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Sample records for poor prognostic characteristics

  1. Factors determining poor prognostic outcomes following diabetic hand infections

    PubMed Central

    Ince, Bilsev; Dadaci, Mehmet; Arslan, Abdullah; Altuntas, Zeynep; Evrenos, Mustafa Kursat; Fatih Karsli, Mehmet

    2015-01-01

    Background and Objective: Hand ulcers are seen in a small percentage of patients with diabetes. The predisposing factors of diabetic hand varies between different countries. However, the effects of predisposing factors on prognosis are not clear in diabetic hand infections. In this study, our aim was to determine the effects of predisposing factors on poor prognostic outcomes in patients with diabetes mellitus. Methods: Thirty-four patients with diabetes mellitus who were treated and followed up for a hand infection in between 2008 and 2014 were investigated retrospectively. Patients were evaluated according to predisposing factors defined in the literature that included disease period, age, gender, admission time, presence of neuropathy, smoking habits, HbA1c levels at admission time, peripheral vascular disease, end-stage renal disease (ESRD), and trauma. Death and minor/major amputation cases during treatment were defined as poor prognosis. Results: Patients who had ESRD, peripheral neuropathy, or an HbA1c level greater than 10% had significantly higher amputation rates. Conclusions: Peripheral neuropathy, ESRD, and HbA1c levels greater than 10% at the time of admission were determined as poor prognosis criteria for diabetic hand treatment. PMID:26150838

  2. Analysis of clinical characteristics and prognostic factors for angioimmunoblastic T-cell lymphoma.

    PubMed

    Kameoka, Yoshihiro; Takahashi, Naoto; Itou, Shigeki; Kume, Masaaki; Noji, Hideyoshi; Kato, Yuichi; Ichikawa, Yoshikazu; Sasaki, Osamu; Motegi, Mutsuhito; Ishiguro, Atsushi; Tagawa, Hiroyuki; Ishizawa, Kenichi; Ishida, Yoji; Ichinohasama, Ryo; Harigae, Hideo; Sawada, Kenichi

    2015-06-01

    Angioimmunoblastic T-cell lymphoma (AITL) is a distinct peripheral T-cell lymphoma entity exhibiting peculiar clinical features and poor prognosis. Its clinical characteristics and prognostic factors are not well established. To clarify the clinical characteristics and prognostic features of AITL, we conducted a multicenter, retrospective study. Fifty-six patients were enrolled. The median patient age was 68 years. Immunohistochemical examinations of tumor cells showed positivity for CD10 and T-cell markers, and chromosomal examination detected several types of abnormalities. More than 80 % of patients show advanced disease at diagnosis and poor prognostic scores. A high proportion of patients showed accompanying B symptoms, splenomegaly, and hepatomegaly at diagnosis. The 5-year overall survival (OS) rate was 48 % and progression-free survival was 25 %. Univariate analysis revealed higher age, fever, poor performance status, anemia, and low albumin level to be poor prognostic factors for OS. In addition to these factors, both IPI and PIT were also predictive of OS. Multivariate analysis indicated only a low level of serum albumin to be a significant prognostic factor for OS. Serum albumin may be one of the important prognostic factors for AITL. Further investigation is needed to confirm these results. PMID:25739382

  3. Clinical characteristics and prognostic analysis of Krukenberg tumor

    PubMed Central

    WU, FANG; ZHAO, XIAOAI; MI, BAIBING; FENG, LU; YUAN, NA; LEI, FUXI; LI, MIN; ZHAO, XINHAN

    2015-01-01

    Krukenberg tumor is a rare metastastic tumor of the ovary, characterized by poor prognosis. In order to analyze the clinical characteristics and prognostic factors, we retrospectively investigated 128 patients who were diagnosed with Krukenberg tumor between January, 1990 and December, 2010. The median patient age was 48 years. The median overall survival (OS) of Krukenberg tumor for all patients was 16 months (95% CI: 15–19 months). The median OS among patients with Krukenberg tumors of gastric, colorectal, breast and other origins (including appendix, gallbladder, small intestine and unknown primary) was 11, 21.5, 31 and 19.5 months, respectively (P<0.0001). In the univariate analysis, synchronous metastasis, no chemotherapy, ovarian metastasis beyond the pelvis, ascites and no metastasectomy were identified as significant poor prognostic factors. The multivariate analysis suggested that synchronous metastasis (P=0.0080), pelvic invasion (P=0.0138), ascites (P<0.0001) and no metastasectomy (P=0.0060) were independent factors for predicting unfavorable OS. It was suggested that the prognosis of Krukenberg tumor is dismal and ovarian metastasectomy may prove beneficial. Adequate treatment planning is required for this group of patients. PMID:26807242

  4. Malignant brainstem gliomas in adults: clinicopathological characteristics and prognostic factors.

    PubMed

    Babu, Ranjith; Kranz, Peter G; Agarwal, Vijay; McLendon, Roger E; Thomas, Steven; Friedman, Allan H; Bigner, Darell D; Adamson, Cory

    2014-08-01

    Adult malignant brainstem gliomas (BSGs) are poorly characterized due to their relative rarity. We have examined histopathologically confirmed cases of adult malignant BSGs to better characterize the patient and tumor features and outcomes, including the natural history, presentation, imaging, molecular characteristics, prognostic factors, and appropriate treatments. A total of 34 patients were identified, consisting of 22 anaplastic astrocytomas (AAs) and 12 glioblastomas (GBMs). The overall median survival for all patients was 25.8 months, with patients having GBMs experiencing significantly worse survival (12.1 vs. 77.0 months, p = 0.0011). The majority of tumors revealed immunoreactivity for EGFR (93.3 %) and MGMT (64.7 %). Most tumors also exhibited chromosomal abnormalities affecting the loci of epidermal growth factor receptor (92.9 %), MET (100 %), PTEN (61.5 %), and 9p21 (80 %). AAs more commonly appeared diffusely enhancing (50.0 vs. 27.3 %) or diffusely nonenhancing (25.0 vs. 0.0 %), while GBMs were more likely to exhibit focal enhancement (54.6 vs. 10.0 %). Multivariate analysis revealed confirmed histopathology for GBM to significantly affect survival (HR 4.80; 95 % CI 1.86-12.4; p = 0.0012). In conclusion, adult malignant BSGs have an overall poor prognosis, with GBM tumors faring significantly worse than AAs. As AAs and GBMs have differing imaging characteristics, tissue diagnosis may be necessary to accurately determine patient prognosis and identify molecular characteristics which may aid in the treatment of these aggressive tumors. PMID:24838419

  5. Prognostic value of clinicopathological characteristics in patients with pancreatic cancer

    PubMed Central

    Geng, Mei; Xu, Haoping; Ren, Ruobing; Qu, Qing; Shangguan, Chengfang; Wu, Junwei; Jiang, Jinsong; Li, Hao

    2015-01-01

    Background The purpose of this study was to analyze the effects of all clinical characteristics on the overall survival time, in order to provide a basis for determining the prognostic factor of patients with pancreatic cancer. Methods A total of 103 pancreatic cancer patients were admitted to the Department of Radiotherapy and Chemotherapy of the Ruijin Hospital, Shanghai Jiaotong University School of Medicine, between January 2002 and December 2012. There were 68 men and 35 women; the median age was 62 years. Diagnoses of pancreatic cancer in all patients were confirmed by histopathology, cytology, or clinical diagnosis. The Kaplan-Meier method was performed to calculate the overall survival rate. The log-rank method was used to examine the univariate analysis. The Cox regression model was performed for multivariate analysis. Results The median survival time was 293 days, the 1-, 2-, and 3-year survival rates were 27.18%, 5.83%, and 1.94%, respectively. Cox regression analysis revealed that age (P=0.015), Karnofsky performance status (PS) (P=0.002), surgical types (P<0.001), and platelet counts (P<0.001) were independent prognostic factors affecting the overall survival of patients with pancreatic cancer. Conclusions Pancreatic cancer had a poor prognosis, the general physical condition, age, the availability of radical surgery, and platelet counts were factors influencing the overall survival of patients with pancreatic cancer. PMID:26543338

  6. Glycodelin A is a prognostic marker to predict poor outcome in advanced stage ovarian cancer patients

    PubMed Central

    2012-01-01

    Background Glycodelin is a cell surface glycoprotein offering a unique gender specific carbohydrate configuration. Sialylated carbohydrate structures, which are unusual for mammals, characterize Glycodelin isolated from amniotic fluid (Glycodelin A, GdA). Glycodelin in general exerts multiple, partly opposing functions ranging from immunosuppression to cell differentiation. As these markedly influence tumorigenesis, this study aimed to clarify whether expression of different Glycodelin isoforms is related to clinicopathological characteristics and prognosis of ovarian cancer patients. Further the use of Glycodelin as a serum marker in benign and malignant ovarian diseases was evaluated. Methods Ovarian cancer specimens (n = 152) were stained for Glycodelin with carbohydrate and peptide specific antibodies. Associations between Glycodelin expression and histological grading, FIGO stage as well as patients prognosis were examined. Glycodelin was correlated to expression of gonadotropin receptors and mucin-1, which are discussed as ovarian cancer tissue markers. In addition, Glycodelin serum concentrations were analyzed in patients suffering from benign (n = 73) or malignant (n = 38) ovarian neoplasias. Results Glycodelin A was found to be an independent prognostic marker for poor prognosis in advanced ovarian cancer patients. GdA staining correlated with gonadotropin receptor (FSHR and LHCGR) and with hCG expression. Gd expression showed a positive correlation with a tumour-associated epitope of mucin 1 (TA-MUC1). Further, compared to ovarian cancer, serum Gd was increased in patients with benign ovarian tumors. Conclusion Glycodelin A might be related to tumor aggressiveness and poor clinical outcome in advanced epithelial ovarian cancer. Glycodelin serum levels found in patients suffering from benign ovarian tumors, might contribute to a more global attenuation during progression of these precursor lesions. PMID:23036050

  7. Tetraspanin CD151 is a novel prognostic marker in poor outcome endometrial cancer

    PubMed Central

    Voss, M A; Gordon, N; Maloney, S; Ganesan, R; Ludeman, L; McCarthy, K; Gornall, R; Schaller, G; Wei, W; Berditchevski, F; Sundar, S

    2011-01-01

    Background: Type II cancers account for 10% of endometrial cancers but 50% of recurrence. Response rates to chemotherapy at recurrence are poor and better prognostic markers are needed to guide therapy. CD151 is a small transmembrane protein that regulates cell migration and facilitates cancer metastasis. High CD151 expression confers poor prognosis in breast, pancreatic and colorectal cancer. The prognostic significance of tetraspanin CD151 expression in poor outcome endometrial cancers was evaluated, along with oestrogen receptor (ER), progesterone receptor (PR), p53, human epidermal growth factor receptor -2 (HER-2), and CD 151 staining compared with ?6?1, ?3?1 integrins, and E-cadherin. Methods: Tissue microarray constructed from 156 poor outcome endometrial cancers, tested with immunohistochemistry and staining correlated with clinicopathological data were used. A total of 131 data sets were complete for analysis. Results: Expression of CD151 was significantly higher in uterine papillary serous and clear cell carcinoma than in grade 3 endometrioid carcinoma, sarcoma or carcinosarcoma (P<0.001). In univariate analysis, age, stage, histology type and CD151 were significant for both recurrence free (RFS) and disease specific survival (DSS). In multivariate analyses, CD151 was significant for RFS and DSS (P=0.036 and 0.033, respectively) in triple negative (ER, PR and HER-2 negative) tumours (88/131). The HER-2, p53, ER and PR were not prognostic for survival. There was strong concordance of CD151 with E-cadherin (98%), but not with ?6?1 (35%), ?3?1 staining (60%). Conclusion: The CD151 is a novel marker in type 2 cancers that can guide therapeutic decisions. CD151 may have an important role in tumourigenesis in some histology types. PMID:21505452

  8. Prognostic characteristics of duodenal gastrointestinal stromal tumours

    PubMed Central

    Zhang, Q; Shou, C-H; Yu, J-R; Yang, W-L; Liu, X-S; Yu, H; Gao, Y; Shen, Q-Y; Zhao, Z-C

    2015-01-01

    Background This study evaluated the clinical characteristics, surgical procedures and prognosis of duodenal gastrointestinal stromal tumours (GISTs). Methods Patients with a diagnosis of primary duodenal GIST treated between January 2000 and December 2012 were analysed. Patients with gastric and small intestinal GISTs were chosen as control groups according to the following parameters: age, tumour size, mitotic index and adjuvant imatinib therapy. Operative procedures for patients with duodenal GIST included pancreaticoduodenectomy or limited resection. Disease-free survival (DFS) was calculated using KaplanMeier analysis. Results Some 71 patients with duodenal, 71 with gastric and 70 with small intestinal GISTs were included in the study. DFS of patients with duodenal GIST was shorter than that of patients with gastric GIST (3-year DFS 84 versus 94 per cent; hazard ratio (HR) 3.67, 95 per cent c.i. 1.21 to 11.16; P?=?0.014), but was similar to that of patients with small intestinal GIST (3-year DFS 84 versus 81 per cent; HR 0.75, 0.37 to 1.51; P?=?0.491). Patients who underwent pancreaticoduodenectomy were older, and had larger tumours and a higher mitotic index than patients who had limited resection. The 3-year DFS was 93 per cent among patients who had limited resection compared with 64 per cent for those who underwent PD (HR 0.18, 0.06 to 0.59; P?=?0.001). Conclusion The prognosis of duodenal GISTs is similar to that of small intestinal GISTs. Prognosis no different than for small bowel gastrointestinal stromal tumours PMID:25980461

  9. Decreased Wnt5a Expression is a Poor Prognostic Factor in Triple-Negative Breast Cancer

    PubMed Central

    Zhong, ZhenBin; Shan, Ming; Wang, Ji; Liu, Tong; Shi, QingYu; Pang, Da

    2016-01-01

    Background Wingless-type MMTV integration site family member 5A (Wnt5a) has been documented to either overexpress or be lost in several malignancies. Our study aimed to investigate the expression and clinical significance of Wnt5a protein in triple-negative breast cancer (TNBC). Material/Methods By using immunohistochemistry, Wnt5a expression was evaluated in 90 TNBC specimens. The association between Wnt5a expression and clinic-pathological factors was assessed by using the chi-square test. The survival analysis of patients was conducted by using the Kaplan-Meier and log-rank tests. Cox regression was utilized for the univariate and multivariate analyses of prognostic factors. Results Results showed that negative Wnt5a expression correlated with positive lymph node metastasis (LNM) (P=0.007) and Ki67 proliferation (P=0.002). Patients with negative Wnt5a expression had significantly poorer recurrence-free survival (RFS) than patients with positive Wnt5a expression (P=0.008). Multivariate Cox regression analysis revealed that decreased Wnt5a expression was an independent prognostic factor for RFS (P=0.014). Conclusions Negative Wnt5a protein expression might contribute to the tumor progression and poor prognosis of TNBC and might be a new therapy target in TNBC. PMID:26721633

  10. Positive expression of pro-opiomelanocortin (POMC) is a novel independent poor prognostic marker in surgically resected non-small cell lung cancer.

    PubMed

    Hao, Ligang; Zhao, Xiaoliang; Zhang, Bin; Li, Chenguang; Wang, Changli

    2015-03-01

    This study aims to investigate the expression level of pro-opiomelanocortin (POMC) and its prognostic value in non-small cell lung cancer (NSCLC). Immunohistochemical staining was used to detect the expression level of POMC. Correlations between POMC expression and clinical and pathological characteristics were evaluated with the chi-square test, and the prognostic value was determined with the Kaplan-Meier method and COX proportional hazards model, ??poorly differentiated tumors, N-stage, p-stage, postoperative failure pattern, expression of vimentin, and expression of E-cadherin (P?prognostic model using pathological stage markedly improved the prognostic potential, and the area under the ROC increased from 0.691 to 0.775. Further study revealed that patients with POMC-negative expression can benefit more from a regimen of paclitaxel and carboplatin chemotherapy than a regimen of vinorelbine and carboplatin compared to patients with POMC-positive expression. We found that POMC-positive expression is a novel, independent poor prognostic marker in patients with NSCLC. Prospective studies are needed to validate the potential prognostic value of POMC in combination with the current staging system and in consideration of adjuvant chemotherapy. PMID:25377161

  11. Primary Non-Hodgkin Lymphoma of the Stomach: Clinicopathological Characteristics and Prognostic Factors in Iranian Patients

    PubMed Central

    Hosseini, Sare; Dehghan, Parvaneh

    2014-01-01

    Background Primary Gastric Lymphoma (PGL) is an uncommon malignancy with various histological subtypes and treatment outcomes. The aim of this study was to investigate the potential prognostic factors and clinicopathological characteristics of Iranian patients with PGL. Methods The clinicopathological characteristics of 60 patients with PGL were retrospectively reviewed from 2001 to 2012. The patients underwent various combinations of chemotherapy, radiotherapy, and surgery. We evaluated multiple potential prognostic factors and their associations with patient survival rate. Results According to the results, Diffuse Large B-cell Lymphoma (DLBCL) and Mucosa-Associated Lymphoid Tissue (MALT) were two predominant histological subtypes. The majority of cases were diagnosed with stage I tumor in the distal part of the stomach. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 60% and 70%, respectively. It was revealed that poor World Health Organization (WHO) performance status, presence of B symptoms, and International Prognostic Index (IPI) score?3 were significantly associated with decreased patient survival. Conclusion Most of the patients with PGL in early stage have a favorable prognosis. PMID:25628842

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

    PubMed Central

    Blink, Marjolein; Zimmermann, Martin; von Neuhoff, Christine; Reinhardt, Dirk; de Haas, Valerie; Hasle, Henrik; OBrien, 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

    2014-01-01

    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 ?20109/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. PMID:23935021

  13. 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

  14. 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. PMID:25323052

  15. Tumor cell expression of MMP3 as a prognostic factor for poor survival in pancreatic, pulmonary, and mammary carcinoma

    PubMed Central

    Mehner, Christine; Miller, Erin; Nassar, Aziza; Bamlet, William R.; Radisky, Evette S.; Radisky, Derek C.

    2015-01-01

    Breast, lung, and pancreatic cancers collectively represent one third of all diagnosed tumors and are responsible for almost 40% of overall cancer mortality. Despite improvements in current treatments, efforts to develop more specific therapeutic options are warranted. Here we identify matrix metalloproteinase 3 (MMP3) as a potential target within all three of these tumor types. MMP3 has previously been shown to induce expression of Rac1b, a tumorigenic splice isoform of Rac1. In this study we find that MMP3 and Rac1b proteins are both strongly expressed by the tumor cells of all three tumor types and that expression of MMP3 protein is prognostic of poor survival in pancreatic cancer patients. We also find that MMP3 gene expression can serve as a prognostic marker for patient survival in breast and lung cancer. These results suggest an oncogenic MMP3-Rac1b signaling axis as a driver of tumor progression in three common poor prognosis tumor types, further suggesting that new therapies to target these pathways could have substantial therapeutic benefit. PMID:26807201

  16. 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; Fo, 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/RAR?-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. PMID:24296270

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

    PubMed Central

    Debald, Manuel; Rostamzadeh, Babak; Thiesler, Thore; Schrder, Lars; Barchet, Winfried; Abramian, Alina; Kaiser, Christina; Kristiansen, Glen; Kuhn, Walther; Kbler, Kirsten

    2015-01-01

    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. PMID:25999351

  18. IgM autoagglutinins in warm autoimmune hemolytic anemia: a poor prognostic feature.

    PubMed

    McCann, E L; Shirey, R S; Kickler, T S; Ness, P M

    1992-01-01

    The presence of both complete IgM autoagglutinins and IgG autoantibodies in warm autoimmune hemolytic anemia (AIHA) is an uncommon finding. Over a 6-year period, only 5 of 115 (4.1%) patients with AIHA had IgM and IgG autoantibodies. In 3 of the 5 cases, the complete IgM autoagglutinins reacted up to 30 degrees C and these patients responded well to corticosteroid or other therapies for warm AIHA. The 2 patients who had warm (37 degrees C) reactive IgM autoagglutinins, were refractory to corticosteroids, splenectomy and cytotoxic drugs, and died due to the complications of hemolytic anemia. The data in these 5 cases suggest that the thermal amplitude of the IgM antibody in these unusual AIHA cases may be predictive of refractoriness to therapy and poor clinical outcome. PMID:1466193

  19. GLI1 expression is an important prognostic factor that contributes to the poor prognosis of rhabdomyosarcoma.

    PubMed

    Wang, Yuanyuan; Sun, Chao; Jiang, Jinfang; Xie, Yuwen; Li, Bingcheng; Cui, Xiaobin; Chen, Yunzhao; Liu, Chunxia; Li, Feng

    2016-03-01

    The GLI1 and MDM2 genes are amplified or exhibit copy number gains in rhabdomyosarcoma (RMS). Here, we used immunohistochemistry to determine the relationships between GLI1 and MDM2 protein expression and several clinicopathological variables of RMS. GLI1 and MDM2-positivity rates were 61.36% and 13.64%, respectively. GLI1 expression correlated with presence of the PAX3-FOXO1 fusion gene (P=0.040) and lymph node metastasis (P=0.034), and a significant association was found between GLI1 expression and overall survival (OS) (P=0.008). However, there was no association between MDM2 expression and any of the clinicopathological parameters or OS. Thus, GLI1 may be a biomarker of poor prognosis in RMS patients, and could itself be a therapeutic target. This contrasts with the apparent lack of clinical importance of MDM2 in RMS pathology, at least in the cohorts we examined. PMID:26544916

  20. 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.

  1. Early-onset acute kidney injury is a poor prognostic sign for allogeneic SCT recipients.

    PubMed

    Shingai, N; Morito, T; Najima, Y; Kobayashi, T; Doki, N; Kakihana, K; Ohashi, K; Ando, M

    2015-12-01

    Acute kidney injury (AKI) following stem-cell transplantation (SCT) contributes to a poor prognosis, yet its impact may vary depending on the timing of AKI onset. A prospective cohort study was performed to understand the significance of the onset timing in 103 allogeneic SCT (allo-SCT) recipients. AKI prior to stem-cell engraftment was defined as early AKI and subsequently occurring AKI as late AKI. Propensity score (PS) for early AKI was calculated using a logistic regression model to reduce confounding effects related to differences in clinical background between the early and late AKI groups. The cumulative incidences of early and late AKI were 22.3% and 54.9%, respectively. Non-relapse mortality (NRM) was 39.1% and 7.0%, and overall survival (OS) was 56.5% and 90.9% in early and late AKI at 100 days after AKI, respectively (P<0.001). The cumulative incidence of chronic kidney disease (CKD) over 2 years after SCT was 41.5% and 19.1% in early and late AKI, respectively (P=0.048). Logistic regression analysis adjusted for the PS showed that early AKI was significantly associated with OS (odds ratio (95% confidence interval); 4.63 (1.15-21.4), P=0.031) but with neither NRM (1.25 (0.28-5.33), P=0.766) nor CKD (1.85 (0.41-8.60), P=0.422). In conclusion, early AKI may portend a poor survival for allo-SCT recipients. PMID:26301965

  2. MicroRNA-711 is a prognostic factor for poor overall survival and has an oncogenic role in breast cancer

    PubMed Central

    HU, JING-YE; YI, WEI; ZHANG, MEI-YIN; XU, RUI; ZENG, LI-SI; LONG, XIAO-RAN; ZHOU, XIAO-MIN; ZHENG, XIAO-FENG STEVEN; KANG, YIBIN; WANG, HUI-YUN

    2016-01-01

    MicroRNAs are important in cancer development and progression. In the present study, the clinical significance and function of microRNA-711 (miR-711) expression in breast cancer were investigated. The expression level of miR-711 was analyzed in breast cancer tissue samples using reverse transcription-quantitative polymerase chain reaction. Cell proliferation, colony formation, apoptosis and Transwell assays were performed in breast cancer cell lines transfected with miR-711 mimics or inhibitors, or control sequence. miR-711 was found to be upregulated in 30 formalin-fixed paraffin-embedded breast cancer tissue samples compared with paired non-cancerous breast tissues (P<0.05). Furthermore, a higher miR-711 expression was demonstrated to be associated with poor overall and disease-free survival times in 161 breast cancer patients, and miR-711 was identified as an independent prognostic factor using multivariate Cox regression analysis. In vitro, overexpression of miR-711 resulted in a significant increase in proliferation, colony formation, migration and invasion of breast cancer cells. By contrast, downregulating miR-711 inhibited cell proliferation, colony formation, migration and invasion and enhanced the rate of apoptosis of breast cancer cells. To the best of our knowledge, the present study is the first to demonstrate that miR-711 is an independent prognostic factor and serves an important oncogenic function in breast cancer, suggesting that miR-711 is a potential biomarker of prognosis and a molecular therapeutic target in breast cancer. PMID:26998141

  3. 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.

  4. Intratumoral Hepatic Stellate Cells as a Poor Prognostic Marker and a New Treatment TargetforHepatocellular Carcinoma

    PubMed Central

    Cheng, Xianshuo; Zhang, Yu; Chen, Lei; Shi, Lehua; Liu, Zhenyu; Qian, Haihua; Wu, Mengchao; Yin, Zhengfeng

    2013-01-01

    Hepatic stellate cells (HSCs), a specialized stromal cytotype in the liver, have been demonstrated to actively contribute to hepatocellular carcinoma (HCC) development. However, the previous studies were performed using HSC cell lines, and the prognostic value of intratumoral HSCs (tHSCs) was unclear. Here we isolated tHSCs from fresh human HCC tissues, and analyzed the abilities of tHSCs to promote HCC progression by using in vitro assays for cell viability, migration and invasion as well as epithelial-mesenchymal transition(EMT)phenotype. 252 HCC patients who underwent hepatectomy were enrolled for analysis of tHSCs and E-cadherin expression in tumor tissues, and 55 HCC patients for analysis of tHSCs in tumor tissues and circulating tumor cells (CTCs) in blood. Prognostic factors were then identified. The results showed that coculture of tHSCs with HCC cells had a stronger effect on HCC cell viability, migration and invasion, accompanied with the acquisition ofepithelial-mesenchymal transition(EMT)phenotype.In vivo cotransplantation of HCC cells with tHSCs into nude mice more efficiently promoted tumor formation and growth. Icaritin, a known apoptosis inducer of HSCs, was demonstrated to effectively inhibit tHSC proliferation in vitro and tHSC-induced HCC-promoting effects in vivo. Clinical evidence indicated that tHSCs were rich in 45% of the HCC specimens, tHSC-rich subtypes were negatively correlated either with E-cadherin expression in tumor tissues (r = -0.256, p < 0.001) or with preoperative CTCs in blood (r = -0.287, p = 0.033), and were significantly correlated with tumor size (p = 0.027), TNM staging (p = 0.018), and vascular invasion (p = 0.008). Overall and recurrence-free survival rates of tHSC-rich patients were significantly worse than those for tHSC-poor patients. Multivariate analysis revealed tHSC-rich as an independent factor for overall and recurrence-free survival. In conclusion, tHSCs provide a promising prognostic biomarker anda new treatment targetfor HCC. PMID:24278260

  5. 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

  6. Phosphorylation of GSK3?/? 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 GSK3? and ? isoforms which inactivates these kinases. In the current study we examine the prognostic role of AKT mediated GSK3 phosphorylation in AML. Methods We analyzed GSK3?/? 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-GSK3?/? 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-GSK3?/? levels were lower. Phosphorylated GSK3?/? expression was compared and contrasted with that of 229 related cell cycle arrest and/or apoptosis proteins. Consistent with p-GSK3?/? as an indicator of AKT activation, RPPA revealed that p-GSK3?/? positively correlated with phosphorylation of AKT, BAD, and P70S6K, and negatively correlated with ?-catenin and FOXO3A. PKC? also positively correlated with p-GSK3?/? expression, suggesting crosstalk between the AKT and PKC signaling pathways in AML cells. Conclusions These findings suggest that AKT-mediated phosphorylation of GSK3?/? may be beneficial to AML cell survival, and hence detrimental to the overall survival of AML patients. Intrinsically, p-GSK3?/? may serve as an important adverse prognostic factor for a subset of AML patients. PMID:26674329

  7. High expression of Bcl-2 predicts poor outcome in diffuse large B-cell lymphoma patients with low international prognostic index receiving R-CHOP chemotherapy.

    PubMed

    Choi, Yong Won; Ahn, Mi Sun; Choi, Jin-Hyuk; Lee, Hyun Woo; Kang, Seok Yun; Jeong, Seong Hyun; Park, Joon Seong; Han, Jae Ho; Kim, Jang-Hee; Sheen, Seung Soo

    2016-02-01

    The prognostic significance of Bcl-2, Bcl-6, p53, topoisomerase II, and ?-tubulin expression was evaluated in diffuse large B-cell lymphoma (DLBCL) patients treated with cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab. Eight-year progression-free survival (PFS, P=0.006) and overall survival (OS, P=0.001) of patients with high Bcl-2 expression were significantly inferior to those of patients with low expression without prognostic significance of Bcl-6, p53, topoisomerase II, and ?-tubulin expression. High expression of Bcl-2 was associated with poor PFS (P=0.045) and OS (P=0.004) only in patients with low international prognostic index (IPI). In multivariate analysis, high expression of Bcl-2 was a significant independent prognostic factor of poor PFS (P=0.026) and OS (P=0.007) along with high IPI. In conclusion, the expression of Bcl-2 may be a useful prognostic factor, especially in DLBCL patients with low IPI. PMID:26586460

  8. 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

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

    PubMed

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

    2014-06-27

    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. PMID:24845563

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

    PubMed

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

    2016-04-01

    Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection and clinical relevance of biomarker analysis in metastatic tissue have barely been investigated. We previously demonstrated an impact of WNT signaling in breast cancer brain metastasis. This study aimed to investigate the value of established prognostic markers and WNT signaling components in liver metastases. Overall N = 34 breast cancer liver metastases (with matched primaries in 19/34 cases) were included in this retrospective study. Primaries and metastatic samples were analyzed for their expression of the estrogen (ER) and progesterone receptor, HER-2, Ki67, and various WNT signaling-components by immunohistochemistry. Furthermore, β-catenin-dependent and -independent WNT scores were generated and analyzed for their prognostic value. Additionally, the influence of the alternative WNT receptor ROR on signaling and invasiveness was analyzed in vitro. ER positivity (HR 0.09, 95 % CI 0.01-0.56) and high Ki67 (HR 3.68, 95 % CI 1.12-12.06) in the primaries had prognostic impact. However, only Ki67 remained prognostic in the metastatic tissue (HR 2.46, 95 % CI 1.11-5.44). Additionally, the β-catenin-independent WNT score correlated with reduced overall survival only in the metastasized situation (HR 2.19, 95 % CI 1.02-4.69, p = 0.0391). This is in line with the in vitro results of the alternative WNT receptors ROR1 and ROR2, which foster invasion. In breast cancer, the value of prognostic markers established in primary tumors cannot directly be translated to metastases. Our results revealed β-catenin-independent WNT signaling to be associated with poor prognosis in patients with breast cancer liver metastasis. PMID:26862065

  11. 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. PMID:21822045

  12. Ribonucleotide reductase small subunit M2 serves as a prognostic biomarker and predicts poor survival of colorectal cancers

    PubMed Central

    Liu, Xiyong; Zhang, Hang; Lai, Lily; Wang, Xiaochen; Loera, Sofia; Xue, Lijun; He, Huiyin; Zhang, Keqiang; Hu, Shuya; Huang, Yasheng; Nelson, RebeccaA.; Zhou, Bingsen; Zhou, Lun; Chu, Peiguo; Zhang, Suzhan; Zheng, Shu; Yen, Yun

    2012-01-01

    The overexpression of RRM2 [RR (ribonucleotide reductase) small subunit M2] dramatically enhances the ability of the cancer cell to proliferate and to invade. To investigate further the relevance of RRM2 and CRCs (colorectal cancers), we correlated the expression of RRM2 with the clinical outcome of CRCs. A retrospective outcome study was conducted on CRCs collected from the COH [(City of Hope) National Medical Center, 217 cases] and ZJU (Zhejiang University, 220 cases). IHC (immunohistochemistry) was employed to determine the protein expression level of RRM2, and quantitative real-time PCR was employed to validate. Multivariate logistic analysis indicated that the adjusted ORs (odds ratios) of RRM2-high for distant metastases were 2.06 [95% CI (confidence interval), 1.014.30] and 5.89 (95% CI, 1.5139.13) in the COH and ZJU sets respectively. The KaplanMeier analysis displayed that high expression of RRM2 had a negative impact on the OS (overall survival) and PFS (progress-free survival) of CRC in both sets significantly. The multivariate Cox analysis further demonstrated that HRs (hazard ratios) of RRM2-high for OS were 1.88 (95% CI, 1.033.36) and 2.06 (95% CI, 1.104.00) in the COH and ZJU sets respectively. Stratification analysis demonstrated that the HR of RRM2 dramatically increased to 12.22 (95% CI, 1.62258.31) in the MMR (mismatch repair) gene-deficient subgroup in the COH set. Meanwhile, a real-time study demonstrated that down-regulation of RRM2 by siRNA (small interfering RNA) could significantly and specifically reduce the cell growth and adhesion ability in HT-29 and HCT-8 cells. Therefore RRM2 is an independent prognostic factor and predicts poor survival of CRCs. It is also a potential predictor for identifying good responders to chemotherapy for CRCs. PMID:23113760

  13. Ubiquitin-specific peptidase 22, a histone deubiquitinating enzyme, is a novel poor prognostic factor for salivary adenoid cystic carcinoma.

    PubMed

    Dai, Wei; Yao, Yuan; Zhou, Qing; Sun, Chang-fu

    2014-01-01

    Salivary Adenoid Cystic Carcinoma (SACC) is characterized by a high rate of local recurrence and infiltration, strong invasion to peripheral nerves or late distant metastasis. Our aim was to investigate the expression of Ubiquitin-specific protease 22 (USP22) in SACC patients and its possible relationship to the outcome of the disease. A total of 135 SACC tissues and adjacent non-cancerous tissues which were diagnosed between 2002 and 2007 were enrolled in this study. Immunohistochemistry was used to compare the expression pattern of USP22 in SACC and adjacent non-cancerous groups, and the prognostic significance was assessed by Kaplan-Meier analysis and Cox proportional hazards regression in SACC patients. The rate of high expression of USP22 was significantly higher in SACC group than that in adjacent non-cancerous group. High expression of USP22 was significantly correlated with histological subtype, lymph node metastasis, grade, Ki-67 and SOX2 expression. Furthermore, USP22 acts as an oncogene by regulation the BMI-1 pathway and c-Myc pathway. SACC patients with high USP22 expression showed the poorer overall survival (OS) and disease-free survival (DFS) than those patients with low USP22 expression. In multivariate analysis, only lymph node metastasis and USP22 expression were the independent prognostic factors for OS and DFS in SACC. Our study provides evidence that USP22 expression is an independent prognostic factor for SACC patients. PMID:24466336

  14. Clinico-pathological characteristics and prognostic factors of gastrointestinal stromal tumors among a Chinese population

    PubMed Central

    Li, Jiehua; Zhang, Haitian; Chen, Zhibai; Su, Ka

    2015-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal tumors of the digestive tract. GISTs include a group of heterogeneous tumors with different morphology, biologic behavior, and genetic characteristics, so their epidemiology, clinico-pathological features and prognosis is distinct in different countries. The objective of this study is to analyze clinico-pathological characteristics and prognostic factors of GISTs among Chinese population. We investigated 112 GIST patients were diagnosed between July 2008 and January 2013 at the First Affiliated Hospital of Guangxi Medical University. Histologic evaluation and immunohistochemistry analysis was performed on paraffin-embedded tissue from the 112 GISTs. Overall survival analysis was carried out using the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed according to Coxs proportional hazards model. Three and 5-year OS rates were 71.4 and 58.6% respectively. Univariate analysis showed that the following factors were significant in predicting OS: tumor site, tumor size, metastasis, resection margin status, cell type, invasion of adjacent organ, invasion of smooth muscle, mitotic rate, P53 and adjuvant therapy with imatinib (P<0.05). Multivariate analysis showed that tumor size, metastasis, resection margin status, mitotic rate, P53 and adjuvant therapy with imatinib were independent prognostic factors associated with OS. This may aid in the prediction of clinical evolution and guide treatments in patients with GIST in China.

  15. Characteristics and prognostic factors of synchronous multiple primary esophageal carcinoma: A report of 52 cases

    PubMed Central

    Li, Mei; Lin, Zhi-xiong

    2014-01-01

    Background To retrospectively analyze the clinical characteristics and prognostic factors of 52 cases of synchronous multiple primary esophageal carcinoma (SMPEC), in order to provide a reference for treatment strategy. Methods Clinical and survival data of 52 patients with SMPEC were analyzed retrospectively. The rates of overall survival (OS), depending on the different factors, were calculated using Kaplan-Meier analysis. A log-rank test was used for univariate survival analysis and Cox's proportional hazards regression model was used for multivariate survival analysis. Results Clinical and survival data of 52 patients with SMPEC, hospitalized from 1 January 2003 to 31 October 2011, were analyzed. Twelve patients underwent surgical resection, five received adjuvant radiotherapy and one received adjuvant radiochemotherapy. Thirty-seven of the 40 non-operative patients received external beam radiation therapy and 20 of them received platinum-based chemotherapy. Another three non-operative patients were given platinum-based chemotherapy alone. The one, three, and five-year OS and the median survival time (MST) were 65.4%, 17.3%, 7.7%, respectively, and 15.0 months for the whole cohort. Tumor length and M stage were independent prognostic factors for the whole cohort by multivariate survival analysis (P = 0.010 and 0.047, respectively). For the radiotherapy subgroup, multivariate analysis of prognostic factors identified that shorter tumor length, M0 stage, and chemotherapy were the predominant independent predictors of long-term survival (P = 0.039, 0.022 and 0.010, respectively). Conclusions SMPEC is a relatively rare and aggressive tumor. Combined radiotherapy with chemotherapy seemed to bring a survival benefit and may be a better management choice for unresectable and non-operative SMPEC.

  16. The Role of FGFR1 Gene Amplification as a Poor Prognostic Factor in Squamous Cell Lung Cancer: A Meta-Analysis of Published Data

    PubMed Central

    Wang, Yang; Gao, Wen; Xu, Jiali; Chen, Xiaojun; Yang, Yang; Zhu, Yizhi; Yin, Yongmei; Guo, Renhua; Liu, Ping; Shu, Yongqian; Liu, Lingxiang

    2015-01-01

    Objectives. The prognostic factors of the fibroblast growth factor receptor 1 (FGFR1) in non-small cell lung cancer (NSCLC) remain controversial. Methods. We conducted a meta-analysis of published studies from 1974 to February 2015. In absence of quality difference between studies of reporting significant and nonsignificant results, the relationship between FGFR1 amplification and clinicopathological parameters in NSCLC was analyzed. And also the combined hazard ratio (HR) and their corresponding 95% confidence interval (CI) were calculated in terms of overall survival. Results. 3178 patients (12 studies) were included in the analysis. It was shown that FGFR1 amplification was significantly more prevalent among male patients (RR 2.03, 95% CI 1.572.63) with squamous cell lung cancer (SQCC) (RR 3.49, 95% CI 2.624.64) and current smokers (RR 2.63, 95% CI 1.923.60). The pooled data also showed that the FGFR1 amplification was a poor prognostic factor in SQCC (HR 1.38, 95% CI 1.071.78), Asian patients (HR 1.78, 95% CI 1.222.60), and fluorescence in situ hybridization (FISH) method (HR 1.30, 95% CI 1.061.58). Conclusions. This meta-analysis strongly suggests that FGFR1 amplification occurs more frequently in male, SQCC and smokers, and it is a risk factor for poor prognosis among Asian patients with SQCC. PMID:26788508

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

    PubMed Central

    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. PMID:26823744

  18. High expression of EVI1 and MEL1 is a compelling poor prognostic marker of pediatric AML.

    PubMed

    Jo, A; Mitani, S; Shiba, N; Hayashi, Y; Hara, Y; Takahashi, H; Tsukimoto, I; Tawa, A; Horibe, K; Tomizawa, D; Taga, T; Adachi, S; Yoshida, T; Ichikawa, H

    2015-05-01

    EVI1 and MEL1 are homolog genes whose transcriptional activations by chromosomal translocations are known in small subsets of leukemia. From gene expression profiling data of 130 Japanese pediatric acute myeloid leukemia (AML) patients, we found that EVI1 and MEL1 were overexpressed in ~30% of patients without obvious translocations of these gene loci, and that their high expression was significantly associated with inferior survival. High EVI1 expression was detected mainly in myelomonocytic-lineage (designated as e-M4/M5 subtype) leukemia with MLL rearrangements and in megakaryocytic-lineage (designated as e-M7 subtype) leukemia, and its prognostic association was observed in the e-M4/M5 subtype but not in the e-M7 subtype. On the other hand, high MEL1 expression was detected in myelocytic-lineage (designated as e-M0/M1/M2 subtype) and e-M4/M5 subtype leukemia without MLL rearrangements, and its prognostic association was independent from the subtypes. Because of their subtype-dependent and mutually exclusive expression, a combined evaluation of their high expression enabled a clear distinction of patients with inferior survival (P<0.00001 in event-free survival (EFS) and overall survival (OS)). This association was confirmed by quantitative reverse transcription PCR analysis of an independent cohort of 81 patients (P=0.00017 in EFS, P=0.00028 in OS). We propose that the combined estimation of EVI1 and MEL1 expression will be an effective method to predict the prognosis of pediatric AML. PMID:25567132

  19. 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

  20. Immunohistochemical and molecular characteristics with prognostic significance in diffuse large B-cell lymphoma.

    PubMed

    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

  1. Prognostic Factors in the Survival of Patients Diagnosed with Primary Non-Metastatic Osteosarcoma with a Poor Response to Neoadjuvant Chemotherapy

    PubMed Central

    Júnior, Rosalvo Zósimo Bispo; de Camargo, Olavo Pires

    2009-01-01

    INTRODUCTION: Identification of variables that determine the prognosis for osteosarcoma may enable stratification of patients into subgroups with better or worse risk of local recurrence, metastases and death due to the disease. Discovery of such prognostic factors would permit selection of a subgroup of at-risk patients, with the aim of improving the therapeutic effectiveness. OBJECTIVE: To identify prognostic factors related to local recurrence-free survival, metastasis-free survival and overall survival among patients with highly malignant primary osteosarcoma that was non-metastatic on diagnosis and had poor response to neoadjuvant chemotherapy. SAMPLE AND METHODS: Out of 45 patients admitted to a referral center in Brazil between 2000 and 2004, 24 were selected for this study. RESULTS: The adverse factors that influenced the risk of local recurrence and the overall survival in univariate analysis were histological subtype other than osteoblastic (p = 0.017) and tumor size greater than 15 cm (p = 0.048). In relation to metastasis-free survival, the non-osteoblastic subtype had a worse prognosis (p = 0.007). The association of histological subtype maintained its significance in multivariate analysis for all studied survival categories. CONCLUSIONS: Tumor size greater than 15 cm is an adverse factor for local recurrence-free survival and overall survival but did not influence metastasis-free survival. The osteosarcoma histological type is a significant independent predictor for local recurrence-free survival, metastasis-free survival and overall survival. PMID:20037705

  2. GOLPH3 is a potential therapeutic target and a prognostic indicatior of poor survival in bladder cancer treated by cystectomy

    PubMed Central

    Zhao, Xiaozhi; Tang, Bo; Yao, Dongwei; Zhao, Wei; Chang, Cunjie; Lu, Qun; Chen, Wei; Zhang, Shiwei; Ji, Changwei; Cao, Lin; Guo, Hongqian

    2015-01-01

    Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. However, its clinical significance and biological role in bladder cancer remains unclear. In this study, we sought to analyze the GOLPH3 expression in bladder cancer samples and cells, and explore its clinical significance and biological role. We found that GOLPH3 was significantly increased in bladder cancer tissues and cells. Overexpression of GOLPH3 had significant correlation with poorer survival for bladder cancer patients treated by cystectomy. Knockdown of GOLPH3 inhibited the proliferation, migration and invasion of cancer cells, and tumor growth in a xenograft mouse model. GOLPH3 silencing inhibited AKT/m-TOR signaling, increased the cyclin-dependent kinase (CDK) inhibitor p27 and decreased the CDK regulator cyclin D1 and matrix metallopeptidase 9 (MMP9). Thus, GOLPH3 is likely to play important roles in bladder cancer progression via modulating AKT/mTOR signaling, and it is a novel prognostic biomarker and promising therapeutic target for bladder cancer. PMID:26375441

  3. Research on Good and Poor Reader Characteristics: Implications for L2 Reading Research in China

    ERIC Educational Resources Information Center

    Pang, Jixian

    2008-01-01

    In reading research, studies on good and poor reader characteristics abound. However, these findings remain largely scattered in applied linguistics and cognitive and educational psychology. This paper attempts to synthesize current theory and research on the topic in the past 20 years along 3 dimensions: language knowledge and processing ability,…

  4. Sp1 is over-expressed in nasopharyngeal cancer and is a poor prognostic indicator for patients receiving radiotherapy

    PubMed Central

    Wang, Jun; Kang, Min; Qin, Yu-Tao; Wei, Zhu-Xin; Xiao, Jing-Jian; Wang, Ren-Sheng

    2015-01-01

    Nasopharyngeal cancer (NPC) is a tumor of epithelial origin with complex etiology. Currently the standard treatment of NPC is radiotherapy, but therapy failure is quite common, making radioresistance an important issue. This study explores the association of specificity protein 1 (Sp1) protein expression with clinicopathological significance and disease prognosis in NPC patients receiving radiotherapy. A total of 82 NPC patients (55 males and 27 females, median age: 48 years old) were enrolled and received radiotherapy between September 2011 and March 2014. Tumor tissue and grossly adjacent normal mucosa were obtained in each patient. Sp1 expression was detected by western blot and immunohistochemical analysis, and the associations with clinicopathological status and radiotherapy response were analyzed. Our Results showed Sp1 protein expression was higher in CNE-1 and CNE-2 nasopharyngeal cancer cells than in normal nasopharyngeal mucosal NP69 cells. All 82 patients tissue sections were stained positive for the Sp1 protein, and 39 (47.6%) patients showed higher level than adjacent normal mucosa. Sp1-overexpression in the tumor tissue was correlated with a higher tumor stage, nodal status, clinical stage and distant metastasis (P < 0.01). Patients with higher Sp1 expression in pretreatment biopsies had a lower radiotherapy response compared to those with lower expression. In conclusion, Sp1 may play roles in radioresistance of nasopharyngeal cancer which attributes to tumor invasiveness, and serve as a novel prognostic marker of NPC radiotherapy. However, further studies are required to validate our findings in larger samples and explore more detailed mechanisms underlying radioresistance of Sp1. PMID:26261581

  5. GP96 is over-expressed in oral cavity cancer and is a poor prognostic indicator for patients receiving radiotherapy

    PubMed Central

    2011-01-01

    Background Oral cavity cancers (ORC) are the most common cancers, and standard treatment is radical surgery with postoperative radiotherapy. However, locoregional failure remains a major problem, indicating radioresistance an important issue. Our previous work has shown that GP96 contributed to radioresistance in nasopharyngeal and oral cancer cell lines. In this study, we determined clinical significance of GP96 in ORC by evaluation of GP96 expression and its association with disease prognosis in patients receiving radiotherapy Methods Total of 79 ORC patients (77 males, median age: 48 years old) receiving radical surgery and postoperative radiotherapy between Oct 1999 and Dec 2004 were enrolled. Patients in pathological stages II, III and IV were 16.5%, 16.5% and 67%, respectively. For each patient, a pair of carcinoma tissue and grossly adjacent normal mucosa was obtained. GP96-expression was examined by western blot analysis, and the association with clinicopathological status was determined. Results Three-year locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) rates were 69%, 79%, 63% and 57%, respectively. We found that 55 patients (70%) displayed GP96-overexpression in the tumor tissue, which correlated with a higher pN stage (p = 0.020) and tumor depth (> 10 mm) (p = 0.045). Nodal extracapsular spreading (ECS) and GP96-overexpression predicted adverse LRC (p = 0.049 and p = 0.008). When stratified by nodal ECS, the adverse impact of GP96 remained significant in three-year LRC (p = 0.004). In multivariate analysis, GP96-overexpression was also an independent predictor of LRC, DSS and OS (p = 0.018, p = 0.011 and p = 0.012). Conclusion GP96 may play roles in radioresistance which attributes to tumor invasiveness in oral cancer patients receiving radiotherapy. GP96 may serve as a novel prognostic marker of radiotherapy. However, further independent studies are required to validate our findings in a larger series. PMID:21992474

  6. CD44 Variant 9 Serves as a Poor Prognostic Marker in Early Gastric Cancer, But Not in Advanced Gastric Cancer

    PubMed Central

    Go, Se-Il; Ko, Gyung Hyuck; Lee, Won Sup; Kim, Rock Bum; Lee, Jeong-Hee; Jeong, Sang-Ho; Lee, Young-Joon; Hong, Soon Chan; Ha, Woo Song

    2016-01-01

    Purpose The present study is to investigate the significance of CD44 variant 9 (CD44v9) expression as a biomarker in primary gastric cancer. Materials and Methods With various gastric tissues, we performed immunohistochemical staining for CD44v9. Results The positive expression rates for CD44v9 in tumor, including adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC), were higher than those in non-tumor tissues (p=0.003). In addition, the higher expression for CD44v9 was observed as the tissue becomes malignant. In the analysis of 333 gastric cancer tissues, we found that positive expression rates for CD44v9 were higher in the intestinal type or well differentiated gastric cancer than in the diffuse type or poorly differentiated gastric cancer. Interestingly, the positive expression indicated poor prognosis in EGC (5-year survival rate [5-YSR] in stage I, 81.7% vs. 95.2%; p=0.013), but not in AGC (5-YSR in stage II, 66.9% vs. 62.2%; p=0.821; 5-YSR in stage III, 34.5% vs. 32.0%; p=0.929). Moreover, strong positive expression (3+) showed a trend suggesting worse prognosis only in EGC, and it appeared to be associated with lymph node metastasis. Conclusion This study suggests that CD44v9 may be a good biomarker for prognosis prediction and for chemoprevention or biomarker-driven therapies only for EGC. PMID:25779358

  7. Facility characteristics as independent prognostic factors of nursing home-acquired pneumonia

    PubMed Central

    Lim, Che Wan; Choi, Younghoon; An, Chang Hyeok; Park, Sang Joon; Hwang, Hee-Jin; Chung, Jae Ho; Min, Joo-Won

    2016-01-01

    Background/Aims: Recently, the incidence of nursing home-acquired pneumonia (NHAP) has been increasing and is now the leading cause of death among nursing home residents. This study was performed to identify risk factors associated with NHAP mortality, focusing on facility characteristics. Methods: Data on all patients ≥ 70 years of age admitted with newly diagnosed pneumonia were reviewed. To compare the quality of care in nursing facilities, the following three groups were defined: patients who acquired pneumonia in the community, care homes, and care hospitals. In these patients, 90-day mortality was compared. Results: Survival analyses were performed in 282 patients with pneumonia. In the analyses, 90-day mortality was higher in patients in care homes (12.2%, 40.3%, and 19.6% in community, care homes, and care hospitals, respectively). Among the 118 NHAP patients, residence in a care home, structural lung diseases, treatment with inappropriate antimicrobial agents for accompanying infections, and a high pneumonia severity index score were risk factors associated with higher 90-day mortality. However, infection by potentially drug-resistant pathogens was not important. Conclusions: Unfavorable institutional factors in care homes are important prognostic factors for NHAP. PMID:26837007

  8. Clinical Characteristics and Prognostic Factors in Dogs with Histiocytic Sarcomas in Japan

    PubMed Central

    TAKAHASHI, Masashi; TOMIYASU, Hirotaka; HOTTA, Eri; ASADA, Hajime; FUKUSHIMA, Kenjiro; KANEMOTO, Hideyuki; FUJINO, Yasuhito; OHNO, Koichi; UCHIDA, Kazuyuki; NAKAYAMA, Hiroyuki; TSUJIMOTO, Hajime

    2014-01-01

    ABSTRACT Canine histiocytic sarcoma (HS) is a rare neoplasm that originates from dendritic cells or macrophages, and there have been a number of cases experienced in Japan. To identify the characteristics and prognostic variables that determine outcome in dogs with HS in Japan, medical records of 73 dogs with HS were retrospectively analyzed. Signalment, clinical signs, complete blood count (CBC), blood chemistry profiles, treatment, response to treatment and overall survival (OS) were analyzed. Diagnosis of HS was determined histologically in 44 cases and cytologically in 29 cases. The most frequently diagnosed breeds were Flat-Coated Retrievers (n=16, odds ratio [OR] 62.0), Pembroke Welsh corgis (n=15, OR 9.7) and Bernese Mountain dogs (n=14, OR 45.0). Median survival time for all dogs in this study was 43 days. In the dogs that received no treatment or only symptomatic treatment, the median OS was 12 days (range 2–254 days) compared with that of dogs that received surgical treatment and/or chemotherapy (85 days, range 4–360 days). Univariate analysis identified anemia, thrombocytopenia, hypoalbuminemia, hypoproteinemia and not receiving antitumor treatment (chemotherapy and/or surgery) as factors significantly associated with shorter OS. Multivariate analysis confirmed that platelet counts, localized/disseminated lesional pattern and whether the dog received antitumor treatment were significantly predictive of survival. PMID:24441652

  9. MTHFR C677T polymorphism and anatomopathological characteristics with prognostic significance in sporadic colorectal cancer.

    PubMed

    Delgado-Plasencia, Luciano; lvarez-Argelles, Hugo; Salido-Ruiz, Eduardo; Castro-Peraza, M Elisa; Bravo-Gutirrez, Alberto; Fernndez-Peralta, Antonia; Gonzlez-Aguilera, Juan; Alarc-Hernndez, Antonio; Medina-Arana, Vicente

    2015-12-01

    Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, and folate is implicated in carcinogenesis due to its role in DNA methylation, repair and synthesis. The MTHFR C677T polymorphism is associated with decreased risk of CRC and increased sensitivity to 5-FU treatment. The present study addressed the relationship between this polymorphism and histopathological and immunohistochemical characteristics of prognostic significance in 50 patients from the Canary Islands. No differences were found between the MTHFR C677T genotypes with respect to tumor budding, tumor necrosis, desmoplastic fibrosis and tumoral eosinophilia. No significant differences were found in Ki-67, bcl-2 (cytoplasmic and nuclear), CD31, CD3+ T lymphocytes (both stromal and intraepithelial) and peritumoral CD20+ B lymphocytes. In carriers of the MTHFR CC variant, tumor margins were infiltrative more frequently (68.7%) than in CT+TT carriers (33.3%, p=0.03). In addition, wild-type CC genotype showed stromal CD20+ B lymphocytes (68.8%) more often than CT+TT carriers (33.3%, p=0.03). Both parameters indicate a better tumor prognosis when the MTHFR 677T variant is present. PMID:26564107

  10. Loss of heterozygosity in tumor tissue in hormonal receptor genes is associated with poor prognostic criteria in breast cancer.

    PubMed

    Iobagiu, Cristina; Lambert, Claude; Raica, Marius; Lima, Suzanne; Khaddage, Abir; Peoc'h, Michel; Genin, Christian

    2015-04-01

    The estrogen receptors (ESR? and ?) and the androgen receptor (AR) mediate genomic and non-genomic effects on breast tumor growth and proliferation. We analyzed 101 breast cancer patients for allelic loss in microsatellites located in regulatory regions of the ESRs and AR genes in breast cancer tumors. The loss of heterozygosity (LOH) at these loci was found in 36.2% of tumor tissues (ductal carcinoma cases), for 19% of cases at the ESR? locus, for 16% at the ESR? locus, and for 10% at the AR locus. The LOH in at least one of the two ESR loci was correlated to poor prognosis criteria: ESR-negative status (P=0.007), PR-negative status (P=0.003), high Scarff-Bloom-Richardson (SBR) grade (P=0.0007), high MIB-1 proliferation index (P=0.02), and diminished apoptosis potential (TP53-positive status, P=0.018). When AR was also considered, the LOH in at least one of the three loci was associated with ESR-negative status (P=0.036), PR-negative status (P=0.027), high SBR grade (P=0.005), high mitotic index (P=0.0002), TP53-positive status (P=0.029), and proliferating index (high MIB-1, P=0.03). Allelic loss was observed in 26% of normal tissue adjacent to tumor with LOH at the ESR? locus and in 7.1% of tumors with LOH at the ESR? locus. The LOH in tumor tissue in the regulatory regions of ESR?, ESR?, and AR genes has potentially synergistic effects on tumor proliferation, histological aggressiveness, down-regulation of ESR? and progesterone receptor (PR) genes, and is an early genetic alteration in cancer that is possibly involved in passage to estrogen independence. PMID:25979597

  11. EMP1, a novel poor prognostic factor in pediatric leukemia regulates prednisolone resistance, cell proliferation, migration and adhesion.

    PubMed

    Aris, I M; Jerchel, I S; van den Dungen, R E S R; van den Berk, L C J; Boer, J M; Horstmann, M A; Escherich, G; Pieters, R; den Boer, M L

    2014-09-01

    Still 20% of pediatric acute lymphoblastic leukemia (ALL) patients relapse on or after current treatment strategies. Treatment failure is associated with resistance to prednisolone. We aimed to find new druggable targets that modulate prednisolone resistance. We generated microarray gene expression profiles of 256 pediatric ALL patient samples and identified a 3.4-fold increase in epithelial membrane protein 1 (EMP1) expression in in vitro prednisolone-resistant compared with -sensitive patients (P=0.003). EMP1 silencing in six precursor-B ALL (BCP-ALL) and T-ALL cell lines induced apoptosis and cell-cycle arrest leading to 84.14.5% reduction in survival compared with non-silencing control transduced cells (non-silencing control short hairpin, shNSC) (P=0.014). Moreover, EMP1 silencing sensitized to prednisolone up to 18.8-fold (P<0.001). EMP1 silencing also abrogated migration and adhesion to mesenchymal stromal cells (MSCs) by 78.39.0 and 29.34.1% compared with shNSC (P<0.05). We discovered that EMP1 contributes to MSC-mediated prednisolone resistance. Pathway analysis indicated that EMP1 signals through the Src kinase family. EMP1-high BCP-ALL patients showed a poorer 5-year event-free survival compared with EMP1-low patients (772 vs. 892%, P=0.003). Multivariate analysis taking along white blood cell count, age, prednisolone resistance and subtype identified EMP1 as an independent predictor for poor outcome in BCP-ALL (P=0.004, hazard ratio: 2.36 (1.31-4.25). This study provides preclinical evidence that EMP1 is an interesting candidate for drug development to optimize treatment of BCP-ALL. PMID:24625531

  12. Generation of a poor prognostic chronic lymphocytic leukemia-like disease model: PKC? subversion induces up-regulation of PKC?II expression in B lymphocytes

    PubMed Central

    Nakagawa, Rinako; Vukovic, Milica; Tarafdar, Anuradha; Cosimo, Emilio; Dunn, Karen; McCaig, Alison M.; Holroyd, Ailsa; McClanahan, Fabienne; Ramsay, Alan G.; Gribben, John G.; Michie, Alison M.

    2015-01-01

    Overwhelming evidence identifies the microenvironment as a critical factor in the development and progression of chronic lymphocytic leukemia, underlining the importance of developing suitable translational models to study the pathogenesis of the disease. We previously established that stable expression of kinase dead protein kinase C alpha in hematopoietic progenitor cells resulted in the development of a chronic lymphocytic leukemia-like disease in mice. Here we demonstrate that this chronic lymphocytic leukemia model resembles the more aggressive subset of chronic lymphocytic leukemia, expressing predominantly unmutated immunoglobulin heavy chain genes, with upregulated tyrosine kinase ZAP-70 expression and elevated ERK-MAPK-mTor signaling, resulting in enhanced proliferation and increased tumor load in lymphoid organs. Reduced function of PKC? leads to an up-regulation of PKC?II expression, which is also associated with a poor prognostic subset of human chronic lymphocytic leukemia samples. Treatment of chronic lymphocytic leukemia-like cells with the selective PKC? inhibitor enzastaurin caused cell cycle arrest and apoptosis both in vitro and in vivo, and a reduction in the leukemic burden in vivo. These results demonstrate the importance of PKC?II in chronic lymphocytic leukemia-like disease progression and suggest a role for PKC? subversion in creating permissive conditions for leukemogenesis. PMID:25616575

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

    PubMed

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

    2016-02-01

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

  14. Generation of a poor prognostic chronic lymphocytic leukemia-like disease model: PKC? subversion induces up-regulation of PKC?II expression in B lymphocytes.

