value of RET promoter CpG island methylation was analyzed by using Cox regression analysis. In the first series, analyzed by MSP, CRC stage II patients (n = 233) with RET methylated tumors had a significantly worse overall survival as compared to those with unmethylated tumors (HRmultivariable = 2.51, 95%-CI: 1.42-4.43). Despite a significant prognostic effect of RET methylation in stage III patients of a second series, analyzed by MSP, the prognostic effect in stage II patients (n = 231) was not statistically significant (HRmultivariable = 1.16, 95%-CI 0.71-1.92). The third series (n = 294), analyzed by pyrosequencing, confirmed a statistically significant association between RET methylation and poor overall survival in stage II patients (HRmultivariable = 1.91, 95%-CI: 1.04-3.53). Our results show that RET promoter CpG island methylation, analyzed by two different techniques, is associated with a poor prognosis in stage II CRC in two independent series and a poor prognosis in stage III CRC in one series. RET methylation may serve as a useful and robust tool for clinical practice to identify high-risk stage II CRC patients with a poor prognosis. This merits further investigation.

  15. Overexpression of AKIP1 predicts poor prognosis of patients with breast carcinoma and promotes cancer metastasis through Akt/GSK-3β/Snail pathway

    PubMed Central

    Mo, Dan; Li, Xinning; Li, Chunhong; Liang, Junrong; Zeng, Tian; Su, Naiwei; Jiang, Qipei; Huang, Jingjing

    2016-01-01

    Recent evidence has demonstrated that A kinase interacting protein 1 (AKIP1), a molecular regulator of protein kinase A, was overexpressed in breast cancer. However, the prognostic and biological role of AKIP1 in breast cancer is still elusive. The purpose of our study was to elucidate the role and molecular mechanism of AKIP1 in breast cancer development. The mRNA levels of AKIP1 in breast cancer and paired normal breast tissues were examined by quantitative real-time PCR. The relationship of AKIP1 expression with clinicopathological characteristics and clinical prognosis of breast cancer patients was investigated. In vitro migration and invasion assays were performed in MCF-7 and SK-BR-3 cells to determine its role in metastasis and the possible mechanism. The result showed that AKIP1 expression was up-regulated in breast cancer tissues compared with that in normal breast tissues. High expression of AKIP1 was associated significantly with advanced tumor stage (P<0.001), tumor size (P=0.029), and lymph node metastasis (P=0.004). Moreover, overexpression of AKIP1 was significantly correlated with poor overall survival and recurrence-free survival (P=0.038 and P=0.005, respectively). Furthermore, down-regulation of AKIP1 remarkably inhibited breast cancer cell motility and invasion through inhibiting the Akt/GSK-3β/Snail pathway. Therefore, AKIP1 may represent a prospective prognostic indicator and a potential therapeutic target of breast cancer. PMID:27904695

  16. Prognostic factors for cerebral palsy and motor impairment in children born very preterm or very low birthweight: a systematic review

    PubMed Central

    Linsell, Louise; Malouf, Reem; Morris, Joan; Kurinczuk, Jennifer J; Marlow, Neil

    2017-01-01

    Aim There is a large literature reporting risk factor analyses for poor neurodevelopment in children born very preterm (VPT: ≤32wks) or very low birthweight (VLBW: ≤1250g), which to date has not been formally summarized. The aim of this paper was to identify prognostic factors for cerebral palsy (CP) and motor impairment in children born VPT/VLBW. Method A systematic review was conducted using Medline, Embase, and Pyscinfo databases to identify studies published between 1 January 1990 and 1 June 2014 reporting multivariable prediction models for poor neurodevelopment in VPT/VLBW children (registration number CRD42014006943). Twenty-eight studies for motor outcomes were identified. Results There was strong evidence that intraventricular haemorrhage and periventricular leukomalacia, and some evidence that the use of postnatal steroids and non-use of antenatal steroids, were prognostic factors for CP. Male sex and gestational age were of limited use as prognostic factors for CP in cohorts restricted to ≤32 weeks gestation; however, in children older than 5 years with no major disability, there was evidence that male sex was a predictive factor for motor impairment. Interpretation This review has identified factors which may be of prognostic value for CP and motor impairment in VPT/VLBW children and will help to form the basis of future prognostic research. PMID:26862030

  17. Histological characterisation and prognostic evaluation of 62 gastric neuroendocrine carcinomas

    PubMed Central

    Chen, Xiaohui; Ye, Yuhong; Shi, Xi; Zhu, Kunshou; Huang, Liming; Zhang, Sheng; Ying, Mingang; Lin, Xuede

    2016-01-01

    Aim of the study To determine the significance of expression of synaptophysin, chromogranin A, and Ki-67 and their association with clinicopathological parameters, and to find out the possible prognostic factors in gastric neuroendocrine carcinoma (G-NEC). Material and methods We investigated the immunohistochemical features and prognosis of 62 G-NECs, and evaluated the association among expressions of synaptophysin, chromogranin A, and Ki-67, clinicopathological variables, and outcome. Results Chromogranin A expression was found more commonly in small-cell NECs (9/9, 100%) than in large-cell NECs (27/53, 51%) (p = 0.008). No statistical significance was found in Ki-67 (p = 0.494) or synaptophysin (p > 0.1) expression between NEC cell types. Correlation analyses revealed that Ki-67 expression was significantly associated with mid-third disease of stomach (p = 0.005) and vascular involvement (p = 0.006), and had a trend of significant correlation with tumour relapse (p = 0.078). High expression of chromogranin A was significantly associated with histology of small-cell NECs (p = 0.008) and lesser tumour greatest dimension (p = 0.038). The prognostic significance was determined by means of Kaplan-Meier survival estimates and log-rank tests, and as a result, early TNM staging and postoperative chemotherapy were found to be correlated with longer overall survival (p < 0.05). Univariate analysis revealed associations between poor prognosis in NECs and several factors, including high TNM staging (p = 0.048), vascular involvement (p = 0.023), relapse (p = 0.004), and microscopic/macroscopic residual tumour (R1/2, p < 0.001). In a multivariate analysis, relapse was identified as the sole independent prognostic factor. Conclusions No significant correlation between survival and expression of synaptophysin, chromogranin A, or Ki-67 has been determined in G-NECs. Our study indicated that early diagnosis, no-residual-tumour resection, and postoperative chemotherapy were

  18. Expression and prognostic significance of unique ULBPs in pancreatic cancer

    PubMed Central

    Chen, Jiong; Zhu, Xing-Xing; Xu, Hong; Fang, Heng-Zhong; Zhao, Jin-Qian

    2016-01-01

    Background Pancreatic cancer is one of the most lethal cancers worldwide, due to the lack of efficient therapy and difficulty in early diagnosis. ULBPs have been shown to behave as important protectors with prognostic significance in various cancers. Materials and methods Immunohistochemistry and enzyme-linked immunosorbent assays were used to explore the expression of ULBPs in cancer tissue and in serum, while survival analysis was used to evaluate the subsequent clinical value of ULBPs. Results Statistics showed that high expression of membrane ULBP1 was a good biomarker of overall survival (18 months vs 13 months), and a high level of soluble ULBP2 was deemed an independent poor indicator for both overall survival (P<0.001) and disease-free survival (P<0.001). Conclusion ULBP1 provides additional information for early diagnosis, and soluble ULBP2 can be used as a novel tumor marker to evaluate the risk of pancreatic cancer patients. PMID:27621649

  19. Prognostic Significance of Initial Serum Albumin and 24 Hour Daily Protein Excretion before Treatment in Multiple Myeloma.

    PubMed

    Chen, Jia-Hong; Hsu, Shun-Neng; Huang, Tzu-Chuan; Wu, Yi-Ying; Lin, Chin; Chang, Ping-Ying; Chen, Yeu-Chin; Ho, Ching-Liang

    2015-01-01

    Renal failure is a common morbidity in multiple myeloma (MM). Although proteinuria has been increasingly reported in malignancies, it is not routinely used to refine risk estimates of survival outcomes in patients with MM. Here we aimed to investigate initial serum albumin and 24-hour daily protein excretion (24-h DPE) before treatment as prognostic factors in patients with MM. We conducted a retrospective analysis of 102 patients with myeloma who were ineligible for haematopoietic stem cell transplantation between October 2000 and December 2012. Initial proteinuria was assessed before treatment by quantitative analysis of 24-hour urine samples. The demographic and laboratory characteristics, survival outcome, and significance of pre-treatment 24-h DPE and albumin in the new staging system of MM were analyzed. Pre-treatment proteinuria (>300 mg/day) was present in 66 patients (64.7%). The optimal cut-off value of 24-h DPE before treatment was 500 mg/day. Analysis of the time-dependent area under the curve showed that the serum albumin and 24-h DPE before treatment were better than 24-h creatinine clearance rate and β2-microglobulin. A subgroup analysis showed that an initial excess proteinuria (24-h DPE ≥ 500 mg) was associated with poor survival status (17.51 vs. 34.24 months, p = 0.002). Furthermore, initial serum albumin was an independent risk factor on multivariate analysis (<2.8 vs. ≥ 2.8, hazard ratio = 0.486, p = 0.029). Using the A-DPE staging system, there was a significant survival difference among patients with stage I, II, and III MM (p < 0.001). Initial serum albumin and 24-h DPE before treatment showed significant prognostic factors in patients with MM, and the new A-DPE staging system may be utilized instead of the International Staging System. Its efficacy should be evaluated by further large prospective studies.

  20. The prognostic value of regional lymph node metastases in patients of Guangdong Province, China with differentiated thyroid cancer

    PubMed Central

    He, Lin-yun; Wang, Wei-wei; Ibrahima, Balde Alpha; Han, Shuai; Li, Zhou; Cai, Zhai; Chen, Miao-liang; Chen, Bao-zhu; Tan, Hui-shi; Zeng, Hai-shan; Dai, Xiao-li; Zhou, Min-wei; Zhang, Gang-qing; Li, Guo-xin

    2016-01-01

    Abstract Although the prognostic value of nodal metastases in differentiated thyroid cancer remains controversial, it is of interest to evaluate and understand the different characteristics of predictive outcomes. A multicenter retrospective study was conducted in 215 untreated patients with differentiated thyroid cancer from July 1997 to July 2015 in 4 medical centers of Guangdong Province. A total of 107 patients with nodal metastases (group A) were compared to 108 patients without metastases (group B). The 5-year disease-free survival (DFS), overall survival (OS), and postoperative complications in both groups were calculated. Variables predictive of DFS and OS were evaluated in group A. The group A had lower 5-year DFS (69.16%, 11 months) and shorter median time of recurrence than those in group B (87.96%, 8.5 months, respectively, P < 0.001). The incidence of temporary hypoparathyroidism in group A is lower; whereas higher incidence of temporary unilateral vocal cord palsy, permanent hypoparathyroidism, permanent unilateral vocal cord palsy, and bilateral vocal cord palsy in group A were observed. Both univariate and multivariate analyses in group A revealed that age, pathological tumor node metastasis (pTNM) stage, and histology were related to DFS (P < 0.05); while pTNM stage and histology were related to OS only in univariate analyses. Positive nodal metastases have significant prognostic value in patients with differentiated thyroid cancer in Guangdong, China and primarily reduce DFS. Moreover, patients with positive nodal metastases who are >45 years and have higher pTNM stage or follicular histology tend to have poor prognosis. Selective lymph node dissection with appropriate postoperative treatment and frequent follow-up should be accorded to these vulnerable groups of patients. PMID:27741112

  1. Prognostic Limitations of Donor T Cell Chimerism after Myeloablative Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    PubMed

    Wong, Eric; Mason, Kate; Collins, Jenny; Hockridge, Barbara; Boyd, Janis; Gorelik, Alexandra; Szer, Jeffrey; Ritchie, David S

    2017-02-06

    Donor T cell chimerism is associated with relapse outcomes after allogeneic stem cell transplantation (alloSCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, measures of statistical association do not adequately assess the performance of a prognostic biomarker, which is best characterized by its sensitivity and specificity for the chosen outcome. We analyzed donor T cell chimerism results at day 100 (D100chim) after myeloablative alloSCT for AML or MDS in 103 patients and determined its sensitivity and specificity for relapse-free survival at 6 months (RFS6) and 12 months (RFS12) post-alloSCT. The area under the receiver operating characteristic curve for RFS6 was .68, demonstrating only modest utility as a predictive biomarker, although this was greater than RFS12 at .62. Using a D100chim threshold of 65%, the specificity for RFS6 was 96.6%; however, sensitivity was poor at 26.7%. This equated to a negative predictive value of 88.5% and positive predictive value of 57.1%. Changing the threshold for D100chim to 75% or 85% modestly improved the sensitivity of D100chim for RFS6; however, this was at the expense of specificity. D100chim is specific but lacks sensitivity as a prognostic biomarker of early RFS after myeloablative alloSCT for AML or MDS. Caution is required when using D100chim to guide treatment decisions including immunologic manipulation, which may expose patients to unwarranted graft-versus-host disease.

  2. Integration of Traditional and Metabolomics Biomarkers Identifies Prognostic Metabolites for Predicting Responsiveness to Nutritional Intervention against Oxidative Stress and Inflammation

    PubMed Central

    Kim, You Jin; Huh, Iksoo; Kim, Ji Yeon; Park, Saejong; Ryu, Sung Ha; Kim, Kyu-Bong; Kim, Suhkmann; Park, Taesung; Kwon, Oran

    2017-01-01

    Various statistical approaches can be applied to integrate traditional and omics biomarkers, allowing the discovery of prognostic markers to classify subjects into poor and good prognosis groups in terms of responses to nutritional interventions. Here, we performed a prototype study to identify metabolites that predict responses to an intervention against oxidative stress and inflammation, using a data set from a randomized controlled trial evaluating Korean black raspberry (KBR) in sedentary overweight/obese subjects. First, a linear mixed-effects model analysis with multiple testing correction showed that four-week consumption of KBR significantly changed oxidized glutathione (GSSG, q = 0.027) level, the ratio of reduced glutathione (GSH) to GSSG (q = 0.039) in erythrocytes, malondialdehyde (MDA, q = 0.006) and interleukin-6 (q = 0.006) levels in plasma, and seventeen NMR metabolites in urine compared with those in the placebo group. A subsequent generalized linear mixed model analysis showed linear correlations between baseline urinary glycine and N-phenylacetylglycine (PAG) and changes in the GSH:GSSG ratio (p = 0.008 and 0.004) as well as between baseline urinary adenine and changes in MDA (p = 0.018). Then, receiver operating characteristic analysis revealed that a two-metabolite set (glycine and PAG) had the strongest prognostic relevance for future interventions against oxidative stress (the area under the curve (AUC) = 0.778). Leave-one-out cross-validation confirmed the accuracy of prediction (AUC = 0.683). The current findings suggest that a higher level of this two-metabolite set at baseline is useful for predicting responders to dietary interventions in subjects with oxidative stress and inflammation, contributing to the emergence of personalized nutrition. PMID:28273855

  3. Validation of prognostic scoring and assessment of clinical benefit for patients with bone sarcomas enrolled in phase I clinical trials

    PubMed Central

    Livingston, J. Andrew; Hess, Kenneth R.; Naing, Aung; Hong, David S.; Patel, Shreyaskumar; Benjamin, Robert S.; Ludwig, Joseph A.; Conley, Anthony; Herzog, Cynthia E.; Anderson, Pete; Meric-Bernstam, Funda; Kurzrock, Razelle; Subbiah, Vivek

    2016-01-01

    Background We sought to validate the Royal Marsden Hospital (RMH) and MD Anderson Cancer Center (MDACC) prognostic scoring systems for the selection of bone sarcoma patients for phase I clinical trials and to identify additional risk factors related to survival. Patients and Methods We retrospectively reviewed the baseline characteristics and outcomes of 92 bone sarcoma patients who were referred to MDACC's Phase I Clinical Trials Program. Results Ninety-two patients with Ewing sarcoma (N = 47), osteosarcoma (N = 22), chondrosarcoma (N = 16), and other tumors (N = 7) were evaluated; 78 were enrolled in at least 1 of 43 different phase I trials. The median overall survival (OS) was 8.8 months (95% confidence interval [CI] = 6.8–13.7 months). Independent factors that predicted shorter survival were male sex, >2 metastatic sites, >3 previous therapies, hemoglobin level <10.5 g/dL, platelet count >200 x103/L, creatinine level ≥1.3 mg/dL, and lactate dehydrogenase level >ULN. Patients with good RMH scores (0-1) had longer OS than patients with poor RMH scores (2-3) (HR = 5.8, 95% CI = 2.9–11.0; P < 0.0001), as did patients with low MDACC scores (0-1) as compared to patients with higher MDACC scores (2–4) (HR = 3.2, 95% CI = 1.9–5.6; P < 0.0001). Conclusion The RMH prognostic score can be used to predict the OS of bone cancer patients referred for phase I trials. The MDACC score added no value to the RMH score and therefore does not have a role in assessment of patients with bone tumors. Patients with advanced bone sarcomas should be considered for phase I trials. PMID:27486883

  4. Prognostic markers of symptomatic congenital cytomegalovirus infection.

    PubMed

    Romanelli, Roberta Maia de Castro; Magny, Jean François; Jacquemard, François

    2008-02-01

    The objective of this research was to identify maternal and fetal characteristics as prognostic markers of congenital cytomegalovirus (CMV) infection. This is a descriptive study of 13 cases of congenital CMV infection referred to Institute de Puericulture et Perinatologie de Paris (IPP) from January 2005 to October 2006. Amniotic fluid puncture was performed to research CMV polimerase chain reaction (PCR). Cordocentesis and cord blood samples at delivery were also analyzed to determinate fetal platelets count, GGT, ASAT, ALAT, CMV-DNA and IgM antibody. Variables of symptomatic and asymptomatic infants were then compared. Data were analyzed by SPSS--15.0. Mean gestational age of amniocentesis was 24.6 weeks and there was no difference of mean viral load in amniotic fluid considering infant features. Mean gestational age of cordocentesis was 26.1 weeks. There were no statistical differences of fetal viral load, IgM, platelets, GGT, ASAT and ALAT analyzed at cordocentesis samples, but at delivery, mean values of IgM and ASAT of fetal blood were increased in symptomatic ones (p= 0.03 for both parameters). When considering groups with normal and abnormal parameters, ASAT of cordon samples was also increased in symptomatic infants (p= 0.02). Sensibility, specificity, positive and negative predictive value of fetal ultrasound anomalies to detect symptomatic infants were, respectively, 80%, 62.5%, 57.1% and 83.3%. Thus, identification of markers of CMV symptomatic infants should be aimed. Prenatal diagnosis, identification and follow up of congenital CMV infected infants are important to consider treatment for symptomatic infants, trying to avoid or reducing some possible sequels.

  5. Prognostic Disclosures to Children: A Historical Perspective

    PubMed Central

    Sisk, Bryan A.; Bluebond-Langner, Myra; Wiener, Lori; Mack, Jennifer; Wolfe, Joanne

    2016-01-01

    Prognostic disclosure to children has perpetually challenged clinicians and parents. In this article, we review the historical literature on prognostic disclosure to children in the United States using cancer as an illness model. Prior to 1948, there was virtually no literature focused on prognostic disclosure to children. As articles began to be published in the 1950s and 1960s, many clinicians and researchers initially recommended a “protective” approach to disclosure, where children were shielded from the harms of bad news. We identified four main arguments in the literature at this time supporting this “protective” approach. By the late 1960s, however, a growing number of clinicians and researchers were recommending a more “open” approach, where children were included in discussions of diagnosis, which at the time was often synonymous with a terminal prognosis. Four different arguments in the literature were used at this time supporting this “open” approach. Then by the late 1980s, the recommended approach to prognostic disclosure in pediatrics shifted largely from “never tell” to “always tell”. In recent years, however, there has been a growing appreciation for the complexity of prognostic disclosure in pediatrics. Current understanding of pediatric disclosure does not lead to simple “black and white” recommendations for disclosure practices. As with most difficult questions, we are left to balance competing factors on a case-by-case basis. We highlight four categories of current considerations related to prognostic disclosure in pediatrics, and we offer several approaches to prognostic disclosure for clinicians who care for these young patients and their families. PMID:27561728

  6. Do pathological variables have prognostic significance in rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and surgery?

    PubMed Central

    Reggiani Bonetti, Luca; Lionti, Simona; Domati, Federica; Barresi, Valeria

    2017-01-01

    AIM To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery. METHODS Tumor regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression analyses. RESULTS cN+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables. CONCLUSION Our data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma. PMID:28293088

  7. A generic probabilistic framework for structural health prognostics and uncertainty management

    NASA Astrophysics Data System (ADS)

    Wang, Pingfeng; Youn, Byeng D.; Hu, Chao

    2012-04-01

    Structural health prognostics can be broadly applied to various engineered artifacts in an engineered system. However, techniques and methodologies for health prognostics become application-specific. This study thus aims at formulating a generic framework of structural health prognostics, which is composed of four core elements: (i) a generic health index system with synthesized health index (SHI), (ii) a generic offline learning scheme using the sparse Bayes learning (SBL) technique, (iii) a generic online prediction scheme using the similarity-based interpolation (SBI), and (iv) an uncertainty propagation map for the prognostic uncertainty management. The SHI enables the use of heterogeneous sensory signals; the sparseness feature employing only a few neighboring kernel functions enables the real-time prediction of remaining useful lives (RULs) regardless of data size; the SBI predicts the RULs with the background health knowledge obtained under uncertain manufacturing and operation conditions; and the uncertainty propagation map enables the predicted RULs to be loaded with their statistical characteristics. The proposed generic framework of structural health prognostics is thus applicable to different engineered systems and its effectiveness is demonstrated with two cases studies.

  8. A Distributed Prognostic Health Management Architecture

    NASA Technical Reports Server (NTRS)

    Bhaskar, Saha; Saha, Sankalita; Goebel, Kai

    2009-01-01

    This paper introduces a generic distributed prognostic health management (PHM) architecture with specific application to the electrical power systems domain. Current state-of-the-art PHM systems are mostly centralized in nature, where all the processing is reliant on a single processor. This can lead to loss of functionality in case of a crash of the central processor or monitor. Furthermore, with increases in the volume of sensor data as well as the complexity of algorithms, traditional centralized systems become unsuitable for successful deployment, and efficient distributed architectures are required. A distributed architecture though, is not effective unless there is an algorithmic framework to take advantage of its unique abilities. The health management paradigm envisaged here incorporates a heterogeneous set of system components monitored by a varied suite of sensors and a particle filtering (PF) framework that has the power and the flexibility to adapt to the different diagnostic and prognostic needs. Both the diagnostic and prognostic tasks are formulated as a particle filtering problem in order to explicitly represent and manage uncertainties; however, typically the complexity of the prognostic routine is higher than the computational power of one computational element ( CE). Individual CEs run diagnostic routines until the system variable being monitored crosses beyond a nominal threshold, upon which it coordinates with other networked CEs to run the prognostic routine in a distributed fashion. Implementation results from a network of distributed embedded devices monitoring a prototypical aircraft electrical power system are presented, where the CEs are Sun Microsystems Small Programmable Object Technology (SPOT) devices.

  9. Evaluating Algorithm Performance Metrics Tailored for Prognostics

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

    2009-01-01

    Prognostics has taken a center stage in Condition Based Maintenance (CBM) where it is desired to estimate Remaining Useful Life (RUL) of the system so that remedial measures may be taken in advance to avoid catastrophic events or unwanted downtimes. Validation of such predictions is an important but difficult proposition and a lack of appropriate evaluation methods renders prognostics meaningless. Evaluation methods currently used in the research community are not standardized and in many cases do not sufficiently assess key performance aspects expected out of a prognostics algorithm. In this paper we introduce several new evaluation metrics tailored for prognostics and show that they can effectively evaluate various algorithms as compared to other conventional metrics. Specifically four algorithms namely; Relevance Vector Machine (RVM), Gaussian Process Regression (GPR), Artificial Neural Network (ANN), and Polynomial Regression (PR) are compared. These algorithms vary in complexity and their ability to manage uncertainty around predicted estimates. Results show that the new metrics rank these algorithms in different manner and depending on the requirements and constraints suitable metrics may be chosen. Beyond these results, these metrics offer ideas about how metrics suitable to prognostics may be designed so that the evaluation procedure can be standardized. 1

  10. Prognostic Value of Admission Blood Glucose in Diabetic and Non-diabetic Patients with Intracerebral Hemorrhage

    PubMed Central

    Sun, Shichao; Pan, Yuesong; Zhao, Xingquan; Liu, Liping; Li, Hao; He, Yan; Wang, Yilong; Wang, Yongjun; Guo, Li

    2016-01-01

    We aimed to validate prognostic value of elevated admission blood glucose (ABG) for clinical outcomes in diabetic and non-diabetic patients with intracerebral hemorrhage (ICH) in a representative large cohort. Data of ICH patients with onset time ≤24 h were derived from the China National Stroke Registry. Clinical outcomes included 3-month poor outcome (death or dependency) and death. Logistic regression was performed for the association between ABG and clinical outcomes, both in the entire cohort and in patients with and without diabetes mellitus. 2951 ICH patients were enrolled, including 267 (9.0%) diabetics. In the entire cohort, there was a trend to increased risk of poor outcome with increasing ABG levels (adjusted OR 1.09; 95% CI, 1.04–1.15; P < 0.001). The risk of poor outcome was significantly greatest for the highest quartile (≥7.53 mmol/L) of ABG (adjusted OR 1.54; 95% CI, 1.17–2.03; p = 0.002, P for trend 0.004). We got similar association in non-diabetics but not in diabetics. Elevated ABG confers a higher risk of poor outcome in non-diabetics than diabetics with similar glucose level. Elevated ABG is an independent predictor of 3-month poor outcome in ICH patients, the prognostic value of which is greater in non-diabetics than diabetics with similar glucose level. PMID:27562114

  11. CD73 is associated with poor prognosis in HNSCC

    PubMed Central

    Cao, Wei; Yang, Rong; Lu, Wei; Liu, Zhe-Qi; Chen, Yi-Ming; Yang, Xi; Tian, Zhen; Wang, Li-Zhen; Li, Jiang; Wang, Xu; Chen, Wan-Tao; Ji, Tong; Zhang, Chen-Ping

    2016-01-01

    CD73 is a cell surface immunosuppressive enzyme involved in tumor progression and metastasis. While patients whose cancer cells express elevated CD73 are typically associated with an unfavorable outcome, the clinical impact of CD73 expression in patients with Head and neck squamous cell carcinoma (HNSCC) remains unclear. In the present study, we investigated the prognostic significance of CD73 in HNSCC using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with reduced overall survival in patients with HNSCC. We also investigated the functional role of CD73 in vitro and demonstrated that CD73 promotes HNSCC migration and invasion through adenosine A3R stimulation and the activation of EGF/EGFR signaling. Moreover, in vivo xenograft studies demonstrated that CD73 promotes tumorigenesis. In conclusion, our study highlights a role for CD73 as a poor prognostic marker of patient survival and also as a candidate therapeutic target in HNSCCs. PMID:27557512

  12. The management of poor performance

    PubMed Central

    Mayberry, John F

    2007-01-01

    Identification of poor performance is in an integral part of government policy. The suggested approach for the identification of such problems, advocated by the General Medical Council, is that of appraisal. However, traditionally, there has been a reluctance to deal with poor performers, as all doctors have made mistakes and are usually only too ready to forgive and be non‐critical of colleagues. The problems are widespread, and 6% of the senior hospital workforce in any 5‐year period may have problems. PMID:17308213

  13. Blue metal-poor stars

    NASA Astrophysics Data System (ADS)

    Preston, George W.; Sneden, Christopher

    2004-12-01

    We review the discovery of blue metal-poor (BMP) stars and the resolution of this population into blue stragglers and intermediate-age Main-Sequence stars by use of binary fractions. We show that the specific frequencies of blue stragglers in the halo field and in globular clusters differ by an order of magnitude. We attribute this difference to the different modes of production of these two populations. We report carbon and s-process enrichment among very metal-poor field blue stragglers and discuss how this result can be used to further resolve field blue stragglers into groups formed during RGB and AGB evolution of their erstwhile primary companions.