    PubMed

    Nakagawa, Rinako; Vukovic, Milica; Tarafdar, Anuradha; Cosimo, Emilio; Dunn, Karen; McCaig, Alison M; Holroyd, Ailsa; McClanahan, Fabienne; Ramsay, Alan G; Gribben, John G; Michie, Alison M

    2015-04-01

    Overwhelming evidence identifies the microenvironment as a critical factor in the development and progression of chronic lymphocytic leukemia, underlining the importance of developing suitable translational models to study the pathogenesis of the disease. We previously established that stable expression of kinase dead protein kinase C alpha in hematopoietic progenitor cells resulted in the development of a chronic lymphocytic leukemia-like disease in mice. Here we demonstrate that this chronic lymphocytic leukemia model resembles the more aggressive subset of chronic lymphocytic leukemia, expressing predominantly unmutated immunoglobulin heavy chain genes, with upregulated tyrosine kinase ZAP-70 expression and elevated ERK-MAPK-mTor signaling, resulting in enhanced proliferation and increased tumor load in lymphoid organs. Reduced function of PKC? leads to an up-regulation of PKC?II expression, which is also associated with a poor prognostic subset of human chronic lymphocytic leukemia samples. Treatment of chronic lymphocytic leukemia-like cells with the selective PKC? inhibitor enzastaurin caused cell cycle arrest and apoptosis both in vitro and in vivo, and a reduction in the leukemic burden in vivo. These results demonstrate the importance of PKC?II in chronic lymphocytic leukemia-like disease progression and suggest a role for PKC? subversion in creating permissive conditions for leukemogenesis. PMID:25616575

  15. Demographic characteristics and prognostic indicators of childhood burn in a developing country.

    PubMed

    Olawoye, O A; Iyun, A O; Ademola, S A; Michael, A I; Oluwatosin, O M

    2014-12-01

    Children constitute a significant proportion of burn victims in most studies from the developing countries. While there has been a progressive improvement in the outcome from childhood burn in many developed nations, the morbidity and mortality remains high in many low and middle income countries. The aim of our study is to evaluate the demographic characteristics and prognostic indicators of childhood burn in a major referral teaching hospital in a developing country. A review of the records of 638 patients with acute burns managed over a 10-year period from January 2001 to December 2010 at the University College Hospital, Ibadan Nigeria was done. The clinical and epidemiological data were retrieved from computerized data base using the ISBI proforma. Information obtained includes Biodata, Etiology, location, TBSA, presence of Inhalation injury and the treatment outcome. Data of patients aged 16 years and below were analyzed using the SPSS version 16. The main outcome measure was the patient's survival. 289 children representing 45.3% of the total number of burn patients were managed over the period. The M:F ratio was 1.1:1. The median age of the cohort was 4.0 years while the median TBSA was 21.0%. Non-intentional causes were responsible for 89.6% cases. Most of the injuries (88.6%) occurred at home. Eighty-three patients had inhalation injury out of which 57 (68.7%) deaths were recorded. The overall mortality rate in the cohort was 39.5% with an LA50 of burn size of 45%. The TBSA was also found to be a determinant of outcome. Majority of childhood burns are from preventable causes with attendant dismal mortality figures. Effective burn prevention strategies and improved quality of care remain pivotal in reducing childhood burn morbidity and mortality in the developing countries. PMID:24933574

  16. 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. PMID:26016821

  17. Prognostic Relevance of Cytokine Receptor Expression in Acute Myeloid Leukemia: Interleukin-2 Receptor ?-Chain (CD25) Expression Predicts a Poor Prognosis

    PubMed Central

    Nakase, Kazunori; Kita, Kenkichi; Kyo, Taiichi; Ueda, Takanori; Tanaka, Isao; Katayama, Naoyuki

    2015-01-01

    A variety of cytokine/cytokine receptor systems affect the biological behavior of acute leukemia cells. However, little is known about the clinical relevance of cytokine receptor expression in acute myeloid leukemia (AML). We quantitatively examined the expression of interleukin-2 receptor ?-chain (IL-2R?, also known as CD25), IL-2R?, IL-3R?, IL-4R?, IL-5R?, IL-6R?, IL-7R?, the common ?-chain (?c), ?c, granulocyte-macrophage colony-stimulating factor (GM-CSF)R?, G-CSFR, c-fms, c-mpl, c-kit, FLT3, and GP130 in leukemia cells from 767 adult patients with AML by flow cytometry and determined their prevalence and clinical significance. All cytokine receptors examined were expressed at varying levels, whereas the levels of IL-3R?, GM-CSFR?, IL-2R?, ?c, c-kit, and G-CSFR exhibited a wide spectrum of ?10,000 sites/cell. In terms of their French-American-British classification types, GM-CSFR? and c-fms were preferentially expressed in M4/M5 patients, G-CSF in M3 patients, and IL-2R? in non-M3 patients. Elevated levels of IL-3R?, GM-CSFR?, and IL-2R? correlated with leukocytosis. In patients ?60 years old, higher levels of these 3 receptors correlated with poor responses to conventional chemotherapy, but only IL-2R? was associated with a shorter overall survival. By incorporating IL-2R? status into cytogenetic risk stratification, we could sort out a significantly adverse-risk cohort from the cytogenetically intermediate-risk group. Analyses with various phenotypical risk markers revealed the expression of IL-2R? as an independent prognostic indicator in patients with intermediate-risk cytogenetics. These findings were not observed in patients >60 years old. Our results indicate that several cytokine receptors were associated with certain cellular and clinical features, but IL-2R? alone had prognostic value that provides an additional marker to improve current risk evaluation in AML patients ?60 years old. PMID:26375984

  18. Prognostic Relevance of Cytokine Receptor Expression in Acute Myeloid Leukemia: Interleukin-2 Receptor ?-Chain (CD25) Expression Predicts a Poor Prognosis.

    PubMed

    Nakase, Kazunori; Kita, Kenkichi; Kyo, Taiichi; Ueda, Takanori; Tanaka, Isao; Katayama, Naoyuki

    2015-01-01

    A variety of cytokine/cytokine receptor systems affect the biological behavior of acute leukemia cells. However, little is known about the clinical relevance of cytokine receptor expression in acute myeloid leukemia (AML). We quantitatively examined the expression of interleukin-2 receptor ?-chain (IL-2R?, also known as CD25), IL-2R?, IL-3R?, IL-4R?, IL-5R?, IL-6R?, IL-7R?, the common ?-chain (?c), ?c, granulocyte-macrophage colony-stimulating factor (GM-CSF)R?, G-CSFR, c-fms, c-mpl, c-kit, FLT3, and GP130 in leukemia cells from 767 adult patients with AML by flow cytometry and determined their prevalence and clinical significance. All cytokine receptors examined were expressed at varying levels, whereas the levels of IL-3R?, GM-CSFR?, IL-2R?, ?c, c-kit, and G-CSFR exhibited a wide spectrum of ?10,000 sites/cell. In terms of their French-American-British classification types, GM-CSFR? and c-fms were preferentially expressed in M4/M5 patients, G-CSF in M3 patients, and IL-2R? in non-M3 patients. Elevated levels of IL-3R?, GM-CSFR?, and IL-2R? correlated with leukocytosis. In patients ?60 years old, higher levels of these 3 receptors correlated with poor responses to conventional chemotherapy, but only IL-2R? was associated with a shorter overall survival. By incorporating IL-2R? status into cytogenetic risk stratification, we could sort out a significantly adverse-risk cohort from the cytogenetically intermediate-risk group. Analyses with various phenotypical risk markers revealed the expression of IL-2R? as an independent prognostic indicator in patients with intermediate-risk cytogenetics. These findings were not observed in patients >60 years old. Our results indicate that several cytokine receptors were associated with certain cellular and clinical features, but IL-2R? alone had prognostic value that provides an additional marker to improve current risk evaluation in AML patients ?60 years old. PMID:26375984

  19. The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression

    PubMed Central

    Atsumi, Tatsuya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Yasuda, Shinsuke; Yamanishi, Yuji; Kita, Yasuhiko; Matsubara, Tsukasa; Iwamoto, Masahiro; Shoji, Toshiharu; Okada, Toshiyuki; Miyasaka, Nobuyuki; Koike, Takao

    2016-01-01

    Objectives To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. Methods MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52. Results 316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p<0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX. Conclusions In MTX-naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients. Trial registration number (NCT01451203). PMID:26139005

  20. Clinical course, characteristics and prognostic indicators in patients presenting with back and leg pain in primary care. The ATLAS study protocol

    PubMed Central

    2012-01-01

    Background Low-back related leg pain with or without nerve root involvement is associated with a poor prognosis compared to low back pain (LBP) alone. Compared to the literature investigating prognostic indicators of outcome for LBP, there is limited evidence on prognostic factors for low back-related leg pain including the group with nerve root pain. This 1 year prospective consultation-based observational cohort study will describe the clinical, imaging, demographic characteristics and health economic outcomes for the whole cohort, will investigate differences and identify prognostic indicators of outcome (i.e. change in disability at 12 months), for the whole cohort and, separately, for those classified with and without nerve root pain. In addition, nested qualitative studies will provide insights on the clinical consultation and the impact of diagnosis and treatment on patients' symptom management and illness trajectory. Methods Adults aged 18 years and over consulting their General Practitioner (GP) with LBP and radiating leg pain of any duration at (n = 500) GP practices in North Staffordshire and Stoke-on-Trent, UK will be invited to participate. All participants will receive a standardised assessment at the clinic by a study physiotherapist and will be classified according to the clinically determined presence or absence of nerve root pain/involvement. All will undergo a lumbar spine MRI scan. All participants will be managed according to their clinical need. The study outcomes will be measured at 4 and 12 months using postal self-complete questionnaires. Data will also be collected each month using brief postal questionnaires to enable detailed description of the course of low back and leg pain over time. Clinical observations and patient interviews will be used for the qualitative aspects of the study. Discussion This prospective clinical observational cohort will combine self-reported data, comprehensive clinical and MRI assessment, together with qualitative enquiries, to describe the course, health care usage, patients' experiences and prognostic indicators in an adult population presenting in primary care with LBP and leg pain with or without nerve root involvement. PMID:22264273

  1. Decreased expression of PinX1 protein is correlated with tumor development and is a new independent poor prognostic factor in ovarian carcinoma.

    PubMed

    Cai, Mu-Yan; Zhang, Bin; He, Wei-Peng; Yang, Guo-Fen; Rao, Hui-Lan; Rao, Zhi-Yue; Wu, Qiu-Liang; Guan, Xin-Yuan; Kung, Hsiang-Fu; Zeng, Yi-Xin; Xie, Dan

    2010-06-01

    Human interacting protein X1 (PinX1) has been identified as a critical telomerase inhibitor and proposed to be a putative tumor suppressor gene. Loss of PinX1 has been found in a large variety of malignancies, but the expression status in epithelial ovarian tumors has not been investigated. In this study, immunohistochemistry for PinX1 protein was performed on a tissue microarray (TMA) of epithelial ovarian tumors (informatively containing 25 cystadenomas, 29 borderline tumors, and 157 invasive carcinomas) and 12 normal ovaries. Receiver-operator curve (ROC) analysis was used to determine cut-off scores for tumor positivity and to evaluate patients' survival status. The threshold for PinX1 positivity was determined to be above 60% (area under the curve = 0.856, P < 0.001) based on the area under the ROC. Positive expression of PinX1 was observed in 100% of normal ovarian tissues, in 84% of cystadenomas, in 75.9% borderline tumors, and 66.2% of ovarian carcinomas. Decreased expression of PinX1 was strongly related to patients with poor prognostic factors regarding presence of lymph node metastasis (P = 0.024), distant metastasis (P < 0.001), and late International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001). In univariate survival analysis, a highly significant correlation between loss of PinX1 and shortened patient survival (mean, 48.2 months vs 99.2 months, P < 0.001) was displayed. Multivariate analysis demonstrated PinX1 expression (P = 0.027) was evaluated as an independent parameter. Our findings suggest that loss of PinX1 is an adverse independent molecular marker for epithelial ovarian carcinoma patients. PinX1 may be a novel target for telomerase-based anticancer therapy due to inhibiting telomerase activity. PMID:20367640

  2. 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

  3. Parent-Adolescent Discrepancies in Perceived Parenting Characteristics and Adolescent Developmental Outcomes in Poor Chinese Families.

    PubMed

    Leung, Janet T Y; Shek, Daniel T L

    2014-01-01

    We examined the relationships between parent-adolescent discrepancies in perceived parenting characteristics (indexed by parental responsiveness, parental demandingness, and parental control) and adolescent developmental outcomes (indexed by achievement motivation and psychological competence) in poor families in Hong Kong. A sample of 275 intact families having at least one child aged 11-16 experiencing economic disadvantage were invited to participate in the study. Fathers and mothers completed the Parenting Style Scale and Chinese Parental Control Scale, and adolescents completed the Social-Oriented Achievement Motivation Scale and Chinese Positive Youth Development Scale in addition to paternal and maternal Parenting Style Scale and Chinese Parental Control Scale. Results indicated that parents and adolescents had different perceptions of parental responsiveness, parental demandingness, and paternal control, with adolescents generally perceived lower levels of parenting behaviors than did their parents. While father-adolescent discrepancy in perceived paternal responsiveness and mother-adolescent discrepancy in perceived maternal control negatively predicted adolescent achievement motivation, mother-adolescent discrepancy in perceptions of maternal responsiveness negatively predicted psychological competence in adolescents experiencing economic disadvantage. The present findings provided support that parent-child discrepancies in perceived parenting characteristics have negative impacts on the developmental outcomes of adolescents experiencing economic disadvantage. The present study addresses parent-child discrepancies in perceived parental behaviors as "legitimate" constructs, and explores their links with adolescent psychosocial development, which sheds light for researchers and clinical practitioners in helping the Chinese families experiencing economic disadvantage. PMID:24482569

  4. A phase III randomized trial of postoperative pelvic irradiation in stage IB cervical carcinoma with poor prognostic features: Follow-up of a gynecologic oncology group study

    SciTech Connect

    Rotman, Marvin . E-mail: mrotman@downstate.edu; Sedlis, Alexander; Piedmonte, Marion R.; Bundy, Brian; Lentz, Samuel S.; Muderspach, Laila I.; Zaino, Richard J.

    2006-05-01

    Purpose: To investigate, in a phase III randomized trial, whether postoperative external-beam irradiation to the standard pelvic field improves the recurrence-free interval and overall survival (OS) in women with Stage IB cervical cancers with negative lymph nodes and certain poor prognostic features treated by radical hysterectomy and pelvic lymphadenectomy. Methods and Materials: Eligible patients had Stage IB cervical cancer with negative lymph nodes but with 2 or more of the following features: more than one third (deep) stromal invasion, capillary lymphatic space involvement, and tumor diameter of 4 cm or more. The study group included 277 patients: 137 randomized to pelvic irradiation (RT) and 140 randomized to observation (OBS). The planned pelvic dose was from 46 Gy in 23 fractions to 50.4 Gy in 28 fractions. Results: Of the 67 recurrences, 24 were in the RT arm and 43 were in the OBS arm. The RT arm showed a statistically significant (46%) reduction in risk of recurrence (hazard ratio [HR] = 0.54, 90% confidence interval [CI] = 0.35 to 0.81, p = 0.007) and a statistically significant reduction in risk of progression or death (HR = 0.58, 90% CI = 0.40 to 0.85, p = 0.009). With RT, 8.8% of patients (3 of 34) with adenosquamous or adenocarcinoma tumors recurred vs. 44.0% (11 of 25) in OBS. Fewer recurrences were seen with RT in patients with adenocarcinoma or adenosquamous histologies relative to others (HR for RT by histology interaction = 0.23, 90% CI = 0.07 to 0.74, p = 0.019). After an extensive follow-up period, 67 deaths have occurred: 27 RT patients and 40 OBS patients. The improvement in overall survival (HR = 0.70, 90% CI = 0.45 to 1.05, p = 0.074) with RT did not reach statistical significance. Conclusions: Pelvic radiotherapy after radical surgery significantly reduces the risk of recurrence and prolongs progression-free survival in women with Stage IB cervical cancer. RT appears to be particularly beneficial for patients with adenocarcinoma or adenosquamous histologies. Circumstances that may have influenced the overall survival differences are considered.

  5. Transurethral microwave thermotherapy for benign prostatic hyperplasia: patient characteristics in good and poor responders.

    PubMed

    Arai, Y; Terai, A; Onishi, H; Oishi, K; Takeuchi, H; Yoshida, O

    1994-09-01

    Transurethral microwave thermotherapy (TUMT) has been shown to produce a clinical benefit in patients with symptomatic benign prostatic hyperplasia. In order to identify the features of the ideal candidate, a retrospective analysis was conducted in 32 patients who were followed for 2 mo or more. Good responders (GR) were defined as having their Siroky peak flow rate (PFR) standard deviation (SD) increase by < 0.5 or a decrease in the International Prostatic Symptom Score (I-PSS) of > 10 (22 patients). Poor responders (PR) were defined as having their PFR SD increase by < or = 0.5 and their I-PSS decrease by < or = 10 (10 patients). The prostate volume, pre-TUMT I-PSS and intravesical opening pressure were significantly greater in the GR group, while there were no significant differences between the 2 groups for the other baseline patient characteristics: age, prostate length, PFR, PFR SD, post-voiding residual volume and quality of life. Concerning the operational parameters, significantly more total energy was delivered to the prostate in the GR group (mean 131 kJ) than in the PR group (mean 101 kJ). Moreover, the 7 patients with anti-androgen therapy pre-TUMT received less total energy and 5 of the 7 were poor responders. These results suggest that patients with apparent obstructive symptoms and with moderate enlargement of prostate could benefit more from this less invasive therapy. Clinical response seems to be dose-dependent and patients with a history of recent anti-androgen treatment may have a less favorable response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7542156

  6. Psycho-Social Characteristics of Secondary School Vocational Trainees Rated by their Instructors as Having Poor Worker Potential.

    ERIC Educational Resources Information Center

    Johnson, Donald Henry

    A study was made of 269 boys and 388 girls enrolled in "capstone" courses in 30 cooperating schools of Wisconsin's Pilot Program in Vocational Education. The purpose was to identify psychosocial characteristics of secondary school trainees rated by their teachers as having poor employment potential. Characteristics were analyzed in terms of

  7. 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

    Background Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity. Methods and Findings In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08–0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22–0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses. Conclusion In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women. PMID:21386992

  8. 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 species. Thus, metabolic activity of gut tissue did not significantly influence the net ammonia transfer. Due to the much higher gut to fork length ratio, the overall transport capacity of the gut of the herbivorous Pacu by far exceeded the transport capacity of their carnivorous and omnivorous relatives, thus compensating for the lower digestibility and the low Na(+), Cl(-), and N-content of the plant diet. Accordingly, in order to cope with the more difficult digestible plant material and the very low nitrogen content of plants, herbivorous fish have not evolved more effective area-specific transport capacities, but rather have increased the length of the gut. PMID:25528145

  9. Clinical Characteristics and Prognostic Factors in Early-Onset Alopecia Totalis and Alopecia Universalis

    PubMed Central

    Cho, Hyun Hee; Jo, Seong Jin; Paik, Seung Hwan; Jeon, Hye Chan; Kim, Kyu Han; Eun, Hee Chul

    2012-01-01

    Alopecia totalis (AT) and alopecia universalis (AU), severe forms of alopecia areata (AA), show distinguishable clinical characteristics from those of patch AA. In this study, we investigated the clinical characteristics of AT/AU according to the onset age. Based on the onset age around adolescence (< or ? 13 yr), 108 patients were classified in an early-onset group and the other 179 patients in a late-onset group. We found that more patients in the early-onset group had a family history of AA, nail dystrophy, and history of atopic dermatitis than those in the late-onset group. These clinical differences were more prominent in patients with AU than in those with AT. In addition, significantly more patients with concomitant medical disorders, especially allergic diseases were found in the early-onset group (45.8%) than in the late-onset group (31.2%). All treatment modalities failed to show any association with the present hair condition of patients. In the early-onset group, patients with AU or a family history of AA showed worse prognosis, whereas this trend was not observed in the late-onset group. Systemic evaluations might be needed in early-onset patients due to the higher incidence of comorbid diseases. It is suggested that patients with AU or family history of AA make worse progress in the early-onset group than in the late-onset group. PMID:22787378

  10. Clinical characteristics and prognostic factors in early-onset alopecia totalis and alopecia universalis.

    PubMed

    Cho, Hyun Hee; Jo, Seong Jin; Paik, Seung Hwan; Jeon, Hye Chan; Kim, Kyu Han; Eun, Hee Chul; Kwon, Oh Sang

    2012-07-01

    Alopecia totalis (AT) and alopecia universalis (AU), severe forms of alopecia areata (AA), show distinguishable clinical characteristics from those of patch AA. In this study, we investigated the clinical characteristics of AT/AU according to the onset age. Based on the onset age around adolescence (< or ? 13 yr), 108 patients were classified in an early-onset group and the other 179 patients in a late-onset group. We found that more patients in the early-onset group had a family history of AA, nail dystrophy, and history of atopic dermatitis than those in the late-onset group. These clinical differences were more prominent in patients with AU than in those with AT. In addition, significantly more patients with concomitant medical disorders, especially allergic diseases were found in the early-onset group (45.8%) than in the late-onset group (31.2%). All treatment modalities failed to show any association with the present hair condition of patients. In the early-onset group, patients with AU or a family history of AA showed worse prognosis, whereas this trend was not observed in the late-onset group. Systemic evaluations might be needed in early-onset patients due to the higher incidence of comorbid diseases. It is suggested that patients with AU or family history of AA make worse progress in the early-onset group than in the late-onset group. PMID:22787378

  11. Pneumocystis Pneumonia in Patients with Autoimmune Diseases: A Retrospective Study Focused on Clinical Characteristics and Prognostic Factors Related to Death

    PubMed Central

    Chen, Minjiang; Tian, Xinlun; Qin, Fang; Zhou, Jiong; Liu, Jinjing; Wang, Mengzhao; Xu, Kai-Feng

    2015-01-01

    Background With the increasing use of immunosuppressive agents, the number of opportunistic infections has risen in patients with autoimmune diseases. Pneumocystis pneumonia (PCP) is one of these opportunistic infections that have a high mortality rate. However, only a few studies have described PCP in these patients, and these studies are limited in scope. We conducted this retrospective study to describe the clinical characteristics and factors associated with outcomes of PCP in patients with autoimmune diseases. Methods A retrospective study was performed in laboratory diagnosed PCP patients with autoimmune diseases in an academic hospital over a 10-year period. Patients with human immunodeficiency virus (HIV) infection were not included. Clinical characteristics were collected and the factors related to death were analysed. Results A total of 69 patients with PCP during the study period were included. Common clinical features included fever (81%), cough (56%), and dyspnea (35%). Ground glass opacity (81%) and reticulation (52%) were the most common radiological findings. Concurrent pulmonary infections including bacterium, aspergillus and cytomegalovirus were found in 34% of the patients. The overall in-hospital mortality rate was 32%. High mortality was associated with lower PaO2/FiO2 ratios and albumin levels. The lymphocyte count, CD4+ T cell count, previous usage of immunosuppressive agents, the duration and dose of glucocorticoids did not affect the outcome. Conclusions The mortality rate in PCP patients with autoimmune diseases is high. Low PaO2/FiO2 ratios and albumin levels are independent prognostic factors of mortality. PMID:26422246

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

    ERIC Educational Resources Information Center

    Sa, Steffani; Schtte, 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

  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. 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,…

  15. Pathway-Centric Integrative Analysis Identifies RRM2 as a Prognostic Marker in Breast Cancer Associated with Poor Survival and Tamoxifen Resistance123

    PubMed Central

    Putluri, Nagireddy; Maity, Suman; Kommangani, Ramakrishna; Creighton, Chad J.; Putluri, Vasanta; Chen, Fengju; Nanda, Sarmishta; Bhowmik, Salil Kumar; Terunuma, Atsushi; Dorsey, Tiffany; Nardone, Agostina; Fu, Xiaoyong; Shaw, Chad; Sarkar, Tapasree Roy; Schiff, Rachel; Lydon, John P.; OMalley, Bert W.; Ambs, Stefan; Das, Gokul M.; Michailidis, George; Sreekumar, Arun

    2014-01-01

    Breast cancer (BCa) molecular subtypes include luminal A, luminal B, normal-like, HER-2enriched, and basal-like tumors, among which luminal B and basal-like cancers are highly aggressive. Biochemical pathways associated with patient survival or treatment response in these more aggressive subtypes are not well understood. With the limited availability of pathologically verified clinical specimens, cell line models are routinely used for pathway-centric studies. We measured the metabolome of luminal and basal-like BCa cell lines using mass spectrometry, linked metabolites to biochemical pathways using Gene Set Analysis, and developed a novel rank-based method to select pathways on the basis of their enrichment in patient-derived omics data sets and prognostic relevance. Key mediators of the pathway were then characterized for their role in disease progression. Pyrimidine metabolism was altered in luminal versus basal BCa, whereas the combined expression of its associated genes or expression of one key gene, ribonucleotide reductase subunit M2 (RRM2) alone, associated significantly with decreased survival across all BCa subtypes, as well as in luminal patients resistant to tamoxifen. Increased RRM2 expression in tamoxifen-resistant patients was verified using tissue microarrays, whereas the metabolic products of RRM2 were higher in tamoxifen-resistant cells and in xenograft tumors. Both genetic and pharmacological inhibition of this key enzyme in tamoxifen-resistant cells significantly decreased proliferation, reduced expression of cell cycle genes, and sensitized the cells to tamoxifen treatment. Our study suggests for evaluating RRM2-associated metabolites as noninvasive markers for tamoxifen resistance and its pharmacological inhibition as a novel approach to overcome tamoxifen resistance in BCa. PMID:25016594

  16. Structural characteristics of oil-poor dilutable fish oil omega-3 microemulsions for ophthalmic applications.

    PubMed

    Lidich, Nina; Aserin, Abraham; Garti, Nissim

    2016-02-01

    Docosahexaenoic acid (DHA) promotes synthesis of anti-inflammatory prostaglandins and relief of dry eye symptoms. However, topical ophthalmic application of DHA is difficult because of its lipophilic property. Therefore, it is important to develop aqueous-based formulation with enhanced capabilities. Novel, unique water-dilutable microemulsions (MEs) were constructed to allow loading of naturally occurring rigid long-chain triglyceride of DHA (TG-DHA). The TG-DHA serves as solubilizate and as the oil phase, therefore preparation is poor in oil. The structural transformations of MEs upon water dilution were studied by SAXS, viscosity, electrical conductivity, self-diffusion NMR, DSC, cryo-TEM, and DLS techniques. At low water content a new type of water-in-oil (W/O) structure is formed. The glycerol/water phase hydrates the headgroups of surfactants, and the oil solvates their tails, forming "ill-defined bicontinuous domains". Upon further water dilution more structured bicontinuous domains of high viscosity are formed. After additional dilution, the mesophases invert to oil-in-water (O/W) droplets of ?8nm. In the structures composed of up to 25wt% water, the TG-DHA spaces and de-entangles the surfactant tails. Once the bicontinuous structures are formed, the surfactants and TG-DHA content decrease and their interfacial layer shrinks, leading to entanglement and buildup of viscous non-Newtonian mesophase. Above 70wt% water TG-DHA is embedded in the core of the O/W droplets, and its effect on the droplets' structure is minimal. This new dilutable ill-defined microemulsion can be a potential delivery vehicle for ophthalmic TG-DHA transport. PMID:26520814

  17. Overexpression of centromere protein K (CENPK) in ovarian cancer is correlated with poor patient survival and associated with predictive and prognostic relevance

    PubMed Central

    Lee, Yi-Chao

    2015-01-01

    Ovarian cancer has a poor prognosis. Most patients are diagnosed with ovarian cancer when the disease has reached an advanced stage and cure rates are generally under 30%. Hence, early diagnosis of ovarian cancer is the best means to control the disease in the long term and abate mortality. So far, cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are the gold-standard tumor markers for ovarian cancer; however, these two markers can be elevated in a number of conditions unrelated to ovarian cancer, resulting in decreased specifically and positive predictive value. Therefore, it is urgent to identify novel biomarkers with high reliability and sensitivity for ovarian cancer. In this study for the first time, we identified a member of the centromere protein (CENP) family, CENPK, which was specifically upregulated in ovarian cancer tissues and cell lines and the overexpression of which was associated with poor prognoses in patients with ovarian cancer. In addition, the presence of CENPK significantly improved the sensitivity of CA125 or HE4 for predicting clinical outcomes of ovarian cancer patients. In conclusion, we identified that CENPK was specifically upregulated in ovarian cancer cells and can be used as a novel tumor marker of ovarian cancer. PMID:26587348

  18. Clinicopathologic characteristics, treatment outcomes, and prognostic factors of primary thoracic soft tissue sarcoma: A multicenter study of the Anatolian Society of Medical Oncology (ASMO)

    PubMed Central

    Unal, Olcun Umit; Oztop, Ilhan; Yasar, Nurgul; Urakci, Zuhat; Ozatli, Tahsin; Bozkurt, Oktay; Sevinc, Alper; Gunaydin, Yusuf; Yapar Taskoylu, Burcu; Arpaci, Erkan; Ulas, Arife; Kodaz, Hilmi; Tonyali, Onder; Avci, Nilufer; Aksoy, Asude; Yilmaz, Ahmet Ugur

    2015-01-01

    Background Soft tissue sarcomas (STSs) are rare malignant tumors of embryogenic mesoderm origin. Primary thoracic STSs account for a small percentage of all STSs and limited published information is available. This study aimed to identify the prognostic factors for thoracic STSs and evaluate the disease's clinical outcomes. Methods The medical records of 109 patients with thoracic STSs who were treated between 2003 and 2013 were retrospectively reviewed. Patients' survival rates were analyzed and potential prognostic factors evaluated. Results The median follow-up period was 29 months (range: 1121 months). STSs were most frequently localized on the chest wall (n = 42; 38.5%) and lungs (n = 42; 38.5%). The most common histological types were malignant fibrous histiocytoma (n = 23; 21.1%), liposarcoma (n = 17; 15.6%), and leiomyosarcoma (n = 16; 14.7%). The median survival time of all patients was 40.3 months (95% confidence interval, 14.2266.37 months), with one and five-year survival rates of 93.4% and 63.5%, respectively. Univariate analysis of all groups revealed that metastatic stage, unresectability, tumor diameter of >10?cm, tumor location other than the chest wall, and grade 3 diseases were predictable of poor survival. However, only grade 3 diseases and tumor location other than the chest wall were confirmed by multivariate analysis as poor prognostic factors. Conclusions Primary thoracic STSs are rarely seen malignant tumors. Our results indicated that patients with low-grade tumors and those localized on the chest wall often experienced better survival outcomes. PMID:26273340

  19. TWIST-1 promotes cell growth, drug resistance and progenitor clonogenic capacities in myeloid leukemia and is a novel poor prognostic factor in acute myeloid leukemia

    PubMed Central

    Wang, Nan; Guo, Dan; Zhao, YangYang; Dong, ChengYa; Liu, XiaoYan; Yang, BinXia; Wang, ShuWei; Wang, Lin; Liu, QingGuo; Ren, Qian; Lin, YongMin; Ma, XiaoTong

    2015-01-01

    Alterations of TWIST-1 expression are often seen in solid tumors and contribute to tumorigenesis and cancer progression. However, studies concerning its pathogenic role in leukemia are scarce. Our study shows that TWIST-1 is overexpressed in bone marrow mononuclear cells of patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Gain-of-function and loss-of-function analyses demonstrate that TWIST-1 promotes cell growth, colony formation and drug resistance of AML and CML cell lines. Furthermore, TWIST-1 is aberrantly highly expressed in CD34+CD38? leukemia stem cell candidates and its expression declines with differentiation. Down-modulation of TWIST-1 in myeloid leukemia CD34+ cells impairs their colony-forming capacity. Mechanistically, c-MPL, which is highly expressed in myeloid leukemia cells and associated with poor prognosis, is identified as a TWIST-1 coexpressed gene in myeloid leukemia patients and partially contributes to TWIST-1-mediated leukemogenic effects. Moreover, patients with higher TWIST-1 expression have shorter overall and event-free survival (OS and EFS) in AML. Multivariate analysis further demonstrates that TWIST-1 overexpression is a novel independent unfavourable predictor for both OS and EFS in AML. These data highlight TWIST-1 as a new candidate gene contributing to leukemogenesis of myeloid leukemia, and propose possible new avenues for improving risk and treatment stratification in AML. PMID:26023795

  20. CB-13PHENOTYPIC CHANGES BY NUCLEAR-ENCODED CYTOCHROME C OXIDASE SUB-UNIT 4, ISOFORM 1 SUPPORTS POOR PROGNOSTIC IN GBM PATIENTS

    PubMed Central

    Oliva, Claudia; Reeve, Nathaniel; Markert, Tara; Griguer, Corinne E.

    2014-01-01

    Cytochrome c Oxidase is a mitochondrial enzyme involved in cellular respiration and production of energy. Previously, we demonstrates that a high enzymaticl activity is associated with poor overall survival in GBM patients () and chemoresistance to Temozolomide. Thus, we hypothesize that CcO may be directly involved in the aggressive phenotype of these tumors. Elevated CcO activity is associated with a switch in CcO subunit 4. We use gene targeting of CcO sub-unit 4 isoform 1 or 2 (COX4i1 and COX4i2) and patient xenoline tumors. Genetic swap between COX4i2 and COX4i1 significantly increased tumor growth and proliferation in vitro and in vivo. However, under hypoxic condition, COX4i1 cells stopped proliferating and became more invasive. Our results support the view that COX subunit 4-1 drives tumor cell growth, proliferation and invasion. Moreover, manipulation of COX4 isoforms uncoupled cell proliferation from cell invasion; this control is hypoxia dependent. This result provides evidence for a novel role for CcO beside its mitochondrial function. Supported by P20 CA151129-02 (NCI SPORE Program) and R01 CA160821 (USPHS/NIH/NCI)

  1. Possible survival benefits from zoledronic acid treatment in patients with bone metastases from solid tumours and poor prognostic featuresAn exploratory analysis of placebo-controlled trials

    PubMed Central

    Coleman, Robert E.; Lipton, Allan; Costa, Luis; Cook, Richard J.; Lee, Ker-Ai; Saad, Fred; Brown, Janet E.; Terpos, Evangelos; Major, Pierre P.; Kohno, Norio; Smith, Matthew; Body, Jean-Jacques

    2013-01-01

    Background Zoledronic acid (ZOL) is an important component of therapy for patients with metastatic bone disease (MBD) to reduce the risk of skeletal-related events (SREs). We evaluated overall survival (OS) in patients with MBD secondary to solid tumours included in placebocontrolled ZOL trials. Patients and methods Exploratory analyses were performed using databases from three randomised trials of ZOL versus placebo. 1126 patients (ZOL, n=731; placebo, n=395) with complete baseline data for 18 predefined parameters were evaluated for OS. Relative risks (RRs) with 95% confidence intervals were assessed using stratified and adjusted Cox regression models. Baseline covariates defining patient populations with significantly different effects of ZOL treatment on OS (identified by stepwise backward elimination) were included in multivariate models. Results Although OS was similar between the overall treatment groups, ZOL significantly improved OS in the subset of patients (n=423; 38%) with elevated baseline NTX (?100nmol/mmol creatinine; RR, 0.692; P=.0028). Notably, this effect was independent of SRE prevention. Additional covariates associated with OS benefits with ZOL (e.g., low albumin, SRE history, elevated lactate dehydrogenase, shorter cancer duration) were characteristic of advanced disease. Conclusion These exploratory analyses suggest a beneficial effect of ZOL on OS in patients with highly aggressive or advanced MBD.

  2. 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

  3. Primary Tumor Vascularity, HIF-1? and VEGF expression in vulvar squamous cell carcinomas: their relationships with clinicopathological characteristics and prognostic impact

    PubMed Central

    2013-01-01

    Background Increased vascularity is a crucial event in the tumor progression and has prognostic significance in various cancers. However, the ultimate role of angiogenesis in the pathogenesis and clinical outcome of vulvar carcinoma patients is still not settled. Methods Tumor vascularity using CD34 stained slides measured by Chalkley counting method as well as hypoxia-inducible factor (HIF)-1? and vascular endothelial growth factor (VEGF) immunoexpression was examined in 158 vulvar squamous cell carcinomas. Associations between vascular Chalkley count, HIF-1? and VEGF expression and clinicopathological factors and clinical outcome were evaluated. Results High CD34 Chalkley count was found to correlate with larger tumor diameter (P = 0.002), deep invasion (P < 0.001) and HIF-1? (P = 0.04), whereas high VEGF expression correlate significantly with poor tumor differentiation (P = 0.007). No significant association between CD34 Chalkley counts and VEGF expression and disease-specific survival was observed. High HIF-1? expression showed better disease specific survival in both univariate and multivariate analyses (P = 0.001). Conclusions A significant association between high tumor vascularity and larger tumor size as well as deeper tumor invasion suggests an important role of angiogenesis in the growth and progression of vulvar carcinomas. HIF-1? expression in vulvar carcinomas was a statistically independent prognostic factor. PMID:24165149

  4. Human mutL homolog 1 expression characteristic and prognostic effect on patients with sporadic colorectal cancer

    PubMed Central

    Pu, Chibin; Ren, Weiguo; Sun, Zhenqiang; Yu, Xianbo; Yuan, Wei; Huang, Mingyu; Shen, Shourong; Wang, Xiaoyan

    2015-01-01

    The aim of the present study was to analyze the relationship between aberrant human mutL homolog 1 (hMLH1) expression and clinicopathological parameters of patients with sporadic colorectal cancer, and to explore the prognostic effect of aberrant hMLH1 expression in these patients. The relationship was measured by chi-square test and Fisher’s exact test. Survival analysis was performed with Kaplan-Meier analysis and Cox regression model to measure 5-year disease-free survival (DFS) and 5-year overall survival (OS) rates. Totally 17.13% of the patients with sporadic colorectal cancer showed aberrant nuclear staining for hMLH1 expression. Aberrant hMLH1 expression was related with tumor pathologic types, tumor location and TNM staging (P<0.05) in the patients with sporadic colorectal cancer. Cox regression analysis indicated important prognostic factors were age (RR: 1.021, 95% CI: 1.003-1.039, P=0.023), mucinous adenocarcinoma (RR: 2.603, 95% CI: 1.705-3.974, P<0.0001), TNM staging (RR: 2.071, 95% CI: 1.170-3.666, P=0.012), lymphangion invasion (RR: 2.013, 95% CI: 1.227-3.303, P=0.006) and aberrant hMLH1 expression (RR: 0.414, 95% CI: 0.216-0.791, P=0.008). Consequently, hMLH1 expression level is related with some clinicopathologic features. Aberrant hMLH1 expression plays a significant part in prognosis for patients with sporadic colorectal cancer and it will promisingly become an independent prognostic factor. PMID:26770629

  5. Evaluation of bovine zona pellucida characteristics in polarized light as a prognostic marker for embryonic developmental potential.

    PubMed

    Koester, M; Mohammadi-Sangcheshmeh, A; Montag, M; Rings, F; Schimming, T; Tesfaye, D; Schellander, K; Hoelker, M

    2011-06-01

    It has previously been demonstrated that zona pellucida imaging of human oocytes using polarized light microscopy is a clinically applicable method for the noninvasive assessment of oocyte quality. This study was designed to investigate whether zona pellucida characteristics of bovine oocytes and zygotes in polarized light may similarly serve as a useful marker for developmental competence in bovine reproductive biotechnologies. Zona birefringence intensity parameters of 2862 oocytes/zygotes were objectively evaluated with an automatic analysis system and correlated with oocyte/zygote quality. In detail, immature oocytes of good quality assessed with brilliant cresyl blue staining showed significantly lower zona birefringence than poor-quality counterparts (P<0.001). After in vitro maturation and classification according to maturational status, the birefringence intensity parameters were significantly different in those oocytes that reached metaphase II compared with arrested stages (P<0.001). Following either parthenogenetic activation or IVF with subsequent in vitro culture in a well-of-the-well system until day 9, superior development as determined by cleavage, blastocyst formation, and hatching ability was associated with lower zona birefringence intensity parameters. When early zygote-stage embryos were selected and assorted in groups based on zona birefringence (high/medium/low), the group of embryos derived from high-birefringence zygotes displayed a significantly compromised developmental potential compared with low-birefringence zygotes. These results clearly show that developmentally competent bovine oocytes/zygotes exhibit lower zona birefringence intensity parameters. Therefore, birefringence imaging of zona pellucida is a suitable technique to predict bovine preimplantation embryo development. PMID:21415090

  6. The demographic features, clinicopathologic characteristics, treatment outcome and disease-specific prognostic factors of solitary fibrous tumor: a population-based analysis

    PubMed Central

    Wushou, Alimujiang; Jiang, Yi-Zhou; Liu, Yi-Rong; Shao, Zhi-Ming

    2015-01-01

    Background Solitary fibrous tumor's (SFT) demographic features, clinicopathologic characteristics, treatment outcome and disease-specific prognostic factors were unexplored comprehensively. Methods SEER program was used to identify patients diagnosed with SFT from 1973 to 2012. Overall collected data were analyzed by using the SPSS 18.0. Results In total, 804 cases were found including 613 cases with SFT-specific mortality and 801 patients were analyzed for overall survival (OS). The 3-year disease specific survival (DSS), 5-year DSS and 10-year DSS were 73.3%, 65.7% and 53.3%. The 3-year OS, 5-year OS and 10-year OS were 71.9%, 63.3% and 47.3%. In the multivariate survival analysis, the age > 51 years (hazard ratio [HR] = 1.851 for DSS, P = 0.024 and HR = 1.652 for OS, P = 0.033; Reference [Ref] ≤ 51 years for DSS and ≤ 53 years for OS), SEER stage metastasized tumor (HR = 4.269 for DSS, P = 0.000 and HR = 2.905 for OS, P = 0.028, Ref - localized + regional tumor), pathologic grade III + IV (HR = 2.734 for DSS, P = 0.001 and HR = 2.585 for OS, P = 0.000, Ref - grade I + II) were adversely associated with DSS and OS. In addition, surgery was favorably associated with DSS (HR = 0.217, P = 0.045, Ref - surgery + radiotherapy). Conclusions The surgery was an independent prognostic factor for DSS. The patient's age, SEER stage and pathologic grade were SFT-specific independent prognostic indicators for DSS and OS. PMID:26496033

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

    PubMed Central

    Li, Shuaijie; Huang, Xiaojia; Yang, Lu; Xiao, Xiangsheng; Xie, Xiaoming

    2015-01-01

    Background Previous studies have indicated the prognostic value of various laboratory parameters in cancer patients. This study was to establish a prognostic index (PI) model for breast cancer patients based on the potential prognostic factors. Methods A retrospective study of 1661 breast cancer patients who underwent surgical treatment between January 2002 and December 2008 at Sun Yat-sen University Cancer Center was conducted. Multivariate analysis (Cox regression model) was performed to determine the independent prognostic factors and a prognostic index (PI) model was devised based on these factors. Survival analyses were used to estimate the prognostic value of PI, and the discriminatory ability of PI was compared with Nottingham Prognostic Index (NPI) by evaluating the area under the receiver operating characteristics curves (AUC). Results The mean survival time of all participants was 123.6 months. The preoperative globulin >30.0g/L, triglyceride >1.10mmol/L and fibrinogen >2.83g/L were identified as risk factors for shorter cancer-specific survival. The novel prognostic index model was established and enrolled patients were classified as low- (1168 patients, 70.3%), moderate- (410 patients, 24.7%) and high-risk groups (83 patients, 5.0%), respectively. Compared with the low-risk group, higher risks of poor clinical outcome were indicated in the moderate-risk group [Hazard ratio (HR): 1.513, 95% confidence interval (CI): 1.1691.959, p = 0.002] and high-risk group (HR: 2.481, 95%CI: 1.6533.724, p< 0.001). Conclusions The prognostic index based on three laboratory parameters was a novel and practicable prognostic tool. It may serve as complement to help predict postoperative survival in breast cancer patients. PMID:26600129

  8. Clinical Characteristics and Prognostic Significance of TERT Promoter Mutations in Cancer: A Cohort Study and a Meta-Analysis

    PubMed Central

    Yuan, Ping; Cao, Jin-lin; Abuduwufuer, Abudumailamu; Wang, Lu-Ming; Yuan, Xiao-Shuai; Lv, Wang; Hu, Jian

    2016-01-01

    Background The prevalence of telomerase reverse transcriptase (TERT) promoter mutations (pTERTm) in non-small-cell lung cancer (NSCLC) have been investigated, but the results were inconsistent. In addition, several studies have analysed the role of pTERTm in the etiology of various types of cancers, however, the results also remain inconsistent. Methods The genomic DNA sequence of 103 NSCLC samples were analysed to investigate the frequency of pTERTm in these patients and to establish whether these mutations are associated with their clinical data. Furthermore, a meta-analysis based on previously published articles and our cohort study was performed to investigate the association of pTERTm with patient gender, age at diagnosis, metastasis status, tumour stage and cancer prognosis (5-year overall survival rate). Results In the cohort study, 4 patients had C228T and 2 had C250T, with a total mutation frequency up to 5.8%. Significant difference of clinical data between pTERTm carriers and noncarriers was only found in age at diagnosis. In the meta-analysis, We found that pTERTm carriers in cancer patients are older than noncarriers (Mean difference (MD) = 5.24; 95% confidence interval [CI], 2.00 to 8.48), male patients were more likely to harbour pTERTm (odds Ratios (OR) = 1.38; 95% CI, 1.22 to 1.58), and that pTERTm had a significant association with distant metastasis (OR = 3.78; 95% CI, 2.45 to 5.82), a higher tumour grade in patients with glioma (WHO grade III, IV vs. I, II: OR, 2.41; 95% CI, 1.88 to 3.08) and a higher tumour stage in other types of cancer (III, IV vs. I, II: OR, 2.48; 95% CI, 1.48 to 4.15). pTERTm was also significantly associated with a greater risk of death (hazard ratio = 1.71; 95% CI, 1.41 to 2.08). Conclusions pTERTm are a moderately prevalent genetic event in NSCLC. The current meta-analysis indicates that pTERTm is associated with patient age, gender and distant metastasis. It may serves as an adverse prognostic factor in individuals with cancers. PMID:26799744

  9. Poor performance validity predicts clinical characteristics and cognitive test performance of OEF/OIF/OND Veterans in a research setting.

    PubMed

    Clark, Alexandra L; Amick, Melissa M; Fortier, Catherine; Milberg, William P; McGlinchey, Regina E

    2014-01-01

    This study examined the performance of 198 Veteran research participants deployed during Operation Enduring Freedom, Operation Iraqi Freedom, and/or Operation New Dawn (OEF/OIF/OND) on four measures of performance validity: the Medical Symptom Validity Test (MSVT), California Verbal Learning Test: Forced Choice Recognition (FCR), Reliable Digit Span (RDS), and TOVA Symptom Exaggeration Index (SEI). Failure on these performance validity tests (PVTs) ranged from 4% to 9%. The overall base rate of poor performance validity, as measured by failure of the MSVT in conjunction with an embedded PVT (FCR, RDS, SEI), was 5.6%. Regression analyses revealed that poor performance validity predicted cognitive test performance and self-reported psychological symptom severity. Furthermore, a greater prevalence of traumatic brain injury (TBI), Post-Traumatic Stress Disorder (PTSD), co-morbid TBI/PTSD, and other Axis I diagnoses, was observed among participants with poor effort. Although poor performance validity is relatively uncommon in a research setting, these findings demonstrate that clinicians should be cautious when interpreting psychological symptoms and neuropsychological test performance of Veteran participants who fail effort measures. PMID:24766521

  10. A Systematic Review and Meta-Analysis of Diagnostic and Prognostic Serum Biomarkers of Colorectal Cancer

    PubMed Central

    Liu, Zhongyu; Zhang, Yingchong; Niu, Yulong; Li, Ke; Liu, Xin; Chen, Huijuan; Gao, Chunfang

    2014-01-01

    Background Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC). Methods The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012. The articles that provided adequate information to meet the requirements of the meta-analysis of diagnostic and prognostic markers were included. A 2-by-2 table of each diagnostic marker and its hazard ratio (HR) and the confidence interval (CI) of each prognostic marker was directly or indirectly extracted from the included papers, and the pooled sensitivity and specificity of the diagnostic marker and the pooled HR and the CI of the prognostic marker were subsequently calculated using the extracted data. Results In total, 104 papers related to the diagnostic markers and 49 papers related to the prognostic serum markers of CRC were collected, and only 19 of 92 diagnostic markers were investigated in more than two studies, whereas 21 out of 44 prognostic markers were included in two or more studies. All of the pooled sensitivities of the diagnostic markers with >?=?3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.3473.744) and MMP-7 with lowest (1.099, CI: 1.0181.187)) pooled HRs are presented. Conclusions The quality of studies addressing the diagnostic and prognostic accuracy of the tests was poor, and the results were highly heterogeneous. The poor characteristics indicate that these tests are of little value for clinical practice. PMID:25105762

  11. Chronic myeloid leukemia with e14a3 BCR-ABL transcript: analysis of characteristics and prognostic significance.

    PubMed

    Xiaomin, Gui; Yong, Zhang; Jinlan, Pan; Huiying, Qiu; Jiannong, Cen; Yongquan, Xue; Suning, Chen; Hongjie, Shen; Li, Yao; Jun, Zhang; Yafang, Wu; Yan, Chen

    2015-12-01

    Chronic myeloid leukemia (CML) is characterized by Philadelphia chromosome (Ph) and BCR-ABL fusion genes. This study retrospectively analyzed 2381 CML patients with Ph chromosome confirmed by cytogenetics, Fluorescence in situ hybridization (FISH) or real-time quantitative polymerase chain reaction (Q-PCR). Among them, five CML patients without e13a2, e14a2 or e1a2 transcripts detected by Q-PCR were identified. DNA sequencing confirmed the fusion of BCR exon 14 and ABL exon 3. Case 1 reponded poorly to imatinib and achieved complete cytogenetic response (CCyR) after converting from imatinib to dasatinib. BCR-ABL transcripts were undetectable in cases after 2, 3 and 4 treated with imatinib after 6, 6 and 3 months, respectively, and in one patient who had undergone allogeneic hematopoietic stem cell transplantation after 4 months. Q-PCR may miss the detection of rare cases that are not covered by the primers used in Q-PCR, unless the proper primers are used. PMID:25962435

  12. 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; Rayn, Chelo; Parody, Ricardo; de la Serna, Javier; Len, Angel; Esteve, Jordi; Milone, Gustavo; Debn, Guillermo; Rivas, Concha; Gonzlez, Marcos; Tormo, Mar; Daz-Mediavilla, Joaqun; Gonzlez, 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 Espaol de Tratamientos en Hematologa [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%). PMID:18945964

  13. Observational studies of the meteorological characteristics associated with poor air quality over the Pearl River Delta in China

    NASA Astrophysics Data System (ADS)

    Wu, M.; Wu, D.; Fan, Q.; Wang, B. M.; Li, H. W.; Fan, S. J.

    2013-11-01

    The structure of the atmospheric boundary layer (ABL) and its influence on regional air quality over the Pearl River Delta (PRD) were examined through two intensive observations in October 2004 and July 2006. Analytical results show the presence of two types of typical weather conditions associated with poor air quality over the PRD. The first is the warm period before a cold front (WPBCF) and the second is the subsidence period controlled by a tropical cyclone (SPCTC). Two typical low air quality situations, which are affected by WPBCF and SPCTC, and one high air quality situation were analysed in detail. Results showed that continuously low or calm ground winds resulted in the accumulation of pollutants, and sea-land breezes had an important role during low air quality conditions. Data on recirculation factors showed that recirculation was significant during low air quality conditions, and steady transportation occurred during high air quality conditions. The ventilation index and the 24 h average ventilation index during high air quality conditions were significantly higher than those during low air quality conditions. Deep and stable inversion layers inside the ABL remarkably affected low air quality. Surface and low-altitude inversions were usually observed during WPBCF, contrary to during SPCTC, during which only the low-altitude inversion appeared frequently.

  14. DNMT3A R882 Mutation with FLT3-ITD Positivity Is an Extremely Poor Prognostic Factor in Patients with Normal-Karyotype Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation.

    PubMed

    Ahn, Jae-Sook; Kim, Hyeoung-Joon; Kim, Yeo-Kyeoung; Lee, Seun-Shin; Jung, Sung-Hoon; Yang, Deok-Hwan; Lee, Je-Jung; Kim, Nan Young; Choi, Seung Hyun; Jung, Chul Won; Jang, Jun-Ho; Kim, Hee Je; Moon, Joon Ho; Sohn, Sang Kyun; Won, Jong-Ho; Kim, Sung-Hyun; Kim, Dennis Dong Hwan

    2016-01-01

    The prognostic relevance of epigenetic modifying genes (DNMT3A, TET2, and IDH1/2) in patients with acute myeloid leukemia (AML) has been investigated extensively. However, the prognostic implications of these mutations after allogeneic hematopoietic cell transplantation (HCT) have not been evaluated comprehensively in patients with normal-karyotype (NK)-AML. A total of 115 patients who received allogeneic HCT for NK-AML were retrospectively evaluated for the FLT3-ITD, NPM1, CEBPA, DNMT3A, TET2, IDH1/2, WT1, NRAS, ASXL2, FAT1, DNAH11, and GATA2 mutations in diagnostic samples and analyzed for long-term outcomes after allogeneic HCT. The prevalence rates for the mutations were as follows: FLT3-ITD positivity (FLT3-ITD(pos)) (32.2%), NPM1 mutation (43.5%), CEBPA mutation (double) (24.6%), DNMT3A mutation (DNMT3A(mut)) (31.3%), DNMT3A R882(mut) (18.3%), TET2 mutation (8.7%), and IDH1/2 mutation (16.5%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 57.3% and 58.1%, respectively. A multivariate analysis revealed that FLT3-ITD(pos) (hazard ratio, [HR], 2.23; P=.006) and DNMT3A R882(mut) (HR, 2.74; P=.002) were unfavorable prognostic factors for OS. In addition, both mutations were significant risk factors for EFS and relapse. People with DNMT3A R882(mut) accompanied by FLT3-ITD(pos) had worse OS and EFS, and higher relapse rates than those with the other mutations, which were confirmed in a propensity score 1:2 matching analysis. These results suggest that DNMT3A R882(mut), particularly when accompanied by FLT3-ITD(pos), is a significant prognostic factor for inferior transplantation survival outcome by increasing relapse risk, even after allogeneic HCT. PMID:26234722

  15. Molecular prognostic prediction in liver cirrhosis

    PubMed Central

    Goossens, Nicolas; Nakagawa, Shigeki; Hoshida, Yujin

    2015-01-01

    The natural history of cirrhosis varies and therefore prognostic prediction is critical given the sizable patient population. A variety of clinical prognostic indicators have been developed and enable patient risk stratification although their performance is somewhat limited especially within relatively earlier stage of disease. Molecular prognostic indicators are expected to refine the prediction, and potentially link a subset of patients with molecular targeted interventions that counteract poor prognosis. Here we overview clinical and molecular prognostic indicators in the literature, and discuss critical issues to successfully define, evaluate, and deploy prognostic indicators as clinical scores or tests. The use of liver biopsy has been diminishing due to sampling variability on fibrosis assessment and emergence of imaging- or lab test-based fibrosis assessment methods. However, recent rapid developments of genomics technologies and selective molecular targeted agents has highlighted the need for biopsy tissue specimen to explore and establish molecular information-guided personalized/stratified clinical care, and eventually achieve precision medicine. PMID:26420954

  16. Molecular prognostic prediction in liver cirrhosis.

    PubMed

    Goossens, Nicolas; Nakagawa, Shigeki; Hoshida, Yujin

    2015-09-28

    The natural history of cirrhosis varies and therefore prognostic prediction is critical given the sizable patient population. A variety of clinical prognostic indicators have been developed and enable patient risk stratification although their performance is somewhat limited especially within relatively earlier stage of disease. Molecular prognostic indicators are expected to refine the prediction, and potentially link a subset of patients with molecular targeted interventions that counteract poor prognosis. Here we overview clinical and molecular prognostic indicators in the literature, and discuss critical issues to successfully define, evaluate, and deploy prognostic indicators as clinical scores or tests. The use of liver biopsy has been diminishing due to sampling variability on fibrosis assessment and emergence of imaging- or lab test-based fibrosis assessment methods. However, recent rapid developments of genomics technologies and selective molecular targeted agents has highlighted the need for biopsy tissue specimen to explore and establish molecular information-guided personalized/stratified clinical care, and eventually achieve "precision medicine". PMID:26420954

  17. 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

  18. Correlation of Foxp3 positive regulatory T cells with prognostic factors in canine mammary carcinomas.

    PubMed

    Kim, J H; Hur, J H; Lee, S M; Im, K S; Kim, N H; Sur, J H

    2012-07-01

    Regulatory T cells (Treg) cells play a crucial role in tumor progression by suppressing anti-tumor immunity, but are not well-documented in veterinary oncology. To identify the characteristics of Treg cells in tumor microenvironments, the numbers of Treg cells were analyzed and compared with histological prognostic factors and molecular biomarkers in canine mammary carcinoma (MC) tissues (n=37). Abundant Treg cells were associated with high histological grade and lymphatic invasion. The numbers of Treg cells infiltrating intratumoral areas markedly increased in tumors with poor prognostic factors, such as high histological grade, lymphatic invasion, and necrosis. These findings suggest that Treg cells play a role in canine MC progression. Furthermore, Treg cell numbers in intratumoral compartments may provide a potential prognostic factor when assessing canine MCs, which may in turn lead to the development of new immunologic therapeutics. PMID:22130461

  19. Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas

    PubMed Central

    Wang, Mo-Jin; Ping, Jie; Li, Yuan; Holmqvist, Annica; Adell, Gunnar; Arbman, Gunnar; Zhang, Hong; Zhou, Zong-Guang; Sun, Xiao-Feng

    2015-01-01

    Abstract Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 19732011), and Linkping Cancer (LC, 19722009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P?poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.0571.096; P?poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients. PMID:26705231

  20. The characteristics of short- and long-term surviving Shiba dogs with chronic enteropathies and the risk factors for poor outcome

    PubMed Central

    2013-01-01

    Background The objectives of this study were to investigate the differences in the characteristics of short- and long-term surviving dogs, and the factors that predict poor outcome in Shiba dogs with chronic enteropathies (CE). Methods A total of 25 Shiba dogs were included in this study, and classified as either short-term (?6 months) survivors (Ss; n=16) or long-term (>6 months) survivors (Ls; n=9). The clinical and clinicopathological variables, histopathology, response to therapy, and outcomes were investigated between groups. Furthermore, these factors were tested for their ability to predict poor outcome. Results All CE dogs were diagnosed as having inflammatory bowel disease (IBD) with lymphocytic-plasmacytic enteritis (LPE). Age and canine inflammatory bowel disease activity index (CIBDAI) were significantly higher in the Ss group than in the Ls group (age: p = 0.035, CIBDAI: p = 0.018), as determined via univariate logistic regression analysis. According to receiver operator characteristic (ROC) curve analysis, the best predictors of poor outcome were age and CIBDAI, with the cutoffs determined as 7 years and 9 points, respectively. The majority of the cases (84%) responded to initial treatment; in particular, 75% of dogs in Ss group responded to therapy. The time to response (days) to the initial treatment in the Ss group (median 42.5 days, range: 20-91 days) was significantly shorter than that of the Ls group (median 285 days, range: 196-1026 days). Approximately half (55.5%) of the dogs in the Ls group died due to relapse of CE. Conclusions This study suggested that there is a high risk of early mortality in Shiba dogs with CE, particularly if the dogs are older (>7 years) and have a high CIBDAI score (>9 points). There appears to be a possibility of early mortality even if the initial treatment was efficacious. Furthermore, Shiba dogs with CE that become less responsive to initial therapy in the short-term (approximately 3 months) are more likely to have an early mortality. Thus, it is necessary to follow-up Shiba dogs with CE in the long-term, as approximately half of the long-term survivors eventually died due to a relapse of the signs. PMID:23594569

  1. Prognostic factors for peritonitis outcome.

    PubMed

    van Esch, Sadie; Krediet, Raymond T; Struijk, Dirk G

    2012-01-01

    Despite advances in treatment and prevention, peritonitis remains a major problem in peritoneal dialysis (PD) patients with often technique failure as a consequence. The last decades the focus of PD peritonitis has changed from lowering peritonitis incidence to improvement of peritonitis outcome. Prognostic factors for peritonitis outcome can influence decision making during the treatment of peritonitis, for example to take out the PD catheter early in the time course of peritonitis and prevent further damage to the peritoneal membrane. In this paper, we give a review of the literature about prognostic factors for peritonitis outcome. In most studies, age, gender, diabetes, time on PD, a precursor of calcitonin:procalcitonin, IL-6 and albumin did not show a significant effect on peritonitis outcome. The following factors have been associated with poor outcome of peritonitis: Gram-negative organisms, Mycobacterium species, fungal peritonitis, polymicrobial peritonitis, concurrent exit site or tunnel infection, Caucasian race, low residual GFR, persistently elevated peritoneal dialysate white cell count, CRP, and low levels of slCAM-1 and hyaluronan at the end of peritonitis treatment. In fungal peritonitis, abdominal pain, bowel obstruction, the catheter remaining in situ and Candidaparapsilosis are factors associated with higher mortality rate and a greater risk of technique failure. Recent antibiotic therapy and peritonitis are associated with poor treatment response in culture-negative peritonitis. Recurrent peritonitis episodes have a poor therapeutic response and high mortality and have a worse prognosis than relapsing ones. Older age, long PD duration and continuous elevated serum CRP levels are predictors of adverse outcomes in PD patients after peritonitis-related catheter removal. Peritonitis remains a serious complication of PD with marked morbidity. It is a common cause of technique failure. The rate of PD-related peritonitis has decreased over the last decades due to advances in treatment and prevention. Nowadays, the focus moved from lowering peritonitis incidence towards improving peritonitis outcome. It is useful to have prognostic factors for peritonitis outcome, because they can influence decision-making during the treatment of peritonitis, for example to take out the PD catheter early in the time course of peritonitis and prevent further damage to the peritoneal membrane. In the last decades, many publications appeared about prognostic factors for peritonitis outcome. This article summarizes those prognostic factors, based on an extensive review of the literature. PMID:22652748

  2. Morphological and molecular characteristics of a poorly known marine ascomycete, Manglicola guatemalensis (Jahnulales: Pezizomycotina; Dothideomycetes, Incertae sedis): new lineage of marine ascomycetes.

    PubMed

    Suetrong, Satinee; Sakayaroj, Jariya; Phongpaichit, Souwalak; Jones, E B Gareth

    2010-01-01

    The poorly known marine ascomycete Manglicola guatemalensis from Trang and Trat provinces, Thailand, were collected in 2005 and 2006 on the brackish water palm Nypa fruticans. This fungus is known only from two previous collections. This paper reports on the morphological characteristics and molecular phylogeny of this unique marine bitunicate ascomycete. Manglicola guatemalensis has large clavate to obtusely fusiform ascomata, wide ostioles, bitunicate asci, cylindrical, thick-walled, unequally one-septate ascospores, constricted at the septum, apical cell larger, chestnut-brown and a smaller light brown basal cell. Ascospores germinate readily, always from the basal cell. Four isolates from different locations were selected for the phylogenetic study. Regions of the rDNA gene, including SSU and LSU, were sequenced and combined. Molecular data places M. guatemalensis in the Jahnulales with high bootstrap support; all strains are monophyletic. In the combined SSU and LSU analyses the Jahnulales comprises four subclades, A, B, C and D. Subclade A comprises Jahnula species and two anamorphic fungi, Brachiosphaera tropicalis and Xylomyces chlamydosporus. In subclade B Manglicola strains form a sister group of the Aliquandostipite species Aliquandostipite crystallinus, A. khaoyaiensis, Jahnula siamensiae and Patescospora separans. Subclade C comprises Jahnula species, Jahnula aquatica, J. granulosa and J. rostrata, while Megalohypha aqua-dulces constitutes subclade D. Therefore Manglicola forms another lineage of marine fungi. PMID:20120232

  3. 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.

  4. Prognostic parameters in early stage Hodgkin's disease

    SciTech Connect

    Mill, W.B.; Lee, F.A.

    1982-05-01

    This report is a retrospective study of 101 patients referred with the diagnosis of Hodgkin's disease, all of whom had a staging laparotomy and were treated initially with radiation therapy alone. The results of treatment are analyzed in terms of the relapse rate and 5-year actuarial survival by the following prognostic factors identified from the literature: age, stage, the presence or absence of systemic symptoms, histology, splenic involvement and intrathoracic involvement. There was a significant difference in the relapse rates and survival rates between those patients without the poor prognostic factors and those with one, or more than one.

  5. 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.

  6. 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. PMID:22875252

  7. Immunology of gynecologic neoplasms: analysis of the prognostic significance of the immune status.

    PubMed

    Bellati, F; Visconti, V; Napoletano, C; Antonilli, M; Frati, L; Panici, P Benedetti; Nuti, M

    2009-06-01

    Gynecologic Oncology has changed in the last few decades. An increasing proportion of patients is benefiting from long term survival although patients diagnosed with advanced disease suffer from a poor prognosis. Unfortunately, several recent studies are confirming that changing the combinations of "traditional" cytotoxic drugs is unlikely to obtain a real breakthrough in survival rates. Furthermore, there is discouraging data regarding consolidation therapies. It is, therefore, necessary to identify new target therapies with a minimal impact on quality of life. It is likely that new breakthroughs are only going to be achieved when changes in therapies are tailored to the entire natural history of the disease and on specific patient characteristic's. Since the discovery that tumor infiltrating lymphocytes represent an independent prognostic factor in ovarian cancer patients, several researchers have dedicated their attention to cancer immune response in order to identify prognostic factors and immunological targets. Analyses on immunophenotype at diagnosis and throughout the entire course of treatment are currently ongoing and are giving the new diagnostic, prognostic and therapeutic tools to the physicians. Furthermore new antigens and new vaccination strategies are being investigated. Encouraging data on selected patient populations have been observed recently. The objective of the present review is to define the immunology of women affected by gynecological malignancies and describe new immunological targets for prognostic and therapeutic use. PMID:19519321

  8. 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 and likely more common entity and often with nonmediastinal presentation, whereas outcomes seem superior when treated with a rituximab-based, DLBCL-specific regimen. PMID:26044261

  9. 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.

  10. 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.

  11. The Identification of Prognostic Factors and Survival Statistics of Conventional Central Chondrosarcoma

    PubMed Central

    Nota, Sjoerd P. F. T.; Braun, Yvonne; Schwab, Joseph H.; van Dijk, C. Niek; Bramer, Jos A. M.

    2015-01-01

    Introduction. Chondrosarcomas are malignant bone tumors that are characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effect on chondrosarcoma, treatment of most patients depends on surgical resection. We conducted this study to identify independent predictive factors and survival characteristics for conventional central chondrosarcoma and dedifferentiated central chondrosarcoma. Methods. A systematic literature review was performed in September 2014 using the Pubmed, Embase, and Cochrane databases. Subsequent to a beforehand-composed selection procedure we included 13 studies, comprising a total of 1114 patients. Results. The prognosis of central chondrosarcoma is generally good for the histologically low-grade tumors. Prognosis for the high-grade chondrosarcoma and the dedifferentiated chondrosarcoma is poor with lower survival rates. Poor prognostic factors in conventional chondrosarcoma for overall survival are high-grade tumors and axial/pelvic tumor location. In dedifferentiated chondrosarcoma the percentage of dedifferentiated component has significant influence on disease-free survival. Conclusion. Despite the fact that there are multiple prognostic factors identified, as shown in this study, there is a need for prospective and comparative studies. The resulting knowledge about prognostic factors and survival can give direction in the development of better therapies. This could eventually lead to an evidence-based foundation for treating chondrosarcoma patients. PMID:26633939

  12. Prognostic Value of the Modified Glasgow Prognostic Score in Patients Undergoing Radical Surgery for Hepatocellular Carcinoma

    PubMed Central

    Ni, Xiao-Chun; Yi, Yong; Fu, Yi-Peng; He, Hong-Wei; Cai, Xiao-Yan; Wang, Jia-Xing; Zhou, Jian; Cheng, Yun-Feng; Jin, Jian-Jun; Fan, Jia; Qiu, Shuang-Jian

    2015-01-01

    Abstract There is increasing and consistent evidence concerning the association of systemic inflammation and poor outcome in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify a superior inflammation-based prognostic scoring system for patients with HCC undergoing hepatectomy. We analyzed two independent cohorts of a total of 723 patients with HCC who underwent radical surgery between 2010 and 2012. The prognostic value of the inflammation scores, including the Glasgow Prognostic Score (GPS), modified GPS (mGPS), neutrophil-to-lymphocyte ratio, platelet lymphocyte ratio, prognostic index, and prognostic nutritional index, as well as the Barcelona Clinic Liver Cancer and Cancer of the Liver Italian Program staging systems was analyzed in a test cohort of 367 patients and validated in a validation cohort of 356 patients. A high score with the mGPS was associated with large tumor size, vascular invasion, and advanced clinical stage. Multivariate analysis showed that the mGPS was independently associated with overall survival and disease-free survival, and had a higher area under the curve value in comparison with other inflammation-based scores. The results of this study demonstrated that the mGPS is an independent marker of poor prognosis in patients with resectable HCC and is superior to other inflammation-based scores. PMID:26356714

  13. Multidisciplinary Prognostication Using the Palliative Prognostic Score in an Australian Cancer Center

    PubMed Central

    Mendis, Ruwani; Soo, Wee-Kheng; Zannino, Diana; Michael, Natasha; Spruyt, Odette

    2015-01-01

    CONTEXT Accurate prognostication is important in oncology and palliative care. A multidisciplinary approach to prognostication provides a novel approach, but its accuracy and application is poorly researched. In this study, we describe and analyze our experience of multidisciplinary prognostication in palliative care patients with cancer. OBJECTIVES To assess our accuracy of prognostication using multidisciplinary team prediction of survival (MTPS) alone and within the Palliative Prognostic (PaP) Score. METHODS This retrospective study included all new patients referred to a palliative care consultation service in a tertiary cancer center between January 2010 and December 2011. Initial assessment data for 421 inpatients and 223 outpatients were analyzed according to inpatient and outpatient groups to evaluate the accuracy of prognostication using MTPS alone and within the PaP score (MTPS-PaP) and their correlation with overall survival. RESULTS Inpatients with MTPS-PaP group A, B, and C had a median survival of 10.9, 3.4, and 0.7 weeks, respectively, and a 30-day survival probability of 81%, 40%, and 10%, respectively. Outpatients with MTPS-PaP group A and B had a median survival of 17.3 and 5.1 weeks, respectively, and a 30-day survival probability of 94% and 50%, respectively. MTPS overestimated survival by a factor of 1.5 for inpatients and 1.2 for outpatients. The MTPS-PaP score correlated better than MTPS alone with overall survival. CONCLUSION This study suggests that a multidisciplinary team approach to prognostication within routine clinical practice is possible and may substitute for single clinician prediction of survival within the PaP score without detracting from its accuracy. Multidisciplinary team prognostication can assist treating teams to recognize and articulate prognosis, facilitate treatment decisions, and plan end-of-life care appropriately. PaP was less useful in the outpatient setting, given the longer survival interval of the outpatient palliative care patient group. PMID:26309410

  14. The prognostic value of intermedin in patients with breast cancer.

    PubMed

    Lu, Yi-Min; Zhong, Jian-Bo; Wang, Hai-Yong; Yu, Xiong-Fei; Li, Zhong-Qi

    2015-01-01

    This study aimed to evaluate the prognostic value of preoperative plasma intermedin levels in breast cancer patients. Plasma intermedin levels of 252 breast cancer women and 100 healthy women were determined using radioimmunoassay kit. Adverse event was defined as first local recurrence, distant metastasis, second primary cancer of another organ, or death from any cause during 5-year follow-up. Disease-free survival was defined as the time between surgery and the date of any adverse event whichever appeared first. Overall survival was defined from surgery to death for any cause. The relationships between plasma intermedin levels and clinical outcomes of breast cancer patients were evaluated using multivariate analysis. The results showed that preoperative plasma intermedin levels were substantially higher in patients than in healthy subjects using t-test. Intermedin was identified as an independent predictor for 5-year mortality, adverse event, disease-free survival, and overall survival using multivariate analysis. Based on receiver operating characteristic curve analysis, preoperative plasma intermedin levels had high predictive value for 5-year mortality and adverse event. In conclusion, preoperative plasma intermedin levels are highly associated with poor patient outcomes and intermedin may be a potential prognostic biomarker for patients with breast cancer. PMID:25694747

  15. Local dynamics of heart rate: detection and prognostic implications.

    PubMed

    Moss, Travis J; Lake, Douglas E; Moorman, J Randall

    2014-10-01

    The original observation that reduced heart rate variability (HRV) confers poor prognosis after myocardial infarction has been followed by many studies of heart rate dynamics. We tested the hypothesis that an entropy-based local dynamics measure gave prognostic information in ambulatory patients undergoing 24-h electrocardiography. In this context, entropy is the probability that short templates will find matches in the time series. We studied RR interval time series from 24-h Holter monitors of 1564 consecutive patients over age 39. We generated histograms of the count of templates as a function of the number of templates matches in short RR interval time series, and found characteristic appearance of histograms for atrial fibrillation, sinus rhythm with normal HRV, and sinus rhythm with reduced HRV and premature ventricular contractions (PVCs). We developed statistical models to detect the abnormal dynamic phenotype of reduced HRV with PVCs and fashioned a local dynamics score (LDs) that, after controlling for age, added more prognostic information than other standard risk factors and common HRV metrics, including, to our surprise, the PVC count and the HRV of normal-to-normal intervals. Addition of the LDs to a predictive model using standard risk factors significantly increased the ROC area and the net reclassification improvement was 27%. We conclude that abnormal local dynamics of heart rate confer adverse prognosis in patients undergoing 24-h ambulatory electrocardiography. PMID:25229393

  16. 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

  17. Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas: A Strobe-Compliant Study.

    PubMed

    Wang, Mo-Jin; Ping, Jie; Li, Yuan; Holmqvist, Annica; Adell, Gunnar; Arbman, Gunnar; Zhang, Hong; Zhou, Zong-Guang; Sun, Xiao-Feng

    2015-12-01

    Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973-2011), and Linkping Cancer (LC, 1972-2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P?poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057-1.096; P?poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients. PMID:26705231

  18. Hyper Expression of Mucin 5ac Indicates Poor Cancer Prognoses

    PubMed Central

    Wang, Xin; Yan, Fei; Shi, Run; Huang, Xing; Lu, Shiming; Xu, Lin; Ren, Binhui

    2016-01-01

    Abstract The aim of the study was to explore the association between mucin 5ac expression and cancer prognosis. A systematically comprehensive search was performed through PubMed, the Web of Science, and the China National Knowledge Infrastructure (CNKI). The prognostic value of mucin 5ac expression in cancer patients was evaluated. The overexpression of mucin 5ac was found to be significantly associated with a poor prognosis in cancer patients (pooled HR: 1.53, 95%CI: 1.1582.028, P?=?0.003). This association was also detected in a biliary subgroup (pooled HR: 1.83, 95%CI: 1.2692.639, P?=?0.001) and a gastrointestinal subgroup (pooled HR: 1.44, 95%CI: 1.0691.949 P?=?0.017). In the geography subgroup analysis, a statistical association was found in the Asian subgroup (pooled HR: 1.69, 95%CI: 1.2002.384, P?=?0.003). In the clinical characteristics analysis, a statistical association was found between the hyper expression of mucin 5ac and lymphatic metastasis. We indicated that mucin 5ac is a promising prognostic predictor for cancer, especially for biliary and gastrointestinal cancer, and is more suitable for predicting cancer prognoses in Asians. PMID:26735541

  19. Poor performance characteristics of conventional PCR in detection of respiratory syncytial virus-experience of a tertiary care centre in Southern India.

    PubMed

    Nandhini, G; Sujatha, S; Jain, N; Dhodapkar, R; Kadhiravan, T; Krishnamurthy, S

    2015-01-01

    Respiratory syncytial virus (RSV) is a significant cause of contagious acute respiratory infections in children and older adults. Since there are contradictory reports regarding the efficacy of different methods to detect RSV, we evaluated the performance of the conventional PCR versus real-time PCR in 222 patients with acute respiratory infections (ARI) recruited between January 2012 and March 2013. Conventional PCR had a very poor sensitivity of 40% (95% CI: 19.2-63.9%) and failed to detect RSV in respiratory samples with low viral load. Thus, it may be prudent to replace it with real-time PCR to achieve precise diagnosis. PMID:25865982

  20. 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.

  1. An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies

    PubMed Central

    Padron, E; Garcia-Manero, G; Patnaik, M M; Itzykson, R; Lasho, T; Nazha, A; Rampal, R K; Sanchez, M E; Jabbour, E; Al Ali, N H; Thompson, Z; Colla, S; Fenaux, P; Kantarjian, H M; Killick, S; Sekeres, M A; List, A F; Onida, F; Komrokji, R S; Tefferi, A; Solary, E

    2015-01-01

    Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been robustly developed and externally validated, these results have been limited by the small size of single-institution cohorts. We developed an international CMML data set that included 1832 cases across eight centers to establish the frequency of key clinical characteristics. Of note, we found that the majority of CMML patients were classified as World Health Organization CMML-1 and that a 7.5% bone marrow blast cut-point may discriminate prognosis with higher resolution in comparison with the existing 10%. We additionally interrogated existing CMML prognostic models and found that they are all valid and have comparable performance but are vulnerable to upstaging. Using random forest survival analysis for variable discovery, we demonstrated that the prognostic power of clinical variables alone is limited. Last, we confirmed the independent prognostic relevance of ASXL1 gene mutations and identified the novel adverse prognostic impact imparted by CBL mutations. Our data suggest that combinations of clinical and molecular information may be required to improve the accuracy of current CMML prognostication. PMID:26230957

  2. ISG15 as a novel prognostic biomarker for hepatitis B virus-related hepatocellular carcinoma

    PubMed Central

    Qiu, Xiaoxin; Hong, Yuan; Yang, Darong; Xia, Man; Zhu, Haizhen; Li, Qinglong; Xie, Hailong; Wu, Qunfeng; Liu, Chen; Zuo, Chaohui

    2015-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Interferon-alpha (IFN-?) has recently been recognized to harbor therapeutic potential in prevention and treatment of HCC. IFN-stimulated gene 15 (ISG15) is an ubiquitin-like molecule that is strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. Several studies have shown that the overexpression of ISG15 is correlated with multiply tumor types. However, the role of ISG15 in hepatitis B virus (HBV)-related HCC remains undetermined. ISG15 expression was found to be obviously higher in HBV-related HCC tissues than that in non-tumor tissues. ISG15 is a novel prognostic marker for predicting 5-year overall survival of HBV-related HCC patients. Overexpression of ISG15 was associated with clinicopathological characteristics and poor patient outcomes. ISG15 may serve as a novel prognostic marker for HBV-related HCC. Therefore, ISG15 may represent a novel HCC marker with prognostic significance and may be helpful in selecting patients for and predicting response to the treatment of HBV-related HCC.

  3. Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrm's macroglobulinemia.

    PubMed

    Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hlne; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hlne; Leblondon, Vronique

    2013-04-01

    Waldenstrm's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenstrm's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenstrm's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics. PMID:23065509

  4. Absolute monocyte and lymphocyte count prognostic score for patients with gastric cancer

    PubMed Central

    Eo, Wan Kyu; Jeong, Da Wun; Chang, Hye Jung; Won, Kyu Yeoun; Choi, Sung Il; Kim, Se Hyun; Chun, Sung Wook; Oh, Young Lim; Lee, Tae Hwa; Kim, Young Ok; Kim, Ki Hyung; Ji, Yong Il; Kim, Ari; Kim, Heung Yeol

    2015-01-01

    AIM: To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score (AMLPS) in patients with gastric cancer. METHODS: We retrospectively examined the combination of absolute monocyte count (AMC) and absolute lymphocyte count (ALC) as prognostic variables in a cohort of 299 gastric cancer patients who underwent surgical resection between 2006 and 2013 and were followed at a single institution. Both AMC and ALC were dichotomized into two groups using cut-off points determined by receiving operator characteristic curve analysis. An AMLPS was generated, which stratified patients into three risk groups: low risk (both low AMC and high ALC), intermediate risk (either high AMC or low ALC), and high risk (both high AMC and low ALC). The primary objective of the study was to validate the impact of AMLPS on both disease-free survival (DFS) and overall survival (OS), and the second objective was to assess the AMLPS as an independent prognostic factor for survival in comparison with known prognostic factors. RESULTS: Using data from the entire cohort, the most discriminative cut-off values of AMC and ALC selected on the receiver operating characteristic curve were 672.4/?L and 1734/?L for DFS and OS. AMLPS risk groups included 158 (52.8%) patients in the low-risk, 128 (42.8%) in the intermediate-risk, and 13 (4.3%) in the high-risk group. With a median follow-up of 37.2 mo (range: 1.7-91.4 mo), five-year DFS rates in the low-, intermediate-, and high-risk groups were 83.4%, 78.7%, and 19.8%, respectively. And five-year OS rates in the low-, intermediate-, and high-risk groups were 89.3%, 81.1%, and 14.4%, respectively. On multivariate analysis performed with patient- and tumor-related factors, we identified AMLPS, age, and pathologic tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS and OS. CONCLUSION: AMLPS identified patients with a poor DFS and OS, and it was independent of age, pathologic stage, and various inflammatory markers. PMID:25759535

  5. 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

  6. Is a perceived supportive physical environment important for self-reported leisure time physical activity among socioeconomically disadvantaged women with poor psychosocial characteristics? An observational study

    PubMed Central

    2013-01-01

    Background Over the past decade, studies and public health interventions that target the physical environment as an avenue for promoting physical activity have increased in number. While it appears that a supportive physical environment has a role to play in promoting physical activity, social-ecological models emphasise the importance of considering other multiple levels of influence on behaviour, including individual (e.g. self-efficacy, intentions, enjoyment) and social (e.g. social support, access to childcare) factors (psychosocial factors). However, not everyone has these physical activity-promoting psychosocial characteristics; it remains unclear what contribution the environment makes to physical activity among these groups. This study aimed to examine the association between the perceived physical environment and self-reported leisure-time physical activity (LTPA) among women living in socioeconomically disadvantaged areas demonstrating different psychosocial characteristics. Methods In 20078, 3765 women (1845?years) randomly selected from low socioeconomic areas in Victoria, Australia, self-reported LTPA, and individual, social and physical environmental factors hypothesised within a social-ecological framework to influence LTPA. Psychosocial and environment scores were created. Associations between environment scores and categories of LTPA (overall and stratified by thirds of perceived environment scores) were examined using generalised ordered logistic regression. Results Women with medium and high perceived environment scores had 20-38% and 44-70% greater odds respectively of achieving higher levels of LTPA than women with low environment scores. When stratified by thirds of psychosocial factor scores, these associations were largely attenuated and mostly became non-significant. However, women with the lowest psychosocial scores but medium or high environment scores had 76% and 58% higher odds respectively of achieving ?120?minutes/week (vs. <120?minutes/week) LTPA. Conclusions Acknowledging the cross-sectional study design, the findings suggest that a physical environment perceived to be supportive of physical activity might help women with less favourable psychosocial characteristics achieve moderate amounts of LTPA (i.e. ?120?minutes/week). This study provides further support for research and public health interventions to target perceptions of the physical environment as a key component of strategies to promote physical activity. PMID:23537188

  7. Prognostic Impacts of Hypoxic Markers in Soft Tissue Sarcoma

    PubMed Central

    Smeland, Eivind; Kilvaer, Thomas K.; Sorbye, Sveinung; Valkov, Andrej; Andersen, Sigve; Bremnes, Roy M.; Busund, Lill-Tove; Donnem, Tom

    2012-01-01

    Background. We aimed to explore the prognostic impact of the hypoxia-induced factors (HIF?s) 1 and 2, the metabolic HIF-regulated glucose transporter GLUT-1, and carbonic anhydrase IX (CAIX) in non-gastrointestinal stromal tumor soft tissue sarcomas (non-GIST STS). Methods. Duplicate cores with viable tumor tissue from 206 patients with non-GIST STS were obtained and tissue microarrays were constructed. Immunohistochemistry (IHC) was used to evaluate expression of hypoxic markers. Results. In univariate analyses, GLUT-1 (P < 0.001) and HIF-2? (P = 0.032) expression correlated significantly with a poor disease-specific survival (DSS). In the multivariate analysis, however, only high expression of GLUT-1 (HR 1.7, CI 95% 1.12.7, P = 0.021) was a significant independent prognostic indicator of poor DSS. Conclusion. GLUT-1 is a significant independent negative prognostic factor in non-GIST STS. PMID:22454562

  8. 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

  9. 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…

  10. Predictive model for patients with poor-grade subarachnoid haemorrhage in 30-day observation: a 9-year cohort study

    PubMed Central

    Szklener, Sebastian; Melges, Anna; Korchut, Agnieszka; Zaluska, Wojciech; Trojanowski, Tomasz; Rejdak, Robert; Rejdak, Konrad

    2015-01-01

    Objective The purpose of this study was to identify prognostic factors and build the predictive model based on poor-grade subarachnoid haemorrhage (SAH) population received only supportive symptomatic treatment. Design Prospective observational cohort study. Setting Intensive care unit at the Clinical Department of Neurology. Participants A total of 101 patients with spontaneous SAH disqualified from neurosurgical operative treatment due to poor clinical condition. Data were collected over a 9-year period. Outcome measures Unfavourable outcome was defined as a modified Rankin Score ?5 at 30?days of observation. Results Multivariable logistic regression analysis indicated the World Federation of Neurosurgical Societies Scale score, increasing age, Fisher grade and admission leucocytosis as independent predictive factors. The proposed scale subdivides the study population into four prognostic groups with significantly different outcomes: grade I: probability of favourable outcome 89.9%; grade II: 47.5%; grade III: 4.2%; grade IV: 0%. The receiver operating characteristic (ROC) curve for the prediction of outcome performed by the new scale had an area under the curve (AUC)=0.910 (excellent accuracy). Conclusions Unfavourable outcome in non-operated patients with poor-grade SAH is strongly predicted by traditional unmodifiable factors such as age, amount of bleeding in CT, level of consciousness as well as leucocytosis. A new predictive scale based on the above parameters seems to reliably predict the outcome and may contribute to more effective planning of therapeutic management in patients with poor-grade SAH. PMID:26070797

  11. 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; Devoldre, 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 (?50G/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 12months 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. PMID:25193356

  12. 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) <60g/L, fasting blood glucose (FBG) >100mg/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?prognostic model had a better prognostic value than did the KPI model alone (p?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. PMID:24782120

  13. Prognostic factors in neuroendocrine cervical carcinoma

    PubMed Central

    Lee, Da Yong; Chong, Chul; Kim, Jae Weon; Park, Noh Hyun; Song, Yong Sang; Park, Sang Yoon

    2016-01-01

    Objective To evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine cervical carcinoma (NECC). Methods The records of 61 patients with NECC diagnosed between 2000 and 2014 at Seoul National University Hospital and the National Cancer Center were retrospectively reviewed. Kaplan-Meier and Cox regression methods were used for analyses. Results Of the 61 patients, 67.2% were diagnosed at early stage (I to IIA) with a median age of 49 years. Of those, 78% underwent surgery and 75.6% received postoperative adjuvant treatment. For patients diagnosed at advanced stage, 60.0% received chemotherapy only and 25.0% received concurrent chemoradiation therapy. In the univariate analysis, advanced stage (77 vs. 40 months, P=0.013), tumor size ≥2 cm (133 vs. 47 months, P=0.002) and mixed tumor (101 vs. 34 months, P=0.004) were shown to be poor prognostic factors. In the multivariate analysis, tumor stage, tumor size and tumor homology were shown to be independent prognostic factors for overall survival. Of the total, 39.3% of the patients experienced recurrence, and 54.1% of the patients had metastasis. Of the patients diagnosed at early stage, 51.2% experienced recurrence. Conclusion Tumor stage, tumor size and tumor homology were found to be independent prognostic factors in patients with NECC. Even in patients diagnosed at early stage, recurrence and distant metastasis were frequently observed. PMID:27004202

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

    PubMed Central

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

    2016-01-01

    Abstract 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. PMID:26871785

  15. [Claudins as prognostic factors of breast cancer].

    PubMed

    Szsz, Marcell A

    2012-09-01

    Different expression of claudins and E-cadherin has been described in the pathogenesis and progression of breast cancer. Changes in the expression of these junctional molecules have also been described as being of prominent importance in other cancers as well. Thus, we aimed at exploring the potential prognostic relevance of these cell junctional molecules in breast carcinoma cases. Expression of claudin-1, -3, -4, -5, -7, -8, -10, -15, -18 and E-cadherin at mRNA level was evaluated in correlation with survival in publicly available datasets containing expression measurements of 1809 breast cancer patients. Breast cancer tissues of 636 patients were evaluated with tissue microarray technique and immunohistochemical method for claudin-1, -2, -3, -4, -5, -7 and E-cadherin protein expression. In 96 cases lymph node metastases were also subjects of the study. Claudin expression bears prognostic information in itself. Based on bioinformatic data analysis, the meta-gene of claudin-3, -4, -7 and E-cadherin has proved the most powerful in predicting survival. An immunohistochemical protein profile consisting of claudin-2, -4 and E-cadherin was able to predict outcome in the most effective manner in the training set. Combining the overlapping members of the distinct methods resulted in the CC index (consisting of claudin-4 and E-cadherin, a.k.a. CURIO), which was able to accurately predict relapse-free survival in the validation cohort (p=0.029) in a more efficient way than its components. Cox regression analysis including clinicopathological variables and the average CC score showed that in univariate analysis most of them were prognostic but most of them lost independent prognostic value in multivariate analysis except for the CC index, the subtypes defined by immunoprofiling and vascular invasion. On the other hand, the CC index was able to further refine prognosis splitting good vs. poor prognosis patients into two clusters in these subgroups. Evaluation of lymph node metastases has shown that decreased expression of claudin-1 and elevated expression of claudin-4 can predict worse prognosis in breast cancers spreading to the regional lymph nodes. The defined claudin-cadherin index provides additional prognostic information besides the routinely utilized diagnostic approaches and factors. The level of expression of certain claudins can be of prognostic significance in regional lymph node metastases. PMID:23139925

  16. Prognostic Inflammation Score in Surgical Patients with Colorectal Cancer

    PubMed Central

    2015-01-01

    Several inflammatory markers have been investigated as prognostic parameters in a variety of cancer population with mostly favorable results. This study aimed to verify the significance of common inflammatory markers as prognostic variables and assess whether a selective combination of them as prognostic inflammation score (PIS) could further improve their prognostic values in surgical patients with colorectal cancer (CRC). A total of 265 patients who had undergone curative resection of CRC were reviewed retrospectively. Preoperative levels of inflammatory markers such as serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and neutrophil/lymphocyte ratio (NLR) were assessed by uni- and multivariate survival analysis with disease-free (DFS) and disease-specific survival (DSS). PIS was constructed with a selective combination of inflammatory markers which were independently significant. On univariate analysis, CRP, ESR, and NLR were significantly associated with DFS and DSS. On multivariate analysis, CRP and NLR were independently significant prognostic variables for DSS and DFS respectively (P=0.013, P=0.021). When PIS was constructed with combination of CRP and NLR, it was independently and significantly associated with both DFS and DSS (P=0.006, P=0.010). Furthermore, PIS was superior to CRP for DSS (HR=15.679 vs. HR=5.183), and NLR for DFS in terms of prognosticating power (HR=4.894 vs. HR=2.687). When PIS is constructed with combination of CRP and NLR, it is a potentially significant prognostic variable associated with poor survival regardless pathologic prognostic variables in patients with CRC after curative resection. PMID:26713054

  17. Prognostic Inflammation Score in Surgical Patients with Colorectal Cancer.

    PubMed

    Seong, Moo-Kyung

    2015-12-01

    Several inflammatory markers have been investigated as prognostic parameters in a variety of cancer population with mostly favorable results. This study aimed to verify the significance of common inflammatory markers as prognostic variables and assess whether a selective combination of them as prognostic inflammation score (PIS) could further improve their prognostic values in surgical patients with colorectal cancer (CRC). A total of 265 patients who had undergone curative resection of CRC were reviewed retrospectively. Preoperative levels of inflammatory markers such as serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and neutrophil/lymphocyte ratio (NLR) were assessed by uni- and multivariate survival analysis with disease-free (DFS) and disease-specific survival (DSS). PIS was constructed with a selective combination of inflammatory markers which were independently significant. On univariate analysis, CRP, ESR, and NLR were significantly associated with DFS and DSS. On multivariate analysis, CRP and NLR were independently significant prognostic variables for DSS and DFS respectively (P=0.013, P=0.021). When PIS was constructed with combination of CRP and NLR, it was independently and significantly associated with both DFS and DSS (P=0.006, P=0.010). Furthermore, PIS was superior to CRP for DSS (HR=15.679 vs. HR=5.183), and NLR for DFS in terms of prognosticating power (HR=4.894 vs. HR=2.687). When PIS is constructed with combination of CRP and NLR, it is a potentially significant prognostic variable associated with poor survival regardless pathologic prognostic variables in patients with CRC after curative resection. PMID:26713054

  18. [Prognostic factors of localised, locally advanced or metastatic prostate cancer].

    PubMed

    Joly, Florence; Henry-Amar, Michel

    2007-07-01

    In prostate cancer, whatever the stage of the disease, the selection of a treatment strategy is based on prognostic factors. Clinical stage, serum PSA concentration and Gleason score are among the most recognised factors. A combination of these three parameters leads to a score used to define prognostic groups that are routinely used in daily practice. More recently, predictive statistical models have been developed that were associated with nomograms. The objective of nomograms is, for a given patient, to calculate his probability to develop disease extension or relapse based on clinical, biological, histological and therapeutic (radiotherapy, hormonotherapy) data. Such nomograms are not all validated and their application in daily practice is more difficult than that of classical prognostic classifications. Nowadays, the progress and accessibility to novel technologies applied to biology will make possible in the near future the assessment of new prognostic profiles based on genetic and/or proteomic tumour characteristics. PMID:17845992

  19. Arteriopathy, D-dimer, and risk of poor neurologic outcome in childhood-onset arterial ischemic stroke.

    TOXLINE Toxicology Bibliographic Information

    Goldenberg NA; Jenkins S; Jack J; Armstrong-Wells J; Fenton LZ; Stence NV; Oleszek J; Boada R; Wilkening GN; Wilkinson C; Soep JB; Miyamoto SD; Bajaj L; Mourani PM; Manco-Johnson MJ; Bernard TJ

    2013-05-01

    OBJECTIVE: To assess whether acute findings of cerebral arteriopathy, large infarct, and acutely elevated plasma D-dimer levels are independently prognostic of poor long-term neurologic outcome as measured at ? 1 year post-event in children with arterial ischemic stroke (AIS).STUDY DESIGN: Sixty-one patients with childhood-onset (ie, >28 days of life) AIS were enrolled in a single-institution cohort study at Children's Hospital Colorado between February 2006 and June 2011. Data on demographic and diagnostic characteristics, antithrombotic treatments, and outcomes were systematically collected.RESULTS: Cerebral arteriopathy and D-dimer levels >500 ng/mL (a measure of coagulation activation) were identified acutely in 41% and 31% of the cohort, respectively. Anticoagulation was administered in the acute period post-event in 40% of the children, in the subacute period in 43%, and in the chronic period in 28%. When not receiving anticoagulation, patients were routinely treated with aspirin 2-5 mg/kg once daily for a minimum of 1 year. Death, major bleeding (including intracranial hemorrhage), and recurrent AIS were infrequent. The Pediatric Stroke Outcome Measure at 1 year demonstrated poor outcome in 54% of the children. Acute cerebral arteriopathy and elevated D-dimer level were identified as putative prognostic factors for poor outcome; after adjustment for D-dimer, arteriopathy was an independent prognostic indicator (OR, 19.0; 95% CI, 1.6-229.8; P = .02).CONCLUSION: Arteriopathy and coagulation activation are highly prevalent in the acute period of childhood AIS. Although recurrent AIS and intracranial hemorrhage were infrequent in our cohort, one-half of children experienced a poor neurologic outcome at 1 year, the risk of which was increased by acute arteriopathy. Substantiation of these findings in multi-institutional cohort studies is warranted, toward risk stratification in childhood-onset AIS.

  20. Prognostic factors of laryngeal solitary extramedullary plasmacytoma: a case report and review of literature

    PubMed Central

    Xing, Yong; Qiu, Jun; Zhou, Min-Li; Zhou, Shui-Hong; Bao, Yang-Yang; Wang, Qin-Ying; Zheng, Zhou-Jun

    2015-01-01

    A paucity of data exists concerning the presentation, natural course and outcome of extramedullary plasmcytoma (EMP). It is difficult to determine the optimal treatment strategy and prognostic factors for EMP. We present an additional case of laryngeal EMP and systemic review relevant reports in the English and Chinese literature. We found, to our knowledge, 147 cases in larynx in the English-language literature and Chinese-literature. The most common treatment modality was radiotherapy alone. The mean survival duration was ~184 months, and the 5- and 10- year survival rates were 76.1% and 67.4%, respectively. The univariate analysis suggested that progression to multiple myeloma and amyloid deposits may be poor prognostic factors. The multivariate analysis suggested that only progression to multiple myeloma may be a poor prognostic factor. Laryngeal EMP is uncommon. Progression to multiple myeloma may be a poor prognostic factor. PMID:26045749

  1. Sterilizing the Poor

    ERIC Educational Resources Information Center

    Rothman, Sheila M.

    1977-01-01

    Suggests that freedom for the middle classes may mean vulnerability for the poor. The enthusiasm for sterilization may be so intense as to deprive the poor of their right not to be sterilized. (Author/AM)

  2. SPOCK1 Overexpression Confers a Poor Prognosis in Urothelial Carcinoma

    PubMed Central

    Ma, Li-Jung; Wu, Wen-Jen; Wang, Yu-Hui; Wu, Ting-Feng; Liang, Peir-In; Chang, I-Wei; He, Hong-Lin; Li, Chien-Feng

    2016-01-01

    Purpose:The majority deaths of cancer patients are related to metastasis, thus genes associated with cell motility interest us. SPOCK1 was elected by data mining and serial evaluation. In addition, SPOCK1 has been reported to be highly expressed in different human cancers and been related to adverse outcomes. Therefore, we validate its prognostic significance in urothelial carcinoma (UC). Materials and Methods:Real-time RT-PCR assay was used to detect SPOCK1 transcript level in 27 urinary tract urothelial carcinoma (UTUC) and 27 urinary bladder urothelial carcinoma (UBUC) samples. Immunohistochemistry evaluated by H-score determined SPOCK1 expressions in 340 UTUCs and 295 UBUCs. The transcript and protein expression were correlated with clinicopathological features. Further evaluations of the prognostic significance of SPOCK1 for disease-specific survival (DSS) and metastasis-free survival (MeFS) were analyzed. Results:The expressions of SPOCK1 in UC were higher than those in normal urothelium by immunohistochemistry. The statistical analysis of clinicopathologic characteristics and immunohistochemistry showed that the higher expression of SPOCK1 was correlated to pT status (P<0.001), lymph node metastasis (UTUC, P=0.006; UBUC, P=0.033), higher histological grade (UTUC, P<0.001; UBUC, P<0.001), vascular invasion (UTUC, P<0.001; UBUC, P<0.001), perineurial invasion (UTUC, P<0.001; UBUC, P=0.001) and frequent mitosis (UTUC, P<0.001; UBUC, P=0.001). The prognosis of SPOCK1 of UC showed high SPOCK1 expression had significantly worse DSS and MeFS. Conclusions:The investigation demonstrated that the higher expression of SPOCK1 correlates with a poor prognosis in UC. PMID:26918061

  3. Current management and prognostic factors in physiotherapy practice for patients with shoulder pain: design of a prospective cohort study

    PubMed Central

    2013-01-01

    Background Shoulder pain is disabling and has a considerable socio-economic impact. Over 50% of patients presenting in primary care still have symptoms after 6months; moreover, prognostic factors such as pain intensity, age, disability level and duration of complaints are associated with poor outcome. Most shoulder complaints in this group are categorized as non-specific. Musculoskeletal ultrasound might be a useful imaging method to detect subgroups of patients with subacromial disorders. This article describes the design of a prospective cohort study evaluating the influence of known prognostic and possible prognostic factors, such as findings from musculoskeletal ultrasound outcome and working alliance, on the recovery of shoulder pain. Also, to assess the usual physiotherapy care for shoulder pain and examine the inter-rater reliability of musculoskeletal ultrasound between radiologists and physiotherapists for patients with shoulder pain. Methods A prospective cohort study including an inter-rater reliability study. Patients presenting in primary care physiotherapy practice with shoulder pain are enrolled. At baseline validated questionnaires are used to measure patient characteristics, disease-specific characteristics and social factors. Physical examination is performed according to the expertise of the physiotherapists. Follow-up measurements will be performed 6, 12 and 26weeks after inclusion. Primary outcome measure is perceived recovery, measured on a 7-point Likert scale. Logistic regression analysis will be used to evaluate the association between prognostic factors and recovery. Discussion The ShoCoDiP (Shoulder Complaints and using Diagnostic ultrasound in Physiotherapy practice) cohort study will provide information on current management of patients with shoulder pain in primary care, provide data to develop a prediction model for shoulder pain in primary care and to evaluate whether musculoskeletal ultrasound can improve prognosis. PMID:23399098

  4. Prognostic value of hyponatremia in heart failure patients: an analysis of the Clinical Characteristics and Outcomes in the Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (COAST) study

    PubMed Central

    Yoo, Byung-Su; Park, Jin Joo; Kang, Seok-Min; Hwang, Juey-Jen; Lin, Shing-Jong; Wen, Ming-Shien; Zhang, Jian; Ge, Junbo

    2015-01-01

    Background/Aims Hyponatremia is a well-known risk factor for poor outcomes in Western studies of heart failure (HF) patients. We evaluated the predictive value of hyponatremia in hospitalized Asian HF patients. Methods The Clinical Characteristics and Outcomes in the Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (the COAST) study enrolled hospitalized patients with systolic HF (ejection fraction < 45%) at eight centers in South Korea, Taiwan, and China. The relationship between admission sodium level and clinical outcomes was analyzed in 1,470 patients. Results The mean admission sodium level was 138 4.7 mmol/L, and 247 patients (16.8%) had hyponatremia defined as Na+ < 135 mmol/L. The 12-month mortality was higher in hyponatremic patients (27.9% vs. 14.6%, p < 0.001), and hyponatremia was an independent predictor of 12-month mortality (hazard ratio, 1.72; 95% confidence interval, 1.12 to 2.65). During hospital admission, 57% of hyponatremic patients showed improvement without improvement in their clinical outcomes (p = 0.620). The proportion of patients with optimal medical treatment was only 26.5% and 44.2% at admission and discharge, respectively, defined as the combined use of angiotensin-converting-enzyme inhibitor/angiotensin receptor blocker and ?-blocker. Underuse of optimal medical treatment was more pronounced in hyponatremic patients. Conclusions In hospitalized Asian HF patients, hyponatremia at admission is common and is an independent predictor of poor clinical outcome. Furthermore, hyponatremic patients receive less optimal medical treatment than their counterparts. PMID:26161012

  5. Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum

    PubMed Central

    Fejzo, Marlena S.; Magtira, Aromalyn; Schoenberg, Frederic Paik; MacGibbon, Kimber; Mullin, Patrick; Romero, Roberto; Tabsh, Khalil

    2014-01-01

    Objective The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors. Study design This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test. Results Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhy- dramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome. Conclusion Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy. PMID:23751910

  6. 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

  7. Elevated preoperative neutrophil-to-lymphocyte ratio is associated with poor prognosis in gastrointestinal stromal tumor patients

    PubMed Central

    Jiang, Chang; Hu, Wan-Ming; Liao, Fang-Xin; Yang, Qiong; Chen, Ping; Rong, Yu-Ming; Guo, Gui-Fang; Yin, Chen-Xi; Zhang, Bei; He, Wen-Zhuo; Xia, Liang-Ping

    2016-01-01

    Purpose To investigate the prognostic relevance of preoperative peripheral neutrophil- to-lymphocyte ratio (NLR) in gastrointestinal stromal tumor (GIST) patients. Materials and methods We enrolled 129 consecutive GIST patients who underwent initial curative surgical resection with or without adjuvant/palliative imatinib treatment in our study. Blood NLR was calculated as neutrophil count (number of neutrophils ×109/L) divided by lymphocyte count (number of lymphocytes ×109/L). Survival curves were constructed by using the Kaplan–Meier method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variable. All tests were two-sided, and P<0.05 was considered statistically significant. Results The optimal cut-off value of NLR was 2.07 in the receiver operating characteristic curve analysis. The median overall survival (OS) of high NLR group was 113.0 months, whereas that of the low NLR group had not reached the median OS both in the general (P<0.001) and subgroup analyses. The elevated NLR suggested shorter OS in the high malignant potential groups (P=0.01) and the combined low and moderate groups (P=0.02). Increased NLR indicated poor OS in patients regardless of whether if received imatinib treatment or not (P=0.005, and P=0.032, respectively). High NLR indicated poor OS of patients in stage I and II disease (P=0.005) and a clear tendency that increased level of NLR is inimical to OS. Conclusion Elevated NLR was detected as an independent adverse prognostic factor. Elevated preoperative NLR predicts poor clinical outcome in GIST patients and may serve as a cost-effective and broadly available independent prognostic biomarker.

  8. LRG1 is an independent prognostic factor for endometrial carcinoma.

    PubMed

    Wen, Shan-Yun; Zhang, Li-Na; Yang, Xiao-Mei; Zhang, Yan-Li; Ma, Li; Ge, Qiu-Lin; Jiang, Shu-Heng; Zhu, Xiao-Lu; Xu, Wei; Ding, Wen-Jing; Yang, Bing-Qing; Zhang, Zhi-Gang; Teng, Yin-Cheng

    2014-07-01

    Endometrial cancer (EC) is one of the most common female malignancies. The patients with high-risk factors may have poor prognosis. Therefore, there is an urgent need to find a new molecule to more accurately predict survival of patients. Leucine-rich-alpha-2-glycoprotein1 (LRG1), one of leucine-rich repeat family, was closely associated with cancer metastasis and poor prognosis. The biological functions and the expression level of LRG1 remain obscure in EC. In this study, by immunohistochemical analysis of 242 EC patient tissues, we found that LRG1 expression was associated with stage and lymphatic metastasis in both test cohort (133 patients) and validation cohort (109 patients). Furthermore, to investigate the prognostic value of LRG1 in endometrial carcinoma, we analyzed the correlation between variables and overall survival with Cox proportional hazard regression. The result showed that LRG1 was an independent prognostic factor for overall survival of endometrial carcinoma patients. To further evaluate the prognostic efficiency of LRG1 in endometrial carcinoma, we compared the sensitivity and specificity of LRG1 in endometrial carcinoma prognosis by logistic regression. The result showed that LRG1 combining with other clinicopathological risk factors was a stronger prognostic model than clinicopathological risk factors alone or their combination. Thus, LRG1 potentially offered clinical value in directing personal treatment for endometrial carcinoma patients. PMID:24760273

  9. Total pelvic exenteration for rectal cancer: outcomes and prognostic factors

    PubMed Central

    Domes, Trustin S.; Colquhoun, Patrick H.D.; Taylor, Brian; Izawa, Jonathan I.; House, Andrew A.; Luke, Patrick P.W.

    2011-01-01

    Background To perform complete resection of locally advanced and recurrent rectal carcinoma, total pelvic exenteration (TPE) may be attempted. We identified disease-related outcomes and prognostic factors. Methods We conducted a single-centre review of patients who underwent TPE for rectal carcinoma over a 10-year period. Results We included 28 patients in our study. After a median follow-up of 35 months, 53.6% of patients were alive with no evidence of disease. The 3-year actuarial disease-free and overall survival rates were 52.2% and 75.1%, respectively. On univariate analysis, recurrent disease, preoperative body mass index greater than 30 and lymphatic invasion were poor prognostic factors for disease-free survival, and only lymphatic invasion predicted overall survival. Additionally, multivariate analysis identified lymphatic invasion as an independent poor prognostic factor for disease-free survival in this patient population with locally advanced and recurrent rectal carcinoma. Conclusion Despite the significant morbidity, TPE can provide long-term survival in patients with rectal carcinoma. Additionally, lymphatic invasion on final pathology was an independent prognostic factor for disease-free survival. PMID:21939606

  10. Comparison of Prognostic MicroRNA Biomarkers in Blood and Tissues for Gastric Cancer

    PubMed Central

    Yan, Wenying; Qian, Laijun; Chen, Jiajia; Chen, Weichang; Shen, Bairong

    2016-01-01

    Gastric cancer (GC) still keeps up high mortality worldwide with poor prognosis. Efficient and non-invasive prognostic biomarkers are urgently needed. MicroRNAs are non-coding RNAs playing roles in post-transcriptional gene regulation, which contribute to various biological processes such as development, differentiation and carcinogenesis. MicroRNA expression profiles have been associated with the prognosis and outcome in GC. MicroRNA prognostic biomarkers have been identified from blood or tissues samples, but with different prognostic features. Understanding the various roles of microRNAs in different sample sources of GC will provide deep insights into GC progression. In this review, we highlight the distinct prognostic roles of microRNAs biomarkers in blood and tissue according to their relationships with prognostic parameters, survival rates and target pathways. This will be useful for non-invasive biomarker development and selection in prognosis of GC. PMID:26722365

  11. Protein Expression of ZEB2 in Renal Cell Carcinoma and Its Prognostic Significance in Patient Survival

    PubMed Central

    Cao, Jiazheng; Zhao, Hongwei; Liao, Bing; Qiu, Shaopeng; Wang, Daohu; Luo, Junhang; Chen, Wei

    2013-01-01

    Background ZEB2 has been reportedly shown to mediate the epithelial-to-mesenchymal transition (EMT) and disease aggressiveness in human tumors. However, the expression status of ZEB2 in renal cell carcinoma (RCC) and ZEB2’s clinicopathologic/prognostic significance are poorly understood. Methodology/Principal Findings In this study, tissue microarray, immunohistochemistry (IHC) and western blot analyses were utilized to investigate the ZEB2 expression status in RCC and adjacent renal tissue samples. In our study, samples from 116 RCC patients treated with radical nephrectomy were used as a training set to generate a ZEB2 optimal cut-point for patient outcome by receiver operating characteristic (ROC) analysis. For validation, the correlation of ZEB2 expression with the clinical characteristics and patient outcomes in another set (including 113 patients) was analyzed to validate the obtained cut-point. In the training and validation sets, high expression of ZEB2, defined by ROC analysis, predicted a poorer overall survival and progression-free survival, as evidenced by the univariate and multivariate analyses. In different subsets of overall patients, ZEB2 expression was also a prognostic indicator in patients with stage I/II, stage III/IV, grade 1/2 and grade 3/4 disease (P<0.05). Downregulation of ZEB2 by shRNA decreased the migration and invasion ability of 769-P cells in vitro. Furthermore, high ZEB2 expression was positively correlated with vimentin expression and inversely linked to E-cadherin expression in RCC. Conclusions/Significance Our findings provide a basis for the concept that high ZEB2 expression in RCC may be important in the acquisition of an aggressive phenotype. This evidence suggests that ZEB2 overexpression (examined by IHC) is an independent biomarker for the poor prognosis of patients with RCC. PMID:23658743

  12. International prognostic scoring system for Waldenstrom macroglobulinemia.

    PubMed

    Morel, Pierre; Duhamel, Alain; Gobbi, Paolo; Dimopoulos, Meletios A; Dhodapkar, Madhav V; McCoy, Jason; Crowley, John; Ocio, Enrique M; Garcia-Sanz, Ramon; Treon, Steven P; Leblond, Veronique; Kyle, Robert A; Barlogie, Bart; Merlini, Giampaolo

    2009-04-30

    Recently, many new drugs have been developed for the treatment of Waldenstrm macroglobulinemia (WM). To optimize the treatment according to the prognosis and to facilitate the comparison of trials, we developed an International Prognostic Scoring System for WM in a series of 587 patients with clearly defined criteria for diagnosis and for initiation of treatment. The median survival after treatment initiation was 87 months. Five adverse covariates were identified: advanced age (>65 years), hemoglobin less than or equal to 11.5 g/dL, platelet count less than or equal to 100 x 10(9)/L, beta2-microglobulin more than 3 mg/L, and serum monoclonal protein concentration more than 7.0 g/dL. Low-risk patients (27%) presented with no or 1 of the adverse characteristics and advanced age, intermediate-risk patients (38%) with 2 adverse characteristics or only advanced age, and high-risk patients (35%) with more than 2 adverse characteristics. Five-year survival rates were 87%, 68%, and 36%, respectively (P < .001). The ISSWM retained its prognostic significance in subgroups defined by age, treatment with alkylating agent, and purine analog. Thus, the ISSWM may provide a means to design risk-adapted studies. However, independent validation and new biologic markers may enhance its significance. PMID:19196866

  13. Prognostic factors of tuberculous meningitis: a single-center study

    PubMed Central

    Gu, Jin; Xiao, Heping; Wu, Furong; Ge, Yanping; Ma, Jun; Sun, Wenwen

    2015-01-01

    Objective: To investigate the prognostic factors of tuberculous meningitis (TBM) and develop strategies for the improvement of clinical efficacy. Methods: A total of 156 TBM patients were retrospectively reviewed. The demographic characteristics, underlying diseases, clinical features, laboratory findings, bacteriologic test, images, use of steroids, mannitol and anti-TB drugs, surgery or drainage, and clinical outcomes were collected and analyzed. Results: Patients with tubercle bacillus in the cerebrospinal fluid had significantly higher rate of consciousness disturbance (78.8%) and greater proportion of Glasgow coma scale (GCS) score of 3 (37.9%) when compared with the possible TBM patients (51.1% and 13.3%, respectively). Patients with definite TBM had a poor outcome and their mortality was significantly higher than in possible TBM patients (42.4% vs. 17.8%, P < 0.05). Univariate regression analysis showed that the advanced age, concomitant hematogenous disseminated pulmonary tuberculosis, change in consciousness, low GCS score on admission and hydrocephalus were associated with a poor prognosis; timely anti-TB treatment and reasonable hormone applications predicted a favorable outcome. Multivariate regression analysis showed that advanced age, change in consciousness, low GSC score and concomitant hydrocephalus were independent risk factors of TBM, and use of prednisone at ? 60 mg/d was protective factor for TBM (P=0.003, OR=0.013). Conclusions: The advanced age, changes in consciousness, low GCS score on admission and concomitant hydrocephalus are independent risk factors of TBM. For patients with risk factors, diagnostic anti-TB therapy and reasonable hormone therapy should be performed timely to reduce mortality and disability. PMID:26064373

  14. 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

  15. 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

  16. Podocalyxin is a marker of poor prognosis in colorectal cancer

    PubMed Central

    2014-01-01

    Background Over two decades ago, a proposal was that two different colorectal cancer (CRC) entities existed, based on tumour location either proximal (right) or distal (left) of the splenic flexure. Proximal and distal tumours exhibit different clinical, epidemiological, and biological characteristics. Improvement of the prognostic evaluation of CRC requires new molecular markers. Podocalyxin-like 1 (PODXL), an anti-adhesive transmembrane sialomucin, is associated with an aggressive tumour phenotype and poor prognosis. For colorectal cancer, it has been suggested to be a marker of poor prognosis. The aim of this study was to investigate the role of PODXL in CRC by use of a novel monoclonal antibody. Methods In 19832001, 840 consecutive colorectal cancer patients were treated at Helsinki University Central Hospital, of whom 767 were successfully scored for PODXL immunohistochemical expression from tumour tissue microarrays by use of a novel monoclonal in-house antibody. Associations of PODXL expression and tumour location with other clinicopathological variables were explored by Fishers exact-test, linear-by- linear association test, and binary logistic regression. Survival analyses were done by the Kaplan-Meier method and Cox proportional hazards model. Results PODXL protein expression was high in 44 (5.7%) specimens. High expression associated strongly with poor differentiation (p?poorly differentiated (p?poor prognosis in colorectal cancer and in the subgroups of left hemicolon and rectum. This is, to our knowledge, the first evidence of such difference in PODXL expression, its function possibly being dependent upon tumour location. PMID:25004863

  17. Twist1 is a potential prognostic marker for colorectal cancer and associated with chemoresistance

    PubMed Central

    Zhu, Da-Jian; Chen, Xiao-Wu; Zhang, Wei-Jie; Wang, Jia-Zhi; Ouyang, Man-Zhao; Zhong, Qiang; Liu, Chang-Chun

    2015-01-01

    Twist1 is a highly conserved basic helix-loophelix transcription factor, and has been shown to play an important role in carcinogenesis of many tumors including colorectal cancer (CRC). Here we aimed to investigate the role of Twist1 in the clinical significance and chemoresistance in CRC. In this study, we examined the correlation between Twist1 expression and clinicopathological characteristics using immunohistochemistry in patients with CRC. The molecular mechanisms of Twist1 expression and its effects on chemosensitivity to 5-Fluorouracil and oxaliplatin were also explored by MTT assay, colony forming assay, flow cytometry assay. The results indicate that Twist1 is overexpressed in cancer tissue, and its positive expression are related to histological grade (P=0.004), T-stage (P=0.033), N-stage (P=0.000), M-stage (P=0.040), TNM stage (P=0.002) and recurrence (P=0.023). Moreover, positive Twist1 expression is correlated with poor overall survival in CRC patients (P<0.0001), and is a significant independent prognostic indicator. In addition, we show that knockdown of Twist1 inhibits proliferation, and increased the percentage of apoptotic cells of CRC cell lines. Our findings suggest that Twist1 promotes proliferation and chemoresistance of CRC cells. Twist1 may be a potential prognostic marker and a molecular target for therapies. PMID:26269759

  18. 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

  19. Long-Term Follow-Up and Prognostic Factors for Advanced Thymic Carcinoma

    PubMed Central

    Wu, Jun-xin; Chen, Hui-qin; Shao, Ling-dong; Qiu, Su-fang; Ni, Qian-yu; Zheng, Bu-hong; Wang, Jie-zhong; Pan, Jian-ji; Li, Jin-luan

    2014-01-01

    Abstract The aim of this study was to evaluate the long-term survival outcomes in patients with advanced thymic carcinoma and identify prognostic factors influencing the survival. We retrospectively analyzed 90 consecutive patients with pathologically confirmed advanced thymic carcinoma (Masaoka III and IV) in our institute, from December 2000 to 2012. Age, sex, clinical characteristics, laboratory findings, Masaoka and tumor node metastasis staging, pathologic grade, and treatment modalities were analyzed to identify prognostic factors associated with the progress-free survival (PFS) and the overall survival (OS) rates. Statistical analysis was conducted using SPSS, version 19.0 (SPSS, Inc, Chicago, IL). A total of 73 (81.1%) male and 17 (18.9%) female patients participated in the study. The median follow-up time was 75 months (range, 20–158 months). The 5-year PFS and OS rates were 23.6% (95% confidence interval [CI], 14.6%–33.8%) and 35.7% (95% CI, 25.1%–46.4%), respectively. The multivariate Cox regression model analysis showed that factors improving the PFS were the normal lactate dehydrogenase (LDH) level (P < 0.001), Masaoka III stage (P = 0.028), and radiotherapy (RT) (P < 0.001). The LDH (P < 0.001), T stage (P < 0.001), and the pathologic grade (P = 0.047) were independently prognostic of OS. Long-term follow-up of the advanced thymic carcinoma showed poor outcomes of PFS and OS. LDH, Masaoka stage, and RT affected the PFS, and LDH, T stage, and pathologic grade seemed to affect the OS. Establishing a better staging system for predicting outcomes would be warranted. PMID:25526488

  20. Low-Level Microsatellite Instability as a Potential Prognostic Factor in Sporadic Colorectal Cancer.

    PubMed

    Lee, Soo Young; Kim, Duck-Woo; Lee, Hye Seung; Ihn, Myong Hoon; Oh, Heung-Kwon; Min, Byung Soh; Kim, Woo Ram; Huh, Jung Wook; Yun, Jung-A; Lee, Kang Young; Kim, Nam Kyu; Lee, Woo Yong; Kim, Hee Cheol; Kang, Sung-Bum

    2015-12-01

    Although microsatellite instability-high (MSI-H) colorectal cancers (CRCs) have been shown to exhibit a distinct phenotype, the clinical value of MSI-low (MSI-L) in CRC remains unclear. We designed this study to examine the clinicopathologic characteristics and oncologic implications associated with MSI-L CRCs.We retrospectively reviewed data of CRC patients from 3 tertiary referral hospitals in Korea, who underwent surgical resection between January 2003 and December 2009 and had available MSI testing results. MSI testing was performed using the pentaplex Bethesda panel. Clinicopathologic features and oncologic outcomes were compared between MSI-L and microsatellite stable (MSS) CRCs; prognostic factors for survival were also examined.Of the 3019 patients reviewed, 2621 (86.8%) were MSS, and 200 (6.6%) were MSI-L; the remaining 198 (6.6%) were MSI-H. MSI-L and MSS CRCs were comparable in terms of their clinicopathologic features, with the exception of proximal tumor location (MSI-L 30.0% vs MSS 22.1%, P?=?0.024) and tumor size (MSI-L 5.2??2.6?cm vs MSS 4.6??2.1?cm, P?=?0.001). No differences were detected in either 3-year disease-free survival (MSI-L 87.2% vs MSS 82.6%, P?=?0.121) or 5-year overall survival (OS) (MSI-L 74.2% vs MSS 78.3%, P?=?0.131) by univariable analysis. However, MSI-L was an independent prognostic factor for poor OS by Cox regression analysis (hazard ratio 1.358, 95% confidence interval 1.014-1.819, P?=?0.040).MSI-L may be an independent prognostic factor for OS in sporadic CRCs despite their clinicopathologic similarity to MSS. Further studies investigating the significance of MSI-L in the genesis and prognosis of CRCs are needed. PMID:26683947

  1. Prognostic Factors in Cholinesterase Inhibitor Poisoning

    PubMed Central

    Sun, In O; Yoon, Hyun Ju; Lee, Kwang Young

    2015-01-01

    Background Organophosphates and carbamates are insecticides that are associated with high human mortality. The purpose of this study is to investigate the prognostic factors affecting survival in patients with cholinesterase inhibitor (CI) poisoning. Material/Methods This study included 92 patients with CI poisoning in the period from January 2005 to August 2013. We divided these patients into 2 groups (survivors vs. non-survivors), compared their clinical characteristics, and analyzed the predictors of survival. Results The mean age of the included patients was 56 years (range, 1688). The patients included 57 (62%) men and 35 (38%) women. When we compared clinical characteristics between the survivor group (n=81, 88%) and non-survivor group (n=11, 12%), there were no differences in renal function, pancreatic enzymes, or serum cholinesterase level, except for serum bicarbonate level and APACHE II score. The serum bicarbonate level was lower in non-survivors than in survivors (12.452.84 vs. 18.364.73, P<0.01). The serum APACHE II score was higher in non-survivors than in survivors (24.365.22 vs. 12.076.67, P<0.01). The development of pneumonia during hospitalization was higher in non-survivors than in survivors (n=9, 82% vs. n=31, 38%, P<0.01). In multiple logistic regression analysis, serum bicarbonate concentration, APACHE II score, and pneumonia during hospitalization were the important prognostic factors in patients with CI poisoning. Conclusions Serum bicarbonate and APACHE II score are useful prognostic factors in patients with CI poisoning. Furthermore, pneumonia during hospitalization was also important in predicting prognosis in patients with CI poisoning. Therefore, prevention and active treatment of pneumonia is important in the management of patients with CI poisoning. PMID:26411989

  2. Prognostic Implication of Semi-quantitative Immunohistochemical Assessment of CD20 Expression in Diffuse Large B-Cell Lymphoma

    PubMed Central

    Choi, Chang Hwan; Park, Young Hoon; Lim, Joo Han; Choi, Suk Jin; Kim, Lucia; Park, In Suh; Han, Jee Young; Kim, Joon Mee; Chu, Young Chae

    2016-01-01

    Background: Immunohistochemical demonstration of CD20 in diffuse large B-cell lymphoma (DLBCL) is prerequisite not only for the diagnosis but also for assigning patients to rituximab-containing chemotherapy. However, little is known about the impact of abundance of CD20 expression assessed by immunohistochemistry on the clinical outcome of DLBCL. We performed a semi-quantitative immunohistochemical analysis of CD20 expression in DLBCL to examine the prognostic implication of the level of CD20 expression. Methods: Pre-treatment diagnostic tissue samples from 48 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen were represented in a tissue microarray and immunostained for CD20. The relative abundance of CD20 expression was semi-quantitatively scored using a web-based ImmunoMembrane plug-in. Receiver operating characteristic curve analysis was used to determine a prognostically relevant cut-off score in order to dichotomize the patients into CD20-high versus CD20-low groups. Results: The levels of CD20 expression were heterogeneous among the patients, with a wide and linear distribution of scores. Patients in CD20-low group showed significantly poor clinical outcome. Conclusions: The levels of CD20 expression in DLBCL are heterogeneous among the patients with DLBCL. A subgroup of the patients with CD20 expression levels below the cut-off score showed poor clinical outcome. PMID:26875759

  3. 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.