  14. Aneuploidy related transcriptional changes in endometrial cancer link low expression of chromosome 15q genes to poor survival.

    PubMed

    Mauland, Karen Klepsland; Wik, Elisabeth; Hoivik, Erling A; Kusonmano, Kanthida; Halle, Mari Kyllesø; Berg, Anna; Haugland, Hans Kristian; Øyan, Anne Margrete; Kalland, Karl-Henning; Stefansson, Ingunn Marie; Akslen, Lars A; Krakstad, Camilla; Trovik, Jone; Werner, Henrica Maria Johanna; Salvesen, Helga Birgitte

    2017-02-07

    Aneuploidy is a widely studied prognostic marker in endometrial cancer (EC), however, not implemented in clinical decision-making. It lacks validation in large prospective patient cohorts adjusted for currently standard applied prognostic markers, including estrogen/progesterone receptor status (ER/PR). Also, little is known about aneuploidy-related transcriptional alterations, relevant for understanding its role in EC biology, and as therapeutic target.We included 825 EC patients with available ploidy status and comprehensive clinicopathologic characterization to analyze ploidy as a prognostic marker. For 144 patients, gene expression data were available to explore aneuploidy-related transcriptional alterations.Aneuploidy was associated with high age, FIGO stage and grade, non-endometrioid histology, ER/PR negativity, and poor survival (p-values<0.001). In patients with ER/PR negative tumors, aneuploidy independently predicted poor survival (p=0.03), lymph node metastasis (p=0.007) and recurrence (p=0.002). A prognostic 'aneuploidy signature', linked to low expression of chromosome 15q genes, was identified and validated in TCGA data.In conclusion, aneuploidy adds prognostic information in ER/PR negative EC, identifying high-risk patients that could benefit from more aggressive therapies. The 'aneuploidy signature' equally identifies these aggressive tumors and suggests a link between aneuploidy and low expression of 15q genes. Integrated analyses point at various dysregulated pathways in aneuploid EC, underlining a complex biology.

  15. Prognostic Significance of Single Progesterone Receptor Positivity

    PubMed Central

    Fan, Ying; Ding, Xiaoyan; Xu, Binghe; Ma, Fei; Yuan, Peng; Wang, Jiayu; Zhang, Pin; Li, Qing; Luo, Yang

    2015-01-01

    Abstract Single progesterone receptor positive (PgR+), especially in form of ER−/PgR+/HER2−, is a nonnegligible phenomenon. Little is known about the characteristics and the role of single PgR positive in this phenotype. Therefore, we explore the significance of single PgR positivity by comparing ER−/PgR+/HER2− breast cancers with triple negative breast cancers (TNBCs). Three thousand nine hundred sixty-six cases of primary invasive breast carcinoma operated consecutively from January 2005 to May 2008 in Cancer Hospital, Chinese Academy of Medical Sciences were examined. Two hundred forty (6%) cases were identified as ER−/PgR+/HER2− breast cancers and 348 (8.8%) cases as TNBCs. Clinicopathological characteristics and survivals were analyzed respectively and then compared between 2 subtypes. Compared with patients with TNBCs, ER−/PgR+/HER2− tumor tended to have lower tumor grade (Grade 3: 45.7% vs. 37.5%, P = 0.051) and smaller tumor size (P = 0.036). However, no differences were found between ER−/PgR+/HER2− and TNBC patients in relapse-free survival (RFS) and OS. The 5-year RFS rates were 80.7% and 77.4%, respectively (P = 0.330) and the 5-year OS rates were 88.0% and 85.2%, respectively (P = 0.290). ER−/PgR+/HER2− patients receiving adjuvant endocrine treatment had better RFS (P = 0.016) and overall survival (OS) (P < 0.0001) than patients receiving no endocrine therapy. This exclusive analysis of patients with ER−/PgR+/HER2− breast cancers showed that this subtype exhibited an aggressive behavior as TNBC, suggesting that it should also be regarded as biologically distinctive group and single PgR positive itself is not a good prognostic factor. However, adjuvant endocrine therapy could still benefit this group of patients. Further investigations should be done to elucidate the underlying mechanism. PMID:26579819

  16. A continuous and prognostic convection scheme based on buoyancy, PCMT

    NASA Astrophysics Data System (ADS)

    Guérémy, Jean-François; Piriou, Jean-Marcel

    2016-04-01

    A new and consistent convection scheme (PCMT: Prognostic Condensates Microphysics and Transport), providing a continuous and prognostic treatment of this atmospheric process, is described. The main concept ensuring the consistency of the whole system is the buoyancy, key element of any vertical motion. The buoyancy constitutes the forcing term of the convective vertical velocity, which is then used to define the triggering condition, the mass flux, and the rates of entrainment-detrainment. The buoyancy is also used in its vertically integrated form (CAPE) to determine the closure condition. The continuous treatment of convection, from dry thermals to deep precipitating convection, is achieved with the help of a continuous formulation of the entrainment-detrainment rates (depending on the convective vertical velocity) and of the CAPE relaxation time (depending on the convective over-turning time). The convective tendencies are directly expressed in terms of condensation and transport. Finally, the convective vertical velocity and condensates are fully prognostic, the latter being treated using the same microphysics scheme as for the resolved condensates but considering the convective environment. A Single Column Model (SCM) validation of this scheme is shown, allowing detailed comparisons with observed and explicitly simulated data. Four cases covering the convective spectrum are considered: over ocean, sensitivity to environmental moisture (S. Derbyshire) non precipitating shallow convection to deep precipitating convection, trade wind shallow convection (BOMEX) and strato-cumulus (FIRE), together with an entire continental diurnal cycle of convection (ARM). The emphasis is put on the characteristics of the scheme which enable a continuous treatment of convection. Then, a 3D LAM validation is presented considering an AMMA case with both observations and a CRM simulation using the same initial and lateral conditions as for the parameterized one. Finally, global

  17. Single Gene Prognostic Biomarkers in Ovarian Cancer: A Meta-Analysis

    PubMed Central

    Willis, Scooter; Villalobos, Victor M.; Gevaert, Olivier; Abramovitz, Mark; Williams, Casey; Sikic, Branimir I.; Leyland-Jones, Brian

    2016-01-01

    Purpose To discover novel prognostic biomarkers in ovarian serous carcinomas. Methods A meta-analysis of all single genes probes in the TCGA and HAS ovarian cohorts was performed to identify possible biomarkers using Cox regression as a continuous variable for overall survival. Genes were ranked by p-value using Stouffer’s method and selected for statistical significance with a false discovery rate (FDR) <.05 using the Benjamini-Hochberg method. Results Twelve genes with high mRNA expression were prognostic of poor outcome with an FDR <.05 (AXL, APC, RAB11FIP5, C19orf2, CYBRD1, PINK1, LRRN3, AQP1, DES, XRCC4, BCHE, and ASAP3). Twenty genes with low mRNA expression were prognostic of poor outcome with an FDR <.05 (LRIG1, SLC33A1, NUCB2, POLD3, ESR2, GOLPH3, XBP1, PAXIP1, CYB561, POLA2, CDH1, GMNN, SLC37A4, FAM174B, AGR2, SDR39U1, MAGT1, GJB1, SDF2L1, and C9orf82). Conclusion A meta-analysis of all single genes identified thirty-two candidate biomarkers for their possible role in ovarian serous carcinoma. These genes can provide insight into the drivers or regulators of ovarian cancer and should be evaluated in future studies. Genes with high expression indicating poor outcome are possible therapeutic targets with known antagonists or inhibitors. Additionally, the genes could be combined into a prognostic multi-gene signature and tested in future ovarian cohorts. PMID:26886260

  18. Prognostic value of circulating tumor cells in advanced gastric cancer patients receiving chemotherapy

    PubMed Central

    Liu, Yongping; Ling, Yang; Qi, Qiufeng; Lan, Feng; Zhu, Ming; Zhang, Yaping; Bao, Yanqing; Zhang, Changsong

    2017-01-01

    The identification of circulating tumor cells (CTCs) may provide important prognostic information in several types of solid tumors, including gastric cancer. The aim of this study was to investigate whether CTC count may be used to predict survival in patients with advanced gastric cancer treated with chemotherapy. The CELLection™ Epithelial Enrich kit was used to isolate and purify CTCs from samples of peripheral blood. Immunofluorescent staining was used for CTC counting. High CTC counts were associated with poor tumor differentiation and high serum CEA levels (P=0.021 and 0.005, respectively). After 3 months, 16 patients with decreasing CTC counts after the first cycle of chemotherapy obtained complete response, partial response or stable disease, while 13 patients with increasing CTC counts developed progressive disease. The patients with decreasing CTC counts also exhibited longer progression-free survival (PFS) (P≤0.001) and overall survival (OS) (P=0.002) compared with those with increasing CTC counts. Among all 59 patients, those with a CTC count of ≤2 cells/5 ml blood exhibited longer PFS (P≤0.001) and OS (P≤0.001) compared with those with a CTC count of >2 cells/5 ml blood. The multivariate analysis suggested that an increase of the CTC count after the first cycle of chemotherapy was only an independent prognostic marker of poor PFS (P=0.019). However, a baseline CTC count of >2 cells/5 ml blood was an independent poor prognostic marker for PFS (P=0.008) and OS (P=0.001) in all 59 patients. Our study suggested that patients with a low baseline CTC count or decrease of the CTC count after the first cycle of chemotherapy may benefit significantly from palliative chemotherapy. In conclusion, CTC count may be a good chemotherapy monitoring marker and an ideal prognostic marker for patients receiving palliative chemotherapy. PMID:28357102

  19. Diagnosis, progression patterns and prognostication in mastocytosis.

    PubMed

    Sperr, Wolfgang R; Valent, Peter

    2012-06-01

    Mastocytosis is a heterogeneous group of disorders defined by abnormal growth and accumulation of clonal mast cells. CM is the predominant variant in childhood, whereas the majority of adult patients present with systemic mastocytosis. In over 80% of the latter patients, the KIT mutation D816V is detectable. Whereas childhood mastocytosis often resolves spontaneously before adolescence and has a good prognosis, in most adult patients mastocytosis is a persistent systemic disorder. The course and prognosis in these patients are variable; in indolent variants, the clinical course remains stable over years or even decades. In advanced mastocytosis, the prognosis is less favorable despite novel drugs counteracting growth of neoplastic mast cells. Although WHO criteria are clearly separating prognostic subsets of mastocytosis, little is known about specific prognostic factors predicting the outcome in individual patients. In this article, we review current concepts in mastocytosis, including prognostic parameters for indolent and advanced systemic mastocytosis.

  20. Prognostic utility of coronary computed tomographic angiography

    PubMed Central

    Otaki, Yuka; Berman, Daniel S.; Min, James K.

    2013-01-01

    Coronary computed tomographic angiography (CCTA) employing CT scanners of 64-detector rows or greater represents a noninvasive method that enables accurate detection and exclusion of anatomically obstructive coronary artery disease (CAD), providing excellent diagnostic information when compared to invasive angiography. There are numerous potential advantages of CCTA beyond simply luminal stenosis assessment including quantification of atherosclerotic plaque volume as well as assessment of plaque composition, extent, location and distribution. In recent years, an array of studies has evaluated the prognostic utility of CCTA findings of CAD for the prediction of major adverse cardiac events, all-cause death and plaque instability. This prognostic information enhances risk stratification and, if properly acted upon, may improve medical therapy and/or behavioral changes that may enhance event-free survival. The goal of the present article is to summarize the current status of the prognostic utility of CCTA findings of CAD. PMID:23809386

  1. A novel gene expression-based prognostic scoring system to predict survival in gastric cancer

    PubMed Central

    Hang, Bo; Zou, Xiaoping; Mao, Jian-Hua

    2016-01-01

    Analysis of gene expression patterns in gastric cancer (GC) can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A network was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system. PMID:27419373

  2. Prognostic value of the lymphocyte monocyte ratio in patients with colorectal cancer

    PubMed Central

    Song, Wei; Wang, Kai; Zhang, Run-jin; Zou, Shu-bing

    2016-01-01

    Abstract Background: Inflammation plays a critical role in the pathogenesis and progression of cancer. A low lymphocyte-to-monocyte ratio (LMR) is reported be a poor prognostic factor in multiple malignancies. We performed a meta-analysis to evaluate the prognostic role of preoperative LMR in colorectal cancer (CRC). Methods: Studies investigating the prognostic role of preoperative LMR on survival in patients with CRC were systematically searched for in MEDLINE, EMBASE, Cochrane databases from inception up to August 2016. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were calculated using fixed-effects/random-effects models. Results: A total of nine studies comprising 8626 patients with CRC were included in the meta-analysis. The pooled analysis demonstrated that low LMR was significantly associated with decreased OS (HR: 0.63, 95% CI: 0.56–0.70, P < 0.001) and DFS/RFS (HR: 0.76, 95% CI: 0.68–0.84, P < 0.001). The negative prognostic impact of low LMR on OS was observed in patients with different ethnicity, treatment methods, cut-off values, and across disease stages. Conclusions: This meta-analysis demonstrates that low preoperative LMR is associated with worse survival in patients with CRC. PMID:27930549

  3. Circulating Endothelial Cells and Procoagulant Microparticles in Patients with Glioblastoma: Prognostic Value

    PubMed Central

    Reynés, Gaspar; Vila, Virtudes; Fleitas, Tania; Reganon, Edelmiro; Font de Mora, Jaime; Jordá, María; Martínez-Sales, Vicenta

    2013-01-01

    Aim Circulating endothelial cells and microparticles are prognostic factors in cancer. However, their prognostic and predictive value in patients with glioblastoma is unclear. The objective of this study was to investigate the potential prognostic value of circulating endothelial cells and microparticles in patients with newly diagnosed glioblastoma treated with standard radiotherapy and concomitant temozolomide. In addition, we have analyzed the methylation status of the MGMT promoter. Methods Peripheral blood samples were obtained before and at the end of the concomitant treatment. Blood samples from healthy volunteers were also obtained as controls. Endothelial cells were measured by an immunomagnetic technique and immunofluorescence microscopy. Microparticles were quantified by flow cytometry. Microparticle-mediated procoagulant activity was measured by endogen thrombin generation and by phospholipid-dependent clotting time. Methylation status of MGMT promoter was determined by multiplex ligation-dependent probe amplification. Results Pretreatment levels of circulating endothelial cells and microparticles were higher in patients than in controls (p<0.001). After treatment, levels of microparticles and thrombin generation decreased, and phospholipid-dependent clotting time increased significantly. A high pretreatment endothelial cell count, corresponding to the 99th percentile in controls, was associated with poor overall survival. MGMT promoter methylation was present in 27% of tumor samples and was associated to a higher overall survival (66 weeks vs 30 weeks, p<0.004). Conclusion Levels of circulating endothelial cells may have prognostic value in patients with glioblastoma. PMID:23922679

  4. Prognostic impact of monocyte count at presentation in mantle cell lymphoma.

    PubMed

    von Hohenstaufen, Kathrin Aprile; Conconi, Annarita; de Campos, Cassio Polpo; Franceschetti, Silvia; Bertoni, Francesco; Margiotta Casaluci, Gloria; Stathis, Anastasios; Ghielmini, Michele; Stussi, Georg; Cavalli, Franco; Gaidano, Gianluca; Zucca, Emanuele

    2013-08-01

    An increased number of circulating monocytes at presentation has recently been associated with shorter survival in Hodgkin lymphoma, follicular lymphoma and diffuse large B cell lymphoma. This study aimed to assess the prognostic impact of the absolute monocyte count (AMC) at diagnosis in mantle cell lymphoma (MCL). AMC at diagnosis was available in 97 MCL cases recorded in the databases of the Oncology Institute of Southern Switzerland in Bellinzona (Switzerland) and the Division of Haematology of the Amedeo Avogadro University of Eastern Piedmont in Novara (Italy). With a median follow up of 7 years, the 5-year overall survival was 29% for patients with AMC >0·50 × 10(9) /l and 62% for patients with AMC ≤0·50 × 10(9) /l (P = 0·008). Elevated AMC and beta-2 microglobulin at diagnosis remained independent outcome predictors at multivariate analysis, controlling for the MCL International Prognostic Index (MIPI), and have been used to build a simple prognostic scoring system. In this relatively small and heterogeneous series an increased AMC identified poor-risk patients. Our results suggest that AMC together with the beta-2 microglobulin level might provide an inexpensive way to stratify MCL patient risk as a complement to the MIPI, which was confirmed to be a very powerful prognostic tool.

  5. ADAM9 Expression Is Associate with Glioma Tumor Grade and Histological Type, and Acts as a Prognostic Factor in Lower-Grade Gliomas

    PubMed Central

    Fan, Xing; Wang, Yongheng; Zhang, Chuanbao; Liu, Li; Yang, Sen; Wang, Yinyan; Liu, Xing; Qian, Zenghui; Fang, Shengyu; Qiao, Hui; Jiang, Tao

    2016-01-01

    The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas. The ADAM9 expression between lower-grade glioma (LGG) and glioblastoma (GBM) patients was compared and its association with progression-free survival (PFS) and overall survival (OS) was assessed to evaluate its prognostic value. Our data suggested that GBM patients had significantly higher expression of ADAM9 in comparison to LGG patients (p < 0.001, t-test). In addition, among the LGG patients, aggressive astrocytic tumors displayed significantly higher ADAM9 expression than oligodendroglial tumors (p < 0.001, t-test). Moreover, high ADAM9 expression also correlated with poor clinical outcome (p < 0.001 and p < 0.001, log-rank test, for PFS and OS, respectively) in LGG patients. Further, multivariate analysis suggested ADAM9 expression to be an independent marker of poor survival (p = 0.002 and p = 0.003, for PFS and OS, respectively). These results suggest that ADAM9 mRNA expression is associated with tumor grade and histological type in gliomas and can serve as an independent prognostic factor, specifically in LGG patients. PMID:27571068

  6. Circulating plasma cells in newly diagnosed symptomatic multiple myeloma as a possible prognostic marker for patients with standard-risk cytogenetics.

    PubMed

    Vagnoni, Davide; Travaglini, Fosco; Pezzoni, Valerio; Ruggieri, Miriana; Bigazzi, Catia; Dalsass, Alessia; Mestichelli, Francesca; Troiani, Emanuela; Falcioni, Sadia; Mazzotta, Serena; Natale, Annalisa; Angelini, Mario; Ferretti, Silvia; Angelini, Stefano; Galieni, Piero

    2015-08-01

    Detection of circulating plasma cells (PCs) in multiple myeloma (MM) patients is a well-known prognostic factor. We evaluated circulating PCs by flow cytometry (FC) in 104 patients with active MM at diagnosis by gating on CD38(+)  CD45(-) cells and examined their relationship with cytogenetic risk. Patients had an average follow-up of 36 months. By using a receiver operating characteristics analysis, we estimated the optimal cut-off of circulating PCs for defining poor prognosis to be 41. Patients with high-risk cytogenetics (n = 24) had poor prognosis, independently of circulating PC levels [PC < 41 vs. PC ≥ 41: overall survival (OS) = 0% vs. OS = 17%, P = not significant (n.s.); progression-free survival (PFS) = 0% vs. 17%, P = n.s.]. Patients with standard-risk cytogenetics (n = 65) showed a better prognosis when associated with a lower number of circulating PCs (PC < 41 vs. PC ≥ 41: OS = 62% vs. 24%, P = 0·008; PFS = 48% vs. 21%, P = 0·001). Multivariate analysis on the subgroup with standard-risk cytogenetics confirmed that the co-presence of circulating PCs ≥ 41, older age, Durie-Salmon stage >I and lack of maintenance adversely affected PFS, while OS was adversely affected only by lactate dehydrogenase, older age and lack of maintenance. Our results indicate that the quantification of circulating PCs by a simple two-colour FC analysis can provide useful prognostic information in newly diagnosed MM patients with standard-risk cytogenetics.

  7. Clinicopathological and prognostic significance of Nestin expression in patients with non-small cell lung cancer: a systematic review and meta-analysis.

    PubMed

    Li, Shuangjiang; Lai, Yutian; Fan, Jun; Shen, Cheng; Che, Guowei

    2016-04-21

    Latest evidence indicates that Nestin expression may be associated with the high malignancy and poor prognosis of non-small cell lung cancer (NSCLC), but a relevant consensus has not been reached until now. Therefore, we conducted this meta-analysis to evaluate the clinicopathological and prognostic significance of Nestin expression in patients with NSCLC. We searched PubMed, EMBASE and the Web of Science for eligible full-text articles. Odds ratio (OR) and hazard ratio (HR) with 95 % confidence interval (95 % CI) severed as the summarized statistics. Q-test and I (2)-statistic were applied to evaluate the heterogeneity, and sensitivity analysis was conducted for adjustments. Publication bias was detected by Begg's test and Egger's test. Finally, eight eligible articles with 834 NSCLC cases were included. Nestin expression was found to be significantly associated with the unfavorable outcomes of differentiation degree (OR: 2.47; 95 % CI 1.61-3.79; P < 0.001), lymphatic metastasis (OR: 2.45; 95 % CI 1.41-4.25; P = 0.001), TNM stage (OR: 1.73; 95 % CI 1.07-2.79; P = 0.025) and tumor size (OR: 2.68; 95 % CI 1.20-5.98; P = 0.016), but not associated with gender, age, smoking status and NSCLC subtypes. Nestin expression could significantly predict the lower overall survival of NSCLC (HR: 2.41; 95 % CI 1.72-3.38; P < 0.001). The prognostic value of Nestin remained statistically reliable in the subgroups stratified by statistical analysis, patients' origins and follow-up periods, but not significant in patients with squamous cell carcinoma. In conclusion, Nestin expression may be an independent predictor for the poor prognosis and clinicopathological characteristics of NSCLC. Further studies are necessary to validate our discoveries.

  8. The Power of Poor Communications

    ERIC Educational Resources Information Center

    Schaub, Alfred R.

    1975-01-01

    Most breakdowns in communications are the result of the quest for power on behalf of organization members, not the result of poor communications training. Organizational power may be accrued by withholding information, sabotaging communications, refusing to communicate bad news to superiors, and avoiding confrontations by not communicating at all.…

  9. Standard and Poor's Rich Website

    ERIC Educational Resources Information Center

    DiMaria, Frank

    2006-01-01

    To help parents investigate and locate quality school districts and to help policy-makers, principals, and superintendents to make well-informed decisions about education, Standard and Poor's has launched a website called SchoolMatters.com. It is recognized by the U.S. Department of Education and featured on its website (www.ed.gov/parents).…

  10. Prospects for the Working Poor

    ERIC Educational Resources Information Center

    Miller, S. M.

    1970-01-01

    Based on a chapter entitled "Barriers to Employment of the Disadvantaged by Martin Deutsch and S. M. Miller in "Manpower Report of the President, 1968. Discusses the Nixon proposals for remediating poverty in relation to the socioeconomic factors operating to maintain the condition of being poor while working. (JM)

  11. Educating Canada's Urban Poor Children.

    ERIC Educational Resources Information Center

    Maynes, Bill; Foster, Rosemary

    2000-01-01

    Presents six critical thoughts and questions about educating poor urban children in Canada. These thoughts were derived from the development of a directory of Canadian educational poverty programs. Findings from that study emphasize the increasing diversity of the student population, the importance of temporary and large-scale funding, and the…

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

    PubMed Central

    Pan, Qun-Xiong; Su, Zi-Jian; Zhang, Jian-Hua; Wang, Chong-Ren; Ke, Shao-Ying

    2015-01-01

    Background 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 differentiation (P=0.002) were independent predictors of gastric cancer survival. GPS and TNM stage had a comparable prognostic value and higher linear trend chi-square value, likelihood ratio chi-square value, and larger area under the receiver operating

  13. Prognostic Factors in Childhood Leukemia (ALL or AML)

    MedlinePlus

    ... Diagnosis, and Types Prognostic Factors in Childhood Leukemia (ALL or AML) Certain factors that can affect a ... myelogenous leukemia (AML). Prognostic factors for children with ALL Children with ALL are often divided into risk ...

  14. Are poor Chinese text comprehenders also poor in written composition?

    PubMed

    Guan, Connie Qun; Ye, Feifei; Meng, Wanjin; Leong, Che Kan

    2013-10-01

    We studied the performance in three genres of Chinese written composition (narration, exposition, and argumentation) of 158 grade 4, 5, and 6 poor Chinese text comprehenders compared with 156 good Chinese text comprehenders. We examined text comprehension and written composition relationship. Verbal working memory (verbal span working memory and operation span working memory) and different levels of linguistic tasks-morphological sensitivity (morphological compounding and morphological chain), sentence processing (syntax construction and syntax integrity), and text comprehension (narrative and expository texts)-were used to predict separately narrative, expository, and argumentation written compositions in these students. Grade for grade, the good text comprehenders outperformed the poor text comprehenders in all tasks, except for morphological chain. Hierarchical multiple regression analyses showed differential contribution of the tasks to different genres of writing. In particular, text comprehension made unique contribution to argumentation writing in the poor text comprehenders. Future studies should ask students to read and write parallel passages in the same genre for better comparison and incorporate both instructional and motivational variables.

  15. Prognostic significance of KLF4 expression in gastric cancer

    PubMed Central

    Hashimoto, Isaya; Nagata, Takuya; Sekine, Shinichi; Moriyama, Makoto; Shibuya, Kazuto; Hojo, Shozo; Matsui, Koshi; Yoshioka, Isaku; Okumura, Tomoyuki; Hori, Takashi; Shimada, Yutaka; Tsukada, Kazuhiro

    2017-01-01

    To understand the roles of pluripotent stem cell-inducing genes in gastric cancer, the expression of Krüppel-like factor 4 (KLF4), Nanog, octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc) and sex-determining region Y-box 2 (SOX2) was examined using the newly developed gastric carcinoma tissue microarray. The associations between the immunohistochemical expression levels of the pluripotency-inducing factors and the clinicopathological data of 108 patients with gastric cancer were analyzed. No associations were identified between the expression levels of the five pluripotency-inducing factors and the tumor-node-metastasis (TNM) classification or clinicopathological characteristics of the patients. In addition, multivariate analysis revealed no association of Nanog, Oct4, SOX2 or c-Myc with the prognosis of the gastric cancer patients; however, low expression of KLF4 was determined to be an independent negative prognostic factor (P=0.0331), particularly in patients who underwent R0 resection (TNM stages 2 and 3; P=0.0048). In summary, low KLF4 expression was found to be negatively associated with overall survival, and may therefore be a useful prognostic marker in gastric cancer patients. PMID:28356964

  16. Prognostic indications of the failure to treat amoebic liver abscesses

    PubMed Central

    Sánchez-Aguilar, Martín; Morán-Mendoza, Onofre; Herrera-Hernández, Miguel F; Hernández-Sierra, Juan Francisco; Mandeville, Peter B; Tapia-Pérez, J Humberto; Sánchez-Reyna, Martín; Sánchez-Rodríguez, José Juan; Gordillo-Moscoso, Antonio

    2012-01-01

    Objectives To identify the variables that predict the failure to treat amoebic liver abscesses. Methods We prospectively carried out a case–control study on a cohort of patients who had been diagnosed with amoebic liver abscesses using clinical, ultrasonic, and serologic methods. Patients with pyogenic abscesses, negative ELISA tests for amoebiasis, immunosuppression status, or previous abdominal surgery were excluded. All patients received metronidazole, and those who demonstrated 4 days of unfavorable clinical responses received percutaneous or surgical draining of the abscess. Demographic, laboratory, and ultrasonographic characteristics were assessed as prognostic indications of failure. Results Of 40 patients with amoebic liver abscess, 24 (mean age: 36.7±11.2 years) responded to medical treatment and 16 (41.8±11.6 years) required drainage, including 14 patients who underwent percutaneous drainage and two patients who required surgery. The albumin level, abscess volume, abscess diameter, and alkaline phosphatase level were all statistically significant (P<0.05) on the bivariate analysis. The highest (>99%) sensitivity and negative predictive value were observed for an abscess volume >500 ml and diameter >10 cm, while the best specificity and positive predictive value were achieved with the combination of low serum albumin level, high alkaline phosphatase level, and large abscess volume or diameter. Conclusions The prognostic indications of the failure to treat amoebic liver abscesses include low albumin, high alkaline phosphatase, and large abscess volume or diameter. The combination of these variables is a useful and easy tool for determining appropriate therapy. PMID:23265424

  17. Prognosis Research Strategy (PROGRESS) 2: prognostic factor research.

    PubMed

    Riley, Richard D; Hayden, Jill A; Steyerberg, Ewout W; Moons, Karel G M; Abrams, Keith; Kyzas, Panayiotis A; Malats, Núria; Briggs, Andrew; Schroter, Sara; Altman, Douglas G; Hemingway, Harry

    2013-01-01

    Prognostic factor research aims to identify factors associated with subsequent clinical outcome in people with a particular disease or health condition. In this article, the second in the PROGRESS series, the authors discuss the role of prognostic factors in current clinical practice, randomised trials, and developing new interventions, and explain why and how prognostic factor research should be improved.