  4. 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. PMID:26948758

  5. DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers

    PubMed Central

    Abdel-Fatah, Tarek M.A.; Arora, Arvind; Moseley, Paul M.; Perry, Christina; Rakha, Emad A.; Green, Andrew R.; Chan, Stephen Y.T.; Ellis, Ian O.; Madhusudan, Srinivasan

    2015-01-01

    Stratification of oestrogen receptor (ER) negative and triple negative breast cancers (TNBCs) is urgently needed. In the current study, a cohort of 880 ER- (including 635 TNBCs) was immuno-profiled for a panel of DNA repair proteins including: Pol ?, FEN1, APE1, XRCC1, SMUG1, PARP1, BRCA1, ATR, ATM, DNA-PKcs, Chk1, Chk2, p53, and TOPO2. Multivariate Cox proportional hazards models (with backward stepwise exclusion of these factors, using a criterion of p < 0.05 for retention of factors in the model) were used to identify factors that were independently associated with clinical outcomes. XRCC1 (p = 0.002), pol ? (p = 0.032) FEN1 (p = 0.001) and BRCA1 (p = 0.040) levels were independently associated with poor BCSS. Subsequently, DNA repair index prognostic (DRPI) scores for breast cancer specific survival (BCSS) were calculated and two prognostic groups (DRPI-PGs) were identified. Patients in prognostic group 2 (DRPI-PG2) have higher risk of death (p < 0.001). Furthermore, in DRPI-PG2 patients, exposure to anthracycline reduced the risk of death [(HR (95% CI) = 0.79 (0.640.98), p = 0.032) by 2126%. In addition, DRPI-PG2 patients have adverse clinicopathological features including higher grade, lympho-vascular invasion, Her-2 positive phenotype, compared to those in DRPI-PG1 (p < 0.01). Receiver operating characteristic (ROC) curves indicated that the DRPI outperformed the currently used prognostic factors and adding DRPI to lymph node stage significantly improved their performance as a predictor for BCSS [p < 0.00001, area under curve (AUC) = 0.70]. BER strongly influences pathogenesis of ER- and TNBCs. The DRPI accurately predicts BCSS and can also serve as a valuable prognostic and predictive tool for TNBCs. PMID:26267318

  6. DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers.

    PubMed

    Abdel-Fatah, Tarek M A; Arora, Arvind; Moseley, Paul M; Perry, Christina; Rakha, Emad A; Green, Andrew R; Chan, Stephen Y T; Ellis, Ian O; Madhusudan, Srinivasan

    2015-09-01

    Stratification of oestrogen receptor (ER) negative and triple negative breast cancers (TNBCs) is urgently needed. In the current study, a cohort of 880 ER- (including 635 TNBCs) was immuno-profiled for a panel of DNA repair proteins including: Pol ?, FEN1, APE1, XRCC1, SMUG1, PARP1, BRCA1, ATR, ATM, DNA-PKcs, Chk1, Chk2, p53, and TOPO2. Multivariate Cox proportional hazards models (with backward stepwise exclusion of these factors, using a criterion of p < 0.05 for retention of factors in the model) were used to identify factors that were independently associated with clinical outcomes. XRCC1 (p = 0.002), pol ? (p = 0.032) FEN1 (p = 0.001) and BRCA1 (p = 0.040) levels were independently associated with poor BCSS. Subsequently, DNA repair index prognostic (DRPI) scores for breast cancer specific survival (BCSS) were calculated and two prognostic groups (DRPI-PGs) were identified. Patients in prognostic group 2 (DRPI-PG2) have higher risk of death (p < 0.001). Furthermore, in DRPI-PG2 patients, exposure to anthracycline reduced the risk of death [(HR (95% CI) = 0.79 (0.64-0.98), p = 0.032) by 21-26%. In addition, DRPI-PG2 patients have adverse clinicopathological features including higher grade, lympho-vascular invasion, Her-2 positive phenotype, compared to those in DRPI-PG1 (p < 0.01). Receiver operating characteristic (ROC) curves indicated that the DRPI outperformed the currently used prognostic factors and adding DRPI to lymph node stage significantly improved their performance as a predictor for BCSS [p < 0.00001, area under curve (AUC) = 0.70]. BER strongly influences pathogenesis of ER- and TNBCs. The DRPI accurately predicts BCSS and can also serve as a valuable prognostic and predictive tool for TNBCs. PMID:26267318

  7. Prognostic and predictive markers in pancreatic adenocarcinoma.

    PubMed

    Le, Nha; Sund, Malin; Vinci, Alessio

    2016-03-01

    Pancreatic ductal adenocarcinoma is characterized by a poor prognosis and a low median survival, despite improvements observed for many other solid tumours. Intensive research efforts have been undertaken during the last decades to discover new prognostic and treatment predictive biomarkers for pancreatic ductal adenocarcinoma. The mainstay of medical treatment for the disease has been the well-tolerated nucleoside analogue, gemcitabine. The only targeted agent currently used in pancreatic ductal adenocarcinoma patients is the epithelial growth factor receptor inhibitor erlotinib in combination with gemcitabine. Recently, treatment regimens such as a combination of fluorouracil-leucovorin-irinotecan-oxaliplatin (FOLFIRINOX) and the combination of nab-paclitaxel with gemcitabine have been introduced for metastatic pancreatic ductal adenocarcinoma. Although these treatment regimens significantly improve survival of patients, there are no good predictive biomarkers available that can be used to identify who would benefit most from them. Therefore, the search for predictive biomarkers that would facilitate personalization of chemotherapy is highly relevant. PMID:26769569

  8. High IDH1 expression is associated with a poor prognosis in cytogenetically normal acute myeloid leukemia.

    PubMed

    Ma, Qiu-Ling; Wang, Jing-Han; Wang, Yun-Gui; Hu, Chao; Mu, Qi-Tian; Yu, Meng-Xia; Wang, Lei; Wang, Dong-Mei; Yang, Min; Yin, Xiu-Feng; Chen, Fei-Fei; Lu, Sha-Sha; Chen, Jian; Zhu, Zhi-Juan; Chen, Sai-Juan; Jin, Jie

    2015-09-01

    The prognostic value of IDH1 mutations has been systematically evaluated in acute myeloid leukemia (AML) patients recently. However, the role of IDH1 expression in AML is still under exploration. To investigate the clinical significance, we analyzed the IDH1/2 expression in 320 patients with cytogenetically normal AML (CN-AML) by quantitative real-time reverse-transcription polymerase chain reaction. High expression of IDH1 was predominant in patients with FLT3-ITD and DNMT3A mutations and less prevalent in cases with CEBPA double allele mutations. Strong association was observed between high IDH1 expression and low expression of microRNA 181 family. Prognosis was adversely affected by high IDH1 expression, with shorter overall survival and event-free survival in the context of clinical characteristics, including age, WBC count, and gene mutations of NPM1, FLT3-ITD, CEBPA, IDH1, IDH2 and DNMT3A in CN-AML. Moreover, the clinical outcome of IDH1 expression in terms of overall survival, event-free survival and complete remission rate still remained in multivariate models in CN-AML. Importantly, the prognostic value was validated using the published microarray data from 79 adult patients treated according to the German AMLCG-1999 protocol. Our results demonstrated that high IDH1 expression is associated with a poor prognosis of CN-AML. PMID:25523507

  9. Clinical Outcomes and Prognostic Factors of Up-Front Autologous Stem Cell Transplantation in Patients with Extranodal Natural Killer/T Cell Lymphoma.

    PubMed

    Yhim, Ho-Young; Kim, Jin Seok; Mun, Yeung-Chul; Moon, Joon Ho; Chae, Yee Soo; Park, Yong; Jo, Jae-Cheol; Kim, Seok Jin; Yoon, Dok Hyun; Cheong, June-Won; Kwak, Jae-Yong; Lee, Je-Jung; Kim, Won Seog; Suh, Cheolwon; Yang, Deok-Hwan

    2015-09-01

    Limited data exist on up-front autologous stem cell transplantation (ASCT) in extranodal natural killer/T cell lymphoma (ENKTL). Sixty-two patients (43 men and 19 women) with newly diagnosed ENKTL who underwent up-front ASCT after primary therapy were identified. Poor-risk characteristics included advanced stage (50%), high-intermediate to high-risk International Prognostic Index (25.8%), and group 3 to 4 of NK/T Cell Lymphoma Prognostic Index (NKPI, 67.7%). Pretransplant responses included complete remission in 61.3% and partial remission in 38.7% of patients, and final post-transplantation response included complete remission in 78.3%. Early progression occurred in 12.9%. At a median follow-up of 43.3 months (range, 3.7 to 114.6), 3-year progression-free survival (PFS) was 52.4% and 3-year overall survival (OS) was 60.0%. Patients with limited disease had significantly better 3-year PFS (64.5% versus 40.1%, P = .017) and OS (67.6% versus 52.3%, P = .048) than those with advanced disease. Multivariate analysis showed NKPI and pretransplant response were independent prognostic factors influencing survival, particularly NKPI in limited disease and pretransplant response in advanced disease. Radiotherapy was an independent factor for reduced progression and survival in patients with limited disease, but anthracycline-based chemotherapy was a poor prognostic factor for progression in patients with advanced disease. Up-front ASCT is an active treatment in ENKTL patients responding to primary therapy. PMID:25963920

  10. MDS prognostic scoring systems past, present, and future.

    PubMed

    Jonas, Brian A; Greenberg, Peter L

    2015-03-01

    The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid haemopathies characterized by defective differentiation of haematopoietic cells and expansion of the abnormal clone. This leads to bone marrow failure with the resulting peripheral blood cytopenias and evolution to or toward acute myeloid leukaemia that characterize MDS clinically. The clinical heterogeneity of MDS has led several groups to analyze patient and clinical characteristics to develop prognostic scoring systems yielding estimates of overall and leukaemia-free survival to guide clinical decision-making. These models have evolved over time as our understanding of the pathogenesis, natural history, and treatment of MDS has improved. Rapid advances in flow cytometric analysis, adjuncts to standard metaphase cytogenetics, and gene mutation analysis are revolutionizing our understanding of MDS pathogenesis and prognosis. Despite the existence of multiple well-validated prognostic scoring systems, further refinements of current models with these new sources of prognostic data are needed and are described herein. PMID:25659725

  11. Impact of the International Prognostic Scoring System cytogenetic risk groups on the outcome of patients with primary myelodysplastic syndromes undergoing allogeneic stem cell transplantation from human leukocyte antigen-identical siblings: a retrospective analysis of the European Society for Blood and Marrow Transplantation-Chronic Malignancies Working Party

    PubMed Central

    Onida, Francesco; Brand, Ronald; van Biezen, Anja; Schaap, Michel; von dem Borne, Peter A.; Maertens, Johan; Beelen, Dietrich W.; Carreras, Enric; Alessandrino, Emilio P.; Volin, Liisa; Kuball, Jürgen H.E.; Figuera, Angela; Sierra, Jorge; Finke, Jürgen; Kröger, Nicolaus; de Witte, Theo

    2014-01-01

    Acquired chromosomal abnormalities are important prognostic factors in patients with myelodysplastic syndromes treated with supportive care and with disease-modifying therapeutic interventions, including allogeneic hematopoietic stem cell transplantation. To assess the prognostic impact of cytogenetic characteristics after hematopoietic stem cell transplantation accurately, we investigated a homogeneous group of 523 patients with primary myelodysplastic syndromes who have received stem cells from human leukocyte antigen-identical siblings. Overall survival at five years from transplantation in good, intermediate, and poor cytogenetic risk groups according to the International Prognostic Scoring System was 48%, 45% and 30%, respectively (P<0.01). Both the disease status (complete remission vs. not in complete remission) and the morphological classification at transplant in the untreated patients were significantly associated with probability of overall survival and relapse-free survival (P<0.01). The cytogenetic risk groups have no prognostic impact in untreated patients with refractory anemia ± ringed sideroblasts (P=0.90). However, combining the good and intermediate cytogenetic risk groups and comparing them to the poor-risk group showed within the other three disease-status-at-transplant groups a hazard ratio of 1.86 (95%CI: 1.41–2.45). In conclusion, this study shows that, in a large series of patients with primary myelodysplastic syndromes, poor-risk cytogenetics as defined by the standard International Prognostic Scoring System is associated with a relatively poor survival after allogeneic stem cell transplantation from human leukocyte antigen-identical siblings except in patients who are transplanted in refractory anemia/refractory anemia with ringed sideroblasts stage before progression to higher myelodysplastic syndrome stages. PMID:25085359

  12. High Levels of Nucleolar Spindle-Associated Protein and Reduced Levels of BRCA1 Expression Predict Poor Prognosis in Triple-Negative Breast Cancer

    PubMed Central

    Hu, Xin; Li, Shan; Yao, Ling; Yang, Xue-Li; Shao, Zhi-Ming

    2015-01-01

    Purpose Nucleolar spindle-associated protein (NuSAP1) is an important mitosis-related protein, and aberrant NuSAP1 expression is associated with abnormal spindles and mitosis. This study investigated the prognostic value of NuSAP1 in breast cancer. Methods Two sets of tissue microarrays (TMAs) that included samples from 450 breast cancer patients were constructed, of which 250 patients were training set and the other 200 patients were validation set. Immunohistochemical staining was performed to determine the NuSAP1 levels. A Kaplan-Meier analysis was used to estimate the prognostic value of NuSAP1 in breast cancer. A stepwise Cox analysis was performed to construct a risk-prediction model for triple-negative breast cancer (TNBC). All statistical analysis was performed with SPSS software. Results There were 108 (43.5%) and 88 (44.0%) patients expressed NuSAP1 in the training set and validation set respectively. High levels of NuSAP1 expression were related to poor disease-free survival (DFS) in both training (P = 0.028) and validation (P = 0.006) cohorts, particularly in TNBC. With combination of two cohorts, both NuSAP1 (HR = 4.136, 95% CI: 1.9568.747, P < 0.001) and BRCA1 (HR = 0.383, 95% CI: 0.1600.915, P = 0.031) were independent prognostic indicators of DFS in TNBC. A receiver operating characteristic (ROC) analysis revealed that the combination of NuSAP1 and BRCA1 significantly improved the prognostic power compared with the traditional model (0.778 versus 0.612, P < 0.001). Conclusions Our study confirms the prognostic value of NuSAP1 in breast cancer. The combination of NuSAP1 and BRCA1 could improve the DFS prediction accuracy in TNBC. PMID:26485712

  13. 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.

  14. A Prognostic Model of Triple-Negative Breast Cancer Based on miR-27b-3p and Node Status

    PubMed Central

    Shen, Songjie; Sun, Qiang; Liang, Zhiyong; Cui, Xiaojiang; Ren, Xinyu; Chen, Huan; Zhang, Xiao; Zhou, Yidong

    2014-01-01

    Objective Triple-negative breast cancer (TNBC) is an aggressive but heterogeneous subtype of breast cancer. This study aimed to identify and validate a prognostic signature for TNBC patients to improve prognostic capability and to guide individualized treatment. Methods We retrospectively analyzed the prognostic performance of clinicopathological characteristics and miRNAs in a training set of 58 patients with invasive ductal TNBC diagnosed between 2002 and 2012. A prediction model was developed based on independent clinicopathological and miRNA covariates. The prognostic value of the model was further validated in a separate set of 41 TNBC patients diagnosed between 2007 and 2008. Results Only lymph node status was marginally significantly associated with poor prognosis of TNBC (P?=?0.054), whereas other clinicopathological factors, including age, tumor size, histological grade, lymphovascular invasion, P53 status, Ki-67 index, and type of surgery, were not. The expression levels of miR-27b-3p, miR-107, and miR-103a-3p were significantly elevated in the metastatic group compared with the disease-free group (P value: 0.008, 0.005, and 0.050, respectively). The Cox proportional hazards regression analysis revealed that lymph node status and miR-27b-3p were independent predictors of poor prognosis (P value: 0.012 and 0.027, respectively). A logistic regression model was developed based on these two independent covariates, and the prognostic value of the model was subsequently confirmed in a separate validation set. The two different risk groups, which were stratified according to the model, showed significant differences in the rates of distant metastasis and breast cancer-related death not only in the training set (P value: 0.001 and 0.040, respectively) but also in the validation set (P value: 0.013 and 0.012, respectively). Conclusion This model based on miRNA and node status covariates may be used to stratify TNBC patients into different prognostic subgroups for potentially individualized therapy. PMID:24945253

  15. Poorly Differentiated Neuroendocrine Tumors.

    PubMed

    Eads, Jennifer R

    2016-02-01

    Poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract are rare and limited data are available to guide treatment. These tumors have been treated akin to small cell lung cancer given the histologic similarities. Their pathology is complex. Over the last decade, these tumors are shown as likely a distinct disease entity that is more heterogeneous than accounted for by the current classification system. This article discusses the epidemiology, prognosis, clinical presentation and pathologic nuances and provides a review of the existing clinical data in poorly differentiated neuroendocrine carcinomas and small cell lung cancers. PMID:26614374

  16. 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.

  17. Preoperative Plasma Fibrinogen Level Represents an Independent Prognostic Factor in a Chinese Cohort of Patients with Upper Tract Urothelial Carcinoma

    PubMed Central

    Jin, Jie; Zhou, Li-Qun; He, Zhi-Song; Shen, Cheng; He, Qun; Li, Jun; Liu, Li-Bo; Wang, Cong; Chen, Xiao-Yu; Fan, Yu; Hu, Shuai; Zhang, Lei; Yu, Wei; Han, Wen-Ke

    2016-01-01

    Background Increased plasma fibrinogen is thought to contribute to tumor progression and metastasis. The association of plasma fibrinogen with clinicopathological characteristics, and the optimal cutoff with an ideal predictive value has not been fully determined in patients with upper tract urothelial carcinoma (UTUC). We aimed to investigate the clinical significance of this parameter in a Chinese cohort of patients with UTUC. Methods A retrospective study was conducted to analyze the clinical data of 184 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). An optimal cutoff was set for further analysis according to validated web-based software. The associations of plasma fibrinogen with clinicopathological characteristics and survival were assessed. Multivariate analyses were performed to determine the independent prognostic factors. Results Elevated plasma fibrinogen was significantly associated with tumor necrosis, lymph node involvement, and a higher preoperative CKD stage, pathological tumor stage and grade (all P < 0.05). Kaplan-Meier analysis showed that plasma fibrinogen ≥ 3.54 g/L predicted a poorer overall and cancer-specific survival than < 3.54 g/L (P < 0.001 for both). Multivariate analyses revealed that elevated preoperative plasma fibrinogen was an independent negative prognostic factor for overall survival (HR = 2.026; 95% CI: 1.226–3.349; P = 0.006) and cancer-specific survival (HR = 1.886; 95% CI: 1.019–3.490; P = 0.043). Conclusions Increased plasma fibrinogen was an independent prognostic risk factor for poor outcomes in UTUC. This parameter may serve as an effective biomarker with easy accessibility for evaluating prognosis for patients with UTUC. PMID:26930207

  18. Prognostic value and clinical correlations of 18-fluorodeoxyglucose metabolism quantifiers in gastric cancer

    PubMed Central

    Grabinska, Kinga; Pelak, Maciej; Wydmanski, Jerzy; Tukiendorf, Andrzej; dAmico, Andrea

    2015-01-01

    AIM: To investigate the correlations of pre-treatment positron emission tomography-computer tomography (PET-CT) metabolic quantifiers with clinical data of unstratified gastric cancer (GC) patients. METHODS: Forty PET-CT scans utilising 18-fluorodeoxyglucose in patients who received no prior treatment were analysed. Analysis involved measurements of maximum and mean standardised uptake volumes (SUV), coefficient of variation (COV), metabolic tumour volumes and total lesion glycolysis of different thresholds above which the tumor volumes were identified. The threshold values were: SUV absolute value of 2.5, 30% of SUVmax, 40% of SUVmax, and liver uptake-based (marked 2.5, 30, 40 and liv, respectively). Clinical variables such as age, sex, clinical stage, performance index, weight loss, tumor histological type and grade, and CEA and CA19.9 levels were included in survival analysis. Patients received various treatment modalities appropriate to their disease stage and the outcome was defined by time to metastasis (TTM) and overall survival (OS). Clinical and metabolic parameters were evaluated by analysis of variance, receiver operating characteristics, univariate Kaplan-Meier, and multivariate Cox models. P < 0.05 was considered statistically significant. RESULTS: Significant differences were observed between initially disseminated and non-disseminated patients in mean SUV (6.05 vs 4.13, P = 0.008), TLG2.5 (802 cm3 vs 226 cm3; P = 0.031), and TLG30 (436 cm3 vs 247 cm3, P = 0.018). Higher COV was associated with poor tumour differentiation (0.47 for G3 vs 0.28 for G1 and G2; P = 0.03). MTV2.5 was positively correlated to patient weight loss (< 5%, 5%-10% and > 10%: 40.4 cm3 vs 123.6 cm3 vs 181.8 cm3, respectively, P = 0.003). In multivariate Cox analysis, TLG30 was prognostic for OS (HR = 1.001, 95%CI: 1.0009-1.0017; P = 0.047) for the whole group of patients. In the same model yet only including patients without initial disease dissemination TLG30 (HR = 1.009, 95%CI: 1.003-1.014; P = 0.004) and MTV2.5 (HR = 1.02, 95%CI: 1.002-1.036; P = 0.025) were prognostic for OS; for TTM TLG30 was the only significant prognostic variable (HR = 1.006, 95%CI: 1.001-1.012; P = 0.02). CONCLUSION: PET-CT in GC may represent a valuable diagnostic and prognostic tool that requires further evaluation in highly standardised environments such as randomised clinical trials. PMID:26019454

  19. Morphosyntax in Poor Comprehenders

    ERIC Educational Resources Information Center

    Adlof, Suzanne M.; Catts, Hugh W.

    2015-01-01

    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

  20. 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

  1. Ki-67 is a valuable prognostic factor in gliomas: evidence from a systematic review and meta-analysis.

    PubMed

    Chen, Wen-Jie; He, De-Shen; Tang, Rui-Xue; Ren, Fang-Hui; Chen, Gang

    2015-01-01

    Ki-67 has been widely used as an indicator of cell proliferation in gliomas. However, the role of Ki-67 as a prognostic marker is still undefined. Thus, we conducted a meta-analysis of the published literatures in order to clarify the impact of Ki-67 on survival in glioma cases. Eligible studies were identified in PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled Trials, Science Direct and Wiley Online Library with the last search updated on August 31, 2014. The clinical characteristics, overall survival (OS) and progression- free survival (PFS) together with Ki-67 expression at different time points were extracted. A total of 51 studies, covering 4,307 patients, were included in the current meta-analysis. The results showed that overexpression of Ki-67 can predict poor OS (HR=1.66, 95%CI: 1.53-1.80; Z=11.87; p=0.000) and poor PFS (HR=1.67, 95%CI: 1.47-1.91; Z=7.67; p=0.000) in gliomas. Moreover, subgroup analyses also indicated that high level of Ki-67 expression was related to poor OS and PFS in glioma patients regardless of region, pathology type, cut-off value and statistical method. In conclusion, the current meta-analysis revealed that Ki-67 expression might be a predicative factor for poor prognosis of glioma patients, emphasizing its importance as a predictor. PMID:25684464

  2. A prognostic index for operable, node-negative breast cancer.

    PubMed

    McCallum, M; Baker, C; Gillespie, K; Cohen, B; Stewart, H; Leonard, R; Cameron, D; Leake, R; Paxton, J; Robertson, A; Purdie, C; Gould, A; Steel, M

    2004-05-17

    Clinical data and samples from patients diagnosed, more than 10 years previously, with operable node-negative breast cancer (participants in the Scottish Adjuvant Tamoxifen trial), were revisited. Cases with two distinct categories of outcome were selected; more than 10 years disease-free survival ('good outcome') or distant relapse within 6 years of diagnosis ('poor outcome'). An initial set of cases was analysed for a range of putative prognostic markers and a prognostic index, distinguishing the two outcome categories, was calculated. This index was then validated by testing its predictive power on a second, independent set of cases. A combination of histological grade plus immunochemical staining for BCL-2, p27 and Cyclin D1, generated a useful prognostic index for tamoxifen-treated patients but not for those treated by surgery alone. The value of the index was confirmed in a second set of tamoxifen-treated, early stage breast cancers. Overall, it correctly predicted good and poor outcome in 79 and 74% of cases, respectively (odds ratio 11.0). Other markers assessed added little to prediction of outcome. In the case of molecular assays, sensitivity and reliability were compromised by the age of the tissue specimens and the variability of fixation protocols. In selecting patients for adjuvant systemic chemotherapy, the proposed index improves considerably on current international guidelines and matches the performance reported for 'gene-expression signature' analysis. PMID:15138474

  3. Prognostication of Bell's palsy using transcranial magnetic stimulation.

    PubMed

    Rimpilinen, I; Eskola, H; Laippala, P; Laranne, J; Karma, P

    1997-01-01

    Transcranial magnetic stimulation (TMS) provides a method to noninvasive excitation of the facial nerve in its intracranial segment close to the internal acoustic meatus. Thus, the site of facial nerve activation with TMS is proximal to or within the site of the lesion in Bell's palsy. To evaluate the prognostic capability of TMS in unilateral Bell's palsy we examined 137 patients with this method, and compared the results with electroneuronography (ENoG). Within 0-4 days from the onset of palsy, the patients with elicitable TMS responses recovered better than those in whom TMS responses were not elicitable. If TMS was performed 5-9 days or 10-28 days after the onset of palsy, it did not provide any prognostic information. Based on amplitude side-to-side differences, ENoG did not contribute prognostic information during the first 9 days from the onset of palsy. Later on, 10-28 days after the onset of palsy, ENoG showed an increased capability to discriminate the patients with poor prognosis. Thus, elicitable facial motor response with TMS predicts good prognosis of Bell's palsy at an early stage whereas poor response with ENoG predicts less favorable prognosis at a later stage. PMID:9288286

  4. Pooled analysis of the prognostic relevance of progesterone receptor status in five German cohort studies.

    PubMed

    Salmen, Jessica; Neugebauer, Julia; Fasching, Peter A; Haeberle, Lothar; Huober, Jens; Wckel, Achim; Rauh, Claudia; Schuetz, Florian; Weissenbacher, Tobias; Kost, Bernd; Stickeler, Elmar; Klar, Maximilian; Orlowska-Volk, Marzenna; Windfuhr-Blum, Marisa; Heil, Joerg; Rom, Joachim; Sohn, Christof; Fehm, Tanja; Mohrmann, Svjetlana; Loehberg, Christian R; Hein, Alexander; Schulz-Wendtland, Ruediger; Hartkopf, Andreas D; Brucker, Sara Y; Wallwiener, Diethelm; Friese, Klaus; Hartmann, Arndt; Beckmann, Matthias W; Janni, Wolfgang; Rack, Brigitte

    2014-11-01

    The progesterone receptor (PR) has been increasingly well described as an important mediator of the pathogenesis and progression of breast cancer. The aim of this study was to assess the role of PR status as a prognostic factor in addition to other well-established prognostic factors. Data from five independent German breast cancer centers were pooled. A total of 7,965 breast cancer patients were included for whom information about their PR status was known, as well as other patient and tumor characteristics commonly used as prognostic factors. Cox proportional hazards models were built to compare the predictive value of PR status in addition to age at diagnosis, tumor size, nodal status, grading, and estrogen receptor (ER) status. PR status significantly increased the accuracy of prognostic predictions with regard to overall survival, distant disease-free survival, and local recurrence-free survival. There were differences with regard to its prognostic value relative to subgroups such as nodal status, ER status, and grading. The prognostic value of PR status was greatest in patients with a positive nodal status, negative ER status, and low grading. The PR-status adds prognostic value in addition to ER status and should not be omitted from clinical routine testing. The significantly greater prognostic value in node-positive and high-grade tumors suggests a greater role in the progression of advanced and aggressive tumors. PMID:25253172

  5. Prognostic factors in acute cardiogenic pulmonary edema.

    PubMed

    Le Conte, P; Coutant, V; N'Guyen, J M; Baron, D; Touze, M D; Potel, G

    1999-07-01

    The purpose of this study was to determine the clinical and biological findings at admission in the Department of Emergency Medicine associated with a poor prognosis, and to evaluate early response to treatment as a prognostic factor. It was a prospective cohort study with a 5-month follow-up. One hundred eighty-six patients admitted for acute cardiogenic pulmonary edema were included. Features were analyzed at the admission and on response to initial treatment. The main outcome measure was survival at 2 end-points: hospital discharge, and 5 months of follow-up. Multivariate analysis showed that in-hospital mortality was associated with marbleization (mottling) odd-ratio (OR) = 9.0), low diuresis (OR = 4.0), high breath rate 6 hours after admission (OR = 4.0), and chronic digoxin use (OR = 3.39). Five-month mortality was associated with a bedridden state (OR = 9.0), marbleization (mottling) (OR = 5.5), myocardial infarction (OR = 3), and poor early response to initial treatment (OR = 3.2). In addition to well-known factors, the response to initial treatment evaluated 6 hours after admission was a major determinant of outcome. PMID:10452425

  6. 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 (P < 0.001). Multivariate logistic regression with stepwise likelihood ratio (LR) method concluded that hypoxia post operatively (P = 0.152), the unmaintained Cerebral Perfusion Pressure (CPP) (P = 0.007) and unstable blood pressure (BP) (P = <0.001). Poor outcome noted 10.2 times higher in post operative hypoxia [OR10.184; 95% CI: 0.424, 244.495]. Odds of having poor outcome if CPP unmaintained was 13.8 times higher [OR: 13.754; CI: 2.050, 92.301]. Highest predictor of poor outcome was the unstable BP, 32 times higher [OR 31.600; CI: 4.530, 220440]. Conclusion: Our series represent both urban and rural population, noted to be the largest series in severe TBI in this region. Severe head injury accounts for significant proportion of neurosurgical admissions, resources with its impact on socio-economic concerns to a growing population like Malaysia. This study concludes that the predictors of outcome in severe TBI post DC were postoperative hypoxia, unmaintained cerebral perfusion pressure and unstable blood pressure as independent predictors of poor outcome. Key words: Decompressive craniectomy, prognostication of decompressive craniectomy, prognostication of severe head injury, prognostication of traumatic brain injury, severe head injury, severe traumatic brain injury, traumatic brain injury. PMID:25685217

  7. Prognostic and predictive significance of immune cells infiltrating cutaneous melanoma.

    PubMed

    Ladnyi, Andrea

    2015-09-01

    The tumor microenvironment is shaped by interactions between malignant cells and host cells representing an integral component of solid tumors. Host cells, including elements of the innate and adaptive immune system, can exert both positive and negative effects on the outcome of the disease. In melanoma, studies on the prognostic impact of the lymphoid infiltrate in general, and that of T cells, yielded controversial results. According to our studies and data in the literature, a high peritumoral density of activated T cells, increased amount of B lymphocytes and mature dendritic cells (DCs) predicted longer survival, while intense infiltration by plasmacytoid DCs or neutrophil granulocytes could be associated with poor prognosis. Besides its prognostic value, evaluation of the components of immune infiltrate could provide biomarkers for predicting the efficacy of the treatment and disease outcome in patients treated with immunotherapy or other, non-immune-based modalities as chemo-, radio-, or targeted therapy. PMID:25818762

  8. 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 assessing screening. PMID:17432552

  9. Pretransplant Elevated Plasma Fibrinogen Level is a Novel Prognostic Predictor for Hepatocellular Carcinoma Recurrence and Patient Survival Following Liver Transplantation.

    PubMed

    Wang, Guo-Ying; Jiang, Nan; Yi, Hui-Min; Wang, Gen-Shu; Zhang, Jian-Wen; Li, Hua; Zhang, Jian; Zhang, Qi; Yang, Yang; Chen, Gui-Hua

    2016-01-01

    BACKGROUND Elevated plasma fibrinogen is associated with tumour progression and poor outcomes in several cancers. The present study investigated the prognostic value of preoperative fibrinogen in hepatocellular carcinoma (HCC) patients after liver transplantation (LT). MATERIAL AND METHODS We analyzed the preoperative plasma fibrinogen levels of 41 patients who underwent LT for HCC. The cut-off value for elevated level of fibrinogen was determined by using a receiver operating characteristic (ROC) curve analysis. Cox regression analysis was performed to analyze the relationship between elevated fibrinogen level and HCC recurrence. The disease-free survival (DFS) and overall survival (OS) rate after transplantation were calculated by Kaplan-Meier method and compared by log-rank test. RESULTS The fibrinogen levels were significantly higher in patients with tumor recurrence (3.310.98 g/L) compared with those in patients without recurrence (2.390.89 g/L) (P<0.01). A cut-off value for elevated fibrinogen level of 2.675 g/L was defined. Cox regression analysis showed that the relative risk for tumor recurrence increased by 6.871 times for patients with elevated fibrinogen. Eleven patients in the elevated fibrinogen group (21 cases) developed recurrence, while only 2 in the normal fibrinogen group (20 cases) developed recurrence. There were significant differences in DFS and OS between the elevated fibrinogen group and normal fibrinogen group (5-year DFS and OS of 44.0% and 42.9% vs. 89.2% and 80.0%, respectively, P<0.05). Vascular invasion and fibrinogen level ?2.675 g/L were the independent prognostic predictors of tumor recurrence and poor outcome. CONCLUSIONS Pretransplant elevated fibrinogen levels are associated with tumor recurrence and poor prognosis in hepatocellular carcinoma patients after liver transplantation. PMID:26903139

  10. 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

  11. Comparison of selected inflammation-based prognostic markers in relapsed or refractory metastatic colorectal cancer patients

    PubMed Central

    Song, Anna; Eo, Wankyu; Lee, Sookyung

    2015-01-01

    AIM: To investigate the impact of systemic inflammation-based prognostic markers on overall survival in relapsed/refractory metastatic colorectal cancer (mCRC) patients. METHODS: To investigate prognostic markers in mCRC patients, this study was performed with patients who have experienced relapsed/refractory mCRC with standard chemotherapy or were inapplicable to conventional treatment modality because of poor performance status, age, or comorbidity. We reviewed the medical records of 177 mCRC patients managed with Korean Medicine (KM) treatment modality using an anticancer agent of Rhus verniciflua Stokes extract from June 2006 to April 2013. The clinicopathologic characteristics, laboratory test, the systemic inflammation markers including the modified Glasgow prognostic score (mGPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte monocyte ratio (LMR), and prognostic nutritional index (PNI) were analyzed. The overall survival of patients was calculated with the Kaplan-Meier method and the statistical significance was compared using with the log-rank test. To compare the impact of systemic inflammation based markers, the hazard ratio (HR) of mGPS, NLR, PLR, LMR, and PNI for overall survival were evaluated with the Cox proportional hazards regression. RESULTS: The majority of mCRC patients had relapsed/refractory to standard chemotherapy; 128 patients (72.3%) had undergone more than second line chemotherapy, and the median time from diagnosis of mCRC to initiation of KM was 9.4 mo. The median overall survival of enrolled patients was 8.3 mo. On univariate analyses, the inflammation markers of higher mGPS (P < 0.001), NLR ≥ 5 (P < 0.001), PLR > 300 (P = 0.004), LMR ≤ 3.4 (P < 0.001), and PNI ≤ 45.3 (P = 0.001) were significantly associated with decreased survival time. On stepwise multivariate proportional hazards model, mGPS at 2 vs 0 (HR = 3.212, 95%CI: 1.437-7.716, P = 0.004), and LMR ≤ 3.4 (HR = 1.658, 95%CI: 1.092-2.518, P = 0.018) as independent predictors associated with poor overall survival along with carbohydrate antigen 19-9 (HR = 1.482, 95%CI: 1.007-2.182, P = 0.046), AST ≥ 40 (HR = 2.377, 95%CI: 1.359-4.155, P = 0.002), and the treatment duration for KM less than 2.9 mo (HR = 1.718, 95%CI: 1.160-2.543, P = 0.007). CONCLUSION: These results indicate that the inflammatory markers, mGPS and LMR are independent prognostic factors for predicting overall survival in relapsed/refractory mCRC patients. PMID:26604648

  12. Systematic review of multivariable prognostic models for mild traumatic brain injury.

    PubMed

    Silverberg, Noah D; Gardner, Andrew J; Brubacher, Jeffrey R; Panenka, William J; Li, Jun Jian; Iverson, Grant L

    2015-04-15

    Prognostic models can guide clinical management and increase statistical power in clinical trials. The availability and adequacy of prognostic models for mild traumatic brain injury (MTBI) is uncertain. The present study aimed to (1) identify and evaluate multivariable prognostic models for MTBI, and (2) determine which pre-, peri-, and early post-injury variables have independent prognostic value in the context of multivariable models. An electronic search of MEDLINE, PsycINFO, PubMed, EMBASE, and CINAHL databases for English-language MTBI cohort studies from 1970-2013 was supplemented by Web of Science citation and hand searching. This search strategy identified 7789 articles after removing duplicates. Of 182 full-text articles reviewed, 26 met eligibility criteria including (1) prospective inception cohort design, (2) prognostic information collected within 1 month post-injury, and (3) 2+variables combined to predict clinical outcome (e.g., post-concussion syndrome) at least 1 month later. Independent reviewers extracted sample characteristics, study design features, clinical outcome variables, predictor selection methods, and prognostic model discrimination, calibration, and cross-validation. These data elements were synthesized qualitatively. The present review found no multivariable prognostic model that adequately predicts individual patient outcomes from MTBI. Suboptimal methodology limits their reproducibility and clinical usefulness. The most robust prognostic factors in the context of multivariable models were pre-injury mental health and early post-injury neuropsychological functioning. Women and adults with early post-injury anxiety also have worse prognoses. Relative to these factors, the severity of MTBI had little long-term prognostic value. Future prognostic studies should consider a broad range of biopsychosocial predictors in large inception cohorts. PMID:25222514

  13. 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

  14. 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 27.6years) 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. PMID:26216494

  15. 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.

  16. αB-Crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer

    PubMed Central

    Moyano, Jose V.; Evans, Joseph R.; Chen, Feng; Lu, Meiling; Werner, Michael E.; Yehiely, Fruma; Diaz, Leslie K.; Turbin, Dmitry; Karaca, Gamze; Wiley, Elizabeth; Nielsen, Torsten O.; Perou, Charles M.; Cryns, Vincent L.

    2006-01-01

    Recent gene profiling studies have identified a new breast cancer subtype, the basal-like group, which expresses genes characteristic of basal epithelial cells and is associated with poor clinical outcomes. However, the genes responsible for the aggressive behavior observed in this group are largely unknown. Here we report that the small heat shock protein α-basic–crystallin (αB-crystallin) was commonly expressed in basal-like tumors and predicted poor survival in breast cancer patients independently of other prognostic markers. We also demonstrate that overexpression of αB-crystallin transformed immortalized human mammary epithelial cells (MECs). In 3D basement membrane culture, αB-crystallin overexpression induced luminal filling and other neoplastic-like changes in mammary acini, while silencing αB-crystallin by RNA interference inhibited these abnormalities. αB-Crystallin overexpression also induced EGF- and anchorage-independent growth, increased cell migration and invasion, and constitutively activated the MAPK kinase/ERK (MEK/ERK) pathway. Moreover, the transformed phenotype conferred by αB-crystallin was suppressed by MEK inhibitors. In addition, immortalized human MECs overexpressing αB-crystallin formed invasive mammary carcinomas in nude mice that recapitulated aspects of human basal-like breast tumors. Collectively, our results indicate that αB-crystallin is a novel oncoprotein expressed in basal-like breast carcinomas that independently predicts shorter survival. Our data also implicate the MEK/ERK pathway as a potential therapeutic target for these tumors. PMID:16395408

  17. AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer.

    PubMed

    Moyano, Jose V; Evans, Joseph R; Chen, Feng; Lu, Meiling; Werner, Michael E; Yehiely, Fruma; Diaz, Leslie K; Turbin, Dmitry; Karaca, Gamze; Wiley, Elizabeth; Nielsen, Torsten O; Perou, Charles M; Cryns, Vincent L

    2006-01-01

    Recent gene profiling studies have identified a new breast cancer subtype, the basal-like group, which expresses genes characteristic of basal epithelial cells and is associated with poor clinical outcomes. However, the genes responsible for the aggressive behavior observed in this group are largely unknown. Here we report that the small heat shock protein alpha-basic-crystallin (alphaB-crystallin) was commonly expressed in basal-like tumors and predicted poor survival in breast cancer patients independently of other prognostic markers. We also demonstrate that overexpression of alphaB-crystallin transformed immortalized human mammary epithelial cells (MECs). In 3D basement membrane culture, alphaB-crystallin overexpression induced luminal filling and other neoplastic-like changes in mammary acini, while silencing alphaB-crystallin by RNA interference inhibited these abnormalities. alphaB-Crystallin overexpression also induced EGF- and anchorage-independent growth, increased cell migration and invasion, and constitutively activated the MAPK kinase/ERK (MEK/ERK) pathway. Moreover, the transformed phenotype conferred by alphaB-crystallin was suppressed by MEK inhibitors. In addition, immortalized human MECs overexpressing alphaB-crystallin formed invasive mammary carcinomas in nude mice that recapitulated aspects of human basal-like breast tumors. Collectively, our results indicate that alphaB-crystallin is a novel oncoprotein expressed in basal-like breast carcinomas that independently predicts shorter survival. Our data also implicate the MEK/ERK pathway as a potential therapeutic target for these tumors. PMID:16395408

  18. Predicting the oral absorption of a poorly soluble, poorly permeable weak base using biorelevant dissolution and transfer model tests coupled with a physiologically based pharmacokinetic model.

    PubMed

    Wagner, Christian; Jantratid, Ekarat; Kesisoglou, Filippos; Vertzoni, Maria; Reppas, Christos; B Dressman, Jennifer

    2012-09-01

    For predicting food effects and simulating plasma profiles of poorly soluble drugs, physiologically based pharmacokinetic models have become a widely accepted tool in academia and the pharmaceutical industry. Up till now, however, simulations appearing in the open literature have mainly focused on BCS class II compounds, and many of these simulations tend to have more of a "retrospective" than a prognostic, predictive character. In this work, investigations on the absorption of a weakly basic BCS class IV drug, "Compound A", were performed. The objective was to predict the plasma profiles of an immediate release (IR) formulation of Compound A in the fasted and fed state. For this purpose, in vitro biorelevant dissolution tests and transfer model experiments were conducted. Dissolution and precipitation kinetics were then combined with in vivo post-absorptive disposition parameters using STELLA software. As Compound A not only exhibits poor solubility but also poor permeability, a previously developed STELLA model was revised to accommodate the less than optimal permeability characteristics as well as precipitation of the drug in the fasted state small intestine. Permeability restrictions were introduced into the model using an absorption rate constant calculated from the Caco-2 permeability value of Compound A, the effective intestinal surface area and appropriate intestinal fluid volumes. The results show that biorelevant dissolution tests are a helpful tool to predict food effects of Compound A qualitatively. However, the plasma profiles of Compound A could only be predicted quantitatively when the results of biorelevant dissolution test were coupled with the newly developed PBPK model. PMID:22652546

  19. 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 36months. 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=0008; PFS=48% vs. 21%, P=0001). 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. PMID:26010293

  20. Prognostic Significance of Preoperative Albumin-Globulin Ratio in Patients with Upper Tract Urothelial Carcinoma

    PubMed Central

    Zhou, Li-Qun; He, Zhi-Song; Shen, Cheng; He, Qun; Li, Jun; Liu, Li-Bo; Wang, Cong; Chen, Xiao-Yu; Fan, Yu; Hu, Shuai; Zhang, Lei; Han, Wen-Ke; Jin, Jie

    2015-01-01

    Background Preoperative albumin-globulin ratio (AGR) reflects both malnutrition and systemic inflammation in cancer patients. In particular, systemic inflammation has been reported to contribute to tumor progression and poor oncological outcome in various malignancies. However, the prognostic value of preoperative AGR in upper tract urothelial carcinoma (UTUC) has not been examined. Methods We retrospectively reviewed medical data of 187 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). AGR was calculated as [AGR = albumin/(serum total proteinalbumin)]. The associations of preoperative AGR with clinicopathologic characteristics and prognosis were assessed. Multivariate analyses using Cox regression models were performed to determine the independent prognostic factors. Results The median (IQR) preoperative AGR was 1.50 (1.301.70), and the optimal cutoff value was determined to be 1.45 according to the receiver operating curve analysis. Low AGR was significantly associated with female gender, high CKD stage and tumor grade (P < 0.05). Eighty-three patients died before the follow-up endpoint. Kaplan-Meier analysis showed that an AGR < 1.45 predicted significantly poorer overall and cancer-specific survivals compared to an AGR ? 1.45 (P < 0.001 and P = 0.008, respectively). Multivariate analyses showed that an AGR < 1.45 was an independent risk factor for poorer overall and cancer-specific survivals (P = 0.002 and P = 0.015, respectively). Conclusions Preoperative AGR can act as an effective biomarker with easy accessibility for evaluating the prognosis of patients with UTUC. AGR should be applied in UTUC patients for risk stratification and determination of optimal therapeutic regimens. PMID:26681341

  1. 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

  2. Modifiable Prognostic Factors of Hepatocellular Carcinoma in Patients with Non-Surgical Treatment

    PubMed Central

    Yeh, Jen-Hao; Hung, Chao-Hung; Wang, Jing-Houng; Chen, Chien-Hung; Kee, Kwong-Ming; Kuo, Chung-Mou; Yen, Yi-Hao; Cheng, Yu-Fan; Chen, Yen-Yang; Hsu, Hsuan-Chi; Lu, Sheng-Nan

    2015-01-01

    Background & aims Current hepatocellular carcinoma (HCC) staging systems only use baseline characteristics to predict outcome. We aimed to explore modifiable factors of the prognosis in HCC cases had undergone non-surgical treatment. Methods All HCC cases in Kaohsiung Chang Gung Memorial hospital in southern Taiwan from 2002 to 2012 must met all below criteria: (1) met international diagnostic guidelines, (2) underwent the initial treatments in our hospital (3) treated by non-surgical treatment modalities and (4) survived more than two years, with follow-up time longer than five years. Results A total 698 patients were enrolled: 451 (24.6%, group A) survivied between 2 to 5 years, and 247 (13.5%, group B) had survived > 5 years. Aside from liver function reserve and BCLC stages, four interventional factors: initial treatment modality, outcomes of 1st or 2nd treatment, and anti-viral therapy to chronic viral hepatitis were associated with prognosis. After propensity score matching, multiple logistic regression of 223 well-matched pairs showed that recurrence within one year after 1st treatment (OR: 2.17, 95% CI: 1.353.48), incomplete 2nd treatment (2.01, 1.273.17) and absence of anti-viral agents (1.68, 1.092.59) were independent poor prognostic factors. Conclusion Complete treatment and anti-viral agents to chronic hepatitis were both independent modifiable prognostic factors of HCC patients had undergone non-surgical treatment. Based on these findings, timely treatment to achieve maximal locoregional control and anti-viral treatment should be provided as possible. PMID:26661388

  3. Platelet to lymphocyte ratio as a novel prognostic tool for gallbladder carcinoma

    PubMed Central

    Pang, Qing; Zhang, Ling-Qiang; Wang, Rui-Tao; Bi, Jian-Bin; Zhang, Jing-Yao; Qu, Kai; Liu, Su-Shun; Song, Si-Dong; Xu, Xin-Sen; Wang, Zhi-Xin; Liu, Chang

    2015-01-01

    AIM: To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio (PLR) in patients with gallbladder carcinoma (GBC). METHODS: Clinical data of 316 surgical GBC patients were analyzed retrospectively, and preoperative serum platelet and lymphocyte counts were used to calculate the PLR. The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic (ROC) curve. The primary outcome was overall survival, which was estimated by the Kaplan-Meier method. The log-rank test was used to compare the differences in survival. Then, we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients. RESULTS: For the PLR, the area under the ROC curve was 0.620 (95%CI: 0.542-0.698, P = 0.040) in detecting death. The cut-off value for the PLR was determined to be 117.7, with 73.6% sensitivity and 53.2% specificity. The PLR was found to be significantly positively correlated with CA125 serum level, tumor-node-metastasis (TNM) stage, and tumor differentiation. Univariate analysis identified carcinoembryonic antigen (CEA), CA125 and CA199 levels, PLR, TNM stage, and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data. Multivariate analysis showed that CA125 > 35 U/mL, CA199 > 39 U/mL, PLR ? 117.7, and TNM stage IV were independently associated with poor survival in GBC. When expressed as a continuous variable, the PLR was still an independent predictor for survival, with a hazard ratio of 1.018 (95%CI: 1.001-1.037 per 10-unit increase, P = 0.043). CONCLUSION: The PLR could be used as a simple, inexpensive, and valuable tool for predicting the prognosis of GBC patients. PMID:26074706

  4. Periodic acid-Schiff-positive loops and networks as a prognostic factor in oral mucosal melanoma.

    PubMed

    Song, Hao; Jing, Guangping; Wang, Lizhen; Guo, Wei; Ren, Guoxin

    2016-04-01

    The prognostic factors of oral mucosal melanoma (OMM), a rare and aggressive neoplasm, remain to be determined. The aim of this study is to investigate the prognostic significance of vasculogenic mimicry in OMM. The clinical data of 62 patients with primary OMM treated in Shanghai Ninth People's Hospital from April 2007 to April 2012 were retrieved and analyzed retrospectively. Staining of periodic acid-Schiff (PAS) and CD31 immunohistochemistry were performed to evaluate the prognostic value of PAS-positive patterns, blood lakes, and microvascular density. PAS-positive loops and networks (P<0.001) as well as blood lakes (P=0.040) were found to be predictors of overall survival (OS). The presence of PAS-positive loops and networks was an independent prognostic factor of poor OS in multivariate analysis (P=0.002). Although the presence of PAS-positive loops and networks was associated with hematogenous metastasis (P=0.041) and lymphogenous metastasis (P=0.041), it was not an independent predictor of both types of metastasis in multivariate analysis. Microvascular density was not associated with OS (P=0.627) and metastasis of OMM patients. PAS-positive loops and networks have a significant prognostic value in OMM. Detection of PAS-positive patterns may lead to better staging and serve as a prognostic parameter of OMM. PMID:26636907

  5. Prognostic models in coronary artery disease: Cox and network approaches.

    PubMed

    Mora, Antonio; Sicari, Rosa; Cortigiani, Lauro; Carpeggiani, Clara; Picano, Eugenio; Capobianco, Enrico

    2015-02-01

    Predictive assessment of the risk of developing cardiovascular diseases is usually provided by computational approaches centred on Cox models. The complex interdependence structure underlying clinical data patterns can limit the performance of Cox analysis and complicate the interpretation of results, thus calling for complementary and integrative methods. Prognostic models are proposed for studying the risk associated with patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress echocardiography, an established technique for CAD detection and prognostication. In order to complement standard Cox models, network inference is considered a possible solution to quantify the complex relationships between heterogeneous data categories. In particular, a mutual information network is designed to explore the paths linking patient-associated variables to endpoint events, to reveal prognostic factors and to identify the best possible predictors of death. Data from a prospective, multicentre, observational study are available from a previous study, based on 4313 patients (2532 men; 6411 years) with known (n=1547) or suspected (n=2766) CAD, who underwent high-dose dipyridamole (0.84?mg?kg(-1) over 6?min) stress echocardiography with coronary flow reserve (CFR) evaluation of left anterior descending (LAD) artery by Doppler. The overall mortality was the only endpoint analysed by Cox models. The estimated connectivity between clinical variables assigns a complementary value to the proposed network approach in relation to the established Cox model, for instance revealing connectivity paths. Depending on the use of multiple metrics, the constraints of regression analysis in measuring the association strength among clinical variables can be relaxed, and identification of communities and prognostic paths can be provided. On the basis of evidence from various model comparisons, we show in this CAD study that there may be characteristic factors involved in prognostic stratification whose complexity suggests an exploration beyond the analysis provided by the still fundamental Cox approach. PMID:26064595

  6. Prognostic models in coronary artery disease: Cox and network approaches

    PubMed Central

    Mora, Antonio; Sicari, Rosa; Cortigiani, Lauro; Carpeggiani, Clara; Picano, Eugenio; Capobianco, Enrico

    2015-01-01

    Predictive assessment of the risk of developing cardiovascular diseases is usually provided by computational approaches centred on Cox models. The complex interdependence structure underlying clinical data patterns can limit the performance of Cox analysis and complicate the interpretation of results, thus calling for complementary and integrative methods. Prognostic models are proposed for studying the risk associated with patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress echocardiography, an established technique for CAD detection and prognostication. In order to complement standard Cox models, network inference is considered a possible solution to quantify the complex relationships between heterogeneous data categories. In particular, a mutual information network is designed to explore the paths linking patient-associated variables to endpoint events, to reveal prognostic factors and to identify the best possible predictors of death. Data from a prospective, multicentre, observational study are available from a previous study, based on 4313 patients (2532 men; 6411 years) with known (n=1547) or suspected (n=2766) CAD, who underwent high-dose dipyridamole (0.84?mg?kg?1 over 6?min) stress echocardiography with coronary flow reserve (CFR) evaluation of left anterior descending (LAD) artery by Doppler. The overall mortality was the only endpoint analysed by Cox models. The estimated connectivity between clinical variables assigns a complementary value to the proposed network approach in relation to the established Cox model, for instance revealing connectivity paths. Depending on the use of multiple metrics, the constraints of regression analysis in measuring the association strength among clinical variables can be relaxed, and identification of communities and prognostic paths can be provided. On the basis of evidence from various model comparisons, we show in this CAD study that there may be characteristic factors involved in prognostic stratification whose complexity suggests an exploration beyond the analysis provided by the still fundamental Cox approach. PMID:26064595

  7. Identification of Common Prognostic Gene Expression Signatures with Biological Meanings from Microarray Gene Expression Datasets

    PubMed Central

    Yao, Jun; Zhao, Qi; Yuan, Ying; Zhang, Li; Liu, Xiaoming; Yung, W. K. Alfred; Weinstein, John N.

    2012-01-01

    Numerous prognostic gene expression signatures for breast cancer were generated previously with few overlap and limited insight into the biology of the disease. Here we introduce a novel algorithm named SCoR (Survival analysis using Cox proportional hazard regression and Random resampling) to apply random resampling and clustering methods in identifying gene features correlated with time to event data. This is shown to reduce overfitting noises involved in microarray data analysis and discover functional gene sets linked to patient survival. SCoR independently identified a common poor prognostic signature composed of cell proliferation genes from six out of eight breast cancer datasets. Furthermore, a sequential SCoR analysis on highly proliferative breast cancers repeatedly identified T/B cell markers as favorable prognosis factors. In glioblastoma, SCoR identified a common good prognostic signature of chromosome 10 genes from two gene expression datasets (TCGA and REMBRANDT), recapitulating the fact that loss of one copy of chromosome 10 (which harbors the tumor suppressor PTEN) is linked to poor survival in glioblastoma patients. SCoR also identified prognostic genes on sex chromosomes in lung adenocarcinomas, suggesting patient gender might be used to predict outcome in this disease. These results demonstrate the power of SCoR to identify common and biologically meaningful prognostic gene expression signatures. PMID:23029298

  8. Correlation of HMGB1 expression to progression and poor prognosis of adenocarcinoma and squamous cell/adenosquamous carcinoma of gallbladder

    PubMed Central

    Shi, Zilu; Huang, Qian; Chen, Jian; Yu, Pengcheng; Wang, Xiaosong; Qiu, Hong; Chen, Yijie; Dong, Yangyang

    2015-01-01

    HMGB1 (High mobility group box 1) expressions in adenocarcinoma (AC) and squamous cell/adenosquamous (SC/ASC) carcinoma of gallbladder, as well as its prognostic significance, have not yet been evaluated. We investigated HMGB1 expression in 80 cases of AC gallbladder cancer and 52 cases of SC/ASC gallbladder cancer. Survival information was concomitantly collected. The association of HMGB1 expression with clinicopathological characteristics and the possible prognostic role of HMGB1 for two aforementioned subtypes of gallbladder cancers were also analyzed. siRNA technique was utilized to explore the role of HMGB1 in proliferation and invasion of gallbladder cancer cells in vitro. HMGB1 overexpression is present in AC and SC/ASC gallbladder cancers. HMGB1 expression significantly associates with growth and metastasis of AC and SC/ASC gallbladder cancers. In vitro cell experiments based on siRNA demonstrated that HMGB1 downregulation inhibits proliferation and invasion of gallbladder cancer cells. Kaplan-Meier analysis revealed that HMGB1 expression is negatively associated with overall survival time of patients with AC or SC/ASC gallbladder cancer. Cox multivariate analysis confirmed that HMGB1 is an independent risk factor for survival of patients with AC or SC/ASC gallbladder cancer. HMGB1 overexpression closely correlates with progression and poor prognosis of AC and SC/ASC gallbladder cancers. PMID:26692945

  9. Prognostic role of pneumonia in supracricoid and supraglottic laryngectomies.

    PubMed

    Gallo, O; Deganello, A; Gitti, G; Santoro, R; Senesi, M; Scala, J; Boddi, V; De Campora, E

    2009-01-01

    The goal of this study was to identify host and tumour factors associated with postoperative pneumonia (PP) in a selected population of laryngeal cancer patients, treated by partial laryngectomy in 20 years at our Institution and to assess its potential prognostic impact. Clinical records of 416 consecutive patients were retrospectively reviewed. Tobacco consumption, body mass index (BMI), previous pulmonary disease, age, sex, preoperative blood gas analysis values, tumour stage and type of surgery were tested as potential risk factors for PP. Finally, the prognostic impact of these variables, including PP, in terms of disease-free and actuarial survival by Kaplan-Meier and Cox analyses were evaluated. PP developed in 73 patients (16.8%). We identified two groups of patients: 26 patients experienced an early PP within the first 7-9 days after surgery, whilst 44 experienced an ab ingestis PP following attempts of oral food intake restoration, three patients died for PP related sepsis. At multivariate Cox analysis, age older than 60 years and BMI greater than 30 were statistically associated with early PP; whereas male gender and laryngectomy with neck dissection were statistically related to a higher risk of ab ingestis PP. Interestingly, the occurrence of early PP was a negative independent prognostic factor for 5-years disease-free and actuarial survival (p=0.049 and p=0.001, respectively). The occurrence of early-onset pneumonia in laryngeal cancer patients selected for conservative laryngectomies is predictable and associated with poor clinical outcome. PMID:18620892

  10. 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 survival of patients with BMs to a more or less satisfactory degree. Among the 5 PIs evaluated in the present study, GPA was the most powerful in predicting survival. Additional studies should include emerging biologic prognostic factors to improve the sensibility of these PIs.

  11. Gastric cancer risk predisposition and prognostic significance of vascular endothelial growth factor (VEGF) gene polymorphisms--a case-control study in an Omani population.

    PubMed

    Al-Moundhri, Mansour S; Al-Nabhani, Maryam; Burney, Ikram A; Al-Farsi, Abdul-Aziz; Al-Bahrani, Bassim

    2009-12-01

    Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis, tumor growth, and metastasis. We investigated the associations between VEGF gene polymorphisms and gastric cancer (GC) risk predisposition and prognostic characteristics in an Omani population, an ethnic group which has not been studied previously. We analyzed three VEGF polymorphisms (+405 G/C, -460 T/C, and +936 C/T) by the extraction of genomic DNA from peripheral blood of 130 GC patients and 130 control subjects followed by VEGF genotyping using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. There were no significant associations between the VEGF polymorphisms and GC risk. There were significant correlations between the +405 C/C genotype and both poor tumor differentiation (P = 0.007) and lymph node metastasis (P = 0.03) and between the -460 T/T genotype and poor tumor differentiation (P = 0.03) with a statistical trend toward lymph node involvement (P = 0.05). VEGF gene polymorphisms had no significant effects on survival, but the VEGF +405 G/G genotype had a statistical trend toward lower survival rate with a hazard ratio of 1.6 [95% CI, 0.9-2.9] compared with the VEGF +405 CC/GC combined genotype (P = 0.049). Multivariate analysis showed that disease stage at diagnosis and the +405 G/G genotype were independent variables of adverse prognostic significance. There were no associations between the six common haplotypes identified and both GC risk predisposition and survival. The current study suggests that VEGF polymorphisms have no role in GC risk predisposition, but may have prognostic significance in GC patients. PMID:19676106

  12. Immunologic functions as prognostic indicators in melanoma.

    PubMed

    Bouwhuis, Marna G; ten Hagen, Timo L M; Eggermont, Alexander M M

    2011-04-01

    Outcome in melanoma patients with advanced disease is poor and systemic treatment seems to benefit only a subset of patients. Predictive markers identifying these patients are currently not available. Early studies showed an association of immune-related side effects such as vitiligo and autoimmune thyroiditis with response to IL-2 or IFNα treatment. However, conflicting data have been reported as well, mentioning the effect of a higher rate of immune-related toxicities during prolonged administration of the drug in responders. The review discusses the prognostic significance of autoimmunity during various forms of immunotherapy and stresses the importance of correcting for guarantee-time bias. In addition, other immune-related factors which have been associated with melanoma prognosis such as, CRP, white blood cell count, absolute lymphocyte count and human leukocyte antigen will be reviewed as well. A better understanding of the immune system and the host-tumor interactions should ultimately lead to more effective treatment. A major challenge expected to be addressed in future is proving ways to uncouple tumor immunity from autoimmunity. PMID:21367679

  13. 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. PMID:26476674

  14. 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.

  15. Clinical examination for prognostication in comatose cardiac arrest patients☆

    PubMed Central

    Greer, David M.; Yang, Jingyun; Scripko, Patricia D.; Sims, John R.; Cash, Sydney; Wu, Ona; Hafler, Jason P.; Schoenfeld, David A.; Furie, Karen L.

    2014-01-01

    Objective To build new algorithms for prognostication of comatose cardiac arrest patients using clinical examination, and investigate whether therapeutic hypothermia influences the value of the clinical examination. Methods From 2000 to 2007, 500 consecutive patients in non-traumatic coma were prospectively enrolled, 200 of whom were post-cardiac arrest. Outcome was determined by modified Rankin Scale (mRS) score at 6 months, with mRS ≤ 3 indicating good outcome. The clinical examination was performed on days 0, 1, 3 and 7 post-arrest, and clinical variables analyzed for importance in prognostication of outcome. A classification and regression tree analysis (CART) was used to develop a predictive algorithm. Results Good outcome was achieved in 9.9% of patients. In CART analysis, motor response was often chosen as a root node, and spontaneous eye movements, pupillary reflexes, eye opening and corneal reflexes were often chosen as splitting nodes. Over 8% of patients with absent or extensor motor response on day 3 achieved a good outcome, as did 2 patients with myoclonic status epilepticus. The odds of achieving a good outcome were lower in patients who suffered asystole (OR 0.187, 95% CI: 0.039–0.875, p = 0.033) compared with ventricular fibrillation or non-perfusing ventricular tachycardia, but some still achieved good outcome. The absence of pupillary and corneal reflexes on day 3 remained highly reliable for predicting poor outcome, regardless of therapeutic hypothermia utilization. Conclusion The clinical examination remains central to prognostication in comatose cardiac arrest patients in the modern area. Future studies should incorporate the clinical examination along with modern technology for accurate prognostication. PMID:23954666

  16. 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

  17. Prognostic Value of VEGF in Hepatocellular Carcinoma Patients Treated with Sorafenib: A Meta-Analysis

    PubMed Central

    Cao, Guangchao; Li, Xiaoyun; Qin, Chao; Li, Jie

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is characterized by rich vascularization in the tumor, and vascular endothelial growth factor (VEGF) plays important roles in vascularization. The results of the roles of VEGF in predicting efficacy of sorafenib in HCC are conflicting. In this meta-analysis, we aimed to investigate the prognostic and predictive value of VEGF in HCC patients receiving sorafenib. Material/Methods PubMed, Embase, and Cochrane library electronic databases were systematically searched for eligible studies. The baseline characteristics were recorded and overall qualities of the eligible studies were assessed by 2 reviewers independently. VEGF levels and data relevant to efficacy of sorafenib were extracted and used for meta-analysis. Results The comprehensive search yielded 9 studies that evaluated the relationship between VEGF level and clinical outcome in advanced HCC patients treated with sorafenib. Pooled estimates suggested that high level of VEGF was associated with poor overall survival (HR=1.85; 95% CI: 1.242.77; P=0.003) and poor progression-free survival (HR=2.09; 95% CI: 1.433.05; P<0.01) in HCC. Mutation of VEGF had a favorable effect on hand-foot skin reaction in HCC patients treated with sorafenib (P<0.05). Conclusions High level of VEGF is associated with poor outcomes in HCC patients treated with sorafenib, indicating that VEGF could be used as an indicator of clinical efficacy in patients with HCC. However, more well-designed studies are needed to strengthen our findings. PMID:26476711

  18. Diagnostic and Prognostic Value of Serum Interleukin-6 in Colorectal Cancer

    PubMed Central

    Xu, Jinming; Ye, Yao; Zhang, Honghe; Szmitkowski, Maciej; Mäkinen, MJ; Li, Peiwei; Xia, Dajing; Yang, Jun; Wu, Yihua; Wu, Han

    2016-01-01

    Abstract The application of serum interleukin-6 (IL-6) in the diagnosis and prognosis of colorectal cancer (CRC) has been evaluated in many studies, whereas the results were contradictive. The aim of this study was to systematically evaluate this issue. An original study was conducted to explore the diagnostic value of serum IL-6 in CRC. Pubmed, Embase, and Cochrane library databases were searched for eligible studies. For diagnostic meta-analysis, aggregate data (AD) and individual participant data (IPD) meta-analyses were both adopted. The sensitivity and specificity were pooled and a summary receiver-operating characteristic (ROC) curve was constructed. For prognostic meta-analysis, study-specific hazard ratios (HRs) of IL-6 for survival were summarized. Secondary analysis of survival data was performed to synthesize the Kaplan–Meier curves. Total 17 studies (including our study) were included in this meta-analysis. The pooled sensitivity, specificity, and area under curve (AUC) of serum IL-6 were 0.72 (95% CI: 0.46–0.88), 0.74 (95% CI: 0.56–0.86), and 0.79 (95% CI: 0.75–0.82) in CRC diagnosis, respectively. Further, IPD meta-analysis strengthened the diagnostic value of serum IL-6 (the AUC, sensitivity, and specificity were 0.794, 0.606, and 0.839, respectively). For prognostic analysis, the high serum level of IL-6 was inversely associated with overall survival (OS) (pooled HR = 1.76, 95% CI: 1.42–2.19, P < 0.001) and disease-free survival (DFS) (pooled HR = 2.97, 95% CI: 1.76–5.01, P < 0.001). The synthesized Kaplan–Meier curves indicated that CRC patients with higher serum IL-6 level had a worse OS (P = 0.0027) and DFS (P < 0.001), which further support the prognostic value of serum IL-6 in CRC patients. The present study confirmed that serum IL-6 may be a potential biomarker for CRC diagnosis, and the high serum IL-6 level was associated with poor prognosis for both CRC overall survival and disease-free survival. The study has been registered in an international registry of systematic reviews PROSPERO (CRD42013006485). PMID:26765465

  19. 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.

  20. 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

    Abstract Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking. To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled 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

  1. Prognostic significance of INF-induced transmembrane protein 1 in colorectal cancer

    PubMed Central

    He, Jingdong; Li, Jin; Feng, Wanting; Chen, Longbang; Yang, Kangqun

    2015-01-01

    Interferon-induced transmembrane protein 1 (IFITM1) has recently been implicated in tumorigenesis. However, the prognostic value of IFITM1 in colorectal cancer remains unknown. The present study aimed to examine the expression and prognostic significance of IFITM1 in human colorectal cancer. IFITM1 expression was analyzed in 144 archived, paraffin-embedded colorectal cancer tissues and corresponding normal colorectal mucosa by immunohistochemistry. The correlation of IFITM1 with clinic-pathological features and overall survival of colorectal cancer patients was evaluated. IFITM1 was overexpressed in colonic cancer tissues but not in rectal cancer tissues, compared to control normal tissues. The expression of IFITM1 was significantly higher in patients with poor differentiation (P=0.031). The patients with higher IFITM1 expression had worse overall survival outcomes than those with lower IFITM1 expression in rectal cancer (P=0.037). Univariate Cox regression suggested that older age and poorly differentiation status predict shorter overall survival in colorectal cancer (P<0.05). However, IFITM1 expression was not a significant prognostic factor for survival by univariate or multivariate analyses. In conclusion, high expression of IFITM1 is associated with poor prognosis of rectal cancer. IFITM1 may serve as an independent prognostic biomarker for colorectal cancer.

  2. Low SIRT3 Expression Correlates with Poor Differentiation and Unfavorable Prognosis in Primary Hepatocellular Carcinoma

    PubMed Central

    Zhang, Chris Zhiyi; Liu, Lili; Cai, Muyan; Pan, Yinghua; Fu, Jia; Cao, Yun; Yun, Jingping

    2012-01-01

    SIRT3, a mitochondrial sirtuin belonging to nicotinamide adenine nucleotide (NAD) dependent deacetylases, is implicated in metabolism, longevity and carcinogenesis. SIRT3 expression and its significance in hepatocellular carcinoma (HCC) remain largely unclear. In this study, we demonstrated that SIRT3 expression in HCC tissue was much lower than that in paracarcinoma tissue, at both mRNA and protein levels. The cutoff value for low SIRT3 expression in HCC was defined according to receiver operating characteristic curve (ROC) analysis. As disclosed by immunohistochemistry (IHC) results, low SIRT3 expression was present in 67.3% (167/248) of HCC cases. Furthermore, low expression of SIRT3 was significantly correlated to differentiation (P = 0.013), clinical stage (P = 0.005), serum AFP level (P<0.01), tumor multiplicity (P = 0.026) and relapse (P = 0.028). Moreover, Kaplan-Meier analysis indicated that low SIRT3 expression associated with unfavorable overall survival (P<0.01) and recurrence-free survival (P = 0.004). The prognostic impact of SIRT3 was further confirmed by stratified survival analysis. Importantly, multivariate analysis revealed that low SIRT3 expression was an independent poor prognostic marker for overall survival (Hazard Ratio (HR) 0.555, 95% confidence interval (95% CI) 0.344–0.897, P = 0.016). Collectively, we conclude that SIRT3 is decreased in HCC and is a novel unfavorable marker for prognosis of patients with this fatal disease. PMID:23272146

  3. 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…

  4. 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

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

    PubMed Central

    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

    2016-01-01

    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. PMID:26893871

  6. Prognostic factors for stereopsis in refractive accommodative esotropia

    PubMed Central

    Guclu, Hande; Gurlu, Vuslat Pelitli; Ozal, Sadik Altan; Ozkurt, Zeynep Gursel

    2015-01-01

    Objective: To determine the prognostic factors affecting stereoacuity in patients with refractive accommodative esotropia (RAE) according to the results of long follow- up period. Methods: We reviewed the charts of 70 patients with RAE between the years 1985-2014. Patients were classified into three groups. G-1: Stereoacuity score 40 second/arc. G-2: Stereoacuity score >40 second/arc (50-3000). G-3: No binocular vision. Initiation age of RAE, duration of deviation, refractive error, amblyopia, amblyopia treatment, anisometropia, visual acuity, family history, angle of deviation for distance and near at each group and the prognostic factors affecting stereoacuity were analyzed. Results: The mean initiation age of RAE was 2.71.5 years, the mean age at first visit was 6.44.2 years. The mean follow up time was 7.34.4 years. Seven patients had 40 second/arc, 48 patients had 50 to 3000 second/arc stereoacuity, 15 patients had no binocular vision. Mean deviation for near was statistically higher in group 2 and 3. Visual acuity levels were higher in group 1 and 2 and was statistically significant. Low visual acuity (p=0.001, 0.008), higher angle of deviation at near (p=0.01), increased duration of deviation (p=0.01), presence of amblyopia (p=0.001) and irregularity of amblyopia treatment (p=0.01) were significantly related with poor stereoacuity. Conclusion: According to the prognostic factors low stereoacuity was mostly related with amblyopia as a result the late presentation of the patients in seeking care. Appropriate treatment as full refractive correction and amblyopia treatment during the RAE is important for development of good stereopsis. Also angle of deviation at near and duration of deviation can be a useful predictor for poor stereoacuity levels. PMID:26430408

  7. Aberrant DNA methylation characterizes juvenile myelomonocytic leukemia with poor outcome.

    PubMed

    Olk-Batz, Christiane; Poetsch, Anna R; Nöllke, Peter; Claus, Rainer; Zucknick, Manuela; Sandrock, Inga; Witte, Tania; Strahm, Brigitte; Hasle, Henrik; Zecca, Marco; Stary, Jan; Bergstraesser, Eva; De Moerloose, Barbara; Trebo, Monika; van den Heuvel-Eibrink, Marry M; Wojcik, Dorota; Locatelli, Franco; Plass, Christoph; Niemeyer, Charlotte M; Flotho, Christian

    2011-05-01

    Aberrant DNA methylation contributes to the malignant phenotype in virtually all types of cancer, including myeloid leukemia. We hypothesized that CpG island hypermethylation also occurs in juvenile myelomonocytic leukemia (JMML) and investigated whether it is associated with clinical, hematologic, or prognostic features. Based on quantitative measurements of DNA methylation in 127 JMML cases using mass spectrometry (MassARRAY), we identified 4 gene CpG islands with frequent hypermethylation: BMP4 (36% of patients), CALCA (54%), CDKN2B (22%), and RARB (13%). Hypermethylation was significantly associated with poor prognosis: when the methylation data were transformed into prognostic scores using a LASSO Cox regression model, the 5-year overall survival was 0.41 for patients in the top tertile of scores versus 0.72 in the lowest score tertile (P = .002). Among patients given allogeneic hematopoietic stem cell transplantation, the 5-year cumulative incidence of relapse was 0.52 in the highest versus 0.10 in the lowest score tertile (P = .007). In multivariate models, DNA methylation retained prognostic value independently of other clinical risk factors. Longitudinal analyses indicated that some cases acquired a more extensively methylated phenotype at relapse. In conclusion, our data suggest that a high-methylation phenotype characterizes an aggressive biologic variant of JMML and is an important molecular predictor of outcome. PMID:21406719

  8. Prognostic factors in hanging injuries.

    PubMed

    Matsuyama, Takeshi; Okuchi, Kazuo; Seki, Tadahiko; Murao, Yoshinori

    2004-05-01

    The objectives of this study were to review variable factors influencing outcomes in hanging and to identify prognostic factors related to outcomes. Forty-seven patients presented to our department. Eleven patients survived and 36 died. A significant difference in mean hanging time was observed between survivor (11.8 +/- 8.37 minutes) and nonsurvivor (50.81 +/- 61.9). In survivors, heartbeat was recognized in 63.6% at the scene and in 90.9% on arrival. Conversely, cardiopulmonary arrest (CPA) was recognized in all nonsurvivors and heartbeat was recognized on arrival in only 5.6%. Thirty-nine (83%) had a Glasgow Coma Score (GCS) of 3 on arrival. Three (7.7%) of theses 39 patients survived. In survivors, eight patients had a GCS greater than 3. A significant difference in outcome existed between patients with a GCS of 3 and those with a GCS greater than 3. Hanging time, presence of CPA at the scene and on arrival, and GCS on arrival represented prognostic factors of outcome in hanging. PMID:15138959

  9. Prognostic markers for urologic cancers.

    PubMed

    Raman, Jay D

    2016-02-01

    Improved prediction of disease related oncologic outcomes is essential for improved patient counseling prior to surgery. The concept of chronic inflammatory states and association with cancer recurrence and survival is a growing area of interest. Indeed a number of studies highlight the potential prognostic benefit across different malignancies. Nonetheless, the impact of neutrophil:lymphocyte ratio (NLR) is variable and certainly not uniform. As highlighted by Bazzi et al (as well as others), NLR had no significant prognostic benefit for recurrence-free and cancer-specific survival for clear cell renal cell carcinoma (ccRCC).1 One wonders if some of these observations are a function of a heterogenous cohort of ccRCC cases ranging from T1a toT4 tumors of various Fuhrman grades. Indeed, a focus on more biologically aggressive ccRCC at higher risk of recurrence and mortality may demonstrate a greater degree of association. Furthermore, whilst these authors noted an association of NLR with overall survival, there was no incremental benefit over a base model constructed from clinical measures of frailty. These observations highlight that accurate pre-surgical notation of baseline clinical morbidities may be invaluable when assessing overall prognosis for urologic oncology patients. In that regard, more refined scales such as ECOG performance status, Charlson-Romano index, or an amalgam to create a Frailty Index Score may be superior to the ASA score alone. PMID:26892056

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. Clinical characteristics of hepatoduodenal lymph node metastasis in gastric cancer

    PubMed Central

    Imamura, Taisuke; Komatsu, Shuhei; Ichikawa, Daisuke; Kosuga, Toshiyuki; Okamoto, Kazuma; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Otsuji, Eigo

    2015-01-01

    AIM: To assess the clinical features of hepatoduodenal lymph node (HDLN) metastasis and to clarify the optimal indication of HDLN dissection. METHODS: We investigated a total of 276 patients who underwent gastrectomy with extended lymphadenectomy, including HDLN dissection, for gastric cancer between 1999 and 2012. Of these, 26 patients (9.4%) had HDLN metastasis. First, we investigated the clinicopathological characteristics, their perioperative clinical outcomes, such as postoperative complications, and prognostic outcomes between patients with and without HDLN metastasis. Second, we detected the prognostic factors, particularly in patients with HDLN metastasis. Third, we assessed the therapeutic value of HDLN dissection to determine its optimal indication. RESULTS: The five-year overall survival rate of the patients with HDLN metastasis was 29%. Univariate and multivariate logistic regression analyses revealed that the tumour location (the middle or lower stomach [P = 0.005, OR = 5.88 (95%CI: 1.61-38.1)] and pT category [T3 or T4, P = 0.017, OR = 4.45 (95%CI: 1.28-21.3)] were independent risk factors for HDLN metastasis. Cox proportional hazard analysis identified pN3 as an independent poor prognostic factor in the patients with HDLN metastasis [P = 0.021, HR = 5.17 (95%CI: 1.8-292)]. For patients who underwent radical HDLN dissection, HDLN metastasis was a prognostic indicator in pN3 gastric cancer (P < 0.0001), but not pN1-2 (P = 0.602). Furthermore, the index of therapeutic value of HDLN dissection for gastric cancer in the middle or lower stomach and the upper stomach was 3.4 and 0.0, respectively. CONCLUSION: We suggest that HDLN dissection should be indicated for pN1 or pN2 gastric cancers located at the middle or lower stomach. PMID:26478677

  15. 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], 0.632.2; p?=?0.60; IC: HR, 0.84; 95% CI, 0.098.1; 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 before the standard procedure was established. Future studies with a standardised patient protocol and improved technique for isolating and detecting DTCs may reveal the clinical applications of DTC detection in patients with micrometastases in the bone marrow. PMID:22963449

  16. Ischemic stroke in children with critical illness: a poor prognostic sign

    PubMed Central

    van Beek, Jackelien G. M.; Gottesman, Rebecca F.; Kossoff, Eric H.; Johnston, Michael V.

    2007-01-01

    A consecutive case series of 55 children (0-17 years old) with arterial ischemic stroke is reported. Twenty of these children were critically ill at the time their stroke occurred. Mortality among these 20 children was 40%, as compared to 3% in non-critically ill children with arterial ischemic stroke; overall mortality in this case series was 16%. Mortality resulted primarily from the underlying illness. Prognosis after stroke is markedly worsened in children with premorbid critical illness. PMID:17437907

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

    PubMed Central

    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. PMID:26884866

  18. Stem cell-associated genes are extremely poor prognostic factors for soft-tissue sarcoma patients.

    PubMed

    Taubert, H; Wrl, P; Greither, T; Kappler, M; Bache, M; Bartel, F; Kehlen, A; Lautenschlger, C; Harris, L C; Kaushal, D; Fssel, S; Meye, A; Bhnke, A; Schmidt, H; Holzhausen, H-J; Hauptmann, S

    2007-11-01

    Cancer stem cells can play an important role in tumorigenesis and tumor progression. However, it is still difficult to detect and isolate cancer stem cells. An alternative approach is to analyse stem cell-associated gene expression. We investigated the coexpression of three stem cell-associated genes, Hiwi, hTERT and survivin, by quantitative real-time-PCR in 104 primary soft-tissue sarcomas (STS). Multivariate Cox's proportional hazards regression analyses allowed correlating gene expression with overall survival for STS patients. Coexpression of all three stem cell-associated genes resulted in a significantly increased risk of tumor-related death. Importantly, tumors of patients with the poorest prognosis were of all four tumor stages, suggesting that their risk is based upon coexpression of stem cell-associated genes rather than on tumor stage. PMID:17525744

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

    PubMed Central

    2010-01-01

    Background Bacterial meningitis (BM) is a severe infection responsible for high mortality and disabling sequelae. Early identification of patients at high risk of these outcomes is necessary to prevent their occurrence by adequate treatment as much as possible. For this reason, several prognostic models have been developed. The objective of this study is to summarize the evidence regarding prognostic factors predicting death or sequelae due to BM in children 0-18 years of age. Methods A search in MEDLINE and EMBASE was conducted to identify prognostic studies on risk factors for mortality and sequelae after BM in children. Selection of abstracts, full-text articles and assessment of methodological quality using the QUIPS checklist was performed by two reviewers independently. Data on prognostic factors per outcome were summarized. Results Of the 31 studies identified, 15 were of moderate to high quality. Due to substantial heterogeneity in study characteristics and evaluated prognostic factors, no quantitative analysis was performed. Prognostic factors found to be statistically significant in more than one study of moderate or high quality are: complaints >48 hours before admission, coma/impaired consciousness, (prolonged duration of) seizures, (prolonged) fever, shock, peripheral circulatory failure, respiratory distress, absence of petechiae, causative pathogen Streptococcus pneumoniae, young age, male gender, several cerebrospinal fluid (CSF) parameters and white blood cell (WBC) count. Conclusions Although several important prognostic factors for the prediction of mortality or sequelae after BM were identified, the inability to perform a pooled analysis makes the exact (independent) predictive value of these factors uncertain. This emphasizes the need for additional well-conducted prognostic studies. PMID:20684796

  20. 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

  1. Expression and Prognostic Significance of Macrophage Inflammatory Protein-3 Alpha and Cystatin A in Nasopharyngeal Carcinoma

    PubMed Central

    Tang, Minzhong; Ou, Ningjiang; Li, Cheng; Lu, Aiying; Li, Jun; Ma, Liping; Zhong, Weiming; Gao, Jianquan; Zheng, Yuming; Cai, Yonglin

    2015-01-01

    This study aims to investigate the expression of macrophage inflammatory protein-3 alpha (MIP-3?) and cystatin A in nasopharyngeal carcinoma (NPC) and their association with clinical characteristics and prognosis. Primary tumor specimens from 114 NPC patients and associated clinical follow-up data were collected, and the expression of MIP-3? and cystatin A proteins was investigated by immunohistochemistry. Expression of MIP-3? was significantly associated with TNM stage in patients with NPC (P < 0.05). NPC patients with positive expression of MIP-3? exhibited shorter median overall survival (OS) and distant metastasis-free survival (DMFS), compared with patients with negative expression (OS: 50.5 months versus 59.0 months, P = 0.013; DMFS: 50.1 months versus 60.2 months, P = 0.003). NPC patients with positive expression of cystatin A exhibited shorter median OS, local recurrence-free survival (LRFS), and DMFS, compared with patients with negative expression (OS: 51.1 months versus 60.0 months, P = 0.004; LRFS: 54.5 months versus 59.5 months, P = 0.036; DMFS: 52.3 months versus 58.8 months, P = 0.036). Both MIP-3? and cystatin A overexpressions in NPC tumor tissues were strong independent factors of poor prognosis in NPC patients. MIP-3? and cystatin A expressions may be valuable prognostic markers in NPC patients. PMID:26634210

  2. Prognostic impact of p16 and p21 on gastroenteropancreatic neuroendocrine tumors

    PubMed Central

    LIU, SHUZHENG; CHANG, YUXI; MA, JIE; LI, XU; LI, XIAOHONG; FAN, JINHU; HUANG, RONG; DUAN, GUANGCAI; SUN, XIBIN

    2013-01-01

    Aberrant expression of the cell cycle kinase inhibitors, p16 and p21, has been associated with poor prognosis in a number of human malignancies. These proteins may also be involved in the development and progression of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The present study aimed to investigate protein levels of p16 and p21 in GEP-NETs and to evaluate their clinical significance. p16 and p21 protein expression was tested immunohistochemically in the tissue samples of 68 GEP-NETs. The association between expression and clinicopathological characteristics and overall survival was assessed. Low expression of p16 (no positive nuclear staining) was found in 37 (54%) cases and high p21 expression (?5% positive nuclear staining) was detected in 23 (34%) cases. Low p16 protein levels indicated a poorer prognosis for patients graded as G2 subgroup in the univariate analysis (relative risk, 4.4; 95% CI, 1.810.6). No significant correlation was found between the expression of p21 and any of the clinicopathological variables. The present study indicates a prognostic relevance for p16 immunoreactivity. Low levels of p16 protein were associated with a shorter survival in the G2 subgroup of GEP-NETs. p21 protein expression was not identified to be useful as a predictive indicator in GEP-NETs. PMID:24260058

  3. Prognostic Factors for Metastatic Colorectal Cancer Patients Undergoing Irinotecan-Based Second-Line Chemotherapy

    PubMed Central

    Shitara, Kohei; Matsuo, Keitaro; Yokota, Tomoya; Takahari, Daisuke; Shibata, Takashi; Ura, Takashi; Inaba, Yoshitaka; Yamaura, Hidekazu; Sato, Yozo; Najima, Mina; Muro, Kei

    2011-01-01

    ABSTRACT Background: No reports about factors that predict prognosis after second-line chemotherapy for metastatic colorectal cancer have been published. Methods: We retrospectively analyzed 124 patients with metastatic colorectal cancer who received irinotecan-based second-line chemotherapy after first-line folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX) with or without bevacizumab. Results: A multivariate Cox model revealed 5 prognostic factors for worse survival: ECOG performance status 2, pathologically poorly differentiated adenocarcinoma, peritoneal metastasis, progression-free survival of first-line FOLFOX < 6 months, and lactate dehydrogenase ≥ 400 IU/L. When patients were categorized into 3 risk groups—patients without any prognostic factors (low-risk, n = 55), patients with one prognostic factor (intermediate-risk, n = 32), and patients with 2 or more prognostic factors (high-risk, n = 37)—overall survival from initiation of second-line chemotherapy was 23.5, 14.6, and 5.5 months, respectively. The proportion of patients who were eligible to receive further chemotherapy after disease progression was significantly lower in the high-risk group (41%) than in the intermediate- (67%) and low-risk (95%) groups. Conclusion: Several prognostic factors for survival after second-line therapy and probability of receiving third-line chemotherapy were identified. This risk classification system might be useful for determining which patients should receive cetuximab in the second-line setting rather than the third-line setting. PMID:22295128

  4. Prognostic model for mantle cell lymphoma in the rituximab era: a nationwide study in Japan.

    PubMed

    Chihara, Dai; Asano, Naoko; Ohmachi, Ken; Kinoshita, Tomohiro; Okamoto, Masataka; Maeda, Yoshinobu; Mizuno, Ishikazu; Matsue, Kosei; Uchida, Toshiki; Nagai, Hirokazu; Nishikori, Momoko; Nakamura, Shigeo; Ogura, Michinori; Suzuki, Ritsuro

    2015-09-01

    Mantle cell lymphoma (MCL) is essentially incurable with conventional chemotherapy. The MCL International Prognostic Index (MIPI) is a validated specific prognostic index, but was derived from patients with advanced-stage disease primarily in the pre-rituximab era. We analysed 501 MCL patients (median age, 67 years; range 22-90) treated with rituximab-containing chemotherapy, and evaluated the prognostic factors adjusted by the treatment. Five-year overall survival (OS) in the low, intermediate and high MIPI groups was 74%, 70% and 35%, respectively. Additional to MIPI risk factors, multivariate analysis revealed that low serum albumin and bone-marrow involvement were also significantly associated with a poor outcome. The revised-MIPI (R-MIPI) was constructed using six factors, namely age, performance status, white blood cell count, serum lactate dehydrogenase, bone-marrow involvement and serum albumin, which is divided into four prognostic groups. Five-year OS in low, low-intermediate (L-I), high-intermediate (H-I) and high R-MIPI groups was 92%, 75%, 61% and 19%, respectively. Hazard ratio for OS of L-I, H-I and high risk to low risk patients were 5·4, 8·3 and 33·0, respectively. R-MIPI, a new prognostic index with easy application to the general patient population, shows promise for identifying low- and high-risk MCL patients in the rituximab era. PMID:25953436

  5. 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.

  6. Assessment of promoter methylation and expression of SIX2 as a diagnostic and prognostic biomarker in Wilms' tumor.

    PubMed

    Song, Dongjian; Yue, Lifang; Wu, Gang; Ma, Shanshan; Guo, Lihua; Yang, Heying; Liu, Qiuliang; Zhang, Da; Xia, Ziqiang; Wang, Lei; Zhang, Junjie; Zhao, Wei; Guo, Fei; Wang, Jiaxiang

    2015-09-01

    This study was designed to evaluate the utility of expression and DNA methylation patterns of the sine oculis homeobox homolog 2 (SIX2) gene in early diagnosis and prognosis of Wilms' tumor (WT). Methylation-specific polymerase chain reaction (MSP), real-time quantitative polymerase chain reaction (qRT-PCR), receiver operating characteristic (ROC), and survival curve analyses were utilized to measure the expression and DNA methylation patterns of SIX2 in a cohort of WT tissues, with a view to assessing their diagnostic and prognostic value. Relative expression of SIX2 mRNA was higher, while the promoter methylation level was lower in the WT than control group (P?poor survival prognosis of WT children (P?poor survival of WT children. PMID:25921281

  7. Monocarboxylate Transporters 14 in NSCLC: MCT1 Is an Independent Prognostic Marker for Survival

    PubMed Central

    Eilertsen, Marte; Andersen, Sigve; Al-Saad, Samer; Kiselev, Yury; Donnem, Tom; Stenvold, Helge; Pettersen, Ingvild; Al-Shibli, Khalid; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy M.

    2014-01-01

    Introduction Monocarboxylate transporters (MCTs) 14 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC. Methods Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage IIIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4. Results In univariate analyses; ?MCT1 (P?=?0.021) and ?MCT4 (P?=?0.027) expression in cancer cells, and ?MCT1 (P?=?0.003), ?MCT2 (P?=?0.006), ?MCT3 (P?=?0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ?MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.32.8, P?=?0.001), ?MCT2 (HR: 2.4, CI 95%: 1.53.9, P<0.001), ?MCT3 (HR: 1.9, CI 95%: 1.13.5, P?=?0.031) and ?MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.12.7, P?=?0.016) were significant independent poor prognostic markers for DSS. Conclusions We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments. PMID:25225794

  8. 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

  9. The Economic Determinants of Labor Supply for the Urban Poor.

    ERIC Educational Resources Information Center

    Hill, Charles Russell

    The study is concerned with empirically deriving a labor supply function for members of poor families. It contains a definition of poverty as well as a brief summary of the characteristics of families in poverty in 1966 and a review of the existing literature on the supply of labor by the poor. A general model of labor supply based on family…

  10. Prognostic value of legumain in uveal melanoma

    PubMed Central

    WU, TONG; SUN, LEI; WU, YING; XIANG, RONG; LI, YUWEI; RONG, WEINING; SUN, FENGYUAN; WANG, NINGLI

    2016-01-01

    The present study aimed to assess the expression of legumain in uveal melanoma (UM) cell lines and primary UM specimens, and to determine the possible association between legumain expression and clinical as well as pathological characteristics to reveal its impact on the prognosis of patients with UM. Records of primary UM cases treated at Beijing Tongren Hospital and Tianjin Eye Hospital between 1996 and 2005 were retrieved for analysis and a total of 82 patients with uveal melanoma were included in the study. The expression of legumain in the formalin-fixed and paraffin-embedded surgical specimens of these 82 patients was determined using immunohistochemical analysis. In addition, the expression of legumain was examined in two uveal melanoma cell lines using polymerase chain reaction and western blot analyses. The association of legumain expression with clinical/pathological characteristics was analyzed using the χ2 and Fisher's exact test. In addition, the impact of legumain on the prognosis of patients with uveal melanoma was examined. Upregulation of legumain was more predominant in the highly invasive uveal melanoma cell line MUM-2B compared with that in the MUM-2C with low invasiveness. Of 82 primary uveal melanoma tissues, 35 exhibited high expression of legumain, while the other 47 specimens exhibited low or negative expression of legumain. High legumain expression was primarily associated with local invasion of UM. Overall survival analysis revealed that the patients with high legumain expression exhibited poorer survival than patients with low/negative legumain expression. These findings suggested that upregulation of legumain is associated with malignant behavior of UM and that legumain may be used as an negative prognostic factor as well as a therapeutic target. PMID:26846877

  11. Simulation of prognostic tsunamis on the Korean Coast

    NASA Astrophysics Data System (ADS)

    Choi, Byung Ho; Hong, Sung Jin; Pelinovsky, Efim

    Prognostic characteristics of potential tsunamis in the East (Japan) Sea are discussed. Zones of tsunami sources for potential danger are selected using the seismic gap theory. Numerical model based on linear long wave theory is used to simulate the tsunami propagation from 28 potential tsunamigenic earthquakes. As a result, the synthetic tsunami catalogue is obtained for each coastal point along the east Korean coast. Statistical analysis of data for tsunami wave height distribution can be described by the log-normal curve. On the average, maximal value of tsunami wave height in each point does not exceed the mean value of computed wave heights by more than six times.

  12. Clinicopathological and prognostic significance of programmed cell death ligand1 (PD-L1) expression in patients with non-small cell lung cancer: a meta-analysis

    PubMed Central

    Pan, Zhen-Kui; Ye, Feng; Wu, Xuan; An, Han-Xiang

    2015-01-01

    Objective Programmed cell death 1 (PD-1) and one of its ligands, PD-L1, are key immune checkpoint proteins. Evidences showed PD-L1 is an emerging biomarker for immunotherapy by anti-PD-1 and anti-PD-L1 antibody in non-small cell lung cancer (NSCLC). To investigate the association of PD-L1 protein expression with clinicopathological features and its impact on survival outcome, we conducted a meta-analysis. Methods A comprehensive literature search of electronic databases (up to July 10, 2014) was performed. Correlation between PD-L1 expression and clinicopathological features and overall survival (OS) was analyzed by synthesizing the qualified data. Publication biases were examined. Results A total of 1,550 NSCLC patients from 9 studies were included. The pooled odds ratios (ORs) indicated high PD-L1 expression was associated with poor tumor differentiation [OR =0.53, 95% confidence interval (CI): 0.39-0.72, P<0.0001]. Whereas, none of other clinicopathological characteristics [gender, smoking status, histological type, invasive depth of tumor, status of lymph node metastasis and tumor node metastasis (TNM) stage] were correlated with PD-L1 expression in current analysis. The combined hazard ratio (HR) for OS showed high expression of PD-L1 impaired the OS in NSCLC (HRpositive/negative =1.47, 95% CI: 1.19-1.83, P=0.0004). Conclusions Our meta-analysis indicated PD-L1 protein expression in NSCLC was not associated with common clinicopathological characteristics, except tumor differentiation. It was a poor prognostic biomarker for NSCLC. Further research should be performed to investigate the precise clinicopathological and prognostic significance of PD-L1 in NSCLC under uniform testing standard. PMID:25922726

  13. MicroRNA-21 and Risk of Severe Acute Kidney Injury and Poor Outcomes after Adult Cardiac Surgery

    PubMed Central

    Du, Juan; Cao, Xiaoqing; Zou, Liang; Chen, Yi; Guo, Jin; Chen, Zujun; Hu, Shengshou; Zheng, Zhe

    2013-01-01

    Background Severe acute kidney injury (AKI) after cardiac surgery is associated with poor clinical outcomes. This study evaluated the potential use of miR-21 as a risk marker for postoperative AKI progression and other poor outcomes. Methodology/Principal Findings The study included 120 adult patients undergoing cardiac surgery: 40 non-AKI controls, 39 patients with progressive AKI, and 41 with non-progressive AKI. Urine and plasma levels of miR-21 were assessed by quantitative real-time PCR (RT-qPCR). Associations between miR-21 levels and AKI progression were determined by estimating areas under receiver operating characteristic curves (AUC). We demonstrated that up-regulated urine and plasma levels of miR-21 in patients with AKI were both associated with AKI progression. The AUCs for urine and plasma levels of miR-21 associated with established AKI were 0.68 (95%CI: 0.59–0.78) and 0.80 (95%CI: 0.73–0.88), respectively. Multiple logistic regression analysis, adjusting for clinical variables, indicated that the prognostic predictive power of urine and plasma miR-21 levels for AKI progression were represented by AUCs of 0.81 (95%CI: 0.72–0.91) and 0.83 (95%CI: 0.74–0.92), respectively. Urinary and plasma miR-21 levels also predicted the need for postoperative renal replacement therapy (RRT), development of Acute Kidney Injury Network (AKIN) stage 3 AKI, 30-day in-hospital mortality and prolonged stay in hospital or ICU. Urine miR-21 was a better outcome predictor than plasma miR-21, being associated with higher (1.4- to 2.6-fold) unadjusted odds ratio for progression of AKI and other poor outcomes. Conclusions Urinary and plasma miR-21 are associated with severe AKI and other poor postoperative outcomes of cardiac surgery, indicating their potential use as prognostic markers. PMID:23717419

  14. Expression of Tiam1 predicts lymph node metastasis and poor survival of lung adenocarcinoma patients

    PubMed Central

    2014-01-01

    Background To assess the value of Tiam1 in predicting lymph node metastasis and survival after curative resection in patients with lung adenocarcinoma. Methods Immunohistochemical staining for Tiam1 was performed on 98 adenocarcinoma and 30 normal lung tissues. The association of Tiam1 protein expression with the clinicopathological characteristics and the prognosis of lung adenocarcinoma were subsequently assessed. Results Immunohistochemical analysis showed that 60 of 98 (61.22%) adenocarcinoma tissues showed high expression of Tiam1, and high Tiam1 expression was significantly associated with advanced TNM stage (P?poor overall survival of patients in stages I?+?II (P?=?0.006). Furthermore, multivariate analysis indicated that high expression of Tiam1 protein was an independent prognostic factor for overall survival (P?=?0.011) in patients with lung adenocarcinoma. Conclusion These findings suggest for the first time that Tiam1 expression may be beneficial in predicting lymph node metastasis and survival of patients with lung adenocarcinoma. A future study will investigate whether Tiam1 can serve as a novel therapeutic target in lung adenocarcinoma. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1377798917111123. PMID:24661909

  15. Secondary acute lymphoblastic leukemia is an independent predictor of poor prognosis.

    PubMed

    Giri, Smith; Chi, Michelle; Johnson, Benny; McCormick, David; Jamy, Omer; Bhatt, Vijaya Raj; Martin, Mike G

    2015-12-01

    Compared to secondary acute myeloid leukemia, secondary acute lymphoblastic leukemia (sALL) is poorly characterized. We utilized data from the Surveillance, Epidemiology, and End Results (SEER) 13 database to further elucidate patient characteristics and prognostic factors in sALL. Cases of adult de novo acute lymphoblastic leukemia (ALL) and sALL in patients with primary breast, rectum, cervix, or ovarian cancers or lymphoma with a latency period of at least 12 months were identified within the SEER 13 database. Survival in sALL and de novo ALL were compared after propensity matching based on age, gender, race, ALL subtype, and year of diagnosis. 4124 cases of de novo ALL and 79 cases of sALL were identified. sALL patients were older at diagnosis (median 62 years vs 44 years; p<0.01). Overall survival (OS) in sALL was lower than de novo ALL (median 8 months vs 11 months), 1 year OS: 35% vs 47% (p=0.05), 2 year OS: 16% vs 31% (p<0.01), and 5 year OS: 7% vs 21% (p<0.01). Multivariate analysis revealed sALL as an independent predictor of worsened survival (adjusted HR 1.54; 95% CI 1.16-2.04, p<0.01) after propensity matching. PMID:26427729

  16. Monoethylglicinexylidide test: a prognostic indicator of survival in cirrhosis.

    PubMed

    Arrigoni, A; Gindro, T; Aimo, G; Cappello, N; Meloni, A; Benedetti, P; Molino, G P; Verme, G; Rizzetto, M

    1994-08-01

    The aim of this study was to assess the value of the monoethylglicinexylidide assay, a dynamic liver function test based on the determination of the serum concentration of lidocaine major metabolite, as a predictor of survival in cirrhosis. For this purpose, the predictive value of monoethylglicinexylidide was evaluated in comparison with the Pugh score, ascites, encephalopathy and a number of different biochemical parameters as collected from the prospective follow-up of 118 patients with cirrhosis. A stepwise regression analysis was performed on the variables of prognostic value according to the Cox model and with respect to 1-yr survival; because Pugh score and monoethylglicinexylidide were the sole variables selected, they were proved to supply independent prognostic information. The most reliable cutoff values for discrimination between death and survival were 25 ng/ml or less for monoethylglicinexylidide and less than 9 for the Pugh score. In 74 patients without overt signs of liver failure (i.e., Pugh < or = 9), monoethylglicinexylidide provided a wide range of results (i.e., 4 to 77 ng/ml), namely values ranging from very low to elevated. Of the 38 patients with satisfactory Pugh scores (< or = 9) but poor monoethylglicinexylidide values (< or = 25), 11 died during follow-up and 3 underwent liver transplantation, despite having shown no clinical signs of liver failure at entry. On the bases of discriminant levels, the monoethylglicinexylidide test is suitable for adoption as a reliable and sensitive indicator of survival in patients with cirrhosis because it supplies more accurate prognostic information compared with the Pugh score.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8045499

  17. Prognostic and predictive biomarkers: tools in personalized oncology.

    PubMed

    Nalejska, Ewelina; M?czy?ska, Ewa; Lewandowska, Marzena Anna

    2014-06-01

    Oncology indispensably leads us to personalized medicine, which allows an individual approach to be taken with each patient. Personalized oncology is based on pharmacogenomics and the effect of genetic differences in individuals (germline and somatic) on the way cancer patients respond to chemotherapeutics. Biomarkers detected using molecular biology tools allow the molecular characterization of cancer signatures and provide information relevant for personalized treatment. Biomarkers can be divided into two main subgroups: prognostic and predictive. The aim of the application of prognostic biomarkers, which provide information on the overall cancer outcome in patients, is to facilitate cancer diagnosis, usually with no need for putting invasive methods into use. Predictive biomarkers help to optimize therapy decisions, as they provide information on the likelihood of response to a given chemotherapeutic. Among the prognostic factors that identify patients with different outcome risks (e.g., recurrence of the disease), the following factors can be distinguished: somatic and germline mutations, changes in DNA methylation that lead to the enhancement or suppression of gene expression, the occurrence of elevated levels of microRNA (miRNA) capable of binding specific messenger RNA (mRNA) molecules, which affects gene expression, as well as the presence of circulating tumor cells (CTCs) in blood, which leads to a poor prognosis for the patient. Biomarkers for personalized oncology are used mainly in molecular diagnostics of chronic myeloid leukemia, colon, breast and lung cancer, and recently in melanoma. They are successfully used in the evaluation of the benefits that can be achieved through targeted therapy or in the evaluation of toxic effects of the chemotherapeutic used in the therapy. PMID:24385403

  18. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: a systematic review and meta-analysis.

    PubMed

    Zhang, Hua; Gao, Liuwei; Zhang, Bin; Zhang, Lianmin; Wang, Changli

    2016-01-01

    The prognostic value of the platelet-to-lymphocyte ratio (PLR) in non-small cell lung cancer (NSCLC) remains controversial. We therefore conducted a meta-analysis of published studies to determine the prognostic value of PLR in NSCLC. A systematic search was performed in PubMed, Web of Science and Embase for relevant studies. The data and characteristics of each study were extracted, and the hazard ratio (HR) at a 95% confidence interval (CI) was calculated to estimate the effect. We also performed subgroup and meta-regression analyses. A total of 2,889 patients in 12 studies were enrolled in this meta-analysis, and the pooled HR of 1.492 (95% CI: 1.231-1.807, P?poor prognosis in NSCLC. Further large-cohort studies are needed to confirm these findings. PMID:26939789

  19. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: a systematic review and meta-analysis

    PubMed Central

    Zhang, Hua; Gao, Liuwei; Zhang, Bin; Zhang, Lianmin; wang, Changli

    2016-01-01

    The prognostic value of the platelet-to-lymphocyte ratio (PLR) in non-small cell lung cancer (NSCLC) remains controversial. We therefore conducted a meta-analysis of published studies to determine the prognostic value of PLR in NSCLC. A systematic search was performed in PubMed, Web of Science and Embase for relevant studies. The data and characteristics of each study were extracted, and the hazard ratio (HR) at a 95% confidence interval (CI) was calculated to estimate the effect. We also performed subgroup and meta-regression analyses. A total of 2,889 patients in 12 studies were enrolled in this meta-analysis, and the pooled HR of 1.492 (95% CI: 1.231–1.807, P < 0.001) indicated that patients with an elevated PLR are expected to have a shorter overall survival (OS) after treatment. This meta-analysis indicates that a high PLR might be a predictive factor of poor prognosis in NSCLC. Further large-cohort studies are needed to confirm these findings. PMID:26939789

  20. Prognostic significance of micropapillary pattern in lung adenocarcinoma and expression of apoptosis-related markers: caspase-3, bcl-2, and p53.

    PubMed

    Cakir, Ebru; Yilmaz, Aydin; Demirag, Funda; Oguztuzun, Serpil; Sahin, Sezgi; Yazici, Ulku Eren; Aydin, Mehtap

    2011-09-01

    We evaluated the clinicopathological characteristics and prognostic significance of lung adenocarcinoma with micropapillary pattern (MPP) and analyzed the expression of apoptosis-related markers: caspase-3, bcl-2, and p53. A series of 166 lung adenocarcinoma that had been surgically resected between 2004 and 2009 were reviewed. Histopathologic patterns, presence of tumor necrosis, mitosis, lymphovascular and perineural invasion, the status of pleura, and tumor differentiation were examined. Of the 166 patients; 71 were stage I, 35 stage II, 51 stage III, and nine stage IV. Histologically they were divided into two groups: MPP-positive (n = 55) and MPP-negative (n = 111). The following items were significantly more frequent in the MPP positive group: female gender (p = 0.03), lymph node metastasis (p = 0.031), and pleural invasion (p = 0.045). Age, smoking status, tumor stage, lymphatic invasion, perineural invasion, mitotic count, and survival rates had no statistically significant difference between groups (p > 0.05). In MPP positive tumors, visceral pleural invasion was identified significantly more frequent than in MPP negative tumors, at stage I. Tumors with MPP showed elevated expressions of caspase-3 (94.5%), p53 (60%), and bcl-2 (54.5%). In MPP positive group, the expression of these three markers had no statistically significant impact on survival. In whole population, bcl-2 expression was correlated with a better outcome. We conclude that MPP is associated with poor prognostic factors both in early and late stages in lung adenocarcinoma. Bcl-2 provides prognostic information independent from the MPP. PMID:21851414

  1. Non-invasive prognostic protein biomarker signatures associated with colorectal cancer

    PubMed Central

    Surinova, Silvia; Radová, Lenka; Choi, Meena; Srovnal, Josef; Brenner, Hermann; Vitek, Olga; Hajdúch, Marián; Aebersold, Ruedi

    2015-01-01

    The current management of colorectal cancer (CRC) would greatly benefit from non-invasive prognostic biomarkers indicative of clinicopathological tumor characteristics. Here, we employed targeted proteomic profiling of 80 glycoprotein biomarker candidates across plasma samples of a well-annotated patient cohort with comprehensive CRC characteristics. Clinical data included 8-year overall survival, tumor staging, histological grading, regional localization, and molecular tumor characteristics. The acquired quantitative proteomic dataset was subjected to the development of biomarker signatures predicting prognostic clinical endpoints. Protein candidates were selected into the signatures based on significance testing and a stepwise protein selection, each within 10-fold cross-validation. A six-protein biomarker signature of patient outcome could predict survival beyond clinical stage and was able to stratify patients into groups of better and worse prognosis. We further evaluated the performance of the signature on the mRNA level and assessed its prognostic value in the context of previously published transcriptional signatures. Additional signatures predicting regional tumor localization and disease dissemination were also identified. The integration of rich clinical data, quantitative proteomic technologies, and tailored computational modeling facilitated the characterization of these signatures in patient circulation. These findings highlight the value of a simultaneous assessment of important prognostic disease characteristics within a single measurement. PMID:26253080

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

    PubMed Central

    CHEN, LUXIA; HE, YANJIN; SUN, SHIZHEN; SUN, BAOCUN; TANG, XIN

    2015-01-01

    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. PMID:26622724

  3. 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.

  4. Plasma cathepsin L: A prognostic marker for pancreatic cancer

    PubMed Central

    Singh, Nidhi; Das, Prasenjit; Gupta, Surabhi; Sachdev, Vikas; Srivasatava, Siddhartha; Datta Gupta, Siddhartha; Pandey, Ravindra Mohan; Sahni, Peush; Chauhan, Shyam S; Saraya, Anoop

    2014-01-01

    AIM: To assess the prognostic significance of cathepsin L, a cysteine protease that degrades the peri-tumoral tissue, in patients with pancreatic cancer. METHODS: Plasma samples from 127 pancreatic cancer patients were analyzed for cathepsin L levels by ELISA. Out of these patients, 25 underwent surgery and their paraffin-embedded tissue was analyzed for cathepsin L expression by immunohistochemistry. Survival of patients and clinicopathological parameters was correlated with cathepsin L expression in plasma and tissue using appropriate statistical analysis. RESULTS: The mean (± SD) cathepsin L in plasma samples of pancreatic cancer patients was 5.98 ± 2.5 ng/mL that was significantly higher compared to the levels in healthy controls (3.83 ± 0.45) or chronic pancreatitis patients (3.97 ± 1.06). Using ROC curve, a cut-off level of 5.0 ng/mL was decided for survival analysis. Elevated plasma levels of cathepsin L were found to be associated with poor prognosis (P = 0.01) in multivariate analysis. The plasma levels of the protease decreased after surgery. Though no significant correlation was seen between plasma and tissue expression of this protease, a trend did emerge that high cathepsin L expression in tissue correlated with its high levels in plasma. CONCLUSION: Cathepsin L levels in plasma of pancreatic cancer patients may be used as a potential prognostic marker for the disease. PMID:25516668

  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. WDR5 Expression Is Prognostic of Breast Cancer Outcome

    PubMed Central

    Zhan, Chunjun; Liu, Xiuxia; Bai, Zhonghu; Yang, Yankun

    2015-01-01

    WDR5 is a core component of the human mixed lineage leukemia-2 complex, which plays central roles in ER positive tumour cells and is a major driver of androgen-dependent prostate cancer cell proliferation. Given the similarities between breast and prostate cancers, we explore the potential prognostic value of WDR5 gene expression on breast cancer survival. Our findings reveal that WDR5 over-expression is associated with poor breast cancer clinical outcome in three gene expression data sets and BreastMark. The eQTL analysis reveals 130 trans-eQTL SNPs whose genes mapped with statistical significance are significantly associated with patient survival. These genes together with WDR5 are enriched with cellular development, gene expression, cell cycle signallings. Knocking down WDR5 in MCF7 dramatically decreases cell viability, but does not alter tumour cell response to doxorubicin. Our study reveals the prognostic value of WDR5 expression in breast cancer which is under long-range regulation of genes involved in cell cycle, and anthracycline could be coupled with treatments targeting WDR5 once such a regimen is available. PMID:26355959

  7. Mortality in heart failure: clinical variables of prognostic value.

    PubMed Central

    Cleland, J G; Dargie, H J; Ford, I

    1987-01-01

    One hundred and fifty two patients with chronic heart failure caused primarily by left ventricular dysfunction were followed prospectively in an open study for a mean period of 21 months. The effects of several clinical variables on subsequent outcome were examined, including the effects of treatment, which was determined by the clinician caring for the patient and was not randomly allocated. In order of importance, frequent ventricular extrasystoles, non-treatment with amiodarone, low mean arterial pressure, and a diagnosis of coronary artery disease were associated with a poor prognosis, with each of these variables providing extra predictive information independently of the others. Initial serum potassium concentration and treadmill exercise time also carried further weak but independent prognostic information. Neither treatment with angiotensin converting enzyme inhibitors nor digoxin appeared to affect outcome. Left ventricular function (as reflected by M mode echocardiography) and the dose of diuretic also failed to predict outcome. There did, however, appear to be a reduction in the frequency of sudden death when angiotension converting enzyme inhibitors were given. Further studies are required to confirm the adverse prognostic significance of ventricular arrhythmias in patients with heart failure and the possible benefit associated with amiodarone treatment. PMID:2447925

  8. Validation of the revised international prognostic scoring system (IPSS-R) in patients with lower-risk myelodysplastic syndromes: a report from the prospective European LeukaemiaNet MDS (EUMDS) registry.

    PubMed

    de Swart, Louise; Smith, Alex; Johnston, Thomas W; Haase, Detlef; Droste, Jackie; Fenaux, Pierre; Symeonidis, Argiris; Sanz, Guillermo; Hellstrm-Lindberg, Eva; Cermk, Jaroslav; Germing, Ulrich; Stauder, Reinhard; Georgescu, Otilia; MacKenzie, Marius; Malcovati, Luca; Holm, Mette S; Almeida, Antonio M; M?dry, Krzysztof; Slama, Borhane; Guerci-Bresler, Agnes; Sanhes, Laurence; Beyne-Rauzy, Odile; Luo, Elisa; Bowen, David; de Witte, Theo

    2015-08-01

    Baseline characteristics, disease-management and outcome of 1000 lower-risk myelodysplastic syndrome (MDS) patients within the European LeukaemiaNet MDS (EUMDS) Registry are described in conjunction with the validation of the revised International Prognostic Scoring System (IPSS-R). The EUMDS registry confirmed established prognostic factors, such as age, gender and World Health Organization 2001 classification. Low quality of life (EQ-5D visual analogue scale score) was significantly associated with reduced survival. A high co-morbidity index predicted poor outcome in univariate analyses. The IPSS-R identified a large group of 247 patients with Low (43%) and Very low (23%) risk score within the IPSS intermediate-1 patients. The IPSS-R also identified 32 High or Very high risk patients within the IPSS intermediate-1 patients. IPSS-R was superior to the IPSS for predicting both disease progression and survival. Seventy percent of patients received MDS-specific treatment or supportive care, including red blood cell transfusions (51%), haematopoietic growth factors (58%) and iron chelation therapy (8%), within 2years of diagnosis; while 30% of the patients only required active monitoring. The IPSS-R proved its utility as a more refined risk stratification tool for the identification of patients with a very good or poor prognosis and in this lower-risk MDS population. PMID:25907546

  9. Gastric Mucinous Cancer Histology: Clinicopathological Characteristics and Prognostic Value

    PubMed Central

    Jian-Hui, Chen; Shi-Rong, Cai; Hui, Wu; Jian-bo, Xu; Kai-Ming, Wu; Si-le, Chen; He, Yu-Long

    2016-01-01

    MC tended toward worse tumor biological behavior and long-term survival outcome compared to WMDC. Moreover, MC also showed worse clinicopathological features and survival outcome in some selected patients. For these reasons, MC should be deemed as a special histological type of gastric cancer with worse clinicopathological features and survival outcome. PMID:26839544

  10. 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

  11. 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. PMID:23423859

  12. Hypoxia induced high expression of thioredoxin interacting protein (TXNIP) in non-small cell lung cancer and its prognostic effect.

    PubMed

    Li, Yan; Miao, Li-Yun; Xiao, Yong-Long; Huang, Mei; Yu, Min; Meng, Kui; Cai, Hou-Rong

    2015-01-01

    Although associations between thioredoxin interacting protein (TXNIP) and cancers have been recognized, the effects of TXNIP on non-small cell lung cancer (NSCLC) prognosis remained to be determined in detail. In addition, while hypoxia is a key characteristic of tumor cell growth microenvironment, the effect of hypoxia on TXNIP expression is controversial. In this study, formaldehyde fixed and paraffin embedded (FFPE) samples of 70 NSCLC patients who underwent resection between January 2010 and December 2011 were obtained. Evaluation of TXNIP and hypoxia inducible factor-1? (HIF-1?) protein expression in FFPE samples was made by immunohistochemistry. By Kaplan-Meier method, patients with high TXNIP expression demonstrated a significantly shorter progression free survival (PFS) compared with those with low TXNIP expression (18.0 months, 95%CI: 11.7, 24.3 versus 23.0 months, 95%CI: 17.6, 28.4, P=0.02). High TXNIP expression level was also identified as an independent prognostic factor by Cox regression analysis (adjusted hazard ratio: 2.46; 95%CI: 1.08, 5.56; P=0.03). Furthermore, TXNIP expression was found to be significantly correlated with HIF- 1? expression (Spearman correlation=0.67, P=0.000). To further confirm correlations, we established a tumor cell hypoxic culture model. Expression of TXNIP was up-regulated in all three NSCLC cell lines (A549, SPC-A1, and H1299) under hypoxic conditions. This study suggests that hypoxia induces increased TXNIP expression in NSCLC and high TXNIP expression could be a poor prognostic marker. PMID:25854388

  13. Assessment of the prognostic significance of endoglin (CD105) in clear cell renal cell carcinoma using automated image analysis.

    PubMed

    Dubinski, William; Gabril, Manal; Iakovlev, Vladimir V; Scorilas, Andreas; Youssef, Youssef M; Faragalla, Hala; Kovacs, Kalman; Rotondo, Fabio; Metias, Shereen; Arsanious, Androu; Plotkin, Anna; Girgis, Andrew H F; Streutker, Catherine J; Yousef, George M

    2012-07-01

    The behavior of clear cell renal cell carcinoma can be difficult to predict. Angiogenesis has proven to be a useful prognostic indicator in different malignancies. Endoglin (CD105) is a new marker of angiogenesis found to have prognostic utility in various tumors. Here, we provide the first automated digital assessment of intratumoral microvascular density in clear cell renal cell carcinoma using endoglin and CD31 and assess their utility as predictors of clinical outcome. Both endoglin and CD31 expression showed association with advanced tumor stage (P = .025 and P = .011, respectively). There was a significant correlation between CD31 and tumor grade (P = .034). Kaplan-Meier survival curves showed that patients with higher endoglin expression had significantly shorter progression-free survival (P = .010). Patients with higher CD31 expression tended to have a worse prognosis, although this was not statistically significant (P = .082). In univariate analysis using endoglin as a continuous variable, increased endoglin was strongly associated with reduced survival (hazard ratio, 1.74; 95% CI, 1.39-2.18; P = <.001). CD31 also correlated with poor outcomes (hazard ratio, 1.52; 95% CI, 1.24-1.86; P = .001). There was no correlation between CD31 and endoglin expression (r = -0.090, P = .541). Receiver operating characteristic analysis showed the area under the curve to be 0.749 for endoglin and 0.550 for CD31. In conclusion, increased endoglin and CD31 expression are associated with a higher tumor stage and decreased progression-free survival. Our automated approach overcomes many limitations of manual quantification. Advances in digital assessment of immunohistochemical markers can be helpful in standardizing the evaluation of tumor biomarkers. PMID:22204709

  14. Prognostic and clinicopathological significance of serum interleukin-6 expression in colorectal cancer: a systematic review and meta-analysis

    PubMed Central

    Wang, Zhen; Wu, Pin; Wu, Dang; Zhang, Zhigang; Hu, Guoming; Zhao, Shuai; Lai, Yucheng; Huang, Jian

    2015-01-01

    Purpose Interleukin-6 (IL-6) plays an important role in human colorectal cancer (CRC) development. However, the exact clinical and prognostic significance of IL-6 in CRC is still unclear. Here, we conducted this meta-analysis to explore this issue in detail. Methods A meta-analysis was performed to clarify the association between serum IL-6 expression and clinical outcomes in articles published up to June 2015. Weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) were used to assess the association between serum IL-6 expression and the clinicopathological characteristics of CRC. Hazard ratio (HR) with 95% CI was used to quantify the predictive value of IL-6 on CRC prognosis. Results Fourteen studies comprising 1,245 patients were included. Analysis of these data showed that serum IL-6 expression was highly correlated with poor 5-year overall survival (OS) rate (HR =0.43, 95% CI: 0.31–0.59, P=0.755). Simultaneously, we also found that serum IL-6 expression was associated with certain clinical parameters of CRC, such as tumor invasion (T category: T0–T2, T3–T4) (WMD =3.15, 95% CI: 1.92–4.39, P=0.816), distant metastasis (M category: M0, M1) (WMD =4.69, 95% CI: 3.33–6.06, P=0.377), and tumor stage (I–II, III–IV) (WMD =2.65, 95% CI: 1.09–4.21, P=0.066). Conclusion A high serum IL-6 expression is associated with adverse OS in CRC. The IL-6 expression can be an important supplement in establishing prognostic score for clinical decision. PMID:26719707

  15. Evaluation of Uric Acid as a Prognostic Blood-Based Marker in a Large Cohort of Pancreatic Cancer Patients

    PubMed Central

    Stotz, Michael; Szkandera, Joanna; Seidel, Julia; Stojakovic, Tatjana; Samonigg, Hellmut; Reitz, Daniel; Gary, Thomas; Kornprat, Peter; Schaberl-Moser, Renate; Hoefler, Gerald; Gerger, Armin; Pichler, Martin

    2014-01-01

    Background Recently, chemical blood parameters gain more attraction as potential prognostic parameters in pancreatic cancer (PC). In the present study we investigated the prognostic relevance of the uric acid (UA) level in blood plasma at the time of diagnosis for overall survival (OS) in a large cohort of patients with PC. Patients and Methods Data from 466 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival (OS) was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of the UA level, univariate and multivariate Cox regression models were calculated. Results None of the clinicopathological parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI) or surgical resection) except gender was associated with UA level. In univariate analysis we observed the elevated UA level (<5.1 versus ?5.1 mg/dl, p?=?0.017) as poor prognostic factor for OS. In the multivariate analysis that included age, gender, tumour grade, tumour stage, surgical resection, CA19-9 level, the KI and UA level we confirmed the UA level as independent prognostic factor for OS (HR?=?1.373%; CI?=?1.0771.751; p?=?0.011). Conclusion In conclusion, we identified the UA level at time of diagnosis as an independent prognostic factor in PC patients. Our results indicate that the UA level might represent a novel and useful marker for patient stratification in PC management. PMID:25133546

  16. Extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 overexpression is associated with loss of hormone receptor expression and poor prognosis in endometrial cancer

    PubMed Central

    YUAN, YUAN; SHEN, NING; YANG, SHU-YAN; ZHAO, LING; GUAN, YONG-MEI

    2015-01-01

    Extracellular matrix metalloproteinase inducer (CD147) and matrix metalloproteinase-2 (MMP-2) have been documented in various malignancies. CD147 is a member of the immunoglobulin superfamily, which promotes the production and release of MMPs in mesenchymal cells and tumor cells. MMP-2 has been extensively studied and is considered to be particularly important in cancer invasion and metastasis. However, studies investigating the expression and prognostic value of CD147 in endometrioid endometrial carcinoma (EEC) are limited. The present study analyzed the expression of CD147 and MMP-2 by immunohistochemistry in endometrial tissue samples from 107 patients with EEC and 30 patients with benign uterus myoma. The association between CD147 and MMP-2 expression and clinicopathological characteristics was evaluated. The results showed that the overexpression of MMP-2 was significantly associated with International Federation of Gynecology and Obstetrics stage (P=0.007), depth of invasion (P=0.037) and reduced expression of progesterone receptor (P=0.005). Kaplan-Meier analyses indicated that CD147 overexpression alone (P<0.05 for disease-specific survival) or in combination with MMP-2 (P<0.001 for disease-specific survival) was correlated with adverse prognosis in EEC patients. Multivariate analysis revealed that the combined overexpression of CD147 and MMP-2 was an independent prognostic factor for disease-specific survival (hazard ratio=5.141, P=0.001) in EEC patients. CD147 and MMP-2 overexpression was positively correlated with aggressive phenotypic features in EEC, however it was negatively correlated with hormone receptor expression. The combination of CD147 and MMP-2 overexpression in EEC further distinguished a subgroup of patients with poor prognosis. Thus, the results of present study indicate that the co-expression of CD147 and MMP-2 may be an independent prognostic factor in EEC patients. PMID:26171027

  17. Critical illness neuromuscular disease: clinical, electrophysiological, and prognostic aspects

    PubMed Central

    Tabarki, B; Coffinieres, A; Van den Bergh, P; Huault, G; Landrieu, P; Sebire, G

    2002-01-01

    Background: Critical illness neuromuscular disease, which has been recognised as a distinct clinical entity in adults, remains poorly described in children. Aims: To assess retrospectively the clinical, electrophysiological, and prognostic features of the disease. Methods: Retrospective study in a children's university hospital. Results: Five critically ill patients presented with generalised paralysis, associated with long lasting failure to breathe in three. The cause of the generalised paralysis was critical illness neuropathy in two, acute myopathy in two, and mixed neuromyopathy in one. Conclusions: Neuromuscular disease should be suspected in critically ill children with muscle weakness. Because corticosteroids and muscle relaxants appear to trigger some types of intensive care unit neuromuscular disease in children, their use should be restricted or administered at the lowest doses possible. PMID:11827903

  18. Prognostic factors and risk stratification in early mycosis fungoides.

    PubMed

    Vonderheid, Eric C; Pavlov, Igor; Delgado, Julio C; Martins, Thomas B; Telang, Gladys H; Hess, Allan D; Kadin, Marshall E

    2014-01-01

    Available demographic, clinical, histologic, immunohistochemical and laboratory findings, including serum cytokine/cytokine receptor levels, obtained at initial evaluation in a cohort of 33 patients with mycosis fungoides (MF) at stages I-IIA who had subsequent progression of disease were compared against 70 stage-matched cases of MF without observed progression. Significant factors that correlated with both disease progression and overall survival were: (1) presence of large Pautrier microabscesses (10 or more atypical lymphocytes), (2) presence of atypical lymphocytes with hyperchromatic or vesicular nuclei in the dermal infiltrate, (3) less than 20% CD8 + cells in the dermal infiltrate and (4) above normal (> 122 U/mL) serum immunoglobulin E (IgE) level. Combination of these factors was used to construct prognostic groupings which, if validated, might be useful to identify patients with clinically early MF at highest risk for disease progression and poor outcome. PMID:23547839

  19. Serum Endocan as a Novel Prognostic Biomarker in Patients with Hepatocellular Carcinoma

    PubMed Central

    Ozaki, Kazuaki; Toshikuni, Nobuyuki; George, Joseph; Minato, Takahiro; Matsue, Yasuhiro; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

    2014-01-01

    Endocan is a vascular endothelium-derived factor regulated by angiogenic factors. The aim of this study was to determine whether serum endocan levels are prognostic for survival in patients with hepatocellular carcinoma (HCC). Serum endocan levels were measured in 64 HCC patients who were nave to treatment, eight apparently healthy subjects, and 68 patients with liver cirrhosis; the latter two groups served as controls. Prognostic factors for the survival of HCC patients were examined using a Cox proportional hazards model. The median serum endocan levels were 1.145 ng/mL (range, 0.93-1.68 ng/mL) in healthy subjects, 1.93 ng/mL (range, 0.45-8.47 ng/mL) in liver cirrhosis patients, and 3.73 ng/mL (range, 0.74-10.95 ng/mL) in HCC patients (P = 0.0001). In HCC patients, elevated serum endocan levels were significantly associated with poor hepatic function (P = 0.015), a greater number of tumors (P = 0.034), and vascular invasion (P = 0.043). The median follow-up period was 23.0 months, and 33 HCC patients died during follow up. Multivariate analysis showed that serum endocan levels ? 2.20 ng/mL (hazard ratio 2.36, 95% confidence interval 1.22-5.36, P = 0.008) as well as elevated serum ?-fetoprotein and des-?-carboxy prothrombin levels were independent prognostic biomarkers for poor survival. The combination of serum endocan and these two additional markers was significantly predictive of worse survival (P < 0.0001). Thus, serum endocan may be a prognostic biomarker for survival in HCC patients, and the combination of serum endocan, ?-fetoprotein, and des-?-carboxy prothrombin levels can result in better prognostic stratification of these patients. PMID:24665346

  20. Immunohistochemical analysis of RTKs expression identified HER3 as a prognostic indicator of gastric cancer

    PubMed Central

    Ema, Akira; Yamashita, Keishi; Ushiku, Hideki; Kojo, Ken; Minatani, Naoko; Kikuchi, Mariko; Mieno, Hiroaki; Moriya, Hiromitsu; Hosoda, Kei; Katada, Natsuya; Kikuchi, Shiro; Watanabe, Masahiko

    2014-01-01

    Standard treatment in Japan for the 13th Japanese Gastric Cancer Association stage II/III advanced gastric cancer is postoperative adjuvant S-1 administration after curative surgery. High expression of receptor type tyrosine kinases (RTKs) has repeatedly represented poor prognosis for cancers. However it has not been demonstrated whether RTKs have prognostic relevance for stage II/III gastric cancer with standard treatment. Tumor tissues were obtained from 167 stage II/III advanced gastric cancer patients who underwent curative surgery and received postoperative S-1 chemotherapy from 2000 to 2010. Expression of the RTKs including EGFR, HER2, HER3, IGF-1R, and EphA2 was analyzed using immunohistochemistry (IHC). Analysis using a multivariate proportional hazard model identified the most significant RTKs that represented independent prognostic relevance. When tumor HER3 expression was classified into IHC 1+/2+ (n = 98) and IHC 0 (n = 69), the cumulative 5-year Relapse Free Survival (5y-RFS) was 56.5 and 82.9%, respectively (P = 0.0034). Significant prognostic relevance was similarly confirmed for IGF-1R (P = 0.014), and EGFR (P = 0.030), but not for EphA2 or HER2 expression. Intriguingly, HER3 expression was closely correlated with IGF-1R (P < 0.0001, R = 0.41), and EphA2 (P < 0.0001, R = 0.34) expression. Multivariate proportional hazard model analysis identified HER3 (IHC 1+/2+) (HR; 1.53, 95% CI, 1.112.16, P = 0.0078) as the sole RTK that was a poor prognostic factor independent of stage. Of the 53 patients who recurred, 40 patients (75.5%) were HER3-positive. Thus, of the RTKs studied, HER3 was the only RTK identified as an independent prognostic indicator of stage II/III advanced gastric cancer with standard treatment. PMID:25455899

  1. A systematic review of prognostic factors for distal upper limb pain

    PubMed Central

    Whibley, Daniel; Martin, Kathryn R; Lovell, Karina; Jones, Gareth T

    2015-01-01

    Background: Musculoskeletal pain in the distal upper limb is relatively common, can be a cause of disability, presents a high cost to society and is clinically important. Previous reviews of prognostic factors have focused on pain in the proximal upper limb, whole upper extremity or isolated regions of the distal upper limb. Aim: To identify factors that predict outcome of distal upper limb pain. Study design: Systematic review Method: Eight bibliographic databases were searched from inception to March 2014. Eligible articles included adults with pain anywhere in the distal upper limb at baseline from randomised controlled trials with a waiting list, expectant policy or usual care group, or observational studies where no treatment or usual care was provided. Data describing the association between a putative prognostic factor and pain or functional outcome at follow-up were required. Quality was assessed using the Quality in Prognostic Studies tool. Results: Seven articles reporting on six studies were identified. Heterogeneity of study populations and outcome measures prevented a meta-analysis so a narrative synthesis of results was undertaken. Three factors (being female, a longer duration of the complaint at initial presentation and having musculoskeletal pain in multiple locations) were significantly associated with poor pain outcome in more than one study. Being female was the only factor significantly associated with poor functional outcome in more than one study. Conclusions: A range of sociodemographic, pain-related, occupational and psychosocial prognostic factors for distal upper limb pain outcomes were investigated in studies included in the review. However, due to the lack of commonality of factors investigated and lack of consistency of results across studies, there is limited evidence for predictors of distal upper limb pain outcomes. Further research is required to identify prognostic factors of distal upper limb pain, particularly modifiable factors that may influence management. PMID:26526466

  2. High Expression of Neuro-Oncological Ventral Antigen 1 Correlates with Poor Prognosis in Hepatocellular Carcinoma

    PubMed Central

    Yin, Jie; Tang, Wen-Qing; Guo, Yan-Mei; Shen, Xi-Zhong; Liu, Tao-Tao

    2014-01-01

    Neuro-oncological ventral antigen 1 (Nova1) is a neuron-specific RNA-binding protein in human paraneoplastic opsoclonus-myoclonus ataxia accompanying with malignant tumors, but its role in hepatocellular carcinoma (HCC) remains elusive. In this study, we found that overexpressed intratumoral Nova1 was associated with poor survival rate and increased recurrence rate of HCC, especially early recurrence, and was an independent prognostic factor for overall survival rate and tumor recurrence. HCC cell lines over-expressing Nova1 exhibited greater potentials in cell proliferation, invasion and migration, while knockdown of Nova1 had the opposite effects. All these findings indicate that Nova1 may act as a prognostic marker for poor outcome and high recurrence in HCC. PMID:24608171

  3. Tuberculous meningitis in children: a retrospective study of 79 patients, with an analysis of prognostic factors.

    PubMed Central

    Delage, G.; Dusseault, M.