  18. Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

    PubMed Central

    Lan, Xiuwen; Li, Sen; Gao, Hongyu; Nanding, Abiyasi; Quan, Lina; Yang, Chunyan; Ding, Shaohua; Xue, Yingwei

    2017-01-01

    Purpose Deregulation of immune checkpoint molecules by tumor cells is related to immune escape. This study was conducted to investigate the relationship between the appearance of B- and T-lymphocyte attenuator (BTLA) and its ligand herpesvirus entry mediator (HVEM) with the prognosis in gastric cancer patients. Patients and methods A total of 136 patients with curative gastrectomy were included. The expression of BTLA and HVEM was detected by immunohistochemistry, and its correlation with the clinical significance of gastric cancer was further analyzed. Results The positivity of BTLA and HVEM was detected in 74.3% (101/136) and 89.0% (121/136) of the gastric cancer specimens, respectively. A high expression of BTLA and HVEM was detected, respectively, in 28.7% (39/136) and 44.9% (61/136) of the specimens. Characteristics analysis showed that the high expression of BTLA was significantly associated with lymph node metastasis (P=0.030). Similarly, the high expression of HVEM was also significantly correlated with lymph node metastasis (P=0.007) and depth of invasion (P=0.011). In addition, there was a positive correlation between the expression of BTLA and HVEM in gastric cancer specimens (r=0.245, P=0.004). Univariate analysis revealed that the high expression of BTLA and HVEM was associated with overall survival of patients along with tumor size, Borrmann type, depth of invasion, lymph node metastasis, and histological grade (P<0.05). Multivariate analysis established that the high expression of HVEM (P=0.010), depth of invasion (P=0.001), lymph node metastasis (P<0.001), and histological grade (P=0.027) were independent prognostic factors associated with overall survival in patients with gastric cancer. Conclusion The increased BTLA and HVEM levels correlate with the development and poor prognosis of gastric cancer. HVEM is an important prognostic indicator, and BTLA/HVEM pathway is considered to be a promising candidate for immunotherapy of gastric cancer. PMID

  19. Copy number gain of PIK3CA and MET is associated with poor prognosis in head and neck squamous cell carcinoma.

    PubMed

    Brauswetter, Diána; Dános, Kornél; Gurbi, Bianka; Félegyházi, Éva Fruzsina; Birtalan, Ede; Meggyesházi, Nóra; Krenács, Tibor; Tamás, László; Peták, István

    2016-05-01

    The incidence of head and neck squamous cell carcinomas is still growing, and the long-term prognosis of advanced disease remains poor. Only a fraction of head and neck cancers are sensitive to the EGFR-inhibitor cetuximab, which is the only registered targeted therapy available today. In several cancers, gene copy number alterations of MET and PIK3CA have been found to be prognostic and predictive for therapy response. The aim of this study was to systematically analyze in head and neck cancers the pathological characteristics and prognostic significance of copy number changes of MET and PIK3CA genes. MET and PIK3CA copy numbers were analyzed by fluorescence in situ hybridization in tumor samples of 152 patients. Expression of EGFR, p16, and Ki67 was studied by immunohistochemistry. High polysomy of PIK3CA (chromosome 3) was found in 20 % of cases and amplification in 4.5 %. Regarding MET, 35 % of cases showed low or high polysomy of the gene (chromosome 7), while no intra-chromosomal amplification of MET was detected. PIK3CA copy number gain (high polysomy or amplification) was significantly associated with shorter disease-specific survival, larger tumor volume, and lower p16 expression. MET copy number gain (low or high polysomy) in tumors was significantly associated with shorter disease-specific survival and lower level of EGFR. PIK3CA and MET may play an important role in oncogenesis of certain specific subtypes of head and neck cancer. There is an urgent need for the development of novel targeted therapies against these tumors associated with poor prognosis.

  20. The coexpression of EphB4 and EphrinB2 is associated with poor prognosis in HER2-positive breast cancer

    PubMed Central

    Li, Xuelu; Song, Chen; Huang, Gena; Sun, Siwen; Qiao, Jingjing; Zhao, Jinbo; Zhao, Zuowei; Li, Man

    2017-01-01

    Objective HER2 overexpression is associated with aggressive phenotypes in breast cancer, including increased tumor proliferation, greater invasiveness, and reduced overall survival. The overall response rate to HER2-targeted therapies remains <30%. There is an urgent need for the identification of efficient markers to predict patients with a poor prognosis. This study was designed to investigate the correlation between EphB4 and EphrinB2 expression and the clinicopathological characteristics of HER2-positive breast cancer. Materials and methods A total of 111 primary HER2-positive breast cancer patients were enrolled in this study (diagnosed since December 2005 to November 2010 from the Second Hospital of Dalian Medical University). The protein expression of EphB4 and EphrinB2 was examined by immunohistochemistry using paraffin-embedded tumor tissues. Results There was a significant correlation between EphB4 and EphrinB2 expression (P=0.013, r=0.255). Kaplan–Meier analysis showed that the prognosis of patients with a high expression of both EphB4 and EphrinB2 was significantly worse than the prognosis of patients with either EphB4 or EphrinB2 expression and patients with negative expression (hazard ratio [HR] =1.935, P=0.0224). However, high expression of EphB4 or EphrinB2 alone was not an independent prognostic factor to predict worse overall survival. To summarize, HER2-positive breast cancer patients with overexpression of both EphB4 and EphrinB2 were associated with the worst prognosis. Conclusion High expression of EphB4 and EphrinB2 correlated with poor overall survival, which can serve as an independent prognostic indicator in primary HER2-positive breast cancer patients. PMID:28356761

  1. Prognostic factors of advanced stage non-small-cell lung cancer.

    PubMed

    Ben Amar, Jihen; Ben Safta, Boutheina; Zaibi, Haifa; Dhahri, Besma; Baccar, Mohamed Ali; Azzabi, Saloua

    2016-05-01

    Background Lung cancer is the main cause of death from cancer in the world. The 5-year survival is about 15%. Despite the progress of medicine the mortality rate decreased only marginally. This poor prognosis is due to late diagnosis. Aim To evaluate overall survival and prognostic factors in patients locally advanced or metastatic non small cell lung cancer (NSCLC). Methods Retrospective study including 180 patients with non-small cell lung cancer hospitalized in the department of Charles Nicolle Hospital of Tunis between January 2007 and December 2014. Results The mean age was 61.5 years with a male predominance (93.3%). The median overall survival was 6 months. The poor prognostic factors were the performans status (PS) and early delays of management (<30 days). The factors that improve survival were surgical treatment and delays of management more than 45 days.  Conclusion The prognostic factors in locally advanced and metastatic NSLC in our patient were: PS, management delay and treatment. These factors should be considered in management of patient with advanced stage NSCLC.

  2. Prognostic significance of CT-emphysema score in patients with advanced squamous cell lung cancer

    PubMed Central

    Kim, Young Saing; Ahn, Hee Kyung; Cho, Eun Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Background Although emphysema is a known independent risk factor of lung cancer, no study has addressed the prognostic impact of computed tomography (CT)-emphysema score in advanced stage lung cancer. Methods For 84 consecutive patients with stage IIIB and IV squamous cell lung cancer that underwent palliative chemotherapy, severity of emphysema was semi-quantitatively scored using baseline chest CT images according to the Goddard scoring system (possible scores range, 0–24). The cutoff of high CT-emphysema score was determined using the maximum chi-squared test and the prognostic significance of the high CT-emphysema score was evaluated using Kaplan-Meier analysis and Cox proportional hazards analysis. Results The median CT-emphysema score was 5 (range, 0–22). Patients with a high CT-emphysema score (≥4) tended to have poorer overall survival (OS) (median: 6.3 vs. 13.7 months) than those with a score of <4 (P=0.071). Multivariable analysis revealed that a higher CT-emphysema score was a significant independent prognostic factor for poor OS [hazard ratio (HR) =2.06; 95% confidence interval (CI), 1.24–3.41; P=0.005), along with no response to first-line therapy (P=0.009) and no second-line therapy (P<0.001). Conclusions CT-emphysema score is significantly associated with poor prognosis in patients with advanced squamous cell lung cancer. PMID:27621848

  3. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia

    PubMed Central

    AZIZI, ZAHRA; RAHGOZAR, SOHEILA; MOAFI, ALIREZA; DABAGHI, MOHAMMAD; NADIMI, MOTAHAREH

    2015-01-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance. PMID:26137238

  4. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia.

    PubMed

    Azizi, Zahra; Rahgozar, Soheila; Moafi, Alireza; Dabaghi, Mohammad; Nadimi, Motahareh

    2015-05-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance.

  5. Prognostic Significance of Concurrent Hypovascular and Hypervascular Nodules in Patients with Hepatocellular Carcinoma

    PubMed Central

    Ogasawara, Sadahisa; Chiba, Tetsuhiro; Motoyama, Tenyu; Kanogawa, Naoya; Saito, Tomoko; Shinozaki, Yusuke; Suzuki, Eiichiro; Ooka, Yoshihiko; Tawada, Akinobu; Kato, Hideyuki; Okabe, Shinichiro; Kanai, Fumihiko; Yoshikawa, Masaharu; Yokosuka, Osamu

    2016-01-01

    Background Hypovascular nodules often occur together with hypervascular hepatocellular carcinoma (HCC). However, it remains controversial whether hypovascular nodules associated with hypervascular HCC have any prognostic value. This study evaluated the prognostic impact of hypovascular nodules co-existing with hypervascular HCC as diagnosed by computed tomography during arterial portography (CTAP) and computed tomography during hepatic arteriography (CTHA), which can sensitively capture the dynamic changes in blood flow through the portal vein and hepatic artery in patients with early stage HCC. Methods A total of 152 patients with hypervascular HCC (≤ 30 mm, ≤ 3 nodules), who underwent initial local ablation, were analyzed retrospectively. All patients received CTAP and CTHA prior to treatment. Overall survival (OS) was compared among group A (hypervascular HCC only, 107 patients) and group B (hypovascular nodules and hypervascular HCC, 45 patients). Results Among all hypovascular nodules, 81% (46 of 57) developed hypervascularization within the follow-up period. The 1- and 2-year hypervascularization rates were 17% and 51%, respectively. OS was significantly longer for group A than for group B (P < 0.001). A Cox proportional-hazards model identified the presence of hypovascular nodules concurrent with hypervascular HCC as an independent poor prognostic factor. Conclusion The prognosis of hypervascular HCC patients with hypovascular nodules detected during CTAP and CTHA is poor. Clinical HCC categories seem to be dissimilar between patients with and without hypovascular nodules. PMID:27649084

  6. Expression and prognostic relevance of centromere protein A in primary osteosarcoma.

    PubMed

    Gu, Xiao-Min; Fu, Jie; Feng, Xiao-Jun; Huang, Xue; Wang, Shou-Mei; Chen, Xin-Feng; Zhu, Ming-Hua; Zhang, Shu-Hui

    2014-04-01

    Centromere protein A (CENP-A) is one of the fundamental components of the human active kinetochore and plays important roles in cell-cycle regulation, cell survival, and genetic stability. The aim of the present study was to explore the expression and prognostic significance of CENP-A in osteosarcoma. The results of real-time quantitative PCR and Western blotting analysis revealed an enhanced expression of CENP-A in osteosarcomas relative to adjacent non-tumorous bone tissues at both mRNA and protein levels. Immunohistochemically, 72 of the 123 osteosarcoma specimens (58.5%) had high expression of CENP-A. CENP-A overexpression was significantly correlated with tumor size (P=0.002), poor response to neoadjuvant chemotherapy (P=0.016), local recurrence/lung metastasis (P=0.001), high Ki-67 index (P=0.004), and P53 positivity (P=0.005). Median overall and recurrence-free survival time was significantly shorter in patients with high-CENP-A osteosarcomas than in those with low-CENP-A osteosarcomas. Multivariate analysis identified CENP-A as an independent poor prognostic factor for osteosarcoma. In conclusion, our results demonstrate that elevated CENP-A expression is significantly associated with osteosarcoma progression and has an independent prognostic value in predicting overall and recurrence-free survival for patients with osteosarcoma.

  7. Health solutions for the poor.

    PubMed

    Castro, J L; Fujiwara, P I; Bhambal, P; Emaille-Léotard, N; Harries, A D

    2014-03-21

    The International Union Against Tuberculosis and Lung Disease (The Union) is the oldest international non-governmental organisation involved in the fight against tuberculosis. In 2008, the Institute of The Union was challenged to think boldly about the future and to develop a diverse work portfolio covering a wide spectrum of lung health and other disease-related problems. The vision adopted by The Union at that time was 'Health solutions for the poor'. More recently, there has been lengthy debate about the need for the Union to concentrate just on its core mandate of tuberculosis and lung health and for the Union's vision to reflect this narrower spectrum of activity as 'Lung health solutions for the poor'. In this viewpoint article we outline our reasons for believing that this narrower vision is incompatible with The Union's mission statement, and we argue that making such a change would be a mistake.

  8. Bioinformatics analyses of significant prognostic risk markers for thyroid papillary carcinoma.

    PubMed

    Min, Xiao-Shan; Huang, Peng; Liu, Xu; Dong, Chao; Jiang, Xiao-Lin; Yuan, Zheng-Tai; Mao, Lin-Feng; Chang, Shi

    2015-09-01

    This study was aimed to identify the prognostic risk markers for thyroid papillary carcinoma (TPC) by bioinformatics. The clinical data of TPC and their microRNAs (miRNAs) and genes expression profile data were downloaded from The Cancer Genome Atlas. Elastic net-Cox's proportional regression hazards model (EN-COX) was used to identify the prognostic associated factors. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve were used to screen the significant prognostic risk miRNA and genes. Then, the target genes of the obtained miRNAs were predicted followed by function prediction. Finally, the significant risk genes were performed literature mining and function analysis. Total 1046 miRNAs and 20531 genes in 484 cases samples were identified after data preprocessing. From the EN-COX model, 30 prognostic risk factors were obtained. Based on the 30 risk factors, 3 miRNAs and 11 genes were identified from the ROC and KM curves. The target genes of miRNA-342 such as B-cell CLL/lymphoma 2 (BCL2) were mainly enriched in the biological process related to cellular metabolic process and Disease Ontology terms of lymphoma. The target genes of miRNA-93 were mainly enriched in the pathway of G1 phase. Among the 11 prognostic risk genes, v-maf avian musculoaponeurotic fibrosarcoma oncogene homologue F (MAFF), SRY (sex-determining region Y)-box 4 (SOX4), and retinoic acid receptor, alpha (RARA) encoded transcription factors. Besides, RARA was enriched in four pathways. These prognostic markers such as miRNA-93, miRNA-342, RARA, MAFF, SOX4, and BCL2 may be used as targets for TPC chemoprevention.

  9. Cancer stem cell markers predict a poor prognosis in renal cell carcinoma: a meta-analysis

    PubMed Central

    Cheng, Bo; Yang, Guosheng; Jiang, Rui; Cheng, Yong; Yang, Haifan; Pei, Lijun; Qiu, Xiaofu

    2016-01-01

    Background Relevant markers of CSCs may serve as prognostic biomarkers of RCC. However, their actual prognostic significance remains inconclusive. Thus, a meta-analysis was performed to reevaluate the association of CSCs-relevant markers (CXCR4, CD133, CD44, CD105) expression with RCC prognosis more precisely. Methods PubMed and Embase were searched to look for eligible studies. The pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were used to reassess the association of CSCs markers expression and RCC prognosis of overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and progression-free survival (PFS). Results There were 25 relevant articles, encompassing 2673 RCC patients, eligible for meta-analysis. Overall pooled analysis suggested that high CSCs markers expression predicted poor OS (HR, 2.10, 95% CI: 1.73–2.55) and DFS (HR, 3.77, 95% CI: 2.30–6.19). High CXCR4 expression predicted worse OS (HR, 2.57, 95% CI: 1.95–3.40), CSS (HR,1.97, 95% CI: 1.50–2.59), and DFS (HR, 5.82, 95% CI: 3.01–11.25). CD44 over-expression correlated with a poor OS(HR,1.58, 95% CI: 1.14–2.18), CSS (HR, 2.58, 95% CI: 1.27–5.23), and DFS (HR, 4.49, 95% CI: 2.12–9.53) in RCC patients. CD133 was an independent favorable prognostic factor for CSS (HR, 0.4, 95% CI: 0.29–0.54). Conclusions The presence of CSCs markers correlates with poor RCC outcome. CSCs may be potentially utilized as prognostic markers to stratify RCC patients, probably representing also a novel potential therapeutic target. PMID:27588469

  10. Advanced Ground Systems Maintenance Prognostics Project

    NASA Technical Reports Server (NTRS)

    Harp, Janicce Leshay

    2014-01-01

    The project implements prognostics capabilities to predict when a component, system or subsystem will no longer meet desired functional or performance criteria, called the "end of life." The capability also provides an assessment of the "remaining useful life" of a hardware component.

  11. Requirements Flowdown for Prognostics and Health Management

    NASA Technical Reports Server (NTRS)

    Goebel, Kai; Saxena, Abhinav; Roychoudhury, Indranil; Celaya, Jose R.; Saha, Bhaskar; Saha, Sankalita

    2012-01-01

    Prognostics and Health Management (PHM) principles have considerable promise to change the game of lifecycle cost of engineering systems at high safety levels by providing a reliable estimate of future system states. This estimate is a key for planning and decision making in an operational setting. While technology solutions have made considerable advances, the tie-in into the systems engineering process is lagging behind, which delays fielding of PHM-enabled systems. The derivation of specifications from high level requirements for algorithm performance to ensure quality predictions is not well developed. From an engineering perspective some key parameters driving the requirements for prognostics performance include: (1) maximum allowable Probability of Failure (PoF) of the prognostic system to bound the risk of losing an asset, (2) tolerable limits on proactive maintenance to minimize missed opportunity of asset usage, (3) lead time to specify the amount of advanced warning needed for actionable decisions, and (4) required confidence to specify when prognosis is sufficiently good to be used. This paper takes a systems engineering view towards the requirements specification process and presents a method for the flowdown process. A case study based on an electric Unmanned Aerial Vehicle (e-UAV) scenario demonstrates how top level requirements for performance, cost, and safety flow down to the health management level and specify quantitative requirements for prognostic algorithm performance.

  12. Prognostic Analysis of the Tactical Quiet Generator

    SciTech Connect

    Hively, Lee M

    2008-09-01

    The U.S. Army needs prognostic analysis of mission-critical equipment to enable condition-based maintenance before failure. ORNL has developed and patented prognostic technology that quantifies condition change from noisy, multi-channel, time-serial data. This report describes an initial application of ORNL's prognostic technology to the Army's Tactical Quiet Generator (TQG), which is designed to operate continuously at 10 kW. Less-than-full power operation causes unburned fuel to accumulate on internal components, thereby degrading operation and eventually leading to failure. The first objective of this work was identification of easily-acquired, process-indicative data. Two types of appropriate data were identified, namely output-electrical current and voltage, plus tri-axial acceleration (vibration). The second objective of this work was data quality analysis to avoid the garbage-in-garbage-out syndrome. Quality analysis identified more than 10% of the current data as having consecutive values that are constant, or that saturate at an extreme value. Consequently, the electrical data were not analyzed further. The third objective was condition-change analysis to indicate operational stress under non-ideal operation and machine degradation in proportion to the operational stress. Application of ORNL's novel phase-space dissimilarity measures to the vibration power quantified the rising operational stress in direct proportion to the less-than-full-load power. We conclude that ORNL's technology is an excellent candidate to meet the U.S. Army's need for equipment prognostication.

  13. The preoperative sensitive-modified Glasgow prognostic score is superior to the modified Glasgow prognostic score in predicting long-term survival for esophageal squamous cell carcinoma

    PubMed Central

    Tian, Rui; Zhang, Fei; Sun, Peng; Wu, Jing; Yan, Hong; Wu, Ai-Ran; Zhang, Min; Jiang, Yu-Lu; Lu, Yan-Hong; Xu, Qiu-Yan; Zhan, Xiao-Hong; Zhang, Rong-Xin; Qian, Li-Ting; He, Jie

    2016-01-01

    The present study was designed to investigate the prognostic significance of the preoperative sensitive-modified Glasgow prognostic score (S-mGPS) and its superiority in esophageal squamous cell carcinoma (ESCC). Clinicopathologic characteristics, preoperative albumin and C-reactive protein (CRP) levels were retrospectively collected in 442 patients who underwent transthoracic esophagectomy. The S-mGPS was calculated before surgery based on optimal cutoff values of 45.6 g/L for albumin and 10.0 mg/L for CRP. 360, 74 and 8 cases were assigned an mGPS of 0, 1 and 2, respectively. In contrast, the S-mGPS was 0 in 114, 1 in 258 and 2 in 70 patients. Of the 360 patients with an mGPS of 0, 246 migrated to the S-mGPS-1 group. Both mGPS and S-mGPS were significantly correlated with tumor length, depth of invasion, pathological tumor-node-metastasis (pTNM) stage and adjuvant treatment. In addition, they were significantly associated with disease free survival (DFS) and overall survival (OS) in univariate analysis. Furthermore, multivariate Cox regression analysis identified S-mGPS as an independent prognostic indicator for both DFS [hazard ratio (HR), 1.577; 95% confidence interval (CI), 1.149-2.163; P = 0.005] and OS (HR, 1.762; 95% CI, 1.250-2.484; P = 0.001), but not mGPS (HR, 0.957; 95% CI, 0.692-1.323; P = 0.790 for DFS and HR, 1.089; 95% CI, 0.781-1.517; P = 0.615 for OS, respectively). Moreover, subgroup analysis revealed that the prognostic impact of the S-mGPS was especially striking in pTNM stage II patients. The preoperative S-mGPS is superior to the mGPS as a prognostic predictor in patients with resectable ESCC. PMID:27528228

  14. Prognostic factors for patients with hepatic metastases from breast cancer.

    PubMed

    Wyld, L; Gutteridge, E; Pinder, S E; James, J J; Chan, S Y; Cheung, K L; Robertson, J F R; Evans, A J

    2003-07-21

    Median survival from liver metastases secondary to breast cancer is only a few months, with very rare 5-year survival. This study reviewed 145 patients with liver metastases from breast cancer to determine factors that may influence survival. Data were analysed using Kaplan-Meier survival curves, univariate and multivariate analysis. Median survival was 4.23 months (range 0.16-51), with a 27.6% 1-year survival. Factors that significantly predicted a poor prognosis on univariate analysis included symptomatic liver disease, deranged liver function tests, the presence of ascites, histological grade 3 disease at primary presentation, advanced age, oestrogen receptor (ER) negative tumours, carcinoembryonic antigen of over 1000 ng ml(-1) and multiple vs single liver metastases. Response to treatment was also a significant predictor of survival with patients responding to chemo- or endocrine therapy surviving for a median of 13 and 13.9 months, respectively. Multivariate analysis of pretreatment variables identified a low albumin, advanced age and ER negativity as independent predictors of poor survival. The time interval between primary and metastatic disease, metastases at extrahepatic sites, histological subtype and nodal stage at primary presentation did not predict prognosis. Awareness of the prognostic implications of the above factors may assist in selecting the most appropriate treatment for these patients.British Journal of Cancer (2003) 89, 284-290. doi:10.1038/sj.bjc.6601038 www.bjcancer.com

  15. Prognostic significance of serum beta-2 microglobulin in patients with diffuse large B-cell lymphoma in the rituximab era

    PubMed Central

    Yoon, Shinkyo; Yoo, Changhoon; Park, Ji Hyun; Lee, Jung Bok; Park, Chan-sik; Huh, Jooryung; Lee, Yoonse; Kim, Kyung Won; Ryu, Jin-Sook; Kim, Seok Jin; Kim, Won Seog; Yoon, Dok Hyun; Suh, Cheolwon

    2016-01-01

    The prognostic value of serum beta-2 microglobulin for diffuse large B-cell lymphoma (DLBCL) is not well known in the rituximab era. A retrospective registry data analysis of 833 patients with de novo DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was conducted to establish the prognostic significance of serum beta-2 microglobulin at a ≥2.5 mg/L cutoff. Five-year progression-free survival (PFS, 76.1% vs. 41.0%; p < 0.001) and overall survival (OS, 83.8% vs. 49.2%; p < 0.001) were significantly worse in patients with elevated serum beta-2 microglobulin (n = 290, 34.8%). Furthermore, the five parameters of the International Prognostic Index, accompanying B symptoms, bone marrow involvement and impaired renal function were associated with worse PFS and OS. In multivariate analysis, elevated beta-2 microglobulin was a significant poor prognostic factor for PFS (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.29–2.24; p < 0.001) and OS (HR, 2.0; 95% CI, 1.47–2.75; p < 0.001). In an independent validation cohort of 258 R-CHOP treated patients with de novo DLBCL, elevated beta-2 microglobulin levels remained a significant poor prognostic factor for PFS (HR, 2.03; 95% CI, 1.23–3.32; p = 0.005) and exhibited a strong trend of association with worse OS (HR, 1.64; 95% CI, 0.98–2.75; p = 0.062). The significance of serum beta-2 microglobulin levels as an independent prognostic factor for patients with DLBCL receiving R-CHOP is confirmed. PMID:27764777

  16. Development of a Bayesian Belief Network Model for personalized prognostic risk assessment in colon carcinomatosis.

    PubMed

    Stojadinovic, Alexander; Nissan, Aviram; Eberhardt, John; Chua, Terence C; Pelz, Joerg O W; Esquivel, Jesus

    2011-02-01

    Multimodality therapy in selected patients with peritoneal carcinomatosis is gaining acceptance. Treatment-directing decision support tools are needed to individualize care and select patients best suited for cytoreductive surgery +/- hyperthermic intraperitoneal chemotherapy (CRS +/- HIPEC). The purpose of this study is to develop a predictive model that could support surgical decisions in patients with colon carcinomatosis. Fifty-three patients were enrolled in a prospective study collecting 31 clinical-pathological, treatment-related, and outcome data. The population was characterized by disease presentation, performance status, extent of peritoneal cancer (Peritoneal Cancer Index, PCI), primary tumor histology, and nodal staging. These preoperative parameters were analyzed using step-wise machine-learned Bayesian Belief Networks (BBN) to develop a predictive model for overall survival (OS) in patients considered for CRS +/- HIPEC. Area-under-the-curve from receiver-operating-characteristics curves of OS predictions was calculated to determine the model's positive and negative predictive value. Model structure defined three predictors of OS: severity of symptoms (performance status), PCI, and ability to undergo CRS +/- HIPEC. Patients with PCI < 10, resectable disease, and excellent performance status who underwent CRS +/- HIPEC had 89 per cent probability of survival compared with 4 per cent for those with poor performance status, PCI > 20, who were not considered surgical candidates. Cross validation of the BBN model robustly classified OS (area-under-the-curve = 0.71). The model's positive predictive value and negative predictive value are 63.3 per cent and 68.3 per cent, respectively. This exploratory study supports the utility of Bayesian classification for developing decision support tools, which assess case-specific relative risk for a given patient for oncological outcomes based on clinically relevant classifiers of survival. Further prospective studies

  17. Serum HE4: An Independent Prognostic Factor in Non-Small Cell Lung Cancer.

    PubMed

    Lamy, Pierre-Jean; Plassot, Carine; Pujol, Jean-Louis

    2015-01-01

    Human epididymis secretory protein 4 (HE4) is a secreted glycosylated protein encoded by the WAP four-disulfide core domain 2 (WFDC2) gene, located on a chromosome 20 segment that is frequently amplified in many cancers. This study aimed at determining serum HE4 prognostic value in non-small cell lung cancer (NSCLC), following the REMARK guidelines. Serum samples from 346 consecutive patients with histologically proven and previously untreated NSCLC and 41 patients with benign pulmonary disease were collected at the Montpellier-Nimes Academic Hospital. Work-up investigations performed to determine the disease characteristics and treatment algorithms were congruent with international guidelines. HE4 levels in serum were measured with an ELISA test (Fujirebio Diagnostics) that uses two monoclonal antibodies, 2H5 and 3D8, against the C-WFDC domain of HE4. The area under the ROC curve (i.e., overall ability of HE4 to discriminate between controls and patients) was 0.78 (95% confidence interval [CI], 0.738-0.821; z test P <0.0001). Serum HE4 levels were significantly higher in patients with worse performance status, advanced TNM stage and positive nodal status. In the Cox model, overall survival was shorter in patients with high pretreatment serum HE4 (above 140 pmol/L) than in patients with serum H4 level ≤ 140 pmol/L [median survival: 17.7 weeks (95% CI, 11.9 to 24.9) and 46.4 weeks (95% CI, 38.6 to 56.3), respectively; hazard ratio: 1.48 (95% CI, 1.12 to 1.95) for high HE4; adjusted P = 0.0057]. High serum HE4 level at diagnosis is an independent determinant of poor prognosis in NSCLC.