    1979-01-01

    A study of 79 cases of tuberculous meningitis in children, with an emphasis on prognostic factors, was conducted by means of a review of hospital records and completion of a follow-up questionnaire. The survival rate was 62%. Stage 3 disease (with severe changes in the sensorium and often severe neurologic abnormalities) at the time of admission, age 3 years or less, associated miliary tuberculosis and delay in the initiation of therapy correlated significantly with poor outcome. Severe neurologic complications in the acute phase were also related to poor outcome and severe sequelae. General recommendations pertaining to treatment are made. PMID:427668

  4. Malignant Peritoneal Mesothelioma: Prognostic Factors and Oncologic Outcome Analysis

    PubMed Central

    Magge, Deepa; Zenati, Mazen S.; Austin, Frances; Mavanur, Arun; Sathaiah, Magesh; Ramalingam, Lekshmi; Jones, Heather; Zureikat, Amer H.; Holtzman, Matthew; Ahrendt, Steven; Pingpank, James; Zeh, Herbert J.; Bartlett, David L.; Choudry, Haroon A.

    2014-01-01

    Background Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM. Methods We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. KaplanMeier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. Results Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001). Conclusions Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC. PMID:24322529

  5. Are Poor Chinese Text Comprehenders Also Poor in Written Composition?

    ERIC Educational Resources Information Center

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

    2013-01-01

    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

  6. 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

  7. 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.

  8. Prognostic DNA Methylation Markers for Prostate Cancer

    PubMed Central

    Strand, Siri H.; Orntoft, Torben F.; Sorensen, Karina D.

    2014-01-01

    Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

  9. 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

  10. Prognostic significance of Ki-67 antigen expression in extranodal natural killer/T-cell lymphoma, nasal type.

    PubMed

    Jiang, Li; Li, Pengfei; Wang, Hua; Liu, Jun; Zhang, Xinke; Qiu, Huijuan; Zhang, Bei

    2014-10-01

    Extranodal natural killer (NK)/T-cell lymphoma, nasal-type (ENKTL) is a clinically heterogeneous disease with poor prognosis and requires risk stratification in affected patients. Recent studies have shown that Ki-67 may serve as a prognostic marker in certain types of lymphoma. We analyzed Ki-67 expression and its correlation with prognosis in 182 patients with ENKTL from January 2002 to June 2013. The patients were classified into two groups through a median value: low (<60%) versus high Ki-67 (?60%). High Ki-67 expression was more common in patients with B symptoms (p=0.02), bulky disease (p=0.001), and extraupper aerodigestive tract NK/T-cell lymphoma (p=0.001). High Ki-67 expression was significantly associated with poor overall survival (p<0.0001) and progression-free survival (p<0.0001). For patients with low-risk IPI or KPI, Ki-67 at diagnosis could contribute to distinguish patients with favorable outcomes from those with poor outcomes. The results of multivariate analysis showed that the high Ki-67 expression is an independent prognostic factor for overall survival and progression-free survival. (OS, p=0.001; PFS, p=0.003). Our data showed that Ki-67 is an effective prognostic indicator of survival in ENKTL patients. This prognostic index may be helpful in identifying high-risk patients with ENKTL. PMID:25204411

  11. 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

  12. Collagen Triple Helix Repeat Containing-1 (CTHRC1) Expression in Oral Squamous Cell Carcinoma (OSCC): Prognostic Value and Clinico-Pathological Implications

    PubMed Central

    Lee, Chia Ee; Vincent-Chong, Vui King; Ramanathan, Anand; Kallarakkal, Thomas George; Karen-Ng, Lee Peng; Ghani, Wan Maria Nabillah; Rahman, Zainal Ariff Abdul; Ismail, Siti Mazlipah; Abraham, Mannil Thomas; Tay, Keng Kiong; Mustafa, Wan Mahadzir Wan; Cheong, Sok Ching; Zain, Rosnah Binti

    2015-01-01

    BACKGROUND: Collagen Triple Helix Repeat Containing 1 (CTHRC1) is a protein often found to be over-expressed in various types of human cancers. However, correlation between CTHRC1 expression level with clinico-pathological characteristics and prognosis in oral cancer remains unclear. Therefore, this study aimed to determine mRNA and protein expression of CTHRC1 in oral squamous cell carcinoma (OSCC) and to evaluate the clinical and prognostic impact of CTHRC1 in OSCC. METHODS: In this study, mRNA and protein expression of CTHRC1 in OSCCs were determined by quantitative PCR and immunohistochemistry, respectively. The association between CTHRC1 and clinico-pathological parameters were evaluated by univariate and multivariate binary logistic regression analyses. Correlation between CTHRC1 protein expressions with survival were analysed using Kaplan-Meier and Cox regression models. RESULTS: Current study demonstrated CTHRC1 was significantly overexpressed at the mRNA level in OSCC. Univariate analyses indicated a high-expression of CTHRC1 that was significantly associated with advanced stage pTNM staging, tumour size ≥ 4 cm and positive lymph node metastasis (LNM). However, only positive LNM remained significant after adjusting with other confounder factors in multivariate logistic regression analyses. Kaplan-Meier survival analyses and Cox model demonstrated that patients with high-expression of CTHRC1 protein were associated with poor prognosis and is an independent prognostic factor in OSCC. CONCLUSION: This study indicated that over-expression of CTHRC1 potentially as an independent predictor for positive LNM and poor prognosis in OSCC. PMID:26664254

  13. 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

  14. Prognostic impact of histological categorisation of epithelial–mesenchymal transition in colorectal cancer

    PubMed Central

    Ueno, H; Shinto, E; Kajiwara, Y; Fukazawa, S; Shimazaki, H; Yamamoto, J; Hase, K

    2014-01-01

    Background: The crosstalk between cancer cells and stroma is involved in the acquired capability for metastasis through the induction of epithelial–mesenchymal transition (EMT). We aimed to clarify the prognostic value of the histological category of EMT in colorectal cancer (CRC). Methods: Tumour EMT was graded into one of three histological categories on the basis of integrated assessment of poorly differentiated clusters and pro-EMT desmoplasia at the leading edge of the primary tumour (HistologyEMT). Stage II and III CRC patients (cohort 1, N=500) and stage IV patients (cohort 2, N=196) were retrospectively analysed. Results: In cohort 1, patients were stratified into three groups with widely different disease-free survival rates (95%, 83% and 39%) on the basis of HistologyEMT (P<0.0001). In cohort 2, HistologyEMT significantly stratified overall survival of patients irrespective of metasectomy. Multivariate analyses indicated that HistologyEMT had a strong prognostic impact independent of staging factors. Statistically, HistologyEMT had a better prognostic stratification power than T and N stages; however, in cohort 2, the power of M substage was superior. Conclusions: A histological model to categorise EMT by integrated assessment of dedifferentiation and desmoplastic environment is a potent prognostic index independent of staging factors. PMID:25247323

  15. Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Chen, Dung-Tsa; Davis-Yadley, Ashley H.; Huang, Po-Yu; Husain, Kazim; Centeno, Barbara A.; Permuth-Wey, Jennifer; Pimiento, Jose M.; Malafa, Mokenge

    2015-01-01

    The outcomes of patients treated with surgery for early stage pancreatic ductal adenocarcinoma (PDAC) are variable with median survival ranging from 6 months to more than 5 years. This challenge underscores an unmet need for developing personalized medicine strategies to refine the current treatment decision-making process. To derive a prognostic gene signature for patients with early stage PDAC, a PDAC cohort from Moffitt Cancer Center (n = 63) was used with overall survival (OS) as the primary endpoint. This was further evaluated using an independent microarray cohort dataset (Stratford et al: n = 102). Technical validation was performed by NanoString platform. A prognostic 15-gene signature was developed and showed a statistically significant association with OS in the Moffitt cohort (hazard ratio [HR] = 3.26; p<0.001) and Stratford et al cohort (HR = 2.07; p = 0.02), and was independent of other prognostic variables. Moreover, integration of the signature with the TNM staging system improved risk prediction (p<0.01 in both cohorts). In addition, NanoString validation showed that the signature was robust with a high degree of reproducibility and the association with OS remained significant in the two cohorts. The gene signature could be a potential prognostic tool to allow risk-adapted stratification of PDAC patients into personalized treatment protocols; possibly improving the currently poor clinical outcomes of these patients. PMID:26247463

  16. Static and dynamic prognostic factors for hepatitis-B-related acute-on-chronic liver failure

    PubMed Central

    Ha, Jung Min; Sohn, Won; Cho, Ju Yeon; Pyo, Jeung Hui; Choi, Kyu; Sinn, Dong Hyun; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Chul; Paik, Seung Woon; Yoo, Byung Chul

    2015-01-01

    Background/Aims Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission. Methods Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals. Results A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (?28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (?grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016). Conclusions Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure. PMID:26523268

  17. Initial Hyperleukocytosis and Neutrophilia in Nasopharyngeal Carcinoma: Incidence and Prognostic Impact

    PubMed Central

    OuYang, Pu-Yun; Tang, Jie; Xie, Fang-Yun

    2015-01-01

    Background This study aimed to evaluate initial hyperleukocytosis and neutrophilia as prognostic indicators in patients with nasopharyngeal carcinoma. Methods A retrospective analysis of 5,854 patients identified from a cohort of 6,035 patients diagnosed with nasopharyngeal carcinoma was performed with initial hyperleukocytosis and neutrophilia analyzed as prognostic factors. Multivariate Cox proportional hazards analyses were applied. Results Hyperleukocytosis was observed in 508 patients (8.7%). Multivariate analysis showed that initial hyperleukocytosis was an independent predictor of death (HR 1.40, 95%CI 1.151.70, p = 0.001), progression (HR 1.25, 95%CI 1.061.47, p = 0.007) and, marginally, distant metastasis (HR 1.21, 95%CI 0.971.52, p = 0.088). Neutrophilia was also an independent predictor of death (HR 1.46, 95%CI 1.181.81, p = 0.001), progression (HR 1.31, 95%CI 1.101.56, p = 0.003), and distant metastasis (HR 1.29, 95%CI 1.021.65, p = 0.036), after adjusting for prognostic factors and excluding hyperleukocytosis. Conclusion Initial hyperleukocytosis and neutrophilia were independent, poor prognostic factors and may be convenient and useful biological markers for survival of patients with nasopharyngeal carcinoma. PMID:26336064

  18. The Fractal Dimension of Nuclear Chromatin as a Prognostic Factor in Acute Precursor B Lymphoblastic Leukemia

    PubMed Central

    Adam, Randall L.; Silva, Rosana C.; Pereira, Fernanda G.; Leite, Neucimar J.; Lorand-Metze, Irene; Metze, Konradin

    2006-01-01

    The fractal nature of the DNA arrangement has been postulated to be a common feature of all cell nuclei. We investigated the prognostic importance of the fractal dimension (FD) of chromatin in blasts of patients with acute precursor B lymphoblastic leukemia (B-ALL). In 28 patients, gray scale transformed pseudo-3D images of 100 nuclei (MayGrnwaldGiemsa stained bone marrow smears) were analyzed. FD was determined by the MinkowskiBouligand method extended to three dimensions. Goodness-of-fit of FD was estimated by the R2 values in the log-log plots. Whereas FD presented no prognostic relevance, patients with higher R2 values showed a prolonged survival. White blood cell count (WBC), age and mean fluorescence intensity of CD45 (MFICD45) were all unfavorable prognostic factors in univariate analyses. In a multivariate Cox-regression, R2, WBC, and MFICD45, entered the final model, which showed to be stable in a bootstrap resampling study. Blasts with lower R2 values, equivalent to accentuated coarseness of the chromatin pattern, which may reflect profound changes of the DNA methylation, indicated a poor prognosis. In conclusion the goodness-of-fit of the MinkowskiBouligand dimension of chromatin can be regarded as a new and biologically relevant prognostic factor for patients with B-ALL. PMID:16675881

  19. IMP3 Protein Expression is an Independent Prognostic Factor in Pediatric Pilocytic and Pilomyxoid Astrocytoma

    PubMed Central

    Barton, Valerie N.; Donson, Andrew M.; Birks, Diane K.; Kleinschmidt-DeMasters, BK; Handler, Michael H.; Foreman, Nicholas K.; Rush, Sarah Z.

    2015-01-01

    Prognostic factors in pilocytic astrocytomas (PA) and pilomyxoid astrocytomas (PMA) include extent of resection, location and age but no molecular markers have been established. Insulin-like growth factor-II messenger RNA binding protein-3 (IMP3, IGF2BP3) is predictive of an unfavorable prognosis in other tumors including high grade astrocytomas but its role in PA/PMA is unknown. This study aimed to determine the expression and prognostic value of IMP3 in pediatric PA/PMAs. IMP3 protein expression was examined by immunohistochemistry (IHC) in 77 pediatric PAs (n=70) and PMAs (n=7) and scored on a subjective scale. Strong diffuse staining for IMP3 was observed in 31% (24/77) of tumors and associated with a shorter progression free survival (HR=2.63; p=0.008). This cohort confirmed previously identified prognostic factors including extent of resection, age and tumor location. Currently, only clinical factors are weighed to stratify risk for patients and to identify those who should receive further therapy. Multivariate analyses identified IMP3 expression as an independent prognostic factor (HR=2.45; p=0.016) when combined with high/low risk stratification. High IMP3 as measured by IHC has potential utility as an additional predictor of poor prognosis in pediatric PA/PMAs and warrants evaluation in larger cohorts. PMID:23584203

  20. Aneurysmal subarachnoid hemorrhage: prognostic features and outcomes.

    PubMed

    Tamargo, R J; Walter, K A; Oshiro, E M

    1997-11-01

    The prognostic features and outcomes associated with aneurysmal subarachnoid hemorrhage (SAH) are reviewed. In the first section, the epidemiology of SAH is discussed with emphasis on prevalence, incidence, risk factors, heredity, activity, and seasonal variability. In the second section, the presentation, diagnosis, and treatment of patients with aneurysmal SAH is briefly reviewed. In the third section, the prognostic features associated with aneurysmal SAH are discussed with emphasis on neurologic condition and SAH grading scales, patient's age, aneurysm size and location, repeat hemorrhage, vasospasm, systemic disease, hypertensive response, computed tomograph features, hydrocephalus, timing of surgery, and expertise of the aneurysm center. Also in the third section, the prognostic features associated with unruptured aneurysms are discussed with emphasis on the actuarial risk of rupture, aneurysm size and location, and multiplicity of lesions. In the fourth and final section, the outcomes of aneurysmal SAH over the past 60 yrs are reviewed. PMID:9433989

  1. Phase Angle for Prognostication of Survival in Patients with Advanced Cancer: Preliminary Findings

    PubMed Central

    Hui, David; Bansal, Swati; Morgado, Margarita; Dev, Rony; Chisholm, Gary; Bruera, Eduardo

    2014-01-01

    Background Accurate survival prediction is essential for decision-making in cancer therapies and care planning. Objective physiologic measures may improve the accuracy of prognostication. In this prospective study, we determined the association of phase angle, hand grip strength, and maximal inspiratory pressure with overall survival in patients with advanced cancer. Methods We enrolled hospitalized patients with advanced cancer who were seen by palliative care for consultation. We collected information on phase angle, hand grip strength, maximal inspiratory pressure and known prognostic factors including Palliative Prognostic Score (PaP), Palliative Prognostic Index, serum albumin and body composition. We conducted univariate and multivariate survival analysis, and examined the correlation between phase angle and other prognostic variables. Results 222 patients were enrolled: average age 55 (range 22–79), female 59%, mean Karnofsky Performance Status 55, and median overall survival 106 days (95% confidence interval [CI] 71–128 days). The median survival for patients with phase angle 2–2.9°, 3–3.9°, 4–4.9°, 5–5.9° and ≥6° was 35, 54, 112, 134 and 220 days, respectively (P=0.001). In multivariate analysis, phase angle (hazard ratio [HR]=0.86 per degree increase; 95% CI 0.74–0.99; P=0.04), PaP (HR=1.07; 95% CI 1.02–1.13, P=0.008), serum albumin (HR=0.67, 95% CI 0.50–0.91; P=0.009), and fat free mass (HR=0.98, CI=0.96–0.99; P=0.02) were significantly associated with survival. Phase angle was only weakly (γ<0.4) associated with other prognostic variables. Conclusions Phase angle was a novel predictor of poor survival, independent of established prognostic factors in the advanced cancer setting. This objective and non-invasive tool may be useful for bedside prognostication. PMID:24899148

  2. 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)

  3. High USP22 expression indicates poor prognosis in hepatocellular carcinoma

    PubMed Central

    Yuan, Shengguang; Xu, Qing; Tomlinson, Stephen; Jin, Junfei; Hu, Wei; He, Songqing

    2015-01-01

    Ubiquitin-specific protease 22 (USP22) removes ubiquitin from histones, thus regulating gene transcription. The expression frequency and expression levels of USP22 were significantly higher in hepatocellular carcinoma (HCC) than in normal liver tissues. High USP22 expression in HCC was significantly correlated with clinical stage and tumor grade. Kaplan-Meier analysis showed that elevated USP22 expression predicted poorer overall survival and recurrence-free survival. High USP22 expression was also associated with shortened survival time in patients at advanced tumor stages and with high grade HCC. Multivariate analyses revealed that USP22 expression is an independent prognostic parameter in HCC. These findings provide evidence that high USP22 expression might be important in tumor progression and serves as an independent molecular marker for poor HCC prognosis. Thus, USP22 overexpression identifies patients at high risk and represents a novel therapeutic molecular target for this tumor. PMID:25909224

  4. Villin expression is frequently lost in poorly differentiated colon cancer.

    PubMed

    Arango, Diego; Al-Obaidi, Sheren; Williams, David S; Dopeso, Higinio; Mazzolini, Rocco; Corner, Georgia; Byun, Do-Sun; Carr, Azadeh A; Murone, Carmel; Tgel, Lars; Zeps, Nikolajs; Aaltonen, Lauri A; Iacopetta, Barry; Mariadason, John M

    2012-04-01

    Colorectal cancers (CRCs) are classified as having microsatellite instability (MSI) or chromosomal instability (CIN); herein termed microsatellite stable (MSS). MSI colon cancers frequently display a poorly differentiated histology for which the molecular basis is not well understood. Gene expression and immunohistochemical profiling of MSS and MSI CRC cell lines and tumors revealed significant down-regulation of the intestinal-specific cytoskeletal protein villin in MSI colon cancer, with complete absence in 62% and 17% of MSI cell lines and tumors, respectively. Investigation of 577 CRCs linked loss of villin expression to poorly differentiated histology in MSI and MSS tumors. Furthermore, mislocalization of villin from the membrane was prognostic for poorer outcome in MSS patients. Loss of villin expression was not due to coding sequence mutations, epigenetic inactivation, or promoter mutation. Conversely, in transient transfection assays villin promoter activity reflected endogenous villin expression, suggesting transcriptional control. A screen of gut-specific transcription factors revealed a significant correlation between expression of villin and the homeobox transcription factor Cdx-1. Cdx-1 overexpression induced villin promoter activity, Cdx-1 knockdown down-regulated endogenous villin expression, and deletion of a key Cdx-binding site within the villin promoter attenuated promoter activity. Loss of Cdx-1 expression in CRC lines was associated with Cdx-1 promoter methylation. These findings demonstrate that loss of villin expression due to Cdx-1 loss is a feature of poorly differentiated CRCs. PMID:22349300

  5. Pleomorphic xanthoastrocytoma in elderly patients may portend a poor prognosis.

    PubMed

    Ng, Wai Hoe; Lim, Tchoyoson; Yeo, Tseng Tsai

    2008-04-01

    Pleomorphic xanthoastrocytoma (PXA) is a rare primary astrocytic tumour of the nervous system usually involving the superficial temporal cortex of children and young adults. Although the tumour may exhibit histological features of pleomorphism or cellular atypia, the overall prognosis is good compared with other glial tumours, with only 30% of PXA recurring and 20% undergoing anaplastic transformation. Increased mitotic activity, high MIB-1 and proliferating cell nuclear antigen labelling indices and necrosis are poor prognostic factors, whereas abundant lymphocytic infiltration is associated with more benign biological behaviour. Rarely, in older patients, PXA may have a poor prognosis as these patients tend to have intracranial hypertension and focal deficits, as well as histological features of mitosis, increased cellularity and necrosis. We report the case of a 76-year-old woman who presented with dysphasia and right hemiparesis. A left fronto-temporal lobe PXA was misdiagnosed as glioblastoma multiforme. Although a rare and benign tumour type, PXA in the elderly tend to be more malignant, may have the radiological appearance of a malignant tumour and have poor prognosis. PMID:18255294

  6. Clinical significance of cytogenetic aberrations in bone marrow of patients with diffuse large B-cell lymphoma: prognostic significance and relevance to histologic involvement

    PubMed Central

    2013-01-01

    Background Although knowledge of the genetics of diffuse large B-cell lymphoma (DLBCL) has been increasing, little is known about the characteristics and prognostic significance of cytogenetic abnormalities and the clinical utility of cytogenetic studies performed on bone marrow (BM) specimens. To investigate the significance of isolated cytogenetic aberrations in the absence of histologic BM involvement, we assessed the implication of cytogenetic staging and prognostic stratification by a retrospective multicenter analysis of newly diagnosed DLBCL patients. Methods We analyzed cytogenetic and clinical data from 1585 DLBCL patients whose BM aspirates had been subjected to conventional karyotyping for staging. If available, interphase fluorescence in situ hybridization (FISH) data were also collected from patients. Results Histologic BM involvement were found in 259/1585 (16.3%) patients and chromosomal abnormalities were detected in 192 (12.1%) patients (54 patients with single abnormalities and 138 patients with 2 or more abnormalities). Isolated cytogenetic aberrations (2 or more abnormalities) without histologic involvement were found in 21 patients (1.3%). Two or more cytogenetic abnormalities were associated with inferior overall survival (OS) compared with a normal karyotype or single abnormality in both patients with histologic BM involvement (5-year OS, 16.5% vs. 52.7%; P < 0.001) and those without BM involvement (31.8% vs. 66.5%; P < 0.001). This result demonstrated that BM cytogenetic results have a significant prognostic impact that is independent of BM histology. The following abnormalities were most frequently observed: rearrangements involving 14q32, 19q13, 19p13, 1p, 3q27, and 8q24; del(6q); dup(1q); and trisomy 18. In univariate analysis, several specific abnormalities including abnormalities at 16q22-q24, 6p21-p25, 12q22-q24, and -17 were associated with poor prognosis. Multivariate analyses performed for patients who had either chromosomal abnormalities or histologic BM involvement, revealed IPI high risk, ? 2 cytogenetic abnormalities, and several specific chromosomal abnormalities, including abnormalities at 19p13, 12q22-q24, 8q24, and 19q13 were significantly associated with a worse prognosis. Conclusions We suggest that isolated cytogenetic aberrations can be regarded as BM involvement and cytogenetic evaluation of BM improves staging accuracy along with prognostic information for DLBCL patients. PMID:24220305

  7. Survival Outcomes According to Adjuvant Treatment and Prognostic Factors Including Host Immune Markers in Patients with Curatively Resected Ampulla of Vater Cancer

    PubMed Central

    Ha, Hye rim; Oh, Do-Youn; Kim, Tae-Yong; Lee, KyoungBun; Kim, Kyubo; Lee, Kyung-Hun; Han, Sae-Won; Chie, Eui Kyu; Jang, Jin-Young; Im, Seock-Ah; Kim, Tae-You; Kim, Sun-Whe; Bang, Yung-Jue

    2016-01-01

    Background Ampulla of Vater cancer (AoV Ca) is a rare tumor, and its adjuvant treatment has not been established. The purpose of this study was to find out prognostic factors including host immunity and role of adjuvant treatment in AoV Ca. Methods and Findings We reviewed 227 AoV Ca patients with curative resection. Clinical characteristics, adjuvant treatment, disease-free survival (DFS) and overall survival (OS) were analyzed. Among all patients, 63.9, 36.1 and 33.9% had T1/T2, T3/T4 stage and lymph node-positive disease (LN+), respectively. OS of all patients was 90.9 months (95% CI: 52.9–129.0). OS was different according to neutrophil-to-lymphocyte ratio (HR 1.651, 95% CI: 1.11–2.47), platelet-to-lymphocyte ratio (HR 1.488, 95% CI: 1.00–2.21) and systemic inflammatory index (HR 1.669, 95% CI: 1.13–2.47). In multivariate analysis, adverse prognostic factors for OS included vascular invasion (HR 2.571, 95% CI: 1.20–5.53) and elevated CA 19–9 (HR 1.794, 95% CI: 1.07–3.05). A total of 104 patients (46.3%) received adjuvant treatment (25 out of 111of T1/T2 & LN (-), 79 out of 116 of T3/T4 or LN (+)). In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the longest OS (5-year OS rate: 47.0 vs. 41.4%). Conclusions Vascular invasion and elevated CA 19–9 were adverse prognostic factors in resected AoV Ca. In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the best survival outcome. Adjuvant treatment should be further defined in AoV Ca, especially with poor prognostic factors. PMID:26974670

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

    MedlinePLUS

    ... for childhood leukemias 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 ...

  9. Proposal of a prognostically relevant grading scheme for pulmonary squamous cell carcinoma.

    PubMed

    Weichert, Wilko; Kossakowski, Claudia; Harms, Alexander; Schirmacher, Peter; Muley, Thomas; Dienemann, Hendrik; Warth, Arne

    2016-03-01

    Recent studies in lung adenocarcinoma established a clinically relevant histomorphology-based classification. In contrast, no morphological classifiers have yet been implemented into routine diagnostics for lung squamous cell carcinoma (SQCC). However, morphology-based characteristics putatively impacting on survival have been proposed.We analysed a cohort of 541 SQCC patients with complete clinical follow-up data for morphological characteristics (keratinisation, tumour cell budding, size of tumour cell nests, nuclear size and stromal content). Morphological characteristics were correlated with clinical data and patient outcome.Keratinisation, budding, stromal content and tumour cell nest size, but not nuclear size, were associated with distinct clinicopathological characteristics and survival. SQCC patients with keratinisation, small cell nest size, high stromal content and extensive budding had shorter overall survival. A combined grading scheme composed of the two most reliable validated prognostic markers, i.e. budding and nest size, resulted in an age-, stage- and sex-independent prognosticator for overall survival with a hazard ratio of 1.6 for grade 2 tumours and a hazard ratio of 3.7 for grade 3 tumours when compared with grade 1 neoplasms (p<0.001).Morphological characteristics of SQCC have significant prognostic impact and could constitute the basis for a diagnostically relevant future SQCC grading scheme. PMID:26541540

  10. Loss of Tumor Suppressor ARID1A Protein Expression Correlates with Poor Prognosis in Patients with Primary Breast Cancer

    PubMed Central

    Cho, Hyun Deuk; Lee, Jong Eun; Jung, Hae Yoen; Oh, Mee-Hye; Lee, Ji-Hye; Jang, Si-Hyong; Kim, Kyung-Ju; Han, Sun Wook; Kim, Sung Yong; Kim, Han Jo; Bae, Sang Byung

    2015-01-01

    Purpose Somatic mutations of the chromatin remodeling AT-rich interactive domain 1A (SWI-like) gene (ARID1A) have been identified in many human cancers, including breast cancer. The purpose of this study was to evaluate the nuclear expression of ARID1A in breast cancers by immunohistochemistry (IHC) and to correlate the findings to clinicopathologic variables including prognostic significance. Methods IHC was performed on tissue microarrays of 476 cases of breast cancer. Associations between ARID1A expression and clinicopathologic characteristics and molecular subtype were retrospectively analyzed. Results Low expression of ARID1A was found in 339 of 476 (71.2%) cases. Low expression of ARID1A significantly correlated with positive lymph node metastasis (p=0.027), advanced pathologic stage (p=0.001), low Ki-67 labeling index (p=0.003), and negative p53 expression (p=0.017). The ARID1A low expression group had significantly shorter disease-free and overall survival than the ARID1A high expression group (p<0.001 and p<0.001, respectively). Multivariate analysis demonstrated that low expression of ARID1A was a significant independent predictive factor for poor disease-free and overall survival in patients with breast cancer (disease-free survival: hazard ratio, 0.38, 95% confidence interval [CI], 0.20-0.73, p=0.004; overall survival: hazard ratio, 0.11, 95% CI, 0.03-0.46, p=0.003). In patients with luminal A type disease, patients with low ARID1A expression had significantly shorter disease-free and overall survival rates than patients with high ARID1A expression (p=0.022 and p=0.018, respectively). Conclusion Low expression of ARID1A is an independent prognostic factor for disease-free and overall survival in breast cancer patients and may be associated with luminal A type disease. Although the biologic function of ARID1A in breast cancer remains unknown, low expression of ARID1A can provide valuable prognostic information. PMID:26770240

  11. Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma

    PubMed Central

    Patard, Jean-Jacques; Fergelot, Patricia; Karakiewicz, Pierre I; Klatte, Tobias; Trinh, Quoc-Dien; Rioux-Leclercq, Nathalie; Said, Jonathan W; Belldegrun, Arie S; Pantuck, Allan J

    2008-01-01

    We attempted to describe, in a series of clear cell Renal Cell Carcinoma (RCC), the relationship between CAIX expression, VHL gene mutations, tumor characteristics and outcome. Radical nephrectomy was performed in 100 patients. Genomic DNA was extracted from frozen tumor samples. Four amplimers covering the whole coding sequence of the VHL gene were synthesized by PCR and sequenced. The monoclonal antibody M75 was used to score the expression of the CAIX protein immunohistochemically. VHL mutations were identified in 58 patients (58%) and high CAIX expression (>85%) was observed in 78 (78%). Tumors with VHL mutation showed higher CAIX expression than those without (p=0.02). Low CAIX expression and absence of VHL mutation were associated with a more advanced tumors e.g. higher T stages and presence of metastases. VHL mutation and high CAIX expression predicted longer progression-free survival (p=0.037) and disease-specific survival (p=0.001), respectively. In combination, they defined three prognostic groups (p=0.002): (1) good prognosis, defined as VHL mutation and high CAIX (2-year survival:86%), (2) intermediate prognosis with either VHL mutation or high CAIX (69%), and (3) poor prognosis with no VHL mutation and low CAIX (45%, median survival 18 months). CAIX expression, but not VHL mutational status, was an independent prognostic factor in multivariate analysis. Taken together, CAIX expression and VHL mutational status are able to stratify patients with clear cell RCC into distinct groups with regards to clinicopathological variables and prognosis, with low CAIX expression and absence of VHL mutation being associated with a poor clinicopathological phenotype and diminished survival. PMID:18464292

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

    PubMed Central

    Snchez-Aguilar, Martn; Morn-Mendoza, Onofre; Herrera-Hernndez, Miguel F; Hernndez-Sierra, Juan Francisco; Mandeville, Peter B; Tapia-Prez, J Humberto; Snchez-Reyna, Martn; Snchez-Rodrguez, Jos 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 casecontrol 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: 36.711.2 years) responded to medical treatment and 16 (41.811.6 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

  13. Triple negative breast cancers: clinical and prognostic implications.

    PubMed

    Dawson, S J; Provenzano, E; Caldas, C

    2009-09-01

    Triple negative breast cancers are defined by the absence of oestrogen, progesterone and HER2 expression. Most triple negative cancers display distinct clinical and pathological characteristics with a high proportion of these tumours occurring at a younger age of onset and in African-American women. Triple negative tumours typically demonstrate high histological grade and are the most common breast cancer subtype in BRCA1 carriers. In addition, many of the features of triple negative cancers are similar to those identified in the basal-like molecular subtype which has recently been characterised by gene expression profiling. Although the two groups overlap, they are not synonymous. Triple negative breast cancers are of pivotal clinical importance given the lack of therapeutic options. The prognostic significance of triple negative tumours remains unclear since the group is heterogeneous and worst prognosis seems to be mostly confined to those that express basal cytokeratins or epidermal growth factor receptor (EGFR). This review focuses on outlining the pathological, molecular, and clinical features of triple negative breast cancers, discusses its prognostic value and summarises current therapeutic approaches and future directions of research. PMID:19775602

  14. Pretreatment Neutrophil to Lymphocyte Ratio as a Prognostic Predictor of Urologic Tumors

    PubMed Central

    Luo, You; She, Dong-Li; Xiong, Hu; Fu, Sheng-Jun; Yang, Li

    2015-01-01

    Abstract The relationship between inflammation and tumor development and progression has been recognized in recent decades. NLR is an easily reproducible and widely used inflammatory response marker. The prognostic value of NLR for urologic tumors has been reported in succession. Here, we perform a systematic review and meta-analysis to summarize the association between the NLR and prognosis of urologic tumors. We conducted a computerized search of PubMed, Embase, and ISI Web of Knowledge to identify clinical studies that had evaluated the association between the pretreatment NLR and prognosis in urologic tumors. Prognostic outcomes included overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), progression-free survival (PFS), and metastasis-free survival (MFS). We extracted and synthesized corresponding hazard ratios (HRs) and confidence intervals (CIs) using Review Manager 5.3 and STATA 13. We identified 34 retrospective cohort studies and conducted the meta-analysis. The results showed that all OS, CSS, RFS, PFS, and MFS risks were significantly different between patients with an elevated NLR and those with a low NLR in various urologic tumors. A high NLR portended poor prognosis. However, no significance was observed for CSS in patients with renal cell carcinoma (HR?=?1.38, 95% CI: 0.961.99). Our meta-analysis suggests that NLR could be a prognostic predictor for urologic tumors. Patients with a high NLR were deemed to have a poor prognosis. PMID:26448011

  15. Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients.

    PubMed

    Martinho, Olga; Simes, Kleber; Longatto-Filho, Adhemar; Jacob, Carlos Eduardo; Zilberstein, Bruno; Bresciani, Cludio; Gama-Rodrigues, Joaquim; Cecconello, Ivan; Alves, Venncio; Reis, Rui Manuel

    2013-02-01

    Gastric cancer is a leading cause of cancer-related mortality, and the presence of lymph node metastasis an important prognostic factor. Downregulation of RKIP has been associated with tumor progression and metastasis in several types of neoplasms, being currently categorized as a metastasis suppressor gene. Our aim was to determine the expression levels of RKIP in gastric tissues and to evaluate its impact in the clinical outcome of gastric carcinoma patients. RKIP expression levels were studied by immunohistochemistry in a series of gastric tissues. Overall, we analysed 222 non-neoplastic gastric tissues, 152 primary tumors and 42 lymph node metastasis samples. We observed that RKIP was highly expressed in ~83% of non-neoplastic tissues (including normal tissue and metaplasia), was lost in ~56% of primary tumors and in ~90% of lymph node metastasis samples. Loss of RKIP expression was significantly associated with several markers of poor clinical outcome, including the presence of lymph node metastasis. Furthermore, the absence of RKIP protein constitutes an independent prognostic marker for these patients. In conclusion, RKIP expression is significantly lost during gastric carcinoma progression being almost absent in lymph node metastasis samples. Of note, we showed that the absence of RKIP expression is associated with poor outcome features of gastric cancer patients, this being also an independent prognostic marker. PMID:23232914

  16. Prognostic factors in tongue cancer relative importance of demographic, clinical and histopathological factors

    PubMed Central

    Kantola, S; Parikka, M; Jokinen, K; Hyrynkangs, K; Soini, Y; Alho, O-P; Salo, T

    2000-01-01

    The incidence of and mortality from squamous cell carcinoma (SCC) of the tongue have increased during the recent decades in the Western world. Much effort has been made to predict tumour behaviour, but we still lack specific prognostic indicators. The aim of our study was to evaluate the relative importance of the known demographic, clinical and histological factors in a homogeneous population-based group of patients with SCC of the mobile tongue. The demographic and clinical factors were reviewed retrospectively from primary and tertiary care patient files. Histological prognostic factors were determined from pre-treatment biopsies. The TNM stage was found to be the most important prognostic factor. In particular, local spread outside the tongue rather than spread to regional lymph nodes was related to poor prognosis. Several demographic and histopathological factors were closely related to TNM stage. When the cases were divided into stage III carcinomas and stage IIIIV carcinomas, it appeared that the patients older age (> 65 years), a high malignancy score and an absence of overexpressed p53 protein were associated with a poorer prognosis in stage III carcinomas. Such cases may require more aggressive treatment. Among patients with stage IIIIV carcinomas, heavy use of alcohol was significantly associated with a poor disease-specific survival time. 2000 Cancer Research Campaign PMID:10944601

  17. Prognostic Impact of Hyaluronan and Its Regulators in Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Cheng, Xiao-Bo; Sato, Norihiro; Kohi, Shiro; Yamaguchi, Koji

    2013-01-01

    Background Although pancreatic ductal adenocarcinoma is characterized by an abundant stroma enriched with hyaluronan (HA), the prognostic impact of HA and its regulators remains unknown. Methods Using immunohistochemistry, expression patterns of HA and its regulators, including a synthesizing enzyme (HAS2), and a degrading enzyme (HYAL1) were investigated in patients who received surgical resection. The prognostic significance of these markers and other clinicopathological variables was determined using univariate and multivariate analyses. The HA levels were determined quantitatively by enzyme-linked immunosorbent assay (ELISA). Results We found that strong expressions of HA (P=0.008) and HAS2 (P=0.022) were significantly associated with shorter survival time after surgery. By contrast, weak expression of HYAL1 was significantly associated with poor survival (P=0.001). In multivariate analysis, tumor stage (hazard ratio (HR)=2.76, 95% confidence interval (CI): 1.14-6.66 P=0.024), strong HA expression (HR=6.04, 95%CI: 1.42-25.69 P=0.015), and weak HYAL1 expression (HR=3.16, 95%CI: 1.19-8.40 P=0.021) were independent factors predicting poor survival. ELISA revealed higher concentration of HA in pancreatic cancer tissues than in normal pancreatic tissues (P=0.001). Conclusion These findings suggest, for the first time, that HA and its regulators may have prognostic impact in patients with pancreatic cancer. PMID:24244714

  18. Imaging features of poorly controlled congenital adrenal hyperplasia in adults.

    PubMed

    Kok, H K; Sherlock, M; Healy, N A; Doody, O; Govender, P; Torreggiani, W C

    2015-09-01

    Congenital adrenal hyperplasia (CAH) is a genetic autosomal recessive condition most frequently as a result of a mutation in the 21-hydroxylase enzyme gene. Patients with poorly controlled CAH can manifest characteristic imaging findings as a result of adrenocorticotrophic hormone stimulation or the effects of cortisol precursor excess on various target organs. We present a spectrum of imaging findings encountered in adult patients with poorly treated CAH, with an emphasis on radiological features and their clinical relevance. PMID:26133223

  19. Seven poor clusters of galaxies

    NASA Technical Reports Server (NTRS)

    Beers, T. C.; Geller, M. J.; Huchra, J. P.; Latham, D. W.; Davis, R. J.

    1984-01-01

    The measurement of 83 new redshifts from galaxies in the region of seven of the poor clusters of galaxies identified by Morgan et al (1975) and Albert et al (1977) has been followed by an estimation of cluster masses through the application of both the virial theorem and the projected mas method. For each system, these two estimates are consistent. For the two clusters with highest X-ray luminosities, the line-of-sight velocity dispersions are about 700 km/sec, while for the five other clusters, the dispersions are of the order of less than about 370 km/sec. The D or cD galaxy in each poor cluster is at the kinematic center of each system.

  20. snoRNPs Regulate Telomerase Activity in Neuroblastoma and Are Associated with Poor Prognosis.

    PubMed

    von Stedingk, Kristoffer; Koster, Jan; Piqueras, Marta; Noguera, Rosa; Navarro, Samuel; Phlman, Sven; Versteeg, Rogier; Ora, Ingrid; Gisselsson, David; Lindgren, David; Axelson, Hkan

    2013-08-01

    Amplification of the MYCN oncogene is strongly associated with poor prognosis in neuroblastoma (NB). In addition to MYCN amplification, many studies have focused on identifying patients with a poor prognosis based on gene expression profiling. The majority of prognostic signatures today are comprised of large gene lists limiting their clinical application. In addition, although of prognostic significance, most of these signatures fail to identify cellular processes that can explain their relation to prognosis. Here, we determined prognostically predictive genes in a data set containing 251 NBs. Gene Ontology analysis was performed on significant genes with a positive hazard ratio to search for cellular processes associated with poor prognosis. An enrichment in ribonucleoproteins (RNPs) was found. Genes involved in the stabilization and formation of the central small nucleolar RNP (snoRNP) complex were scrutinized using a backward conditional Cox regression resulting in an snoRNP signature consisting of three genes: DKC1, NHP2, and GAR1. The snoRNP signature significantly and independently predicted prognosis when compared to the established clinical risk factors. Association of snoRNP protein expression and prognosis was confirmed using tissue micro-arrays. Knockdown of snoRNP expression in NB cell lines resulted in reduced telomerase activity and an increase in anaphase bridge frequency. In addition, in patient material, expression of the snoRNP complex was significantly associated with telomerase activity, occurrence of segmental aberrations, and expression-based measurements of chromosomal instability. Together, these results underscore the prognostic value of snoRNP complex expression in NB and suggest a role for snoRNPs in telomere maintenance and genomic stability. PMID:23908688

  1. snoRNPs Regulate Telomerase Activity in Neuroblastoma and Are Associated with Poor Prognosis12

    PubMed Central

    von Stedingk, Kristoffer; Koster, Jan; Piqueras, Marta; Noguera, Rosa; Navarro, Samuel; Phlman, Sven; Versteeg, Rogier; ra, Ingrid; Gisselsson, David; Lindgren, David; Axelson, Hkan

    2013-01-01

    Amplification of the MYCN oncogene is strongly associated with poor prognosis in neuroblastoma (NB). In addition to MYCN amplification, many studies have focused on identifying patients with a poor prognosis based on gene expression profiling. The majority of prognostic signatures today are comprised of large gene lists limiting their clinical application. In addition, although of prognostic significance, most of these signatures fail to identify cellular processes that can explain their relation to prognosis. Here, we determined prognostically predictive genes in a data set containing 251 NBs. Gene Ontology analysis was performed on significant genes with a positive hazard ratio to search for cellular processes associated with poor prognosis. An enrichment in ribonucleoproteins (RNPs) was found. Genes involved in the stabilization and formation of the central small nucleolar RNP (snoRNP) complex were scrutinized using a backward conditional Cox regression resulting in an snoRNP signature consisting of three genes: DKC1, NHP2, and GAR1. The snoRNP signature significantly and independently predicted prognosis when compared to the established clinical risk factors. Association of snoRNP protein expression and prognosis was confirmed using tissue micro-arrays. Knockdown of snoRNP expression in NB cell lines resulted in reduced telomerase activity and an increase in anaphase bridge frequency. In addition, in patient material, expression of the snoRNP complex was significantly associated with telomerase activity, occurrence of segmental aberrations, and expression-based measurements of chromosomal instability. Together, these results underscore the prognostic value of snoRNP complex expression in NB and suggest a role for snoRNPs in telomere maintenance and genomic stability. PMID:23908688

  2. 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.

  3. 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.

  4. DGKI Methylation Status Modulates the Prognostic Value of MGMT in Glioblastoma Patients Treated with Combined Radio-Chemotherapy with Temozolomide

    PubMed Central

    Idbaih, Ahmed; Vauleon, Elodie; Marie, Yannick; Menei, Philippe; Boniface, Rachel; Figarella-Branger, Dominique; Karayan-Tapon, Lucie; Quillien, Veronique; Sanson, Marc; de Tayrac, Marie; Delattre, Jean-Yves; Mosser, Jean

    2014-01-01

    Background Consistently reported prognostic factors for glioblastoma (GBM) are age, extent of surgery, performance status, IDH1 mutational status, and MGMT promoter methylation status. We aimed to integrate biological and clinical prognostic factors into a nomogram intended to predict the survival time of an individual GBM patient treated with a standard regimen. In a previous study we showed that the methylation status of the DGKI promoter identified patients with MGMT-methylated tumors that responded poorly to the standard regimen. We further evaluated the potential prognostic value of DGKI methylation status. Methods 399 patients with newly diagnosed GBM and treated with a standard regimen were retrospectively included in this study. Survival modelling was performed on two patient populations: intention-to-treat population of all included patients (population 1) and MGMT-methylated patients (population 2). Cox proportional hazard models were fitted to identify the main prognostic factors. A nomogram was developed for population 1. The prognostic value of DGKI promoter methylation status was evaluated on population 1 and population 2. Results The nomogram-based stratification of the cohort identified two risk groups (high/low) with significantly different median survival. We validated the prognostic value of DGKI methylation status for MGMT-methylated patients. We also demonstrated that the DGKI methylation status identified 22% of poorly responding patients in the low-risk group defined by the nomogram. Conclusions Our results improve the conventional MGMT stratification of GBM patients receiving standard treatment. These results could help the interpretation of published or ongoing clinical trial outcomes and refine patient recruitment in the future. PMID:25233099

  5. Prognostic value of caveolin-1 in genitourinary cancer: a meta-analysis

    PubMed Central

    Liu, Jia-Ming; Cheng, Si-Hang; Liu, Xiao-Xiao; Xia, Chao; Wang, Wei-Wen; Ma, Xue-Lei

    2015-01-01

    We aimed to obtain the most comprehensive picture to date of the prognostic value of caveolin-1 (Cav-1) in genitourinary carcinoma by meta-analyzing all eligible studies in PubMed and EMBASE. Data on patient clinical characteristics, cancer-specific survival (CSS) and recurrence-free survival (RFS) were extracted. The meta-analysis included 6 articles on prostate cancer, 5 on renal cancer, 1 on bladder cancer and 1 on transition cell carcinoma of the upper urinary tract. Two studies examining the association of ELISA-measured Cav-1 levels in serum with RFS in 621 patients with prostate cancer gave a combined hazard ratio (HR) of 1.25 (95% CI 0.36 to 4.36). The other 4 studies on prostate cancer examined the association of immunohistochemically determined Cav-1 levels in cancerous tissue with RFS and gave a combined HR of 1.83 (95% CI 1.36 to 2.47). Three studies on renal cancer examining the association of Cav-1 levels with CSS gave a multivariate HR of 1.98 (95% CI 1.35 to 2.90). The single studies on bladder carcinoma and upper urinary tract carcinoma gave, respectively, a multivariate HR of 2.28 (95% CI 1.09 to 4.74) for the relationship of Cav-1 levels to DFS, and a multivariate HR of 5.08 (95% CI 1.799 to 14.342) for the relationship of Cav-1 levels to CSS. This meta-analysis of available evidence suggests that elevated Cav-1 levels in serum can predict poor survival in patients with genitourinary cancer, which may help identify high-risk patients earlier and guide clinical decision-making. PMID:26884999

  6. Serum HE4: An Independent Prognostic Factor in Non-Small Cell Lung Cancer

    PubMed Central

    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. PMID:26030627

  7. The use of transcranial magnetic stimulation in diagnosis, prognostication and treatment evaluation in multiple sclerosis.

    PubMed

    Simpson, Marion; Macdonell, Richard

    2015-09-01

    Despite advances in brain imaging which have revolutionised the diagnosis and monitoring of patients with Multiple Sclerosis (MS), current imaging techniques have limitations, including poor correlation with clinical disability and prognosis. There is growing evidence that electrophysiological techniques may provide complementary functional information which can aid in diagnosis, prognostication and perhaps even monitoring of treatment response in patients with MS. Transcranial magnetic stimulation (TMS) is an underutilised technique with potential to assist diagnosis, predict prognosis and provide an objective surrogate marker of clinical progress and treatment response. This review explores the existing body of evidence relating to the use of TMS in patients with MS, outlines the practical aspects and scope of TMS testing and reviews the current evidence relating to the use of TMS in diagnosis, disease classification, prognostication and response to symptomatic and disease-modifying therapies. PMID:26346791

  8. Squamous cell carcinoma of the vagina: natural history, treatment modalities and prognostic factors.

    PubMed

    Gadducci, Angiolo; Fabrini, Maria Grazia; Lanfredini, Nora; Sergiampietri, Claudia

    2015-03-01

    Squamous cell carcinoma of the vagina accounts for less than 2% of all gynecologic malignancies. Surgery has a role in selected cases only. The standard treatment is radiotherapy, external beam radiation and/or brachytherapy, depending on the extent, thickness, location and morphology of the lesion. The role of chemotherapy is still under evaluation. Radiotherapy obtained 5-year overall survival rates ranged from 35% to 78%, with severe late complication rates of 9.4-23.1%. Tumor stage is the strongest prognostic factor. Tumor size >4cm, tumor location outside the upper third of the vagina, and old age at presentation are additional predictors of poor survival in most papers, whereas the prognostic value of histological grade, prior hysterectomy, and hemoglobin levels is controversial. High-risk HPV DNA and low MIB-1 index are associated with better clinical outcome. Because of the rarity of this tumor, future multicenter studies would be strongly warranted. PMID:25476235

  9. A simple and effective prognostic staging system based on clinicopathologic features of intrahepatic cholangiocarcinoma

    PubMed Central

    Zhou, Huabang; Jiang, Xiaolan; Li, Qiaomei; Hu, Jingyi; Zhong, Zhengrong; Wang, Hao; Wang, Hui; Yang, Bing; Hu, Heping

    2015-01-01

    Incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing. However, its prognostic predictive system associated with outcome after surgery remains poorly defined. In this study, we conducted retrospective survival analyses in a primary cohort of 370 patients who underwent partial hepatectomy for ICC (2005 and 2009). We found that seven variables were significantly independent predictors for overall survival (OS): serum prealbumin (hazard ratio [HR]: 1.447; p = 0.015), carbohydrate antigen 19-9 (HR: 1.438; p = 0.009), carcinoembryonic antigen (HR: 1.732; p = 0.002), tumor number (HR: 1.781; p < 0.001), vascular invasion (HR: 1.784; p < 0.001), regional lymphatic metastasis (HR: 2.003; p < 0.001) and local extrahepatic metastasis (HR: 1.506; p = 0.008). Using these independent predictors, we created a simple clinicopathologic prognostic staging system for predicting survival of ICC patients after resection. The validity of the prognostic staging system was prospectively assessed in 115 patients who underwent partial hepatectomy between January 2010 and December 2010 at the same institution. The prognostic power was quantified using likelihood ratio test and Akaike information criteria. Compared with the 6th and 7th AJCC staging systems, the new staging system in the primary cohort had a higher predictive accuracy for OS in terms of homogeneity and discriminatory ability. In the validation cohort, the homogeneity and discrimination of the new staging system were also superior to the two other staging systems. Conclusions: The new staging system based on clinicopathologic features may provide relatively higher accuracy in prognostic prediction for ICC patients after tumor resection. PMID:26175951

  10. Distinct prognostic values of ALDH1 isoenzymes in breast cancer.

    PubMed

    Wu, Shaokun; Xue, Weiping; Huang, Xiaobo; Yu, Xiaoli; Luo, Ming; Huang, Ying; Liu, Yimin; Bi, Zhuofei; Qiu, Xingsheng; Bai, Shoumin

    2015-04-01

    Aldehyde dehydrogenase 1 (ALDH1), also known as aldehyde dehydrogenase 1 family, is composed of six enzymes that are expressed at high levels in stem cells and are involved in the regulation of stem cell function. Increased ALDH1 activity has been found in the stem cell populations of leukemia and some solid tumors including breast cancer (BC). However, which ALDH1's isoenzymes are contributing to ALDH1 activity has not been determined. In addition, the prognostic value of individual ALDH1 isoenzyme is not clear. In the current study, we investigated the prognostic value of ALDH1 isoenzymes in BC patients through "the Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information are from a total of 3455 BC patients. ALDH1A1 messenger RNA (mRNA) high expression was found to be correlated to worsen overall survival (OS) for all BC patients. ALDH1A2 and ALDH1L1 mRNA high expressions were found to be correlated to better OS for all BC patients. Both of ALDH1A3 and ALDH1B1 mRNA high expressions were not found to be correlated to OS for all BC patients. These results strongly support that ALDH1A1 was only a biomarker for predicting poor survival of BC patients among ALDH1 isoenzymes. ALDH1A1 might be a major contributor of ALDH1 activity in BC, since only ALDH1A1 mRNA high expression was found to be significantly correlated to worsen OS for all BC patients. PMID:25582316

  11. Expression and prognostic role of SKIP in human breast carcinoma.

    PubMed

    Liu, Xiaobing; Ni, Qichao; Xu, Junfei; Sheng, Chenyi; Wang, Qingqing; Chen, Jinpeng; Yang, Shuyun; Wang, Hua

    2014-04-01

    Ski-interacting protein (SKIP) is a nuclear hormone receptor-interacting cofactor, interactions with the proto-oncogene Ski, appears to modulate a number of signalling pathways involved in control of cell proliferation and differentiation, and may play a critical role in oncogenesis. In the present study, to investigate the potential roles of SKIP in breast cancer, expression patterns, interaction and the correlation with clinical/prognostic factors of SKIP and Ki-67 were examined among patients with breast cancer. Immunohistochemistry and Western blot analysis were performed for SKIP in 85 breast carcinoma samples. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance. We found that SKIP was over expressed in breast carcinoma as compared with the adjacent normal tissues. High expression of SKIP was positively associated with histological grade (P = 0.01) and Ki-67 (P = 0.004). Univariate analysis showed that SKIP expression was associated with a poor prognosis (P = 0.006). While in vitro, following release of breast cancer cell lines from serum starvation, the expression of SKIP was up-regulated, whereas p27 was down-regulated. In addition, we employed small interfering RNA (siRNA) technique to knock down SKIP expression and observed it effects on MDA-MB-231 cells growth. SKIP depletion by siRNA inhibited cell proliferation, blocked S phase and decreased cyclin A and cyclin B levels. On the basis of these results, we suggested that SKIP overexpression was involved in the pathogenesis of breast cancer, which might serve as a future target for breast cancer. PMID:24150787

  12. Patient-Specific Data Fusion Defines Prognostic Cancer Subtypes

    PubMed Central

    Markowetz, Florian

    2011-01-01

    Different data types can offer complementary perspectives on the same biological phenomenon. In cancer studies, for example, data on copy number alterations indicate losses and amplifications of genomic regions in tumours, while transcriptomic data point to the impact of genomic and environmental events on the internal wiring of the cell. Fusing different data provides a more comprehensive model of the cancer cell than that offered by any single type. However, biological signals in different patients exhibit diverse degrees of concordance due to cancer heterogeneity and inherent noise in the measurements. This is a particularly important issue in cancer subtype discovery, where personalised strategies to guide therapy are of vital importance. We present a nonparametric Bayesian model for discovering prognostic cancer subtypes by integrating gene expression and copy number variation data. Our model is constructed from a hierarchy of Dirichlet Processes and addresses three key challenges in data fusion: (i) To separate concordant from discordant signals, (ii) to select informative features, (iii) to estimate the number of disease subtypes. Concordance of signals is assessed individually for each patient, giving us an additional level of insight into the underlying disease structure. We exemplify the power of our model in prostate cancer and breast cancer and show that it outperforms competing methods. In the prostate cancer data, we identify an entirely new subtype with extremely poor survival outcome and show how other analyses fail to detect it. In the breast cancer data, we find subtypes with superior prognostic value by using the concordant results. These discoveries were crucially dependent on our model's ability to distinguish concordant and discordant signals within each patient sample, and would otherwise have been missed. We therefore demonstrate the importance of taking a patient-specific approach, using highly-flexible nonparametric Bayesian methods. PMID:22028636

  13. 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. PMID:26385324

  14. A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma.

    PubMed

    Perry, Anamarija M; Cardesa-Salzmann, Teresa M; Meyer, Paul N; Colomo, Luis; Smith, Lynette M; Fu, Kai; Greiner, Timothy C; Delabie, Jan; Gascoyne, Randy D; Rimsza, Lisa; Jaffe, Elaine S; Ott, German; Rosenwald, Andreas; Braziel, Rita M; Tubbs, Raymond; Cook, James R; Staudt, Louis M; Connors, Joseph M; Sehn, Laurie H; Vose, Julie M; López-Guillermo, Armando; Campo, Elias; Chan, Wing C; Weisenburger, Dennis D

    2012-09-13

    Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell-like subtype, SPARC (secreted protein, acidic, and rich in cysteine) < 5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies. PMID:22740447

  15. Expression profile and prognostic value of glypican-3 in post-operative South Korean hepatocellular carcinoma patients.

    PubMed

    Jeon, Yejoo; Kim, Haeryoung; Jang, Eun Sun; Hong, Sukho; Kim, Jin Wook; Yoon, Yoo-Seok; Cho, Jai Young; Han, Ho-Seong; Jeong, Sook-Hyang

    2016-03-01

    Hepatocellular carcinoma (HCC) patients commonly experience poor overall survival (OS) and disease-free survival (DFS) after curative surgical resection. Glypican-3 (GPC3) has been suggested as a prognostic biomarker for post-operative survival. However, few to none of these studies have included South Korean patients. This study aimed to determine GPC3 expression rate, clinical correlation, and post-operative prognostic value in South Korean HCC patients who underwent curative surgical resection. Surgically resected tissues from 185 HCC patients were collected and assembled into tissue microarrays (TMAs), which were stained for GPC3 by immunohistochemistry. GPC3 expression rates were correlated with clinicopathological information, and survival analyses were performed to assess the prognostic value of GPC3. GPC3 expression was present in 153 patients (82.7%). GPC3-positive patients were younger with higher frequencies of microvascular invasion and higher AFP levels than GPC3-negative patients. There was no significant difference in survival between GPC3-negative and GPC3-positive patients. Based on multivariate analysis, GPC3 expression was not a prognostic marker for post-operative survival. In South Korean HCC patients, GPC3 expression was more frequent in HCCs with aggressive features, but it was not an independent prognostic biomarker. PMID:26764243

  16. Prognostic Typing in Breast Cancer

    PubMed Central

    Hartveit, F.

    1971-01-01

    Infiltrating breast carcinomas in which recurrence takes place 10 years or more after operation are reported to contain tumour cells of characteristic morphology. The cytological features of these tumour cells form the basis of the system of classification described here. Three cytological types are recognized, prognosis being best in type III. Typing is carried out on specimens stained with haematoxylin and eosin. The results of typing were reproducible in over 90% of cases and independent of the histology of the lesion. Correlation to survival time was shown in a total of 222 cases. ImagesFIG. 1 PMID:4107964

  17. Prognostic Implications of Primary Tumor Resection in Stage IVB Colorectal Cancer in Elderly Patients

    PubMed Central

    Ahn, Heui-June; Oh, Ho-Suk; Ahn, Yongchel; Lee, Sang Jin; Kim, Hyun Joong; Kim, Moon Ho; Eom, Dae-Woon; Kwak, Jae Young; Han, Myoung Sik

    2014-01-01

    Purpose The aim of this study was to identify prognostic factors in stage IVB colorectal cancer in elderly patients, focusing on the influence of treatment modalities, including palliative chemotherapy and primary tumor resection. Methods A cohort of 64 patients aged over 65 years who presented with stage IVB colorectal cancer at the Gangneung Asan Hospital between July 1, 2001, and December 31, 2009, was analyzed. Demographics, tumor location, tumor grade, performance status, levels of carcinoembryonic antigen (CEA), level of aspartate aminotransferase (AST), and distant metastatic site at diagnosis were analyzed. Using the treatment histories, we analyzed the prognostic implications of palliative chemotherapy and surgical resection of the primary tumor retrospectively. Results The cohort consisted of 30 male (46.9%) and 34 female patients (53.1%); the median age was 76.5 years. Primary tumor resection was done on 28 patients (43.8%); 36 patients (56.2%) were categorized in the nonresection group. The median survival times were 12.43 months in the resection group and 3.58 months in the nonresection group (P < 0.001). Gender, level of CEA, level of AST, Eastern Cooperative Oncology Group performance status, tumor location, and presence of liver metastasis also showed significant differences in overall survival. On multivariate analysis, male gender, higher level of CEA, higher AST level, and no primary tumor resection were independent poor prognostic factors. In particular, nonresection of the primary tumor was the most potent/poor prognostic factor in the elderly-patient study group (P = 0.001; 95% confidence interval, 2.33 to 21.99; hazard ratio, 7.16). Conclusion In stage IVB colorectal cancer in elderly patients, resection of the primary tumor may enhance survival. PMID:25210686

  18. The Prognostic Significance of Neuroendocrine Differentiation in Colorectal Carcinomas: Our Experience

    PubMed Central

    Suresh, Pooja Kundapur; Pai, Radha Ramachandra; Sridevi, Hanaganahalli Basaviah; Ballal, Kirthinath; Khandelia, Binit; Minal, Jessica; Annappa, Rajendra

    2015-01-01

    Introduction Neuroendocrine differentiation in colorectal carcinomas, detected using immunohistochemistry and ultrastructural techniques, has been studied as a prognostic marker for invention of targeted therapy. There are a few studies done on this aspect which have shown conflicting results ranging from poor prognosis to no prognostic significance. Aim The aim of the study was to determine the clinical significance of neuroendocrine differentiation in colorectal carcinomas using immunohistochemical stains such as chromogranin A & synaptophysin in relation to its prognostic significance. Materials and Methods A retrospective study was conducted wherein all the colorectal carcinomas, received in the Department of Pathology, over a period of 3 years, were reviewed. Neuroendocrine markers were done on 53 cases of moderately, poorly and undifferentiated adenocarcinomas. Based on the degree of immunoreactivity for these markers, tumours were divided into group 0, group 1, group 2, group 3 & group 4. Group 0 & 1 were categorized as neuroendocrine differentiation absent & group 2, 3 & 4 as present. Neuroendocrine differentiation was correlated with age, sex, grade, stage, diagnosis & survival. Follow up data of the cases was recorded. Results Neuroendocrine differentiation was present in 18 cases (33.9%). The degree of immunoreactivity for neuroendocrine markers in present study were; group 0- 58%, 1- 7.5%, 2- 9%, 3- 13% & 4- 11%. The mean age of patients was 54 years with a slight male preponderance {M:F::1.6:1}. Most of the carcinomas with neuroendocrine differentiation belonged to Grade II (61%) & Stage II & III (83%). Neuroendocrine differentiation did not show any significant association with age, sex, location, histological type, grade, stage & survival. Conclusion The above results indicate that the presence of neuroendocrine differentiation cannot be recommended as a prognostic marker in colorectal carcinomas. PMID:26816894

  19. Significance of Tumor Length as Prognostic Factor for Esophageal Cancer

    PubMed Central

    Zeybek, Arife; Erdo?an, Abdullah; Glkesen, Kemal Hakan; Ergin, Makbule; Sarper, Alpay; Dertsiz, Levent; Demircan, Abid

    2013-01-01

    Our study indicated the relationship between tumor length and clinicopathologic characteristics as well as long-term survival in esophageal cancer. A total of 116 patients who underwent curative surgery for thoracic esophageal cancer with standard lymphadenectomy in 2 fields between 2000 and 2010 were included in the study. The medical records of these patients were retrospectively reviewed. The patients with tumor length ?3 cm had a highly significant difference in the involvement of adventitia and lymph node stations. The patients with tumor length ?3 cm had significantly lower rates of involvement of the adventitia and lymph node stations. Tumor length could have a significant impact on both the overall survival and disease-free survival of patients with resected esophageal carcinomas and may provide additional prognostic value to the current tumor, node, and metastasis staging system before patients receive any cancer-specific treatment. PMID:23971777

  20. Why are the many poor?

    PubMed

    Townsend, P

    1986-01-01

    In this article the author restates the same arguments put forward in the first Fabian Tract of 1884 entitled Why Are the Many Poor? Today, mass poverty is still the central problem facing the British nation and all nations. The only long-term remedy is to restrict the power and wealth of the rich, to dismantle the present structures of social privilege, and to build social institutions based on fair allocation of wealth and on social equality. The public debate of one hundred years ago on the connections between poverty and wealth is revived in this article. PMID:3957507

  1. 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.

  2. 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. PMID:23178213

  3. Livestock services and the poor.

    PubMed

    Ahuja, V; Redmond, E

    2004-04-01

    This paper reviews the economic framework for the delivery of livestock services to the poor. It is argued that the demand for livestock products is likely to increase rapidly and the ability of the poor to participate in the opportunities presented by this growth is linked critically to the availability of good service support, both on the input and output side. Governments therefore have a responsibility to supply the necessary public goods (including the institutions and legal frameworks), and the market infrastructure for facilitating the emergence of efficient markets for livestock services. The paper further argues that the dynamics of public policy in developing countries are much more complex than the simple application of economic logic. It is the larger political economy that often dictates policy choices. It is therefore important to integrate political economy and governance issues into the economic debate on livestock service delivery. The paper also reviews the context in which the markets for livestock services will need to function. Different countries are facing very different sets of issues, and the identification of possible interventions in livestock service markets would require careful field research and analysis. In this context, the paper suggests the elements of a research agenda for the next few years. PMID:15080541

  4. Mutations in residues of TP53 that directly contact DNA predict poor outcome in human primary breast cancer.

    PubMed Central

    Berns, E. M.; van Staveren, I. L.; Look, M. P.; Smid, M.; Klijn, J. G.; Foekens, J. A.

    1998-01-01

    The tumour-suppressor gene TP53 is frequently mutated in breast tumours, and the majority of the mutations are clustered within the core domain, the region involved in DNA binding. We searched for alterations in this central domain of the TP53gene in 222 human breast cancer specimens using polymerase chain reaction-single-strand conformation analysis (PCR-SSCA) followed by sequencing. TP53 gene mutations were observed in 66 tumours (31%), including three tumours that contain two mutations. Fifty-four (78%) of these mutations were missense point mutations, one was a nonsense mutation and four were deletions and/or insertions causing disruption of the protein reading frame, whereas four mutations were either silent or a polymorphism (at codon 213; n = 6). Interestingly, the majority of missense mutations were observed at codon 248. The outcome has been related with patient and tumour characteristics, and with prognosis in 177 patients who were eligible for analysis of both relapse-free and overall survival (median survival for patients alive was 115 months). There was no significant association between the frequency of TP53 mutations and menopausal or nodal status, or tumour size. In a Cox univariate analysis, TP53 gene mutation was significantly associated with poor relapse-free survival (RFS: P = 0.02) but not with overall survival (OS: P = 0.07). In a Cox multivariate analysis, including classical prognostic factors, TP53 gene mutation independently predicted poor RFS and OS (RHR = 1.8 and 1.6 respectively). Unexpectedly, the median relapse-free survival of patients with a polymorphism at codon 213 or with a silent mutation was shorter (median 11 months) than the median relapse-free survival of patients with or without a TP53 gene mutation (median 34 or 48 months respectively). In an exploratory subset analysis, mutations in codons that directly contact DNA were related with the poorest relapse-free (P < 0.05) and overall survival (P < 0.02). These data imply that in the analysis of the prognostic value of TP53, the type of mutation and its biological function should be considered. PMID:9569050

  5. What Number of Oocytes Is Appropriate for Defining Poor Ovarian Response?

    PubMed Central

    Kim, Seul Ki; Lee, Jung Ryeol; Suh, Chang Suk; Kim, Seok Hyun

    2015-01-01

    Purpose This study attempted to derive an objective and sophisticated definition of poor ovarian response (POR). Materials and Methods A total of 176 consecutive in vitro fertilization (IVF) cycles (137 patients) with conventional ovarian stimulation during 2009 to 2012 were studied by retrospective analysis. Optimal oocyte number (total or mature) was determined by statistics-based (distribution of oocyte number) and prognosis-based approaches (prediction for IVF outcome). Receiver operating characteristics curve analysis was used to show what number of oocytes could predict IVF pregnancy and whether clinical and laboratory variables could predict newly defined POR. Results The 25th percentile of the distribution corresponded to total oocytes ?2 and mature oocyte ?1. The cut-off values for the prediction of IVF outcomes were total oocytes >5 and mature oocyte >1. Considering the incidence of POR (34.1%), a reasonable definition of POR was decided as total oocytes ?2 or mature oocyte ?1. For the prediction of this new definition, the extreme cut-off value (by setting a false positive rate of 5%) of serum anti-Mullerian hormone (AMH) was ?0.76 ng/mL, which was better than serum follicle stimulating hormone or age. A new simple definition of POR was derived as total oocytes ?2 or mature oocyte ?1 in a previous cycle or a serum AMH level of ?0.76 ng/mL. When this simple criterion was re-applied to our data, the predictive performance was similar to the Bologna criteria. Conclusion We here propose a new definition of POR, which is simple and supported by statistical and prognostic analyses. PMID:25683999

  6. Lymph node metastases and elevated postoperative calcitonin: Predictors of poor survival in medullary thyroid carcinoma.

    PubMed

    Siironen, Pivi; Hagstrm, Jaana; Menp, Hanna O; Louhimo, Johanna; Arola, Johanna; Haglund, Caj

    2016-03-01

    Background Total thyroidectomy is the treatment of choice for medullary thyroid carcinoma (MTC), but the extent of neck dissection is controversial. Lymph node metastases, distant metastases, and old age are known predictors of poor survival. Patients Patients treated for primary MTC at Helsinki University Hospital from 1990 to 2009 were included (n?=?54). Their clinical characteristics, treatment, and outcome were analysed retrospectively, these patients were followed until death or their last follow-up date. Results At last follow-up (3.4-23 years), of 54 MTC patients, 19 (35%) were disease-free, 17 (32%) were alive with disease, and 12 (22%) had died of MTC; six patients died of unrelated causes (11%). All disease-free patients were node negative and had normal postoperative calcitonin level. Of 19 disease-free patients, only four (21%) had undergone lymph node dissection. All patients who died of MTC were Stage IV at diagnosis and died with distant metastases. Disease-specific five-and 10-year survival was 84% and 76.2%. Advanced T-stage (p?=?0.004), lymph node metastases (p?prognostic factors. Patients with lymph node metastasis and/or elevated postoperative calcitonin with present treatments cannot become disease-free, but most of them can live a long life with metastasis. PMID:26339947

  7. High levels of SIRT1 expression enhance tumorigenesis and associate with a poor prognosis of colorectal carcinoma patients

    PubMed Central

    Chen, Xiaojing; Sun, Kai; Jiao, Shufan; Cai, Ning; Zhao, Xue; Zou, Hanbing; Xie, Yuexia; Wang, Zhengshi; Zhong, Ming; Wei, Lixin

    2014-01-01

    SIRT1, a NAD+ dependent class III deacetylase, takes part in many important biological processes. Previous studies show that SIRT1 is overexpressed in some cancers and plays an essential role in tumorigenesis. However, the association between SIRT1 and colorectal cancer (CRC) is still unclear. We found that many CRC specimens had strong SIRT1 expression, which had an obvious correlation with poor prognosis of CRC patients. Meanwhile, SIRT1 expression had a co-localization with CD133, a current universal marker to characterize colorectal cancer stem cells (CSCs). In vitro studies also revealed that SIRT1 was overexpressed in colorectal CSC-like cells. Moreover, SIRT1 deficiency decreased percentage of CD133+ cells, attenuated the abilities of colony and sphere formation, and inhibited tumorigenicity in vivo in CRC cells. Further study demonstrated that the expressions of several stemness-associated genes, including Oct4, Nanog, Cripto, Tert and Lin28, were reduced by SIRT1 knockdown in CRC cells. Taken together, our findings suggest that SIRT1 plays a crucial role in keeping the characteristics of CSCs cells. SIRT1 is a potential independent prognostic factor of CRC patients after tumor resection with curative intent, and will contribute to providing a promising new approach to target at CSCs in CRC treatment. PMID:25500546

  8. Bile duct invasion can be an independent prognostic factor in early stage hepatocellular carcinoma

    PubMed Central

    Jang, Ye-Rang; Kim, Hyeyoung; Lee, Jeong-Moo; Yi, Nam-Joon; Suh, Kyung-Suk

    2015-01-01

    Backgrounds/Aims In hepatocellular carcinoma (HCC), bile duct invasion occurs far more rarely than vascular invasion and is not well characterized. In addition, the pathologic finding of bile duct invasion is not considered an independent prognostic factor for HCC following surgery. In this study, we determined the characteristics of HCC with bile duct invasion, and assessed the clinical significance of bile duct invasion. Methods We retrospectively reviewed the medical records of 363 patients who underwent hepatic resection for HCC at Seoul National University Hospital (SNUH) from January 2009 to December 2011. Preoperative, operative, and pathological data were collected. The risk factors for recurrence and survival were analyzed. Subsequently, the patients were divided into 2 groups according to disease stage (American Joint Committee on Cancer/International Union Against Cancer 7th edition): early stage (T1 and 2) and advanced stage (T3 and 4) group; and risk factors in the sub-groups were analyzed. Results Among 363 patients, 13 showed bile duct invasion on pathology. Patients with bile duct invasion had higher preoperative total bilirubin levels, greater microvascular invasion, and a higher death rate than those without bile duct invasion. In multivariate analysis, bile duct invasion was not an independent prognostic factor for survival for the entire cohort, but, was an independent prognostic factor for early stage. Conclusions Bile duct invasion accompanied microvascular invasion in most cases, and could be used as an independent prognostic factor for survival especially in early stage HCC (T1 and T2). PMID:26693236

  9. 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

  10. Clinical Features and Prognostic Factors of Hodgkins Lymphoma: A Single Center Experience

    PubMed Central

    K?l?kap, Saadettin; Bar??ta, ?brahim; lger, ?kran; elik, ?smail; Selek, U?ur; Y?ld?z, Ferah; Kars, Ay?e; z???k, Yavuz; Tekuzman, Glten

    2013-01-01

    Background: Hodgkins lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. Aims: We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. Study Design: Retrospective study. Methods: Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. Results: We analysed data of 391 HL patients (61% male, 39% female; mean age 35.715.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of B symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. Conclusion: This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country. PMID:25207097

  11. Mortality after hip fracture with vertebral compression fracture is poor.

    PubMed

    Imai, Norio; Endo, Naoto; Hoshino, Tadashi; Suda, Ken; Miyasaka, Dai; Ito, Tomoyuki

    2016-01-01

    Due to the increasing elderly population, the prevalence of osteoporotic hip fractures in Japanese patients continues to rise. It is well established that patients with either hip fracture or both symptomatic and asymptomatic morphometric vertebral compression fracture (VCF) have a poor health prognosis compared with the general population. The purpose of this study was to retrospectively investigate vertebral fracture rates among patients with hip fracture and their influence on mortality. We examined 182 cases of osteoporotic hip fracture in patients admitted to our institution between January 2009 and May 2011. The average age at the time of fracture was 85years. Radiographs of the lumbar spine were obtained from all of the participants and the lateral spinal radiographs were examined for evidence of VCF. The patients were classified into two groups, those with VCF and those without. A VCF was identified in approximately 78% of the patients. The mortality rate 1year after the hip fracture was approximately 22% and it was significantly higher in patients with VCF. Through multivariate statistics we found that VCF, post-operative complication, loss of ambulation after operation and medication for osteoporosis were statistically significant. In other words, VCF, post-operative complication and loss of ambulation were considered to be poor prognostic factors and medication for osteoporosis was likely to improve the prognosis. We concluded that the risk of mortality after hip fracture is significantly greater in patients who also have VCF compared to patients without VCF, and that medication for osteoporosis is likely to improve prognosis. PMID:25501699

  12. LSD1 Overexpression Is Associated with Poor Prognosis in Basal-Like Breast Cancer, and Sensitivity to PARP Inhibition

    PubMed Central

    Nagasawa, Satoi; Sedukhina, Anna S.; Nakagawa, Yuko; Maeda, Ichiro; Kubota, Manabu; Ohnuma, Shigeko; Tsugawa, Koichiro; Ohta, Tomohiko; Roche-Molina, Marta; Bernal, Juan A.; Narvez, Ana J.; Jeyasekharan, Anand D.; Sato, Ko

    2015-01-01

    LSD1, a lysine-specific histone demethylase, is overexpressed in several types of cancers and linked to poor outcomes. In breast cancer, the significance of LSD1 overexpression is not clear. We have performed an in silico analysis to assess the relationship of LSD1 expression to clinical outcome. We demonstrate that LSD1 overexpression is a poor prognostic factor in breast cancer, especially in basal-like breast cancer, a subtype of breast cancer with aggressive clinical features. This link is also observed in samples of triple negative breast cancer. Interestingly, we note that overexpression of LSD1 correlates with down-regulation of BRCA1 in triple negative breast cancer. This phenomenon is also observed in in vitro models of basal-like breast cancer, and is associated with an increased sensitivity to PARP inhibitors. We propose therefore that high expression levels of the demethylase LSD1 is a potential prognostic factor of poor outcome in basal-like breast cancer, and that PARP inhibition may be a therapeutic strategy of interest in this poor prognostic subtype with overexpression of LSD1. PMID:25679396

  13. Activated leukocyte cell adhesion molecule in breast cancer: prognostic indicator

    PubMed Central

    King, Judy A; Ofori-Acquah, Solomon F; Stevens, Troy; Al-Mehdi, Abu-Bakr; Fodstad, Oystein; Jiang, Wen G

    2004-01-01

    Introduction Activated leukocyte cell adhesion molecule (ALCAM) (CD166) is an immunoglobulin molecule that has been implicated in cell migration. The present study examined the expression of ALCAM in human breast cancer and assessed its prognostic value. Methods The immunohistochemical distribution and location of ALCAM was assessed in normal breast tissue and carcinoma. The levels of ALCAM transcripts in frozen tissue (normal breast, n = 32; breast cancer, n = 120) were determined using real-time quantitative PCR. The results were then analyzed in relation to clinical data including the tumor type, the grade, the nodal involvement, distant metastases, the tumor, node, metastasis (TNM) stage, the Nottingham Prognostic Index (NPI), and survival over a 6-year follow-up period. Results Immunohistochemical staining on tissue sections in ducts/acini in normal breast and in breast carcinoma was ALCAM-positive. Differences in the number of ALCAM transcripts were found in different types of breast cancer. The level of ALCAM transcripts was lower (P = 0.05) in tumors from patients who had metastases to regional lymph nodes compared with those patients without, in higher grade tumors compared with Grade 1 tumors (P < 0.01), and in TNM Stage 3 tumors compared with TNM Stage 1 tumors (P < 0.01). Tumors from patients with poor prognosis (with NPI > 5.4) had significantly lower levels (P = 0.014) of ALCAM transcripts compared with patients with good prognosis (with NPI < 3.4), and tumors from patients with local recurrence had significantly lower levels than those patients without local recurrence or metastases (P = 0.04). Notably, tumors from patients who died of breast cancer had significantly lower levels of ALCAM transcripts (P = 0.0041) than those with primary tumors but no metastatic disease or local recurrence. Patients with low levels of ALCAM transcripts had significantly (P = 0.009) more incidents (metastasis, recurrence, death) compared with patients with primary breast tumors with high levels of ALCAM transcripts. Conclusions In the present panel of breast cancer specimens, decreased levels of ALCAM correlated with the nodal involvement, the grade, the TNM stage, the NPI, and the clinical outcome (local recurrence and death). The data suggest that decreased ALCAM expression is of clinical significance in breast cancer, and that reduced expression indicates a more aggressive phenotype and poor prognosis. PMID:15318930

  14. Child Health: Reaching the Poor

    PubMed Central

    Wagstaff, Adam; Bustreo, Flavia; Bryce, Jennifer; Claeson, Mariam

    2004-01-01

    In most countries, rates of mortality and malnutrition among children continue to decline, but large inequalities between poor and better-off children exist, both between and within countries. These inequalities, which appear to be widening, call into question the strategies for child mortality reduction relied upon to date. We review (1) what is known about the causes of socioeconomic inequalities in child health and where programs aimed at reducing inequalities may be most effectively focused and (2) what is known about the success of actual programs in narrowing these inequalities. We end with lessons learned: the need for better evidence, but most of all for a new approach to improving the health of all children that is evidence based, broad, and multifaceted. PMID:15117689

  15. Poor commissioning discussed in depth.

    PubMed

    Towse, Bob; Whitby, Robin; Wignall, Stephen; Barrass, Chris; Newman, Alan; Shaw, Christopher; Johnston-Stuart, Chris; James, Chris

    2014-05-01

    Last October's Healthcare Estates 2013 conference saw one of the first day's 'Engineering' sessions debate the topic, 'Why do so many buildings disappoint their owners and occupants?' Much of the discussion centered on the problems caused by 'inadequate management of the commissioning process'. A roundtable debate jointly staged recently in London by IHEEM and the B&ES, the leading U.K. trade association for building services engineering contractors, took the debate forward. As HEJ editor, Jonathan Baillie reports, the discussions confirmed that one of the key contributors to poor commissioning is a failure to involve specialist building services contractors sufficiently early. It was also agreed that finding a really effective 'client-side' project manager, with the panoply of skills and experience the role requires, can be 'a tough ask'. In this issue of HEJ we report on the debate's first 'half'; in June's edition, we will cover 'part two' of a lively, forthright, and positive debate. PMID:24930183

  16. 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.

  17. [Prognostic factors of early breast cancer].

    PubMed

    Almagro, Elena; Gonzlez, 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. PMID:25726309

  18. 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. PMID:12227146

  19. 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

  20. Nectin-2 and DDX3 are biomarkers for metastasis and poor prognosis of squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder.

    PubMed

    Miao, Xiongying; Yang, Zhu-Lin; Xiong, Li; Zou, Qiong; Yuan, Yuan; Li, Jinghe; Liang, Lufeng; Chen, Meigui; Chen, Senlin

    2013-01-01

    The clinicopathological and biological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of gallbladder have not been well documented because it is a rare subtype of gallbladder cancer. In this study, the protein expression of Nectin-2 and DDX3 in 46 SC/ASCs and 80 adenocarcinomas was measured using immunohistochemistry. We demonstrated that positive Nectin-2 and DDX3 expression was significantly associated with large tumor size, high TNM stage, and lymph node metastasis of SC/ASC and AC. Positive Nectin-2 and DDX3 expression was significantly associated with invasion and surgical curability of AC. Univariate Kaplan-Meier analysis showed that positive Nectin-2 and DDX3 expression, degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis, and surgical curability were significantly associated with post-operative survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive Nectin-2 and DDX3 expression, degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis, and no surgical curability are independent poor-prognostic factors in both SC/ASC and AC patients. Our study suggested that positive Nectin-2 and DDx3 expression is closely correlated with clinical, pathological, and biological behaviors as well as poor-prognosis of gallbladder cancer. PMID:23330003

  1. 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.

  2. 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. PMID:25001988

  3. Genomic imbalance defines three prognostic groups for risk stratification of patients with chronic lymphocytic leukemia.

    PubMed

    Houldsworth, Jane; Guttapalli, Asha; Thodima, Venkata; Yan, Xiao Jie; Mendiratta, Geetu; Zielonka, Tania; Nanjangud, Gouri; Chen, Weiyi; Patil, Sujata; Mato, Anthony; Brown, Jennifer R; Rai, Kanti; Chiorazzi, Nicholas; Chaganti, R S K

    2014-04-01

    Array comparative genomic hybridization (aCGH) has yet to be fully leveraged in a prognostic setting in chronic lymphocytic leukemia (CLL). Genomic imbalance was assessed in 288 CLL specimens using a targeted array. Based on 20 aberrations in a hierarchical manner, all 228 treatment-naive specimens were classified into a group with poor outcome (20.6%) exhibiting at least one aberration that was univariately associated with adverse outcome (gain: 2p, 3q, 8q, 17q, loss: 7q, 8p, 11q, 17p, 18p), good outcome (32.5%) showing 13q14 loss without any of the other 10 aberrations (gain: 1p, 7p, 12, 18p, 18q, 19, loss: 4p, 5p, 6q, 7p) or intermediate outcome (remainder). The three groups were significantly separated with respect to time to first treatment and overall survival (p < 0.001), and validation of the stratification scheme was performed in two independent datasets. Gain of 3q and 8q, and 17p loss were determined to be independent unfavorable prognostic biomarkers. TP53, NOTCH1 and SF3B1 mutations correlated with the presence of one poor outcome aCGH marker, at a considerably higher frequency than when only considering poor risk aberrations routinely detected by fluorescence in situ hybridization (FISH). These data support genomic imbalance evaluation in CLL by aCGH to assist in risk stratification. PMID:24047479

  4. 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.

  5. 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…

  6. 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

  7. 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

  8. Prognostic relevance of histological findings on bone marrow biopsy in myelodysplastic syndromes.

    PubMed

    Lambertenghi-Deliliers, G; Annaloro, C; Oriani, A; Soligo, D; Pozzoli, E; Polli, E E

    1993-02-01

    Bone marrow biopsy (BMB) has aroused growing interest as a possible aid in the diagnostic and prognostic evaluation of myelodysplastic syndromes (MDS). Previous reports have pointed out that MDS patients with blastic aggregates or severe bone marrow (BM) fibrosis are characterized by a worse clinical outcome. BMBs of 106 MDS patients were retrospectively reviewed, and relationships among the different histological parameters as well as clinicopathological correlations were looked for. Three patterns of BM blastic infiltration ("diffuse," "cluster," and "large") were recognized. Overt leukemic transformation and overall survival were selected as prognostic end points. BM infiltration was "diffuse" in 18, "cluster" in 48, and "large" in 40 cases. RAEB-t patients accounted for about half of the "large" cases, and none had a "diffuse" pattern (p < 0.01). Nineteen patients showed extensive BM fibrosis; most of them were characterized by "cluster" blastic infiltration and megakaryocyte hyperplasia. Leukemic transformation occurred in 67% of "large" cases (p< 0.001) and in none of the "cluster" cases with severe BM fibrosis (p < 0.01); however, survival was equally poor in these two groups because of early leukemic transformation (large cases) and BM failure (cluster cases). The FAB classification did not significantly correlate with prognosis. Patients with "cluster" BM infiltration and severe fibrosis can be regarded as a true separate MDS subset characterized by unique clinicopathological and prognostic features. Because of the subacute clinical behavior of most cases, and the poor performance status of many elderly patients, there is still controversy as to the best therapeutic approach in MDS. Histological analysis allowed two groups of MDS patients to be identified, both characterized by poor life expectancy, who could benefit from early aggressive chemotherapy. PMID:8448244

  9. 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

  10. APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma

    PubMed Central

    Walker, Brian A; Wardell, Christopher P; Murison, Alex; Boyle, Eileen M; Begum, Dil B; Dahir, Nasrin M; Proszek, Paula Z; Melchor, Lorenzo; Pawlyn, Charlotte; Kaiser, Martin F; Johnson, David C; Qiang, Ya-Wei; Jones, John R; Cairns, David A; Gregory, Walter M; Owen, Roger G; Cook, Gordon; Drayson, Mark T; Jackson, Graham H; Davies, Faith E; Morgan, Gareth J

    2015-01-01

    We have sequenced 463 presenting cases of myeloma entered into the UK Myeloma XI study using whole exome sequencing. Here we identify mutations induced as a consequence of misdirected AID in the partner oncogenes of IGH translocations, which are activating and associated with impaired clinical outcome. An APOBEC mutational signature is seen in 3.8% of cases and is linked to the translocation mediated deregulation of MAF and MAFB, a known poor prognostic factor. Patients with this signature have an increased mutational load and a poor prognosis. Loss of MAF or MAFB expression results in decreased APOBEC3B and APOBEC4 expression, indicating a transcriptional control mechanism. Kataegis, a further mutational pattern associated with APOBEC deregulation, is seen at the sites of the MYC translocation. The APOBEC mutational signature seen in myeloma is, therefore, associated with poor prognosis primary and secondary translocations and the molecular mechanisms involved in generating them. PMID:25904160

  11. 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

  12. High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma

    PubMed Central

    MA, RUIMIN; KANG, XIXIONG; ZHANG, GUOJUN; FANG, FANG; DU, YAMEI; LV, HONG

    2016-01-01

    Ubiquitin-conjugating enzyme E2C (UBE2C) is a key regulator of cell cycle progression and is involved in the tumorigenesis of a variety of cancers. Previous studies have demonstrated that UBE2C is an important factor in the malignant progression of astrocytic tumors. However, the association between UBE2C expression and clinical prognosis of glioma patients has not been defined. In the present study, the expression of UBE2C in gliomas and non-cancerous brain tissues were detected by microarray and immunohistochemical analysis. The association between UBE2C expression and clinicopathological characteristics of the glioma patients was evaluated. The Kaplan-Meier method and multivariate Cox's proportional hazards model were used to analyze the survival time of the patients. The results demonstrated that the expression levels of UBE2C in anaplastic gliomas and glioblastoma (GBM) patients were significantly higher compared to low-grade gliomas, in microarray and immunohistochemistry analysis. A higher UBE2C expression was associated with a significantly decreased overall survival time in patients possessing anaplastic gliomas (P<0.01) and GBMs (P<0.05). Multivariate analysis of 80 GBM patients revealed that UBE2C expression was an independent prognostic factor. To the best of our knowledge, the present data suggest for the first time that UBE2C overexpression is strongly associated with an aggressive progression and poor outcome of malignant glioma. Therefore, UBE2C overexpression may be used as a predictor of poor prognosis in patients with malignant glioma.

  13. Prognostic Role of Serum Antibody Immunity to p53 Oncogenic Protein in Ovarian Cancer: A Systematic Review and a Meta-Analysis

    PubMed Central

    Garziera, Marica; Montico, Marcella; Bidoli, Ettore; Scalone, Simona; Sorio, Roberto; Giorda, Giorgio; Lucia, Emilio; Toffoli, Giuseppe

    2015-01-01

    Objective Serum p53 autoantibodies (p53-AAbs) are the product of an endogenous immune response against p53 overexpression driven by the ovarian tumour. The p53-AAbs are detectable only in a subset of patients. To date, the evidence of an association between the presence of p53-AAbs and ovarian cancer outcomes has been poorly investigated. Methods A systematic literature search was performed to identify eligible studies investigating the association of serum p53-AAbs and overall survival (OS) and disease free survival (DFS). Associations between presence of serum p53-AAbs and baseline tumour characteristics were also evaluated. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were computed to estimate the prognostic impact of serum p53-AAbs. Heterogeneity between studies was assessed. Results A total of 583 patients (7 studies) for OS and 356 patients (4 studies) for DFS were included in the meta-analysis. Presence of p53-AAbs was not associated to OS (pooled uni- multivariate HR = 1.09; 95% CI: 0.552.16), and a large heterogeneity was found. When only multivariate HRs were pooled together (4 studies), presence of p53-AAbs was significantly associated to a better OS (pooled HR = 0.57; 95% CI: 0.400.81), and no significant heterogeneity was observed. A reduced DFS was associated to p53-AAbs (pooled uni- multivariate HR = 1.37; 95% CI: 0.832.25), though not significantly and with a moderate heterogeneity. Conclusions The prognostic significance of serum p53-AAbs in ovarian cancer was diverging according to uni or multivariate models used. Since the results of this work were based on only few investigations, large prospective studies are needed to better define the role of antibody immunity against p53. PMID:26451959

  14. Prognostic significance of the mRNA expression of ERCC1, RRM1, TUBB3 and TYMS genes in patients with non-small cell lung cancer

    PubMed Central

    SUN, SHENGJIE; SHI, WEIWEI; WU, ZHIYONG; ZHANG, GUOQING; YANG, BO; JIAO, SHUNCHANG

    2015-01-01

    The present study aimed to investigate the prognostic value of excision repair cross-complementing 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), class III ?-tubulin (TUBB3) and thymidylate synthase (TYMS) in patients with non-small cell lung cancer (NSCLC) receiving platinum-based adjuvant chemotherapy. The mRNA expression of these genes was assessed in 72 tumor tissue samples obtained following surgery, using multiplex branched-DNA technology. Subsequent to surgery, all 72 patients with NSCLC were treated with platinum-based chemotherapy. The expression of these five genes was analyzed and the correlation with clinical characteristics and patient survival was investigated. Among the 72 samples, the incidence rate of mRNA expression of ERCC1 was 38.9% (28/72), RRM1 was 55.6% (40/72), TUBB3 was 47.2% (34/72) and TYMS was 62.5% (45/72). The incidence rate of ERCC1 expression in adenocarcinoma (34.2%) was significantly lower than that in non-adenocarcinoma (44.1%; P<0.05). Furthermore, the incidence rates of TYMS and TUBB3 expression in the high-median differentiation tissue samples were significantly lower than those in the low differentiation tissue samples (P<0.05). When the correlation of gene expression and patient survival was analyzed, high expression of ERCC1, RRM1, TUBB3 or TYMS was found to be associated with poor prognosis (P<0.001, P=0.001, P=0.001 and P=0.001, respectively). ERCC1, RRM1, TUBB3 and TYMS are key factors involved in survival following surgical treatment in patients with NSCLC. The mRNA expression of these genes may have prognostic value for patients with NSCLC treated with platinum-based chemotherapy. PMID:26622418

  15. 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

  16. MicroRNA in pancreatic adenocarcinoma: predictive/prognostic biomarkers or therapeutic targets?

    PubMed Central

    Brunetti, Oronzo; Russo, Antonio; Scarpa, Aldo; Santini, Daniele; Reni, Michele; Bittoni, Alessandro; Azzariti, Amalia; Aprile, Giuseppe; Delcuratolo, Sabina; Signorile, Michele; Gnoni, Antonio; Palermo, Loredana; Lorusso, Vito; Cascinu, Stefano; Silvestris, Nicola

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a poor prognosis, short overall survival and few chemotherapeutic choices. MicroRNAs (miRNAs) are non-coding, single-stranded RNAs of around 22 nucleotides involved in the pathogenic mechanisms of carcinogenesis and metastasis. They have been studied in many tumors in order to identify potential diagnostic, prognostic or therapeutic targets. In the current literature, many studies have analyzed the role of miRNAs in PDAC. In fact, the absence of appropriate biomarkers, the difficultly of early detection of this tumor, and the lack of effective chemotherapy in patients with unresectable disease have focused attention on miRNAs as new, interesting advance in this malignancy. In this review we analyzed the role of miRNAs in PDAC in order to understand the mechanisms of action and the difference between the onco-miRNA and the tumor suppressor miRNA. We also reviewed all the data related to the use of these molecules as predictive as well as prognostic biomarkers in the course of the disease. Finally, the possible therapeutic use of miRNAs or anti-miRNAs in PDAC is also discussed. In conclusion, although there is still no clinical application for these molecules in PDAC, it is our opinion that the preclinical evidence of the role of specific miRNAs in carcinogenesis, the possibility of using miRNAs as diagnostic or prognostic biomarkers, and their potential therapeutic role, warrant future studies in PDAC. PMID:26259238

  17. MicroRNA in pancreatic adenocarcinoma: predictive/prognostic biomarkers or therapeutic targets?

    PubMed

    Brunetti, Oronzo; Russo, Antonio; Scarpa, Aldo; Santini, Daniele; Reni, Michele; Bittoni, Alessandro; Azzariti, Amalia; Aprile, Giuseppe; Delcuratolo, Sabina; Signorile, Michele; Gnoni, Antonio; Palermo, Loredana; Lorusso, Vito; Cascinu, Stefano; Silvestris, Nicola

    2015-09-15

    Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a poor prognosis, short overall survival and few chemotherapeutic choices. MicroRNAs (miRNAs) are non-coding, single-stranded RNAs of around 22 nucleotides involved in the pathogenic mechanisms of carcinogenesis and metastasis. They have been studied in many tumors in order to identify potential diagnostic, prognostic or therapeutic targets. In the current literature, many studies have analyzed the role of miRNAs in PDAC. In fact, the absence of appropriate biomarkers, the difficultly of early detection of this tumor, and the lack of effective chemotherapy in patients with unresectable disease have focused attention on miRNAs as new, interesting advance in this malignancy. In this review we analyzed the role of miRNAs in PDAC in order to understand the mechanisms of action and the difference between the onco-miRNA and the tumor suppressor miRNA. We also reviewed all the data related to the use of these molecules as predictive as well as prognostic biomarkers in the course of the disease. Finally, the possible therapeutic use of miRNAs or anti-miRNAs in PDAC is also discussed. In conclusion, although there is still no clinical application for these molecules in PDAC, it is our opinion that the preclinical evidence of the role of specific miRNAs in carcinogenesis, the possibility of using miRNAs as diagnostic or prognostic biomarkers, and their potential therapeutic role, warrant future studies in PDAC. PMID:26259238

  18. MT1-MMP is not a good prognosticator of cancer survival: evidence from 11 studies.

    PubMed

    Wu, Kun-Peng; Li, Qiang; Lin, Fu-Xiang; Li, Jun; Wu, Lu-Min; Li, Wei; Yang, Qiao-Zhu

    2014-12-01

    MT1-MMP exhibits diverse expressions in patients with cancer and could be considered as potential prognostic biomarker of cancer. We performed a meta-analysis aiming to provide more sufficient evidence that MT1-MMP expression is associated with poor overall survival in several types of cancers. We systematically searched the studies from databases and carefully identified based on eligibility criteria. The association between MT1-MMP expression and overall survival in cancers was estimated using Review Manager. A total of 11 literatures which included 1,918 cancer patients were combined in the final analysis. Meta-analysis revealed that MT1-MMP overexpression was associated with an unfavorable overall survival and the pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) was 2.46 (95% CI 1.75-3.47). From subgroup analyses, we identified that MT1-MMP was an independent prognostic factor for lung cancer and gastric cancer, and HRs (95% CI) were 3.73 (95% CI 2.67-5.21) and 2.46 (95% CI 1.69-3.59), respectively. In conclusion, MT1-MMP is a potential prognostic factor in human cancers. PMID:25195136

  19. Clinical and pathologic prognostic factors for curative resection for pancreatic cancer

    PubMed Central

    Montagnini, A.L.; Jukemura, J.; Penteado, S.; Abdo, E.E.; Patzina, R.; Cecconello, I.; Cunha, J.E.M.

    2008-01-01

    Background. Pancreatic cancer is the fifth leading cause of cancer-related deaths in the world. Operative resection is the only therapeutic option with curative potential for this disease. Objective. The aim of the present study was to correlate clinical and pathologic parameters with survival in patients submitted to pancreatic resection for pancreatic adenocarcinoma. Methods. Surgical resection with curative intent (R0 and R1 resections) was performed in 65 pancreatic cancer patients between 1990 and 2006. The overall results of surgical treatment were retrospectively analyzed and compared with the clinicopathologic features of these patients. Results. Pylorus-preserving pancreatoduodenectomy was performed in 37 patients (56.9%), classic resection in 35.4%, distal pancreatectomy in 4.6% and total pancreatectomy in 3.6%. The inhospital mortality was 5% (three patients). Postoperative complications occurred in 28 patients (43%). Mean survival and five-year survival rate after curative resection were 27 months and 9.0%, respectively. Sex, TNM stage, tumor differentiation, neural invasion, tumor size and involvement of resection margin were significant prognostic factors on univariate analysis. Multivariate analysis showed tumor differentiation and neural invasion as prognostic factors. Conclusion. Patients with pancreatic cancer, even those with poor prognostic factors should be given the opportunity of surgical resection with curative intent. PMID:18982152

  20. 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

  1. 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.

  2. Medulloblastoma. The identification of prognostic subgroups and implications for multimodality management

    SciTech Connect

    Kopelson, G.; Linggood, R.M.; Kleinman, G.M.

    1983-01-15

    For 43 medulloblatoma patients who had five-and ten-year actuarial survival rates of 56%, prognostic factors of statistical significance included: T-stage, M-stage and histopathologic tumor score. Posterior fossa local control rates were also function of T-stage and TS. Combining TS with T-stage, patients fell into three prognostic and local control groups, which may have different future management implications: Small (T1,2) tumors of favorable (TS less than or equal to 5) histology had a 92% ten-year actuarial survival rate with 100% (8/8) local control; no change from current management is suggested. For the intermediate prognosis group, increasing the irradiation dose alone may improve survival because these tumors exhibited an irradiation dose-response relationship. However, it is the poor prognosis group which might be suitable for future adjuvant chemotherapy or radiosensitizer trials since there is no evidence that higher irradiation doses improve local control. This article identifies prognostic subgroups based on histologic type and TM staging in medulloblastoma patients which potentially may be utilized to improve therapeutic results, and confirms the value of staging patients with central nervous system malignancies.

  3. 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: 1.662.19) for OS, 1.42 (95% CI: 1.161.74) for DFS and 2.2 (95% CI: 1.642.96) 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: 1.184.9) 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

  4. Drug holiday as a prognostic factor of medication-related osteonecrosis of the jaw

    PubMed Central

    Kim, Yoon Ho; Lee, Ho Kyung; Song, Seung Il

    2014-01-01

    Objectives To identify post-treatment prognostic factors for medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods We evaluated 54 MRONJ patients who visited the Department of Dentistry, Ajou University Hospital, from May 2007 to March 2014. Twenty-one patients were surgically managed with debridement or sequestrectomy and 33 patients were conservatively managed using antibiotics. Correlations of age, sex, stage, bisphosphonate duration and type, and drug holiday with the prognosis of MRONJ were investigated. Correlations were verified by logistic regression analysis and t-tests with a significance level of 0.05. Results Clinical outcomes were evaluated on the basis of both clinical and radiographic findings. Twelve out of 21 surgically managed patients showed a favorable prognosis and nine patients relapsed. Thirty-one of the 33 conservatively managed patients showed no specific change in prognosis, and two patients worsened. Statistical analyses of the conservative management group did not reveal any correlation of the above factors with the prognosis of conservative management. Drug holiday was the only prognostic factor in the surgical management group (P=0.031 in logistic regression analysis, P=0.004 in t-test). Conclusion Drug holiday is a prognostic factor in the surgical management of MRONJ. Because the drug holiday in the patients of the poor prognosis group occurred 1.5 to 4 months prior to surgical management, we recommend a drug holiday more than 4 months before surgery. PMID:25368832

  5. Prognostic and predictive response factors in colorectal cancer patients: Between hope and reality

    PubMed Central

    De Divitiis, Chiara; Nasti, Guglielmo; Montano, Massimo; Fisichella, Rossella; Iaffaioli, Rosario Vincenzo; Berretta, Massimiliano

    2014-01-01

    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. PMID:25386053

  6. Prognostic role of copeptin after stroke: A systematic review and meta-analysis of observational studies.

    PubMed

    Choi, Kyu-Sun; Kim, Hyun Jung; Chun, Hyoung-Joon; Kim, Jae Min; Yi, Hyeong-Joong; Cheong, Jin-Hwan; Kim, Choong-Hyun; Oh, Suck-Jun; Ko, Yong; Kim, Young-Soo; Bak, Koang-Hum; Ryu, Je-Il; Kim, Wonhee; Lim, Taeho; Ahn, Hyeong Sik; Ahn, Il Min; Lee, Seon-Heui

    2015-01-01

    Copeptin, the C-terminal part of provasopressin, has emerged as a novel prognostic marker after hemorrhagic or ischemic stroke. The aim of this study was to quantitatively assess the prognostic significance of plasma copeptin level on functional outcome and mortality in patients with acute stroke using a meta-analysis of the available evidence. Thirteen relevant studies from 2,746 patients were finally included in our study. An elevated plasma copeptin level was associated with an increased risk of unfavorable outcome and mortality after stroke (OR 1.77; 95% CI, 1.44-2.19 and OR 3.90; 95% CI 3.07-4.95, respectively). The result of the pooled measure on standardized mean difference (SMD) was that plasma copeptin levels were found to be significantly higher in patients who died compared to survivors (SMD 1.70; 95% CI, 1.36-2.03). A stratified analysis by study region showed significant differences in SMD of copeptin, and the heterogeneity among studies was significantly decreased. However, the positive association of copeptin with poor prognosis after stroke was consistent in each stratified analysis. The present meta-analysis suggests that early measurement of plasma copeptin could provide better prognostic information about functional outcome and mortality in patients with acute stroke. PMID:26119473

  7. Histopathological grading and DNA ploidy as prognostic markers in metastatic prostatic cancer.

    PubMed Central

    Jrgensen, T.; Yogesan, K.; Skjrten, F.; Berner, A.; Tveter, K. J.; Danielsen, H. E.

    1995-01-01

    The present study compares the prognostic potential of tumour grade and DNA ploidy status in patients with advanced-stage prostatic cancer. Two outcome groups were selected on the basis of time to progression and survival after orchiectomy. A poor-outcome group consisted of 32 therapy-resistant patients who experienced disease progression during the first year after orchiectomy and subsequently death due to prostatic cancer during the following year. A good-outcome group consisted of 27 therapy-responsive patients who showed disease regression and no signs of progression during a 3 year follow-up. The primary tumours were graded twice according to WHO and Gleason classification systems by two pathologists. Final agreement between the pathologists was obtained after a consensus meeting. The analysis revealed no prognostic importance of the two histological classification systems (P = 0.62 and P = 0.70) and disclosed weak inter- and intra-observer reproducibility (kappa < 0.70). DNA ploidy analyses were performed by image cytometry on formalin-fixed, paraffin-embedded samples of the primary tumours. Overall, 48% of the tumours were diploid, 20% tetraploid and 32% anueploid. DNA ploidy status did not discriminate between the two outcome groups (P = 0.46). Histological grade and DNA ploidy showed no prognostic importance in patients with prostatic cancer and skeletal metastases. PMID:7734299

  8. Opposing prognostic roles of nuclear and cytoplasmic RACGAP1 expression in colorectal cancer patients.

    PubMed

    Yeh, Chung-Min; Sung, Wen-Wei; Lai, Hung-Wen; Hsieh, Ming-Ju; Yen, Hsu-Heng; Su, Tzu-Cheng; Chang, Wei-Hsiang; Chen, Chia-Yu; Ko, Jiunn-Liang; Chen, Chih-Jung

    2016-01-01

    Rac GTPase activating protein 1 (RACGAP1) plays a regulatory role in initiation of cytokinesis, control of cell growth and differentiation, and tumor malignancy, making it a potential prognostic biomarker. RACGAP1 is present in the nucleus, but a diffuse distribution in the cytoplasm also occurs. The aim of this study was to determine the impact of nuclear and cytoplasmic expression of RACGAP1 on clinical outcome to provide further evidence of a role in colorectal cancer. RACGAP1 expression was analyzed by immunohistochemistry in 166 cancer specimens from primary colorectal cancer patients. The mean follow-up time after surgery was 5.4 years (range, 0.01-13.10 years). The prognostic value of RACGAP1 on overall survival was validated by Kaplan-Meier analysis and Cox regression models. RACGAP1 is expressed in colorectal specimen and is present in both the nucleus and cytoplasm in different amounts. Colorectal cancer patients had opposite prognoses depending on the site of RACGAP1 expression. Patients with high nuclear RACGAP1 expression had poor outcomes, whereas those with high cytoplasmic RACGAP1 expression had favorable prognosis (P = .003 and P = .001, respectively). Patients with low nuclear but high cytoplasmic RACGAP1 expression had better survival compared with those with other combinations (P < .001). We suggest that RACGAP1 expression levels in the nucleus and cytoplasm, determined by immunohistochemical staining, predict opposite clinical outcomes and that both could be independent prognostic markers for colorectal cancer. PMID:26508373

  9. Tumor-Associated Macrophages Provide Significant Prognostic Information in Urothelial Bladder Cancer

    PubMed Central

    Bostrm, Minna M.; Irjala, Heikki; Mirtti, Tuomas; Taimen, Pekka; Kauko, Tommi; lgars, Annika; Jalkanen, Sirpa; Bostrm, Peter J.

    2015-01-01

    Inflammation is an important feature of carcinogenesis. Tumor-associated macrophages (TAMs) can be associated with either poor or improved prognosis, depending on their properties and polarization. Current knowledge of the prognostic significance of TAMs in bladder cancer is limited and was investigated in this study. We analyzed 184 urothelial bladder cancer patients undergoing transurethral resection of a bladder tumor or radical cystectomy. CD68 (pan-macrophage marker), MAC387 (polarized towards type 1 macrophages), and CLEVER-1/Stabilin-1 (type 2 macrophages and lymphatic/blood vessels) were detected immunohistochemically. The median follow-up time was 6.0 years. High macrophage counts associated with a higher pT category and grade. Among patients undergoing transurethral resection, all studied markers apart from CLEVER-1/Stabilin-1 were associated with increased risk of progression and poorer disease-specific and overall survival in univariate analyses. High levels of two macrophage markers (CD68/MAC387+/+ or CD68/CLEVER-1+/+ groups) had an independent prognostic role after transurethral resection in multivariate analyses. In the cystectomy cohort, MAC387, alone and in combination with CD68, was associated with poorer survival in univariate analyses, but none of the markers were independent predictors of outcome in multivariate analyses. In conclusion, this study demonstrates that macrophage phenotypes provide significant independent prognostic information, particularly in bladder cancers undergoing transurethral resection. PMID:26197470

  10. Prognostic role of copeptin after stroke: A systematic review and meta-analysis of observational studies

    PubMed Central

    Choi, Kyu-Sun; Kim, Hyun Jung; Chun, Hyoung-Joon; Kim, Jae Min; Yi, Hyeong-Joong; Cheong, Jin-Hwan; Kim, Choong-Hyun; Oh, Suck-Jun; Ko, Yong; Kim, Young-Soo; Bak, Koang-Hum; Ryu, Je-Il; Kim, Wonhee; Lim, Taeho; Ahn, Hyeong sik; Ahn, Il Min; Lee, Seon-Heui

    2015-01-01

    Copeptin, the C-terminal part of provasopressin, has emerged as a novel prognostic marker after hemorrhagic or ischemic stroke. The aim of this study was to quantitatively assess the prognostic significance of plasma copeptin level on functional outcome and mortality in patients with acute stroke using a meta-analysis of the available evidence. Thirteen relevant studies from 2,746 patients were finally included in our study. An elevated plasma copeptin level was associated with an increased risk of unfavorable outcome and mortality after stroke (OR 1.77; 95% CI, 1.442.19 and OR 3.90; 95% CI 3.074.95, respectively). The result of the pooled measure on standardized mean difference (SMD) was that plasma copeptin levels were found to be significantly higher in patients who died compared to survivors (SMD 1.70; 95% CI, 1.362.03). A stratified analysis by study region showed significant differences in SMD of copeptin, and the heterogeneity among studies was significantly decreased. However, the positive association of copeptin with poor prognosis after stroke was consistent in each stratified analysis. The present meta-analysis suggests that early measurement of plasma copeptin could provide better prognostic information about functional outcome and mortality in patients with acute stroke. PMID:26119473

  11. Cytokeratin7 expression in gastric and colorectal adenocarcinoma: Correlation with prognostic factors

    PubMed Central

    Jalali-Nadooshan, Mohammadreza; Siadati, Sepideh; Davati, Ali; Torabi_Parizi, Gholamreza; Ghasemi, Samira

    2015-01-01

    Background: Gastric and colorectal adenocarcinoma are the second and the fifth most common cancers in Iran, respectively. Expression of cytokeratin 7 (CK7) is established in most malignancies including gastric and colorectal adenocarcinoma. Demonstration of Ck7 could be related to prognostic factors and help to the better management of the patients. The objective of our study was to evaluate the CK7 expression in gastric and colorectal adenocarcinoma and its correlation with other prognostic factors. Methods: This cross-sectional study was performed on 99 tissue blocks from patients with gastric or colorectal adenocarcinoma undergoing surgery. Tumor grade, tumor size, depth of invasion and metastasis to lymph nodes were determined. Then, the expression of CK7 was studied using immunohistochemistry staining. Results: Expression of CK7 was 50% and 33.8% in gastric and colorectal adenocarcinoma, respectively. There was not only a significant correlation between CK7 expression and tumor size (r=0.267, P=0.009) but also histologic grade (r=0.222, P=0.028). Conclusion: CK7 could be more expressed with the increase in tumor size and was associated with poorly differentiated gastric and colorectal adenocarcinoma. However, with these results gathered, it is highly recommended that further studies will be conducted to reveal the exact prognostic role of this factor. PMID:26644898

  12. Prognostic implication of neuropilin-1 upregulation in human nasopharyngeal carcinoma

    PubMed Central

    2013-01-01

    Objective As a receptor for both vascular endothelial growth factors and semaphorin, neuropilin-1 (NRP-1) is reported to be up-regulated in cells of several cancers. However, its roles in human nasopharyngeal carcinoma (NPC) are still unclear. Therefore, the goal of this study was to investigate the expression pattern of NRP-1 in NPC tissues, to clarify the clinical significance of NRP-1 expression in NPC as well as the potential prognostic implication of NRP-1 expression. Methods Immunohistochemistry was performed to detect the expression of NRP-1 in tumor tissue samples from 266 NPC patients. The association of NRP-1 protein expression with the clinicopathological characteristics and the prognosis of NPC were subsequently assessed. Results Immunohistochemical analysis showed that 176 of 266 (66.17%) paraffin-embedded archival NPC biopsies showed high expression of NRP-1, but no non-cancerous nasopharyngeal specimens showed positive expression of NRP-1. In addition, high NRP-1 expression was significantly associated with advanced clinical stage (P?=?0.02), positive recurrence (P?=?0.001) and metastasis status (P?=?0.001) of NPC. Moreover, the NPC patients with higher NRP-1 expression had shorter overall survival, whereas patients with lower NRP-1 expression had better survival (P?prognostic factor for overall survival (P?=?0.001) in NPC patients. Conclusion These findings suggest for the first time that NRP-1 upregulation may be a novel biomarker for the prediction of advanced tumor progression and unfavorable prognosis in NPC patients who may benefit from alternative treatment strategy and targeted treatment. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1507827881105018. PMID:24053763

  13. A new simplified comorbidity score as a prognostic factor in non-small-cell lung cancer patients: description and comparison with the Charlson's index

    PubMed Central

    Colinet, B; Jacot, W; Bertrand, D; Lacombe, S; Bozonnat, M-C; Daurès, J-P; Pujol, J-L

    2005-01-01

    Treatment of non-small-cell lung cancer (NSCLC) might take into account comorbidities as an important variable. The aim of this study was to generate a new simplified comorbidity score (SCS) and to determine whether or not it improves the possibility of predicting prognosis of NSCLC patients. A two-step methodology was used. Step 1: An SCS was developed and its prognostic value was compared with classical prognostic determinants in the outcome of 735 previously untreated NSCLC patients. Step 2: the SCS reliability as a prognostic determinant was tested in a different population of 136 prospectively accrued NSCLC patients with a formal comparison between SCS and the classical Charlson comorbidity index (CCI). Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The SCS summarised the following variables: tobacco consumption, diabetes mellitus and renal insufficiency (respective weightings 7, 5 and 4), respiratory, neoplastic and cardiovascular comorbidities and alcoholism (weighting=1 for each item). In step 1, aside from classical variables such as age, stage of the disease and performance status, SCS was a statistically significant prognostic variable in univariate analyses. In the Cox model weight loss, stage grouping, performance status and SCS were independent determinants of a poor outcome. There was a trend towards statistical significance for age (P=0.08) and leucocytes count (P=0.06). In Step 2, both SCS and well-known prognostic variables were found as significant determinants in univariate analyses. There was a trend towards a negative prognostic effect for CCI. In multivariate analysis, stage grouping, performance status, histology, leucocytes, lymphocytes, lactate dehydrogenase, CYFRA 21-1 and SCS were independent determinants of a poor prognosis. CCI was removed from the Cox model. In conclusion, the SCS, constructed as an independent prognostic factor in a large NSCLC patient population, is validated in another prospective population and appears more informative than the CCI in predicting NSCLC patient outcome. PMID:16234816

  14. Prognostic value of a 92-probe signature in breast cancer

    PubMed Central

    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

    2015-01-01

    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. PMID:25883221

  15. 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.

  16. Hyponatremia in Cirrhosis--Pathogenesis, Treatment, and Prognostic Significance.

    PubMed

    Sinha, Vikash K; Ko, Benjamin

    2015-09-01

    Cirrhosis is characterized by systemic and splanchnic vasodilation that leads to excessive nonosmotic secretion of vasopressin (antidiuretic hormone). Hyponatremia is a common electrolyte abnormality in advanced liver disease that results from the impaired ability of the kidney to excrete solute-free water that leads to "dilutional" hyponatremia-water retention disproportionate to the retention of sodium. Hyponatremia in liver diseases carries the prognostic burden, correlates with the severity of cirrhosis, and, in recent studies, has also been implicated in the pathogenesis of hepatic encephalopathy. The current treatment options are limited to conventional therapies like fluid restriction, and the outcomes are unsatisfactory. Although currently available vasopressin (V2 receptors) antagonists have been shown to increase serum sodium concentrations and improve ascites control, their role in the treatment of hyponatremia in liver disease patients remains questionable because of adverse effect profiles, high cost, and poor data on long-term mortality benefits. More information is needed to argue the benefits vs risks of short-term use of vaptans for correction of hyponatremia especially just hours-to-days before liver transplant. PMID:26311597

  17. 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

  18. Elevated expression of Cripto-1 correlates with poor prognosis in hepatocellular carcinoma

    PubMed Central

    Xu, Jing; Guo, Zhi-xing; Xiao, Cheng-zuo; Zhang, Yong-fa; Jian, Pei-en; Wu, Xiao-liang; Shi, Ming; Guo, Rong-ping

    2015-01-01

    Cripto-1 could promote tumorigenesis in a wide range of carcinomas, yet little is known in hepatocellular carcinoma (HCC). The expression of Cripto-1 and MMP-9 were assessed by immunohistochemistry in 205 HCC specimens. The correlation between Cripto-1 and MMP-9, clinicopathological/prognostic value in HCC was examined. Cripto-1 overexpression was correlated with larger tumor, TNM stage, BCLC stage and tumor recurrence. In multivariate analyses, Cripto-1 was an independent predictor for overall survival (OS) and time to recurrence (TTR). Cripto-1 expression was increased in TNM and BCLC stage-dependent manner. Cripto-1 overexpression was associated with poor prognosis in patients subgroups stratified by tumor size, tumor differentiation, TNM and BCLC stage. In addition, Cripto-1 was positively correlated with MMP-9 among 205 HCC samples. Patients with Cripto-1 upregulation had poor OS and shorter TTR in low and high aggressiveness groups. Furthermore, Cripto-1 had predictive validity for early and late recurrence in HCC patients. Combination of Cripto-1 and serum AFP was correlated with OS and TTR. In conclusion, Cripto-1 overexpression contributes to aggressiveness and poor prognosis of HCC. Cripto-1/AFP expression could be a potential prognostic biomarker for survival in HCC patients. PMID:26375669

  19. Thrombocytosis as a prognostic marker in gastrointestinal cancers

    PubMed Central

    Voutsadakis, Ioannis A

    2014-01-01

    Thrombocytosis is an adverse prognostic factor in many types of cancer. These include breast cancer, ovarian and other gynecologic cancers, renal cell carcinoma and lung cancers. In gastrointestinal cancers of various locations and histologic types, thrombocytosis has been reported in general to be associated with adverse clinical outcomes. Platelet count measurement is well standardized and available in every clinical laboratory, making its use as a prognostic marker practical. This paper will discuss the data on the prognostic value of thrombocytosis in gastrointestinal cancers as well as pathogenic aspects of the association that strengthen the case for its use in clinical prognostication. PMID:24567794

  20. Thrombocytosis as a prognostic marker in gastrointestinal cancers.

    PubMed

    Voutsadakis, Ioannis A

    2014-02-15

    Thrombocytosis is an adverse prognostic factor in many types of cancer. These include breast cancer, ovarian and other gynecologic cancers, renal cell carcinoma and lung cancers. In gastrointestinal cancers of various locations and histologic types, thrombocytosis has been reported in general to be associated with adverse clinical outcomes. Platelet count measurement is well standardized and available in every clinical laboratory, making its use as a prognostic marker practical. This paper will discuss the data on the prognostic value of thrombocytosis in gastrointestinal cancers as well as pathogenic aspects of the association that strengthen the case for its use in clinical prognostication. PMID:24567794

  1. 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. PMID:26792832

  2. Prognostic Impact of the 6th and 7th American Joint Committee on Cancer TNM Staging Systems on Esophageal Cancer Patients Treated With Chemoradiotherapy

    SciTech Connect

    Nomura, Motoo; Shitara, Kohei; Kodaira, Takeshi; Hatooka, Shunzo; Mizota, Ayako; Kondoh, Chihiro; Yokota, Tomoya; Takahari, Daisuke; Ura, Takashi; Muro, Kei

    2012-02-01

    Purpose: The new 7th edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT. Methods and Materials: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of the 6th and 7th staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition. Results: There were significant differences between Stages I and III (p < 0.01) according to both editions. However, the 7th edition poorly distinguishes the prognoses of Stages III and IV (p = 0.36 by multivariate analysis) in comparison to the 6th edition (p = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (p < 0.05). For the Stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for Stage IIA. However, there were no significant differences seen between each prognostic stage. Conclusions: Our study indicates there are several problems with the 7th TNM staging system regarding prognostic factors in patients undergoing CRT.