  18. mTOR pathway activation is a favorable prognostic factor in human prostate adenocarcinoma

    PubMed Central

    Stelloo, Suzan; Sanders, Joyce; Nevedomskaya, Ekaterina; de Jong, Jeroen; Peters, Dennis; van Leenders, Geert J.L.H.; Jenster, Guido; Bergman, Andries M.; Zwart, Wilbert

    2016-01-01

    Prostate cancer patients with localized disease are treated with curative intent. However, the disease will recur in approximately 30% of patients with a high incidence of morbidity and mortality. Prognostic biomarkers are needed to identify patients with high risk of relapse. mTOR pathway activation is reported in prostate cancer, but clinical trials testing efficacy of mTOR inhibitors were unsuccessful. To explain this clinical observation, we studied the expression and prognostic impact of mTOR-S2448 phosphorylation in localized prostate carcinomas. mTOR-S2448 phosphorylation is indicative for an activated mTOR pathway in prostate cancer. Surprisingly, the mTOR signaling pathway is activated specifically in prostate cancer patients with a favorable outcome. Since tumors from poor-outcome patients have low levels of mTOR-S2448 phosphorylation, this may explain why mTOR inhibitors proved unsuccessful in prostate cancer trials. PMID:27096957

  19. The prognostic factors for patients with hematological malignancies admitted to the intensive care unit.

    PubMed

    Cheng, Qian; Tang, Yishu; Yang, Qing; Wang, Erhua; Liu, Jing; Li, Xin

    2016-01-01

    Owing to the nature of acute illness and adverse effects derived from intensive chemotherapy, patients with hematological malignancies (HM) who are admitted to the Intensive Care Unit (ICU) often present with poor prognosis. However, with advances in life-sustaining therapies and close collaborations between hematologists and intensive care specialists, the prognosis for these patients has improved substantially. Many studies from different countries have examined the prognostic factors of these critically ill HM patients. However, there has not been an up-to-date review on this subject, and very few studies have focused on the prognosis of patients with HM admitted to the ICU in Asian countries. Herein, we aim to explore the current situation and prognostic factors in patients with HM admitted to ICU, mainly focusing on studies published in the last 10 years.

  20. Evaluation of Minichromosome Maintenance Protein 7 and c-KIT as Prognostic Markers in Feline Cutaneous Mast Cell Tumours.

    PubMed

    Dobromylskyj, M J; Rasotto, R; Melville, K; Smith, K C; Berlato, D

    2015-11-01

    Mast cell tumours (MCTs) are a common skin tumour in cats, but there is currently no histological grading system or reliable prognostic marker for this species (unlike the situation for dogs). This study utilized a set of 71 feline cutaneous MCTs with known clinical outcomes to assess the potential of various prognostic markers, including the cellular proliferation marker minichromosome maintenance protein (MCM)-7, mitotic index and various KIT labelling characteristics, including KIT positivity, KIT labelling pattern and KIT immunoreactivity score (IS). Of the factors studied, the mitotic index and the KIT labelling pattern were the only features associated significantly with survival times, while the proliferation marker MCM7 and the KIT IS were not. The study also highlights the variability of KIT labelling characteristics between tumours, which may prevent use of this marker as a diagnostic and prognostic tool.

  1. Expression and prognostic significance of apolipoprotein D in breast cancer.

    PubMed Central

    Díez-Itza, I.; Vizoso, F.; Merino, A. M.; Sánchez, L. M.; Tolivia, J.; Fernández, J.; Ruibal, A.; López-Otín, C.

    1994-01-01

    Apolipoprotein D (apo D) is a glycoprotein involved in the human plasma lipid transport system and present at large amounts in cyst fluid from women with gross cystic disease of the breast. Apo D expression in breast carcinomas was examined by immunoperoxidase staining of a series of 163 tumors. A total of 60 (36.8%) tumors were negative for apo D immunostaining, 28 (17.2%) carcinomas were weakly positive, 33 (20.2%) were moderately stained, whereas the remaining 42 (25.8%) tumors were strongly stained with the specific antibodies. No significant correlation was found between apo D content and tumor size, lymph node involvement, or biochemical parameters such as estrogen receptors, cathepsin D, or pS2 protein. However, the finding of a significant association between apo D and menopausal status of patients or differentiation grade of tumors, with apo D values being lower in tumors from premenopausal women or in poorly differentiated carcinomas, suggested a potential value of this glycoprotein as a prognostic factor in breast cancer. Preliminary analysis of relapse-free survival and overall survival in a subgroup of 152 women with a mean follow-up of 42 months confirmed that low apo D values were significantly associated to a shorter relapse-free survival and poorer survival. According to these data, we propose that apo D in combination with other well-established prognostic factors may contribute to more accurately identify subgroups of breast cancer patients with low or high risk for relapse and death. Images Figure 1 Figure 2 Figure 3 PMID:8311115

  2. Evaluation of EGFR as a prognostic and diagnostic marker for head and neck squamous cell carcinoma patients

    PubMed Central

    Polanska, Hana; Raudenska, Martina; Hudcová, Kristyna; Gumulec, Jaromir; Svobodova, Marketa; Heger, Zbynek; Fojtu, Michaela; Binkova, Hana; Horakova, Zuzana; Kostrica, Rom; Adam, Vojtech; Kizek, Rene; Masarik, Michal

    2016-01-01

    Approximately 90% of all head and neck tumors are squamous cell carcinomas. The overall survival of patients with head and neck squamous cell carcinoma (HNSCC) is low (≤50%). A non-invasive marker of disease progression is sorely required. The present study focused on the plasmatic levels of epidermal growth factor receptor (EGFR) in HNSCC patients (N=92) compared with healthy (N=29) and diabetic [type 2 diabetes mellitus (T2DM); N=26] controls. Enzyme-linked immunosorbent assay using antibodies against the extracellular region of EGFR (L25-S645) was performed. No significant changes were observed between diabetic and healthy controls. However, there were significantly higher EGFR plasma levels in HNSCC patients compared with both control groups (P=0.001 and 0.005, respectively). Receiver operating characteristic curve analysis identified a sensitivity of 76.09%, a specificity of 67.27% and an area under curve of 0.727 for this comparison. No significant association was observed between EGFR plasma levels and tumor stage, tumor grade, lymph node or distant metastasis occurrence, smoking habit or hypertension. However, the presence of human papillomavirus infection and T2DM in HNSCC patients had borderline effect on the plasma EGFR levels. Survival analysis revealed no significant influence of plasmatic EGFR levels on the overall and disease-specific survival of HNSCC patients. In conclusion, EGFR plasma levels appear to be a relatively promising diagnostic, but poor prognostic, HNSCC marker. PMID:27602151

  3. Prognostic role of pretreatment neutrophil-lymphocyte ratio in patients with diffuse large B-cell lymphoma treated with RCHOP

    PubMed Central

    Wang, Jing; Zhou, Min; Xu, Jing-Yan; Yang, Yong-Gong; Zhang, Qi-Guo; Zhou, Rong-Fu; Chen, Bing; Ouyang, Jian

    2016-01-01

    Abstract This study aims to investigate whether neutrophil to lymphocyte ratio (NLR) is an independent predictor in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. Data from newly diagnosed DLBCL patients at Nanjing Drum Tower Hospital from 2006 to 2015 were retrospectively reviewed. We used the receiver operating characteristic (ROC) curve analysis to generate the optimal cutoff value for NLR. Among those 156 patients enrolled, the NLR was < 3.0 in 46.8% (73/156) of the patients, and the remaining 53.2% (83/156) had an NLR ≥ 3.0. Patients with higher pretreatment NLR were found to correlate with poorer OS and PFS than these with lower NLR (hazard ratio [HR] = 2.66, 95% confidence interval [CI] = 1.43–4.97, P = 0.002 and HR = 1.79, 95% CI = 1.05–3.07, P = 0.034, respectively). The multivariate Cox proportional hazard model analysis further showed that high NLR was found independently predictive of poor OS (HR = 0.40; CI = 0.19–0.84, P = 0.015) and PFS (HR = 0.57; CI = 0.33–0.98, P = 0.042). Consequently, pretreatment NLR was an independent prognostic predictor in patients with DLBCL in the rituximab era. PMID:27661033

  4. Epidermal growth factor receptor gene amplification and protein expression in glioblastoma multiforme: prognostic significance and relationship to other prognostic factors.

    PubMed

    Layfield, Lester J; Willmore, Carlynn; Tripp, Sheryl; Jones, Claudia; Jensen, Randy L

    2006-03-01

    Epidermal growth factor receptor (EGFR) overexpression occurs in a significant percentage of cases of glioblastoma multiforme (GBM), and amplification has been found in approximately 40% of these neoplasms. Controversy exists as to the prognostic significance of EGFR gene amplification: some reports have indicated that amplification is associated with a poor prognosis, while other authors have reported no relationship between gene amplification and prognosis. Some reports have found a poor prognosis to be associated with amplification of the EGFR gene in patients of all ages with GBM, while other authors have found EGFR amplification to be an independent predictor of prolonged survival in patients with GBM who are older than 60 years of age. The authors studied a series of 34 specimens (32 patients) with histologically proven GBM by immunohistochemistry for the presence of EGFR overexpression and by fluorescence in situ hybridization (FISH) for gene amplification of the EGFR gene. Results of these studies and data on patient age, sex, functional status, therapy, and survival were correlated to determine which variables were predictive of survival. p53 expression was also determined by immunohistochemistry and correlated with the other variables and survival.

  5. Prognostic utility of Hyams histological grading and Kadish-Morita staging systems for esthesioneuroblastoma outcomes.

    PubMed

    Bell, Diana; Saade, Rami; Roberts, Dianna; Ow, Thomas J; Kupferman, Michael; DeMonte, Franco; Hanna, Ehab Y

    2015-03-01

    Esthesioneuroblastoma (ENB) is derived from the specialized olfactory neuroepithelium. Hyams grading and Kadish staging have been used to prognosticate and to guide treatment decisions. In this study, we sought to validate the prognostic utility of these systems in a large ENB cohort. We retrospectively analyzed the records of patients with ENB who had been evaluated and treated at our institution. The association of grade and stage with prognostic outcome was assessed; the Kaplan-Meier estimator was used to generate 5-year OS and DFS curves. Out of 124 cases we identified, 121 were assessed for grading and 109 for staging. Review of the tissue samples revealed that 62 % of tumors were low grade (I/II) and 21 % were high grade (III/IV); 17 % of tumors were metastasis. The OS rate was 75 % at 5 years. The DFS was 60 % at 5 years. The OS was significantly worse for metastatic ENB (low-grade ENB vs metastatic ENB p = 0.01598); the DFS was significantly worse for high grade versus low grade ENB. Of the 109 cases that had been staged, 16 % were stage A, 33 % stage B, 43 % stage C, and 8 % stage D. In the A, B, and C groups, there were no significant differences between recurrence, distant metastasis, or 5-year survival rates. Statistical significance was not reached with the T, N, M and overall staging system. Age cutoff of 65 years reliably predicted OS. High grade of ENB was significantly associated with poor outcome, while advanced stage was not associated with poor outcome in this large cohort. Grading should certainly be considered in prognostication and treatment decisions for ENB.

  6. Prognostic Impact of Time to Ipsilateral Breast Tumor Recurrence after Breast Conserving Surgery

    PubMed Central

    Gosset, Marie; Hamy, Anne-Sophie; Mallon, Peter; Delomenie, Myriam; Mouttet, Delphine; Pierga, Jean-Yves; Lae, Marick; Fourquet, Alain; Rouzier, Roman; Reyal, Fabien; Feron, Jean-Guillaume

    2016-01-01

    Background The poor prognosis of patients who experience ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) is established. A short time between primary cancer and IBTR is a prognostic factor but no clinically relevant threshold was determined. Classification of IBTR may help tailor treatment strategies. Purpose We determined a specific time frame, which differentiates IBTR into early and late recurrence, and identified prognostic factors for patients with IBTR at time of the recurrence. Methods We analyzed 2209 patients with IBTR after BCS. We applied the optimal cut-points method for survival data to determine the cut-off times to IBTR. A subgroup analysis was performed by hormone receptor (HR) status. Survival analyses were performed using a Cox proportional hazard model to determine clinical features associated with distant-disease-free survival (DDFS) after IBTR. We therefor built decision trees. Results On the 828 metastatic events observed, the majority occurred within the first 3 months after IBTR: 157 in the HR positive group, 98 in the HR negative group. We found different prognostic times to IBTR: 49 months in the HR positive group, 33 in the HR negative group. After multivariate analysis, time to IBTR was the first discriminant prognostic factor in both groups (HR 0.65 CI95% [0.54–0.79] and 0.42 [0.30–0.57] respectively). The other following variables were significantly correlated with the DDFS: the initial number of positive lymph nodes for both groups, the initial tumor size and grade for HR positive tumors. Conclusion A short interval time to IBTR is the strongest factor of poor prognosis and reflects occult distant disease. It would appear that prognosis after IBTR depends more on clinical and histological parameters than on surgical treatment. A prospective trial in a low-risk group of patients to validate the safety of salvage BCS instead of mastectomy in IBTR is needed. PMID:27494111

  7. Distributed Prognostic Health Management with Gaussian Process Regression

    NASA Technical Reports Server (NTRS)

    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.

  8. Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia

    PubMed Central

    Hou, Hsin-An; Liu, Chieh-Yu; Kuo, Yuan-Yeh; Chou, Wen-Chien; Tsai, Cheng-Hong; Lin, Chien-Chin; Lin, Liang-In; Tseng, Mei-Hsuan; Chiang, Ying-Chieh; Liu, Ming-Chih; Liu, Chia-Wen; Tang, Jih-Luh; Yao, Ming; Li, Chi-Cheng; Huang, Shang-Yi; Ko, Bor-Sheng; Hsu, Szu-Chun; Chen, Chien-Yuan; Lin, Chien-Ting; Wu, Shang-Ju; Tsay, Woei; Tien, Hwei-Fang

    2016-01-01

    Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but the prognostic relevance of these genes mutations in acute myeloid leukemia (AML) remains unclear. In this study, we investigated mutations of three SF genes, SF3B1, U2AF1 and SRSF2, by Sanger sequencing in 500 patients with de novo AML and analysed their clinical relevance. SF mutations were identified in 10.8% of total cohort and 13.2% of those with intermediate-risk cytogenetics. SF mutations were closely associated with RUNX1, ASXL1, IDH2 and TET2 mutations. SF-mutated AML patients had a significantly lower complete remission rate and shorter disease-free survival (DFS) and overall survival (OS) than those without the mutation. Multivariate analysis demonstrated that SFmutation was an independent poor prognostic factor for DFS and OS. A scoring system incorporating SF mutation and ten other prognostic factors was proved very useful to risk-stratify AML patients. Sequential study of paired samples showed that SF mutations were stable during AML evolution. In conclusion, SF mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression. These mutations may be potential targets for novel treatment and biomarkers for disease monitoring in AML. PMID:26812887

  9. Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma

    PubMed Central

    Taskinen, Minna; Louhimo, Riku; Koivula, Satu; Chen, Ping; Rantanen, Ville; Holte, Harald; Delabie, Jan; Karjalainen-Lindsberg, Marja-Liisa; Björkholm, Magnus; Fluge, Øystein; Pedersen, Lars Møller; Fjordén, Karin; Jerkeman, Mats; Eriksson, Mikael; Hautaniemi, Sampsa; Leppä, Sirpa

    2014-01-01

    Background Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods We analysed 51 prospectively collected pretreatment tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients. Results We identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis. Conclusion COMMD1 is a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL. Trial Registration ClinicalTrials.gov NCT01502982 PMID:24625556

  10. Prognostic significance of preoperative aspartate aminotransferase to neutrophil ratio index in patients with hepatocellular carcinoma after hepatic resection

    PubMed Central

    Guo, Zhiyong; Pang, Hui; Chen, Dubo; Wang, Xiaoping; Ju, Weiqiang; Wang, Dongping; He, Xiaoshun; Hua, Yunpeng; Peng, Baogang

    2016-01-01

    Objectives Various inflammation-based prognostic scores have been associated with poor survival in patients with hepatocellular carcinoma (HCC), and neutrophils display important roles. However, few studies have illuminated the relationship between preoperative aspartate aminotransferase (AST) to neutrophil ratio index (ANRI) and poor prognosis of HCC. We aimed to clarify the prognostic value of ANRI and evaluate the ability of different inflammation-based prognostic scores such as ANRI, AST to lymphocyte ratio index (ALRI), AST to platelet count ratio index (APRI), neutrophil-lymphocyte ratio index (NLR), and platelet-lymphocyte ratio index (PLR). Methods Data were collected retrospectively from 303 patients who underwent curative resection for HCC. Preoperative ANRI, ALRI, APRI, NLR, PLR and clinico-pathological variables were analyzed. Univariate, multivariate and Kaplan-Meier analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS). Results ANRI was correlated with presence of HBsAg, AST, presence of cirrhosis, tumor size, PVTT, cancer of the liver Italian program (CLIP) score, recurrence. Univariate analysis showed ANRI, ALRI, APRI, NLR, PLR were significantly associated with DFS and OS in HCC patients with curative resection. After multivariate analysis, ANRI was demonstrated to be superior to ALRI, APRI, NLR, PLR, which were independently correlated with DFS and OS. Survival analysis showed that preoperative ANRI > 7.8 predicted poor prognosis of patients with HCC after hepatectomy. preoperative ANRI also showed different prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of ANRI and NLR. Conclusions preoperative ANRI is an independent effective predictor of prognosis for patients with HCC, higher levels of ANRI predict poorer outcomes and the combining ANRI and NLR increases the prognostic accuracy of testing. PMID

  11. Surgical outcomes and prognostic factors of oral cancer associated with betel quid chewing and tobacco smoking in Taiwan.

    PubMed

    Liu, Shyun-Yeu; Lu, Chin-Li; Chiou, Chang-Ta; Yen, Ching-Yu; Liaw, Gwo-An; Chen, Yi-Chun; Liu, Yu-Chi; Chiang, Wei-Fan

    2010-04-01

    Oral squamous cell carcinoma (OSCC) is one of the most common cancers in geographic regions where betel quid (BQ) chewing is prevalent; OSCC is an extremely malignant neoplasm whose prognostic factors are multiple and complex. The purpose of this study was to assess clinicopathological prognostic factors and treatment outcomes in 698 consecutive OSCC patients who had undergone surgery as the primary treatment in an area with a high prevalence of both betel quid chewing and tobacco smoking. The prognostic factors were predicted using Cox's proportional-hazards regression model, and the survival rate was calculated using Kaplan-Meier analysis. The median followup for all patients was 44 months. The 5-year cumulative overall, disease-specific, and locoregional control survival rates were 61%, 62%, and 46%, respectively. Multivariate analysis showed that the lower level of nodal metastasis, advanced stage, tumor thickness >7 mm, and treatment failures were independent risk factors of overall survival. Furthermore, history of alcohol drinking, lower level of nodal metastasis, advanced stage, poor cell differentiation, and treatment failures were independent predictors of poor disease-specific survival. However, we did not find any significant factor that affected locoregional recurrence. Due to the high frequencies of locoregional recurrence and second primary cancer, our findings emphasize that aggressive surgical excision, adjuvant treatments according to clinicopathological prognostic factors and close surveillance are important to the survival of OSCC patients in an area with a high prevalence of betel quid chewing and tobacco smoking.

  12. Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

    PubMed Central

    Yang, Fang; Cao, Lulu; Sun, Zijia; Jin, Juan; Fang, Hehui; Zhang, Wenwen; Guan, Xiaoxiang

    2016-01-01

    Triple-negative breast cancer (TNBC) is a tumor subtype with aggressive behavior and poor clinical outcome for lacking effective therapies. Breast cancer stem cells (BCSCs) have been suggested to have tumor-initiating properties, but it remains unclear whether their presence contributes to the increased aggressiveness and poor prognosis of TNBC. Also, the breast cancers display frequent inter- and intra-tumor heterogeneity, which adds the complexity in diagnosis and predicting prognosis. Here we investigated the clinical relevance and prognostic value of the BCSC markers, CD44+/CD24-, aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and CD133 in 88 TNBC cases. We found that a few patients displayed spatial heterogeneity of the BCSC markers in expression, which was defined as intratumor stemness heterogeneity (ITSH) below. There was no significant correlation between any BCSC marker alone or ITSH and progression-free survival (PFS). Interestingly, the combined BCSC phenotype by CD44+/CD24- and ALDH1A1 was significantly associated with worse PFS (P = 0.009). Further stratification analysis revealed that this combined BCSC phenotype was an independent prognostic factor for PFS in some subgroups. In conclusion, we demonstrated the existence of ITSH in TNBC and found that the ITSH as well as a single BCSC marker was not significantly associated with survival, whereas combing the analysis of BCSC markers could improve prognostic value. Our findings may lead to an improvement of prognostic indicators in TNBC. PMID:27994520

  13. External validation of a prognostic model predicting overall survival in metastatic castrate-resistant prostate cancer patients treated with abiraterone.

    PubMed

    Ravi, Praful; Mateo, Joaquin; Lorente, David; Zafeiriou, Zafeiris; Altavilla, Amelia; Ferraldeschi, Roberta; Sideris, Spyridon; Grist, Emily; Smith, Alan; Wong, Sophia; Bianchini, Diletta; Attard, Gerhardt; de Bono, Johann S

    2014-07-01

    A prognostic model was derived from the population of the COU-AA-301 phase 3 trial for metastatic castrate-resistant prostate cancer patients treated with abiraterone after docetaxel, and it stratifies patients into three risk groups based on clinical parameters. We validated this model in an independent cohort of patients treated with abiraterone after docetaxel outside a clinical trial (group A; n=94) and explored its utility in patients treated with abiraterone in the prechemotherapy setting (group B; n=64). For group A, median overall survival (mOS) was significantly different across the three prognostic groups (good: n=39, mOS: 21.8 mo; intermediate: n=44, mOS: 10.6 mo; poor: n=7, mOS: 6.8 mo; p<0.001; area under the curve [AUC]: 0.71). Analysis of group B confirmed the ability of the model to prognosticate for survival in the prechemotherapy setting: (good: n=44, mOS: 45.6 mo; intermediate or poor: n=20, mOS: 34.5 mo; p=0.042; AUC: 0.61). These results serve to validate the prognostic model in an independent population treated with abiraterone after docetaxel and support clinical implementation of the score. Calibration of the model was poorer in patients receiving abiraterone prechemotherapy. Prospective evaluation of this model in clinical trials is needed.

  14. Prognostic studies of canine and feline mammary tumours: the need for standardized procedures.

    PubMed

    Matos, A J F; Baptista, C S; Gärtner, M F; Rutteman, G R

    2012-07-01

    For several years, veterinary oncologists have been struggling with the prognosis of mammary tumours in dogs and cats. Translation of tumour characteristics into prognostic information is an invaluable tool for the use of the most appropriate therapies, as well as for planning innovative therapeutic trials. Moreover, canine and feline spontaneous mammary gland tumours are good models for the study of human breast cancer. Collecting and interpreting information regarding the prognosis of canine and feline mammary tumours is difficult due to the fact that different methods have been applied to study various components and characteristics. This review identifies some of the challenges of prognostic studies of spontaneous canine and feline mammary tumours and suggests standardized procedures to overcome these challenges and facilitate reproducibility and assessment of results.

  15. Metropolitan Influences on Migration into Poor and Nonpoor Neighborhoods*

    PubMed Central

    South, Scott J.; Pais, Jeremy; Crowder, Kyle

    2011-01-01

    Data from the Panel Study of Income Dynamics and three decennial U.S. censuses are used to examine the influence of metropolitan-area characteristics on black and white households' propensity to move into poor versus nonpoor neighborhoods. We find that a nontrivial portion of the variance in the odds of moving to a poor rather to a nonpoor neighborhood exists between metropolitan areas. Net of established individual-level predictors of inter-neighborhood migration, black and white households are more likely to move to a poor or extremely poor tract rather than to a nonpoor tract in metropolitan areas containing many poor neighborhoods and a paucity of recently-built housing in nonpoor areas. Blacks are especially likely to move to a poor tract in metropolitan areas characterized by high levels of racial residential segregation and in which poor tracts have a sizeable concentration of blacks. White households are more likely to move to a poor than to a nonpoor tract in metropolitan areas that have comparatively few African Americans. PMID:21625368

  16. Melt extrusion with poorly soluble drugs.

    PubMed

    Shah, Sejal; Maddineni, Sindhuri; Lu, Jiannan; Repka, Michael A

    2013-08-30

    Melt extrusion (ME) over recent years has found widespread application as a viable drug delivery option in the drug development process. ME applications include taste masking, solid-state stability enhancement, sustained drug release and solubility enhancement. While ME can result in amorphous or crystalline solid dispersions depending upon several factors, solubility enhancement applications are centered around generating amorphous dispersions, primarily because of the free energy benefits they offer. In line with the purview of the current issue, this review assesses the utility of ME as a means of enhancing solubility of poorly soluble drugs/chemicals. The review describes major processing aspects of ME technology, definition and understanding of the amorphous state, manufacturability, analytical characterization and biopharmaceutical performance testing to better understand the strength and weakness of this formulation strategy for poorly soluble drugs. In addition, this paper highlights the potential advantages of employing a fusion of techniques, including pharmaceutical co-crystals and spray drying/solvent evaporation, facilitating the design of formulations of API exhibiting specific physico-chemical characteristics. Finally, the review presents some successful case studies of commercialized ME based products.

  17. Prognostic Significance of Preoperative Circulating Monocyte Count in Patients With Breast Cancer

    PubMed Central

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

    2015-01-01

    Abstract Growing evidence showed that inflammation response plays an important role in cancer development and progression, and absolute lymphocyte count (ALC), absolute monocyte count (AMC), and lymphocyte to monocyte ratio (LMR) have been used as parameters of systemic inflammation in several tumors. In this study, we evaluated the prognostic significance of preoperative ALC, AMC and LMR in breast cancer and 2000 patients between January 2002 and December 2008 at Sun Yat-Sen University Cancer Center were enrolled. Patients were grouped by the cut-off value according to the receiver operating characteristics (ROC) curve analysis. Kaplan–Meier analysis showed that patients with elevated AMC levels (>0.48 × 109/L) had shorter overall survival (OS, P < 0.001). In multivariate analysis, preoperative AMC was identified as an independent prognostic parameter for OS in breast cancer patients (hazard ratio = 1.374, 95% confidence interval: 1.045–1.807). Subgroup analyses revealed that AMC was an unfavorable prognostic factor in stage II–III breast cancer patients and Luminal B, human epithelial growth factor receptor-2 overexpressing subtype, and triple-negative breast cancer (all P < 0.05). Additionally, the prognostic value of ALC and LMR could not be proven in the current study. Preoperative AMC may serve as an easily available and low-priced parameter to predict the outcomes of breast cancer. PMID:26656374

  18. The Impact of Various Platelet Indices as Prognostic Markers of Septic Shock

    PubMed Central

    Yu, Xuezhong; Guo, Shigong; Ji, Xu; Sun, Tongwen; Lan, Chao; Lavergne, Valery; Ghannoum, Marc; Li, Li

    2014-01-01

    Introduction Platelet indices, including mean platelet volume (MPV), are readily available blood tests, although their prognostic value in patients with septic shock has not been fully explored. Current evidence has found contradictory results. This study aims to explore the behavior of platelet indices in septic shock and their clinical prognostic value. Methods Charts of septic shock patients from January to December 2012 in a tertiary medical center in Northern China were reviewed retrospectively. Platelet indices were recorded during the first five consecutive days after admission, as well as the penultimate and the last day of hospital stay. The data were compared between surviving and non-surviving patients. Results A total of 124 septic shock patients were enrolled. Thirty-six of the patients survived and 88 of them expired. MPV in the non-survivor group was higher than that of the survivor group, especially on the last day. PDW and PLCR showed increased trends, while PCT and PLT decreased in the non-survivor group. Among the PLT indices, MPV had the highest area under the receiver operating characteristic curve (0.81) with a precision rate of 75.6% at a cut-off of 10.5.Compared with other more usual septic shock prognostic markers, MPV is second only to lactate for the highest area under the curve. Conclusion A statistically significant difference was seen between survivors and non-survivors for platelet indices which make them easily available and useful prognostic markers for patients in septic shock. PMID:25118886

  19. Prognostic significance of the preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer

    PubMed Central

    Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Iseki, Yasuhito; Ikeya, Tetsuro; Hirakawa, Kosei

    2017-01-01

    A correlation between the lymphocyte-to-monocyte ratio (LMR) and the survival of patients with hematological malignancies has been reported previously. However, there have been few studies investigating the prognostic significance of LMR in patients with solid tumors. The aim of the present study was to evaluate the prognostic significance of preoperative LMR in patients with colorectal cancer (CRC). A total of 189 patients undergoing potentially curative surgery for CRC were enrolled. The LMR was calculated from preoperative blood samples by dividing absolute lymphocyte count by absolute monocyte count. A cut-off value of 4.8 was set based on the receiver operating characteristic curve; 116 patients were classified as high-LMR, and 73 patients classified as low-LMR. The high-LMR group exhibited significantly better relapse-free survival (P=0.0018) and overall survival (P=0.0127) rates than the low-LMR group. According to the multivariate analysis of survival, preoperative LMR was identified as an independent prognostic factor for relapse-free survival (P=0.041) and overall survival (P=0.031). Therefore, preoperative LMR is a useful prognostic marker in patients with CRC.

  20. Prognostic Value of Discs Large Homolog 7 Transcript Levels in Prostate Cancer

    PubMed Central

    Gomez, Christian R.; Kosari, Farhad; Munz, Jan-Marie; Schreiber, Claire A.; Knutson, Gaylord J.; Ida, Cristiane M.; El Khattouti, Abdelouahid; Karnes, R. Jeffrey; Cheville, John C.; Vasmatzis, George; Vuk-Pavlović, Stanimir

    2013-01-01

    Hypoxia has been associated with malignant progression, metastasis and resistance to therapy. Hence, we studied expression of hypoxia–regulated genes in 100 prostate cancer (CaP) bulk tissues and 71 adjacent benign tissues. We found 24 transcripts significantly overexpressed (p≤0.02). Importantly, higher transcript levels of disc large (drosophila) homolog-associated protein 5 (DLGAP5)/discs large homolog 7 (DLG7)/hepatoma up-regulated protein (HURP), hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were associated with higher Gleason score and more advanced systemic progression. Since the products of HMMR and CCNB1 have been identified recently as molecular markers of CaP progression, we postulated that DLG7 has prognostic value too. To test this hypothesis, we measured transcript levels for DLG7 in a 150-pair case-control cohort. The cases (progression to systemic disease within six years of surgery) and controls (no progression within eight years) were matched for clinical and pathologic prognostic variables, including grade, stage, and preoperative serum levels of PSA. The overall prognostic ability of DLG7, as tested in receiver operating characteristic analysis was of 0.74 (95% CI, 0.68 to 0.8). Overall, our data indicate that expression of DLG7, a hypoxia-controlled gene, holds prognostic potential in high-risk CaP; this also demonstrates that variation of oxygen tension may constitute a tool for identification of novel biomarkers for CaP. PMID:24349376

  1. Are there recognized prognostic factors for patients undergoing pulmonary metastasectomy for colorectal carcinoma?

    PubMed

    Tsitsias, Thomas; Toufektzian, Levon; Routledge, Tom; Pilling, John

    2016-12-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether there is a specific subgroup of patients that would benefit from pulmonary metastasectomy for colorectal carcinoma (CRC). A total of 524 papers were identified using the reported search, of which 1 meta-analysis, 1 systematic review and 17 retrospective studies represented the best evidence to answer the clinical question. The authors, date, journal, country, study type, population, outcomes and key results are tabulated. Single pulmonary metastasis (PM) was identified as an independent prognostic favourable factor of survival in 5 of the studies (P = 0.059-0.001), whereas in 2 of the retrospective studies there was linear inverse correlation between the number of PMs and survival (P = 0.005-0.001). The presence of involved hilar and/or mediastinal lymph nodes was reported as a significant negative prognostic factor on multivariate analysis in 7 of the studies (P = 0.042 to <0.001), whereas the level and number of lymph node stations affected were not statistically significant. Seven studies showed an elevated pre-thoracotomy carcinoembrionic antigen (CEA) level (>5 ng/ml) to be a significant predictor of poor survival (P = 0.047-0.0008). In one of the studies, sublobar resection (wedge or segmentectomy) was associated with better survival compared with anatomic resection (P = 0.04). The size of the tumour (maximum diameter >3.75 cm) was associated with worse survival in 1 of the studies (P = 0.04), while another one reported size as a continuous variable to be a prognostic factor of poor survival. Synchronous chemotherapy (P = 0.027) on one study and neo-adjuvant chemotherapy prior to pulmonary metastasectomy (P = 0.0001) on another were found to be favourable prognostic factors, while disease progression during chemotherapy was associated with poor outcome in another paper (P < 0.0001). Patients older than 70 years were shown to have a

  2. Single versus Serial Measurements of Neuron-Specific Enolase and Prediction of Poor Neurological Outcome in Persistently Unconscious Patients after Out-Of-Hospital Cardiac Arrest – A TTM-Trial Substudy

    PubMed Central

    Wiberg, Sebastian; Hassager, Christian; Stammet, Pascal; Winther-Jensen, Matilde; Thomsen, Jakob Hartvig; Erlinge, David; Wanscher, Michael; Nielsen, Niklas; Pellis, Tommaso; Åneman, Anders; Friberg, Hans; Hovdenes, Jan; Horn, Janneke; Wetterslev, Jørn; Bro-Jeppesen, John; Wise, Matthew P.; Kuiper, Michael; Cronberg, Tobias; Gasche, Yvan; Devaux, Yvan; Kjaergaard, Jesper

    2017-01-01

    Background Prediction of neurological outcome is a crucial part of post cardiac arrest care and prediction in patients remaining unconscious and/or sedated after rewarming from targeted temperature management (TTM) remains difficult. Current guidelines suggest the use of serial measurements of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition, this study sought to investigate if serial NSE measurements add incremental prognostic information compared to a single NSE measurement at 48 hours in this population. Methods This study is a post-hoc sub-study of the TTM trial, randomizing OHCA patients to a course of TTM at either 33°C or 36°C. Patients were included from sites participating in the TTM-trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and follow-up was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score) of 3 to 5. Results A total of 685 (73%) patients participated in the study. At day three after OHCA 63 (9%) patients had died and 473 (69%) patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC) of 0.83. A combination of all three NSE measurements yielded the highest discovered AUC (0.88, p = .0002). Easily applicable combinations of serial NSE measurements did not significantly improve prediction over a single measurement at 48 hours (AUC 0.58–0.84 versus 0.83). Conclusion NSE is a strong predictor of poor outcome after OHCA in persistently unconscious patients undergoing TTM, and NSE is a promising surrogate marker of outcome in clinical trials. While combinations

  3. Phyllodes tumors of the breast: diagnosis, treatment and prognostic factors related to recurrence

    PubMed Central

    Zhou, Zhi-Rui; Wang, Chen-Chen; Yang, Zhao-Zhi

    2016-01-01

    Phyllodes tumors of the breast are rare tumor types that consist of 0.3–1.0% in all breast tumors. The naming and classification of breast phyllodes tumor have been debated for years. Based on the classification criteria modified by WHO in 2003, this review mainly introduced the clinicopathologic characteristics, pre-operational diagnosis and the treatment of breast phyllodes tumors, and also summarized the prognostic factors related to tumor recurrence. PMID:28066617

  4. Comparison of Prognostic and Diagnostic Approaches to Modeling Evapotranspiration in the Nile River Basin

    NASA Astrophysics Data System (ADS)

    Yilmaz, M.; Anderson, M. C.; Zaitchik, B. F.; Crow, W. T.; Hain, C.; Ozdogan, M.; Chun, J. A.

    2012-12-01

    Actual evapotranspiration (ET) can be estimated using both prognostic and diagnostic modeling approaches, providing independent yet complementary information for hydrologic applications. Both approaches have advantages and disadvantages. When provided with temporally continuous atmospheric forcing data, prognostic models offer continuous sub-daily ET information together with the full set of water and energy balance fluxes and states (i.e. soil moisture, runoff, sensible and latent heat). On the other hand, the diagnostic modeling approach provides ET estimates over regions where reliable information about available soil water is not known (e.g., due to irrigation practices or shallow ground water levels not included in the prognostic model structure, unknown soil texture or plant rooting depth, etc). Prognostic model-based ET estimates are of great interest whenever consistent and complete water budget information is required or when there is a need to project ET for climate or land use change scenarios. Diagnostic models establish a stronger link to remote sensing observations, can be applied in regions with limited or questionable atmospheric forcing data, and provide valuable observation-derived information about the current land-surface state. Analysis of independently obtained ET estimates is particularly important in data poor regions. Such comparisons can help to reduce the uncertainty in the modeled ET estimates and to exclude outliers based on physical considerations. The Nile river basin is home to tens of millions of people whose daily life depends on water extracted from the river Nile. Yet the complete basin scale water balance of the Nile has been studied only a few times, and the temporal and the spatial distribution of hydrological fluxes (particularly ET) are still a subject of active research. This is due in part to a scarcity of ground-based station data for validation. In such regions, comparison between prognostic and diagnostic model output

  5. Clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma: a meta-analysis

    PubMed Central

    Qu, Hai-Xia; Zhao, Li-Ping; Zhan, Shu-Hui; Geng, Chang-Xin; Xu, Lin; Xin, Yong-Ning

    2016-01-01

    Background The clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma (ESCC) remains controversial. To investigate this question, we conducted a meta-analysis. Methods A comprehensive literature search of electronic databases (up to July 10, 2016) was performed for relevant studies using multiple search strategies. Correlation between PD-L1 expression and clinicopathological features/overall survival (OS) was analyzed. Results A total of 1,350 ESCC patients from eight studies were included. The pooled odds ratios (ORs) indicated that none of the clinicopathological characteristics was correlated with PD-L1 expression, including gender [OR =0.84; 95% confidence interval (CI): 0.59–1.18; P=0.31], histological differentiation (OR =1.33; 95% CI: 0.95–1.85; P=0.09), tumor depth (OR =0.66; 95% CI: 0.33–1.35; P=0.26), status of lymph node metastasis (OR =0.67; 95% CI: 0.30–1.52; P=0.34), distal metastasis (OR =0.66; 95% CI: 0.40–1.09; P=0.10) and tumor node metastasis (TNM) stage (OR =0.93; 95% CI: 0.49–1.75; P=0.82). The combined hazard ratio (HR) for OS showed a trend that overexpression of PD-L1 might be associated with the survival outcome of ESCC, though the difference was not statistically significant (HR =1.65; 95% CI 0.95–2.85; P=0.07). Conclusions Based on the published studies, PD-L1 overexpression in ESCC was not associated with common clinicopathological characteristics. PD-L1 might be a poor prognostic biomarker for ESCC. Further large-scale research should be performed to reveal the precise clinicopathological and prognostic significance of PD-L1 in ESCC by unified testing standard. PMID:28066599

  6. Bcl-2 expression is a poor predictor for hepatocellular carcinoma prognosis of andropause-age patients

    PubMed Central

    Zhang, Xiao-Fei; Yang, Xin; Jia, Hu-Liang; Zhu, Wen-Wei; Lu, Lu; Shi, Wei; Zhang, Hao; Chen, Jin-Hong; Tao, Yi-Feng; Wang, Zheng-Xin; Yang, Jun; Wang, Lian-Xin; Lu, Ming; Zheng, Yan; Zhao, Jing; Dong, Qiong-Zhu; Qin, Lun-Xiu

    2016-01-01

    Objective: The expression of B-cell lymphoma 2 (Bcl-2) seems to be influenced by the endocrine environment. Numerous reports demonstrate the diverse expression of Bcl-2 family members under sex steroid regulation. With the exception of estrogen-related tumors, androgen-related tumors have shown their characteristics in Bcl-2 expression. In this study, the status of Bcl-2 expression in male hepatocellular carcinoma (HCC) patients was examined to verify the high incidence of HCC in males. Methods: Tumor tissue microarray was used to examine Bcl-2 expression levels in 374 HCC cases including 306 males and 68 females. Kaplan-Meier method, log-rank test, and Cox proportional hazards model were applied to investigate the predictive value of Bcl-2 in HCC patients. Results: Immunohistochemistry analysis showed that male patients with higher Bcl-2 levels had significantly longer median survival time and recurrence time than those with lower levels. However, no significant differences in outcomes were found between different Bcl-2 levels in female patients. When the male patients were stratified into several age points, the level of Bcl-2 expression showed poorer predictive efficiency in the 45–49 and 55–60 age groups in andropause-age patients compared with other age groups. Bcl-2 was an independent prognostic factor for both overall survival (P < 0.0001) and recurrence time (P = 0.0001) in male patients. After excluding male patients in the 45–60 age group, the predictive efficiency was enhanced (n = 147, OS, P = 0.0002, TTR, P < 0.0001). Conclusions: Bcl-2 expression is an independent predictor of survival and recurrence in male HCC. Bcl-2 levels may also be regulated by androgens or androgen receptors in male HCC patients. Bcl-2 levels change and exhibit poor predictive efficiency when androgen levels vary dramatically (andropause age). PMID:28154777

  7. Prognostics for Electronics Components of Avionics Systems

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Saha, Bhaskar; Wysocki, Philip F.; Goebel, Kai F.

    2009-01-01

    Electronics components have and increasingly critical role in avionics systems and for the development of future aircraft systems. Prognostics of such components is becoming a very important research filed as a result of the need to provide aircraft systems with system level health management. This paper reports on a prognostics application for electronics components of avionics systems, in particular, its application to the Isolated Gate Bipolar Transistor (IGBT). The remaining useful life prediction for the IGBT is based on the particle filter framework, leveraging data from an accelerated aging tests on IGBTs. The accelerated aging test provided thermal-electrical overstress by applying thermal cycling to the device. In-situ state monitoring, including measurements of the steady-state voltages and currents, electrical transients, and thermal transients are recorded and used as potential precursors of failure.

  8. Diagnostic and prognostic epigenetic biomarkers in cancer.

    PubMed

    Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

    2015-01-01

    Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

  9. [Maternal and foetal prognostic during severe toxemia].

    PubMed

    Rachdi, Radhouane; Kaabi, Mehdi; Zayene, Houssine; Basly, Mohamed; Messaoudi, Fathi; Messaoudi, Lotfi; Chibani, Mounir

    2005-02-01

    Severe gravidic toxemia gives heavy maternal and foetal morbidity and mortality. The purpose of our study is to loosen the factors of bad maternal and foetal prognostic. It's a retrospective study about 100 cases of severe and complicated gravidic toxemia repertorieted in the maternity of Military Hospital of Tunis. Maternal morbidity is dominated by the complications of hypertension and a blood disorders. We raised 4 cases of eclampsia, 9 cases of retro placental hematome and 5 cases of HELLP syndrome. We don't deplore any maternal death. Perinatal mortality is 28.8%. The rate of delay intra-uterine growth was 43.8% and the prematurity 65.9%. More toxemia appears early during pregnancy more maternal and foetal prognostic is compromised.

  10. [Prognostic factors of early breast cancer].

    PubMed

    Almagro, Elena; González, Cynthia S; Espinosa, Enrique

    2016-02-19

    Decision about the administration of adjuvant therapy for early breast cancer depends on the evaluation of prognostic factors. Lymph node status, tumor size and grade of differentiation are classical variables in this regard, and can be complemented by hormonal receptor status and HER2 expression. These factors can be combined into prognostic indexes to better estimate the risk of relapse or death. Other factors are less important. Gene profiles have emerged in recent years to identify low-risk patients who can forgo adjuvant chemotherapy. A number of profiles are available and can be used in selected cases. In the future, gene profiling will be used to select patients for treatment with new targeted therapies.

  11. [Drug access in poor countries].

    PubMed

    Sebbag, Robert

    2007-11-01

    As a responsible player in the global pharmaceutical industry, Sanofi-Aventis recognizes its special responsibility to provide poor countries with access to drugs and vaccines. This is a key component of the Group's approach to sustainable development. As such, the Access to Medicines department draws on Sanofi-Aventis' expertise in order to address major public health issues, starting with the treatment of malaria, tuberculosis, sleeping sickness, leishmaniasis and epilepsy, as well as access to vaccines. The department has four main activities: research and development of new drugs; improvement of existing treatments; information, communication and education of patients and healthcare professionals; and development of a differential pricing and distribution policy adapted to patients' income, with a "no profit-no loss" equilibrium.

  12. Serving the world's poor, profitably.

    PubMed

    Prahalad, C K; Hammond, Allen

    2002-09-01

    By stimulating commerce and development at the bottom of the economic pyramid, multi-nationals could radically improve the lives of billions of people and help create a more stable, less dangerous world. Achieving this goal does not require MNCs to spearhead global social-development initiatives for charitable purposes. They need only act in their own self-interest. How? The authors lay out the business case for entering the world's poorest markets. Fully 65% of the world's population earns less than $2,000 per year--that's 4 billion people. But despite the vastness of this market, it remains largely untapped. The reluctance to invest is easy to understand, but it is, by and large, based on outdated assumptions of the developing world. While individual incomes may be low, the aggregate buying power of poor communities is actually quite large, representing a substantial market in many countries for what some might consider luxury goods like satellite television and phone services. Prices, and margins, are often much higher in poor neighborhoods than in their middle-class counterparts. And new technologies are already steadily reducing the effects of corruption, illiteracy, inadequate infrastructure, and other such barriers. Because these markets are in the earliest stages of economic development, revenue growth for multi-nationals entering them can be extremely rapid. MNCs can also lower costs, not only through low-cost labor but by transferring operating efficiencies and innovations developed to serve their existing operations. Certainly, succeeding in such markets requires MNCs to think creatively. The biggest change, though, has to come from executives: Unless business leaders confront their own preconceptions--particularly about the value of high-volume, low-margin businesses--companies are unlikely to master the challenges or reap the rewards of these developing markets.

  13. Contrast-Enhanced Ultrasonography Features of Breast Malignancies with Different Sizes: Correlation with Prognostic Factors

    PubMed Central

    Zhao, Li-Xia; Liu, Hui; Wei, Qing; Xu, Guang; Wu, Jian; Xu, Hui-Xiong; Wu, Rong; Pu, Huan

    2015-01-01

    This study was to investigate the correlation between contrast-enhanced ultrasonography (CEUS) characteristics with prognostic factors in breast cancers with different sizes. A retrospective analysis of CEUS characteristics of 104 pathologically proven malignant lesions from 104 women was conducted. Lesions were divided into two groups according to their size measured by US (Group 1: maximum diameter ≤20 mm; Group 2: maximum diameter >20 mm). Features including enhancement degree, order and pattern, enlargement of the enhancement area, and penetrating vessels on CEUS were evaluated. Pathologic prognostic factors, including estrogen and progesterone receptor status, and the expression of c-erb-B2, p53, Ki-67, and VEGF were assessed. Comparison of enhancement pattern parameters between Group 1 and Group 2 showed statistically significant differences (P < 0.0001). A significant correlation was found between enlargement of the enhancement area and ER positivity in Group 1 (P = 0.032). In Group 2 the absence of penetrating vessels was significantly associated with VEGF negativity (P = 0.022) and ER negativity (P = 0.022). Centripetal enhancement reflected VEGF negativity (P = 0.033) in lesions with diameter >20 mm. Thus, breast cancers with different sizes show different CEUS features; small breast cancers show homogeneous enhancement pattern while cancers with diameter >20 mm show homogeneous enhancement pattern. Some CEUS characteristics of differently sized breast cancers could be correlated with prognostic factors, which may be useful in prognosis assessment. PMID:26881202

  14. Vehicle Integrated Prognostic Reasoner (VIPR) Final Report

    NASA Technical Reports Server (NTRS)

    Bharadwaj, Raj; Mylaraswamy, Dinkar; Cornhill, Dennis; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

    2013-01-01

    A systems view is necessary to detect, diagnose, predict, and mitigate adverse events during the flight of an aircraft. While most aircraft subsystems look for simple threshold exceedances and report them to a central maintenance computer, the vehicle integrated prognostic reasoner (VIPR) proactively generates evidence and takes an active role in aircraft-level health assessment. Establishing the technical feasibility and a design trade-space for this next-generation vehicle-level reasoning system (VLRS) is the focus of our work.

  15. Towards Performance Prognostics of a Launch Valve

    DTIC Science & Technology

    2014-10-02

    works are related to this paper’s efforts. Gomes et. al. developed a health monitoring system for a pneumatic valve using a Probability Integral...Transform based technique (Gomes 2010) and Daigle et. al. developed a model-based prognostics approach for pneumatic valves (Daigle 2011). While the...Launch Valve in this work is hydraulically controlled, the methods used for pneumatic valve PHM are quite relevant. Diagle et. al. used a Probability

  16. Identification of Prostate Cancer Prognostic Markers

    DTIC Science & Technology

    2014-10-01

    Assessment post- Surgical ( CAPRA -S) nomogram (pɘ.05 respectively). Importantly, the 16p13.3 gain status was found to significantly predict early...operative PSA levels, GS, T-Stage and CAPRA -S risk scores respectively, improved the overall prognostication in these patients (log rank, Pɘ.001...Risk Assessment post-Surgical ( CAPRA -S) nomogram (pɘ.05 respectively). Importantly, the 16p13.3 gain status was found to significantly predict

  17. Identification of Prostate Cancer Prognostic Markers

    DTIC Science & Technology

    2013-10-01

    aims. Ethics approval has been obtained for the samples collection of AIM1. The chromosome 16p13.3 gain was found to be associated with high Gleason...Prostate cancer, Genomic alteration, Fluorescence in situ hybridization (FISH), Prognostic markers, ectopic expression, gene silencing, cDNA cloning ...In regard to AIM1 and AIM2, we have recently obtained the final approval from the Ethics committee of our hospital after a lengthy process. We have

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

    PubMed Central

    Orlow, Irene; Kanetsky, Peter A.; Thomas, Nancy E.; Fang, Shenying; Lee, Jeffrey E.; Berwick, Marianne; Lee, Ji-Hyun

    2017-01-01

    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. PMID:28323902

  19. A Distributed Approach to System-Level Prognostics

    NASA Technical Reports Server (NTRS)

    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.

  20. Co-expression of midkine and pleiotrophin predicts poor survival in human glioma.

    PubMed

    Ma, Jinyang; Lang, Bojuan; Wang, Xiongwei; Wang, Lei; Dong, Yuanxun; Hu, Huojun

    2014-11-01

    The aim of this study was to investigate whether co-expression of midkine (MK) and pleiotrophin (PTN) has prognostic relevance in human gliomas. Immunohistochemistry was used to investigate the expression of MK and PTN proteins in 168 patients with gliomas. The levels of MK and PTN mRNA in glioma tissues and paratumor tissues were evaluated in 45 paired cases by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis was performed to assess prognostic significance. The expression levels of MK and PTN proteins in glioma tissue were both significantly higher (both p<0.001) than those in paratumor tissues on immunohistochemistry analysis, which was confirmed by qRT-PCR analysis. Additionally, the overexpression of either MK or PTN was significantly associated with the World Health Organization Grade (p=0.001 and 0.034, respectively), low Karnofsky Performance Status (KPS) score (p=0.022 and 0.001, respectively), time to recurrence (p=0.043 and 0.011, respectively) and poor overall survival (p=0.018 and 0.001, respectively). Multivariate Cox proportional-hazards regression analysis revealed that increased expressions of MK and PTN were both independent prognostic factors for poor overall survival (p=0.030 and 0.022, respectively). Furthermore, the co-expression of MK and PTN was more significantly (p=0.003) associated with adverse prognosis in patients with gliomas than the respective expression of MK or PTN alone. To our knowledge, these findings are the first to indicate that the co-expression of MK and PTN is significantly correlated with prognosis in glioma patients, suggesting that the co-expression of these proteins may be used as both an early diagnostic and independent prognostic marker.

  1. Overexpression of MutSα Complex Proteins Predicts Poor Prognosis in Oral Squamous Cell Carcinoma

    PubMed Central

    Wagner, Vivian Petersen; Webber, Liana Preto; Salvadori, Gabriela; Meurer, Luise; Fonseca, Felipe Paiva; Castilho, Rogério Moraes; Squarize, Cristiane Helena; Vargas, Pablo Agustin; Martins, Manoela Domingues

    2016-01-01

    Abstract The DNA mismatch repair (MMR) system is responsible for the detection and correction of errors created during DNA replication, thereby avoiding the incorporation of mutations in dividing cells. The prognostic value of alterations in MMR system has not previously been analyzed in oral squamous cell carcinoma (OSCC). The study comprised 115 cases of OSCC diagnosed between 1996 and 2010. The specimens collected were constructed into tissue microarray blocks. Immunohistochemical staining for MutSα complex proteins hMSH2 and hMSH6 was performed. The slides were subsequently scanned into high-resolution images, and nuclear staining of hMSH2 and hMSH6 was analyzed using the Nuclear V9 algorithm. Univariable and multivariable Cox proportional hazard regression models were performed to evaluate the prognostic value of hMSH2 and hMSH6 in OSCC. All cases in the present cohort were positive for hMSH2 and hMSH6 and a direct correlation was found between the expression of the proteins (P < 0.05). The mean number of positive cells for hMSH2 and hMSH6 was 64.44 ± 15.21 and 31.46 ± 22.38, respectively. These values were used as cutoff points to determine high protein expression. Cases with high expression of both proteins simultaneously were classified as having high MutSα complex expression. In the multivariable analysis, high expression of the MutSα complex was an independent prognostic factor for poor overall survival (hazard ratio: 2.75, P = 0.02). This study provides a first insight of the prognostic value of alterations in MMR system in OSCC. We found that MutSα complex may constitute a molecular marker for the poor prognosis of OSCC. PMID:27258499

  2. New prognostic markers in liver cirrhosis

    PubMed Central

    Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry

    2015-01-01

    Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of “inflammatory stress” and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value. PMID:26019739

  3. [Prognostic factors in acute nonlymphoid leukemias].