  3. Prognostic implication of gene mutations on overall survival in the adult acute myeloid leukemia patients receiving or not receiving allogeneic hematopoietic stem cell transplantations.

    PubMed

    Chou, Sheng-Chieh; Tang, Jih-Luh; Hou, Hsin-An; Chou, Wen-Chien; Hu, Fu-Chang; Chen, Chien-Yuan; Yao, Ming; Ko, Bor-Sheng; Huang, Shang-Yi; Tsay, Woei; Chen, Yao-Chang; Tien, Hwei-Fang

    2014-11-01

    Several gene mutations have been shown to provide clinical implications in patients with acute myeloid leukemia (AML). However, the prognostic impact of gene mutations in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We retrospectively evaluated the clinical implications of 8 gene mutations in 325 adult AML patients; 100 of them received allo-HSCT and 225 did not. The genetic alterations analyzed included NPM1, FLT3-ITD, FLT3-TKD, CEBPA, RUNX1, RAS, MLL-PTD, and WT1. In patients who did not receive allo-HSCT, older age, higher WBC count, higher lactate dehydrogenase level, unfavorable karyotype, and RUNX1 mutation were significantly associated with poor overall survival (OS), while CEBPA double mutation (CEBPA(double-mut)) and NPM1(mut)/FLT3-ITD(neg) were associated with good outcome. However, in patients who received allo-HSCT, only refractory disease status at the time of HSCT and unfavorable karyotype were independent poor prognostic factors. Surprisingly, RUNX1 mutation was an independent good prognostic factor for OS in multivariate analysis. The prognostic impact of FLT3-ITD or NPM1(mut)/FLT3-ITD(neg) was lost in this group of patients receiving allo-HSCT, while CEBPA(double-mut) showed a trend to be a good prognostic factor. In conclusion, allo-HSCT can ameliorate the unfavorable influence of some poor-risk gene mutations in AML patients. Unexpectedly, the RUNX1 mutation showed a favorable prognostic impact in the context of allo-HSCT. These results need to be confirmed by further studies with more AML patients. PMID:25260824

  4. Explaining the Role of Proximate Determinants on Fertility Decline among Poor and Non-Poor in Asian Countries

    PubMed Central

    Majumder, Nabanita; Ram, Faujdar

    2015-01-01

    Objectives We examined the overall contributions of the poor and non-poor in fertility decline across the Asian countries. Further, we analyzed the direct and indirect factors that determine the reproductive behaviour of two distinct population sub-groups. Design Data from several new rounds of DHS surveys are available over the past few years. The DHS provides cross-nationally comparable and useful data on fertility, family planning, maternal and child health along with the other information. Six selected Asian countries namely: Bangladesh, India, Indonesia, Nepal, Philippines, and Vietnam are considered for the purpose of the study. Three rounds of DHS surveys for each country (except Vietnam) are considered in the present study. Methods Economic status is measured by computing a “wealth index”, i.e. a composite indicator constructed by aggregating data on asset ownership and housing characteristics using principal components analysis (PCA). Computed household wealth index has been broken into three equal parts (33.3 percent each) and the lowest and the highest 33.3 percent is considered as poor and non-poor respectively. The Bongaarts model was employed to quantify the contribution of each of the proximate determinants of fertility among poor and non-poor women. Results Fertility reduction across all population subgroups is now an established fact despite the diversity in the level of socio-economic development in Asian countries. It is clear from the analysis that fertility has declined irrespective of economic status at varying degrees within and across the countries which can be attributed to the increasing level of contraceptive use especially among poor women. Over the period of time changing marriage pattern and induced abortion are playing an important role in reducing fertility among poor women. Conclusions Fertility decline among majority of the poor women across the Asian countries is accompanied by high prevalence of contraceptive use followed by changing marriage pattern and induced abortion. PMID:25689843

  5. Suppressor of cytokine signaling 1 gene mutation status as a prognostic biomarker in classical Hodgkin lymphoma

    PubMed Central

    Bubolz, Anna-Maria; Lessel, Davor; Welke, Claudia; Rther, Nele; Viardot, Andreas; Mller, Peter

    2015-01-01

    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. PMID:26336985

  6. Expression and prognostic significance of contactin 1 in human hepatocellular carcinoma

    PubMed Central

    Li, Guang-Yao; Huang, Mei; Pan, Ting-Ting; Jia, Wei-Dong

    2016-01-01

    Background CNTN1, a member of the CNTN family of neural cell-recognition molecules, is involved in tumor invasion and metastasis. Although the expression of CNTN1 has been reported in several human malignancies, the expression of CNTN1 in hepatocellular carcinoma (HCC) and its correlation with prognosis remain unclear. The aim of this study was to evaluate the expression of CNTN1 and determine the clinicopathological parameters and prognostic value of CNTN1 in HCC patients. Materials and methods Quantitative real-time polymerase chain-reaction and Western blotting assays were performed to assess messenger RNA and protein levels of CNTN1 in 20 matched HCC specimens. The clinical and prognostic significance of CNTN1 in 90 cases of HCC was determined by immunohistochemistry. Results CNTN1 expression was higher in HCC compared to the expression found in adjacent tissues at both messenger RNA and protein levels (P<0.01). Notably, immunohistochemical results revealed that CNTN1 expression was significantly higher in HCC compared to adjacent tissues (54.4% vs 12.2%, P=0.01). Furthermore, positive CNTN1 expression was associated with tumor size, tumor capsulae, status of metastasis, and tumor–node–metastasis stage. Kaplan–Meier survival analysis showed that high CNTN1 was correlated with reduced overall survival (OS) rate (P<0.001) and disease-free survival (DFS) rate (P=0.001). Multivariate analysis identified CNTN1 as an independent poor prognostic factor of OS and DFS in HCC patients (P=0.007 and P=0.002, respectively). Conclusion Our results suggest that CNTN1 could play an important role in HCC and serve as an independent unfavorable prognostic factor for OS and DFS and a potential therapeutic target for HCC. PMID:26855587

  7. Plasma hyaluronic acid level as a prognostic and monitoring marker of metastatic breast cancer.

    PubMed

    Peng, Cike; Wallwiener, Markus; Rudolph, Anja; Ćuk, Katarina; Eilber, Ursula; Celik, Muhabbet; Modugno, Caroline; Trumpp, Andreas; Heil, Jörg; Marmé, Frederik; Madhavan, Dharanija; Nees, Juliane; Riethdorf, Sabine; Schott, Sarah; Sohn, Christof; Pantel, Klaus; Schneeweiss, Andreas; Chang-Claude, Jenny; Yang, Rongxi; Burwinkel, Barbara

    2016-05-15

    Conventional tumor markers have limited value for prognostication and treatment monitoring in metastatic breast cancer (MBC) patients and novel circulating tumor markers therefore need to be explored. Hyaluronic acid (HA) is a major macropolysaccharide in the extracellular matrix and is reported to be associated with tumor progression. In our study, we investigated plasma HA level with respect to progression free survival (PFS) and overall survival (OS), as well as the treatment monitoring value in MBC patients. The prognostic value of plasma HA level was investigated in a discovery cohort of 212 MBC patients with 2.5-year follow-up and validated in an independent validation cohort of 334 patients with 5-year follow-up. The treatment monitoring value of plasma HA level was investigated in 61 MBC patients from discovery cohort who had been radiographically examined after first complete cycle of chemo therapy. We found a robust association between high plasma HA level and poor prognosis of MBC patients in both discovery (pPFS  = 7.92 × 10(-6) and pOS  = 5.27 × 10(-5) ) and validation studies (pPFS  = 3.66 × 10(-4) and pOS  = 1.43 × 10(-4) ). In the discovery cohort, the plasma HA level displayed independent prognostic value after adjusted for age and clinicopathological factors, with respect to PFS and OS. Further, the decrease of plasma HA level displayed good concordance with treatment response evaluated by radiographic examination (AUC = 0.79). Plasma HA level displays prognostic value, as well as treatment monitoring value for MBC patients. PMID:26686298

  8. 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. PMID:26187126

  9. Prognostic value of Diabetes in Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiation Therapy.

    PubMed

    Peng, Hao; Chen, Lei; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    The prognostic value of diabetes remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed medical records of 1489 patients with non-metastatic, histologically-proven NPC treated using IMRT. 81/1489 (5.4%) patients were diabetic, 168/1489 (11.3%) were prediabetic, and 1240/1489 (83.3%) were normoglycemic. The 4-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates were 77.1% vs. 82.4% (P?=?0.358), 85.8% vs. 91.0% (P?=?0.123), 90.9% vs. 91.7% (P?=?0.884), and 85.5% vs. 89.2% (P?=?0.445) for diabetic vs. normoglycemic patients, and 82.4% vs. 82.4% (P?=?0.993), 88.7% vs. 91.0% (P?=?0.285), 90.6% vs. 91.7% (P?=?0.832) and 91.5% vs. 89.2% (P?=?0.594) for preidabetic vs. normoglycemic patients. Multivariate analysis did not established diabetes as poor prognostic factors in NPC patients treated with IMRT (P?=?0.332 for DFS, P?=?0.944 for OS, P?=?0.977 for LRRFS, P?=?0.157 for DMFS), however, triglycerides and low density lipoprotein cholesterol were independent prognostic factors. In conclusion, diabetes does not appear to be a prognostic factor in NPC patients treated with IMRT, and attention should be paid to hyperglycemia-associated hyperlipaemia. PMID:26927312

  10. The Prognostic Significance of HbF in Childhood Haematological Malignancies.

    PubMed

    Mallick, Debjani; Karmakar, Rupam; Barui, Gopinath; Gon, Sonia; Chakrabarti, Sudipta

    2015-03-01

    The degree of increase infoetal haemoglobin(HbF) synthesis in haematological malignancies may be associated with the degree of malignancy. The aim of the present study was to quantify HbF levels in various childhood haematological malignancies and also, to ascertain its prognostic significance by comparing the results with the already established standard prognostic factors. Newly diagnosed cases of haematological malignancies in the paediatric age group were included in the study. HbF levels were estimated in each case of the study group along with HbF levels of control group comprising healthy children of same age group. The estimation was done by HPLC and Modified Betke's method. 50 cases of newly diagnosed haematological malignancies were studied out of which most of the cases were of acute lymphoblastic leukaemia (ALL) [n=30(60%)] followed by acute myeloid leukaemia (AML) [n=8(16%)], Hodgkin's lymphoma [n=7(14%)], non-Hodgkin's lymphoma [n=5(10%)]. Raised HbF levels were found in 43.3% cases of ALL (13/30) and 37.5% cases of AML (3/8). No significant rise in HbF level was found in cases of lymphomas. There was correlation between raised HbF level and poor prognostic factors in cases of ALL but no such correlation was found in cases of AML. HbF levels are often elevated in childhood leukaemias as compared to childhood lymphomas. Thus, the concentration of HbF in acute childhood leukaemia may be considered as a prognostic factor. PMID:25548456

  11. 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

  12. Prognostic value of Diabetes in Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiation Therapy

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    The prognostic value of diabetes remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed medical records of 1489 patients with non-metastatic, histologically-proven NPC treated using IMRT. 81/1489 (5.4%) patients were diabetic, 168/1489 (11.3%) were prediabetic, and 1240/1489 (83.3%) were normoglycemic. The 4-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates were 77.1% vs. 82.4% (P = 0.358), 85.8% vs. 91.0% (P = 0.123), 90.9% vs. 91.7% (P = 0.884), and 85.5% vs. 89.2% (P = 0.445) for diabetic vs. normoglycemic patients, and 82.4% vs. 82.4% (P = 0.993), 88.7% vs. 91.0% (P = 0.285), 90.6% vs. 91.7% (P = 0.832) and 91.5% vs. 89.2% (P = 0.594) for preidabetic vs. normoglycemic patients. Multivariate analysis did not established diabetes as poor prognostic factors in NPC patients treated with IMRT (P = 0.332 for DFS, P = 0.944 for OS, P = 0.977 for LRRFS, P = 0.157 for DMFS), however, triglycerides and low density lipoprotein cholesterol were independent prognostic factors. In conclusion, diabetes does not appear to be a prognostic factor in NPC patients treated with IMRT, and attention should be paid to hyperglycemia-associated hyperlipaemia. PMID:26927312

  13. CD5-positive follicular lymphoma characterized by CD25, MUM1, low frequency of t(14;18) and poor prognosis.

    PubMed

    Miyoshi, Hiroaki; Sato, Kensaku; Yoshida, Maki; Kimura, Yoshizo; Kiyasu, Junichi; Ichikawa, Ayako; Ishibashi, Yukinao; Arakawa, Fumiko; Nakamura, Yukihiko; Nakashima, Shinji; Niino, Daisuke; Sugita, Yasuo; Ohshima, Koichi

    2014-03-01

    CD5-positive follicular lymphoma (FL), although rare, has been described in a number of case reports. However, a statistically valid, clinicopathological comparison between CD5-positive FL and CD5-negative FL has never been performed because of its rarity. We statistically compared clinicopathological characteristics of 22 cases of CD5-positive FL, diagnosed by immunohistochemistry, flow cytometry and morphological findings, with those of 62 cases of FL without CD5 expression (control cases). CD5-positive FL patients showed a higher tendency of peripheral blood involvement (P = 0.076) and a higher frequency of CD25 expression (P = 0.0004) and MUM1 protein expression (P = 0.0008), and a lower frequency of t(14;18)(q32;q21) (P = 0.017). The overall survival (OS) curve of CD5-positive FL was significantly worse than that of control cases (P = 0.0266), although progression-free survival curves did not show a significant difference (P = 0.7899). Moreover, CD5 expression was shown to be an independent poor prognostic factor for OS in both univariate analysis [Hazard Ratio (HR), 3.63; P = 0.0464] and multivariate analysis (HR, 57.16; P = 0.0001). CD5-positive FL showed different clinicopathological characteristics from FL lacking CD5 expression. These results suggest that CD5-positive FL should be considered a different type of FL, and its clinicopathological management should be conducted differently. PMID:24698419

  14. High GINS2 transcript level predicts poor prognosis and correlates with high histological grade and endocrine therapy resistance through mammary cancer stem cells in breast cancer patients.

    PubMed

    Zheng, Ming; Zhou, Yinghui; Yang, Xiangmin; Tang, Juan; Wei, Ding; Zhang, Yang; Jiang, Jian-Li; Chen, Zhi-Nan; Zhu, Ping

    2014-11-01

    GINS2, a subunit of the GINS complex, is overexpressed in lung adenocarcinoma and metastatic breast tumor; however, its prognostic power and possible molecular mechanisms in breast cancer (BC) remain unclear. In this study, we aimed to explore the function of GINS2 in BC. The association between GINS2 transcript level and the clinical outcome of BC patients were estimated using Kaplan-Meier plots, multivariate cox regression analysis, forest plots, and receiver operating characteristics curves. Gene set enrichment analysis (GSEA) was performed to explore the mechanisms underlying the effects of the GINS2 transcript. High GINS2 transcript level was correlated with poor relapse free survival (log-rank P ≤ 0.001 in six cohorts; forest plot: total n = 1,420, total RR = 1.72, 95% CI 1.45-2.03; multivariate cox regression analysis: n = 906, HR 2.36, 95% CI 1.88-2.97), and distant metastasis free survival (log-rank P < 0.01 in 3 cohorts; forest plot: total n = 691, total RR 1.91, 95% CI 1.36-2.67; multivariate cox regression analysis: n = 442, HR 2.43, 95% CI 1.70-3.47). BC patients with higher GINS2 transcript levels showed poorer tamoxifen efficacy in a dose-dependent manner. GINS2 expression was significantly downregulated under mutated p53-depleted condition in MDA-468 and MDA-MB-231 cells, upregulated in mammary cancer stem cells (MaCSCs) (P = 0.003), and correlated with upregulated genes in mammary stem cells (GSEA: P < 0.01). Our study, for the first time, demonstrates that GINS2 is an independent prognostic marker and is associated with lung metastasis, histological grade, and endocrine therapy resistance in BC patients, which may attribute to mutant p53 and MaCSCs. PMID:25348432

  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. PMID:26774144

  17. 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 to be associated with glioma. Furthermore, glioma patients with higher miR-125b, miR-221, and miR-222 expression were manifested to have poorer prognostic status, which might be attributed to their attenuated sensitivity to chemotherapy and radiotherapy. PMID:25502291

  18. Prognostic factors of spontaneously ruptured hepatocellular carcinoma

    PubMed Central

    Han, Xiang-Jun; Su, Hong-Ying; Shao, Hai-Bo; Xu, Ke

    2015-01-01

    AIM: To evaluate the prognostic factors in patients with spontaneously ruptured hepatocellular carcinoma (HCC). METHODS: Seventy-nine patients experiencing spontaneous rupture of HCC between April 2004 and August 2014 were enrolled in this study. The clinical features, treatment modalities and outcomes were reviewed. The statistical methods used in this work included univariate analysis, Kaplan-Meier survival analysis with log-rank tests, and multivariate analysis using a Cox regression hazard model. RESULTS: Of the 79 patients with HCC rupture, 17 (21.5%) underwent surgery, 32 (40.5%) underwent transarterial embolization (TAE), and 30 (38%) received conservative treatment. The median survival time was 125 d, and the mortality rate at 30 d was 27.8%. Multivariate analysis revealed that lesion length (HR = 1.46, P < 0.001), lesion number (HR = 1.37, P = 0.042), treatment before tumor rupture (HR = 4.36, P = 0.019), alanine transaminase levels (HR = 1.0, P = 0.011), bicarbonate levels (HR = 1.18, P < 0.001), age (HR = 0.96, P = 0.026), anti-tumor therapy during the follow-up period (HR = 0.21, P = 0.008), and albumin levels (HR = 0.89, P = 0.010) were independent prognostic factors of survival after HCC rupture. The Barcelona-Clinic Liver Cancer (BCLC) stage was also an important prognostic factor; the median survival times for BCLC stages A, B and C were 251, 175 and 40 d, respectively (P < 0.001). CONCLUSION: Anti-tumor therapy during the follow-up period, without a history of anti-tumor therapy prior to HCC rupture, small tumor length and number, and early BCLC stage are the most crucial predictors associated with satisfactory overall survival. Other factors play only a small role in overall survival. PMID:26139994

  19. Stress testing on silicon carbide electronic devices for prognostics and health management.

    SciTech Connect

    Kaplar, Robert James; Brock, Reinhard C.; Marinella, Matthew; King, Michael Patrick; Smith, Mark A.; Atcitty, Stanley

    2011-01-01

    Power conversion systems for energy storage and other distributed energy resource applications are among the drivers of the important role that power electronics plays in providing reliable electricity. Wide band gap semiconductors such as silicon carbide (SiC) and gallium nitride (GaN) will help increase the performance and efficiency of power electronic equipment while condition monitoring (CM) and prognostics and health management (PHM) will increase the operational availability of the equipment and thereby make it more cost effective. Voltage and/or temperature stress testing were performed on a number of SiC devices in order to accelerate failure modes and to identify measureable shifts in electrical characteristics which may provide early indication of those failures. Those shifts can be interpreted and modeled to provide prognostic signatures for use in CM and/or PHM. Such experiments will also lead to a deeper understanding of basic device physics and the degradation mechanisms behind failure.

  20. Prognostic variables and surgical management of foot melanoma: review of a 25-year institutional experience.

    PubMed

    Rashid, Omar M; Schaum, Julia C; Wolfe, Luke G; Brinster, Nooshin K; Neifeld, James P

    2011-01-01

    Introduction. Cutaneous foot melanoma is rare, challenging to manage, and not adequately examined in the literature. This study evaluated the prognostic variables and surgical management of foot melanoma. Materials and Methods. Foot melanoma cases managed at an academic center from 1985 to 2010 were retrospectively reviewed. Results. 46 patients were identified with a broad range of demographic characteristics. Overall recurrence was 32.6%: 19% acral lentiginous, 57% nodular, 66% superficial spreading, 30% melanoma unspecified, 50% severely atypical; 53% ulcerated, 23% nonulcerated; 29% on the dorsum of the foot, 17% heel, 60% ankle, 22% toe, 50% plantar; 0%?<1?mm thick, 47%?1-4?mm, 33% >4?mm. 13 had positive nodes, 4 (31%) of whom recurred. Prognostic factors and recurrence did not correlate, and survival was 96% with a median followup of 91 months. Conclusions. Aggressive management of foot melanoma may result in excellent long-term survival even following disease recurrence. PMID:22363851

  1. 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 rates were no different in these two groups; however, when unchanged hearing rates were compared, it was statistically significantly lower in the early treatment group (p<0.05). When hearing outcomes were compared according to initial audiological pattern, significant recovery and unchanged hearing rates did not differ between groups; however, slight recovery rate was highest in the “flat” type audiological configuration (p<0.05). Conclusion: According to this patient series, oral steroid therapy does not have any influence on the outcomes of SSNHL. However, mid-frequency hearing loss of flat type and initiation of treatment earlier than 5 days from the onset of symptoms, seem to have positive prognostic effects. Further randomized controlled subject groups might contribute to determine prognostic factors of SSNHL. PMID:26966623

  2. Cellular prognostic markers in hepatocellular carcinoma.

    PubMed

    Buonaguro, Luigi; Tagliamonte, Maria; Petrizzo, Annacarmen; Damiano, Elvira; Tornesello, Maria Lina; Buonaguro, Franco M

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the five big killers worldwide and is frequently associated with chronic hepatitis B and C virus (HBV and HCV) infections. Tumor microenvironment consists of a complex network of cells and factors that plays a key role in the tumor progression and prognosis. This is true also for HCC. Several studies have shown strikingly strong correlation between HCC clinical prognosis and intratumoral infiltration of cells affecting tumor growth, invasion, angiogenesis and metastasis. None of such cells is yet validated for routine diagnostic and prognostic assessment. The present review aims at providing a state-of-the-art of such studies. PMID:26043213

  3. A new prognostic index to make short-term prognoses in MDS patients treated with azacitidine: A combination of p53 expression and cytogenetics.

    PubMed

    Nishiwaki, Satoshi; Ito, Masafumi; Watarai, Rie; Okuno, Shingo; Harada, Yasuhiko; Yamamoto, Satomi; Suzuki, Kotaro; Kurahashi, Shingo; Iwasaki, Toshihiro; Sugiura, Isamu

    2016-02-01

    TP53 mutation is associated with various hematological malignancies and immunohistochemistry of p53 has been used as a simple method to establish the presence of a TP53 mutation. Since the significance of p53 expression is controversial in myelodysplastic syndrome (MDS) patients treated with azacitidine (Aza), we analyzed the prevalence of p53 expression as a prognostic factor in 60 MDS patients treated with Aza. To assess p53 expression, immunohistochemical analyses of bone marrow clot sections were performed. Overall survival (OS) was significantly lower in p53-positive patients compared with p53-negetive patients (59% vs. 85% at 12 months; P=0.006). Multivariate analysis demonstrated that p53-positive was a significant prognostic factor for OS along with poor cytogenetics. Here, we propose a new prognostic index to make short-term prognoses of MDS patients in the era of Aza treatment; high: p53-positive and poor cytogenetics, low: p53-negative and absence of poor cytogenetics, and intermediate: the others. OS was significantly different among the three groups according to this index (Low 92%, Intermediate 65% and High 27% at 12 months; P<0.0001). In conclusion, p53 expression was a significant prognostic factor in MDS patients treated with Aza. In combination with cytogenetic abnormalities, it is possible to make short-term prognoses. PMID:26651421

  4. Continuous Amplitude-Integrated Electroencephalographic Monitoring Is a Useful Prognostic Tool for Hypothermia-Treated Cardiac Arrest Patients

    PubMed Central

    Oh, Sang Hoon; Shon, Young-Min; Kim, Young-Min; Kim, Han Joon; Youn, Chun Song; Kim, Soo Hyun; Choi, Seung Pill; Kim, Seok Chan

    2015-01-01

    Background Modern treatments have improved the survival rate following cardiac arrest, but prognostication remains a challenge. We examined the prognostic value of continuous electroencephalography according to time by performing amplitude-integrated electroencephalography on patients with cardiac arrest receiving therapeutic hypothermia. Methods and Results We prospectively studied 130 comatose patients treated with hypothermia from September 2010 to April 2013. We evaluated the time to normal trace (TTNT) as a neurological outcome predictor and determined the prognostic value of burst suppression and status epilepticus, with a particular focus on their time of occurrence. Fifty-five patients exhibited a cerebral performance category score of 1 to 2. The area under the curve for TTNT was 0.97 (95% confidence interval, 0.920.99), and the sensitivity and specificity of TTNT<24 hours after resuscitation as a threshold for predicting good neurological outcome were 94.6% (95% confidence interval, 84.9%98.9%) and 90.7% (95% confidence interval, 81.7%96.2%), respectively. The threshold displaying 100% specificity for predicting poor neurological outcome was TTNT>36 hours. Burst suppression and status epilepticus predicted poor neurological outcome (positive predictive value of 98.3% and 96.4%, respectively). The combination of these factors predicted a negative outcome at a median of 6.2 hours after resuscitation (sensitivity and specificity of 92.0% and 96.4%, respectively). Conclusions A TTNT<24 hours was associated with good neurological outcome. The lack of normal trace development within 36 hours, status epilepticus, and burst suppression were predictors of poor outcome. The combination of these negative predictors may improve their prognostic performance at an earlier stage. PMID:26269576

  5. Development and Validation of a Prognostic Score to Predict Survival in Adult Patients With Solid Tumors and Bone Marrow Metastases

    PubMed Central

    Chou, Wen-Chi; Yeh, Kun-Yun; Peng, Meng-Ting; Chen, Jen-Shi; Wang, Hung-Ming; Lin, Yung-Chang; Liu, Chien-Ting; Chang, Pei-Hung; Wang, Cheng-Hsu; Chen, Ping-Tsung; Hung, Yu-Shin; Lu, Chang-Hsien

    2015-01-01

    Abstract Bone marrow metastasis (BMM) in patients with solid cancers is indicative of advanced-stage disease with a poor prognosis. The clinical features and outcomes remain unclear. We aimed to develop a scoring system to predict survival in these patients to help with clinical decision making. A total of 165 adult patients diagnosed with solid cancers and BMM between 2000 and 2014 were selected as the derivation cohort. A risk model was developed using multivariate logistic regression from the derivation cohort and a marrow metastases prognostic score (MMPS) was generated. An independent cohort of 156 patients from 3 other hospitals was selected using the same recruiting criteria to validate the MMPS as a predictor of survival. The MMPS was calculated based on 4 independent prognostic variables: the Eastern Cooperative Oncology Group performance scale, site of cancer, platelet count, and neutrophil-to-lymphocyte ratio. Patients in both the derivation and validation cohorts were stratified into good, intermediate, and poor prognostic groups based on their MMPS. The median survival in each risk group of the derivation cohort was 241, 58, and 11 days for the good, intermediate, and poor prognostic groups, respectively, and 305, 65, and 9 days, respectively, in the validation cohort. The c-statistic values for prediction of mortality at 3, 6, and 12 months were significantly higher for the MMPS than for the Eastern Cooperative Oncology Group performance scale in both cohorts. We developed a risk model that accurately predicted survival in adult patients with solid cancers and BMM. This scoring system may help patients and clinicians with treatment decisions. PMID:26061333

  6. Tumour location within the breast: Does tumour site have prognostic ability?

    PubMed Central

    Rummel, Seth; Hueman, Matthew T; Costantino, Nick; Shriver, Craig D; Ellsworth, Rachel E

    2015-01-01

    Introduction Tumour location within the breast varies with the highest frequency in the upper outer quadrant (UOQ) and lowest frequency in the lower inner quadrant (LIQ). Whether tumour location is prognostic is unclear. To determine whether tumour location is prognostic, associations between tumour site and clinicopathological characteristics were evaluated. Materials and Methods All patients enrolled in the Clinical Breast Care Project whose tumour siteUOQ, upper inner quadrant (UIQ), central, LIQ, lower outer quadrant (LOQ)was determined by a single, dedicated breast pathologist were included in this study. Patients with multicentric disease (n = 122) or tumours spanning multiple quadrants (n = 381) were excluded from further analysis. Clinicopathological characteristics were analysed using chi-square tests for univariate analysis with multivariate analysis performed using principal components analysis (PCA) and multiple logistic regression. Significance was defined as P < 0.05. Results Of the 980 patients with defined tumour location, 30 had bilateral disease. Tumour location in the UOQ (51.5%) was significantly higher than in the UIQ (15.6%), LOQ (14.2%), central (10.6%), or LIQ (8.1%). Tumours in the central quadrant were significantly more likely to have higher tumour stage (P = 0.003) and size (P < 0.001), metastatic lymph nodes (P < 0.001), and mortality (P = 0.011). After multivariate analysis, only tumour size and lymph node status remained significantly associated with survival. Conclusions Evaluation of tumour location as a prognostic factor revealed that although tumours in the central region are associated with less favourable outcome, these associations are not independent of location but rather driven by larger tumour size. Tumours in the central region are more difficult to detect mammographically, resulting in larger tumour size at diagnosis and thus less favourable prognosis. Together, these data demonstrate that tumour location is not an independent prognostic factor. PMID:26284116

  7. Technical Needs for Prototypic Prognostic Technique Demonstration for Advanced Small Modular Reactor Passive Components

    SciTech Connect

    Meyer, Ryan M.; Coble, Jamie B.; Hirt, Evelyn H.; Ramuhalli, Pradeep; Mitchell, Mark R.; Wootan, David W.; Berglin, Eric J.; Bond, Leonard J.; Henager, Charles H.

    2013-05-17

    This report identifies a number of requirements for prognostics health management of passive systems in AdvSMRs, documents technical gaps in establishing a prototypical prognostic methodology for this purpose, and describes a preliminary research plan for addressing these technical gaps. AdvSMRs span multiple concepts; therefore a technology- and design-neutral approach is taken, with the focus being on characteristics that are likely to be common to all or several AdvSMR concepts. An evaluation of available literature is used to identify proposed concepts for AdvSMRs along with likely operational characteristics. Available operating experience of advanced reactors is used in identifying passive components that may be subject to degradation, materials likely to be used for these components, and potential modes of degradation of these components. This information helps in assessing measurement needs for PHM systems, as well as defining functional requirements of PHM systems. An assessment of current state-of-the-art approaches to measurements, sensors and instrumentation, diagnostics and prognostics is also documented. This state-of-the-art evaluation, combined with the requirements, may be used to identify technical gaps and research needs in the development, evaluation, and deployment of PHM systems for AdvSMRs. A preliminary research plan to address high-priority research needs for the deployment of PHM systems to AdvSMRs is described, with the objective being the demonstration of prototypic prognostics technology for passive components in AdvSMRs. Greater efficiency in achieving this objective can be gained through judicious selection of materials and degradation modes that are relevant to proposed AdvSMR concepts, and for which significant knowledge already exists. These selections were made based on multiple constraints including the analysis performed in this document, ready access to laboratory-scale facilities for materials testing and measurement, and potential synergies with other national laboratory and university partners.

  8. Elevated RABEX-5 expression predicts poor prognosis in non-small-cell lung cancer

    PubMed Central

    Zhang, Fuliang; Jia, Yingjie; Kong, Fanming; Hu, Guohua; Cai, Qiling; Xu, Tongbai

    2015-01-01

    RABEX-5 has been studied in various solid tumors, but its role in non-small-cell lung cancer (NSCLC) remains unknown. This study is aimed to investigate the expression, the potential relevance to clinicopathological characters and prognostic significance of RABEX-5 in patients with NSCLC. A total of 120 NSCLC patients who underwent radical surgery between 2005 and 2010 were enrolled in the study. The clinicopathological data and survival time were reviewed. The mRNA and protein expression of RABEX-5 from the paired tumor specimens and adjacent normal tissues were determined, and its relationship with clinicopathological variables and prognosis was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of RABEX-5 for NSCLC. We found the mRNA and protein expression levels of RABEX-5 were significantly elevated in NSCLC tissues. The increased RABEX-5 expression was correlated strongly with tumor recurrence (P=0.005). The 5-year median OS and DFS were significantly shorter in the higher RABEX-5 expression group compared to that in the lower RABEX-5 expression group. Multivariate Cox analysis indicated that high RABEX-5 expression was an independent prognostic factor for OS and DFS (P<0.001). This data suggests that RABEX-5 is a potentially useful indicator for a poor prognosis for NSCLC. PMID:26609490

  9. Abnormal expression of calcyphosine is associated with poor prognosis and cell biology function in colorectal cancer

    PubMed Central

    Shao, Weiwei; Wang, Quhui; Wang, Feiran; Jiang, Yasu; Xu, Meirong; Xu, Junfei

    2016-01-01

    The aim of this study was to investigate the calcyphosine (CAPS) expression in human colorectal cancer (CRC) and to explore its clinical and prognostic significances. CAPS expression was measured by Western blot, real-time polymerase chain reaction analysis, and immunohistochemistry. The relationships between the CAPS expression levels and the clinicopathological factors were investigated. The Kaplan–Meier method and log-rank test were used to investigate the overall survival of the patients. Moreover, the effects of CAPS on biological roles of CRC cells were also evaluated by MTT assay, colony formation assay, and transwell assay. CAPS was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent nontumor tissue and a normal human intestinal epithelial cell line. Overexpression of CAPS was significantly associated with histological grade (P=0.004), invasive depth (P<0.001), lymph node metastasis (P=0.003), tumor node metastasis stage (P=0.017), and distant metastasis (P=0.042). Furthermore, silencing of CAPS expression in CRC cells inhibited their proliferation, colony formation, migration, and invasion. Kaplan–Meier survival analysis showed that high CAPS expression might demonstrate poor prognosis in CRC patients. Cox regression analysis revealed that CAPS expression was an independent prognostic factor of CRC. Our data suggested that the upregulation of CAPS might play a role in the carcinogenesis and progression of CRC. CAPS could be used as a potential diagnostic factor and be an independent good prognostic indicator for CRC patients. PMID:26889086

  10. Protein Z efficiently depletes thrombin generation in disseminated intravascular coagulation with poor prognosis.

    PubMed

    Lee, Nuri; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Kim, Inho; Yoon, Sung-Soo; Park, Seonyang; Han, Kyou-Sup; Kim, Hyun Kyung

    2016-01-01

    Disseminated intravascular coagulation (DIC) is characterized by consumption of coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives useful information about global hemostatic status. We developed a new TGA system that anticoagulant addition can deplete thrombin generation in plasma, which may reflect defective anticoagulant system in DIC. TGAs were measured on the calibrated automated thrombogram with and without thrombomodulin or protein Z in 152 patients who were suspected of having DIC, yielding four parameters including lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak in TGA-protein Z system, which was performed with added protein Z. In multivariate Cox regression analysis, lag time and time-to-peak in TGA system were significant independent prognostic factors. In TGA-protein Z system, lag time and time-to-peak were revealed as independent prognostic factors of DIC. Protein Z addition could potentiate its anticoagulant effect in DIC with poor prognosis, suggesting the presence of defective protein Z system. The prolonged lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to be used as independent prognostic factors of DIC. PMID:26203764

  11. Algae -- a poor man's HAART?

    PubMed

    Teas, Jane; Hebert, James R; Fitton, J Helen; Zimba, Paul V

    2004-01-01

    Drawing inferences from epidemiologic studies of HIV/AIDS and in vivo and in vitro HIV inhibition by algae, we propose algal consumption as one unifying characteristic of countries with anomalously low rates. HIV/AIDS incidence and prevalence in Eastern Asia ( approximately 1/10000 adults in Japan and Korea), compared to Africa ( approximately 1/10 adults), strongly suggest that differences in IV drug use and sexual behavior are insufficient to explain the 1000-fold variation. Even in Africa, AIDS/HIV rates vary. Chad has consistently reported low rates of HIV/AIDS (2-4/100). Possibly not coincidentally, most people in Japan and Korea eat seaweed daily and the Kanemba, one of the major tribal groups in Chad, eat a blue green alga (Spirulina) daily. Average daily algae consumption in Asia and Africa ranges between 1 and 2 tablespoons (3-13 g). Regular consumption of dietary algae might help prevent HIV infection and suppress viral load among those infected. PMID:15050097

  12. Increased expression of SOX4 is a biomarker for malignant status and poor prognosis in patients with non-small cell lung cancer.

    PubMed

    Wang, Dingmiao; Hao, Ting; Pan, Yang; Qian, Xiaowei; Zhou, Daixing

    2015-04-01

    The aim of the present study was to analyze the expression of sex-determining region Y-related high mobility group box 4 (SOX4) in non-small cell lung cancer (NSCLC) and its correlation with clinicopathologic characteristics, including the survival of NSCLC patients. To observe initially the expression status of SOX4 in lung squamous cell carcinoma and adenocarcinoma at gene expression omnibus. The expression of SOX4 mRNA and protein was examined in NSCLC tissues and normal lung tissues through real-time PCR and immunohistochemistry. Meanwhile, the relationship of SOX4 expression levels with clinical characteristics of 168 NSCLC patients was analyzed by immunohistochemistry. Univariate and multivariate analyses were performed to determine the association between SOX4 expression and prognosis of NSCLC patients. In our results, SOX4 expression was increased in NSCLC tissues compared with paired normal lung tissues in microarray data (GSE3268). SOX4 mRNA and protein expression were markedly higher in NSCLC tissues than in normal lung tissues (P = 0.001 and P = 0.001, respectively). Using immunohistochemistry, high levels of SOX4 protein were positively correlated with status of differentiated degree (high vs. middle, P = 0.004; high vs. low, P < 0.001), clinical stage (I-II vs. III-IV, P < 0.001), T classification (T1-T2 vs. T3-T4, P = 0.004), N classification (N0-N1 vs. N2-N3, P = 0.002), and M classification (M0 vs. M1, P = 0.011) in NSCLC. Moreover, the higher level of SOX4 expression was markedly correlated with poor overall survival in NSCLC patients (P < 0.001). Multivariate analysis suggested that increased SOX4 expression was a poor independent prognostic predictor for NSCLC patients (P = 0.002). In conclusion, SOX4 plays an important role on NSCLC progression and prognosis and may serve as a convictive prognostic biomarker for NSCLC patients. PMID:25567207

  13. Prognostic Model for Survival in Patients with Metastatic Renal Cell Carcinoma: Results from the International Kidney Cancer Working Group

    PubMed Central

    Manola, Judith; Royston, Patrick; Elson, Paul; McCormack, Jennifer Bacik; Mazumdar, Madhu; Ngrier, Sylvie; Escudier, Bernard; Eisen, Tim; Dutcher, Janice; Atkins, Michael; Heng, Daniel Y. C.; Choueiri, Toni K.; Motzer, Robert; Bukowski, Ronald

    2011-01-01

    Purpose To develop a single validated model for survival in metastatic renal cell carcinoma (mRCC) using a comprehensive international database. Experimental Design A comprehensive database of 3748 patients including previously reported clinical prognostic factors was established by pooling patient-level data from clinical trials. Following quality control and standardization, descriptive statistics were generated. Univariate analyses were conducted using proportional hazards models. Multivariable analysis using a log-logistic model stratified by center and multivariable fractional polynomials was performed to identify independent predictors of survival. Missing data were handled using multiple imputation methods. Three risk groups were formed using the 25th and 75th percentiles of the resulting prognostic index. The model was validated using an independent dataset of 645 patients treated with tyrosine kinase inhibitor (TKI) therapy. Results Median survival in the favorable, intermediate and poor risk groups was 26.9 months, 11.5 months, and 4.2 months, respectively. Factors contributing to the prognostic index included treatment, performance status, number of metastatic sites, time from diagnosis to treatment, and pre-treatment hemoglobin, white blood count, lactate dehydrogenase, alkaline phosphatase, and serum calcium. The model demonstrated good concordance when tested among patients treated with TKI therapy (C statistic=0.741, 95% confidence interval 0.714 to 0.768). Conclusions Nine clinical factors can be used to model survival in mRCC and form distinct prognostic groups. The model demonstrates utility among patients treated in the TKI era. PMID:21828239

  14. Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?

    PubMed Central

    Vidal, Fabien; Guerby, Paul; Luyckx, Mathieu; Haddad, Pascale; Stoeckle, Eberhard; Morice, Philippe; Leblanc, Eric; Lecuru, Fabrice; Daraï, Emile; Classe, Jean Marc; Pomel, Christophe; Filleron, Thomas; Ferron, Gwenael; Querleu, Denis; Rafii, Arash

    2016-01-01

    Objective Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients. Study Design We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis. Results The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758, p = 0.017 and HR = 8.641, p = 0.001 respectively). The relative risk of death within 12 months following relapse in ER patients was 1.61 according to RD status. However, RD did not affect DFS (HR = 0.889, p = 0.5). Conclusion ER in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters. PMID:26820579

  15. Prognostic value of body mass index before treatment for laryngeal squamous cell carcinoma

    PubMed Central

    Li, Zhao-Qu; Zou, Lan; Liu, Tian-Run; Yang, An-Kui

    2015-01-01

    Objective Patients with head and neck cancer often suffer from malnutrition. This study aims to investigate the influence of body mass index (BMI) on the prognosis of laryngeal squamous cell carcinoma (LSCC). Methods A total of 473 patients with LSCC initially treated at Sun Yat-sen University Cancer Center between January 2005 and July 2009 were retrospectively reviewed. Survival analysis was performed by the Kaplan-Meier method and Cox regression model. Results Low BMI before treatment was significantly associated with poor overall survival in patients with LSCC (P<0.001). BMI was an independent prognostic factor for patients with LSCC. Conclusion Leanness before treatment was associated with poor prognosis in patients with LSCC. Good nutritional status is favorable to improve survival in patients with LSCC. PMID:26779376

  16. Prognostic markers and tumour growth kinetics in melanoma patients progressing on vemurafenib.

    PubMed

    Seifert, Heike; Fisher, Rosalie; Martin-Liberal, Juan; Edmonds, Kim; Hughes, Peta; Khabra, Komel; Gore, Martin; Larkin, James

    2016-04-01

    The BRAF inhibitor vemurafenib is an effective drug in patients with BRAF mutant metastatic melanoma, but resistance occurs after a median of 6 months. The anti-CTLA4-antibody, ipilimumab, is a standard first-line and second-line treatment option in Europe, with a median time to response of 2-3 months, but some patients show rapid clinical deterioration before that. The aim of this analysis was to identify prognostic markers for survival after failure of vemurafenib treatment to identify patients who have a sufficient life expectancy to respond to new immunotherapy treatments. We retrospectively analysed 101 consecutive unselected patients treated with vemurafenib for metastatic melanoma at a single institution. The association between clinical parameters and death within 3 months after cessation of vemurafenib (n=69) was assessed by binary logistic and Cox regression. Of the patients, 45% died within 3 months of progression on vemurafenib. Elevated baseline serum lactate dehydrogenase, absence of normalization of serum lactate dehydrogenase on vemurafenib therapy, performance status of at least 2 at progression and time from primary tumour to metastatic disease less than 5 years were identified as poor prognostic markers. In an exploratory tumour growth kinetics analysis (n=16), we found that following cessation of vemurafenib, approximately a third each showed a stable, decelerated or accelerated rate of tumour growth. Patients with these poor prognostic markers are unlikely to have sufficient life expectancy to complete ipilimumab treatment after failure with vemurafenib. Consideration needs to be given to the elective use of immunotherapy before patients become resistant to vemurafenib. This requires prospective randomized evaluation. Our tumour growth kinetics analysis requires confirmation; however, it may suggest that intermittent vemurafenib treatment should be investigated in clinical trials. PMID:26684061

  17. Prognostic impact of persistent cytogenetic abnormalities at complete remission in adult patients with acute lymphoblastic leukemia.

    PubMed

    Short, Nicholas J; Kantarjian, Hagop M; Jabbour, Elias J; O'Brien, Susan M; Faderl, Stefan; Burger, Jan A; Garris, Rebecca; Qiao, Wei; Huang, Xuelin; Jain, Nitin; Konopleva, Marina; Kadia, Tapan M; Daver, Naval; Borthakur, Gautam; Cortes, Jorge E; Ravandi, Farhad

    2016-06-01

    In acute myelogenous leukemia, the persistent detection of abnormal cytogenetics at complete remission (ACCR) is associated with inferior outcomes. However, the prognostic significance of ACCR in adult patients with acute lymphoblastic leukemia (ALL) is unknown. We evaluated 272 adult patients with ALL and abnormal cytogenetics at baseline who were treated with frontline induction chemotherapy, achieved complete remission (CR) and had cytogenetic analysis performed at the time of CR. ACCR was observed in 26 patients (9.6%). Median relapse-free survival was 22 months (95% CI, 12 months to not reached) for patients with ACCR vs. 48 months (range, 30-125 months) in patients with normal cytogenetics at CR (NCCR; P = 0.31). Median overall survival also did not differ significantly between the ACCR (99 months [range, 17 months to not reached]) and NCCR groups (67 months [range, 47 months to not reached], P = 0.86). The specificity of ACCR for minimal residual disease (MRD) positivity by multi-parameter flow cytometry (MFC) was 43%, and there was overall poor correlation between these two methods for the detection of residual disease. When patients were stratified by MRD status, the presence or absence of persistent cytogenetic abnormalities at CR did not add additional prognostic information. This study suggests that there is poor association between MRD assessment by MFC and the presence or absence of cytogenetic abnormalities at CR in adult patients with ALL. ACCR was not associated with adverse outcomes in ALL and did not add additional prognostic information when MRD status by MFC was known. Am. J. Hematol. 91:385-389, 2016. © 2016 Wiley Periodicals, Inc. PMID:26800008

  18. Prognostic significance of glypican-3 in hepatocellular carcinoma: a meta-analysis

    PubMed Central

    2014-01-01

    Backgrounds Glypican-3(GPC3) has been implicated in tumor development and progression for several years. However, the prognostic significance of GPC3 expression in patients with hepatocellular carcinoma (HCC) is controversial. We performed a meta-analysis of available studies to assess whether GPC3 can be used as a prognostic factor in patients with HCC. Methods We searched PubMed and Ovid EBM Reviews databases and evaluated the reference list of relevant articles for studies that assessed the prognostic relevance of GPC3 in patients with HCC. Meta-analysis was performed using hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (95% CIs) as effect measures. Results A meta-analysis of eight studies included 1070 patients was carried out to evaluate the association between GPC3 and overall survival (OS) and disease-free survival (DFS) in HCC patients. The relation between GPC3 and tumor pathological features was also assessed. Our analysis results indicated that high GPC3 expression predicted poor OS (HR: 1.96, 95% CI: 1.512.55) and DFS (HR: 1.99, 95% CI: 1.57-2.51) of patients with HCC. GPC3 overexpression was significantly associated with high tumor grade (OR: 3.30, 95% CI: 2.045.33), late TNM stage (OR: 2.26, 95% CI: 1.005.12), and the presence of vascular invasion (OR: 2.43, 95% CI: 1.234.82). Conclusions GPC3 overexpression indicates a poor prognosis for patients with HCC, and it may also have predictive potential for HCC invasion and metastasis. PMID:24548704

  19. Clinical and prognostic relevance of EZH2 in breast cancer: A meta-analysis.

    PubMed

    Wang, Xu; Hu, Bo; Shen, Hugang; Zhou, Hao; Xue, Xiaofeng; Chen, Yan; Chen, Shaoji; Han, Ye; Yuan, Bin; Zhao, Hong; Zhi, Qiaoming; Kuang, Yuting

    2015-10-01

    The polycomb group protein enhancer of zeste homolog 2 (EZH2) is regarded as a tightly linking oncogene in many types of cancer. However, the prognostic role of EZH2 in breast cancer (BC) still remains controversial. Our study aimed to evaluate the clinical and prognostic relevance of EZH2 in BC patients based on published studies. 11 studies totally containing 2330 patients (1052 EZH2-positive and 1278 EZH2-negative) were included in our meta-analysis. Our data showed that EZH2 over-expression was significantly associated with estrogen receptor (ER) negativity [OR=0.227, 95% CI=0.174-0.297, P=0.000], progesterone receptor (PR) negativity [OR=0.454, 95% CI=0.300-0.687, P=0.000], human epidermal growth factor receptor type 2 (HER-2) positivity [OR=1.846, 95% CI=1.366-2.496, P=0.000], invasive ductal cancer (IDC) [OR=2.237, 95% CI=1.489-3.361, P=0.000], race (Caucasian) [OR=0.707, 95% CI=0.522-0.957, P=0.025], high histological grade [OR=3.177, 95% CI=2.012-5.014, P=0.000] and triple-negative status (TNBCs) [OR=5.380, 95% CI=1.065-27.187, P=0.042], which led to a poor OS rate in BC [RR=2.193, 95% CI=1.495-3.217, P=0.000]. In conclusion, EZH2 participated in the progression of BC as a putative factor, and over-expression of EZH2 was distinctly correlated with a poor patient survival. EZH2 may serve as a prognostic biomarker and target in BC patients. PMID:26271144

  20. The prognostic value of gray-white-matter ratio in cardiac arrest patients treated with hypothermia

    PubMed Central

    2013-01-01

    Background Mild therapeutic hypothermia alters the validity of a number of parameters currently used to predict neurological outcome after cardiac arrest and resuscitation. Thus, additional parameters are needed to increase certainty of early prognosis in these patients. A promising new approach is the determination of the gray-white-matter ratio (GWR) in cranial computed tomography (CCT) obtained early after resuscitation. It is not known how GWR relates to established outcome parameters such as neuron specific enolase (NSE) or somatosensory evoked potentials (SSEP). Methods Cardiac arrest patients (n?=?98) treated with hypothermia were retrospectively analyzed with respect to the prognostic value of GWR, NSE and SSEP. Results A GWR?poor outcome with 100% specificity and 38% sensitivity. In 62 patients NSE, SSEP and CCT were available. The sensitivity of poor outcome prediction by both NSE?>?97?g/L and bilateral absent SSEP was 43%. The sensitivity increased to 53% in a multi-parameter approach predicting poor outcome using at least two of the three parameters (GWR, NSE and SSEP). Conclusion Our results suggest a strong association of a low GWR with poor outcome following cardiac arrest. Determination of the GWR increases the sensitivity in a multi-parameter approach for prediction of poor outcome after cardiac arrest. PMID:23566292

  1. Expression of heat-shock protein gp96 in gallbladder cancer and its prognostic clinical significance

    PubMed Central

    Chen, Yongli; Chen, Chuanqi; Ma, Chengzhi; Sun, Shibo; Zhang, Jing; Sun, Yan

    2015-01-01

    Purpose: To detect the expression and prognostic clinical significance of heat-shock protein gp96 (HSP gp96) in gallbladder cancer. Methods: Immunohistochemistry was used to detect and compare the rate of HSP gp96 expression in 107 samples of gallbladder cancer, 70 of gallbladder adenoma and 67 of chronic cholecystitis. The association of clinicopathological factors and patients’ survival were calculated by univariate and multivariate (Cox proportional hazard regression method) analysis. Results: The expression positive rate of HSP gp96 was 90.7% (97/107) in gallbladder cancer, 71.4% (50/70) in gallbladder adenoma and 47.76% (32/67) in chronic cholecystitis respectively. The positive rate of HSP gp96 in gallbladder cancer tissues was significantly higher than that in gallbladder adenoma and chronic cholecystitis tissues (P < 0.01). Multivariate and Cox regression analysis showed that positive of HSP gp96 (P = 0.026) expression was an independent poor prognostic predictor in gallbladder cancer. Conclusions: HSP gp96-positive expression is closely correlated with poor survival in gallbladder cancer. PMID:25973087

  2. Prognostic value of long noncoding RNA MALAT1 in digestive system malignancies

    PubMed Central

    Zhai, Hui; Li, Xiao-Mei; Maimaiti, Ailifeire; Chen, Qing-Jie; Liao, Wu; Lai, Hong-Mei; Liu, Fen; Yang, Yi-Ning

    2015-01-01

    Background: MALAT1, a newly discovered long noncoding RNA (lncRNA), has been reported to be highly expressed in many types of cancers. This meta-analysis summarizes its potential prognostic value in digestive system malignancies. Methods: A quantitative meta-analysis was performed through a systematic search in PubMed, Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI) for eligible papers on the prognostic impact of MALAT1 in digestive system malignancies from inception to Apr. 25, 2015. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to summarize the effect. Results: Five studies were included in the study, with a total of 527 patients. A significant association was observed between MALAT1 abundance and poor overall survival (OS) of patients with digestive system malignancies, with pooled hazard ratio (HR) of 7.68 (95% confidence interval [CI]: 4.32-13.66, P<0.001). Meta sensitivity analysis suggested the reliability of our findings. No publication bias was observed. Conclusions: MALAT1 abundance may serve as a novel predictive factor for poor prognosis in patients with digestive system malignancies.

  3. Novel prognostic markers for patients with triple-negative breast cancer.

    PubMed

    Zhou, Ling; Li, Ke; Luo, Yanli; Tian, Ling; Wang, Min; Li, Chuanyuan; Huang, Qian

    2013-10-01

    Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by poor prognosis. Currently, no reliable markers have been identified as having a predictive role for the prognosis of TNBC patients. In this study, 119 breast cancer samples, including 31 TNBC and 89 non-TNBC subtypes, were collected. The protein levels of cleaved caspase-3 (CC3), aldehyde dehydrogenase 1 (ALDH1), cyclooxygenase-2, Ki-67, H2A histone family member X, and phosphorylated protein kinase B protein were measured by immunohistochemical staining. The percentage of positive CC3 (P = .017), ALDH1 (P = .015), Ki-67 (P = .001), and H2A histone family member X (P = .016) staining was significantly higher in TNBC than in non-TNBC cases. Positive CC3 and ALDH1 staining significantly correlated with poor prognosis of breast cancer, the TNBC subtype and non-TNBC subtype. Positive cyclooxygenase-2 expression significantly correlated with the survival of patients with TNBC. Multivariate analysis demonstrated that CC3 and ALDH1 are independent prognostic factors for BC and non-TNBC. ALDH1 is a prognostic marker for TNBC patients. PMID:23845466

  4. Clinical and prognostic differences among patients with light chain deposition disease, myeloma cast nephropathy and both.

    PubMed

    Zand, Ladan; Nasr, Samih H; Gertz, Morie A; Dispenzieri, Angela; Lacy, Martha Q; Buadi, Francis K; Kumar, Shaji; Kyle, Robert A; Fervenza, Fernando C; Sethi, Sanjeev; Dingli, David; Rajkumar, S Vincent; Kapoor, Prashant; McCurdy, Arleigh; Leung, Nelson

    2015-12-01

    In some patients with light chain deposition disease (LCDD) there is also evidence of myeloma cast nephropathy (MCN) on renal biopsy. The purpose of this study was to evaluate the renal and survival outcome of patients with concomitant diagnosis of MCN and LCDD to LCDD and MCN alone. Eighty seven patients were identified and divided into LCDD (n = 45), MCN (n = 29), and LCDD+ MCN (n = 13). Patients with LCDD+ MCN had a worse overall survival (OS) compared to patients with LCDD (p = 0.03), but similar to patients with MCN (p = 0.4). Death-censored renal survival was no different amongst the groups. Presenting with acute renal failure at time of renal biopsy (HR 7.2, p = 0.0002) was an independent poor renal prognostic factor while older age (HR 1.06, p = 0.0002), presence of osteolytic lesions (HR 4.4, p < 0.0001), and requirement for dialysis or creatinine ? 5 mg/dL (HR 3.2, p = 0.0006) at time of renal biopsy were independent poor prognostic factors for OS. PMID:25860232

  5. The Major Prognostic Features of Nuclear Receptor NR5A2 in Infiltrating Ductal Breast Carcinomas

    PubMed Central

    Chang, Li-Yun; Liu, Li-Yu D.; Roth, Don A.; Kuo, Wen-Hung; Hwa, Hsiao-Lin; Chang, King-Jen; Hsieh, Fon-Jou

    2015-01-01

    Background. Gene expression profiles of 181 breast cancer samples were analyzed to identify prognostic features of nuclear receptors NR5A1 and NR5A2 based upon their associated transcriptional networks. Methods. A supervised network analysis approach was used to build the NR5A-mediated transcriptional regulatory network. Other bioinformatic tools and statistical methods were utilized to confirm and extend results from the network analysis methodology. Results. NR5A2 expression is a negative factor in breast cancer prognosis in both ER(−) and ER(−)/ER(+) mixed cohorts. The clinical and cohort significance of NR5A2-mediated transcriptional activities indicates that it may have a significant role in attenuating grade development and cancer related signal transduction pathways. NR5A2 signature that conditions poor prognosis was identified based upon results from 15 distinct probes. Alternatively, the expression of NR5A1 predicts favorable prognosis when concurrent NR5A2 expression is low. A favorable signature of eight transcription factors mediated by NR5A1 was also identified. Conclusions. Correlation of poor prognosis and NR5A2 activity is identified by NR5A2-mediated 15-gene signature. NR5A2 may be a potential drug target for treating a subset of breast cancer tumors across breast cancer subtypes, especially ER(−) breast tumors. The favorable prognostic feature of NR5A1 is predicted by NR5A1-mediated 8-gene signature. PMID:26366408

  6. Albumin and Neutrophil Combined Prognostic Grade as a New Prognostic Factor in Non-Small Cell Lung Cancer: Results from a Large Consecutive Cohort

    PubMed Central

    Shen, Hongchang; Dong, Wei; Zhang, Tiehong; Liu, Qi; Du, Jiajun

    2015-01-01

    Objectives It has been reported nutritional status and systemic inflammation were associated with the outcome of patients with malignancies. However, the prognostic value of combination of them was really scarce, especially in non-small cell lung cancer (NSCLC). In order to find a more simple and efficient predictor, we hypothesized that pretreatment albumin and neutrophil combined prognostic grade (ANPG) could offer an improved prognostic ability in NSCLC patients. Methods We collected pretreatment albumin and neutrophil, clinicopathological, treatment and follow-up data of 1033 consecutive NSCLC patients treated between 2006 and 2011 in this retrospective study. The ANPG was calculated according to pretreatment albumin and neutrophil levels dichotomized by the optimal cut-off values, the quartile values and the clinical reference values. Kaplan-Meier (K-M) curves and Cox proportional regression were used for survival analyses. All the data was analyzed by SPSS 20.0. Results According to optimal cut-off values and quartile values, significant differences were found in different pretreatment albumin, neutrophil levels and ANPG from the K-M curve (all p<0.05). Univariate analyses and multivariate analyses disclosed ANPG was a more sensitive independent predictor for both overall survival (OS) and progression free survival (PFS) than either albumin level or neutrophil level (HRs were higher for ANPG). As for clinical reference values, no significant difference of pretreatment albumin levels was found in K-M curve and univariate analyses. All three indexes lost their significance in multivariate analyses. Conclusion Higher ANPG predicts worse OS and PFS in NSCLC patients independently, and it is more sensitive than hypoalbuminaemia and neutrophilia. It might be used as a reliable, convenient and more sensitive predictor to assist the identification of patients with poor prognosis and be a hierarchical factor in the future NSCLC clinical trials. PMID:26656866

  7. New prognostic factors in breast cancer.

    PubMed

    Adam Maciejczyk, Adam

    2013-01-01

    For many years, the age of the patient, the condition of axillar lymph nodes, the size of the tumour, histological traits (in particular histological grade of malignancy and invasion of lymphatic vessels), condition of hormonal receptors and HER2 represented principal factors used for the stratification of breast cancer patients for the purposes of evaluating the prognosis and determining the appropriate strategy of treatment. Although the variables are useful for the prognostic evaluation of individual groups of breast cancer patients, their role in determining the individual risk level of the patient and in the selection of supplementary treatment is quite restricted. This article shows the prognostic value of additional parameters, whose expression is associated with chemioresistance (MRP2, BCRP, YB1) or individual assessment of the dynamics of tumor progression (S100P, BUBR1). In addition, it describes the role of an online database of "The Kaplan-Meier plotter" which contains the assessment of the effects of expression of various genes on the clinical outcome of patients with breast cancer. PMID:23468257

  8. Epidemiologic and molecular prognostic review of glioblastoma.

    PubMed

    Thakkar, Jigisha P; Dolecek, Therese A; Horbinski, Craig; Ostrom, Quinn T; Lightner, Donita D; Barnholtz-Sloan, Jill S; Villano, John L

    2014-10-01

    Glioblastoma multiforme (GBM) is the most c