    PubMed

    Capelli, D; Tedeschi, A; Montillo, M; Corvatta, L; Bartocci, C; Montroni, M; Leoni, P

    1996-10-01

    Our retrospective study was aimed at assessing parameters affecting the prognosis of acute non lymphoid leukemia (ANLL). Since 1988 to 1994 we observed 84 patients: 52 males, 32 females. For each patient we considered at diagnosis: age, fever, performance status, platelets, hemoglobin and white blood cell count, extramidollary disease, bone marrow blastosis, phenotype and cytogenetic abnormalities of blasts cells. All the parameters listed above were correlated with the time to achieve the complete remission (CR), CR duration and the overall survival. Statistical tests as t-student and chi square test were used. Statistical analysis of the parameters considered revealed that the only value affecting the achievement of a CR was the age. The prognostic significance of immunophenotyping in ANLL has been a controversial issue, with a number of conflicting reports. In our study only the terminal deoxynucleotidyl transferase was significantly associated with prognosis. Our study, as data reported in literature, confirms that the prognostic impact of the various parameters in ANLL is controversial. The study of prognostic factors and of the immunophenotype is important to identify the clinical and the biologic profile of the disease and to evaluate the optimal post-remission treatment.

  4. Angiogenesis: a prognostic determinant in pancreatic cancer?

    PubMed

    van der Zee, Jill A; van Eijck, Casper H J; Hop, Wim C J; van Dekken, Herman; Dicheva, Bilyana M; Seynhaeve, Ann L B; Koning, Gerben A; Eggermont, Alexander M M; ten Hagen, Timo L M

    2011-11-01

    Angiogenesis has been associated with disease progression in many solid tumours, however the statement that tumours need angiogenesis to grow, invade and metastasise seems no longer applicable to all tumours or to all tumour subtypes. Prognostic studies in pancreatic cancer are conflicting. In fact, pancreatic cancer has been suggested an example of a tumour in which angiogenesis is less essential for tumour progression. The aim of the present study was therefore to measure angiogenesis in two anatomically closely related however prognostically different types of pancreatic cancer, pancreatic head and periampullary cancer, and investigate its relation with outcome. Vessels were stained by CD31 on original paraffin embedded tissue from 206 patients with microscopic radical resection (R0) of pancreatic head (n=98) or periampullary cancer (n=108). Angiogenesis was quantified by microvessel density (MVD) and measured by computerised image analysis of three randomly selected fields and investigated for associations with recurrence free survival (RFS), cancer specific survival (CSS), overall survival (OS) and conventional prognostic factors. MVD was heterogeneous both between and within tumours. A higher MVD was observed in periampullary cancers compared with pancreatic head cancers (p<.01). Furthermore, MVD was associated with lymph node involvement in pancreatic head (p=.014), but not in periampullary cancer (p=.55). Interestingly, MVD was not associated with RFS, CSS or with OS. In conclusion, angiogenesis is higher in periampullary cancer and although associated with nodal involvement in pancreatic head cancer, pancreatic cancer prognosis seems indeed angiogenesis independent.

  5. New prognostic markers in liver cirrhosis.

    PubMed

    Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry

    2015-05-28

    Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of "inflammatory stress" and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value.

  6. Abnormalities in Chromosomes 1q and 13 Independently Correlate With Factors of Poor Prognosis in Multiple Myeloma

    PubMed Central

    Kim, Miyoung; Ju, Young-Su; Lee, Eun Jin; Kang, Hee Jung; Kim, Han-Sung; Cho, Hyoun Chan; Kim, Hyo Jung; Kim, Jung-Ah; Lee, Dong Soon

    2016-01-01

    Background We comprehensively profiled cytogenetic abnormalities in multiple myeloma (MM) and analyzed the relationship between cytogenetic abnormalities of undetermined prognostic significance and established prognostic factors. Methods The karyotype of 333 newly diagnosed MM cases was analyzed in association with established prognostic factors. Survival analysis was also performed. Results MM with abnormal karyotypes (41.1%) exhibited high international scoring system (ISS) stage, frequent IgA type, elevated IgG or IgA levels, elevated calcium levels, elevated creatine (Cr) levels, elevated β2-microglobulin levels, and decreased Hb levels. Structural abnormalities in chromosomes 1q, 4, and 13 were independently associated with elevated levels of IgG or IgA, calcium, and Cr, respectively. Chromosome 13 abnormalities were associated with poor prognosis and decreased overall survival. Conclusions This is the first study to demonstrate that abnormalities in chromosomes 1q, 4, and 13 are associated with established factors for poor prognosis, irrespective of the presence of other concurrent chromosomal abnormalities. Chromosome 13 abnormalities have a prognostic impact on overall survival in association with elevated Cr levels. Frequent centromeric breakpoints appear to be related to MM pathogenesis. PMID:27578511

  7. Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma

    PubMed Central

    Spolverato, Gaya; Pawlik, Timothy M.; Huo, Teh-la; Lee, Yun-Hsuan; Frigo, Anna Chiara; Giacomin, Anna; Giannini, Edoardo G.; Ciccarese, Francesca; Piscaglia, Fabio; Rapaccini, Gian Lodovico; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Cabibbo, Giuseppe; Sacco, Rodolfo; Morisco, Filomena; Biasini, Elisabetta; Foschi, Francesco Giuseppe; Gasbarrini, Antonio; Svegliati Baroni, Gianluca; Virdone, Roberto; Trevisani, Franco; Cillo, Umberto

    2016-01-01

    Background Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC. Methods and Findings Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child–Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26–106 mo) and 39 mo for Taiwanese patients (interquartile range, 12–61 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score ≤ 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2–3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4–5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese

  8. Prognostic significance of neutrophil-lymphocyteratio/platelet-lymphocyteratioin lung cancers: a meta-analysis

    PubMed Central

    Yang, Hong-Bo; Xing, Meng; Ma, Lei-Na; Feng, Ling-Xin; Yu, Zhuang

    2016-01-01

    Setting For now, hematological markers of inflammatory response have emerged as prognostic factors for patients with cancer. Many articles have confirm that neutrophil to lymphocyte ratio(NLR) and platelet–lymphocyte ratio (PLR) are relate with poor prognosis in various types of tumors. Objective To investigate the association between NLR/PLR and progression free survival (PFS), overall survival (OS) and clinicopathologic parameters in lung cancer patients. Design We performed relevant searches in PubMed database, Google Scholar, Springer Link. We included retrospective cohort studies that reported hazard ratios with 95% confidence intervals for the NLR or PLR and PFS or OS. Results Both high NLR (P < 0.00001) and high PLR (P = 0.01) were significantly predictive of poorer OS. It also demonstrated that elevated NLR predicted poorer PFS (P = 0.0002). High NLR was significantly associated with deeper Invasive of tumor, (P = 0.006) extensive lymph nodetastasis(N2–3) (P = 0.01), poor differentiation (P = 0.0002) and vascular invasion(P = 0.002). There was no evidence of publication bias. Subgroup analysis indicated that little evidence of heterogeneity. However, PLR has no prognostic significance for SCLC. Conclusions We provides further evidence in support of elevated NLR and PLR were predictors of poor OS and PFS in patients with lung cancer. Given this, NLR and PLR may be markers to report treatment outcomes. PMID:27732958

  9. Clinicopathological characteristics, treatment and outcomes in uterine carcinosarcoma and grade 3 endometrial cancer patients: a comparative study

    PubMed Central

    2016-01-01

    .9; p=0.046) and ascites fluid (HR, 5.1; 95% CI, 1.1 to 22.7; p=0.032) were independently correlated with poor prognosis for G3EC patients. Conclusion The distinctions in both clinicopathological and prognostic characteristics between UCS and G3EC suggest that this subtype should be treated separately from high-risk epithelial endometrial carcinoma. PMID:26463439

  10. Poor Facial Affect Recognition among Boys with Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    Hinton, V. J.; Fee, R. J.; De Vivo, D. C.; Goldstein, E.

    2007-01-01

    Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a…

  11. Intraductal carcinoma of the prostate: a distinct histopathological entity with important prognostic implications.

    PubMed

    Henry, P C; Evans, A J

    2009-07-01

    Intraductal carcinoma of the prostate (IDCP) has been described as a lesion associated with poor prognostic features in prostate cancer. Its recognition and reporting in prostate specimens, particularly in needle biopsies, is critical as it carries significant implications for patient management. Recent histological definitions have been proposed to assist in the recognition of IDCP and to help distinguish it from lesions with similar appearance, but different clinical behaviour. In this review, a historical overview of the description of IDCP will be presented followed by a summary of the current histological diagnostic criteria and the recommendations for management and reporting of IDCP.

  12. Expression of CRM1 and CDK5 shows high prognostic accuracy for gastric cancer

    PubMed Central

    Sun, Yu-Qin; Xie, Jian-Wei; Xie, Hong-Teng; Chen, Peng-Chen; Zhang, Xiu-Li; Zheng, Chao-Hui; Li, Ping; Wang, Jia-Bin; Lin, Jian-Xian; Cao, Long-Long; Huang, Chang-Ming; Lin, Yao

    2017-01-01

    AIM To evaluate the predictive value of the expression of chromosomal maintenance (CRM)1 and cyclin-dependent kinase (CDK)5 in gastric cancer (GC) patients after gastrectomy. METHODS A total of 240 GC patients who received standard gastrectomy were enrolled in the study. The expression level of CRM1 and CDK5 was detected by immunohistochemistry. The correlations between CRM1 and CDK5 expression and clinicopathological factors were explored. Univariate and multivariate survival analyses were used to identify prognostic factors for GC. Receiver operating characteristic analysis was used to compare the accuracy of the prediction of clinical outcome by the parameters. RESULTS The expression of CRM1 was significantly related to size of primary tumor (P = 0.005), Borrmann type (P = 0.006), degree of differentiation (P = 0.004), depth of invasion (P = 0.008), lymph node metastasis (P = 0.013), TNM stage (P = 0.002) and distant metastasis (P = 0.015). The expression of CDK5 was significantly related to sex (P = 0.048) and Lauren’s classification (P = 0.011). Multivariate Cox regression analysis identified that CRM1 and CDK5 co-expression status was an independent prognostic factor for overall survival (OS) of patients with GC. Integration of CRM1 and CDK5 expression could provide additional prognostic value for OS compared with CRM1 or CDK5 expression alone (P = 0.001). CONCLUSION CRM1 and CDK5 co-expression was an independent prognostic factors for GC. Combined CRM1 and CDK5 expression could provide a prognostic model for OS of GC. PMID:28373767

  13. Novel immunological and nutritional-based prognostic index for gastric cancer

    PubMed Central

    Sun, Kai-Yu; Xu, Jian-Bo; Chen, Shu-Ling; Yuan, Yu-Jie; Wu, Hui; Peng, Jian-Jun; Chen, Chuang-Qi; Guo, Pi; Hao, Yuan-Tao; He, Yu-Long

    2015-01-01

    AIM: To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio in gastric cancer. METHODS: We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between 1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Propensity score analysis was performed to adjust variables to control for selection bias. RESULTS: Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring (hazard ratio, 1.668; 95% confidence interval: 1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage II-III disease (P = 0.019, P < 0.001), T3-T4 tumors (P < 0.001), or lymph node metastasis (P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS (P = 0.022, P = 0.030, P < 0.001, and P = 0.024, respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively. CONCLUSION: PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer. PMID:26019461

  14. Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker.

    PubMed

    Chavan, S S; He, J; Tytarenko, R; Deshpande, S; Patel, P; Bailey, M; Stein, C K; Stephens, O; Weinhold, N; Petty, N; Steward, D; Rasche, L; Bauer, M; Ashby, C; Peterson, E; Ali, S; Ross, J; Miller, V A; Stephens, P; Thanendrarajan, S; Schinke, C; Zangari, M; van Rhee, F; Barlogie, B; Mughal, T I; Davies, F E; Morgan, G J; Walker, B A

    2017-02-24

    The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.

  15. Clinical and pathological prognostic markers for survival in adult patients with post-transplant lymphoproliferative disorders in solid transplant.

    PubMed

    Oton, Ana B; Wang, Hong; Leleu, Xavier; Melhem, Mona F; George, Diane; Lacasce, Ann; Foon, Kenneth; Ghobrial, Irene M

    2008-09-01

    We sought to determine the clinical and immunohistopathological prognostic factors for overall survival (OS) in adult patients with post-transplant lymphoproliferative disorders (PTLDs). Eighty-four patients diagnosed with PTLDs between 1980 and 2004 at the University of Pittsburgh Medical Center were identified. Immunohistochemical staining was performed on tumor tissue at the time of diagnosis for the following proteins: Bcl-2, Bcl-6, c-myc and p53. The median survival for all patients was 20.8 months, 95% CI: (7.4-77.6). On univariate analysis for OS, the following poor prognostic factors were identified: age at transplant >60 years (p = 0.024), multiorgan transplant (p = 0.019), ECOG > 2 (p < 0.0001), grafted organ involvement (p < 0.0001), extranodal disease (p = 0.011), early (<1 year) PTLDs (p < 0.0001), stage IV (p = 0.0017), EBV positive (p = 0.012) and elevated white blood count (p = 0.010). Good prognostic factors included ECOG<2 (p < 0.0001), late (>1 year) PTLDs (p = 0.002), early stage at diagnosis (stages I and II, p = 0.005), nodal disease (p = 0.0053), monomorphic disease (0.0034), initial immunosuppression reduction (p = 0.0015) and use of rituximab (p = 0.045). Bcl-2 but not Bcl-6, c-myc, or p53 correlated with poor survival, p = 0.0036. This study identifies new clinical and pathological markers for poor survival in PTLDs.

  16. Biomarkers in Tumor Microenvironment? Upregulation of Fibroblast Activation Protein-α Correlates with Gastric Cancer Progression and Poor Prognosis.

    PubMed

    Hu, Mengmou; Qian, Chengjia; Hu, Ziwei; Fei, Bojian; Zhou, Haibo

    2017-01-01

    Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recent evidence points to importance of cross talk between cancer cells and the surrounding stroma on gastric cancer progression. Tumor microenvironment biomarkers thus represent a new opportunity for diagnostics innovation. Reactive stromal fibroblasts selectively express the fibroblast activation protein alpha (FAP-α), a homodimeric integral membrane gelatinase that belongs to the serine protease family. We report here that FAP-α expression is significantly elevated in gastric cancer samples by more than fivefold (p < 0.05), using transcriptome data from The Cancer Genome Atlas. Notably, the greatest FAP-α upregulation was observed in the poorly differentiated group (p < 0.001). Moreover, elevated FAP-α expression levels correlated with adverse clinical-pathological characteristics, such as diffuse histological subtype (p < 0.001), advanced pathological stage (p < 0.01) and poor survival. Functional annotation analysis demonstrated that FAP-α upregulation was associated with activation of biological processes implicated in tumor progression, including cell migration and angiogenesis pathways. These observations underscore the possible prognostic significance of FAP-α in gastric cancer and its potential as a novel biomarker for personalized medicine. We caution, however, that further multiomics, biochemical, and animal studies are necessary to ascertain the role of FAP-α as a causative and mechanistic biomarker. Based on pathway analyses, we hypothesize that gastric cancer patients exhibiting FAP-α upregulation might presumably benefit from antiangiogenic drugs in addition to standard therapeutic regimens. We call for future research focusing on the tumor microenvironment biomarkers in clinical oncology.

  17. Pyruvate Kinase M2 and Lactate Dehydrogenase A Are Overexpressed in Pancreatic Cancer and Correlate with Poor Outcome.

    PubMed

    Mohammad, Goran Hamid; Olde Damink, S W M; Malago, Massimo; Dhar, Dipok Kumar; Pereira, Stephen P

    2016-01-01

    Pancreatic cancer has a 5-year survival rate of less than 4%. Despite advances in diagnostic technology, pancreatic cancer continues to be diagnosed at a late and incurable stage. Accurate biomarkers for early diagnosis and to predict treatment response are urgently needed. Since alteration of glucose metabolism is one of the hallmarks of cancer cells, we proposed that pyruvate kinase type M2 (M2PK) and lactate dehydrogenase A (LDHA) enzymes could represent novel diagnostic markers and potential therapeutic targets in pancreatic cancer. In 266 tissue sections from normal pancreas, pancreatic cystic neoplasms, pancreatic intraepithelial neoplasia (PanIN) and cancer, we evaluated the expression of PKM2, LDHA, Ki-67 and CD8+ by immunohistochemistry and correlated these markers with clinicopathological characteristics and patient survival. PKM2 and LDHA expression was also assessed by Western blot in 10 human pancreatic cancer cell lines. PKM2 expression increased progressively from cyst through PanIN to cancer, whereas LDHA was overexpressed throughout the carcinogenic process. All but one cell line showed high expression of both proteins. Patients with strong PKM2 and LDHA expression had significantly worse survival than those with weak PKM2 and/or LDHA expression (7.0 months vs. 27.9 months, respectively, p = 0.003, log rank test). The expression of both PKM2 and LDHA correlated directly with Ki-67 expression, and inversely with intratumoral CD8+ cell count. PKM2 was significantly overexpressed in poorly differentiated tumours and both PKM2 and LDHA were overexpressed in larger tumours. Multivariable analysis showed that combined expression of PKM2 and LDHA was an independent poor prognostic marker for survival. In conclusion, our results demonstrate a high expression pattern of two major glycolytic enzymes during pancreatic carcinogenesis, with increased expression in aggressive tumours and a significant adverse effect on survival.

  18. Pyruvate Kinase M2 and Lactate Dehydrogenase A Are Overexpressed in Pancreatic Cancer and Correlate with Poor Outcome

    PubMed Central

    Mohammad, Goran Hamid; Olde Damink, S. W. M.; Malago, Massimo; Dhar, Dipok Kumar; Pereira, Stephen P.

    2016-01-01

    Pancreatic cancer has a 5-year survival rate of less than 4%. Despite advances in diagnostic technology, pancreatic cancer continues to be diagnosed at a late and incurable stage. Accurate biomarkers for early diagnosis and to predict treatment response are urgently needed. Since alteration of glucose metabolism is one of the hallmarks of cancer cells, we proposed that pyruvate kinase type M2 (M2PK) and lactate dehydrogenase A (LDHA) enzymes could represent novel diagnostic markers and potential therapeutic targets in pancreatic cancer. In 266 tissue sections from normal pancreas, pancreatic cystic neoplasms, pancreatic intraepithelial neoplasia (PanIN) and cancer, we evaluated the expression of PKM2, LDHA, Ki-67 and CD8+ by immunohistochemistry and correlated these markers with clinicopathological characteristics and patient survival. PKM2 and LDHA expression was also assessed by Western blot in 10 human pancreatic cancer cell lines. PKM2 expression increased progressively from cyst through PanIN to cancer, whereas LDHA was overexpressed throughout the carcinogenic process. All but one cell line showed high expression of both proteins. Patients with strong PKM2 and LDHA expression had significantly worse survival than those with weak PKM2 and/or LDHA expression (7.0 months vs. 27.9 months, respectively, p = 0.003, log rank test). The expression of both PKM2 and LDHA correlated directly with Ki-67 expression, and inversely with intratumoral CD8+ cell count. PKM2 was significantly overexpressed in poorly differentiated tumours and both PKM2 and LDHA were overexpressed in larger tumours. Multivariable analysis showed that combined expression of PKM2 and LDHA was an independent poor prognostic marker for survival. In conclusion, our results demonstrate a high expression pattern of two major glycolytic enzymes during pancreatic carcinogenesis, with increased expression in aggressive tumours and a significant adverse effect on survival. PMID:26989901

  19. The Prognostic Role of SIRT1-Autophagy Axis in Gastric Cancer

    PubMed Central

    Qiu, Guanglin

    2016-01-01

    Aim. Sirtuin 1 (SIRT1) can induce autophagy through deacetylation of Beclin-1 and other autophagy mediators. However, the relationship between SIRT1 and autophagy in GC has not been defined. Therefore, the aim of this study was to confirm the prognostic value of SIRT1 and Beclin-1 and their relationship in GC patients. Methods. Transmission electron microscopy (TEM) was performed to examine the autophagy in GC patients. Immunohistochemistry was used to examine the expression of SIRT1, Beclin-1 in GC, and adjacent nonneoplastic mucosa. Results. In 7 out of 8 GC patients' samples examined by TEM, more autophagic vesicles were observed in GC tissues compared to adjacent nonneoplastic mucosa tissue. A positive correlation between SIRT1 and Beclin-1 expression was observed. Furthermore, Beclin-1 or SIRT1 expression alone or their combined expression were significantly correlated with advanced clinicopathological parameters. High Beclin-1 and SIRT1 expression alone and their combined high expression predicted shorter overall survival and relapse-free survival. Both high Beclin-1 and SIRT1 expressions were independent prognostic factors for poor survival of GC. Conclusions. Based on our results we can conclude that SIRT1 and Beclin-1 expression alone or in combination can be used as prognostic indicator and may represent new therapeutic targets in GC. PMID:28070138

  20. Initial absolute lymphocyte count as a prognostic factor for outcome in acute myeloid leukemia.

    PubMed

    Le Jeune, Caroline; Bertoli, Sarah; Elhamri, Mohamed; Vergez, Francois; Borel, Cecile; Huguet, Françoise; Michallet, Mauricette; Dumontet, Charles; Recher, Christian; Thomas, Xavier

    2014-04-01

    The absolute lymphocyte count (ALC) at presentation has been associated with survival in various malignancies. However, its prognostic value in acute myeloid leukemia (AML) has not been established. In a series of 1702 newly diagnosed patients with AML, we evaluated the prognostic value of ALC at diagnosis with regard to induction chemotherapy response, disease-free survival (DFS) and overall survival (OS). Low initial ALC (< 1 × 10(9)/L) appeared as a poor prognostic factor for DFS (p = 0.01) and OS (p = 0.02), while higher ALC (> 4.5 × 10(9)/L) showed a lower response rate after one (p = 0.004) or two induction chemotherapy courses (p = 0.01). However, ALC did not appear as an independent predictor of outcome in a multivariate analysis model also including age, cytogenetics and white blood cell count. Examination of lymphocyte subsets is warranted to specify the relationship between ALC at diagnosis and clinical outcome in AML.

  1. Prognostic Value of miR-21 in Various Cancers: An Updating Meta-Analysis

    PubMed Central

    Huang, Zebo; Wang, Jian; Zhu, Wei; Shu, Yongqian; Liu, Ping

    2014-01-01

    Background Recently, more and more studies investigated the value of microRNA (miRNA) as a diagnostic or prognostic biomarker in various cancers. MiR-21 was found dysregulated in almost all types of cancers. While the prognostic role of miR-21 in many cancers has been studied, the results were not consistent. Methods We performed a meta-analysis to investigate the correlation between miR-21 and survival of general cancers by calculating pooled hazard ratios (HR) and 95% confidence intervals (CI). Results The pooled results of 63 published studies showed that elevated miR-21 was a predictor for poor survival of general carcinomas, with pooled HR of 1.91 (95%CI: 1.66–2.19) for OS, 1.42 (95% CI: 1.16–1.74) for DFS and 2.2 (95% CI: 1.64–2.96) for RFS/CSS. MiR-21 was also a prognostic biomarker in the patients who received adjuvant therapy, with pooled HR of 2.4 (95%CI: 1.18–4.9) for OS. Conclusions Our results showed that miR-21 could act as a significant biomarker in the prognosis of various cancers. Further studies are warranted before the application of the useful biomarker in the clinical. PMID:25019505

  2. Clinical significance and prognostic value of Vav1 expression in Non-small cell lung cancer

    PubMed Central

    Qi, Yao; Kong, Fan-Ming; Deng, Qi; Li, Jing-Yi; Cui, Rui; Pu, Ye-Di; Zhai, Qiong-Li; Jia, Ying-Jie; Li, Yu-Ming

    2015-01-01

    Vav1 has been reported to be involved in human cancers, however, the expression and clinical significance of Vav1 in NSCLC are not fully understood. In the present study, we examined the expression of Vav1 in 170 NSCLC patients who underwent radical resection by the immunohistochemical analyses. The association between the Vav1 expression and clinicopathological variables was analyzed. The multivariate Cox proportional hazards model was conducted to determine the prognostic value of Vav1 on the long-term survival. The results showed that the elevated Vav1 expression was correlated positively with lymph node metastasis (P<0.001), T stage (P<0.001) and poor histological differentiation (P<0.001). Patients with negative or low Vav1 expression had better prognoses than those with high Vav1 expression (P<0.001). Multivariate analysis indicated that Vav1 was independent prognostic factor for overall survival (OS) (HR 2.079, 95% CI 1.564 to 2.762, P<0.001) and disease-free survival (DFS) (HR 1.810, 95% CI 1.391 to 2.356, P<0.001). Our findings showed that overexpressed Vav1 was correlated with aggressive tumor behavior. Val1 was an independent factor for NSCLC prognosis, which may serve as a novel prognostic factor and potential target to improve the long-term outcome of NSCLC. PMID:26396925

  3. Expression and prognostic significance of zinc fingers and homeoboxes family members in renal cell carcinoma

    PubMed Central

    Jeong, Dae Cheon; Han, Myoung-Eun; Kim, Ji-Young; Liu, Liangwen; Jung, Jin-Sup; Oh, Sae-Ock

    2017-01-01

    Zinc fingers and homeoboxes (ZHX) is a transcription repressor family that contains three members; ZHX1, ZHX2, and ZHX3. Although ZHX family members have been associated with the progression of cancer, their values as prognostic factors in cancer patients have been poorly examined. Renal cell carcinoma (RCC) is a highly heterogeneous, aggressive cancer that responds variably to treatment. Thus, prognostic molecular markers are required to evaluate disease progression and to improve the survival. In clear cell RCC (ccRCC), ZHX1 and ZHX3 expression were found to be down-regulated but ZHX2 was up-regulated, and the expressions of ZHX1 and ZHX3 were significantly associated with pathological stage. Furthermore, Kaplan-Meier and multivariate regression analysis showed that reduction in the mRNA expression of ZHX1 was associated with poorer survival. Taken together, the present study shows loss of ZHX1 is correlated with ccRCC progression and suggests it is an independent prognostic marker in ccRCC. PMID:28152006

  4. Prognostic value of serum tumor abnormal protein in gastric cancer patients

    PubMed Central

    LAN, FENG; ZHU, MING; QI, QIUFENG; ZHANG, YAPING; LIU, YONGPING

    2016-01-01

    Aberrant glycosylation of protein occurs in nearly all types of cancers and has been confirmed to be associated with tumor progression, metastasis and the survival rate of patients. The present study aimed to explore the prognostic value of tumor abnormal protein (TAP) in gastric cancer patients. TAP was detected in the blood of 42 gastric cancer patients and 56 healthy volunteers by using the TAP testing kit. Univariate and multivariate Cox regression analysis were performed to evaluate the prognostic value of TAP. In total, 64.3% of gastric cancer patients were positive for TAP, and TAP was significantly correlated with poor prognosis [progression-free survival (PFS), 4.2 vs. 12.6 months; P=0.043]. TAP [hazard ratio (HR), 64.487; P<0.01), differentiation (HR, 17.279; P<0.01) and TNM stage (HR, 45.480; P<0.01) were found to be independent predictive factors for PFS. Furthermore, Kaplan-Meier curves indicated that TAP is associated with a reduced PFS in gastric cancer patients. The results of the present study therefore indicated that the TAP test has significant prognostic value for gastric cancer patients. PMID:27330802

  5. A Linearized Prognostic Cloud Scheme in NASAs Goddard Earth Observing System Data Assimilation Tools

    NASA Technical Reports Server (NTRS)

    Holdaway, Daniel; Errico, Ronald M.; Gelaro, Ronald; Kim, Jong G.; Mahajan, Rahul

    2015-01-01

    A linearized prognostic cloud scheme has been developed to accompany the linearized convection scheme recently implemented in NASA's Goddard Earth Observing System data assimilation tools. The linearization, developed from the nonlinear cloud scheme, treats cloud variables prognostically so they are subject to linearized advection, diffusion, generation, and evaporation. Four linearized cloud variables are modeled, the ice and water phases of clouds generated by large-scale condensation and, separately, by detraining convection. For each species the scheme models their sources, sublimation, evaporation, and autoconversion. Large-scale, anvil and convective species of precipitation are modeled and evaporated. The cloud scheme exhibits linearity and realistic perturbation growth, except around the generation of clouds through large-scale condensation. Discontinuities and steep gradients are widely used here and severe problems occur in the calculation of cloud fraction. For data assimilation applications this poor behavior is controlled by replacing this part of the scheme with a perturbation model. For observation impacts, where efficiency is less of a concern, a filtering is developed that examines the Jacobian. The replacement scheme is only invoked if Jacobian elements or eigenvalues violate a series of tuned constants. The linearized prognostic cloud scheme is tested by comparing the linear and nonlinear perturbation trajectories for 6-, 12-, and 24-h forecast times. The tangent linear model performs well and perturbations of clouds are well captured for the lead times of interest.

  6. Promoter DNA Methylation Pattern Identifies Prognostic Subgroups in Childhood T-Cell Acute Lymphoblastic Leukemia

    PubMed Central

    Borssén, Magnus; Palmqvist, Lars; Karrman, Kristina; Abrahamsson, Jonas; Behrendtz, Mikael; Heldrup, Jesper; Forestier, Erik; Roos, Göran; Degerman, Sofie

    2013-01-01

    Background Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided. Design and Methods Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n = 43) using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n = 32). Results Based on CpG island methylator phenotype (CIMP), T-ALL samples were subgrouped as CIMP+ (high methylation) and CIMP− (low methylation). CIMP− T-ALL patients had significantly worse overall and event free survival (p = 0.02 and p = 0.001, respectively) compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes. Conclusions We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL. PMID:23762353

  7. Prognostic and predictive response factors in colorectal cancer patients: between hope and reality.

    PubMed

    De Divitiis, Chiara; Nasti, Guglielmo; Montano, Massimo; Fisichella, Rossella; Iaffaioli, Rosario Vincenzo; Berretta, Massimiliano

    2014-11-07

    Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers worldwide. It is the second leading cause of cancer death in Western Countries. In the last decade the survival of patients with metastatic CRC has improved dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and target therapies (i.e., bevacizumab, cetuximab and panitumab), the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently. Many questions needing of right collocations and more clearness still exist regarding the prognostic factors and the predictive factors of response to therapy. Despite advances in dosing and scheduling of chemotherapy in both adjuvant and advanced settings, and a greater emphasis on early detection, the outlook still remains poor for most patients. Molecular analyses have shown that the natural history of all CRCs is not the same. Individual patients with same stage tumours may have different long term prognosis and response to therapy. In addition, some prognostic variables are likely to be more important than others. Here we review the role of prognostic factors and predictive factors according to the recently published English literature.

  8. Long noncoding RNAs are novel potential prognostic biomarkers for esophageal squamous cell carcinoma: an overview.

    PubMed

    Deng, Han-Yu; Wang, Yun-Cang; Ni, Peng-Zhi; Lin, Yi-Dan; Chen, Long-Qi

    2016-08-01

    Esophageal squamous cell carcinoma (ESCC) still has a poor prognosis. The prognostic biomarkers of ESCC are not yet well established. Long noncoding RNAs (lncRNAs) have recently been intensively investigated in various cancers including ESCC, and are found to be closely correlated to ESCC. Dysregulated expression of lncRNAs was widely observed in ESCC tumor tissue and was closely related to the tumorigenesis and progression of ESCC. More and more studies have found that lncRNAs were significantly correlated with the prognosis and diagnosis of patients with ESCC. Therefore, all those accumulating evidence indicated that lncRNAs could serve as a prognostic biomarker of ESCC. In this, we summarized the relation between lncRNAs and ESCC as well as the potential biomarker role of lncRNAs in ESCC, especially the prognostic value of lncRNAs. Our current review highlighted the need of further studies to explore the biomarker functions as well as therapeutic values of lncRNAs in ESCC.

  9. A novel inflammation-based prognostic score for patients with esophageal squamous cell carcinoma: the c-reactive protein/prognostic nutritional index ratio

    PubMed Central

    Chen, Sheng; Yang, Xun; Feng, Ji-Feng

    2016-01-01

    Background Inflammation plays a critical role in cancer prognosis. In the current study, we proposed a novel inflammation-based prognostic score, named c-reactive protein/prognostic nutritional index ratio (CRP/PNI ratio), for predicting the prognosis for patients with resectable esophageal squamous cell carcinoma (ESCC). Results The optimal cut-off value was 0.10 for CRP/PNI ratio according to the ROC curve. Patients with CRP/PNI ratio ≤0.10 had a significantly better 5-year CSS compared to CRP/PNI ratio >0.10 (44.5% vs. 15.7%, P<0.001). On multivariate analyses, we revealed that CRP/PNI ratio was a significant predictive factor of CSS (P=0.009). A nomogram could be more accuracy for CSS. The Harrell's c-index for CSS prediction was 0.688. Materials and Methods A total of 308 patients with resectable ESCC were enrolled in this retrospective study. The optimal cuf-off value for CRP/PNI ratio was calculated by a receiver operating characteristic (ROC) curve. Kaplan-Meier methods were used to analyse the cancer-specific survival (CSS). Univariate and multivariate analyses were evaluated for CSS. A nomogram was also established to predict the prognosis for CSS. Conclusion The CRP/PNI ratio is a novel and useful prognostic score for CSS in patients with resectable ESCC. PMID:27557504

  10. Diagnosing the Poor Performance of Self-Worth Protective Students: A Product of Future Outcome Uncertainty, Evaluative Threat, or Both?

    ERIC Educational Resources Information Center

    Thompson, Ted; Parker, Cathryn

    2007-01-01

    Self-worth protective students characteristically perform well on some occasions yet on other occasions they perform poorly. In this study, two accounts of the poor performance of self-worth protective students are assessed. The first is that their poor performance is an outcome of evaluative threat. The second is that their poor performance is an…

  11. Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers.

    PubMed

    Aradottir, Margret; Reynisdottir, Sigridur T; Stefansson, Olafur A; Jonasson, Jon G; Sverrisdottir, Asgerdur; Tryggvadottir, Laufey; Eyfjord, Jorunn E; Bodvarsdottir, Sigridur K

    2015-01-01

    Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5 mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A nuclear staining was estimated in relation to clinical markers and adjuvant treatment, using multivariate Cox's proportional hazards ratio regression model. BRCA2 wild-type allele loss was measured by TaqMan in BRCA2 mutated tumour samples. All statistical tests were two sided. Multivariate analysis of breast cancer-specific survival, including proliferative markers and treatment, indicated independent prognostic value of Aurora A nuclear staining for BRCA2 mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23-40.6; p = 0.028). Poor breast cancer-specific survival of BRCA2 mutation carriers was found to be significantly associated with combined Aurora A nuclear expression and BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis indicated independent prognostic value of both positive Aurora A nuclear staining (hazards ratio = 10.09; 95% confidence interval = 1.19-85.4, p = 0.034) and BRCA2 wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81-51.0, p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to be a significant prognostic marker for BRCA2 mutation carriers, independent of clinical parameters and adjuvant treatment. Our conclusion is that treatment benefits for BRCA2 mutation carriers and sporadic breast cancer patients with Aurora A positive tumours may be enhanced by giving attention to Aurora A

  12. Evaluation of prognostic markers for patients with curatively resected thoracic esophageal squamous cell carcinomas

    PubMed Central

    Ikeguchi, Masahide; Kouno, Yusuke; Kihara, Kyoichi; Suzuki, Kazunori; Endo, Kanenori; Nakamura, Seiichi; Sawada, Takashi; Shimizu, Tetsu; Matsunaga, Tomoyuki; Fukumoto, Yoji; Saito, Hiroaki

    2016-01-01

    The Glasgow Prognostic Score (GPS), neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI) are prognostic parameters for malignancies. Additionally, serum squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA 21-1) are tumor markers for squamous cell carcinoma. In the present study, the prognostic importance of these markers in patients with resectable thoracic esophageal cancer was investigated. In this retrospective study, 84 enrolled patients diagnosed with resectable clinical stage I–III thoracic esophageal squamous cell carcinomas (ESCCs) underwent thoracic esophageal resection and three-field lymph node dissection at Tottori University Hospital between January 2007 and December 2013. The correlations among preoperative patient markers (GPS, NLR, PNI, SCC-Ag and CYFRA 21-1) and the occurrence of postoperative complications and patient survival were analyzed. The operative mortality was 2.4%, and morbidity was 42.9%. Strong correlations between occurrence of postoperative complications and open thoracotomy (P=0.083) and high-serum CYFRA 21-1 (P=0.007) were observed. In 15 patients with high-serum CYFRA 21-1, postoperative complications were detected in 11 of them (73.3%); on the other hand, complications occurred in 25 of 69 (36.2%) with low-serum CYFRA 21-1. The 5-year disease-free survival rate and 5-year overall survival rate of all the patients were 52.2 and 50.8%, respectively. Among the prognostic parameters, preoperative high NLR was determined to be a poor prognostic factor, independent of the tumor stage in the multivariate analysis. These results may indicate that, in patients with preoperative high-serum CYFRA 21-1, more attention should be paid to the occurrence of postoperative complications. Therefore, in such cases, anastomosis between blood vessels of the substitute esophagus and cervical vessels would be recommended. Furthermore, in patients with high preoperative NLR, effective adjuvant

  13. Evaluation of prognostic factors in liver-limited metastatic colorectal cancer: a preplanned analysis of the FIRE-1 trial

    PubMed Central

    Giessen, C; Fischer von Weikersthal, L; Laubender, R P; Stintzing, S; Modest, D P; Schalhorn, A; Schulz, C; Heinemann, V

    2013-01-01

    Background: Liver-limited disease (LLD) denotes a specific subgroup of metastatic colorectal cancer (mCRC) patients. Patients and Methods: A total of 479 patients with unresectable mCRC from an irinotecan-based randomised phase III trial were evaluated. Patients with LLD and non-LLD and hepatic resection were differentiated. Based on baseline patient characteristic, prognostic factors for hepatic resection were evaluated. Furthermore, prognostic factors for median overall survival (OS) were estimated via Cox regression in LLD patients. Results: Secondary liver resection was performed in 38 out of 479 patients (resection rate: 7.9%). Prognostic factors for hepatic resection were LLD, lactate dehydrogenase (LDH), node-negative primary, alkaline phosphatase (AP) and Karnofsky performance status (PS). Median OS was significantly increased after hepatic resection (48 months), whereas OS in LLD (17 months) and non-LLD (19 months) was comparable in non-resected patients. With the inapplicability of Koehne's risk classification in LLD patients, a new score based on only the independent prognostic factors LDH and white blood cell (WBC) provided markedly improved information on the outcome. Conclusion: Patients undergoing hepatic resection showed favourable long-term survival, whereas non-resected LLD patients and non-LLD patients did not differ with regard to progression-free survival and OS. The LDH levels and WBC count were confirmed as prognostic factors and provide a useful and simple score for OS-related risk stratification also in LLD. PMID:23963138

  14. Predicting the onset of psychosis in patients at clinical high risk: practical guide to probabilistic prognostic reasoning.

    PubMed

    Fusar-Poli, P; Schultze-Lutter, F

    2016-02-01

    Prediction of psychosis in patients at clinical high risk (CHR) has become a mainstream focus of clinical and research interest worldwide. When using CHR instruments for clinical purposes, the predicted outcome is but only a probability; and, consequently, any therapeutic action following the assessment is based on probabilistic prognostic reasoning. Yet, probabilistic reasoning makes considerable demands on the clinicians. We provide here a scholarly practical guide summarising the key concepts to support clinicians with probabilistic prognostic reasoning in the CHR state. We review risk or cumulative incidence of psychosis in, person-time rate of psychosis, Kaplan-Meier estimates of psychosis risk, measures of prognostic accuracy, sensitivity and specificity in receiver operator characteristic curves, positive and negative predictive values, Bayes' theorem, likelihood ratios, potentials and limits of real-life applications of prognostic probabilistic reasoning in the CHR state. Understanding basic measures used for prognostic probabilistic reasoning is a prerequisite for successfully implementing the early detection and prevention of psychosis in clinical practice. Future refinement of these measures for CHR patients may actually influence risk management, especially as regards initiating or withholding treatment.

  15. Nuclear osteopontin-c is a prognostic breast cancer marker

    PubMed Central

    Zduniak, K; Ziolkowski, P; Ahlin, C; Agrawal, A; Agrawal, S; Blomqvist, C; Fjällskog, M-L; Weber, G F

    2015-01-01

    Background: Although Osteopontin has been known as a marker for cancer progression, the elevated production of this cytokine is not specific for cancer. We have identified the splice variant Osteopontin-c as being absent from healthy tissue but associated with about 75% of breast cancer cases. However, in previous studies of Osteopontin-c, follow-up information was not available. Methods: Here we have analysed 671 patients, comprising a cohort of 291 paraffin blocks plus a population-based case-control study of 380 arrayed breast tumor tissues. Results: We find that high staining intensity of nuclear Osteopontin-c is strongly associated with mortality in patients with early breast cancer. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome. By contrast, total Osteopontin does not correlate with prognosis. These diverse assessments of Osteopontin also do not correlate with each other, suggesting distinct expression patterns for the variant forms. Consistent with its role in tumor progression, not tumor initiation, Osteopontin-c is not correlated with proliferation markers (Ki-67, cyclin A, cyclin B, cyclin E and cyclin D), neither is it correlated with ER, PR or HER2. Conclusions: The addition of Osteopontin-c immunohistochemistry to standard pathology work-ups may have prognostic benefit in early breast cancer diagnosis. PMID:25625274

  16. Fault diagnosis and prognostic of solid oxide fuel cells

    NASA Astrophysics Data System (ADS)

    Wu, XiaoJuan; Ye, Qianwen

    2016-07-01

    One of the major hurdles for solid oxide fuel cell (SOFC) commercialization is poor long-term performance and durability. Accurate fault diagnostic and prognostic technologies are two important tools to improve SOFC durability. In literature, plenty of diagnosis techniques for SOFC systems have been successfully designed. However, no literature studies SOFC fault prognosis approaches. In this paper a unified fault diagnosis and prognosis strategy is presented to identify faults (anode poisoning, cathode humidification or normal) and predict the remaining useful life for SOFC systems. Using a squares support vector machine (LS-SVM) classifier, a diagnosis model is built to identify SOFC different types of faults. After fault detection, two hidden semi-Mark models (HSMMs) are respectively employed to estimate SOFC remaining useful life in the case of anode poisoning and cathode humidification. The simulation results show that the fault recognition rates with the LS-SVM model are at best 97%, and the predicted error of the remaining useful life is within ±20%.

  17. Age as a prognostic factor in carcinoma of the cervix.

    PubMed

    Lybeert, M L; Meerwaldt, J H; van Putten, W L

    1987-06-01

    To investigate whether age is a prognostic factor in patients with carcinoma of the cervix, a retrospective study was undertaken of 261 patients, aged 45 years or less, who were referred to the Rotterdamsch Radio-Therapeutisch Instituut (RRTI) between 1973 and 1982. Patients were referred for either primary treatment--surgery or radiotherapy--or for adjuvant radiotherapy. Overall 5-year survival figures were rather low, which may be explained by negative patient selection as the RRTI is a referral hospital: stage IB, 72%; stage IIA; 61%; stage IIB; 52%; stage III; 29%. A particular poor survival was noted for patients (n = 22) aged 28 or less. Overall 5-year survival of these patients was only 39% in contrast to 67% 5-year survival of older patients. This difference was highly significant (p less than 0.002). Even if corrected for stage, very young patients had a poorer prognosis (stage IB: 45% versus 75% 5-year survival of older patients). Within the older age group, no trend towards a better prognosis with increasing age could be identified. As a treatment was similar for all patients, no explanation is available for this observation.

  18. [Prognostic factors in Guillain-Barré syndrome].

    PubMed

    Kaida, Kenichi

    2013-01-01

    The prognosis of Guillain-Barré syndrome (GBS) is not as good as might be expected. Among GBS patients, 30% do not respond to intravenous immunoglobulin therapy (IVIg) and 10% may worsen after initial treatment (treatment-related fluctuation). Recent prospective trials show that 16% of GBS patients are unable to walk independently a year after onset of the disease. The prognosis of GBS is influenced by clinical, electrophysiological and biological factors, of which the clinical factors are most important. The Erasmus GBS Respiratory Insufficiency Score (EGRIS) and the modified EGOS (Erasmus GBS Outcome Score) are very useful for prediction of mechanical ventilation or aided walking. A small increase in serum IgG (delta IgG) two weeks after IVIg treatment is useful as a biological prognostic marker that is significantly associated with slow recovery and aided walking at 6 months. Use of these factors makes it possible to predict the prognosis of GBS patients, and to identify patients with a poor prognosis in the early phase of the disease and provide these patients with intensive treatment. An accurate prediction of the level of disability is important for improvement of the prognosis of GBS.

  19. Outcome and Prognostic Factors of Radiation Therapy for Medulloblastoma

    SciTech Connect

    Rieken, Stefan; Mohr, Angela; Habermehl, Daniel; Welzel, Thomas; Lindel, Katja; Witt, Olaf; Kulozik, Andreas E.; Wick, Wolfgang; Debus, Juergen; Combs, Stephanie E.

    2011-11-01

    Purpose: To investigate treatment outcome and prognostic factors after radiation therapy in patients with medulloblastomas (MB). Methods and Materials: Sixty-six patients with histologically confirmed MB were treated at University Hospital of Heidelberg between 1985 and 2009. Forty-two patients (64%) were pediatric ({<=}18 years), and 24 patients (36%) were adults. Tumor resection was performed in all patients and was complete in 47%. All patients underwent postoperative craniospinal irradiation (CSI) delivering a median craniospinal dose of 35.5 Gy with additional boosts to the posterior fossa up to 54.0 Gy. Forty-seven patients received chemotherapy, including 21 in whom chemotherapy was administered before CSI. Statistical analysis was performed using the log-rank test and the Kaplan-Meier method. Results: Median follow-up was 93 months. Overall survival (OS) and local and distant progression-free survival (LPFS and DPFS) were 73%, 62%, and 77% at 60 months. Both local and distant recurrence predisposed for significantly reduced OS. Macroscopic complete tumor resection, desmoplastic histology and early initiation of postoperative radiation therapy within 28 days were associated with improved outcome. The addition of chemotherapy did not improve survival rates. Toxicity was moderate. Conclusions: Complete resection of MB followed by CSI yields long survival rates in both children and adults. Delayed initiation of CSI is associated with poor outcome. Desmoplastic histology is associated with improved survival. The role of chemotherapy, especially in the adult population, must be further investigated in clinical studies.

  20. Prognostic value of a 92-probe signature in breast cancer.

    PubMed

    Akter, Salima; Choi, Tae Gyu; Nguyen, Minh Nam; Matondo, Abel; Kim, Jin-Hwan; Jo, Yong Hwa; Jo, Ara; Shahid, Muhammad; Jun, Dae Young; Yoo, Ji Youn; Nguyen, Ngoc Ngo Yen; Seo, Seong-Wook; Ali, Liaquat; Lee, Ju-Seog; Yoon, Kyung-Sik; Choe, Wonchae; Kang, Insug; Ha, Joohun; Kim, Jayoung; Kim, Sung Soo

    2015-06-20

    Clinical applications of gene expression signatures in breast cancer prognosis still remain limited due to poor predictive strength of single training datasets and appropriate invariable platforms. We proposed a gene expression signature by reducing baseline differences and analyzing common probes among three recent Affymetrix U133 plus 2 microarray data sets. Using a newly developed supervised method, a 92-probe signature found in this study was associated with overall survival. It was robustly validated in four independent data sets and then repeated on three subgroups by incorporating 17 breast cancer microarray datasets. The signature was an independent predictor of patients' survival in univariate analysis [(HR) 1.927, 95% CI (1.237-3.002); p < 0.01] as well as multivariate analysis after adjustment of clinical variables [(HR) 7.125, 95% CI (2.462-20.618); p < 0.001]. Consistent predictive performance was found in different multivariate models in increased patient population (p = 0.002). The survival signature predicted a late metastatic feature through 5-year disease free survival (p = 0.006). We identified subtypes within the lymph node positive (p < 0.001) and ER positive (p = 0.01) patients that best reflected the invasive breast cancer biology. In conclusion using the Common Probe Approach, we present a novel prognostic signature as a predictor in breast cancer late recurrences.

  1. Clinical Characteristics and Treatment Outcomes of Primary Pulmonary Artery Sarcoma in Korea

    PubMed Central

    2016-01-01

    Pulmonary artery sarcomas (PAS) are rare malignant neoplasms. Right heart failure due to tumour location is the main cause of death in PAS patients. The hemodynamic influence of PAS may effect prognosis, but this has not been proven. We aimed to identify the clinical characteristics and prognostic factors of PAS in Korea, their association with pulmonary hypertension (PH). PAS patients treated at the Asan Medical Center between 2000 and 2014 were reviewed. We examined demographic characteristics, diagnostic and treatment modalities. Potential prognostic factors were evaluated by univariate and multivariate analysis. Twenty patients were diagnosed with PAS. Ten patients were male, the median age was 54 years (range, 33–75 years). The most common symptom observed was dyspnea (65%). The most common histologic type was spindle cell sarcoma (30%). Ten patients had a presumptive diagnosis of pulmonary embolism (PE) and received anticoagulation therapy. Seventeen patients underwent surgery, but only 5 patients had complete resection. Eleven patients received post-operative treatment (chemotherapy = 3, radiotherapy = 5, chemoradiotherapy = 3). PH was observed in 12 patients before treatment and in 6 patients after treatment. Overall median survival was 24 months. Post-treatment PH was associated with poor prognosis (HR 9.501, 95% CI 1.79–50.32; P = 0.008) while chemotherapy was negatively associated with mortality (HR 0.102, 95% CI 0.013–0.826; P = 0.032) in univariate analysis. Post-treatment PH was also associated with poor prognosis in multivariate analysis (HR 5.7, 95% CI 1.08–30.91; P = 0.041). PAS patients are frequently misdiagnosed with PE in Korea. Post-treatment PH is associated with a poor prognosis. PMID:27709853

  2. Cyclophilin A in Ruptured Intracranial Aneurysm: A Prognostic Biomarker.

    PubMed

    Kao, Hung-Wen; Lee, Kwo-Whei; Chen, Wei-Liang; Kuo, Chen-Ling; Huang, Ching-Shan; Tseng, Wan-Min; Liu, Chin-San; Lin, Ching-Po

    2015-09-01

    Cyclophilin A (CyPA), an oxidative stress-induced factor, was found to play an important role in the aneurysm formation. Our working hypothesis was that the plasma level of CyPA in ruptured intracranial aneurysm could predict the neurological outcome. From 2011 to 2013, a total of 36 patients with ruptured saccular intracranial aneurysm were recruited in our study. Before coil embolization, we draw blood samples at the orifice of a culprit aneurysm and in the remote peripheral vein for measurements of the CyPA levels. We utilized the modified Rankin scale 30 days after aneurysm rupture as the outcome measure. Generalized linear models were used to estimate the adjusted odds ratios of the poor neurological outcome given the presence of high plasma level of CyPA. The aneurysmal and venous CyPA levels were significantly associated with the initial clinical severity (P = 0.004 and 0.03, respectively) and 30-day outcome (P = 0.01 and 0.02, respectively). The aneurysmal CyPA levels modestly correlated with age and high Fisher grade (ρ = 0.39 and 0.41; P = 0.02 and 0.01, respectively). The aneurysmal CyPA levels strongly correlated with the venous counterpart (ρ = 0.89; P < 0.001). Patients with high levels of aneurysmal CyPA were 15.66 times (95% CI, 1.48-166.24; P = 0.02) more likely to have worse neurological outcome than those with the low levels after adjustment of the age, gender, and the documented confounding factors. High plasma level of CyPA is a significant prognostic biomarker for poor neurological outcome in patients with ruptured intracranial aneurysm.

  3. Prognostic Factors for Myositis-Associated Interstitial Lung Disease

    PubMed Central

    Fujisawa, Tomoyuki; Hozumi, Hironao; Kono, Masato; Enomoto, Noriyuki; Hashimoto, Dai; Nakamura, Yutaro; Inui, Naoki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Shirai, Toshihiro; Yasuda, Kazumasa; Hayakawa, Hiroshi; Suda, Takafumi

    2014-01-01

    Background Interstitial lung disease (ILD) is a common manifestation of polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM); however, little is known about the factors influencing the prognosis for PM/DM/CADM-associated ILD. (PM/DM/CADM-ILD). The aim of the present study is to assess prognostic factors for PM/DM/CADM-ILD. Methods The clinical features and survival of 114 consecutive patients diagnosed with PM/DM/CADM-ILD (39 men and 75 women; median age, 56 years) were analyzed retrospectively. Results The study group included 30 PM-associated ILD, 41 DM-associated ILD, and 43 CADM-associated ILD cases. The clinical presentation of ILD was acute/subacute form in 59 patients (51.8%) and chronic form in 55 patients (48.2%). The major pulmonary symptoms were dyspnea, cough, and fever. High-resolution computed tomography frequently revealed ground-glass opacities, traction bronchiectasis, and consolidation. Most of the patients were treated with corticosteroids or corticosteroids in combination with immunosuppressive agents. The all-cause mortality was 27.2%. Acute/subacute form, % forced vital capacity (FVC), age, % of neutrophils in bronchoalveolar lavage (BAL) fluid, and a diagnosis of CADM (vs. PM) were significantly associated with poor outcome in univariate Cox proportional hazards models. Multivariate Cox proportional hazards analysis validated acute/subacute ILD, %FVC, age, and diagnosis of CADM (vs. PM) as significant predictors of overall mortality. Patients with acute/subacute ILD had a much lower survival rate than those with the chronic form (p<0.001). Patients with CADM-ILD had a lower survival rate than those with PM-ILD (p = 0.034). Conclusions Acute/subacute form, older age, lower level of FVC and diagnosis of CADM predict poor outcome in PM/DM/CADM-ILD. PMID:24905449

  4. Suppressor of cytokine signaling 1 gene mutation status as a prognostic biomarker in classical Hodgkin lymphoma.

    PubMed

    Lennerz, Jochen K; Hoffmann, Karl; Bubolz, Anna-Maria; Lessel, Davor; Welke, Claudia; Rüther, Nele; Viardot, Andreas; Möller, Peter

    2015-10-06

    Suppressor of cytokine signaling 1 (SOCS1) mutations are among the most frequent somatic mutations in classical Hodgkin lymphoma (cHL), yet their prognostic relevance in cHL is unexplored. Here, we performed laser-capture microdissection of Hodgkin/Reed-Sternberg (HRS) cells from tumor samples in a cohort of 105 cHL patients. Full-length SOCS1 gene sequencing showed mutations in 61% of all cases (n = 64/105). Affected DNA-motifs and mutation pattern suggest that many of these SOCS1 mutations are the result of aberrant somatic hypermutation and we confirmed expression of mutant alleles at the RNA level. Contingency analysis showed no significant differences of patient-characteristics with HRS-cells containing mutant vs. wild-type SOCS1. By predicted mutational consequence, mutations can be separated into those with non-truncating point mutations ('minor' n = 49/64 = 77%) and those with length alteration ('major'; n = 15/64 = 23%). Subgroups did not differ in clinicopathological characteristics; however, patients with HRS-cells that contained SOCS1 major mutations suffered from early relapse and significantly shorter overall survival (P = 0.03). The SOCS1 major status retained prognostic significance in uni-(P = 0.016) and multivariate analyses (P = 0.005). Together, our data indicate that the SOCS1 mutation type qualifies as a single-gene prognostic biomarker in cHL.

  5. New prognostic factors and scoring system for patients with skeletal metastasis

    PubMed Central

    Katagiri, Hirohisa; Okada, Rieko; Takagi, Tatsuya; Takahashi, Mitsuru; Murata, Hideki; Harada, Hideyuki; Nishimura, Tetsuo; Asakura, Hirofumi; Ogawa, Hirofumi

    2014-01-01

    The aim of this study was to update a previous scoring system for patients with skeletal metastases, that was proposed by Katagiri et al. in 2005, by introducing a new factor (laboratory data) and analyzing a new patient cohort. Between January 2005 and January 2008, we treated 808 patients with symptomatic skeletal metastases. They were prospectively registered regardless of their treatments, and the last follow-up evaluation was performed in 2012. There were 441 male and 367 female patients with a median age of 64 years. Of these patients, 749 were treated nonsurgically while the remaining 59 underwent surgery for skeletal metastasis. A multivariate analysis was conducted using the Cox proportional hazards model. We identified six significant prognostic factors for survival, namely, the primary lesion, visceral or cerebral metastases, abnormal laboratory data, poor performance status, previous chemotherapy, and multiple skeletal metastases. The first three factors had a larger impact than the remaining three. The prognostic score was calculated by adding together all the scores for individual factors. With a prognostic score of ≥7, the survival rate was 27% at 6 months, and only 6% at 1 year. In contrast, patients with a prognostic score of ≤3 had a survival rate of 91% at 1 year, and 78% at 2 years. Comparing the revised system with the previous one, there was a significantly lower number of wrongly predicted patients using the revised system. This revised scoring system was able to predict the survival rates of patients with skeletal metastases more accurately than the previous system and may be useful for selecting an optimal treatment. PMID:25044999

  6. New prognostic factors and scoring system for patients with skeletal metastasis.

    PubMed

    Katagiri, Hirohisa; Okada, Rieko; Takagi, Tatsuya; Takahashi, Mitsuru; Murata, Hideki; Harada, Hideyuki; Nishimura, Tetsuo; Asakura, Hirofumi; Ogawa, Hirofumi

    2014-10-01

    The aim of this study was to update a previous scoring system for patients with skeletal metastases, that was proposed by Katagiri et al. in 2005, by introducing a new factor (laboratory data) and analyzing a new patient cohort. Between January 2005 and January 2008, we treated 808 patients with symptomatic skeletal metastases. They were prospectively registered regardless of their treatments, and the last follow-up evaluation was performed in 2012. There were 441 male and 367 female patients with a median age of 64 years. Of these patients, 749 were treated nonsurgically while the remaining 59 underwent surgery for skeletal metastasis. A multivariate analysis was conducted using the Cox proportional hazards model. We identified six significant prognostic factors for survival, namely, the primary lesion, visceral or cerebral metastases, abnormal laboratory data, poor performance status, previous chemotherapy, and multiple skeletal metastases. The first three factors had a larger impact than the remaining three. The prognostic score was calculated by adding together all the scores for individual factors. With a prognostic score of ≥7, the survival rate was 27% at 6 months, and only 6% at 1 year. In contrast, patients with a prognostic score of ≤3 had a survival rate of 91% at 1 year, and 78% at 2 years. Comparing the revised system with the previous one, there was a significantly lower number of wrongly predicted patients using the revised system. This revised scoring system was able to predict the survival rates of patients with skeletal metastases more accurately than the previous system and may be useful for selecting an optimal treatment.

  7. Adverse Prognostic Impact of Bone Marrow Microvessel Density in Multiple Myeloma

    PubMed Central

    Lee, Nuri; Lee, Hyewon; Moon, Soo Young; Sohn, Ji Yeon; Hwang, Sang Mee; Yoon, Ok Jin; Youn, Hye Sun

    2015-01-01

    Background Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM. Methods The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR). Results Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including β2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; P=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (P=0.025). However, no difference was observed in the OS (P=0.428). Conclusions Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM. PMID:26354343

  8. Prognostic and therapeutic value of mitochondrial serine hydroxyl-methyltransferase 2 as a breast cancer biomarker.

    PubMed

    Zhang, Lahong; Chen, Zhaojun; Xue, Dan; Zhang, Qi; Liu, Xiyong; Luh, Frank; Hong, Liquan; Zhang, Hang; Pan, Feng; Liu, Yuhua; Chu, Peiguo; Zheng, Shu; Lou, Guoqiang; Yen, Yun

    2016-11-01

    Mitochondrial serine hydroxylmethyltransferase 2 (SHMT2) is a key enzyme in the serine/glycine synthesis pathway. SHMT2 has been implicated as a critical component for tumor cell survival. The aim of the present study was to evaluate the prognostic value and efficiency of SHMT2 as a biomarker in patients with breast cancer. Individual and pooled survival analyses were performed on five independent breast cancer microarray datasets. Gene signatures enriched by SHMT2 were also analyzed in these datasets. SHMT2 protein expression was detected using immunohistochemistry (IHC) assay in 128 breast cancer cases. Gene set enrichment analysis revealed that SHMT2 was significantly associated with gene signatures of mitochondrial module, cancer invasion, metastasis and poor survival among breast cancer patients (p<0.05). The clinical relevance of SHMT2 was validated on IHC data. The mitochondrial localization of SHMT2 protein was visualized on IHC staining. Independent and pooled analysis confirmed that SHMT2 expression was associated with breast cancer tumor aggressiveness (TNM staging and Elson grade) in a dose-dependent manner (p<0.05). The prognostic performance of SHMT2 mRNA was comparable to other gene signatures and proved superior to TNM staging. Further analysis results indicated that SHMT2 had better prognostic value for estrogen receptor (ER)-negative breast cancer patients, compared to ER-positive patients. In cases involving stage IIb breast cancer, chemotherapy significantly extended survival time among patients with high SHMT2 expression. These results indicate that SHMT2 may be a valuable prognostic biomarker in ER-negative breast cancer cases. Furthermore, SHMT2 may be a potential target for breast cancer treatment and drug discovery.

  9. Moderate HER2 expression as a prognostic factor in hormone receptor positive breast cancer.

    PubMed

    Eggemann, Holm; Ignatov, Tanja; Burger, Elke; Kantelhardt, Eva Johanna; Fettke, Franziska; Thomssen, Christoph; Costa, Serban Dan; Ignatov, Atanas

    2015-10-01

    Overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis in breast cancer and predicts response to anti-HER2 therapy in breast cancer. The prognostic relevance of moderate expression of HER2 is unclear. Data of 9872 patients with primary nonmetastatic breast cancer from the cancer registries of Magdeburg and Halle, Germany, were analyzed retrospectively. A total of 5907 patients with complete data sets including follow-up were eligible for analysis. HER2 status was determined as recommended by international guidelines. Of 5907 patients investigated, 5023 (68.4%) had HER2 0 and 1+ expression and 884 (12.0%) had HER2 (2+)/HER2- expression. Patients with hormone receptor positive (HR+) and HER2 (2+) tumors had a shorter median disease-free survival (DFS; P<0.0001) and breast cancer specific survival (BCSS; P=0.019) than HR+ patients with HER2 (0/1+) tumors. Among patients with HR- breast cancer there was no significant difference between HER2 (2+) and HER2 (0/1+) tumors. In multivariate analysis after adjustment for other prognostic factors, HER2 (2+) status remained an unfavorable prognostic factor for DFS (hazard ratio (HR)=1.217, 95% CI=1.052-1.408; P=0.008) but not for BCSS (HR=1.045, 95% CI=0.926-1.178; P=0.474). The HER2 (2+) status is an unfavorable prognostic factor for survival of patients with HR+ breast cancer. The impact of anti-HER2 therapy in this group of patients should be evaluated.

  10. Expression and Prognostic Value of Oct-4 in Astrocytic Brain Tumors

    PubMed Central

    Dahl Sørensen, Mia; Winther Kristensen, Bjarne

    2016-01-01

    Background Glioblastomas are the most frequent type of malignant primary brain tumor with a median overall survival less than 15 months. Therapy resistance of glioblastomas has been attributed to the presence of tumor initiating stem-like cells (TSCs). TSC-related markers have therefore been suggested to have promising potentials as prognostic markers in gliomas. Methodology/Principal Findings The aim of the present study was to investigate the expression and prognostic impact of the TSC-related marker Oct-4 in astrocytic brain tumors of increasing grade. In total 114 grade II, III and IV astrocytic brain tumors were immunohistochemically stained for Oct-4, and the fraction and intensity of Oct-4 positive cells were determined by morphometric analysis of full tumor sections. Oct-4 was expressed in all tumors, and the Oct-4 positive cell fraction increased with tumor grade (p = 0.045). There was no association between survival and Oct-4 positive cell fraction, neither when combining all tumor grades nor in analysis of individual grades. Oct-4 intensity was not associated with grade, but taking IDH1 status into account we found a tendency for high Oct-4 intensity to be associated with poor prognosis in anaplastic astrocytomas. Double immunofluorescence stainings showed co-localization in the perivascular niches of Oct-4 and two other TSC markers CD133 and nestin in glioblastomas. In some areas Oct-4 was expressed independently of CD133 and nestin. Conclusions In conclusion, high Oct-4 fraction was associated with tumor malignancy, but seemed to be without independent prognostic influence in glioblastomas. Identification of a potential prognostic value in anaplastic astrocytomas requires additional studies using larger patient cohorts. PMID:28030635

  11. CD147 and Ki-67 overexpression confers poor prognosis in squamous cell carcinoma of oral tongue: A tissue microarray study

    PubMed Central

    Yu, Yau-Hua; Morales, Jose; Feng, Lei; Lee, J. Jack; El-Naggar, Adel K.; Vigneswaran, Nadarajah

    2015-01-01

    Squamous cell carcinoma of the oral tongue (SCCOT) exhibits high risk for recurrence and regional metastasis even after surgical resection. We assessed the clinicopathologic and prognostic significance of a group of functionally related biomarkers. We used a tissue microarray consisting SCCOT from 32 patients for this study. These patients were treated at the UT- M.D. Anderson Cancer Center from 1995 to 2008. Biomarker expression levels were examined by immunohistochemistry and graded semiquantitatively to determine their prognostic significance. CD147 and Tp63 expressions were significantly associated with a higher T-stage and Ki-67 labelling index as well as shorter overall survival (OS). Expression of Tp63 associated positively with poorly-differentiated histology. There was significant association of Tp63 with the expression levels of CD147 and Glut-1. Glut-1 overexpression was marginally associated with a higher T-stage. There was no prognostic significance of CD44v6 expression in SCCOT. SCCOT with CD147 overexpression in combination with high Ki-67 labelling index had poor OS. CD147 and Ki-67 overexpression is associated with aggressive disease with poor prognosis in SCCOT. PMID:25747176

  12. Prognostic Factors in Sudden Sensorineural Hearing Loss

    PubMed Central

    Atay, Gamze; Kayahan, Bahar; çınar, Betül çiçek; Saraç, Sarp; Sennaroğlu, Levent

    2016-01-01

    Background: Sudden sensorineural hearing loss (SSNHL) is still a complex and challenging process which requires clinical evidence regarding its etiology, treatment and prognostic factors. Therefore, determination of prognostic factors might aid in the selection of proper treatment modality. Aims: The aim of this study is to analyze whether there is correlation between SSNHL outcomes and (1) systemic steroid therapy, (2) time gap between onset of symptoms and initiation of therapy and (3) audiological pattern of hearing loss. Study Design: Retrospective chart review. Methods: Patients diagnosed at our clinic with SSNHL between May 2005 and December 2011 were reviewed. A detailed history of demographic features, side of hearing loss, previous SSNHL and/or ear surgery, recent upper respiratory tract infection, season of admission, duration of symptoms before admission and the presence of co-morbid diseases was obtained. Radiological and audiological evaluations were recorded and treatment protocol was assessed to determine whether systemic steroids were administered or not. Treatment started ≤5 days was regarded as “early” and >5 days as “delayed”. Initial audiological configurations were grouped as “upward sloping”, “downward sloping”, “flat” and “profound” hearing loss. Significant recovery was defined as thresholds improved to the same level with the unaffected ear or improved ≥30 dB on average. Slight recovery was hearing improvement between 10–30dB on average. Hearing recovery less than 10 dB was accepted as unchanged. Results: Among the 181 patients who met the inclusion criteria, systemic steroid was administered to 122 patients (67.4%), whereas 59 (32.6%) patients did not have steroids. It was found that steroid administration did not have any statistically significant effect in either recovered or unchanged hearing groups. Early treatment was achieved in 105 patients (58%) and 76 patients (42%) had delayed treatment. Recovery

  13. Elevated serum levels of vascular endothelial growth factor predict a poor prognosis of platinum-based chemotherapy in non-small cell lung cancer

    PubMed Central

    Zang, Jialan; Hu, Yong; Xu, Xiaoyue; Ni, Jie; Yan, Dali; Liu, Siwen; He, Jieyu; Xue, Jing; Wu, Jianzhong; Feng, Jifeng

    2017-01-01

    Aim This study was designed to investigate the predictive and prognostic values of serum vascular endothelial growth factor (VEGF) level in non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Methods Patients’ peripheral blood samples were collected prior to chemotherapy and after 1 week of the third cycle of combination chemotherapy. Serum VEGF levels were evaluated through Luminex multiplex technique. Between September 2011 and August 2015, a total of 135 consecutive advanced or recurrent histologically verified NSCLC patients were enrolled in the study. Moreover, all the patients received platinum-based combination chemotherapy as a first-line treatment. Results No significant associations were found between pretreatment serum VEGF levels and clinical characteristics, such as sex (P=0.0975), age (P=0.2522), stage (P=0.1407), lymph node metastasis (P=0.6409), tumor location (P=0.3520), differentiated degree (P=0.5608), pathological (histological) type (P=0.4885), and response to treatment (P=0.9859). The VEGF load per platelet (VEGFPLT) levels were not correlated with sex, age, primary tumor site, and pathological type in NSCLC patients (all P>0.05). The median survival time of progression-free survival (PFS) was 6.407 and 5.29 months in the low and high groups, respectively, when using 280 pg/mL VEGF level as the cutoff point (P=0.024). Conclusion In conclusion, the serum VEGF levels were found to be a poor prognostic biomarker for the efficacy of platinum-based chemotherapy in terms of PFS, but it was not shown to be a suitable predictive marker for clinical response to platinum-based chemotherapy. PMID:28176920

  14. Decreased pretreatment lymphocyte/monocyte ratio is associated with poor prognosis in stage Ib1–IIa cervical cancer patients who undergo radical surgery

    PubMed Central

    Chen, Liang; Zhang, Fang; Sheng, Xiu-gui; Zhang, Shi-qian

    2015-01-01

    Background Recently, pretreatment monocyte counts and the lymphocyte/monocyte ratio (LMR) have been proven to be significantly associated with the clinical outcomes of several types of cancer. In this study, we analyzed the prognostic significance of the LMR in stage Ib1–IIa cervical cancer patients who underwent a radical operation. Methods A total of 485 patients with stage Ib1–IIa cervical cancer were included in this retrospective study. We evaluated the prognostic values of the absolute lymphocyte count, absolute monocyte count, and LMR by applying receiver operating characteristic curves. Kaplan–Meier curves and multivariate Cox proportional analyses were used to determine the recurrence-free survival (RFS) and overall survival (OS). Results The area under the curve was 0.640 for the RFS and 0.647 for the OS using the LMR. In the univariate analysis, an elevated preoperative LMR was significantly associated with an increased RFS (hazard ratio [HR], 0.373; 95% confidence interval [CI]: 0.247–0.563; P<0.001), and this result remained significant in the multivariate analysis (HR, 0.439; 95% CI: 0.279–0.693; P<0.001). In the univariate analysis, an elevated LMR was also significantly associated with an increased OS (HR, 0.381; 95% CI: 0.233–0.622; P<0.001), and the significance persisted in the multivariate analysis (HR, 0.417; 95% CI: 0.244–0.714; P=0.001). Conclusion A decreased pretreatment LMR is associated with a poor prognosis in stage Ib1–IIa cervical cancer patients who undergo a radical operation. A prospective study is warranted for further validation of our findings. PMID:26089685

  15. Involvement of Difference in Decrease of Hemoglobin Level in Poor Prognosis of Stage I and II Nasopharyngeal Carcinoma: Implication in Outcome of Radiotherapy

    SciTech Connect

    Gao Jin; Tao Yalan; Li Guo; Yi Wei; Xia Yunfei

    2012-03-15

    Purpose: To investigate the effect of hemoglobin (Hb) concentration and the difference in its decrease during treatment on outcome of radiotherapy (RT) alone for patients with Stage I and II nasopharyngeal carcinoma. Methods and Materials: A total of 572 patients with Stage I-II nasopharyngeal carcinoma with RT alone between January 2001 and December 2004 were retrospectively analyzed. Patient characteristics, tumor variables, and Hb level, including pre-RT Hb, mid-RT Hb, and dynamic change of Hb between pre- and post- RT and its difference in decrease ( White-Up-Pointing-Small-Triangle Hb) were subjected to univariate and multivariable analysis to identify factors that predict disease-specific survival (DSS), local regional recurrence-free survival (LRFS), and metastases-free survival (MFS). Results: The 5-year DSS was poorer in the Hb continuous decrease group than in the Hb noncontinuous decrease group (84% vs. 89%; p = 0.008). There was poorer 5-year DSS in patients with White-Up-Pointing-Small-Triangle Hb of >11.5 g/L than in those with White-Up-Pointing-Small-Triangle Hb of {<=}11.5 g/L (82% vs. 89%; p = 0.001), and poorer LRFS (79% vs. 83%; p = 0.035). Univariate and multivariate analysis showed that Hb decrease difference with greater than 11.5 g/L was an independent prognostic factor for DSS and LRFS. Conclusions: The difference in decrease of Hb level during the course of radiation treatment appeared as a poor prognostic factor in Stage I and II nasopharyngeal carcinoma patients.

  16. H19 serves as a diagnostic biomarker and up-regulation of H19 expression contributes to poor prognosis in patients with gastric cancer.

    PubMed

    Chen, J S; Wang, Y F; Zhang, X Q; Lv, J M; Li, Y; Liu, X X; Xu, T P

    2016-01-01

    Emerging evidences indicate that dysregulated long noncoding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be used as diagnosis and prognosis biomarker, or potential therapeutic targets. LncRNA H19 has been reported to be upregulated in diverse human cancers; however, its clinical significance in gastric cancer (GC) remains elusive. Expression levels of H19 in 128 pairs of GC and adjacent normal tissues, GC cell lines and GC juices compared to their corresponding controls were detected by real-time quantitative polymerase chain reaction (qPCR) assay. A receiver operating characteristic (ROC) curve and Kaplan-Meier analysis were constructed to evaluate the diagnostic and prognostic values. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. H19 expression was remarkably increased in GC tissues and cell lines compared with that in the normal control, and its up-regulation was significantly correlated to invasion depth (P < 0.001), advanced TNM stage (P = 0.002) and regional lymph nodes metastasis (P < 0.001) in GC. H19 levels were robust in differentiating GC tissues from controls [area under the curve (AUC) = 0.697; 95% confidence interval (CI) = 0.636-0.752, p<0.01]. Kaplan-Meier analysis demonstrated that increased H19 expression contributed to poor overall survival (P = 0.017) and disease-free survival (P = 0.024) of patients. A multivariate survival analysis also indicated that H19 could be an independent prognostic marker. The levels of H19 in gastric juice from gastric patients were significantly higher than those from normal subjects (P = 0.034). Furthermore, knockdown of H19 expression by siRNA could inhibit cell migration and invasion in GC cells partly via regulating E-cadherin protein expression. H19 might serve as a promising biomarker for early detection and prognosis prediction of GC.

  17. Expression of CDKN1C in the bone marrow of patients with myelodysplastic syndrome and secondary acute myeloid leukemia is associated with poor survival after conventional chemotherapy.

    PubMed

    Radujkovic, Aleksandar; Dietrich, Sascha; Andrulis, Mindaugas; Benner, Axel; Longerich, Thomas; Pellagatti, Andrea; Nanda, Kriti; Giese, Thomas; Germing, Ulrich; Baldus, Stefan; Boultwood, Jacqueline; Ho, Anthony D; Dreger, Peter; Luft, Thomas

    2016-09-15

    We tested the hypothesis that proliferative activity of hematopoietic stem cells has impact on survival in newly diagnosed patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML). RNA expression profiles of CD34(+) cells were analyzed in 125 MDS patients and compared to healthy controls. Prognostic impact on overall survival (OS) of mRNA proliferation signatures established for solid tumor cells was analyzed retrospectively. For validation on the protein level, immunofluorescence and immunohistochemistry analyses in bone marrow (BM) biopsies were performed, and an independent cohort of 223 MDS and secondary AML patients was investigated. Lower proliferative activity correlated with the expression of cyclin-dependent kinase inhibitor 1C (CDKN1C) and with shorter OS (p < 0.001). In multivariable analysis, higher CDKN1C expression was associated with worse OS (p = 0.02). On the BM level, a total of 84 (38%) patients showed CDKN1C protein expression before start of treatment. Patient, disease and treatment characteristics did not differ between CDKN1C-positive and -negative patients. Positive CDKN1C BM status was associated with shorter OS in multivariable analysis (HR 1.54, p = 0.04). There was an interaction between CDKN1C BM status and subsequent treatment with negative impact on OS being most pronounced in patients receiving conventional cytotoxic chemotherapy (n = 83, 2-year OS 30% versus 58%, p = 0.002). In conclusion, low-proliferative phenotype and CDKN1C expression were associated with shorter OS. CDKN1C protein expression in the BM of newly diagnosed, treatment-naïve MDS and secondary AML patients was identified as a prognostic factor for poor survival in patients treated with antiproliferative chemotherapy.

  18. P13.10SURGICAL TREATMENT FOR GLIOBLASTOMA MULTIFORME: OUTCOME AND ANALYSIS OF PROGNOSTIC FACTORS ESPECIALLY ORIENTED TO THE EXTENT OF SURGICAL RESECTION

    PubMed Central

    Di Somma, L.; Iacoangeli, M.; Alvaro, L.; Di Rienzo, A.; Liverotti, V.; Della Costanza, M.; Brunozzi, D.; Polonara, G.; Scarpelli, M.; Scerrati, M.

    2014-01-01

    INTRODUCTION: The prognosis of Glioblastoma Multiforme (GBM) remains poor despite recent therapeutic advances. The surgical treatment of GBM (supported by functional imaging, neuronavigation and electrophysiological monitoring) remains a fundamental step. The methylation of the enzyme O6-methylguanine-DNA methyltransefrase (MGMT) seems to improve the effectiveness of alkylating agents on this tumour, but other factors can influence the survival. An evaluation of all prognostic factors is essential to individuate subgroups of patients for a better selection of different treatment modalities. Our study confirms the prognostic values of both new recognized factors (MGMT presence, IDH1, news schedule of TM2 etc.) and the well-recognized prognostic factors particularly to the extent of surgical removal with the help of new technologies and in the era where people is asking more and more a better quality of life. METHODS: We retrospectively analysed 172 operated patients (115 males and 57 females), 55 of which located in eloquent areas, between March 2008 and December 2012. For each patient age, sex, preoperative clinical evaluation (Karnofsky score, KPS), tumour location, extent of surgical removal, genetic and epigenetic profile (MGMT, IDH1,etc) and postoperative treatments were recorded. We used Kaplan Meier method for the univariate analysis and the Cox regression for the multivariate one. Surgical strategy was always planned for a total tumour resection, when allowed by the intrinsic characteristics of the tumour using the so called “extracapsular “ technique. RESULTS: Overall median survival time after surgery was 10 months. At univariate analysis the gross total removal (p<0,0001), a postoperative KPS>70 (p<0,0001) and radiotherapy (p<0,0001) improve survivals. Deep structures involved or multifocal lesions (p<0,0001) resulted as negative factors in term of the quod vitam prognosis, whereas lesions arising in insula, deep structures or in primary motor cortex

  19. Predictive and Prognostic Roles of Abnormal Expression of Tissue miR-125b, miR-221, and miR-222 in Glioma.

    PubMed

    Li, Xinxing; Zheng, Jihui; Chen, Liangyu; Diao, Hongyu; Liu, Yunhui

    2016-01-01

    Glioma is the most prevalent primary brain tumors in adults. In addition to the high incidence and mortality rate, the 5-year survival rate of glioma is also extremely low. MicroRNAs (miRNAs), as a class of small non-coding RNAs, may play an important role in carcinogenesis. It was also proposed that miRNAs might also be associated with glioma diagnosis and prognosis. In this study, we aimed at investigating the predictive and prognostic values of miR-125b, miR-221, and miR-222 in glioma and, hopefully, to provide some evidence for novel therapy of glioma. Tissue specimens were obtained from tumor tissue and adjacent non-tumor tissue. RNA was extracted and qRT-PCR was performed with U6 being the internal control. Receiver-operating characteristic (ROC) curves were constructed, and the area under the ROC curves (AUC) was calculated to evaluate the significance of candidate miRNAs in distinguishing glioma tumor tissues and adjacent normal tissues. Survival curves of Kaplan-Meier method were constructed for both high expression group and low expression group, and the difference between curves was evaluated by log-rank test. All the statistical analyses were performed using Stata version 12.0 software, and graphs were generated by GraphPad Prism 5.0. The significance of miR-125b, miR-221, and miR-222 expression level in distinguishing glioma tumor from adjacent non-tumor tissues was further validated. Combination of miR-125b, miR-221, and miR-22 was significantly superior compared to the clinical standard of using these miRNAs alone. A clear demarcation was shown by survival analysis between patients with high miR-125b, miR-221, and miR-222 expression and patients with poor prognosis. Similarly, panel of these miRNAs could play a better prognostic role in glioma. In this study, we confirmed the significance of miR-125b, miR-221, and miR-222 in distinguishing glioma tumor from adjacent non-tumor tissues. Higher expressions of miR-125b and miR-222 have also been proved

  20. Aberrant expression of long noncoding RNA PVT1 and its diagnostic and prognostic significance in patients with gastric cancer.

    PubMed

    Yuan, C L; Li, H; Zhu, L; Liu, Z; Zhou, J; Shu, Y

    2016-01-01

    Emerging evidences indicate that dysregulated long noncoding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be used as diagnosis and prognosis biomarker, or potential therapeutic targets. LncRNA PVT1 has been reported to be upregulated in diverse human cancers; however, its clinical significance in gastric cancer (GC) remains elusive. This study was to evaluate the expression of PVT1 in GC and further explore its clinical significance.Previous microarray datasets were analyzed to conduct a preliminary screening for candidate lncRNAs of gastric cancer biomarkers in human gastric cancer tissues. Expression levels of PVT1 in 111pairs of gastric cancer and adjacent normal tissues, gastric cancer cell lines and gastric cancer juices compared to their corresponding controls were detected by real-time quantitative RT-PCR assay. A receiver operating characteristic (ROC) curve and Kaplan-Meier analysis were constructed to evaluate the diagnostic and prognostic values. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis.PVT1 expression was remarkably increased in gastric cancer tissues and cell lines compared with that in the normal control, and its up-regulation was significantly correlated to invasion depth (P < 0.001), advanced TNM stage (P = 0.002) and regional lymph nodes metastasis (P < 0.001) in gastric cancer. PVT1 levels were robust in differentiating gastric cancer tissues from controls [area under the curve (AUC) = 0.728; 95 % confidence interval (CI) = 0.665-0.786, p<0.01]. Kaplan-Meier analysis demonstrated that increased PVT1 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that PVT1 could be an independent prognostic marker. T